Effect of prior olaparib maintenance therapy for platinum sensitive recurrent ovarian cancer on response to subsequent platinum-based chemotherapy.

AIM: Several years have passed since olaparib maintenance therapy was approved in patients with platinum sensitive recurrent ovarian cancer (PSROC). We speculated that the response to platinum-based chemotherapy (PBC) would be impaired at the time of recurrence after olaparib maintenance therapy. We conducted a noninterventional retrospective study to clarify this clinical question in a single institution. METHODS: We included all patients with PSROC who received olaparib after second or later line of PBC between April 18, 2018, and August 31, 2021. We evaluated the effect of olaparib maintenance therapy on PBC after progression. RESULTS: We identified 42 patients who received olaparib maintenance therapy after second or later line of PBC. Twenty-four patients relapsed after olaparib maintenance therapy, and 17 patients received PBC again. Four of 17 patients (complete response 2, partial response 2) responded to the PBC. The median progression-free survival was longer in patients with platinum-free interval ≥12 months than platinum-free interval of 6-12 months (9.7 vs 2.6 months, hazard ratio, 0.20: 95% confidence interval, 0.04-0.90; p = 0.04). CONCLUSIONS: In the patients with PSROC who experienced disease progression after olaparib maintenance therapy, especially in those with platinum-free interval of 6-12 months, the response to subsequent PBC was extremely poor. The efficiency of re-administration of PBC for PSROC patients with a short-term recurrence after olaparib treatment may need to be reconsidered.

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.

Survival impact of adjuvant concurrent chemoradiotherapy after radical hysterectomy in FIGO stage IIIC1 cervical adenocarcinoma.

BACKGROUND: We evaluated the survival effect of adjuvant concurrent chemoradiotherapy after radical hysterectomy in patients with clinical pelvic node-positive cervical adenocarcinoma. METHODS: Patients with pelvic node-positive cervical adenocarcinoma diagnosed between 2000 and 2016 at our institution were identified. Survival was compared between patients who underwent radical hysterectomy alone and those who received concurrent chemoradiotherapy as an adjuvant treatment. Survival analysis using log-rank test and Cox proportional hazards model was performed. RESULTS: We identified 80 patients who underwent radical hysterectomy for clinical pelvic node-positive cervical adenocarcinoma; of these, four with pathological pelvic node-negative adenocarcinoma were excluded. Of the 76 patients, 27 underwent radical hysterectomy alone and 49 received radical hysterectomy followed by concurrent chemoradiotherapy. With a median follow-up of 53 months, the 5-year overall survival rate was 51.0% in patients who underwent radical hysterectomy alone versus 53.0% in patients who received additional concurrent chemoradiotherapy (log-rank p = 0.455). CONCLUSION: The addition of concurrent chemoradiotherapy after radical hysterectomy did not significantly improve survival among patients with pelvic node-positive cervical adenocarcinoma. More appropriate treatment strategies are needed to improve the survival outcomes of these patients.

Treatment strategy for locally advanced squamous cell cervical cancer with clinically positive pelvic lymph nodes metastasis.

AIM: To determine the optimal treatment for locally advanced squamous cell cervical cancer with clinical positive pelvic lymph nodes metastasis (cN1). METHODS: We enrolled patients with squamous cell cervical cancer with 2008 FIGO stages IB, IIA, or IIB diagnosed with cN1, who were treated at Hyogo Cancer Center between April 2010 and December 2016. Patients with para-aortic lymph nodes metastasis were excluded. RESULTS: Of the 69 eligible patients, 24 underwent concurrent chemoradiotherapy (CCRT), 11 underwent radical hysterectomy with pelvic lymphadenectomy (RH) with or without adjuvant RT, and 34 underwent neoadjuvant chemotherapy (NAC) followed by RH as initial treatment. The regimens of NAC included dose-dense TC (paclitaxel 80 mg/m2 , days 1, 8, 15; and carboplatin at an area under the curve = 6 on day 1, every 3 weeks) and dose-dense TP (paclitaxel 80 mg/m2 on days 1, 8, 15; and cisplatin 75 mg/m2 on day 1, every 3 weeks). The median observation period was 57 (12-107) months. The 5-year disease-free survival rates of the CCRT, RH, and NAC groups were 78.7%, 63.6%, and 88.2%, respectively (p = 0.14). The 5-year overall survival rates of the CCRT, RH, and NAC groups were 78.6%, 70.1%, and 94.1%, respectively (p = 0.11). CONCLUSIONS: We recommend avoiding RH as primary treatment for cN1 with locally advanced squamous cell cervical cancer. Although CCRT should be considered for cN1, further studies are required to determine if NAC followed by RH will serve as an effective option.

Quality of life assessment of cell-free and concentrated ascites reinfusion therapy during initial treatment for advanced ovarian cancer: A prospective cohort study.

AIM: Cell-free and concentrated ascites reinfusion therapy (CART) is applied to relieve symptoms in patients with malignant ascites. We performed a prospective cohort study to evaluate the efficacy and safety of CART performed on patients with advanced ovarian and peritoneal cancers with massive ascites during the initial treatment. METHODS: From April 2018 to July 2020, CART was performed during the initial treatment of 31 patients with advanced ovarian and peritoneal cancers with cancerous ascites. Patient characteristics and clinical information before and after CART were collected. We performed quality of life assessment using the Japanese version of the M.D. Anderson Symptom Inventory (MDASI-J) 24 h before and after CART. RESULTS: CART was performed 38 times in 24 patients before or during neoadjuvant chemotherapy and 11 times in 11 patients prior to surgery. Four patients underwent CART before primary surgery and before and/or during chemotherapy. Grade 1-2 fever was observed in 18 of 31 cases (58%), and all were controllable by nonsteroidal anti-inflammatory drugs. CART did not adversely affect the main treatment, chemotherapy, or surgery. CART significantly improved the MDASI-J symptom and interference scores within 24 h after the procedure. The symptom and interference scores decreased from 2.4 to 1.8 and from 4.8 to 3.0, respectively. CONCLUSIONS: CART can be safely performed and is useful for symptom relief and improvement of general condition prior to initial surgery and during initial chemotherapy in ovarian and peritoneal cancers. Performing CART at the time of initial treatment may facilitate initiation of the main treatment.

Pathological processes and pretreatment cytologic diagnosis of neuroendocrine carcinoma of the endometrium: addendum report of the Kansai Clinical Oncology Group/Intergroup study in Japan.

A previous retrospective study of a neuroendocrine carcinoma of the endometrium including 42 cases employed a central pathologic review to ensure the reliability of the findings. However, the pathological processes were not described in detail. In this study, we further analyzed these processes and the results of pretreatment endometrial cytology of neuroendocrine carcinoma. Of the 65 patients from 18 institutions registered in the study, 42 (64.6%) were diagnosed with neuroendocrine carcinoma of the endometrium based on the central pathological review. Thirteen of the 23 excluded cases conflicted from their original diagnoses: 5 (38.5%) were diagnosed with endometrioid adenocarcinoma, 5 (38.5%) with undifferentiated carcinoma, and 3 (23.1%) with carcinosarcoma. Immunohistochemical staining led to a change in diagnosis for 8 (61.5%) of the 13 cases. Pretreatment endometrial cytology was examined in 38 (90.5%) cases; 34 (89.5%) of these 38 cases were found, or suspected, to be positive. To ensure the selection of appropriate therapy and keeping patients correctly informed, it is important to distinguish neuroendocrine carcinoma from other similar histologic types. Endometrial cytology may help in the early detection of this disease.

Suppressive effect upon carboplatin hypersensitivity reaction via pegylated liposomal doxorubicin combination therapy.

BACKGROUND: Occurrence of hypersensitivity reaction (HSR) in patients having received multiple doses of carboplatin has been reported. Several studies demonstrated reduction of carboplatin-associated HSR with in combination with pegylated liposomal doxorubicin (PLD). The objective of this study was to determine the suppressive effect on carboplatin-induced HSR via combined treatment with PLD within clinical practice. METHODS: We reviewed the medical records of women with primary or recurrent ovarian, fallopian tube, or peritoneal cancer treated with carboplatin containing regimen at our hospital between January 2009 and March 2019. We compared the incidence of carboplatin-induced HSR among patients who received more than one cycle of PLD plus carboplatin (PLD-C) therapy (i.e., PLD-C group) versus patients who never received PLD-C therapy (non-PLD-C group). RESULTS: A total of 414 women were included in this study (48: PLD-C group, 366: non-PLD-C group). Carboplatin-induced HSR occurred in 34 total patients (8.2%) [1/48 (2.1%) in the PLD-C group and 33/366 (9.0%) in the non-PLD-C group], with a median cycle number of carboplatin administration at onset of HSR being 9. Incidences of carboplatin-induced HSR within the PLD-C versus non-PLD-C group at the 8th, 12th, and 16th cycles of carboplatin administration were 2.2% vs 11.2%, 2.2% vs 28.6%, and 2.2% vs 39.1%, respectively [hazard ratio: 19.2 (95% confidence interval: 9.82-39.4), p < 0.0001]. CONCLUSION: Based on the data analyzed here, a suppressive effect on carboplatin-induced HSR via combination therapy with PLD was confirmed within clinical practice.

Dose-dense paclitaxel and carboplatin vs. conventional paclitaxel and carboplatin as neoadjuvant chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer: a retrospective study.

BACKGROUND: The purpose of this study was to determine the optimal regimen of neoadjuvant chemotherapy (NAC) for advanced epithelial ovarian, fallopian tube, and peritoneal cancers. METHODS: A clinical information survey involving 171 patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer was conducted. These patients underwent NAC followed by interval debulking surgery at the Hyogo Cancer Center (Hyogo, Japan) between January 2006 and December 2015. RESULTS: The median observation period was 41 (range 4-138) months. Dose-dense paclitaxel and carboplatin (TC) was administered in 101 patients (59%); tri-weekly TC was administered 70 patients (41%). Median progression-free survival was 21 [95% confidence interval (CI) 18-23] months and 15 (95% CI 13-17) months in the dose-dense TC and conventional-TC group [hazard ratio (HR) = 0.69, 95% CI 0.46-0.96; p = 0.02], respectively. The median overall survival was 59 (95% CI 46-72) and 40 (95% CI 32-57) months in the dose-dense TC group and conventional-TC group (HR = 0.72, 95% CI 0.48-1.06; p = 0.09). Multivariate analysis for progression-free survival demonstrated that dose-dense TC represented an independent prognostic factor (HR = 0.70, 95% CI 0.50-0.99; p = 0.04). CONCLUSIONS: Dose-dense TC is a promising regimen of NAC for advanced epithelial ovarian cancer.

Phase II trial of paclitaxel, carboplatin, and bevacizumab for advanced or recurrent cervical cancer.

OBJECTIVE: We evaluated the efficacy and safety of the combination of paclitaxel, carboplatin, and bevacizumab in patients with advanced or recurrent cervical cancer. METHODS: Subjects included patients with advanced or recurrent cervical cancer not amenable to curative treatment with surgery or radiation therapy. Treatment consisted of paclitaxel 175 mg/m2, carboplatin area under the curve 6 mg/mL/min, and bevacizumab 15 mg/kg every 21 days until disease progression, complete remission, or limiting toxicity. The primary endpoint was the objective response. RESULTS: In total, 34 patients received a median of 6 treatment cycles (range 2-25). The median follow-up period was 18.5 months (range 2-29). The objective response was 88% (95% confidence interval: 72.5%-96.7%). Seventeen patients (50%) experienced complete response, whereas 13 patients experienced (38%) partial response with a median duration of 6 months. Grades 3 and 4 hematologic toxicities manifested as neutropenia in 14 (41.2%), leukopenia in 14 (41.2%), anemia in 11 (32.4%), and thrombocytopenia in 9 (26.5%) patients. One patient who underwent prior pelvic irradiation developed grade 2 rectovaginal fistula. CONCLUSION: The combination of paclitaxel, carboplatin, and bevacizumab is effective and safe in patients with advanced or recurrent cervical cancer.

Correlation between pre-operative and final histological diagnosis on endometrial cancer.

OBJECTIVE: We conducted a retrospective study to evaluate the correlation between pre-operative and post-operative histological diagnoses on endometrial cancer, and to describe the treatments and outcomes when post-operative diagnoses are downgraded from pre-operative histology. METHODS: Patients who underwent surgery for endometrial cancer in our facility between 2010 and 2013 were enrolled in the study. The definition of downgrade discordance is in accordance with the following criteria: 1) the pre-operative and post-operative histological diagnoses were both endometrioid and the final pathology was a lower grade than the pre-operative pathology and 2) the pre-operative diagnosis was not endometrioid, whereas the post-operative diagnosis was endometrioid grade 2 or less. RESULTS: A total of 250 patients were enrolled, and the concordance rates were 56% for endometrioid adenocarcinoma grade 1 (EMG1), 67% for EMG2, 67% for EMG3, 82% for carcinosarcoma, 71% for serous carcinoma, and 67% for clear cell carcinoma. Eighteen cases (6.6%) were identified as downgrade discordancy. Of the 18 patients, the triage for adjuvant therapy remained the same for 15 cases (83%), all of whom had no evidence of disease at their last visit. Three cases had discordances with respect to triage for adjuvant therapy; the therapies were triaged based on post-operative diagnosis. Of these patients one had a recurrence. CONCLUSIONS: Good correlation was observed between pre-operative and final histological diagnoses of endometrioid carcinoma (56%-67%) and type 2 carcinoma (67%-82%). Approximately 7% (18/250) of patients had downgrade discordancy; however, triage for adjuvant therapy did not change for approximately 80% (15/18) of the patients with downgrade discordancy. Further studies are needed to evaluate the effectiveness of triages that are based on post-operative diagnoses.

Pelvic fractures after definitive and postoperative radiotherapy for cervical cancer: A retrospective analysis of risk factors.

OBJECTIVES: This study clarified the incidence of and identified the risk factors for post-radiation pelvic insufficiency fractures (PIFs) in women who received postoperative definitive or adjuvant radiotherapy (RT) for cervical cancer. PATIENTS AND METHODS: The medical records and data of imaging studies, including computed tomography scan and magnetic resonance imaging, of women with cervical cancer who received external-beam RT for the entire pelvic area between January 2003 and December 2012 at our institution were reviewed. RESULTS: A total of 533 patients with histologically diagnosed cervical cancer who received RT (298: definitive RT, 235: adjuvant RT) were included in this study. Eighty-four patients (15.8%) developed PIF in the irradiated field. Median age at onset of PIF was 72.5years (range: 54-95years), and 82 of them (98%) were postmenopausal women. Sixty-nine patients (80%) developed PIF within 3years from the completion of RT. The median time for the development of PIF was 14months (range: 1-81months). The most commonly involved fracture site was the sacral bone. Postmenopausal state, coexistence of rheumatoid arthritis, and high-dose-rate intracavitary brachytherapy (HDR-ICBT) use were significant predisposing factors for the development of PIF, according to multivariate analysis. CONCLUSIONS: The incidence rate of PIF among patients who received RT for locally advanced cervical cancer was 15.8%. The principal predisposing factors for post-radiation PIF were postmenopausal state, rheumatoid arthritis, and HDR-ICBT use. Active interventions, including bone density screening followed by medication, should be considered during the early stage of RT for women with high-risk factors of PIF.

Does positive peritoneal cytology not affect the prognosis for stage I uterine endometrial cancer?: the remaining controversy and review of the literature.

OBJECTIVE: The objective of this study was to elucidate factors that affect prognosis in patients with stage I endometrial cancer. METHODS: The study group comprised 265 patients with stage I endometrial cancer treated surgically at either of our facilities between January 1998 and December 2010 (238 patients with negative peritoneal cytology and 27 patients with positive peritoneal cytology). Progression-free survivals were evaluated between the 2 groups, and multivariate analysis was conducted with correlation factors including positive peritoneal cytology, vessel permeation, lymph node dissection, histologic diagnosis, age at diagnosis, adjuvant chemotherapy, and the depth of myometrial invasion. RESULTS: Disease-free survival was significantly poorer for patients with positive peritoneal cytology than those with negative peritoneal cytology on stage I disease (P = 0.000). The stratified log-rank test with vessel permeation shows the similar results. By univariate Cox model, positive peritoneal cytology, vessel permeation, and systemic lymph node dissection at surgery are significant factors on stage I endometrial cancer. CONCLUSIONS: Although this is a small-scale preliminary study with adjustment of other factors, positive peritoneal cytology can contribute to the risk of progression-free survival in patients with stage I endometrial cancer.

Association of CXC chemokine receptor type 4 expression and clinicopathologic features in human vulvar cancer.

OBJECTIVE: Although CXC chemokine receptor type 4 (CXCR4) is known to be expressed in various solid tumors and plays an integral role in cancer invasion and metastasis, expression of CXCR4 in human vulvar cancer has not yet been investigated. We examined distribution and expression of this chemokine receptor in specimens of invasive and noninvasive human vulvar neoplasms to elucidate its clinical significance. METHODS: Study patients were 38 consecutive patients (31 with primary vulvar cancers and 7 with intraepithelial neoplasms) treated at one of our hospitals. Sections of all specimens were evaluated for CXCR4 expression by means of immunohistochemistry. Relations between CXCR4 expression and clinicopathologic features including prognosis were investigated. RESULTS: None of the 7 vulvar intraepithelial lesions expressed CXCR4. Of the 31 invasive vulvar tumor samples examined, 19 (61%) stained positively for CXCR4; 15 (68%) of 22 squamous cell carcinomas and 2 (29%) of 7 Paget tumors were CXCR4 positive. The difference in expression between invasive cancers and intraepithelial neoplasms was significant (P = 0.003). FIGO (International Federation of Gynecology and Obstetrics) stage III-IV cancers, in comparison to FIGO stage I-II cancers, were more likely to be positive for CXCR4 (82% vs 50%, P = 0.08). In terms of disease-free survival, prognosis of cancers that expressed CXCR4 was poorer than that of CXCR4-negative cancers (P = 0.013), but in terms of disease-specific survival, prognosis did not differ significantly between CXCR4-positive and -negative cancers (P = 0.111). CONCLUSIONS: More than half of invasive squamous cell vulvar cancers can be expected to express CXCR4, and CXCR4 expression correlates with poor disease prognosis.

Large or persistent lymphocyst increases the risk of lymphedema, lymphangitis, and deep vein thrombosis after retroperitoneal lymphadenectomy for gynecologic malignancy.

PURPOSE: This retrospective study examined the incidence of lymphocyst formation after retroperitoneal lymphadenectomy in patients with gynecologic malignancy as well as the relation between lymphocyst formation and such complications as lymphedema, lymphangitis, ileus, and deep vein thrombosis (DVT). METHODS: Three hundred twenty-one patients who underwent primary surgery with pelvic (90 patients) or combined pelvic and paraaortic lymphadenectomy (231 patients) for gynecologic malignancy between January 2001 and December 2009 were enrolled. The incidences of lymphocyst identified by computed tomography at 3 weeks and 1 year after surgery were analyzed in relation to the types of surgery and types of complications. RESULTS: At 3 weeks after surgery, lymphocysts were observed in 282/321 patients (88 %). At 1 year after surgery, lymphocysts persisted in 69 patients (21 %). Lymphedema was observed in 34/321 (11 %) patients, lymphangitis in 36/321 (11 %), ileus in 14/321 (4 %), and DVT in 24/321 (7 %). The incidence of lymphedema was significantly greater in patients with persistent lymphocyst than in those with without (17 vs. 9 %) (p = 0.038); the incidences of lymphangitis (20 vs. 9 %) (p = 0.007) were also greater in this group. Multivariate analysis showed a large lymphocyst (>50 mm) at 3 weeks after surgery to be an independent risk factor for lymphedema (odds ratio 2.76, p = 0.009). CONCLUSIONS: A large lymphocyst at 3 weeks after surgery or persistent lymphocyst increases the risk of lymphedema, lymphangitis, and DVT.

A case series title: femoral nerve injury with an episode of motor neuropathy caused by gynecological surgery: a case series.

Background: Although iatrogenic nerve injury is sometimes diagnosed after gynecological surgery, its incidence is underestimated because most cases are self-limiting and underreported. Herein, we report on six cases of femoral nerve injury after gynecological surgery with both sensory and motor neuropathy. Methods: We retrospectively analyzed 785 patients with gynecological cancer requiring surgery, including lymph node dissection, between 2012 and 2016 at our center. The functional damage due to femoral nerve injury was postoperatively assessed and classified according to the Medical Research Council (MRC) scale by an orthopedist and a physiatrist. The eligibility criteria were grade 3 or less hip joint bending and muscular weakness due to nerve injury. Patients were excluded if they had been diagnosed with an isolated sensory disorder. Results: We found six cases (0.76%) of femoral motor neuropathy resulting from gynecological surgery. All six patients underwent laparotomy using energy devices under general anesthesia with epidural anesthesia in the lithotomy position. Four of them recovered fully within 8 months from surgery with either physical therapy or no treatment, while the other two died within a year post-treatment; thus, recovery evaluation could not be accurately performed. Conclusion: Postoperative femoral nerve injury can be diagnosed based on gait disturbances and difficulties climbing stairs. It is difficult to identify risk factors for femoral nerve injury as they may involve a combination of features, such as intraoperative compression with self-retaining retractors, the lithotomy position, and the use of energy devices. The surgeon should be familiar with the nature of energy devices, make every effort to understand the necessary anatomy, and make every effort to avoid femoral nerve injury. Iatrogenic femoral nerve injury caused by gynecological surgery should be further investigated regarding the patients' quality of life postoperatively.

A case of usual (basaloid)-type vulvar intraepithelial neoplasia that failed to respond to imiquimod cream: clinical implications.

The authors report a case of usual-type (basaloid-type) vulvar intraepithelial neoplasia (VIN) 3 that failed to respond to imiquimod cream. A 51-year-old Japanese woman visited her local gynecologist complaining of vulvar itching. Atypical cells were noted in cytology smears, but nine vulvar biopsy specimens showed benign proliferation of epithelial tissue. The patient was placed under careful observation for 8 months, when the vulvar smears once again showed atypical cells and biopsy specimens revealed VIN3. The patient was then referred to our hospital where she was given a diagnosis of VIN 3, basaloid type of usual type. The biopsy specimens were positive for p16 and the lesions were confirmed to be human papilloma virus (HPV)-related. We recommended simple vulvectomy but the patient requested conservative treatment with imiquimod cream. With her written informed consent, we prescribed imiquimod cream to be self-administered 3 times a week. Colposcopy and pap smear test were performed every 2 weeks. Four weeks after the start of treatment, a fingertip-sized papule was detected at the patient's vaginal introitus. By 6 weeks, the lesion had enlarged, and biopsy specimens revealed invasive squamous cell carcinoma. At 7 weeks, we performed simple vulvectomy. The surgical specimen showed stage pT1b keratinizing-type squamous cell carcinoma. HPV-16 DNA was detected in the specimen.

Efficacy of a sodium hyaluronate-carboxycellulose membrane (seprafilm) for reducing the risk of early postoperative small bowel obstruction in patients with gynecologic malignancies.

OBJECTIVE: To evaluate the effect of a sodium hyaluronate and carboxymethylcellulose membrane (Seprafilm) on early postoperative small bowel obstruction (EPSBO) in patients with gynecologic malignancies. METHODS: One hundred forty-five patients who had Seprafilm placed during gynecological surgery between April 2002 and March 2007 (Seprafilm group) were compared with a historical control group of patients managed without Seprafilm between January 1997 and March 2002. All patients undergoing primary surgery with pelvic or combined pelvic and para-aortic lymphadenectomy for gynecological malignancies were retrospectively assessed for EPSBO and surgical infections. RESULTS: The incidence of EPSBO was significantly lower (P < 0.05) in the Seprafilm group (3.1%, 6/191) than in the control group (13.9%, 25/180). According to logistic regression analysis, the use of Seprafilm (odds ratio, 0.18; 95% confidence interval, 0.07-0.47; P < 0.0005) and the performance of pelvic lymphadenectomy alone (odds ratio, 0.27; 95% confidence interval, 0.09-0.78; P < 0.02) were independent predictors of a lower rate of EPSBO. The incidence of surgical infection showed no significant difference between the Seprafilm group (3.6%) and the control group (6.7%). CONCLUSIONS: Placement of Seprafilm helped to prevent EPSBO and had no significant adverse effect on surgical infections in patients who underwent lymphadenectomy for gynecological malignancy.

A phase II study of the combination chemotherapy of bevacizumab and gemcitabine in women with platinum-resistant recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer.

INTRODUCTION: Bevacizumab and gemcitabine are key drugs for treating recurrent epithelial ovarian cancer. However, information about the combination of bevacizumab and gemcitabine is insufficient. We conducted a phase II study to assess the feasibility, clinical activity, and toxicity of this combination chemotherapy. METHODS: This study included women with platinum-resistant recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer who received one to three regimens of platinum-based chemotherapy between April 1, 2015 and December 31, 2018. The patients received bevacizumab 15 mg/kg intravenously on day 1 and gemcitabine 1000 mg/m2 intravenously on days 1 and 8 every 21 days until disease progression or unacceptable toxicity. The primary endpoint was the completion rate of three cycles of chemotherapy. This study was registered in the University Medical Information Network (UMIN) Clinical Trials Registry (UMIN000016619). RESULTS: Among the 19 patients, 18 (95%) received ≥3 and 9 (47%) received ≥6 cycles of the study therapy. The objective response rate was 42% (complete response of 16% and partial response of 26%), and the clinical control rate was 84%. Hematological toxicity included neutropenia grade 3/4 in 9 patients (47%), anemia grade 3/4 in 2 (11%), and thrombocytopenia grade 3/4 in 1 (5%). One patient (5%) had grade 3 hypertension, and 1 (5%) had grade 3 protein urea. Possibly related grade 3 pulmonary toxicity was observed in 1 patient. Three patients needed dose reduction of gemcitabine to 800 mg/m2 due to treatment delay by 15 to 21 days on day1. There was no treatment delay more than 14 days on day 8. The median progression-free survival duration was 5.1 months and median overall survival duration was 21.3 months. CONCLUSION: The combination chemotherapy with gemcitabine and bevacizumab was feasible, effective and safe. This combination chemotherapy may be explored in a further randomized trial.

Clinicopathologic features, treatment, prognosis and prognostic factors of neuroendocrine carcinoma of the endometrium: a retrospective analysis of 42 cases from the Kansai Clinical Oncology Group/Intergroup study in Japan.

OBJECTIVE: We conducted a retrospective, multi-institutional, collaborative study to accumulate cases of neuroendocrine carcinoma of the endometrium, to clarify its clinicopathologic features, treatment, prognosis and prognostic factors to collate findings to establish future individualized treatment regimens. To our knowledge, this is the largest case study and the first study to statistically analyze the prognosis of this disease. METHODS: At medical institutions participating in the Kansai Clinical Oncology Group/Intergroup, cases diagnosed at a central pathologic review as neuroendocrine carcinoma of the endometrium between 1995 and 2014 were enrolled. We retrospectively analyzed the clinicopathologic features, treatment, prognosis and prognostic factors of this disease. RESULTS: A total of 65 cases were registered from 18 medical institutions in Japan. Of these, 42 (64.6%) cases were diagnosed as neuroendocrine carcinoma of the endometrium based on the central pathological review and thus included in the study. Advanced International Federation of Gynecology and Obstetrics stages (stage III and IV) and pure type small cell neuroendocrine carcinoma cases had a significantly worse prognosis. Upon multivariate analysis, only histologic subtypes and surgery were significant prognostic factors. Pure type cases had a significantly worse prognosis compared to mixed type cases and complete surgery cases had a significantly better prognosis compared to cases with no or incomplete surgery. CONCLUSION: Our findings suggest that complete surgery improves the prognosis of neuroendocrine carcinoma of the endometrium. Even among cases with advanced disease stages, if complete surgery is expected to be achieved, clinicians should consider curative surgery to improve the prognosis of neuroendocrine carcinoma of the endometrium.

Weekly low-dose paclitaxel and carboplatin therapy in gynecological cancer patients with venous thrombosis.

BACKGROUND: To evaluate the safety and toxicity of weekly low-dose paclitaxel plus carboplatin therapy in gynecological cancer patients with venous thrombosis (VT). MATERIALS AND METHODS: Ovarian or endometrial cancer patients with VT who were scheduled to receive neoadjuvant or adjuvant chemotherapy were eligible. Each 21-day cycle of treatment consisted of carboplatin (AUC 2.0) and paclitaxel (80 mg/m2) on days 1, 8 and 15. At the end of chemotherapy, each patient's VT was checked by ultrasonography. RESULTS: Twenty-five gynecological cancer patients who received warfarin therapy with a target international normalized ratio (INR) of 1.5-2.5 were enrolled in this study. Neutropenia and peripheral neuropathy (grades 3 or 4) occurred in 26% and 4% of the patients, respectively. Chemotherapy did not cause any changes of the INR in any patient. After chemotherapy, the VT showed resolution in 19 patients (76%) and no patient developed fresh thrombosis. CONCLUSION: Weekly low-dose paclitaxel plus carboplatin therapy is a reasonable treatment option for gynecological cancer patients with VT.