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In the present study, we report the analysis of NK cells derived from patients suffering from a rare ovarian cancer histotype of clear cell carcinoma (OCCC) resistant to conventional chemotherapies. We analyzed the phenotype of NK cells derived from peripheral blood (PB) and peritoneal fluid (PF) and evaluated cytotoxic interactions between NK cells and autologous tumor cells (ATC) derived from patients. We provided evidence of impaired degranulation capacity of NK cells derived from patients' PF in the presence of ATC. Analyzing tumor cell ligands recognized by NK cell receptors, we found that ATC are characterized by an HLA class I + phenotype (although the level of HLA-I expression varies among all patients) and by a heterogeneous expression of ligands for activating NK receptors (from normal to decreased expression of some markers). Furthermore, we observed a down-regulation of crucial NK cell activating receptors, primarily DNAX Accessory Molecule-1 (DNAM-1), on tumor-associated NK cells. Based on these results, we propose that this severe lysis defect may be due to both negative interactions between HLA-I-specific inhibitory NK cell receptors/HLA-I molecules and to defective interactions between activating NK receptors and cognate ligands. In conclusion, for the first time, the phenotypic and functional properties of tumor-associated NK cells and their ATC derived from PF of patients with advanced stage of OCCC were characterized. Taken together results indicate altered interactions between NK cells and ATC and shed light on the aggressive mechanisms of this cancer histotype. Further studies on this rare tumor will be helpful to improve and define more effective therapies., (©2020 Society for Leukocyte Biology.)

Study Objective: To analyze the complications experienced and describe laparoscopic surgery using a gasless optical trocar., Design: A retrospective study., Setting: A department of obstetrics and gynecology in a tertiary center in Italy., Patients: Seven thousand four hundred thirty-one surgical procedures were performed., Interventions: From the hospital database, data were evaluated regarding major complications of laparoscopy with the ENDOPATH XCEL Bladeless Trocar (Ethicon, Johnson & Johnson, Somerville, NJ) performed between 2000 and 2017 by different laparoscopic surgeons., Measurements and Main Results: The mean age of the patients was 40.66 ± 12.06 years (range, 13-91 years). The mean body mass index was 22.12 ± 3.64 kg/m 2 (range, 15.74-41.51 kg/m 2 ). The overall complication rate was 0.31% (23/7431 cases). Major complications included stomach perforation in 1 procedure (0.014%), ileal perforation in 2 procedures (0.028%), and blood vessel perforation in 1 procedure (0.014%). Twelve procedures were completed with initial access through the omentum and 2 through an ovarian cyst. In 5 procedures (0.067%), conversion to laparotomy was required because the optical trocar failed to reach the abdominal cavity. With regard to complications requiring further intervention (n = 9), the rate of complications was 0.12%., Conclusions: The optical gasless trocar is a feasible laparoscopic entry technique. The complication rate is lower than those reported previously., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Teratomas of extragonadal origin are extremely rare, and the most common extragonadal site to find teratomas is the omentum. Teratomas are typically found in women of reproductive age, but they are also seen in young girls and postmenopausal women. Generally, teratomas arise from germ cells that may induce different cells to originate from the 3 primitive embryonic layers. Three main theories have been proposed to explain their location. The present report summarizes these theories as well as describes a case of a mature cystic teratoma of the omentum that was managed by laparoscopic resection., (Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.)

Background: Programmed death 1 (PD-1) is an immunologic checkpoint that limits immune responses by delivering potent inhibitory signals to T cells on interaction with specific ligands expressed on tumor/virus-infected cells, thus contributing to immune escape mechanisms. Therapeutic PD-1 blockade has been shown to mediate tumor eradication with impressive clinical results. Little is known about the expression/function of PD-1 on human natural killer (NK) cells., Objective: We sought to clarify whether human NK cells can express PD-1 and analyze their phenotypic/functional features., Methods: We performed multiparametric cytofluorimetric analysis of PD-1 + NK cells and their functional characterization using degranulation, cytokine production, and proliferation assays., Results: We provide unequivocal evidence that PD-1 is highly expressed (PD-1 bright ) on an NK cell subset detectable in the peripheral blood of approximately one fourth of healthy subjects. These donors are always serologically positive for human cytomegalovirus. PD-1 is expressed by CD56 dim but not CD56 bright NK cells and is confined to fully mature NK cells characterized by the NKG2A - KIR + CD57 + phenotype. Proportions of PD-1 bright NK cells were higher in the ascites of a cohort of patients with ovarian carcinoma, suggesting their possible induction/expansion in tumor environments. Functional analysis revealed a reduced proliferative capability in response to cytokines, low degranulation, and impaired cytokine production on interaction with tumor targets., Conclusions: We have identified and characterized a novel subpopulation of human NK cells expressing high levels of PD-1. These cells have the phenotypic characteristics of fully mature NK cells and are increased in patients with ovarian carcinoma. They display low proliferative responses and impaired antitumor activity that can be partially restored by antibody-mediated disruption of PD-1/programmed death ligand interaction., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

In this study the phenotype and function of tumor-associated NK cells from peritoneal fluids of a selected cohort of patients with seropapillary ovarian carcinoma were analyzed. In > 50% of these patients, the expression of the activating receptor NKp30 in tumor-associated NK cells was substantially reduced as compared to autologous peripheral blood (PB) NK cells. The impaired expression of this receptor was associated with the presence of one of its cellular ligands (B7-H6), which was detectable as a surface/cytosolic molecule in tumor cells and as a soluble molecule in the peritoneal fluid. NK cells from patients expressing this NKp30low phenotype displayed an impaired interferon-gamma (IFNγ) production and cytolytic function when tested against target cells expressing surface B7-H6. Our data also suggest that in these patients, the defective expression and function of NKp30 may be induced by the chronic engagement of this receptor by soluble B7-H6 or by tumor cells expressing this ligand. The impairment of NK cell functions described herein could represent a novel mechanism by which the tumor microenvironment may contribute to the escape from immune surveillance.

Objective: To present our experience with a new technique for laparoscopic rectosigmoid resection in patients with endometriosis., Design: Prospective collaborative cohort study., Setting: Gynecologic departments of two university hospitals., Patient(s): Thirty-three women with rectosigmoid endometriotic lesions requiring segmental bowel resection., Intervention(s): Laparoscopic intracorporeal division of the distal bowel and exteriorization of the affected segment via a colpotomy incision to complete the resection., Main Outcome Measure(s): Intraoperative and postoperative complications, and relief from symptoms., Result(s): The only intraoperative complication was bleeding from the inferior mesenteric artery that required conversion to laparotomy to obtain hemostasis. No patient required a temporary colostomy. No anastomotic complications were identified. Postoperative complications included a symptomatic pelvic seroma that required operative drainage in 1 patient and urinary retention that required intermittent self-catheterization in 3 women. The median follow-up duration was 13 months (range, 3-27 mo). Twenty-seven women were symptom free at the time of last follow-up evaluation. No patient had recurrent cyclic rectal bleeding, rectal pain on defecation, or tenesmus. Postoperatively, 4 of 13 patients who tried to conceive were successful., Conclusion(s): Segmental colorectal resection with a combined laparoscopic-transvaginal approach, avoiding the extension of port-site incisions, represents a viable option for the treatment of bowel endometriosis.

Objective: To compare the surgicopathologic outcome of total laparoscopic radical hysterectomy (LRH) with that of abdominal radical hysterectomy (ARH) for the treatment of early-stage cervical cancer., Methods: Radical hysterectomy specimens of sequential patients undergoing LRH (N=50) were compared with those of historical controls selected from consecutive women who have had conventional ARH (N=48), and who met the same criteria for eligibility as the cases. To evaluate the extent of parametrial resection, parametrial tissues were systematically measured at their widest dimensions before tissue processing., Results: No difference was found in demographics, histologic type, tumor stage and grade between the two groups. The parametrial width was similar between LRH and ARH in both type II (right parametrium: 2.4 cm (1-3) vs. 2.3 (1.8-4.0), p=0.28; left parametrium: 2.3 cm (1.8-4) vs. 2.2 (1.2-3.0), p=0.54) and type III radical hysterectomy (right parametrium: 3.8 cm (2.3-6.5) vs. 3.4 (1.7-7.0), p=0.59; left parametrium: 3.6 cm (2-6) vs. 3.5 (1.5-6.5), p=0.82). There were no significant differences between the two groups with regard to lymph nodes yield and likelihood of identifying positive margins or metastatic disease., Conclusion: Our results suggest that laparoscopically managed patients with cervical cancer undergo a similar extent of surgery as those treated with the traditional ARH, as judged by objective pathologic criteria.

The distribution of intrinsic components (Laminin and Type IV Collagen) and extrinsic component (Fibronectin) of the Basement Membrane (BM) has been studied in normal uterine cervix (16 cases), in cervical dysplasia (14 cases) and in invasive carcinoma (45 cases). We found that BM staining for Laminin and Type IV collagen is linear and continuous underlying normal and dysplastic epithelium (CIN 1-CIN 2), it shows minor breaks in continuity and alterations of linearity in situ carcinomas (CIN 3), and it disappears in microinvasive areas. In well differentiated invasive carcinomas only focal disruptions of BM around neoplastic nests is noted; in contrast, in moderately and poorly differentiated neoplasias, is found a progressive reduction and loss of staining for Laminin and Type IV Collagen. The results of this study suggest that the distribution patterns of BM intrinsic components are in relation to the histological grade of cervical neoplasias and their invasion ability. On the contrary Fibronectin doesn't show any distribution pattern related to the grade of cervical neoplasias, its immunostaining increased with the rise of both connective tissue stroma production and of vascularity.