記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To investigate a prognostic score for stage II-III colorectal cancer (CRC) based on post-CEA and pT4 levels. METHODS: Two cohorts of stage II-III CRC patients who underwent curative surgery between 2011 and 2017 were included. The prognostic score (T-CEA score) was calculated as follows: T-CEA-0, post-CEA ≤ 5 ng/mL and pT1-3; T-CEA-1, post-CEA > 5 ng/mL or pT4; T-CEA-2, post-CEA > 5 ng/mL and pT4. RESULTS: The T-CEA scores of the 587 patients were as follows: T-CEA-0 (n = 436; 74%), T-CEA-1 (n = 129; 22%), and T-CEA-2 (n = 10; 2%). The 5-year recurrence-free survival (RFS) rates of the T-CEA-0, 1, and 2 groups were 80.3%, 54.8%, and 0%, respectively (P < 0.01), and the 5-year overall survival (OS) rates were 90.9%, 74.2%, and 0%, respectively (T-CEA-0 vs T-CEA-1: P < 0.01, T-CEA-1 vs T-CEA-2: P = 0.04). Multivariate analysis revealed that an elevated T-CEA score of 1 or 2 was a significant risk factor for poor RFS (HR: 2.89, P < 0.01) and OS (HR: 2.85, P < 0.01). CONCLUSION: The T-CEA score is a reliable and convenient prognostic score for stage II-III CRC.

DOI： 10.1007/s00595-023-02644-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: In this study, we aimed to investigate the oncological impact of postoperative infection in patients with malignant large bowel obstruction managed by self-expandable metallic stent placement as a bridge to surgery. METHODS: The cohort of this multicenter retrospective study comprised 129 patients with pathological stage II/III malignant large bowel obstruction who had undergone bridge to surgery. Patients were allocated to no-postoperative infection (n = 116) and postoperative infection groups (n = 13). RESULTS: The postoperative infection group had a significantly greater proportion of men, fewer harvested lymph nodes, and longer postoperative hospital stays than did the no-postoperative infection group. Self-expandable metallic stent-related variables, including clinical failure, were not associated with postoperative infection. Male sex and low body mass index were identified as risk factors for postoperative infection by multivariate logistic regression. Three-year relapse-free survival rates were 75.5% and 30.8% in the no-postoperative infection and postoperative infection groups, respectively; this difference is statistically significant. Male sex, postoperative infection, and T4 were identified as independent prognostic factors by multivariate Cox proportional hazard analysis. The postoperative infection group had a significantly higher total recurrence rate and shorter interval to recurrence than did the no-postoperative infection group. CONCLUSION: To the best of our knowledge, this is the first study to show that postoperative infection in bridge to surgery patients has a negative oncological impact. This finding indicates that further improvement in perioperative management of bridge to surgery patients is required to minimize postoperative infection and that patient-risk stratification and additional therapy would contribute to improving oncological outcomes.

DOI： 10.1007/s00384-022-04290-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Angiogenesis is regulated by interactions between vascular endothelial growth factors (VEGFs) and VEGF receptors. VEGF-A, VEGF-D, placental growth factor (PlGF) and plasminogen activator inhibitor-1 (PAI-1) have tumor angiogenic activity. VEGF-A and PAI-1 levels in the blood may impact the activity of bevacizumab, and VEGF-D levels may similarly diminish the efficacy of ramucirumab. However, the dynamics of these angiogenic biomarkers for anti-VEGF therapy have not been well established; therefore, they were evaluated in this retrospective study, which included two cohorts. Cohort 1 included patients who were treated with cytotoxic agents and bevacizumab as first-line chemotherapy, and Cohort 2 comprised patients who were treated with cytotoxic agents and anti-VEGF drugs (bevacizumab, ramucirumab or aflibercept) as second-line chemotherapy. VEGF-A, VEGF-D, PlGF and PAI-1 levels were measured before starting chemotherapy and were re-assessed every 1-2 months until disease progression. Bevacizumab had reduced benefit as a first-line chemotherapeutant in patients with very low or very high levels of VEGF-A. Bevacizumab increased VEGF-A and PlGF levels, but not VEGF-D or PAI-1. Anti-VEGF drugs offered the greatest benefit to patients with high PAI-1 before first- and second-line chemotherapy. PAI-1 levels were not affected by anti-VEGF drugs. Since ramucirumab increased VEGF-D, it offered less benefit to patients with high VEGF-D in second-line chemotherapy. Conversely, aflibercept offered greater benefits to patients with high VEGF-D, without increasing VEGF-D. These biomarkers may be useful for the prediction of drug efficacy and may predict resistance to anti-VEGF drugs.

DOI： 10.3892/ol.2022.13583

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Epithelial-mesenchymal transition (EMT) plays a pivotal role in cancer progression and metastasis in many types of malignancies, including colorectal cancer. Although the importance of EMT is also considered in colorectal neuroendocrine carcinoma (NEC), its regulatory mechanisms have not been elucidated. We recently established a human colorectal NEC cell line, SS-2. In this study, we aimed to clarify whether these cells were sensitive to transforming growth factor beta 1 (TGF-β1) and whether EMT could be induced through TGF-β1/Smad signaling, with the corresponding NEC cell-specific changes in invasiveness. In SS-2 cells, activation of TGF-β1 signaling, as indicated by phosphorylation of Smad2/3, was dose-dependent, demonstrating that SS-2 cells were responsive to TGF-β1. Analysis of EMT markers showed that mRNA levels changed with TGF-β1 treatment and that E-cadherin, an EMT marker, was expressed in cell-cell junctions even after TGF-β1 treatment. Invasion assays showed that TGF-β1-treated SS-2 cells invaded more rapidly than non-treated cells, and these cells demonstrated increased metalloproteinase activity and cell adhesion. Among integrins involved in cell-to-matrix adhesion, α2-integrin was exclusively upregulated in TGF-β1-treated SS-2 cells, but not in other colon cancer cell lines, and adhesion and invasion were inhibited by an anti-α2-integrin blocking antibody. Our findings suggest that α2-integrin may represent a novel therapeutic target for the metastasis of colorectal NEC cells.

DOI： 10.1016/j.bbrep.2022.101239

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記述言語：日本語   出版者・発行元：日本外科代謝栄養学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Surgical site infections (SSIs) remain one of the most common serious surgical complications and are the second most frequent healthcare-associated infection. Patients with SSIs have a significantly increased postoperative length of hospital stay, hospital expenses, and mortality risk compared with patients without SSIs. The prevention of SSI requires the integration of a range of perioperative measures, and approximately 50% of SSIs are preventable through the implementation of evidence-based preventative strategies. Several international guidelines for SSI prevention are currently available worldwide. However, there is an urgent need for SSI prevention guidelines specific to Japan because of the differences in the healthcare systems of Japan versus western countries. In 2018, the Japan Society for Surgical Infection published SSI prevention guidelines for gastroenterological surgery. Although evidence-based SSI prevention guidelines are now available, it is important to consider the appropriateness of these guidelines depending on the actual conditions in each facility. A systemic inflammatory host response is a hallmark of bacterial infection, including SSI. Therefore, blood inflammatory markers are potentially useful in SSI diagnosis, outcome prediction, and termination of therapeutic intervention. In this review, we describe the current guideline-based perioperative management strategies for SSI prevention, focusing on gastroenterological surgery and the supplemental utility of blood inflammatory markers.

DOI： 10.1272/jnms.JNMS.2023_90-102

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

後期高齢者は化学療法に対する忍容性が低く、標準治療を長期間行うのは困難である。早期結腸癌術後の肺転移に対し、UFT/UZEL/bevacizumab(Bev)療法が長期奏効した後期高齢者の1例を報告する。症例は82歳、男性。他院にてS状結腸癌に対し腹腔鏡補助下S状結腸切除術を施行された。pT1b、ly1、v0、N0、M0、pStage Iであったが、術後6ヵ月で右中葉に小結節を指摘され、5ヵ月後に増大傾向を認め肺転移と診断された。高齢者であるため標準的化学療法の導入は困難と考え、また腫瘍径も小さいため術後1年2ヵ月目よりUFT/UZEL/Bevを開始した。食欲不振で一段階減量を行ったがその後は大きな副作用もなく継続可能であり、2年6ヵ月時点までpartial response(PR)を維持している。UFT/UZEL/BevはFOLFOXなどの標準治療と比較するとエビデンスは十分ではないが、vulnerableな症例に対する選択肢と考えられた。(著者抄録)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J00296&link_issn=&doc_id=20220524520021&doc_link_id=%2Fab8gtkrc%2F2022%2F004905%2F022%2F0593b0596%26dl%3D3&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2022%2F004905%2F022%2F0593b0596%26dl%3D3&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_4.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Preoperative colonic stenting for malignant large bowel obstruction (MLBO), also called bridge to surgery (BTS), is considered a great substitute treatment for emergency resection (ER) in the left-sided colon. However, its efficacy in the right-sided colon remains controversial. This systematic review and meta-analysis aimed to compare the postoperative short-term outcomes between BTS and ER for right-sided MLBO. METHODS: A comprehensive electronic literature search throughout December 2020 was performed to identify studies comparing short-term outcomes between BTS and ER for right-side MLBO. The main outcome measures were postoperative complications and mortality rates. A meta-analysis was performed using a fixed-effect or a random-effect method to calculate odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: Seven studies were included in this meta-analysis, comprising 5136 patients, of whom 1662 (32.4%) underwent BTS and 3474 (67.6%) underwent ER. This meta-analysis demonstrated that BTS resulted in reductions in postoperative complications (OR = 0.78; 95% CI: 0.66-0.92) and mortality (OR = 0.51; 95% CI: 0.28-0.92) than ER. CONCLUSION: The results of this meta-analysis indicate that BTS for right-sided MLBO confers preferable short-term outcomes as well as for left-sided. This suggests that BTS results in a reduction of postoperative complications and mortality for right-sided MLBO than ER.

DOI： 10.1007/s00464-022-09071-7

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Late-stage elderly patients have low tolerance to chemotherapy, and they have difficulties when they are treated with standard chemotherapy. We report a case of a late-stage elderly patient who had a long-term response to UFT/UZEL/bevacizumab( Bev)therapy for lung metastasis after surgery for early-stage colon cancer. He was 82-years-old and underwent laparoscopy-assisted sigmoid colectomy for sigmoid colon cancer at another hospital. The pathological diagnosis was pT1b, ly1, v0, N0, M0, pStage Ⅰ. Six months after the surgery, a small nodule was noted in the middle lobe of the right lung. It grew five months later and was definitely diagnosed as lung metastasis. Considering his physical condition and tumor size, we opted to introduce less invasive chemotherapy instead of standard chemotherapy. UFT/UZEL/Bev was started 14 months after surgery. Although he required dose reduction due to anorexia, he safely continued the treatment with partial response (PR), which was maintained for 2 years and 6 months. While UFT/UZEL/Bev has no convincing evidence, it may be an option for vulnerable patients, especially those with non-life-threatening disease.

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

後期高齢者は化学療法に対する忍容性が低く、標準治療を長期間行うのは困難である。早期結腸癌術後の肺転移に対し、UFT/UZEL/bevacizumab(Bev)療法が長期奏効した後期高齢者の1例を報告する。症例は82歳、男性。他院にてS状結腸癌に対し腹腔鏡補助下S状結腸切除術を施行された。pT1b、ly1、v0、N0、M0、pStage Iであったが、術後6ヵ月で右中葉に小結節を指摘され、5ヵ月後に増大傾向を認め肺転移と診断された。高齢者であるため標準的化学療法の導入は困難と考え、また腫瘍径も小さいため術後1年2ヵ月目よりUFT/UZEL/Bevを開始した。食欲不振で一段階減量を行ったがその後は大きな副作用もなく継続可能であり、2年6ヵ月時点までpartial response(PR)を維持している。UFT/UZEL/BevはFOLFOXなどの標準治療と比較するとエビデンスは十分ではないが、vulnerableな症例に対する選択肢と考えられた。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The prognosis for metastatic colorectal cancer patients (mCRC) with the BRAFV600E mutation is poor. BRAFV600E mutation frequency is reportedly low among Asians; however, the frequency of the BRAFV600E mutation in right-side colon cancer may not be low, even among Asians. In addition, spatial heterogeneity of BRAFV600E mutations also exists, as for RAS mutations. In this prospective observational study, we evaluated BRAFV600E mutations in cancer tissue and plasma of Japanese right-side colon cancer patients. METHOD: 215 patients with right-side colon cancer were included. BRAFV600E mutations of cancer tissue and plasma were detected using droplet digital PCR. Blood plasma of patients with BRAFV600E mutations in cancer tissue or plasma was drawn at intervals throughout chemotherapy, and BRAFV600E mutations were evaluated. RESULTS: BRAFV600E mutations were detected in tissue samples from 35 of 215 patients (16.3%, cecum; 22.4%, ascending colon; 17.8%, and transverse colon; 9.0%). BRAFV600E mutations were detected in plasma of 10 of 215 (4.7%) patients. Eight of the ten patients had BRAFV600E mutations in their primary tumours, but two (both were Stage IV) patients did not. Sensitivity of liquid biopsy to detect BRAFV600E mutations was 10.3% (3/29) in Stage I-III patients and 83.3% (5/6) in Stage IV patients. CONCLUSION: BRAFV600E mutations are observed in right-side colon cancer at high frequency, especially in the cecum. BRAFV600E mutations can be detected in plasma and the detection rate is high in patients with advanced cancer. Spatial heterogeneity was observed using liquid biopsy.

DOI： 10.1016/j.ejso.2022.01.016

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記述言語：日本語   出版者・発行元：(一社)日本腹部救急医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腹部救急医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腹部救急医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Colorectal cancer (CRC) is the third most common cancer worldwide, and surgical treatment remains the first-line treatment to provide a cure. In addition to the aging population, obesity, low physical activity, and smoking habits increase CRC risk. Despite advances in surgical techniques, chemotherapy, and radiotherapy, colorectal cancer remains the second leading cause of cancer-related deaths worldwide. For early-stage CRC, endoscopic treatment, including endoscopic mucosal resection and endoscopic submucosal dissection, has been performed. However, lymph node dissection is an integral part of surgical treatment for advanced-stage cancer because of the high incidence of lymph node metastasis. Conventional open surgery has evolved into laparoscopic and robotic surgery. Although prospective studies have confirmed the safety and feasibility of laparoscopic surgery for CRC, relevant treatment models of transverse colon cancer and rectal cancer still need to be further explored and validated. Furthermore, multidisciplinary treatment is needed to cure CRC completely. This review aimed to provide an update on recent advances in the surgical treatment of CRC.

DOI： 10.1272/jnms.JNMS.2022_89-310

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A peritoneal loose body (PLB) is a tissue completely separated from other intraperitoneal organs. It is rare and usually found incidentally during laparotomy, examination, or autopsy. It is usually located free in the peritoneal cavity and does not exist in the extraperitoneal space. It is generally thought to originate from the epiploic appendices released into the abdominal cavity following ischemic necrosis. We report a case of a giant PLB outside the peritoneal cavity, adjacent to the rectovesical excavation, inan asymptomatic 83-year-old man who underwent evaluation for cholecystolithiasis, preoperatively. Computed tomography revealed a mass with well-defined margins in the rectovesical excavation, consisting of a calcified core and peripheral soft tissue measuring 60 mm in diameter; it did not seem to invade adjacent organs. Although there were no symptoms or tumor growth over time, for a definitive diagnosis, we scheduled a laparoscopic extraction. On laparoscopic exploration, a white oval mass was found in the rectovesical excavation; there was no invasion of adjacent organs. We diagnosed the patient with a giant PLB.Postoperative recovery was uneventful. Most PLBs are asymptomatic and do not require surgery except when symptomatic, large in size, or suspicious for malignancy. The PLB is rarely extraperitoneal and usually freely mobile; however, in our patient, it was fixed and outside the abdominal cavity, near the rectovesical fossa. Although it could not be diagnosed preoperatively as being extra-peritoneal, it showed the typical imaging findings of PLB; thus, it was possible to remove the mass laparoscopically without bowel resection.

DOI： 10.1272/jnms.JNMS.2023_90-302

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Anorectal melanoma is a rare disease with poor prognosis and nonspecific symptoms, leading to difficulties in preoperative diagnosis. Here, we describe the establishment of MELS, a novel anorectal melanoma cell line derived from tumor resection of the rectum in a 40-year-old Japanese man. METHODS: Histological, electron microscopic, and immunohistochemical features of S-100, HMB-45, Melan-A, and NSE positivity in the patient's tumor were confirmed as typical of surgically resected anorectal melanoma. RESULTS: MELS cells are round or oval cells with sharp thorn-like protrusions on some or all of the cell membrane. They form irregular attached colonies with numerous floating cells in two-dimensional culture. Transmission electron microscopy revealed that some MELS cells possess cytoplasmic melanosomes. Immunocytochemically, MELS cells showed the same staining patterns as surgical tissues. MELS cells had lower growth rates than Caco-2 (a colon adenocarcinoma cell line) and A375 (a cutaneous melanoma cell line) cells. Oxaliplatin and irinotecan were more effective in MELS cells than in Caco-2 and A375 cells. CONCLUSIONS: Prior to our study, no reports had provided detailed clinical information on anorectal melanoma cell lines. Thus, MELS cells should improve current knowledge on the biological behaviors of anorectal melanoma, while providing a novel platform for examining the effects of anorectal therapies.

DOI： 10.1272/jnms.JNMS.2022_89-402

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：日本ストーマ・排泄リハビリテーション学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Kyphosis makes abdominal surgery difficult. Here, we report a case of rectal cancer in a patient with kyphosis on whom laparoscopic surgery was adequately performed owing to preoperative simulation. An 81-year-old woman with rectal cancer was admitted to our department, and laparoscopic surgery was planned. On physical examination, the patient showed severe kyphosis. To adequately perform laparoscopic surgery, a detailed and thorough preoperative simulation was conducted. 1) Simulations of port arrangement and anatomy with 3-D CT, 2) body position simulation, 3) selection of surgical instruments, 4) preoperative discussion with the anesthesiologist were conducted. We planned to insert the first port from the umbilical region for pneumoperitoneum and the camera port from the ventral region under pneumoperitoneum. We planned to insert the ports on the right side of the patient's body from caudal regions, considering the location of the inferior mesenteric artery and the limited degrees and space due to the costal arch and the promontorium. Beach chair position was planned. We used a fan-shaped retractor and a sponge-made retractor to remove the small intestine from the surgical view. We discussed with the anesthesiologist preoperatively, and decided to keep the pneumoperitoneum pressure under 8 mmHg during the operation considering the respiratory function. Lower anterior resection with D2 lymph node dissection was performed without any intraoperative complications, and at 2 years post-surgery, the patient was healthy with no signs of recurrence. Laparoscopic surgery may be a good choice in patients with kyphosis, and we believe that preoperative simulation will result in an uneventful surgery.

DOI： 10.1272/jnms.JNMS.2022_89-608

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Prevention of postoperative anastomotic leakage in rectal surgery is still required. This study investigated the feasibility of endoscopic hand suturing (EHS) on rectal anastomosis ex vivo. By using isolated porcine colon, we prepared ten anastomoses 6-10 cm from the virtual anus. Then, we sutured anastomoses intraluminally by EHS, which involved a continuous suturing method in 5 cases and a nodule suturing method with extra corporeal ligation in 5 cases. Completeness of suturing, number of stitches, procedure time and presence of stenosis were investigated. Furthermore, the degree of stenosis was compared between the two suturing methods. In all cases, EHS were successfully completed. The median number of stitches and procedure time was 8 and 5.8 min, respectively. Stenosis was created in all continuous suturing cases whereas none was seen in nodule suturing cases. The shortening rate was significantly greater in the continuous suturing method than in the nodule suturing method. Intraluminal reinforcement of rectal anastomosis by EHS using nodule suturing with extra corporeal ligation is feasible without stenosis, which may be helpful as a countermeasure against possible postoperative anastomotic leakage in rectal surgery.

DOI： 10.1038/s41598-021-01396-y

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科感染症学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Small intestinal metastasis from lung cancer is a relatively rare occurrence, and often causes intestinal obstruction, gastrointestinal perforation, and/or gastrointestinal bleeding making it is an oncological emergency. Many patients have been reported to undergo emergency surgery owing to the rapid progression of the intestinal metastatic lesion; however, information regarding the changes that occur in such metastases over time remains lacking. Therefore, we analyzed 4 patients who had small intestinal metastases arising from lung cancer, who were treated during a 10-year period (January 2011 to December 2020), and whose tumor diameter changes were recorded. The average tumor volume growth rate was 1.48 (1.31-1.78) -fold, and the median observation period was 22 (4-39) days, showing a rapid increase. Histopathologically, in patients with a high degree of primary tumor atypia, rapid tumor growth caused by intratumoral hemorrhage may occur. This was considered to be one of the factors responsible for the rapid increase in tumor volume.

DOI： 10.1272/jnms.JNMS.2022_89-501

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(株)南江堂  

＜文献概要＞閉塞性大腸癌に対する大腸ステント治療の普及に伴い,ステント留置後の腹腔鏡手術も多く行われるようになっている.しかし,開腹移行率は非閉塞性症例と比べて高く,周囲組織への癌浸潤や炎症の波及,術中操作による腸管穿孔の回避,口側腸管の評価,適切な切離ラインの決定など,配慮すべき点も多い.また,ステント留置後から手術までの待機期間などの周術期管理も,短期成績のみならず長期成績に影響する.本稿では,大腸ステント留置後の腹腔鏡手術を安全に行うために注意すべき点および当科の取り組みについて概説し,今後の展望を述べる.

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00393&link_issn=&doc_id=20210824070010&doc_link_id=10.15106%2Fj_geka83_1112&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_geka83_1112&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(株)南江堂  

＜文献概要＞閉塞性大腸癌に対する大腸ステント治療の普及に伴い,ステント留置後の腹腔鏡手術も多く行われるようになっている.しかし,開腹移行率は非閉塞性症例と比べて高く,周囲組織への癌浸潤や炎症の波及,術中操作による腸管穿孔の回避,口側腸管の評価,適切な切離ラインの決定など,配慮すべき点も多い.また,ステント留置後から手術までの待機期間などの周術期管理も,短期成績のみならず長期成績に影響する.本稿では,大腸ステント留置後の腹腔鏡手術を安全に行うために注意すべき点および当科の取り組みについて概説し,今後の展望を述べる.

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00393&link_issn=&doc_id=20210824070010&doc_link_id=10.15106%2Fj_geka83_1112&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_geka83_1112&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：日本外科代謝栄養学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Circulating tumour DNA (ctDNA) is very useful for purposes of cancer genetics; however, it has some limitations. Recently, ctDNA in body fluids, such as urine, sputum, and pleural effusion, has been investigated. The aim of this study was to evaluate the quantity of ctDNA derived from urine (trans-renal ctDNA) and the accuracy of KRAS mutation detection in relation to disease stage in colorectal cancer. METHODS: Urine, plasma, and tissue samples were collected from consecutively resected colorectal cancer patients. DNA was extracted from each sample and the quantity was determined. From each DNA sample, KRAS mutations were detected using droplet digital PCR. RESULTS: 200 patients participated and KRAS mutations were detected in 84 patients (42.0%) from tumour tissue. The concentration of trans-renal ctDNA (trtDNA) was significantly lower than that of plasma; however, there was no significant difference between the sensitivity using ctDNA and that using trtDNA (29.8% VS 33.3%, p = 0.62). Concordance between these two tests was only 17.5%. Combination analysis (ctDNA + trtDNA) improved the sensitivity to 53.6%, and sensitivity was significantly higher than that of corresponding single assays (p = 0.003). In early cancer stages, trtDNA had greater sensitivity for detecting KRAS mutations than ctDNA (37.7% vs. 21.3%, p = 0.047). Conversely, it was less useful for advanced cancer stages (21.7% vs. 52.2%, p = 0.07). Notably, KRAS mutations were detected using ctDNA or trtDNA in 12 of 116 (10.3%) patients who had no KRAS mutations in their tissue samples. CONCLUSIONS: trtDNA and ctDNA have equal potential and combination analysis significantly improved the sensitivity.

DOI： 10.1016/j.ejso.2021.07.017

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: High preoperative carcinoembryonic antigen (CEA) is a well-known risk factor for stage II-III colorectal cancer (CRC); however, in most cases, cancer does not recur. Conversely, postoperative CEA (post-CEA) is occasionally measured, and high post-CEA patients often develop recurrence; however, the clinical significance of post-CEA testing is unknown. The purpose of this study was to determine whether post-CEA elevation might indicate a poor prognosis for stage II-III CRC patients who underwent curative surgery. PATIENTS AND METHODS: 482 patients with pathological stage II-III CRC were included. Univariate and multivariate analyses were performed to evaluate post-CEA levels. RESULTS: Multivariate analysis showed that elevated post-CEA (hazard ratio (HR): 3.14, P < 0.001), pathological lymph node metastasis (pN+), and pathological T4 (pT4) are associated with poor recurrence-free survival (RFS), and that elevated post-CEA (HR: 3.12; P = 0.002), pN+, pT4, age >70, and smoking are independently associated with poor overall survival. Subgroup analysis among stage III patients, in combination with the risk classification of the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) study, showed that elevated post-CEA is a significant indicator of poor prognosis for RFS in both low-risk (73.8% vs. 21.2%, P < 0.001) and high-risk (49.9% vs. 25.0%, P = 0.04) groups. CONCLUSIONS: Post-surgical CEA elevation is independently associated with poor prognosis in stage II-III CRC. Adding post-CEA levels to the IDEA risk classification may provide a more reliable indicator of the need for individualized surveillance and adjuvant chemotherapeutic strategies.

DOI： 10.1016/j.ejso.2021.05.041

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: This study investigated the short- and long-term outcomes of 18- and 22-mm-diameter self-expandable metallic stent (SEMS) as a bridge to surgery (BTS) in patients with malignant large bowel obstruction (MLBO). METHODS: Sixty-nine pathological stage II and III colorectal cancer patients who underwent BTS were included in this multi-institutional retrospective study. Patients were divided into two groups regarding the diameter of SEMS: an 18-mm group (n = 30) and a 22-mm group (n = 39). RESULTS: There was no significant difference in the clinical success rate, but both of the two re-obstructions observed occurred in the 18-mm group. The 18-mm group showed a trend toward a higher incidence of overall postoperative complications (Clavien-Dindo grading ≥ II) than the 22-mm group (33.3% vs. 10.3%, P = 0.061). The 3-year disease-free and overall survival showed no significant differences between the 18- and 22-mm groups (78.2% vs. 68.8%, P = 0.753 and 92.8% vs. 82.1%, P = 0.471, respectively). CONCLUSION: SEMS of 18 and 22 mm diameter confer statistically equivalent short- and long-term outcomes as a BTS.

DOI： 10.1007/s00595-020-02185-2

PubMed

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：日本語   出版者・発行元：(株)南江堂  

＜文献概要＞虫垂炎の治療は,単純性虫垂炎(uncomplicated appendicitis:UA),複雑性虫垂炎(complicated appendicitis:CA),腹膜炎を伴う虫垂炎に分けて考える必要がある.穿孔性虫垂炎はCAに含まれるが,腹膜炎を伴わないCAに対する緊急手術の術後合併症発症率は小さくなく,死亡率は0.1%である.保存的治療後に行うinterval appendectomyは合併症が少なく安全性が高いが,保存的治療の成功率は90%程度であること,約1%に悪性腫瘍が合併することに注意が必要である.

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00393&link_issn=&doc_id=20210301230007&doc_link_id=10.15106%2Fj_geka83_236&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_geka83_236&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Polyvinyl alcohol (PVA) is a water-soluble synthetic polymer used in eye drops, embolization particles, and artificial cartilage. It has also been shown to cause expansion of functional multipotent self-renewing hematopoietic stem cells under serum-free conditions. In this study, we examined the effects of PVA on human pancreatic ductal adenocarcinoma (PDAC) cell lines using 2-dimensional (2D) and 3D-cultures with serum-free medium. In the 2D-culture, PVA-treatment induced an aggregated colony-like appearance in PDAC cells. It increased the growth of PK-8 cells in a dose-dependent manner as well as significantly increasing migration and invasion abilities. qRT-PCR showed an increase in α2 integrin and a decrease in matrix metalloprotease levels in PVA-treated PK-8 cells. Through qRT-PCR analysis, β1 integrin expression at the mRNA level was found to be decreased; however, it was unaltered at the protein level when assessed using FACS analysis. PVA further induced mesenchymal to epithelial transition-like alterations, including increased E-cadherin and decreased Vimentin and N-cadherin expression. Four cancer stem cell (CSC) markers were higher in PVA-treated PK-8 cells compared to controls. In 3D-culture, PVA-treated PK-8 cells showed a rod-like appearance with larger sphere size and higher growth ability. qRT-PCR showed that CSC markers did not increase and 2 of 4 drug transporters had decreased in PVA-treated PK-8 cells. These findings suggest that PVA increases the growth, migration, invasion, and sphere size of PK-8 cells, but does not increase the proportion of pancreatic CSCs under 3D-culture conditions with serum-free medium.

DOI： 10.1016/j.heliyon.2021.e06182

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Approximately 10% of patients with colorectal cancer (CRC) develop malignant large bowel obstruction (MLBO) at diagnosis. Furthermore, for 35% of patients with MLBO, curative primary tumor resection is unfeasible because of locally advanced disease and comorbidities. The practice of placing a self-expandable metallic stent (SEMS) has dramatically increased as an effective palliative treatment. Recent advances in systemic chemotherapy for metastatic CRC have significantly contributed to prolonging patients' prognosis and expanding the indications. However, the safety and efficacy of systemic chemotherapy in patients with SEMS have not been established. This review outlines the current status of this relatively new therapeutic strategy and future perspectives. Some reports on this topic have demonstrated that 1) systemic chemotherapy and the addition of molecular targeted agents contribute to prolonged survival in patients with SEMS; 2) delayed SEMS-related complications are a major concern, and this requires strict patient monitoring; however, primary tumor control by chemotherapy might result in decreased complications, especially regarding re-obstruction; and 3) using bevacizumab could be a risk factor for SEMS-related perforation, which may be lethal. Although this relatively new approach for unresectable stage IV obstructive CRC requires a well-planned clinical trial, this therapy could be promising for patients who are unideal candidates for emergency surgery and require immediate systemic chemotherapy.

DOI： 10.23922/jarc.2020-061

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

症例は60歳代、女性。盲腸癌に対して腹腔鏡補助下回盲部切除術を施行した(pT3、pN2b、pM0、pStage IIIc)。術後補助化学療法としてFOLFOXを12コース施行したが、終了24ヵ月後にCEAの上昇を認め、PET-CTにてFDG集積を伴う腹膜播種結節を多数認めた。CAPOX/bevacizumab療法を4コース施行し、PET-CTで結節の縮小を認めたため腹膜播種切除術、両側卵巣切除術によりR0切除が行えた。腹膜播種再発症例ではCAPOX/bevacizumab投与により病勢コントロールが可能となり、R0切除が得られる可能性がある。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00296&link_issn=&doc_id=20210118600089&doc_link_id=%2Fab8gtkrc%2F2020%2F004713%2F089%2F2006b2008%26dl%3D3&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2020%2F004713%2F089%2F2006b2008%26dl%3D3&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_4.gif

記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

症例は60歳代、女性。盲腸癌に対して腹腔鏡補助下回盲部切除術を施行した(pT3、pN2b、pM0、pStage IIIc)。術後補助化学療法としてFOLFOXを12コース施行したが、終了24ヵ月後にCEAの上昇を認め、PET-CTにてFDG集積を伴う腹膜播種結節を多数認めた。CAPOX/bevacizumab療法を4コース施行し、PET-CTで結節の縮小を認めたため腹膜播種切除術、両側卵巣切除術によりR0切除が行えた。腹膜播種再発症例ではCAPOX/bevacizumab投与により病勢コントロールが可能となり、R0切除が得られる可能性がある。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00296&link_issn=&doc_id=20210118600089&doc_link_id=%2Fab8gtkrc%2F2020%2F004713%2F089%2F2006b2008%26dl%3D3&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2020%2F004713%2F089%2F2006b2008%26dl%3D3&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_4.gif

記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

症例は60歳女性で、排便障害を主訴とした。胸腹部造影CT検査で左側横行結腸に全周性の腫瘍および口側腸管に便の貯留を認め、その他多発肺・肝・卵巣転移も認めた。大腸内視鏡検査では細径内視鏡でも卵巣腫瘍による癒着とS状結腸の過伸展により内視鏡挿入・把持は困難であった。生検はGroup 5、tub2の診断で切除不能閉塞性横行結腸癌と診断した。ショートタイプダブルバルーン内視鏡を用いることで狭窄部までの到達、内視鏡保持は比較的容易であり、ガイドワイヤーを通過させ腫瘍に対しHANAROSTENT Naturfitを留置した。ステント留置翌日から食事を再開し、3日後に一時退院した。16日後に開腹横行結腸部分切除吻合術、両側卵巣切除、腹膜播種切除術を施行した。術後47日後から全身化学療法を施行し、5ヵ月経過し生存中である。

J-GLOBAL

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J04450&link_issn=&doc_id=20201225120033&doc_link_id=%2Fdw9poden%2F2020%2F009701%2F046%2F0125-0127%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdw9poden%2F2020%2F009701%2F046%2F0125-0127%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床栄養代謝学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1002/jso.26245

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jso.26245

記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

本邦で2012年に保険収載された大腸ステントは,閉塞性大腸癌治療に大きなparadigm shiftを起している.術前減圧目的の大腸ステント留置(bridge to surgery:BTS)は,良好な短期成績が報告されている一方,長期予後への懸念から,欧州消化器内視鏡学会(ESGE)のガイドラインにおいて否定的な推奨であった.しかし,近年,長期予後の安全性を示唆する報告が多数出され,2020年のupdate版では一転,推奨する形となった.今後,さらに広がることが予想されるBTS治療戦略であるが,長期予後のみならず,手術までの至適待機期間,ステントの種類,右側結腸癌での効果,経肛門的減圧管との比較など,解決すべきclinical questionは多い.本稿では,BTSのこれまでの治療成績を概説し,今後の展望も含めて述べる.(著者抄録)

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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掲載種別：研究論文（学術雑誌）  

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. BACKGROUND/AIM: The efficacy of aflibercept plus 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) therapy has been demonstrated in patients with metastatic colorectal cancer (mCRC) in global and Japanese clinical trials. However, a practical biomarker to predict its efficacy is lacking. PATIENTS AND METHODS: This was a single-institution retrospective study of 21 patients with mCRC consecutively treated with aflibercept plus FOLFIRI from March 2018 to July 2019. We investigated the association and predictive value of pretreatment blood inflammation and immune-based scores, including the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio, using their median values as cut-offs, in regard to disease control (DC), progression-free (PFS), and overall (OS) survival. RESULTS: The number of patients in each treatment line of aflibercept was as follows: Second, 14 (66.7%); third, four (19.0%); fourth, two (9.5%); eighth, one (4.8%). The median number of aflibercept treatment courses was seven (range=2-17). The median follow-up time was 391 days. In univariate analysis, patients with DC had a significantly lower PLR than those without DC. Only the PLR was significantly negatively associated with PFS, but not with OS. Multivariate analysis showed a significantly poor prognostic impact of a high PLR on PFS (hazard ratio=10.28; p=0.003). CONCLUSION: A low pretreatment PLR might be a predictor of aflibercept efficacy in patients with mCRC and may be clinically useful for selecting patient responders.

DOI： 10.21873/invivo.12086

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2020, Japan Society of Clinical Oncology. Oncogenic RAS mutations are negative biomarkers of response to epidermal growth factor receptor (EGFR) blockade. RAS mutations are usually detected in biopsies of primary colorectal tumors. However, the genomic profiles of primary tumors and metastases are not always concordant, and chemotherapeutic agents can alter the tumor molecular landscape. Cell-free DNA (cfDNA) is a novel tool to detect molecular heterogeneity. This study evaluated the clinical utility of cfDNA to predict primary or secondary resistance to EGFR blockade in patients with metastatic colorectal cancer. Thirty metastatic colorectal cancer patients without RAS and BRAF mutations were prospectively enrolled and treated with cytotoxic agents and EGFR blockade as first-line therapy. cfDNA was analyzed for the presence of RAS, BRAF, and EGFR (S492R) point mutations before initiating chemotherapy and every 2 months during chemotherapy. The analysis was performed in 223 plasma samples from all 30 patients. Of the 30 patients, five had RAS mutations in their cfDNA before starting chemotherapy and did not respond. Twenty-four of the remaining 25 patients without cfDNA RAS mutations had a response. Twenty of the 24 responders developed secondary resistance and cfDNA RAS mutations were found in 17 of the 20. cfDNA BRAF mutations were found in seven, and EGFR mutations were found in eight of the 20 patients. Emerging RAS, BRAF, and EGFR mutations occurred in patients with primary and secondary resistance to EGFR blockade. The detection of these mutations in cfDNA is a promising approach to predict treatment response and secondary resistance.

DOI： 10.1007/s10147-020-01691-0

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：金原出版(株)  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00620&link_issn=&doc_id=20200730220017&doc_link_id=10.18888%2Fop.0000001786&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fop.0000001786&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2020 International Institute of Anticancer Research. All rights reserved. Background/Aim: Although weekly administration of cetuximab is the standard regimen in patients with metastatic colorectal cancer (mCRC), the efficacy and safety of a biweekly regimen is a pending issue. We conducted this meta-analysis to compare the efficacy and safety of a biweekly vs. a weekly regimen of cetuximab in the treatment of mCRC. Patients and Methods: We conducted a comprehensive electronic literature search up to January 2020 to identify studies directly comparing the efficacy and safety of biweekly cetuximab administration and conventional weekly administration in patients with mCRC. We then performed a meta-analysis using random-effects models to calculate risk ratios and mean differences with 95% confidence intervals. Results: Four studies with a total of 381 patients were included in this meta-analysis. The meta-analysis showed that biweekly administration conferred equivalent efficacy, including objective response rate, disease-control rate, progression-free survival, and overall survival, as well as safety, including skin toxicity, gastrointestinal toxicity, and hematologic toxicity, compared with weekly administration in patients with mCRC. Conclusion: Results from this meta-analysis support the administration of biweekly instead of weekly cetuximab, which is beneficial for both patients and health resources.

DOI： 10.2196/10.21873/anticanres.14333

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記述言語：日本語   出版者・発行元：(株)へるす出版  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: A transomental hernia is defined as bowel invagination into an abnormal hiatus of the omentum. It is a rare type of internal hernia that is sometimes lethal. We herein report a case of a transomental hernia developing shortly after laparoscopic sigmoidectomy. CASE PRESENTATION: A 71-year-old man underwent laparoscopic sigmoidectomy. He was admitted to our hospital because of abdominal pain and nausea on postoperative day 12. Laboratory investigation showed increased levels of inflammatory markers. Abdominal computed tomography showed a closed loop and mesenteric edema of the small intestine with ascites. We performed an emergency operation under the diagnosis of strangulated bowel obstruction. Operative findings showed internal herniation of strangulated ileal loops through a defect of the omentum with hemorrhagic ascites. The incarcerated small bowel was resected and reconstructed because the ischemic change was irreversible after the reduction. We partially resected the omentum that had formed the defect. The patient's postoperative progress was good, and he was discharged on postoperative day 8. CONCLUSIONS: Almost all internal hernias after intestinal surgery are mesenteric hernias; however, we should bear in mind that the more lethal transomental hernia is also possible. Therefore, immediate surgical exploration should be performed in a timely manner for internal hernias, especially for patients with early-onset symptoms after laparoscopic intestinal surgery.

DOI： 10.1186/s40792-020-0783-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. The incidence of rare neuroendocrine tumors (NET) is rapidly increasing. Neuroendocrine carcinoma (NEC) is a NET with poorly differentiated histological features, high proliferative properties and associated poor prognoses. As these carcinomas are so rare and, thus, affect only a small number of patients allowing for few cell lines to be derived from patient biopsies, the histological, immunohistochemical, and clinical characteristics associated with colorectal NEC and NEC in other organs have yet to be clearly defined. Herein, we describe the establishment of a novel NEC cell line (SS-2) derived from a tumor resection of the ascending colon from a 59-year-old Japanese woman. The histological, electron microscopic and immunohistochemical features of chromogranin A (CgA) as well as confirmation of synaptophysin positivity in this tumor were typical of those commonly observed in surgically resected colorectal NEC. Further, the Ki-67 labeling index of the resected tumor was >20% and, thus, the tumor was diagnosed as an NEC of the ascending colon. The SS-2 cell line maintained characteristic features to those of the resected tumor, which were further retained following implantation into subcutaneous tissues of nude mice. Additionally, when SS-2 cells were seeded into ultra-low attachment plates, they formed spheres that expressed higher levels of the cancer stem cell (CSC) marker CD133 compared to SS-2 cells cultured under adherent conditions. SS-2 cells may, therefore, contribute to the current knowledge on midgut NEC biological function while providing a novel platform for examining the effects of colorectal NEC drugs, including CSC.

DOI： 10.1111/cas.14221

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Ovarian metastasis of colorectal cancer is associated with poor prognosis. Recent advances in chemotherapy may improve this prognosis. In this retrospective study, we evaluated indicators of poor prognosis for ovarian metastasis of colorectal cancer. Twenty patients, who were diagnosed with ovarian metastasis of colorectal cancer from April 2000 to December 2017, were enrolled. Oophorectomy was performed in 18 of the 20 patients. Postoperative chemotherapy was provided to 13 patients, and molecular targeting agents were administered in 5 patients. Metastases to other organs besides the ovaries, premenopausal condition, undifferentiated histologic type of the primary tumor, and no resection of ovarian metastases were identified as indicators of poor prognosis. The 3-year survival rate was 15%, and the 5-year survival rate was 0%. In conclusion, oophorectomy can improve the prognosis of patients with ovarian metastasis of colorectal cancer. However, prognostic improvement due to molecular target agents was not shown.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Chemoradiotherapy(CRT)for locally recurrent rectal cancer can shrink the tumor and permit R0 resection; however, its effectiveness and safety have not been established. Herein, we report a case of a 60s man with locally recurrent rectal cancer invading the surrounding organs who was administered CRT followed by R0 laparoscopic-assisted abdominoperineal resection( APR). Local recurrence was detected 11 months after laparoscopic-assisted low anterior resection(pT3N0M0, pStage Ⅱ). After tumor shrinkage by CRT(capecitabine 3,000mg/day plus 45 Gy/25 Fr), laparoscopic-assisted APR was performed. The pathological findings showed a pathological complete response(pCR). The patient had not experienced recurrent disease at 6 months after the second surgery. CRT may improve the prognosis of patients with locally recurrent rectal cancer, especially those with possibly unresectable tumors.

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. We recruited 56 colorectal cancer patients and compared the mutational spectrum of tumor tissue DNA, circulating cell-free DNA (ccfDNA) and circulating tumor cell (CTC) DNA (ctcDNA) to evaluate the potential of liquid biopsy to detect heterogeneity of cancer. Tumor tissue DNA, ccfDNA, and ctcDNA were extracted from each patient and analyzed using next-generation sequencing (NGS) and digital PCR. To maximize yields of CTC, three antibodies were used in the capture process. From 34 untreated patients, 53 mutations were detected in tumor tissue DNA using NGS. Forty-seven mutations were detected in ccfDNA, including 20 not detected in tissues. Sixteen mutations were detected in ctcDNA, including five not detected in tissues. In 12 patients (35.3%), mutations not found in tumor tissues were detected by liquid biopsy: nine (26.5%) in ccfDNA only and three (8.8%) in ctcDNA only. Combination analysis of the two liquid biopsy samples increased the sensitivity to detect heterogeneity. From 22 stage IV patients with RAS mutations in their primary tumors, RAS mutations were detected in 14 (63.6%) ccfDNA and in eight (36.4%) ctcDNA using digital PCR. Mutations not detected in primary tumors can be identified in ccfDNA and in ctcDNA, indicating the potential of liquid biopsy in complementing gene analysis. Combination analysis improves sensitivity. Sensitivity to detect cancer-specific mutations is higher in ccfDNA compared with ctcDNA.

DOI： 10.1111/cas.14186

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(株)南江堂  

＜文献概要＞2012年の保険収載以降,閉塞性大腸癌に対する大腸ステント治療が急速に広まっている.緩和治療目的の留置は,人工肛門を伴う緊急手術の回避などのメリットからガイドラインでも推奨されている.術前減圧(bridge to surgery:BTS)においては,良好な短期成績が数多く報告されている一方,長期予後への影響など未解決な問題がある.現在,BTSの腫瘍学的安全性を検証すべく本邦において多施設共同ランダム化試験(COBRA Trial)が進行中である.本稿では,安全な大腸ステント留置のためのコツ,特に直腸癌に対するステンティング,これまでの治療成績を概説し,今後の展望も含めて述べる.

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00393&link_issn=&doc_id=20190902150010&doc_link_id=10.15106%2Fj_geka81_1064&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_geka81_1064&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

© 2019 by American Society of Clinical Oncology. PURPOSE The International Union Against Cancer highlighted tumor budding as a tumor-related prognostic factor. International assessment criteria for tumor budding were recently defined by the 2016 International Tumor Budding Consensus Conference (ITBCC2016). This study aimed to clarify the prognostic and predictive values of tumor budding in a randomized controlled trial evaluating the superiority of adjuvant chemotherapy with oral tegafur-uracil over surgery alone for stage II colon cancer (SACURA trial; ClinicalTrials.gov identifier: NCT00392899). PATIENTS AND METHODS Between 2006 and 2010, we enrolled 991 patients from 123 institutions with stage II colon cancer. Tumor budding was diagnosed by central review on the basis of the criteria adopted in the ITBCC2016. We prospectively recorded all clinical and pathologic data, including the budding grade, and performed prognostic analyses after 5 years of completing the patients’ registration. RESULTS Of 991 tumors, 376, 331, and 284 were classified as BD1, BD2, and BD3, respectively; the 5-year relapse-free survival (RFS) rate was 90.9%, 85.1%, and 74.4%, respectively (P, .001), and ranged widely in T4 tumors (86.6% to 53.3%). The budding grade significantly correlated with recurrence in the liver, lungs, lymph nodes, and peritoneum (P, .001 to .01). Multivariable analysis revealed that budding and T stage exerted an independent impact on RFS, and on the basis of the Harrell concordance index, these two factors substantially contributed to the improvement of the Cox model for predicting RFS. Both the BD2 and BD3 groups demonstrated greater improvement in the 5-year recurrence rate in the adjuvant chemotherapy group than the surgery-alone group by approximately 5%, but the difference was statistically nonsignificant. CONCLUSION Tumor budding grade on the basis of the ITBCC2016 criteria should be routinely evaluated in pathologic practice and could improve the benefit of adjuvant chemotherapy for stage II colon cancer.

DOI： 10.1200/JCO.18.02059

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：日本手術医学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology Introduction: Most patients with colorectal liver metastases, who undergo hepatectomy, experience recurrence. Although the prognosis is poorer for patients with early recurrence (within 6 months after hepatectomy) compared with later recurrence, no biomarker has been identified to predict early recurrence. Minimal residual disease (MRD) in patients who undergo curative surgery is the main cause of recurrence. In cancer patients, long fragment cell-free DNA is detected, and the presence of long fragments of cell-free DNA after surgery can indicate MRD. In this study, we developed a novel biomarker to predict early recurrence of colorectal liver metastases using cell-free DNA. Materials and methods: Forty-one patients with colorectal liver metastases were enrolled. Peripheral blood samples were collected before and at 1 month after hepatectomy. Cell-free DNA was extracted from 1 ml plasma, and the long fragment/β-globin ratio, which can indicate MRD, was measured by real-time polymerase chain reaction. Results: Three of 21 patients (14.3%) with decreases in the long cell-free DNA fragment/β-globin ratio after hepatectomy developed early recurrence compared with twelve of 20 patients (60.0%) with an increased ratio (P = 0.002). Patients with a decreased long fragment/β-globin ratio after hepatectomy had significantly longer recurrence-free survival compared with patients with an increased ratio (366 vs 102 days, P < 0.001). Conclusion: The cell-free DNA long fragment/β-globin ratio may serve as an effective biomarker of early recurrence in patients with colorectal liver metastases, who undergo hepatectomy.

DOI： 10.1016/j.ejso.2019.08.010

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© The Japan Society for Analytical Chemistry. Membrane dynamic structures such as filopodia, lamellipodia, and ruffles have important cellular functions in phagocytosis and cell motility, and in pathological states, such as cancer metastasis. Phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ) is a crucial lipid that regulates PIP 3 dynamics. Investigations of how PIP 3 is involved in these functions have mainly relied on pharmacological interventions, and therefore have not generated detailed spatiotemporal information concerning membrane dynamics upon PIP 3 production. In the present study, we applied an optogenetic approach using the CRY2- CIBN system. Using this system, we revealed that local PIP 3 generation induced directional cell motility and membrane ruffles in COS7 cells. Furthermore, combined with structured illumination microscopy (SIM), membrane dynamics were investigated with high spatial resolution. We observed PIP 3 -induced apical ruffles and unique actin fiber behavior in that a single actin fiber protruded from the plasma membrane was taken up into the plasma membrane without depolymerization. This system has the potential to investigate other high-level cell motility and dynamic behaviors, such as cancer cell invasion and wound healing with high spatiotemporal resolution, and could provide new insights of biological sciences for membrane dynamics.

DOI： 10.2116/analsci.18SDP06

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2018 The Author(s). The infiltration and proliferation of cancer cells in the secondary organs are of great interest, since they contribute to cancer metastasis. However, cancer cell dynamics in the secondary organs have not been elucidated at single-cell resolution. In the present study, we established an in vivo model using two-photon microscopy to observe how infiltrating cancer cells form assemblages from single T-cell lymphomas, EL4 cells, in the secondary organs. Using this model, after inoculation of EL4 cells in mice, we discovered that single EL4 cells infiltrated into the colon. In the early stage, sporadic elongated EL4 cells became lodged in small blood vessels. Real-time imaging revealed that, whereas more than 70% of EL4 cells did not move during a 1-hour observation, other EL4 cells irregularly moved even in small vessels and dynamically changed shape upon interacting with other cells. In the late stages, EL4 cells formed small nodules composed of several EL4 cells in blood vessels as well as crypts, suggesting the existence of diverse mechanisms of nodule formation. The present in vivo imaging system is instrumental to dissect cancer cell dynamics during metastasis in other organs at the single-cell level.

DOI： 10.1038/s41598-018-22399-2

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

© 2018 S. Karger AG, Basel. Background: Liquid biopsy is a collective term that refers to the analysis of tumor-derived biomarkers isolated from biological fluids of cancer patients. Recently, many authors reported the usefulness of liquid biopsy for the management of malignancy. Summary and Key Messages: The peripheral blood of cancer patients is a pool of cells and/or cell products derived from the primary or metastatic tumor, including circulating tumor cells (CTCs), circulating free (cf) DNA or RNA, and exosomes containing proteins, nucleic acids, and lipids. CTCs are tumor cells that can be isolated from peripheral blood. Free circulating DNA with a tumor-specific mutation is called circulating tumor DNA (ctDNA). Some patients who undergo curative surgery experience recurrent disease, which can be due to the presence of minimal residual disease (MRD). Thus, MRD indicates a high risk of relapse. Detection of ctDNA or CTC after surgery is a direct proof of MRD. Molecular volume (e.g., the number of CTCs and level of ctDNA) might reflect tumor burden, thus high molecular volume may indicate poor prognosis. The most notable application of liquid biopsy in cancer is to understand spatial and temporal heterogeneities. Heterogeneity is one of the causes of refractoriness and hampers prediction of chemotherapeutic effect. Emerging mutations that are not present in primary tumors but are found in their metastases can be detected in ctDNA. Some colorectal cancer patients with wild-type RAS do not respond to epidermal growth factor receptor blockade. In a subset of these patients, RAS mutation is detected in ctDNA, indicating heterogeneity.

DOI： 10.1159/000494411

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2018 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd. Primary small intestinal volvulus is defined as torsion in the absence of congenital malrotation, band, or postoperative adhesions. Its occurrence as an early postoperative complication is rare. A 40-year-old woman presented with rectal prolapse, and laparoscopic rectopexy was uneventfully performed. She could not have food on the day after surgery. She started oral intake on postoperative day 3 but developed abdominal pain after the meal. Contrast-enhanced CT revealed torsion of the small intestinal mesentery. An emergent laparotomy showed small intestinal volvulus, without congenital malformation or intestinal adhesions. We diagnosed it as primary small intestinal volvulus. The strangulated intestine was resected, and reconstruction was performed. The patient recovered uneventfully after the second surgery. To the best of our knowledge, this is the first report of primary small intestinal volvulus occurring after rectopexy for rectal prolapse. Primary small intestinal volvulus could be a postoperative complication after laparoscopy.

DOI： 10.1111/ases.12462

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Nature  

© 2018 The Author(s). Background: Anastomotic leakage (AL) is the most serious and common complication of surgery for rectal cancer, and associated risk factors remain unknown despite developments in laparoscopic surgery. The present study aimed to determine risk factors for AL after laparoscopic anterior resection (AR) of rectal cancer. Methods: This retrospective cohort study extracted information from a prospective database of all consecutive colorectal resections that proceeded at Nippon Medical School Hospital between January 2011 and December 2015 (n = 865). We identified 154 patients with rectal cancer treated by elective laparoscopic AR with anastomosis using primary double-stapling. Clinical variables and comorbidity, habits, and surgery-related variables were assessed by univariate and multivariate analyses to determine preoperative risk factors for clinical AL. Results: The overall rate of clinical AL was 11.7% (18 of 154 patients), and 5 (27.8%) of 18 patients required revised laparotomy. Data from males were analyzed because AL occurred only in males. Univariate analysis of male patients (n = 100) significantly associated preoperative creatinine values (p = 0.03) and a history of ischemic heart disease (IHD) (p = 0.012) with AL. The frequency of AL tended to increase (p = 0.06) when patients had low AR (p = 0.06) and transanal drainage. Having AL significantly prolonged hospital stays compared with patients without leakage (36.2 vs. 11.1 days; p < 0.01). Multivariate analysis identified a history of IHD (odds ratio [OR], 4.73; 95% confidence interval [CI], 1.27-17.5; p = 0.025] as an independent risk factor for AL. Conclusions: Male sex and a history of IHD are possible risk factors for AL after elective laparoscopic rectal cancer surgery.

DOI： 10.1186/s12876-018-0846-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology Background: Detection of gene mutations is important for planning molecular targeted therapy. Although most gene mutations are concordant between primary colon cancers and their liver metastases, new mutations can emerge in metastases. The liquid biopsy is a newly developed, gene analytic method to detect mutations in metastatic tumors. In this prospective study, we evaluated the applicability of liquid biopsies in the detection of mutations in primary and metastatic tumors. Methods: We included 22 patients with liver metastases from colorectal cancer and extracted DNA from primary colorectal tumors, metastatic liver tumors, and peripheral blood (liquid biopsy). Next-generation sequencing (NGS) and digital PCR were performed to detect mutations in these three sample types. Results: We found a total of 36 different mutations in samples from primary tumors, liver metastases, and liquid biopsies using NGS. Twenty-eight of these mutations were found in all three types of samples, whereas liquid biopsy did not identify four mutations that had been found in both primary tumors and liver metastases, but did identify four mutations that were found in liver tumors but not in primary tumors. The sensitivity of liquid biopsies for detecting mutations in liver metastases was 64% (23/36) using NGS and 89% (32/36, P = 0.02) using dPCR. The specificities of NGS and dPCR were 100% (23/23) and 100% (32/32), respectively. Conclusions: Emerging mutations, which are not found in primary tumors, can be detected in their metastases and liquid biopsies.

DOI： 10.1016/j.ejso.2018.01.224

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掲載種別：研究論文（学術雑誌）  

© 2018 Universidade Federal Rural do Semi-Arido. All Rights Reserved. Background/Aim: The combination of oxaliplatin, leucovorin and fluorouracil (FOLFOX) has been established as postoperative adjuvant chemotherapy for stage III colon cancer. However, the safety and efficacy of neoadjuvant FOLFOX in patients with rectal cancer are still controversial. This prospective pilot study aimed to evaluate the feasibility of neoadjuvant FOLFOX therapy without radiation for baseline resectable rectal cancer (RC). Patients and Methods: The study included 30 patients with clinical stage II/III RC between February 2012 and December 2015. The patients were treated with six cycles of FOLFOX followed by elective surgery. The primary endpoint was the R0 resection rate. The secondary endpoints were the scheduled treatment completion rate, adverse events, pathological response and the disease-free survival (DFS) rate. Results: All the patients underwent elective R0 resection after neoadjuvant FOLFOX therapy. The completion rate of the 6-cycle regimen was 93.3% (28/30 patients). Grade 3-4 adverse events occurred in seven patients (23.3%). Pathological complete response was noted in two patients (6.7%). The 3-year DFS rate was 77.5% (95% confidence interval, 61.4%-93.7%). Conclusion: Neoadjuvant FOLFOX therapy without radiation is a feasible therapeutic strategy for baseline resectable RC.

DOI： 10.21873/invivo.11332

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2017, Society of Surgical Oncology. Background: The self-expanding metallic stent (SEMS) provides effective decompression for patients with malignant large bowel obstruction (MLBO); however, mechanical damage to malignant cells from insertion may negatively affect prognosis, similar to surgical manipulation, and its oncological safety is unclear. We examined mechanical damage from SEMS placement using circulating cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA). Methods: Between 1 November 2014 and 30 June 2017, 35 MLBO patients were analyzed, comprising 25 SEMS patients and 10 transanal decompression tube (TDT) patients (control). Blood samples were collected before and after decompression on days 0, 1, 3, and 7. cfDNA, ctDNA, white blood cells, C-reactive protein, and lactate dehydrogenase were analyzed. Results: The clinical success rates of SEMS and TDT were 88 and 90%, respectively (p = 1.0). The cfDNA concentration on day 7 was significantly higher in the SEMS group than in the TDT group (992 vs. 308 ng/mL; p = 0.005). A significant increase in ctDNA was observed in the SEMS group compared with the TDT group (83% vs. 22%; p = 0.002). The cfDNA concentration showed strong positive correlations with ctDNA and lactate dehydrogenase (R 2  = 0.838 and 0.593, respectively), and a weak positive correlation with C-reactive protein (R 2  = 0.263). Conclusions: Despite equivalent clinical success rates, SEMS placement increased plasma levels of cfDNA and ctDNA by tumor manipulation, but TDT did not. Colonic stenting showed oncological risk in terms of molecular analysis.

DOI： 10.1245/s10434-017-6300-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© Shinji et al. Purpose: Diagnostic markers for recurrence of colorectal cancer have not been established. The aim of the present study was to identify new diagnostic markers for recurrence after curative surgery of stage II colon cancer. Materials and Methods: In this study, the prognostic values of the preoperative lymphocyte count and the post/preoperative lymphocyte count ratio (PPLR) were evaluated in 142 patients with localized colon cancer treated with surgery at a single medical center. The associations of patient demographics, blood chemistry, and serum biochemical indices with recurrence-free survival (RFS) and cancer-specific survival (CSS) were examined by univariate and multivariate analyses. Results: Receiver operating characteristic (ROC) curve analysis showed that the optimal cut-off values of the lymphocyte count and PPLR were, respectively, 1555.2/ μl and 1.151 for RFS. On univariate analysis, tumor depth of invasion, carbohydrate antigen 19-9 (CA19-9), and preoperative low lymphocyte count (≤1555.2/μl) were all correlated with poorer RFS (p < 0.05). On multivariate analysis, T4, low lymphocyte count, and low PPLR were independent predictors of poor RFS. Furthermore, the patients were categorized into four categories based on preoperative lymphocyte count high/low and PPLR high/low. Patients with a low preoperative lymphocyte count and low PPLR had the poorest RFS and CSS compared to the other patients. Conclusion: The combination of the preoperative lymphocyte count and the PPLR appears to be a potential marker for predicting recurrence of stage II colon cancer.

DOI： 10.18632/oncotarget.23510

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

BACKGROUND AND OBJECTIVES: Oxaliplatin can cause hepatic sinusoidal obstruction syndrome (SOS). SOS can cause chemotherapy-related adverse effects or morbidity after liver resection. Conventionally, SOS is diagnosed using liver biopsy. Recently, it was reported that increased splenic volume (SV) can be used to detect SOS. In this study, we evaluated the changes in SV during adjuvant chemotherapy. METHODS: We enrolled 103 consecutive patients with stage III and high-risk stage II colorectal cancer treated with mFOLFOX6 (n = 37) or oral fluorouracil and leucovorin (n = 66) after curative surgery. SV was measured three times; pre-operatively, after chemotherapy, and 1 year after chemotherapy. RESULTS: SV was higher after mFOLFOX6 (median 135.89 mL) than pre-operatively (105.75 mL) (P < 0.001); SV at 1-year after finishing mFOLFOX6 (114.16 mL) returned to the same level as before surgery (P = 0.0015). SV increased in 28 patients (75.7%) treated with mFOLFOX6 (95%CI, 61.8-89.5), but had not recovered in 12 of these cases (42.9%) 1 year after finishing treatment (95%CI, 17.3-47.5). In contrast, oral fluorouracil and leucovorin did not change SV. CONCLUSIONS: SV increased after adjuvant mFOLFOX6, and had not recovered in almost half of cases 1-year after finishing chemotherapy. This increase may indicate continuous SOS, which can adversely affect treatment after recurrence.

DOI： 10.1002/jso.24756

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

The patient was a 70-year-old woman who was diagnosed with obstructive transverse colon cancer suspected of invading the abdominal wall by abdominal CT imaging. Since the preoperative electrocardiogram showed an ischemic change, echocardiography and coronary angiography were performed. We diagnosed chronic heart failure and angina pectoris because echocardiography showed low cardiac function(left ventricular ejection fraction; LVEF 37%)and coronary angiography indicated triple-vessel disease. We firstly performed coronary artery bypass graft surgery following self-expanding metallic stent placement as a bridge to surgery(BTS), because we judged this patient as a perioperative high-risk case. After improvement of cardiac function(LVEF 49%), expanded right hemicolectomy with partial resection of abdominal wall could be performed without perioperative complications. Colonic stenting as a BTS allowed us to treat comorbidities properly, and perform a radical surgery safely for such a high-risk patient.

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

PURPOSE: Daikenchuto (DKT) has a stimulant effect on intestinal motility and reportedly has a positive effect on postoperative intestinal motility in patients with sigmoid colon cancer. In this study, we investigated the effects of DKT in patients with right-side colon cancer. METHODS: This retrospective study included 88 patients with right-side colon cancer. We orally administered 7.5 g of DKT in the DKT group and did not administer any DKT to patients in the no-DKT group. All patients ingested radiopaque markers 2 h before surgery, which were used to assess intestinal motility. The postoperative intestinal motility was radiologically assessed by counting the numbers of residual markers in the large and small intestines. RESULTS: The DKT and no-DKT groups showed no marked differences in the total number of residual markers or number of residual markers in the small intestine. However, in the elderly subgroup, the total number of residual markers in the DKT group was significantly less than in the no-DKT group. CONCLUSION: Although DKT had some small effect on the postoperative intestinal motility for most patients, it may have positive effects in elderly patients.

DOI： 10.1007/s00595-016-1449-7

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DOI： 10.1158/1538-7445.AM2017-5682

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

INTRODUCTION: Single-port laparoscopic surgery has some technical limitations with respect to control of the forceps inserted through the single-access site, which results in increased internal collisions due to coaxial alignment of the instruments, as well as and decreased range of motion and visualization. To overcome these limitations, we employ a "modified marionette technique" as a way to carry out laparoscopic colorectal surgery. Materials and Surgical Technique: The procedures for the modified marionette technique are performed as follows: An Internal Organ Retractor (IOR)™ and an atraumatic clip designed to firmly grasp tissue, with 1-0 nylon thread, are inserted through a 12-mm trocar and secured in place where adequate visualization and traction for cutting with a radio knife is required. A looped 1-0 nylon thread put through an 18-gauge injection needle is pierced through the abdominal wall, the looped nylon extruded, and the nylon attached to the IOR is pulled out by threading the looped nylon thread. This allows for adequate traction from outside the body through the abdominal wall and appropriate placing adjustments. CONCLUSION: The "modified marionette technique" using IOR introduced here is an easy, economical, effective and safe traction technique for colorectal surgeries. This technique will be a useful tool for performing both reduced port and multiport laparoscopic colorectal surgeries.

DOI： 10.1272/jnms.84.49

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Meckel's diverticulum may sometimes present as an intraluminal polypoid mass causing small bowel obstruction; however, gastrointestinal bleeding due to Meckel's diverticulum with a polypoid lesion is rare. A 14-year-old girl presented with tarry stool and syncope in our hospital. Laboratory examination showed iron-deficiency anemia with a low hemoglobin level of 5.8 g/dl. The bleeding site was detected by neither upper gastrointestinal endoscopy nor colonoscopy. Transanal double-balloon enteroscopy showed a diverticulum with an ulceration at a site approximately 50 cm from the ileocecal valve and a polypoid lesion inside of the diverticulum. Histopathological examination of a polypoid lesion revealed an ectopic gastric mucosa of the fundic type. Furthermore, technetium-99m pertechnetate scintigraphy showed a hot spot in her lower right abdomen. On the basis of these findings, she was diagnosed as having hemorrhagic Meckel's diverticulum. Single-incision laparoscopy-assisted segmental bowel resection of the ileum was performed. The patient recovered well, and she was discharged from the hospital on postoperative day 7. She was doing well 6 months later without evidence of reoccurrence. In this report, we describe a case of Meckel's diverticulum with a polypoid lesion; hemorrhage may have occurred owing to the ulceration of the ileal mucosa with which the polypoid lesion directly came in contact. We consider this case to be of interest to gain insight into the site and mechanism of ulceration associated with Meckel's diverticulum.

DOI： 10.1186/s40792-016-0252-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In this study, we evaluated the clinical utility of detecting KRAS mutations in circulating cell-free (ccf)DNA of metastatic colorectal cancer patients. We prospectively recruited 94 metastatic colorectal cancer patients. Circulating cell-free DNA was extracted from plasma samples and analyzed for the presence of seven KRAS point mutations. Using the Invader Plus assay with peptide nucleic acid clamping method and digital PCR, KRAS mutations were detected in the ccfDNA in 35 of 39 patients previously determined to have primary tumors containing KRAS mutations using the Luminex method, and in 5 of 55 patients with tumors containing wild-type KRAS. Curative resection was undertaken in 7 of 34 patients with primary and ccfDNA KRAS mutations, resulting in the disappearance of the mutation from the cell-free DNA in five of seven patients. Three of these patients had tumor recurrence and KRAS mutations in their ccfDNA reappeared. Epidermal growth factor receptor blockade was administered to 24 of the KRAS tumor wild-type patients. Of the 24 patients with wild-type KRAS in their primary tumors, three patients had KRAS mutations in their ccfDNA and did not respond to treatment with epidermal growth factor receptor (EGFR) blockade. We also detected a new KRAS mutation in five patients during chemotherapy with EGFR blockade, before disease progression was detectable with imaging. The detection of KRAS mutations in ccfDNA is an attractive approach for predicting both treatment response and acquired resistance to EGFR blockade, and for detecting disease recurrence.

DOI： 10.1111/cas.12959

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記述言語：英語  

We report a case involving a patient with colon cancer who underwent 5-fluorouracil (5-FU) rechallenge and maintained an oncological effect for a long period after encephalopathy caused by 5-FU. Our patient was a 61-year-old man who was diagnosed with adenocarcinoma of the ascending colon with direct liver invasion. He underwent right hemicolectomy with partial liver resection followed by adjuvant chemotherapy with modified FOLFOX6 (mFOLFOX6). Ten months after completion of mFOLFOX6, his carcinoembryonic antigen concentration increased, and ascites was revealed by computed tomography 2 months later. We started FOLFIRI, and he was taken to our hospital by ambulance because of loss of consciousness 10 days after the start of the third cycle of FOLFIRI. Laboratory investigations showed hyperammonemia and elevations of his serum creatinine and blood urea nitrogen concentrations. Brain computed tomography demonstrated no abnormalities. Transfusion of 1500 ml of crystalloid fluid resulted in gradual recovery over the next 12 h. His ammonia concentration decreased to a normal level. Twelve days after onset of the encephalopathy, we restarted FOLFIRI, but the dose of continuous 5-FU was decreased by 20 %. The patient's carcinoembryonic antigen concentration considerably decreased from 376.5 to 19.9 ng/ml, and his ascites disappeared. Nineteen months after the resumption of FOLFIRI, he underwent 34 courses of FOLFIRI and maintained stable disease. The encephalopathy did not recur.

DOI： 10.1007/s13691-016-0243-0

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We report a case of jejunal perforation related to cholesterol crystal embolism (CCE) in a woman in her seventies. The jejunum was partially resected;histological examination of the resected tissue revealed that the perforation was caused by CCE. On postoperative day 12, computed tomography (CT) showed free air in the abdomen. We then performed a second operation to alleviate the anastomotic leakage. Subsequently, 26 days after the second surgery, CT again showed free air in the abdomen. A third operation was performed, and multiple perforations of the jejunum were detected. She died of multiple organ failure 43 days after the first surgery. The prognosis of CCE with gastrointestinal perforation is reported to beextremely poor, and there is a high rate of anastomotic leakage. Partial resection of the intestine and ileostomy might be useful for removing the intestinal perforations caused by a CCE. Steroid administration should be continued, however, because discontinuation may worsen the problem.

DOI： 10.11405/nisshoshi.113.804

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記述言語：英語  

BACKGROUND: RNA analysis of surgical specimens is one of the most useful methods for exploring biomarkers of advanced cancer. The most readily available source for RNA is formalin-fixed, paraffin-embedded (FFPE) specimens, but RNA isolated from FFPE tissue is of limited use. The PAXgene Tissue (PAX) system is a formalin-free system designed to improve the quality of molecular analysis without diminishing the quality of histopathological analysis. In this human colorectal cancer tissue study, we aimed to evaluate whether surgical specimens fixed with PAX can preserve high-quality RNA in comparison with FFPE and fresh-frozen tissue specimens. METHODS: Ten consecutive advanced colorectal cancer patients undergoing colectomy were examined. Each specimen was processed in three ways: as frozen tissue, as PAX-fixed tissue, and as formalin-fixed tissue. RNA integrity numbers (RINs) were assessed using an Agilent Bioanalyzer. RNA transcript levels and stability were investigated by quantitative real-time PCR. We also evaluated the immunohistochemical intensity of Ki-67, CEA, and EGFR in the PAX samples. RESULTS: The average RINs of RNA extracted from frozen and PAX samples were significantly higher than those from FFPE samples (p < 0.001). The cycle threshold (Ct) values were similar in PAX and frozen samples, but significantly increased in FFPE samples (p < 0.001). Most of the ΔCt values in the PAX samples did not differ significantly from those in the matched frozen samples. On the other hand, most of the ΔCt values in the FFPE samples differed significantly from those in the matched frozen samples. The immunohistochemical intensity in the PAX samples was well preserved. CONCLUSIONS: The quality of RNA extracted from PAX samples may be slightly inferior to that from frozen samples, but is greatly superior to that from FFPE samples.

DOI： 10.1089/bio.2014.0101

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Skeletal mass depletion has been reported to be a prognostic factor for cancer patients. However, special and expensive devices are required to measure skeletal mass, and this is a major reason why skeletal mass is not used extensively for prognostic marker in clinical settings. We developed a new method to measure skeletal mass for use as a prognostic marker using CT images without special and expensive devices. In this study, we evaluated the usefulness of skeletal mass as measured by this new method as a prognostic marker for gastrointestinal cancer patients. METHOD: Patients who died from gastrointestinal cancer between March 2010 and October 2013 were included. We measured the right-sided maximum psoas muscle cross sectional area (MPCA) by using CT images before surgery and after the patients developed a terminal condition. The maximum psoas muscle cross sectional area ratio (MPCA-R) was defined as follows: MPCA-R=MPCA before surgery/MPCA after developing a terminal condition. We evaluated the correlation between MPCA-R and survival. RESULT: Fifty-nine patients were included. The median survival was 44 days, and MPCA-R was significantly correlated with survival (p=0.001). On receiver operating characteristic (ROC) analysis, the area under the curve (AUC) to predict 30-day and 90-day survival was 0.710 and 0.748, respectively. CONCLUSION: MPCA-R is a new and novel prognostic marker for gastrointestinal cancer patients in terminal condition.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Superior mesenteric artery (SMA) syndrome is an uncommon disease resulting from compression and partial obstruction of the third portion of the duodenum from the SMA. A 77-year-old man, who did not have a history of surgery, experienced repeated vomiting and developed abdominal distension. Abdominal CT showed a narrowed third portion of the duodenum, with a distended stomach and proximal duodenum. The patient was diagnosed as having SMA syndrome and was initially treated conservatively, but his condition did not improve. Single-incision laparoscopy-assisted duodenojejunostomy was performed. The patient recovered well and was discharged from hospital on postoperative day 8. Laparoscopic treatment is feasible for the treatment of SMA syndrome given its safety and minimal invasiveness. This is a report of the first case of single-incision laparoscopy-assisted duodenojejunostomy. This procedure is safer and less invasive than a conventional laparoscopic approach in a patient with SMA syndrome.

DOI： 10.1111/ases.12140

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Portal venous gas has traditionally been considered an indicator of a poor prognosis due to bowel necrosis. Portal venous gas has recently been detected in patients with various clinical conditions, such as Crohn's disease, chemotherapy, and blunt abdominal injury without bowel necrosis. We herein report the first case of a patient with rectal cancer in whom portal venous gas developed after low anterior resection without anastomotic leakage or bowel necrosis. A 66-year-old man who had undergone low anterior resection started having severe diarrhea the day after the operation. A fever was present for 2 days after the operation but resolved on postoperative day 3. The patient complained of abdominal pain 5 days postoperatively. Computed tomography showed portal venous gas. Emergency open laparotomy was performed, but only limited ascites fluid without leakage or bowel necrosis was found. We irrigated the abdominal cavity and performed an ileostomy with insertion of a drainage tube in the rectovesical pouch. Only serous ascites was discharged through the drainage tube. The portal venous gas disappeared 3 days after the second operation. The patient was discharged in good condition 21 days after the first operation. Portal venous gas can develop after rectal surgery without anastomotic leakage or bowel necrosis. Conservative treatment is reasonable for patients without signs of bowel necrosis or panperitonitis. However, patients with portal venous gas must be carefully observed because portal venous gas may be life threatening.

DOI： 10.1272/jnms.82.202

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The ErbB family consists of four proteins including (EGFR)/ErbB1, ErbB2, ErbB3, and ErbB4, and plays a crucial role in the promotion of multiple tumorigenic processes. In addition to the traditional pathways of EGFR signaling, EGFR translocates to the nucleus and acts as a transcription factor in the proliferation of cancer cells. Heregulin is known as both an ErbB3 and an ErbB4 ligand. This study aimed to investigate the expression of heregulin and its relevant EGFR family members as well as their phosphorylated forms in human colorectal cancer (CRC) tissues and to determine the relationship between their expression and clinicopathological factors including patient prognosis. METHODS: We analyzed the effects of exogenous heregulin on ErbB2, ErbB3 and ErbB4 phosphorylation in Caco-2, DLD-1, and HCT 116 colon cancer cell lines by western blot analysis. We examined 155 surgical resections from colorectomy patients. Cellular localization of ErbB1-4, their phosphorylated forms and heregulin protein was analyzed in CRC surgical resections by immunohistochemical analysis. Immunohistochemical results were compared with clinicopathological factors and patient prognosis. RESULTS: Phosphorylated ErbB2 (pErbB2) and phosphorylated ErbB3 (pErbB3) were detected in both nuclear and cytosolic fractions of Caco-2 and DLD-1 cells stimulated by exogenous heregulin. Whereas, phosphorylated ErbB4 (pErbB4) was detected only in cytosolic fractions of HCT 116 cells stimulated by exogenous heregulin. Phosphorylated EGFR (pEGFR) immunoreactivity was observed in the cytoplasm and nuclei of cancer cells, whereas the pattern of EGFR staining was membranous and cytoplasmic. Subcellular localization of pErbB2, cytoplasmic, membranous, or nuclear, varied among cases. pErbB3 immunoreactivity was exclusively observed in the nuclei of cancer cells. pErbB4 immunoreactivity was observed in the cell membrane of cancer cells. Statistically, heregulin immunoreactivity correlated with pErbB2 and pErbB4 expression. In multivariate analysis for disease free survival, lymph node status, pErbB3 and pErbB4 expression retained independent prognostic significance. In multivariate analysis for overall survival, lymph node status, pEGFR and pErbB4 retained independent prognostic significance. CONCLUSIONS: ErbB2 and ErbB3 phosphorylated by heregulin localized in the nucleus of CRC cells. Phosphorylated ErbB1-4 and heregulin contribute to poorer patient prognosis in CRC. This heregulin-ErbB family member autocrine loop may be a candidate for targeted treatment of CRC.

DOI： 10.1186/1471-2407-14-863

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記述言語：英語  

BACKGROUND: The effects of mechanical bowel preparation (MBP) on morbidity (e.g., anastomotic leakage and surgical site infection) have been evaluated. Its effect on early recovery after surgery has drawn renewed attention, and its use is discouraged in the postsurgical management of enhanced recovery. However, most surgeons in Japan prefer polyethylene glycol (PEG) for MBP. We investigated the effect of MBP with PEG on postoperative intestinal motility. MATERIALS AND METHODS: We prospectively evaluated a consecutive series of 258 colon cancer patients who underwent colonic resection and primary anastomosis. We orally administered 2000 mL of PEG in the PEG group and did not administer PEG to patients in the no-PEG group. Postoperative gastrointestinal motility was assessed with radiopaque markers. All patients ingested radiopaque markers 2 h before surgery. Postoperative intestinal motility was radiologically assessed by counting the number of residual markers. Abdominal radiography was conducted on postoperative days 1, 3, and 5 to count residual markers in the large and small intestines. RESULTS: The total number of residual markers in the no-PEG group was less than that in the PEG group on day 5 (P < 0.01) but not on days 1 and 3. On all 3 d, the numbers of residual markers in the small intestine were significantly less in the no-PEG group than in the PEG group (P < 0.001). There were no differences in postoperative complications between the no-PEG and PEG groups. CONCLUSIONS: PEG can negatively affect postoperative intestinal motility, and MBP using PEG is unnecessary in elective colon cancer surgery.

DOI： 10.1016/j.jss.2014.03.001

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 62-year-old woman, with a past history of long-term non-steroidal anti-inflammatory drug use and gastric ulcer, was hospitalized for intestinal obstruction in April 2012. Two stenoses were identified in the ileum in association with small intestinal ulcers, and she underwent partial resection of the small intestine. Histologically, the two lesions were poorly differentiated adenocarcinomas; metastatic small intestinal cancer was suspected, but whole body examination revealed no other lesions. The final diagnosis was multiple primary small intestinal malignancies, necessitating additional resection of the small intestine in July. We report this case to raise awareness among physicians of the possibility of primary small intestinal cancer in patients with multiple small intestinal stenoses.

DOI： 10.11405/nisshoshi.111.1594

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記述言語：英語  

It has previously been reported that gene profiles in surgically-resected colorectal cancer tissues are altered over time possibly due to the different tissue-acquisition methods and sample extraction timing that were used. However, the changes that occur are still not clearly understood. In the present study, time-dependent changes in gene expression profiling in colorectal surgical specimens were analyzed. Normal and tumor tissues at several time-points (0, 30, 60 and 120 min) were extracted, and RNA quality, microarray experiments, quantitative PCR and bioinformatics clustering were performed. Although RNA integrity was preserved 2 h after resection, inherent increased/decreased gene expression was observed from 30-120 min in approximately 10% of genes. Bioinformatics clustering could not distinguish case-by-case, probably due to gene profiling changes. Irregular changes in gene expression after surgical resection were found, which could be a crucial confounding factor for quantitative analyses.

DOI： 10.3892/or.2014.3053

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：英語  

We herein present a rare case of enterovesical fistula caused by ileal non-Hodgkin's lymphoma. A 75-year-old Japanese male presented with macrohematuria at Kosei General Hospital in December 2010. An egg-sized mass was palpable in his right lower abdominal region, and computed tomography (CT) revealed that the ileal tumor had invaded the right posterior wall of the urinary bladder (UB). A histopathological examination of a CT-guided needle biopsy specimen revealed diffuse large B-cell lymphoma involving the ileum and the UB. Thereafter, fecaluria appeared. A transurethral catheter was put in place, and there were no symptoms of cystitis. The patient received chemotherapy for the lymphoma, which produced a partial response. However, the fecaluria continued, and an examination of the small intestine with contrast revealed a thick and irregular wall of the ileum and a fistula between the ileum and UB. A partial resection of the ileum and a partial cystectomy were carried out in April 2011. The surgical specimen demonstrated two tumors 5 cm apart in the ileum, measuring 4.5 × 7 and 4 × 3 cm in size. The proximal tumor had directly invaded the UB and formed an ileovesical fistula. The patient made a good recovery and was doing well 5 months after the surgery without any evidence of recurrence.

DOI： 10.1007/s00595-012-0177-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aim of this study is to investigate the expression of three prostaglandin E synthase (PGES) isomers in colorectal cancer (CRC) tissue and to evaluate their relationship to clinicopathological factors and patient prognosis. Microsomal PGES (mPGES)-1, mPGES-2, cytosolic PGES (cPGES) and cyclooxygenase (COX)-2 protein expression were analyzed by real-time polymerase chain reaction and Western blot. The localization of each PGES and COX-2 protein was examined by immunohistochemistry in 155 surgical resections and correlated to clinicopathological factors and patient prognosis. mPGES-1 mRNA and protein levels were significantly higher in CRC than in paired normal tissues. mPGES-1 immunoreactivity localized in cancer cells in 43% of cases. mPGES-2 immunoreactivity was significantly more pronounced in cancer cells than in adjacent normal epithelium in 36% of cases. cPGES immunoreactivity was homogeneous in cancer cells and thus determined constitutive. mPGES-1 and mPGES-2 correlated with significantly worse prognosis in stage I-III patients. These results indicate that mPGES-1 and mPGES-2 may each play a role in CRC progression.

DOI： 10.1007/s00428-009-0777-z

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記述言語：英語  

An inflammatory fibroid polyp (IFP) is a rare benign lesion, originating in the submucosa of the gastrointestinal tract. It is histopathologically characterized by distinctively arranged fibrous connective tissue and blood vessels with inflammatory cell infiltration. It typically arises in the stomach and small intestine but also arises infrequently in the colon. This report describes a case of IFP of the cecum. A 63-year-old woman presented with persistent bloody stool for more than 1 month. Colonoscopy revealed a polypoid lesion, measuring 2.5 cm in diameter and 4 cm in length, with a thick pedicle in the cecum. Histopathological examination of the biopsy specimen showed hyperplastic changes of the mucosa. The lesion was diagnosed to be a submucosal tumor. We concluded that endoscopic mucosal resection would be difficult because the polyp showed signs of infiltration into the submucosa. Furthermore, the possibility of malignancy could not be ruled out. Laparoscopy-assisted ileocecal resection with lymphnode dissection was performed after the patient's informed consent was obtained. The lesion was finally diagnosed to be IFP on the basis of histopathological examination of the resected specimen. Immunohistochemical staining of the spindle-shaped cells, which were present around the small vessels in the stroma of the tumor, showed that the tissue expressed vimentin but not alpha-smooth muscle actin, desmin, S-100, c-kit or CD 34. IFP is difficult to diagnose without the recognition of its clinical and pathological characteristics. It is also important to determinate the depth of the lesion before selecting the therapeutic method.

DOI： 10.1272/jnms.75.181

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記述言語：日本語  

Paclitaxel (PTX), which is used for ovarian cancer, lung cancer, breast cancer and gastric cancer, is administered at a dose of 210 mg/m(2) once every three weeks. However, WHO grade 3-4 hematological and non-hematological toxicity occurred frequently in this manner. In recent studies about ovarian cancer and lung cancer, a schedule in which PTX was given weekly could have the same or better efficacy, with fewer side effects. The response rate of PTX administered every three weeks for gastric cancer, was 23.3 to approximately 28.0%, while that of PTX administered weekly was 24.0 to approximately 25.8%. Because of fewer adverse events, weekly PTX is widely used for gastric cancer in Japan. To prove the validity of PTX weekly administration, we performed a study using six specimens removed surgically and one specimen collected from ascites. A chemosensitivity test was performed on the basis of two assumptions: a high concentration for a short time, and a low concentration for a long time. A similar PTX effect was obtained when the AUC was equal. In this study, we demonstrated that the effect of low-dose PTX was equal to the effect of high-dose PTX in gastric cancer.

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記述言語：英語  

Here we report the case of a patient with advanced gastric cancer with esophageal invasion who was treated with chemotherapy using S-1 and cisplatin (CDDP) preoperatively. The patient was a 72-year-old woman who was diagnosed with advanced gastric cancer (T3N2M0) with esophageal invasion. S-1 was orally administered at 80 mg/day (60 mg/m(2) per day) on days 1-14 and CDDP was infused at 80 mg/day (60 mg/m(2) per day) on day 8, followed by a 1-week rest. Marked reductions in the sizes of the primary tumor and metastatic lymph nodes around the stomach were observed after two cycles of the therapy. Adverse reactions occurring during the therapy were only grade 2 gastrointestinal disorder and grade 1 leukocytopenia. Radiological and endoscopic examinations before surgery showed that a partial response (PR) had been achieved. The patient underwent curative surgery consisting of total gastrectomy, D2 lymph node dissection, and splenectomy. Her postoperative course was uneventful, without surgical complications. No gastric cancer cells were detected in the primary lesion or lymph nodes by immunohistochemical staining with cytokeratin, confirming a histological complete response (CR). As Epstein-Barr virus-encoded small RNA (EBER) had been detected by in-situ hybridization in the gastric cancer cells of a biopsy specimen, this tumor was diagnosed as an Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC), which was effectively treated with S-1 and cisplatin chemotherapy.

DOI： 10.1007/s10147-007-0682-x

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記述言語：英語  

Here, we report the case of patient with multiple gastric carcinoids showing histopathological behavior similar to that of type I carcinoid tumors of the stomach. The patient was a 61-year-old man diagnosed as having a gastric tumor, which was revealed by follow-up computed tomography. Upper gastrointestinal endoscopy revealed a protruded tumor in the greater curvature and a small polyp in the anterior wall of the upper stomach. A biopsy revealed gastric carcinoid. Because he refused to be operated for gastric carcinoid, upper gastrointestinal endoscopy was performed 5 months later. A malignant transformation of the gastric carcinoid was strongly suspected. Therefore, the patient was admitted for operation. Laboratory findings were normal. With the diagnosis of type III gastric carcinoid, total gastrectomy was performed. Microscopic examination revealed that the carcinoid tumor was confined to the submucosa and that the small polyp mentioned earlier was also a carcinoid. Microcarcinoids and numerous enterochromaffin-like cell hyperplasias were observed along the muscularis propria of the fundus. The tumor differed from typical type I gastric carcinoids in several ways. Immunohistochemical staining for chromogranin A, synaptophysin, and cytokeratin was positive. However, p53 was absent, and the MIB-1 index was low. Two years after surgery, the patient is alive without recurrence.

DOI： 10.1272/jnms.74.430

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記述言語：英語   出版者・発行元：BLACKWELL PUBLISHING  

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記述言語：英語  

We report on a patient with rectal malignant melanoma. The patient was a 40-year-old man who complained of anal bleeding. His grandmother had died of pancreatic cancer and his mother had been operated for rectal cancer. Physical examination revealed a hard mass at the 12 o'clock position, 2 cm from the anal verge. A colonoscopic examination revealed an irregular surface mass, approximately 4.0 cm in size, located on the anterior wall of the lower rectum. A biopsy of the rectal tumor showed the proliferation of epithelioid cells with pleomorphic features. Immunohistochemical analysis was performed. S-100 protein, CD-56, and KIT expression were positive, but HMB-45 expression was negative. Abdominopelvic computed tomography (CT) revealed multiple liver and lymph node metastases. With the diagnosis of neuroendocrine carcinoma of the rectum, abdominoperineal resection was performed. After the operation, the serum lactate dehydrogenase level had rapidly increased. An abdominal CT showed progressive liver metastases. Thirteen days after the surgery, abdominal angiography was performed, which showed multiple hypervascular tumor stains in the liver. The reservoir was implanted transcutaneously with the aid of angiography and the catheter was fixed to the proper hepatic artery. Neoadjuvant chemotherapy using cisplatin and irinotecan via the subcutaneous reservoir port was performed and a partial response was obtained. However, the final pathological diagnosis of the surgically resected specimen was malignant amelanotic melanoma of the rectum. Immunohistochemical expression differed between rectal biopsy specimens and surgically resected specimens. HMB-45 expression was positive and KIT expression was negative in the resected specimen. As preoperative pathological diagnosis showed rare rectal tumor, we measured the chemosensitivity of the rectal tumor using the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) to determine the most appropriate chemotherapy regimen for the patient. However, there were no anticancer drugs tested by CD-DST for malignant melanoma. With informed consent, the patient received two cycles of immunochemotherapy consisting of dacabazine, nimustine hydrochloride, vincristine sulfate, and interferon -beta. Although the patient was treated with immunochemotherapy for metastatic liver tumor, he died because of progression of metastases.

DOI： 10.1272/jnms.74.377

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記述言語：英語  

Here, we report on a patient with squamous cell carcinoma (SCC) arising from recurrent anal fistula. The patient was a 57-year-old woman who had 32-year history of having a recurrent perianal abscesses that ruptured spontaneously. Six months before her admission to our hospital, anal pain developed. She had no history of inflammatory bowel disease. Physical examination revealed three external fistulous openings at the two o'clock position, 2 cm from the anal verge. One internal opening in the lower rectum was found with proctoscopy. The patient underwent fistulectomy. Microscopic examination showed SCC arising from the anal fistula, which was accompanied by vessel invasion. The tumor was observed to be continuous from the external opening but was not exposed to the internal opening of the rectal mucosa. Because human papillomavirus (HPV) infection was suspected, immunohistochemical analysis was performed, but showed no HPV infection. Two weeks after fistulectomy, abdominoperineal resection with lymph node dissection was performed. Histopathological examination revealed no remnant cancer tissue or lymph node metastasis. She was discharged after surgery without complications. Eight years after the operation, she complained of constant pain during micturition. Urological examination revealed urinary bladder cancer, and transurethral resection of the bladder tumor was performed. Histopathological examination revealed transitional cell carcinoma of the urinary bladder. Two years later, the patient died of metastatic urinary bladder cancer, without recurrence of the fistula cancer. Because the patients mother had died of urinary bladder cancer and she herself had metachronous urinary bladder cancer in addition to fistula cancer, we investigated whether microsatellite instability (MSI) and chromosomal instability correlated with fistula cancer development. Immunohistochemical analysis of formalin-fixed, paraffin-embedded surgical tumor specimens for p53, MLH1, and MSH2 was performed. The tumor specimens showed no MLH1 expression but did show normal MSH2 expression. p53 was not expressed. Five microsatellite loci were examined using the tumor specimens to detect MSI, namely two loci with mononucleotide runs (i.e., BAT25 and BAT26) and three loci with dinucleotide repeats (i.e., APC, Mfd15, and D2S123). The tumor specimens showed alternations in the repeated sequences of two loci (i.e., BAT26 and D2S123). As a result, the tumor was classified as MSI-H (high) according to the Bethesda criteria. Our patient had MSI and one of the smallest reported SCCs arising from recurrent anal fistulae.

DOI： 10.1272/jnms.74.319

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記述言語：英語  

BACKGROUND: Recent studies have shown that the Th1/Th2 balance shifts toward Th2 dominance in cancer-bearing state or under surgical stress. This study was designed to investigate whether perioperative impaired Th1/Th2 balance is associated with the occurrence of postoperative infection following colorectal cancer surgery. METHODS: From 53 patients with colorectal cancer, peripheral blood samples were collected, before surgery, and on the 3rd, 7th, and 14th postoperative days. The proportions of CD4(+) T-helper cells producing intracellular cytokines including interferon-gamma (Th1 cells) and interleukin-4 (Th2 cells) were measured by flow cytometry. The patients were divided into two groups according to the presence (infected group) and absence (noninfected group) of postoperative infection. RESULTS: The infected group showed serum hypoalbuminemia and higher frequency of blood transfusion compared with the noninfected group. No significant difference in the proportion of Th1 cells was observed between the two groups. In contrast, the infected group showed significantly higher proportions of Th2 cells than the noninfected group (1.9 +/- 0.9% for noninfected group and 2.8 +/- 1.3% for infected group; P<0.05). Regarding Th1/Th2 ratio, the infected group showed a lower ratio than the noninfected group (14.7 +/- 8.8 for noninfected group and 9.0 +/- 3.2 for infected group; P<0.05). Throughout the postoperative period, the Th1/Th2 ratio in the infected group was significantly lower than that in the noninfected group. CONCLUSIONS: This study demonstrated that perioperative Th2 dominance in addition to hypoalbuminemia and blood transfusion is associated with the occurrence of infection following colorectal cancer surgery. These results provide further information that may direct future treatments based on the Th1/Th2 concept focusing on decreasing the risk of postoperative infection.

DOI： 10.1016/j.jss.2006.10.029

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記述言語：日本語  

We report 3 gastric cancer patients with peritoneal dissemination who were successfully treated with weekly paclitaxel and cisplatin. The patients were 2 men and 1 woman from 57 to 70 years in age. The histological types were 2 poorly-differentiated adenocarcinomas and 1 moderately-differentiated adenocarcinoma. Intravenous infusion of PTX (80 mg/m(2)) and CDDP (25 mg/m(2)) after short premedication was continued for 3 weeks followed by 1 week rest. Ascites improved only after administration of 1 course in all patients.PTX/CDDP is thought to be an effective chemotherapy showing acceptable toxicity against advanced gastric cancer with ascites.

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記述言語：英語   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：英語  

CD34 is commonly used as an endothelial cell marker of tumor vessels. However, this marker detects not only newly formed, but also pre-existing large blood vessels. Nestin, a class VI intermediate filament protein, has recently received attention as a marker for detecting newly formed endothelial cells. In this study, whether nestin is a novel angiogenesis marker in colorectal cancer was examined. HCT-15, a human colon cancer cell line, was subcutaneously implanted into the dorsum of nude mice. After the tumor grew, the mice were perfused with fluorescent beads (Fluospheres). Then, the tumor tissues were used for immunofluorescence staining using nestin and the CD34 antibody. Immunohistochemistry was performed with nestin and CD34 on 101 human colorectal cancer tissue samples. Proliferating endothelial cells were detected immunohistochemically by a proliferating cell nuclear antigen (PCNA) antibody. Clinicopathological factors and prognosis were compared between two groups: that with a microvessel density (MVD) higher than the median MVD and that with MVD lower than the median MVD, as detected by nestin and CD34 labellings. Nestin was localized in endothelial cells in small blood vessels (median, 9.06 microm), whereas CD34 was localized in large blood vessels (median, 9.67 microm) in nude mice. The diameter of nestin-positive vessels was smaller than that of CD34-positive vessels in human colorectal cancer. The number ratio of PCNA-positive cells to nestin-positive vascular endothelial cells was higher than that of PCNA-positive to CD34-positive cells (p=0.002). There were no correlations between nestin-positive blood vessels and clinicopathological factors, but the prognosis was worse in the highly nestin-positive MVD group (p=0.071). Nestin is considered a novel angiogenesis marker of proliferating endothelial cells in colorectal cancer tissue.

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記述言語：英語  

DOI： 10.1272/jnms.74.77

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記述言語：英語  

DOI： 10.1272/jnms.74.87

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記述言語：英語  

Lumican is a member of a small leucine-rich proteoglycan family, and it is reportedly overexpressed in human breast cancer. The expression of lumican in the extracellular matrix in breast cancer is associated with a high tumor grade, low estrogen receptor levels and young age. Lumican expression has been previously reported in colorectal cancer, but the role of lumican in the tumor is not well understood. In this study, we examined the expression and role of lumican in advanced colorectal cancer. Immunohistochemical staining was performed on 158 patients who underwent curative surgery for advanced colorectal cancer with lymph node metastasis. In the normal colorectal tissues, lumican immunoreactivity was observed in the fibroblasts and neural cells, but not in the colorectal epithelial cells. Lumican was localized in the cytoplasm of the cancer cells and its overexpression was detected in 99 of the 158 (62.7%) colorectal cancer patients. Clinicopathologically, there was no association of lumican expression with age, sex, histological typing, or venous and lymphatic invasion. However, lumican expression tended to correlate with the spread of lymph node metastasis and the depth of tumor invasion (p=0.136 and 0.135, respectively). Furthermore, the survival rate was significantly lower in patients with a high lumican expression level than in those with a low lumican expression level (p=0.048). These results indicate that lumican expression is a potential prognostic factor in patients with advanced colorectal cancer with nodal metastasis.

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記述言語：英語  

Cyclo-oxygenase (COX)-2 is not usually detectable in normal tissues but is induced in inflammation and carcinogenesis. The level of COX-2 is elevated in cancer tissues of the colon, bladder, and skin. In the esophagus, squamous cell carcinoma and adenocarcinoma are known to express COX-2. The purpose of this study was to clarify the association of COX-2 expression with clinicopathological factors of squamous cell carcinoma. The immunohistochemical expression of COX-2 was examined in 48 surgical specimens of esophageal squamous cell carcinoma. Although COX-2 over-expression was more frequently observed in tumors invading the submucosa (T1b, 76.4%), muscularis propria (T2, 57.1%), adventitia, or adjacent organs (T3 approximately 4, 83.3%), even 33.3% of mucosal cancers, such as T1a, showed COX-2 over-expression. COX-2 over-expression was present in 82.3% of lymph node-negative patients but in only 54.8% of lymph node positive patients. There was no difference in COX-2 over-expression between the earlier stages (0 and I, 60%) and more advanced stages (II approximately IV, 69.6%). COX-2 over-expression did not correlate with survival during 3 years of follow-up. These findings suggest that COX-2 is associated with the phenotype of the esophageal squamous cell carcinoma cells, including superficial cancer cells, and may be related to tumor growth in esophageal squamous cell carcinoma.

DOI： 10.1272/jnms.73.308

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記述言語：日本語  

BACKGROUND: 5-Fluorouracil (5-FU) and its derivatives are widely known as some of the most commonly prescribed anticancer drugs, especially for gastrointestinal cancer. Orotate phosphoribosyl transferase (OPRT), dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are initial key enzymes in the 5-FU metabolic pathway. The activities of these enzymes may have the potential to affect the chemosensitivity of 5-FU. PURPOSE: This study was designed to investigate the effect of OPRT, DPD and TS in sensitivity to 5-FU. METHOD: We measured OPRT, DPD and TS activities in 11 colonic cancer tissues. The Collagen Gel Droplet Embedded Culture Drug Sensitivity Test (CD-DST) was used in an in vitro chemosensitivity assay. In these samples, the correlation between sensitivity to 5-FU and enzyme activities was investigated. RESULTS: There were no correlations among OPRT, TS activities and sensitivity to 5-FU. In contrast, there was a significant inverse correlation (r=-0.738) between DPD activity and 5-FU sensitivity. With regression analysis, the coefficient of determination of the activity of the three enzymes versus the sensitivity to 5-FU was 0.61. CONCLUSION: Though measuring OPRT, DPD, TS activities is valuable for prediction of sensitivity to 5-FU, DPD is considered to be the most important predictive factor of 5-FU sensitivity. To improve its accuracy, the finding of a fourth factor such as P-glycoprotein and multidrug resistance-associated proteins (MRP), to be added to OPRT, DPD and TS, is desired.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Elevated expression of cyclooxygenase-2 has been found in colorectal cancer. One of the mechanisms through which cyclooxygenase-2 affects tumorigenesis is through its overexpression, which leads to increased invasiveness of cancer cells. A crucial step in this pathway is thought to be the induction of membrane-type-1 matrix metalloproteinase, which activates matrix metalloproteinase-2. However, to date there have been few clinicopathologic studies concerning cyclooxygenase-2-mediated invasiveness in human colorectal cancer tissues. METHODS: We performed immunohistochemical analysis of the respective antigens on colorectal cancer specimens obtained by surgical resections from 96 patients with colorectal cancer. RESULTS: Cyclooxygenase-2 and membrane-type-1 matrix metalloproteinase expression was positive exclusively in cancer cells in 88 cases (92 percent) and 23 cases (24 percent), respectively. All 23 cases expressing membrane-type-1 matrix metalloproteinase also expressed cyclooxygenase-2. Matrix metalloproteinase-2 expression was positive in cancer cells in 20 cases (21 percent) and stromal cells in 52 cases (54 percent). Expression of matrix metalloproteinase-2 in cancer cells correlated with lymphatic invasion and local recurrence. Statistically, a significant correlation was found between cyclooxygenase-2 and membrane-type-1 matrix metalloproteinase expression, and membrane-type-1 matrix metalloproteinase and matrix metalloproteinase-2 expression in cancer cells. There was no association between cyclooxygenase-2 expression and matrix metalloproteinase-2 expression. However, immunostaining of serial sections revealed that in the majority of cases examined, nearly 100 percent of cancer cells expressing matrix metalloproteinase-2 also coexpressed cyclooxygenase-2. CONCLUSIONS: This study indicates strong association between both cyclooxygenase-2 and membrane-type-1 matrix metalloproteinase expression, and membrane-type-1 matrix metalloproteinase and matrix metalloproteinase-2 in colorectal cancer. These results support our thesis of a direct correlation between cyclooxygenase-2 and membrane-type-1 matrix metalloproteinase expression--with consequent association between cyclooxygenase-2 and matrix metalloproteinase-2 activation, and tumor invasiveness andrecurrence in certain cases of colorectal cancer.

DOI： 10.1007/s10350-006-0588-0

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記述言語：英語  

Poorly differentiated (PD) adenocarcinoma often retains the capacity for neuroendocrine (NE) cell differ-entiation; however, it is difficult to distinguish the NE cell differentiation by routine hematoxylin and eosin staining. It is important to detect the presence of NE cell differentiation in advanced colorectal carcinomas because these carcinomas have been shown to produce distant metastasis at the time of diagnosis and to have a particularly poor prognosis. In this study, the characteristics of PD adenocarcinoma with NE cell differentiation and its biological metastatic mechanisms were investigated. Forty-eight of 2204 colorectal cancer patients, diagnosed as having PD adenocarcinoma (2.2%) were enrolled in this study. Immunohistochemical analysis was performed with anti-chromogranin A anti-synaptophysin, anti-CD34, anti-D2-40, and anti-VEGF antibodies. The clinicopathological factors for PD adenocarcinoma with NE cell differentiation were compared with those for PD adenocarcinoma without NE cell differentiation. Microvessel density (MVD) was assessed using immunostained slides with anti-CD34 antibody and vascular endothelial growth factor (VEGF) expression in PD adenocarcinoma with NE cell differentiation was confirmed by in situ hybridization. By immunohistochemical staining for chromogranin A and synaptophysin, NE cell differentiation was detected in eight of 48 patients (16.7%) with PD adenocarcinoma. The frequency of liver metastasis at the time of diagnosis was significantly higher in patients having PD adenocarcinoma with NE cell differentiation (p=0.03). Moreover, MVD and VEGF expression level tended to be higher in patients having PD adenocarcinoma with NE cell differentiation (p=0.13 and 0.068, respectively). NE cell differentiation in PD adenocarcinoma may produce liver metastasis through microvessel formation in the tumor induced by VEGF. In PD colorectal adenocarcinoma, immunohistochemical analysis of NE markers is important for establishing the presence of NE cell differentiation and further study is necessary to evaluate the effectiveness of anti-angiogenic drugs to PD adenocarcinoma with NE cell differentiation.

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記述言語：英語   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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PURPOSE: Recent studies have shown that the type 1/2 CD4+ T cell (Th1/Th2) balance shifts toward Th2 dominance in cancer-bearing state or by surgical stress. Perioperative immunonutrition is reported to improve the outcome in patients with gastrointestinal cancer. This study was designed to investigate whether preoperative immunonutrition corrects the impaired Th1/Th2 balance in the perioperative period. METHODS: Thirty-six patients with colorectal cancer were prospectively divided into two groups as follows: preoperative oral intake supplementation with a formula enriched with arginine, omega-3 fatty acids and ribonucleic acid for five days (supplemented group; n = 19); and (control group; n = 17). Blood sampling was performed before supplementation, on the morning of surgery, and 3, 7, and 14 days postoperatively. The proportions of CD4+ T cells producing intracellular cytokines (interferon-gamma and interleukin-4) were measured by flow cytometry. RESULTS: In the preoperative period, the proportions of CD4+ T cells producing interleukin-4 significantly decreased and Th1/Th2 ratio significantly increased on the morning of surgery compared with those before supplementation. In the postoperative period, the proportions of CD4+ T cells producing interferon-gamma in both groups maintained the preoperative level. The proportions of CD4+ T cells producing interleukin-4 in the control group showed a gradual increase from the preoperative level, which implies Th2 dominant shift. In contrast, the supplemented group maintained the preoperative level of Th1/Th2 ratio. CONCLUSIONS: Preoperative immunonutrition corrects impaired Th1/Th2 balance in both cancer-bearing state and the postoperative period. This correction may be one of the important determinants of the clinical benefits of immunonutrition.

DOI： 10.1007/s10350-005-0292-5

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記述言語：英語   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Ubiquitin-specific protease 14, also known as the 60 kDa subunit of tRNA-guanine transglycosylase (USP14/TGT60 kD), belongs to the ubiquitin-specific processing protease (UBP) family. USP14/TGT60 kD expression in leukemic and colorectal cancer cell lines, and the suppression of such an expression after the induction of cell differentiation have been reported. In the present study, we attempted to clarify whether USP14/TGT60 kD overexpression affects the clinicopathological features of colorectal cancer. Immunohistochemically, USP14/TGT60 kD was absent or weakly localized in the cytoplasm of normal colorectal epithelial cells. In 18 of 99 (18.2%) colorectal cancer patients, USP14/TGT60 kD was strongly detected in the cytoplasm of cancer cells. USP14/TGT60 kD expression correlated with pathological stage (P=0.03), and lymph node (P=0.03) and liver (P=0.03) metastases. Furthermore, the percentage of patients strongly positive for USP14/TGT60 kD expression increased with pathological stage. The overall survival rate was worse in patients with a high USP14/TGT60 kD expression level than in those with a low USP14/TGT60 kD expression level. Our results suggest that USP14/TGT60 kD also controls the fate of proteins that regulate tumor invasion and metastasis.

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記述言語：英語   出版者・発行元：The Medical Association of Nippon Medical School  

DOI： 10.1272/jnms.73.38

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PURPOSE: The management of rectal tumors is complex, because of the balance between preserving rectoanal function and curing the patient. Transanal endoscopic microsurgery (TEM) is both an effective treatment for benign rectal tumors and early cancers, and a diagnostic tool for determining tumor depth, or for residual tumors of post endoscopic mucosal resection. In the present study, we evaluated the role of TEM in the management of rectal tumors. METHODS: Twenty-six patients with rectal tumors underwent TEM from December 2000 through March 2005 in our department. The operations were performed by a single surgeon, and the indications were mainly limited to a) benign tumors for which endoscopic resection was difficult, b) early cancers that had invaded the submucosa within 500 microm of the muscularis mucosae, c) submucosal tumors, i.e., gastrointestinal stromal tumor, carcinoid tumors, d) local excision for diagnosis, and e) palliative resection for high-risk cases. Anesthesia, operation time, sizes of the tumor and of resected specimens, postoperative complications, length of hospitalization, pathological results, and postoperative recurrence rate were reviewed. RESULTS: The mean age of patients was 61.9 years, and the cases included 14 rectal cancers, 7 adenomas, 1 gastrointestinal stromal tumor, and 3 rectal carcinoid tumors. The mean operation time was 96 min (range, 40 approximately 235 min.). The average postoperative hospital stay was 4.8 days. All tumors were resected with horizontal and vertical safety margin. The mean size of the resected specimens was 9.0 cm(2). In one case, the tumor had infiltrated the proper muscle layer, as shown by intraoperative frozen sectioning, which necessitated abdominoperineal resection. In 3 cases, pathological examination revealed massive infiltration into the submucosal layer. 2 patients underwent low anterior resection, and the remaining patient refused additional surgery despite our recommendation. No deaths occurred. No major postoperative complications were noted. The mean follow-up period was 27.2 months. Only one case of lymph node metastasis was observed, in the left iliac lymph node 3 years after TEM. CONCLUSIONS: TEM is a minimally invasive surgical procedure for rectal tumors, which allows the whole depth of the rectal wall to be resected with a safety surgical margin. Although TEM requires technical skill and accurate preoperative diagnosis, the procedure is safe, facilitates accurate diagnosis of tumor depth, and limits the need for additional surgery.

DOI： 10.1272/jnms.72.278

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記述言語：英語  

Hypoxia inducible factor (HIF)-1alpha is a transcription factor that regulates the transcription of genes associated with cell proliferation and vascular development. In various cancer tissues, HIF-1alpha is associated with clinicopathological factors, such as the tumor size, histological grade, and lymph node status. Although HIF-1alpha plays a critical role in tumor growth by inducing vascular endothelial growth factor (VEGF), it is unclarified whether HIF-1alpha affects lymphatic metastasis. The purpose of this study is to clarify the correlation of HIF-1alpha protein expression with lymph node metastasis in esophageal squamous cell carcinoma (ESCC). The expressions of HIF-1alpha and VEGF-C, which is one of the main lymphangiogenic factors, were examined in five ESCC cell lines and 48 surgical specimens of ESCC. HIF-1alpha and VEGF-C mRNAs were expressed in all the five ESCC cell lines as determined by RT-PCR analysis. Immunohistochemically, 34 of the 48 patients (70.8%) were positive for HIF-1alpha and 29 patients (60.4%) were positive for VEGF-C. Clinicopathologically, HIF-1alpha expression correlated with lymphatic invasion and VEGF-C expression (P = 0.003 and P = 0.01, respectively). Furthermore, HIF-1alpha expression tended to correlate with lymph node metastasis (P = 0.09). These findings suggest that HIF-1alpha plays a role in lymphatic invasion and lymph node metastasis through the induction of VEGF-C in ESCC.

DOI： 10.1016/j.yexmp.2004.11.002

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記述言語：英語  

Lumican is a member of the small leucine-rich proteoglycan (SLRP) family and participates in the maintenance of tissue structures and tumor growth. Neuroendocrine cell tumors (NETs) including carcinoid tumors and NE cell carcinomas (NECs) possess numerous neuroendocrine (NE) granules, and differences between these tumors are in terms of their biological and metastatic aggressiveness during tumor progression. The purpose of this study was to examine the expression of lumican in NETs, and to determine whether the presence of lumican may be associated with the growth of NETs by comparing its expression between carcinoid tumors and NECs. Immunohistochemically, the positivity rates of lumican expression in the cytoplasm of the tumor cells were 87.5% in carcinoid tumors and 37.5% in NECs. Those of lumican expression in the stroma adjacent to the tumors were 90.1% in carcinoid tumors and 79.2% in NECs. In situ hybridization analysis revealed the lumican mRNA expression in the cytoplasm of carcinoid tumor and NEC cells. Ultrastructurally, the lumican protein was observed in the rough endoplasmic reticulum and NE granules of NETs and interspaces of collagen fibers. Furthermore, RT-PCR analysis revealed the presence of lumican mRNA in NEC cell lines. These results indicate that the higher expression level of cytoplasmic lumican in carcinoid tumors than in NECs may play a role in the slow growth of these tumors.

PubMed

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記述言語：英語  

A rare case of carcinoid tumor in the duodenal bulb associated with early gastric carcinoma is reported. An 85-year-old asymptomatic male was admitted to our hospital, referred by his neighboring doctor because of early gastric carcinoma shown by endoscopic examination. X-ray studies of the upper gastrointestinal tract showed irregular lesser curvature of the gastric antrum and a filling defect (phi1 cm) at the duodenal bulb. Gastric biopsy revealed the histological findings of Group V. Distal gastrectomy including the duodenal bulb with D2 lymph node dissection was performed. A resected specimens showed superficial depressed type carcinoma at the lesser curvature of the antrum, and an isolated submucosal tumor of 7x7 mm in size at the duodenal bulb. Histological examination disclosed papillary adenocarcinoma in the gastric mucosa and a carcinoid tumor of the duodenal bulb in the submucosal layer without high malignant findings. The patient has been well for 5 years since the surgery. In conclusion, we discussed 46 collected cases of carcinoid tumor of the duodenum associated with gastric carcinoma in Japan. Preoperative diagnosis of carcinoid tumor of the duodenum is very difficult, and thorough examinations are needed for submucosal lesion.

DOI： 10.1272/jnms.71.198

PubMed

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記述言語：英語  

Whole-body optical imaging is an external and noninvasive procedure that enables the continuous visual monitoring of malignant growth and spread within intact animals. The human colon adenocarcinoma cell-line HCT-15 was transfected with a pIRES 2-EGFP vector, and stable enhanced green fluorescence protein (EGFP) expression was established (Fig.1). Approximately 10(6) HCT-15 EGFP stable transfectant cells were subcutaneously injected into the left flank of six-week-old male Balb/c-nu/nu mice. On post-injection day 78, the size of the subcutaneous tumor was 13.1 mm x 15.4 mm in diameter, as observed using an ORCA-C 7780-20 three-chip cooled color charge-coupled-device camera (Hamamatsu Photonics Systems, Hamamatsu City, Japan). An external fluorescent image of the tumor was acquired through the skin (Fig.2B). The tumor could be seen more clearly once the skin was removed (Fig.2D). Furthermore, in the peritoneal metastasis (Fig.3B) and liver metastasis models (Fig.3D), metastasis could also be seen through the skin. This new technology is a useful method for investigating tumor growth in vivo. In the future, this method could be applied to the detection of peritoneal, liver and lung metastasis in living animals.

DOI： 10.1272/jnms.70.462

PubMed

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記述言語：日本語   出版者・発行元：日本分子腫瘍マーカー研究会  

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記述言語：日本語   出版者・発行元：日本分子腫瘍マーカー研究会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科感染症学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：日本分子腫瘍マーカー研究会  

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記述言語：日本語   出版者・発行元：日本分子腫瘍マーカー研究会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：日本外科代謝栄養学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

血液をはじめとし,体液中には様々な核酸や腫瘍細胞が存在し,これらを用いた検査をLiquid biopsyと総称する.Liquid biopsyではCirculating tumor cell(CTC),circulating tumor DNA(ctDNA),exosomeを利用するが,ctDNAの研究が最も進んでいる.single-cellのRNA解析技術が開発されたため,今後CTC研究から様々な新知見が得られることが期待されており,exosome内のDNAはctDNAと比較して断片化が軽度であり,半減期が長い可能性があることから,これまでctDNAではできなかったLiquid biopsyを用いた悪性腫瘍の早期診断への応用が期待されている.Liquid biopsyは,空間的・時間的heterogeneityを同定することによる薬剤感受性の判断や,根治切除後の微小転移(Minimal residual disease:MRD)の有無に基づいた予後リスクの判定,等で臨床応用が期待されている.MRDの有無により術後補助化学療法の必要性や治療期間を個別化できる可能性があることから世界中でMRD研究が行われている.(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本腹部救急医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腹部救急医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腹部救急医学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本腹部救急医学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本創傷治癒学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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