Peritoneal natural killer cell chemotaxis is decreased in women with pelvic endometriosis.

PROBLEM: NK cell and macrophage function are decreased in endometriosis, and the disease may involve reduced immune surveillance in the peritoneal cavity. NK cell cytotoxicity and migration ability (chemotaxis) are considered important; the former has been investigated, but the latter has not. METHOD OF STUDY: We compared chemotaxis of immunocompetent cells (NK cells, macrophages, T cells) in peritoneal fluid obtained during laparoscopy in 27 women with and 13 without endometriosis. Peripheral blood NK cells were also obtained by the peripheral blood antibody beads method. Micro-cultured cells were examined by time-lapse photography, and the mean migration speed per cell was calculated as the chemotaxis. We investigated the relationship between chemotaxis and endometriosis. RESULTS: NK cell chemotaxis was significantly lower in the endometriosis group. Macrophages and lymphocytes were not significantly different between the groups. During menstruation, NK cell chemotaxis decreased in both groups. Postmenstrual chemotaxis was increased significantly in women without endometriosis but remained low in women with endometriosis. The Revised-American Society for Reproductive Medicine score was not correlated with chemotaxis; in women with endometriosis, chemotaxis was decreased even at early stages. Peripheral blood NK cells showed no significant differences. CONCLUSIONS: In women with endometriosis, not only cytotoxicity but also chemotaxis by NK cells in peritoneal cavity is significantly decreased, and particularly chemotaxis is decreased throughout the menstrual cycle. Therefore, antigens in retrograde menstrual blood that enters the peritoneal cavity might be left unprocessed. Repetition of this immune process in the peritoneal cavity may lead to the onset and subsequent progression of endometriosis.

One-step nucleic acid amplification (OSNA) assay for detecting lymph node metastasis in cervical and endometrial cancer: a preliminary study.

OBJECTIVE: To evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay for the diagnosis of lymph node (LN) metastasis in uterine cancer. METHODS: A total of 116 LNs from 30 patients with cervical and endometrial cancer, enrolled in this prospective study, were used. Excised LNs were cut into 4 to 6 blocks at 2 mm intervals, and nonadjacent blocks were alternately subjected to either histological examination or the OSNA assay. RESULTS: The concordance rate between histological examination and the OSNA assay in cervical cancer and in endometrial cancer was 95.9% and 95.2%, respectively. The sensitivity, specificity, and negative predictive value of the OSNA assay were 80%, 97.7%, and 97.7% in cervical cancer, and 85.7%, 93.3%, and 98.2% in endometrial cancer, respectively. In cervical cancer, discordant results were observed in 2 out of 49 LNs (4.1%); 1 was OSNA assay-positive and histological examination-negative, and 1 was OSNA assay-negative and histological examination-positive. In endometrial cancer, discordant results were observed in 5 out of 67 LNs (7.5%); 4 were OSNA assay-positive and histological examination-negative, and 1 was OSNA assay-negative and histological examination-positive. CONCLUSION: The OSNA assay showed high concordance rate with histological examination, sensitivity, and specificity in uterine cancer, suggesting that it could enhance the accuracy of conventional pathological examination for the detection of LN metastasis by reducing false negative rate.

Comparison of radio-isotope method with 99m technetium and near-infrared fluorescent imaging with indocyanine green for sentinel lymph node detection in endometrial cancer.

BACKGROUND: We aimed to compare the detection rate of pelvic sentinel lymph node between the radio-isotope with 99m technetium (99mTc)-labeled phytate and near-infrared fluorescent imaging with indocyanine green in patients with endometrial cancer. METHODS: This study included 122 patients who had undergone sentinel lymph node mapping using 99mTc and indocyanine green. In the radio-isotope method, sentinel lymph nodes were detected using uterine cervix 99mTc injections the day before surgery. Following injection, the number and locations of the sentinel lymph nodes were evaluated by lymphoscintigraphy. In addition, indocyanine green was injected into the cervix immediately before surgery. RESULTS: The overall pelvic sentinel lymph node detection rate (at least one pelvic sentinel lymph node detected) was not significantly different between 99mTc (95.9% [117/122]) and indocyanine green (94.3% [115/122]). Similarly, the bilateral sentinel lymph node detection rate was not significantly different between 99mTc (87.7% [107/122]) and indocyanine green (79.5% [97/122]). More than two sentinel lymph nodes per unilateral pelvic lymph node were found in 12.3% (15/122) and 27% (33/122) of cases with 99mTc and indocyanine green, respectively, in the right pelvic side, and 11.5% (14/122) and 32.8% (40/122) of cases with 99mTc and indocyanine green, respectively, in the left pelvic side. indocyanine green showed that there were significantly more than two sentinel lymph nodes in either the left or right pelvic sentinel lymph nodes (P < 0.0001). There was a significant difference in the mean number of total pelvic sentinel lymph nodes between 99mTc (2.2) and indocyanine green (2.5) (P = 0.028) methods. CONCLUSION: Although indocyanine green is useful for sentinel lymph node identification, we believe it is better to use it in combination with 99mTc until the surgeon is accustomed to it.

Zinc supplementation during chemotherapy for gynecological malignancy.

OBJECTIVE: To determine the significance of zinc supplementation for zinc deficiency during chemotherapy for gynecologic malignancies. METHODS: Twenty-eight patients suspected of zinc deficiency before chemotherapy were prospectively evaluated. Gustatory test, serum zinc, blood count, and biochemical examinations were made pre-chemotherapy at 3- and 6-week intervals. Patients with serum zinc levels <70 µg were prescribed oral zinc acetate hydrate (167.8 mg/day) for 3 weeks. The primary outcome was efficacy of zinc supplementation, the secondary outcomes were zinc deficiency rates and adverse effects of the zinc supplement. RESULTS: Fifteen (mean serum zinc level: 67.4 ± 6.2 µg/dL) out of 28 patients were administered zinc supplementation pre-chemotherapy, and subsequent serum zinc levels reached 83.2 ± 15.3 µg/dL in 3 weeks. Factors associated with chemotherapy (vs. chemoradiation, p = 0.041) and taxane + platinum (p = 0.048) were significant risk factors for decreasing zinc levels following chemotherapy. Although patients that required zinc supplementation showed decreased serum zinc levels after chemotherapy and tended to experience taste alteration (sour: p = 0.041), zinc supplementation for zinc deficiency during chemotherapy did not alter taste perception. CONCLUSION: Zinc supplementation promptly increased serum levels without major complications and may prevent an alteration in taste perception.

The use of bevacizumab is correlated with improved post-progression survival in advanced recurrent ovarian cancer.

BACKGROUND: The recent improvements in anti-cancer therapy following first-line treatment can potentially impact post-progression survival. We evaluated the factors that influence post-progression survival in advanced recurrent ovarian cancer. METHODS: Eighty-nine patients who underwent first-line treatment between June 2005 and December 2017 were included. The post-progression survival was defined as the difference between overall survival and initial progression-free survival. The effects of age, histology, stage, optimal surgery, secondary debulking surgery, bevacizumab administration, platinum sensitivity, and olaparib maintenance in recurrence were compared and independent risk factors were determined. RESULTS: The median follow-up duration was 60.0 months (range: 2-181). Platinum-sensitive recurrence had longer post-progression survival than platinum-resistant (P < 0.001). Inclusion of bevacizumab in first-line treatment did not produce a significant difference in post-progression survival (P = 0.462). Secondary debulking surgery (P = 0.013), bevacizumab administration (P < 0.001), and olaparib maintenance (P = 0.001) during recurrence increased post-progression survival. In multivariate analysis, histologies other than serous or endometrioid (hazard ratio = 2.389; 95% confidence interval = 1.200-4.754; P = 0.013) and non-bevacizumab usage in recurrence (hazard ratio = 4.484; 95% confidence interval = 1.939-10.370; P < 0.001) were independently correlated with poorer prognosis. Bevacizumab administration beyond progressive disease elicited improved post-progression survival (P < 0.001). In patients receiving bevacizumab in first-line treatment, exclusion of bevacizumab in the recurrent therapy (hazard ratio = 5.507; 95% confidence interval = 2.301-12.124; P < 0.001) was independently correlated with poorer prognosis. CONCLUSIONS: The continuous use of bevacizumab beyond progressive disease improves post-progression survival suggesting its important role in first-line and recurrence treatment for ovarian cancer.

Importance of Cervical Elongation Assessment for Laparoscopic Sacrocolpopexy.

Cervical elongation in patients with pelvic organ prolapse (POP), who previously underwent laparoscopic sacrocolpopexy (LSC), is not fully understood. We report a case of a second surgery for endometrial cancer complicated with POP recurrence, which seemed to be related to cervical elongation following LSC. A 65-year-old woman was referred for invasive treatment following LSC. Although preoperative endometrial cytology was negative, the resected uterine specimen revealed endometrioid carcinoma. The patient also had complications of cervical prolapse with cystocele Stage III. Repeat surgery was performed with a trachelectomy, anterior-posterior colporrhaphy, and vaginal apex suspension. Mesh had been adequately sutured to the upper cervix in the previous surgery, and the resected cervix was elongated up to 9 cm. Cervical elongation may be correlated with the inaccurate preoperative endometrial examination, and it may also promote POP recurrence leading to a poorly supported pelvic floor. We suggest that cervical elongation should be identified before POP surgery.

Correlation of World Health Organization 2010 Classification for Gastroenteropancreatic Neuroendocrine Neoplasms with the Prognosis of Ovarian Neuroendocrine Neoplasms: Kansai Clinical Oncology Group-Protocol Review Committee/Intergroup Study.

BACKGROUND: In 2014, the World Health Organization (WHO) released a classification system introducing neuroendocrine neoplasms (NENs) of the female reproductive tract, excluding the ovaries. This study aimed to evaluate whether retrospective adaption of the gastroenteropancreatic (GEP)-NEN classification is feasible for ovarian NENs (O-NENs) and correlates with prognosis. METHODS: Sixty-eight patients diagnosed with carcinoid, small cell carcinoma (pulmonary type), paraganglioma, non-small/large cell neuroendocrine carcinoma (NEC), mixed NEC, or undifferentiated carcinomas at 20 institutions in Japan were included in this retrospective cross-sectional study. We identified O-NENs through central pathological review using a common slide set, followed by reclassification according to WHO 2010 guidelines for GEP-NENs. A proportional hazards model was used to assess the association of prognostic factors (age, stage, performance status, histology, and residual disease) with overall survival (OS) and progression-free survival (PFS). RESULTS: Of the 68 enrolled patients, 48 were eligible for analysis. All carcinoids (n = 32) were reclassified as NET G1/G2, whereas 14 of 16 carcinomas were reclassified as NEC/mixed adeno-NEC (MANEC) (Fisher's exact test; p < 0.01). The OS/PFS was 49.0/42.5 months and 6.5/3.9 months for NET G1/G2 and NEC/MANEC, respectively. Histology revealed that NEC/MANEC was associated with increased risk of death (HR = 48.0; 95% CI, 3.93-586; p < 0.01) and disease progression (HR = 51.6; 95% CI, 5.54-480; p < 0.01). CONCLUSION: Retrospective adaption of GEP-NEN classification to O-NENs is feasible and correlates well with the prognosis of O-NENs. This classification could be introduced for ovarian tumors.

Current status of tertiary debulking surgery and prognosis after secondary debulking surgery for recurrent Müllerian epithelial cancer in Japan: a retrospective analysis of 164 patients (KCOG-G1402).

BACKGROUND: This study aimed to evaluate the current status of secondary debulking surgery (SDS) and tertiary debulking surgery (TDS; performed for recurrence after SDS) and to assess the overall survival after recurrence of Müllerian epithelial cancer in Japan. We also evaluated the data of patients who underwent a fourth debulking surgery (i.e., quaternary debulking surgery (QDS)). METHODS: We conducted a retrospective study of 164 patients with recurrent Müllerian epithelial cancers (i.e., ovarian, tubal, and peritoneal cancers). The SDS was performed between January 2000 and September 2014 in 20 Japanese hospitals. Clinicopathological data were collected and analyzed. RESULTS: Of the 164 patients, 66 patients did not have a recurrence or died after SDS. Ninety-eight patients had a recurrence after SDS. Forty-three of the 98 patients underwent TDS; 55 of the 98 patients did not undergo TDS and were classified into the non-TDS group. The overall survival (OS) after SDS was significantly better in the TDS group than in the non-TDS group. The median OS after SDS was 123 and 42 months in the TDS group and non-TDS group, respectively. Of the 43 patients who received TDS, 11 patients were further treated with QDS. The median OS after SDS was 123 months for patients who underwent QDS. CONCLUSIONS: This multicenter study on the prognosis of post-SDS is apparently the first report on QDS in Japan. Patients undergoing TDS have a good prognosis, compared to patients in the non-TDS group. Novel drugs are being evaluated; however, debulking surgery remains a necessary treatment for recurrence.