記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: To investigate the accuracy and clinical value of an adhesion scoring system using transvaginal ultrasonography for endometriotic adhesion. METHODS: In this prospective observational study, we included 131 patients with endometriosis who underwent surgery. Before surgery, transvaginal ultrasonography and adhesion mapping were performed to determine the presence or absence of adhesions at 10 sites of the pelvis. Mapping accuracy was determined by comparing the mapping findings with the surgical findings. To determine the severity of pelvic adhesions, we developed an adhesion score (0-10). With the adhesion score, we assessed the effect of surgical adhesiolysis and evaluated the relationship between postoperative adhesions and infertility. RESULTS: Of the 10 sites assessed for adhesions, the most frequent site of adhesions was the site between the left ovary and the uterus (70.5%). The overall sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and accuracy of adhesion mapping were 80.4%, 86.1%, 78.8%, 87.2%, 5.79, 0.23 and 83.9%, respectively. The adhesion score in this system was significantly correlated with the adhesion-related score in the revised American Society for Reproductive Medicine classification (R2 = 0.734). Surgical adhesiolysis yielded only about 30% improvement postoperatively. The adhesion score 1 month after surgery in the non-in vitro fertilization (IVF) pregnancy group was significantly lower than that in the IVF pregnancy group (3.45 vs 5.21; P = 0.02). CONCLUSION: Our adhesion scoring system allowed an accurate prediction of the pelvic adhesion status and may potentially be an indicator of postoperative adhesions and infertility.

DOI： 10.1111/jog.14191

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Laparoscopic sacrocolpopexy (LSC) is attracting increasing attention as a minimally invasive surgery that provides excellent therapeutic effects on apical vaginal prolapse. However, its therapeutic effects on multi-compartmental pelvic organ prolapse (POP) remain unclear. Therefore, the aim of this review was to evaluate the efficacy of LSC on multi-compartmental POP compared with abdominal sacrocolpopexy (ASC). We extracted three articles on randomized controlled trials that compared LSC and ASC. A total of 247 patients (123 for LSC, 124 for ASC) were evaluated. There was no evidence of recurrence or reoperation in either group for the apical vaginal compartment. Regarding recurrence within the anterior vaginal compartment, there were no significant between-group differences in either of the two randomized controlled trials targeting vaginal vault prolapse. In contrast, in the randomized controlled trial targeting POP including cases with uteruses, there were more recurrent POP with grade II or more in the LSC group than in the ASC group (11/60 [18.3%] vs 1/60 [1.6%], P = 0.004). Reoperation for the posterior vaginal compartment was performed in three cases (2.5%) in the LSC group and in one case (0.8%) in the ASC group. The combined repeat surgery and mesh removal surgery rate was higher in the LSC group (8/119 [6.7%]) than in the ASC group (2/121 [1.7%], P = 0.049). LSC has an excellent therapeutic effect and is comparable to ASC for the treatment of apical prolapse. However, cystocele recurrence, repeat surgery of the posterior compartment, and mesh-related complications were more frequent in patients who had undergone LSC.

DOI： 10.1111/ases.12478

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.gmit.2017.02.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The major effector cells for cellular adaptive immunity are CD8(+) cytotoxic T lymphocytes (CTLs), which can recognize and kill virus-infected cells and tumor cells. Although CTLs exhibit strong cytolytic activity against target cells in vitro, a number of studies have demonstrated that their function is often impaired within tumors. Nevertheless, CTLs can regain their cytotoxic ability after escaping from the tumor environment, suggesting that the milieu created by tumors may affect the function of CTLs. As for the tumor environment, the patho-physiological situation present in vivo has been shown to differ from in vitro experimental conditions. In particular, low pH and hypoxia are the most important microenvironmental factors within growing tumors. In the present study, to determine the effect of these factors on CTL function in vivo, we examined the cytolytic activity of CTLs against their targets using murine CTL lines and the induction of these cells from memory cells under low pH or hypoxic conditions using antigen-primed spleen cells. The results indicated that both cytotoxic activity and the induction of functional CTLs were markedly inhibited under low pH. In contrast, in hypoxic conditions, although cytotoxic activity was almost unchanged, the induction of CTLs in vitro showed a slight enhancement, which was completely abrogated in low pH conditions. Therefore, antigen-specific CTL functions may be more vulnerable to low pH than to the oxygen concentration in vivo. The findings shown here provide new therapeutic approaches for controlling tumor growth by retaining CTL cytotoxicity through the maintenance of higher pH conditions.

DOI： 10.1016/j.imlet.2015.07.003

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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-BLACKWELL  

AimThe aim of this study was to assess the cut-off age of the risk factors for postoperative recurrence of ovarian endometriomas and to evaluate the end-points of follow-up after laparoscopic excision of ovarian endometriomas.
Material and MethodsWe retrospectively reviewed 167 patients who underwent laparoscopic excision of ovarian endometriomas at our hospital between 2000 and 2009, and followed up the patients until 2010. Following surgery, patients chose to receive gonadotrophin-releasing hormone agonist, oral contraceptive pills (OCP), dienogest, or no medication and underwent regular ultrasonographic examinations. Potential risk factors for recurrence, including age at surgery, were assessed in the patients receiving no medication. Postoperative recurrence, defined as re-appearance of an ovarian endometrioma>2cm in size, was assessed for each treatment group.
ResultsAge at surgery was the only significant risk factor for recurrence, at a cut-off of 32 years, obtained through receiver-operator curve analysis. In patients not receiving medication, the recurrence rate gradually increased up to 50% over 5 years; there was no recurrence 5 years after surgery. Although no recurrence was seen in patients during continuous treatment with OCP or dienogest, the disease recurred in 55.5% of patients after discontinuing OCP.
ConclusionsAlthough adjuvant therapy for all patients may represent overtreatment, the findings of the present study suggest that, in the interest of fertility preservation, continuous postoperative hormonal treatment should be administered, at least to patients younger than 32 years. In patients who decline hormonal treatment, we recommend that they undergo follow-up for recurrence until 5 years after surgery.

DOI： 10.1111/jog.12164

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The recent emergence of laparoendoscopic single-site surgery (LESS) has had a great impact on gynecology. As LESS grows in popularity, attention has been paid to the procedure's cosmetic benefits. Although in theory LESS is an ideal approach that leaves no visible scars and improves patients' quality of life, the outcomes are not always ideal according to recently published data. Therefore, alternative approaches, such as mini-laparoscopy, are also becoming more popular. Herein, we review randomized trials studying the benefits of LESS in gynecology and discuss alternative approaches. Finally, we propose the mimic approach as the next generation for non-visible scar surgery.

DOI： 10.1111/ases.12041

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Abdominal sacrocolpopexy is the gold standard for treating pelvic organ prolapse (POP) because of safety and durable good results. More recently laparoscopic sacrocolpopexy (LSC), a less invasive approach, has become popular. Although these surgeries are versatile and can treat almost all patients with POP, these techniques have shortcomings. Specifically, reinforcement of lateral vaginal defects are not very strong, thus patients with POP and a severe paravaginal defect are not good candidates for abdominal or laparoscopic sacrocolpopexy. To overcome this problem, we developed a novel type of LSC, which can reinforce severe paravaginal defects by using a reversed T-shaped anterior mesh combining the advantage of transvaginal mesh surgery. We refer to this novel surgery as 'hybrid LSC'. Thus far, eight patients have successfully undergone this surgery. Hybrid LSC is a simple and secure method, and is an alternative treatment for POP with a severe paravaginal defect.

DOI： 10.1111/j.1447-0756.2012.01987.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Minimally invasive surgery is widely used in gynecology. Women who seek a cosmetic advantage (i.e., concealed scars) choose minimally invasive surgery. Although laparoendoscopic single-site surgery could be an ideal solution, some of our patients have had cosmetic problems, such as pigmentation and cicatrix of the umbilicus. In addition, umbilical eversion and umbilical herniation occasionally develop. Therefore, mini-laparoscopic surgery using 3-mm trocars can be recommended for patients who do not want the natural appearance of the navel to be altered. We have developed an approach to achieve a superior cosmetic outcome by direct placement of 3-mm trocars in the lateral wall of the abdomen and at the lower border of the pubic hair. We refer to this method as mimic mini-laparoscopic surgery and report cases in which this procedure was used.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTS: Laparoendoscopic single-site surgery (LESS) is an ideal approach for gynecologic surgery and yields better cosmetic results. However, a standard umbilical approach with LESS is not appropriate for gynecologic surgery requiring intra-abdominal suturing and dissection requiring traction. Therefore, we have developed a new multitrocar access system for gynecologic LESS. The purpose of this study was to evaluate the efficacy of gynecologic LESS using this access system. METHODS: This access system consists of one 12-mm trocar, two 5-mm trocars, and a 5-mm flexible laparoscope. Two 5-mm trocars with small port heads were inserted cross-wise on opposite sides of the sleeve of the centrally positioned 12-mm trocar to maintain triangulation. Thirty-eight patients with various gynecologic conditions underwent LESS with this access system. The results of these surgeries were retrospectively compared to those of conventional laparoscopic procedures. RESULTS: Of the 38 LESS procedures performed with this access system, none was up-converted, converted to an open laparotomy, or required blood transfusion. The Salpingo-oophorectomy with LESS had several benefits, such as no extension of the skin incision of the trocar site and no leakage of the contents of the ovarian cyst into the peritoneal cavity, over that with conventional laparoscopy. A comparison of LESS (11 patients) and conventional laparoscopy (16 patients) for total hysterectomy showed no significant difference in total blood loss (234.0 mL vs. 221.6 mL) or the weight of the resected uterus (276.0 g vs. 285.0 g), although the mean total operative time was greater with LESS (199.0 min vs. 168.5 min). CONCLUSION: Our multitrocar access system is safe and secure, and can be adapted for various gynecologic surgeries involving complicated procedures. LESS with this access system achieves results comparable to those of conventional laparoscopy with 4 ports, although the operative time is longer.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Mesh surgeries, such as sacrocolpopexy and transvaginal mesh surgery, are commonly used to treat pelvic organ prolapse. Although mesh surgeries have a high success rate, they are unsuitable for some patients. For a patient with pelvic organ prolapse and highly calcified multiple fibroids, we performed hybrid sacrocolpopexy combined with transvaginal mesh surgery with a method modified for the patient's condition. Three months after surgery, the results were highly satisfactory. This approach is simple, secure, and versatile for patients who are not good candidates for conventional mesh surgeries. This novel hybrid mesh surgery is an option for treating various types of pelvic organ prolapse.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: To examine the efficacy of local methotrexate (MTX) administration following linear salpingostomy for tubal pregnancy in the prevention of persistent ectopic pregnancy (PEP). METHODS: Patients who underwent a laparoscopic linear salpingostomy between January 1996 and December 2006 were enrolled in the study. Patients who were assigned to the prophylaxis group were administered MTX (50 mg) into the tubal wall in the vicinity of the lesion immediately following linear salpingostomy (n=41). Patients who were treated without MTX were assigned to the control group (n=40). Serum human chorionic gonadotrophin levels were followed in both groups postoperatively once every 3 days until they became undetectable. The incidence of PEP was compared between the two groups. RESULTS: Persistent ectopic pregnancy occurred in seven patients (17.5%) in the control group compared with zero patients in the prophylaxis group (P<0.05). There were no side-effects attributable to MTX in the prophylaxis group. CONCLUSION: A single prophylactic intratubal injection of MTX following laparoscopic linear salpingostomy is a safe and effective regimen for the prevention of PEP.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The majority of human and rodent cancers display various antigens which could elicit cellular and humoral immune responses. Such immunity, however, often fails to prevent progressive growth of cancers. It has long been speculated that tumor antigens may not be presented in appropriate fashion, which subsequently fails to elicit a strong immune response. Recent studies, however, indicate that immunization by formulated tumor antigens or even transfer of pre-activated T lymphocytes also have limited impact on cancer growth despite the fact that these methods could often enhance immune responses in cancer patients. These findings imply that even afferent arm of immunity are strengthen, it is not necessarily being translated to tumor regression. It is possible that the development of evasion mechanisms in tumor microenvironment play a critical role in the resistance of therapeutic immune responses. Recent studies provide compelling evidence that human and rodent cancers develop evasion mechanisms by aberrantly expressing normal proteins, which are required for normal tissue homeostasis, to either build a microenvironment locally or reach other organs systemically. In this review, we will focus our discussion on two recently described molecules, B7-H1 and B7-H4, in the context of their roles in the evasion of tumor immunity and possible approaches for therapeutic manipulation.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Contemporary approaches for vaccination and immunotherapy are often capable of eliciting strong T-cell responses against tumor antigens. However, such responses are not parallel to clinical tumor regression. The development of evasion mechanisms within tumor microenvironment may be responsible for poor therapeutic responses. We report here that constitutive or inducible expression of B7-H1, a B7 family molecule widely expressed by cancers, confers resistance to therapeutic anti-CD137 antibody in mice with established tumors. The resistance is accompanied with failure of antigen-specific CD8+ CTLs to destroy tumor cells without impairment of CTL function. Blockade of B7-H1 or PD-1 by specific monoclonal antibodies could reverse this resistance and profoundly enhance therapeutic efficacy. Our findings support that B7-H1/PD-1 forms a molecular shield to prevent destruction by CTLs and implicate new approaches for immunotherapy of human cancers.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recent findings suggest that macrophage-tropic human immunodeficiency virus type 1 (HIV-1) produced in colostrum/early breast milk may hold a clue to determine the mechanisms of transmission of HIV-1 via breast-feeding. Here, we show that the majority of CD4(+) cells in the colostrum are CD14(+) macrophages expressing both chemokine receptors and DC-SIGN, a dendritic cell-specific receptor for HIV-1. The R5-type macrophage-tropic HIV-1 isolate NL(AD8) infected such breast-milk macrophages and caused them to secrete virus particles efficiently; however, the secreted virions showed only a weak transmissibility to their susceptible target, MAGIC-5 cells. When stimulated with interleukin-4, the breast-milk macrophages demonstrated a striking enhancement of expression of DC-SIGN and showed a strong capacity to transmit NL(AD8) virions to MAGIC-5 cells, which was specifically blocked by anti-DC-SIGN-specific antibody. These results suggest that HIV-1 virions captured by DC-SIGN, but not secreted cell-free virions, may be more efficiently transmitted to other compartments, such as the gastrointestinal tract, through acidic gastric juice.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Peripheral blood monocytes extravasate and differentiate into tissue macrophages to mediate effective local defence, but how tissue-specific stimuli and environments may influence their functions remains unknown. Here, we found that peripheral blood monocytes gained the ability to produce granulocyte-macrophage colony-stimulating factor (GM-CSF) upon exposure to breast milk and differentiated into CD1+ dendritic cells (DCs) in the presence of exogenous interleukin-4 (IL-4) alone. This in vitro observation appeared physiologically relevant since macrophages that were freshly isolated from breast milk were also found to produce GM-CSF spontaneously. Furthermore, in contrast to peripheral blood monocytes that differentiated into DCs only in the presence of both exogenous GM-CSF and IL-4, differentiation of breast milk macrophages into DCs was induced by incubation with exogenous IL-4 alone. These IL-4-stimulated breast milk macrophages were efficient in stimulating T cells, suggesting their potential role in mediating T-cell-dependent immune responses in situ. On the other hand, unexpected expression of DC-SIGN, a DC-specific receptor for human immunodeficiency virus (HIV), even in unstimulated breast milk macrophages, may favour HIV infection, resulting in an increased risk of mother-to-infant vertical transmission of the virus via breast milk. Thus, tissue-specific development of macrophages is often linked to effective local immunity, but may potentially provide an opportunity for a pathogen to spread and transmit.

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