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PURPOSE To investigate the efficacy and safety of trastuzumab deruxtecan, an antibody-drug conjugate targeting human epidermal growth factor receptor 2 (HER2) with a topoisomerase I inhibitor payload, in patients with uterine carcinosarcoma (UCS) expressing HER2. PATIENTS AND METHODS Patients with recurrent UCS with HER2 immunohistochemistry scores ≥1+ previously treated with chemotherapy were included. Patients were assigned to the HER2-high (immunohistochemistry score ≥2+; n = 22) or low (immunohistochemistry score of 1+; n = 10) groups for primary and exploratory analyses, respectively. Trastuzumab deruxtecan 6.4 or 5.4 mg/kg was administered intravenously once every 3 weeks until unacceptable toxicity or disease progression. Dose modification was based on the updated recommended phase II dose for breast cancer to be 5.4 mg/kg. The primary end point was the objective response rate by central review in the HER2-high group. Secondary end points included the overall response rate (ORR) in the HER2-high group by investigator assessment, ORR in the HER2-low group, progression-free survival (PFS), overall survival (OS), and safety. RESULTS The ORR by central review in the HER2-high and HER2-low groups were 54.5% (95% CI, 32.2 to 75.6) and 70.0% (95% CI, 34.8 to 93.3) and those by investigator assessments were 68.2% and 60.0%, respectively. The median PFS and OS in the HER2-high and HER2-low groups were 6.2 and 13.3 months and 6.7 months and not reached, respectively. Grade ≥ 3 adverse events occurred in 20 patients (61%). Grades 1-2 and 3 pneumonitis/interstitial lung disease occurred in eight (24%) and one (3%) patient, respectively. CONCLUSION Trastuzumab deruxtecan has efficacy in patients with UCS, regardless of HER2 status. The safety profile was generally consistent with that previously reported. Toxicities were manageable with appropriate monitoring and treatment.

Uterine carcinosarcoma (UCS) is an uncommon and highly aggressive tumor. There is no HER2 testing protocol for UCS despite the development of HER2 antibody conjugates. We aimed to elucidate histopathological HER2 expression details in UCS, to compare HER2 scores between ASCO/CAP criteria for gastric and breast cancer, and to propose requirements for HER2 testing for UCS. Eighty-nine specimens from 84 patients with metastatic/recurrent UCS were prospectively collected from May 2018 to July 2020. We performed HER2 immunohistochemistry (IHC) for 89 specimens and FISH for 44 specimens. HER2 expression details and HER2 score were evaluated according to the latest ASCO/CAP criteria for gastric (2016) and breast cancer (2018). HER2 IHC scores according to the gastric cancer criteria were 0 in 31 cases (35%), 1+ in 26 (29%), 2+ in 22 (25%), and 3+ in 10 cases (11%) of the 89 specimens. A lateral/basolateral membranous staining pattern was observed in 28/32 (88%) specimens with HER2 scores of 2+/3+. HER2 intratumoral heterogeneity was identified in 28/32 (88%) of the specimens with HER2 scores of 2+/3+. The overall concordance rate of HER2 score was 70% between the gastric and breast criteria. FISH revealed HER2 gene amplification in 10/44 (23%) specimens containing only lateral/basolateral membranous staining pattern. Based on the histopathological features of HER2 expression in UCS, a scoring system that accepts lateral/basolateral staining patterns should be applied. Furthermore, we proposed specific requirements for UCS testing, including specimen selection, scoring system, and calculating the proportion of HER2-positive cells.

Objective: Malignant transformation of a mature cystic teratoma (MTMCT) of the ovary is extremely rare; the occurrence rate is ∼1%–3% of all mature cystic teratomas. Because of the rarity of MTMCT,...

To analyze the clinical behavior of neuroendocrine tumors (NETs) of the uterine cervix, we conducted a multicenter, retrospective study of 193 patients.We evaluated the prognosis of NETs according to the new International Federation of Gynecology and Obstetrics (FIGO) staging system, compared the clinical response to different chemotherapy regimens, and compared different histological subtypes of NETS.Diagnoses of the subjects were atypical carcinoid tumor (ACT, n = 37), small cell neuroendocrine carcinoma (SCNEC, n = 126), large cell neuroendocrine carcinoma (LCNEC, n = 22), and NET, not elsewhere classified (n = 8), according to central pathological review. According to FIGO 2018, 69, 17, 74, and 33 patients were at stage I, II, III, or IV, respectively. Five-year survival was 64.5%, 50.1%, 30.2%, and 3.4% for patients at stage I, II, III and IV. About 40% of patients with stage IIIC1 survived5 years. On multivariate analyses, locally-advanced disease, para-aortic node metastasis, distant metastasis, and4 cycles of chemotherapy were associated with poor survival. Histological subtype and pelvic node metastasis had no prognostic significance. Response rates to etoposide-platinum (EP) or irinotecan-platinum (CPT-P) regimens were 43.8% (28/64), but only 12.9% to a taxane-platinum (TC) regimen (4/31). The response rate for ACT was 8.7% (2/23), significantly less than the 36.6% for high-grade neuroendocrine carcinomas (HGNEC: both SCNEC and LCNEC, 41/111).Locally-advanced, extra-pelvic disease and insufficient chemotherapy were independent prognostic factors for cervical NET. HGNEC showed good responses to EP or CPT-P but not TC. Chemotherapy was less effective for ACT, which had a prognosis identical to HGNEC.

Aim Serous carcinoma of the uterine cervix (USCC) is a very rare malignant tumor, while this histological subtype is common in the ovary, fallopian tube, uterine corpus and peritoneum. Because of its rarity, details of the clinicopathological features of USCC are largely unknown. We retrospectively analyzed the clinicopathological characteristics of five cases of pure USCC. Methods We reviewed the medical records and pathological specimens of five USCC cases who were treated at the Gynecology Service of the National Hospital Organization Kyushu Cancer Center, Japan, between 2000 and 2017. The clinicopathological features were also compared with those of serous carcinomas of the endometrium and ovary who were treated during the same period. Results Five patients were treated at our hospital between 2000 and 2017. Three tumors were stage IB1, one was stage IIB, and one was stage IVB. The median follow‐up time was 104 months (range 26–210). Four patients other than stage IVB were treated with radical hysterectomy and have been free of relapse. One patient with stage IVB tumor was treated with platinum‐based combination chemotherapy and is currently on maintenance therapy with bevacizumab and remains free of relapse. Conclusion USCC has a distinctive clinicopathological feature that differentiates it from serous carcinomas of other female organs. USCC had been thought to be a poor prognostic disease; however, it could be curable if it is not accompanied by lymph node metastasis or peritoneal dissemination. We might conquer USCC even if it is accompanied by lymph node metastasis with the use of multimodal therapy.

Objective The prognosis of ovarian cancer has improved because of platinum- and taxane-containing chemotherapy. We investigated the 5-year disease-specific overall survival and prognostic factors of patients with advanced ovarian cancer to elucidate the change in clinical course of ovarian cancer with the advance of chemotherapy for patients who developed relapse in the era before the addition of molecular targeting therapy. Methods We reviewed the clinical course of 134 patients with advanced ovarian cancer (FIGO Stage III and IV) treated in the past 11 years (1999-2010). We classified the patients into two groups: those who had been diagnosed with ovarian cancer from 1999 to 2005 (Group A) and those who had been diagnosed from 2006 to 2010 (Group B). We compared the 5-year disease-specific overall survival and median survival rates between these two groups. We also investigated the prognostic factors of 104 patients who developed relapse. Results The 5-year disease-specific overall survival rate was significantly higher in Group B than A (67.0% vs. 38.6%; P = 0.032). Chemotherapy containing pegylated liposomal doxorubicin hydrochloride, non-clear cell adenocarcinoma and intestinal resection were independent prognostic factors. Conclusions The induction of new chemotherapeutic drugs and the increased variation of second- or third-line chemotherapy affected the improvement in overall survival of patients with advanced epithelial ovarian cancer.

Objective The aim of this study was to compare the outcomes associated with the use of a novel monopolar scalpel with those associated with the use of an ultrasonic scalpel for cervical conization of cervical intraepithelial neoplasia. Materials and methods We conducted a retrospective cross-sectional study in patients treated in our institute between April 2010 and March 2017. We used either the VIO monopolar scalpel (VIO) or Harmonic ultrasonic scalpel (HS) for cervical conization. We analyzed operative outcomes, postoperative complications, and pathological findings associated with the use of the 2 devices. Results In 500 patients treated with cervical conization, VIO and HS were used in 249 and 251 patients, respectively. No significant difference in patient background was found between the groups. The mean operative time was shorter with VIO than with HS (18.2 min vs. 27.4 min). The mean estimated blood loss was greater with VIO (7.2 g vs. 3.1 g), but the postoperative bleeding rate was higher with HS (5% vs. 20%). Regarding other complications, cervical stenosis was only noted with VIO (4 cases, 1.6%). The positive margin (11% vs. 16%) and positive endocervical curettage rates (7% vs 10%) were not significantly different between the groups. No significant differences were also found in the pathological results and need for additional treatment (the rate of the additional treatment: 20% vs. 23%). Conclusions Considering short operating time and less postoperative bleeding, VIO was preferred to HS. However, the excessive coagulation in VIO is considered to lead to cervical stenosis.

With the population aging, development of safe and effective treatments for elderly patients with cancer is needed. Although old age is considered a poor prognostic factor, this is not only because of the patient's disease condition or response to treatment, but also because of treatment strategy and intensity. The purpose of this study was to clarify the influence of age on treatment and prognosis in patients with cervical cancer.Women with stage Ib-IV cervical cancer treated at our institution between 1997 and 2014 were retrospectively analyzed. Patients were stratified by age into groups for analysis,65 years and ≥65 years. Categorical variables were compared using chi-squared and Fisher's exact tests. Survival analyses were performed using the Kaplan-Meier method, and comparisons were made using the log-rank test. Subsequently, Cox proportional hazards models were developed to find independent prognostic factors.Of 959 patients included in our study, 247 were ≥65 and 712 were65 years of age. Elderly patients tended to be at a more advanced stage than younger patients (p 0.001). Elderly patients more commonly had comorbidities. More received standard treatment in the younger patient group at any disease stage than in the elderly patient group (p 0.001). Similar rates of adverse effects caused by surgery or radiotherapy were seen in patients from both groups. Although overall survival was statistically shorter in elderly patients (74.7 vs. 57.1%, p 0.001), there was no significant difference in disease-specific survival for patients treated only with standard treatment. In multivariate analyses, clinical stage, histological type, treatment intensity, and primary surgery remained independent prognostic factors. Age was not an independent prognostic factor.The influence of age on prognosis in patients with cervical cancer was less than we expected. Elderly patients might have better outcomes depending on the type of standard treatment they receive. The appropriate modality and intensity of treatment should be based on the patient's general condition and background.

A primitive neuroectodermal tumor (PENT) belongs to the category of a Ewing sarcoma. A PENT of the uterus is rare and has been known to be very aggressive by nature. Owing to the rarity of the tumor, there is no optimal treatment at present. In many cases, after hysterectomy, chemotherapy or radiation therapy has been performed. However, an effective chemotherapy regimen was unclear. In the soft tissue sarcoma area, the chemotherapy approach has recently greatly improved. Vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide (VDC-IE) therapy has improved the survival rate of patients with Ewing sarcoma/PENT. Thus, VDC-IE therapy may be used for a uterine PENT. Here, we report a case of a uterine PENT in a premenopausal woman successfully treated with multimodality treatment including VDC-IE therapy and discuss the optimal chemotherapy for a uterine PENT through a literature review.

We describe a case of immune thrombocytopenia (ITP) associated with ovarian cancer. At the patient's first visit to hospital, high platelet-associated IgG and low platelet count (74 × 10(9)/L) were noted on blood test. She was diagnosed as having ITP complicated by ovarian cancer. Four days after surgery, the platelet count had increased to within the normal range. This is the first report of a patient with ITP complicated by ovarian cancer in which the platelet count reverted to normal soon after surgery for the ovarian cancer. We also investigated the characteristics of similar solid cancers with ITP at National Kyushu Cancer Center, Fukuoka, Japan.

Background Vulvar cancer and vaginal cancer are relatively rare tumors, and there had been no established treatment principles or guidelines to treat these rare tumors in Japan. The first version of the Japan Society of Gynecologic Oncology (JSGO) guidelines for the treatment of vulvar cancer and vaginal cancer was published in 2015 in Japanese. Objective The JSGO committee decided to publish the English version of the JSGO guidelines worldwide, and hope it will be a useful guide to physicians in a similar situation as in Japan. Methods The guideline was created according to the basic principles in creating the guidelines of JSGO. Results The guidelines consist of five chapters and five algorithms. Prior to the first chapter, basic items are described including staging classification and history, classification of histology, and definition of the methods of surgery, radiation, and chemotherapy to give the reader a better understanding of the contents of the guidelines for these rare tumors. The first chapter gives an overview of the guidelines, including the basic policy of the guidelines. The second chapter discusses vulvar cancer, the third chapter discusses vaginal cancer, and the fourth chapter discusses vulvar Paget’s disease and malignant melanoma. Each chapter includes clinical questions, recommendations, backgrounds, objectives, explanations, and references. The fifth chapter provides supplemental data for the drugs that are mentioned in the explanation of clinical questions. Conclusion Overall, the objective of these guidelines is to clearly delineate the standard of care for vulvar and vaginal cancer with the goal of ensuring a high standard of care for all women diagnosed with these rare diseases. Electronic supplementary material The online version of this article (doi:10.1007/s10147-017-1193-z) contains supplementary material, which is available to authorized users.

Background We aimed to clarify renal functional changes long term and serious urological complications in women with cervical cancer who undergo radical hysterectomy followed by pelvic radiotherapy and/or platinum-based chemotherapy to treat the initial disease. Methods Data on 380 women who underwent radical hysterectomy at the National Kyushu Cancer Center from January 1997 to December 2013 were reviewed. Main outcome measures were the estimated glomerular filtration rate (eGFR) and monitored abnormal urological findings. Results Postoperative eGFR was significantly lower than preoperative eGFR in 179 women with surgery alone and in 201 women with additional pelvic radiotherapy and/or chemotherapy (both P < 0.01). Two types of univariate analyses for eGFR reduction in women after treatment showed that older age, advanced stage, pelvic radiotherapy, and platinum-based chemotherapy were significant variables on both analyses. Two types of multivariate analyses showed that platinum-based chemotherapy or pelvic radiotherapy were associated with impaired renal function (odds ratio 1.96, 95% confidence interval 1.08-3.54 and odds ratio 2.85, 95% confidence interval 1.12-7.24, for the respective analyses). There was a higher rate of bladder wall thickening in women with pelvic radiotherapy had than those without it (17.4% vs. 2.7%, P < 0.01). One serious urological complication (intraperitoneal rupture of the bladder) occurred among women who underwent pelvic radiotherapy (0.6% vs. 0%). Conclusions Surgeons should be aware that eGFR is reduced after platinum-based chemotherapy and/or postoperative pelvic radiotherapy. Serious and life-threatening urological complications are rare, but surgeons should be aware of the possibility during the long follow-up.

We have developed a collaborative hospital-based approach to monitoring the impact of a human papillomavirus vaccine on cervical cancer, its precursor lesions and human papillomavirus type-specific prevalence in Japan. The monitoring will be conducted for a total period of 21 years on women aged

Aim Few studies have examined the accuracy of preoperative endometrial cytology in diagnosing low- and high-risk histology in women with endometrial cancer (EC). This single-institutional retrospective study compared the accuracy of endometrial cytology and biopsy in preoperatively predicting low-risk and high-risk histology of EC. Methods Between January 2006 and March 2013, 198 women with EC were examined by endometrial cytology, endometrial biopsy and hysterectomy specimen in National Kyushu Cancer Center. Among these women, 110 had endometrial cytology samples available to compare with endometrial biopsy, and were enrolled in our study (mean age ± standard deviation: 59.57 ± 10.32 years). Single-use plastic endometrial suction curettes were used in 12 of the 110 cases and thin metallic curettes for the rest. Results For type 2 EC, which includes grade 3 endometrioid adenocarcinoma and non-endometrioid histology, biopsy was 67.6% sensitive (25/37) and 84.9% specific (62/73); whereas cytology was 70.3% sensitive (26/37) and 91.8% specific (67/73). Cytology precisely diagnosed only one of 14 cases of serous carcinoma, but it diagnosed 11 of the 14 cases as type 2 EC, and its accuracy in distinguishing EC types was not inferior to endometrial biopsy (10/14). For EC, 9.1% (10/110) were unevaluable using biopsy, significantly more than the 0% (0/110) by cytology (P = 0.002). Conclusion Although preoperative prediction of serous carcinoma was difficult, endometrial cytology had a higher evaluable rate for EC types. Endometrial cytology may complement endometrial biopsy in preoperative women with EC.

ObjectiveSecondary leukemia is a known complication of chemotherapy and radiotherapy. It was generally recognized that leukemia secondary to chemotherapy was due to the use of alkylating agents in the treatment of ovarian cancer. Recently, many types of chemotherapeutic agents have been used in the treatment of gynecologic malignancies in addition to ovarian cancer. We analyzed the clinical characteristics and outcome of patients with recent onset of secondary leukemia after the treatment of gynecologic cancer to consider the diagnosis and management of secondary leukemia.Materials and MethodsWe reviewed the clinical charts and follow-up data of patients with gynecologic malignancies treated in the past 20 years. During this period, 2482 newly diagnosed invasive gynecologic cancers were treated in our institution. All patients with secondary leukemia were analyzed for clinical background, latency period (interval between the diagnosis of primary carcinoma and the development of leukemia), treatment, and outcome. We also reviewed the literature for secondary leukemia under gynecology using the PubMed.ResultsFour patients were found to have developed secondary leukemia after the treatment of gynecologic malignancies during this period. The cumulative risk of secondary leukemia was approximately 0.38%. All patients received platinum-based chemotherapy. Two patients received combination chemotherapy and/or bone marrow transplantation, and 1 of these 2 patients lived more than 6 years but died of recurrent ovarian cancer.ConclusionsLong survival time might be expected in patients who show complete response to bone marrow transplantation and/or combination chemotherapy for secondary leukemia. In recent years, we have aggressively used various types of anticancer drugs for the treatment of not only ovarian cancer but also uterine cervical cancer and endometrial cancer. Physicians need to keep in mind the risk of secondary leukemia in the follow-up of long-term survivors after several courses of chemotherapy and radiotherapy.

Introduction Clostrioides difficile enterocolitis (CDAD) varies from asymptomatic soft feces to severe cases that cause intestinal perforation and toxic megacolon. We experienced a case of CDAD ovarian cancer that developed after multidisciplinary therapies without prior antibiotics administration. We here report a pivotal role of team medicine for CDAD. Case A 66-year-old woman had medical history of gastric cancer (endoscopic resection) at 60 years old. Her family history was as follows: father: prostate cancer; mother: breast cancer; maternal grandfather: gastric cancer; and maternal grandmother: rectal cancer. We conducted interval debulking surgery after 4 courses of paclitaxel and carboplatin (TC) therapy as the initial treatment in diagnosis of ovarian cancer stage IIIC (ypT3CpN0pM0, serous carcinoma). Six courses of TC therapy were postoperatively performed, but intraperitoneal recurrence was diagnosed 1 year and 10 months after the initial treatment. Then, 7 courses of TC and bevacizumab (Bev) therapy were performed followed by 9 courses of Bev maintenance treatment. A second recurrence (para-aortic lymph node) was confirmed 1 year and 2 months after the end of chemotherapy, and 3 courses of TC/Bev treatment and intensity-modulated radiation therapy (IMRT) were performed. On the 7th day after IMRT, she complained of fever, abdominal pain and bloody mucous stools. Although antibiotics were administered with a diagnosis of CDAD, CDAD relapsed during the treatment. In this case, we worked on patient mental support and infection spread prevention with nutritional management mainly based on oral intake. Conclusion In treatment of CDAD, multi-professional team medicine is essential. In gynecologic cancers where multidisciplinary therapies are performed, CDAD has been reported to be not rare. Both prompt diagnose and adequate multi-professional team medicines are considered to be important for CDAD.

Malignant transformation of a mature cystic teratoma of the ovary is rare, occurring in approximately 2% of all cases. The most common malignancy arising in mature cystic teratoma is squamous cell carcinoma. Much less frequently, the malignant transformation is represented by sarcomas. Dedifferentiated chondrosarcoma usually develops in bone. There has been no case of a dedifferentiated chondrosarcoma arising in mature cystic teratoma of the ovary since the establishment of this diagnostic entity. This is a report of a definitive dedifferentiated chondrosarcoma arising in a mature cystic teratoma of the ovary, presenting clinicopathologic features.

Nogitecan hydrochloride(topotecan)has shown efficacy in patients with recurrent ovarian cancer, but has not been used widely in Japan. We evaluated the efficacy and adverse effects of topotecan in 12 patients (median age, 62 years) treated for recurrent ovarian cancer between 2000 and 2013. Four patients had relapsed after primary treatment, and 8 had relapsed at least twice. Seven patients had been treated with more than 3 prior regimens. Initial treatment of the 12 patients consisted of intravenous topotecan (1.0-1.4 mg/m2/day) for 5 consecutive days. Initial doses were based on previous chemotherapy and/ or renal function, with reduced doses administered to patients with severe adverse effects during prior courses of treatment. The 12 patients received a total of 54 courses of topotecan(range, 1-15 courses). Of these 12 patients, one achieved a partial response and 6 had stable disease. The median time to progression was 14.4 weeks. All 12 patients had grade 3-4 myelosuppression, while none had febrile neutropenia or severe non-hematologic toxicities. Patients who received higher doses or increased courses of chemotherapy had apparently more severe adverse events. These findings suggested that topotecan should be used as a second- or third-line treatment, rather than later, in patients with tumor recurrence, with its dose reduced according to the physical status of each patient. Such strategies may enhance both the efficacy and safety of topotecan in patients with recurrent ovarian cancer.

We describe a case of immune thrombocytopenia (ITP) associated with ovarian cancer. At the patient's first visit to hospital, high platelet-associated IgG and low platelet count (74 × 10(9)/L) were noted on blood test. She was diagnosed as having ITP complicated by ovarian cancer. Four days after surgery, the platelet count had increased to within the normal range. This is the first report of a patient with ITP complicated by ovarian cancer in which the platelet count reverted to normal soon after surgery for the ovarian cancer. We also investigated the characteristics of similar solid cancers with ITP at National Kyushu Cancer Center, Fukuoka, Japan.

Doxorubicin and cisplatin are the most commonly used chemotherapeutic agents in the treatment of endometrial cancer, but their clinical efficacy is still controversial. The aim of this study was to retrospectively assess the efficacy and toxicity of combination chemotherapy using cisplatin, cyclophosphamide, and anthracy-clines in patients with stage III/IV adenocarcinoma of the endometrium. Forty patients with advanced endometrial cancer received postoperative adjuvant combination chemotherapy, using cisplatin (50 or 70 mg/m2), cyclophosphamide (500 mg/m2), and one of three anthracyclines (10 patients with doxorubicin [50 mg/m2], 18 with epirubicin [50 mg/m2], and 12 with pirarubicin [40 mg/m2]), from 1987 to 1999. All patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, with pelvic lymph node dissection in 36 patients and paraaortic lymph node biopsy in 38 patients. Patients were considered eligible if they had adnexal metastasis, paraaortic lymph node metastasis, positive peritoneal cytology, or distant metastasis. The patients were divided into two groups: patients with no measurable lesion (group 1; n = 27), and those with residual measurable lesion (group 2; n = 13) after surgery. The response rate and progression-free survival rate were evaluated in group 2. In group 1, 7 patients (26%) had recurrence, and all of them died of the disease. No patients in stage IIIa (n = 10), however, had recurrence. In group 2, 6 of the 13 (46%) showed response to chemotherapy (complete response [CR], 31%; partial response [PR], 15%). Toxicity was moderate: 10 patients had grade 4 neutropenia; and dose reductions were mandated in 12 patients. In group 1, the survival of patients receiving chemotherapy was considered favorable, but patients with recurrent lesions had poor prognosis. On the other hand, in group 2, the efficacy of the chemotherapy was almost equal to that reported in the literature; however, this regimen did not contribute to an improvement in the survival rate. In conclusion, a new effective regimen of postoperative adjuvant therapy is highly desirable in patients with measurable residual lesions.

Although several authors have reported on neovaginal prolapse, the reasons for such prolapse are not understood. We report a rare case of sigmoid neovagina 40 years after operation. A 22-year-old woman with vaginal agenesis underwent vaginoplasty using sigmoid colon. Almost 40 years after initial operation, she came to our hospital complaining of a bearing-down sensation and an increase in vaginal discharge. At vaginal examination, the neovagina protruded approximately 5 cm beyond the hymen, but the apex of the neovagina was not prolapsed. A resection of the redundant neovagina was performed. By histopathologic examination of the excised specimen, we recognized thick colonic mucosa. We diagnosed the prolapsed vagina as hyperplasia of colonic mucosa. Hyperplasia of transplanted colonic epithelium can be a cause of neovaginal prolapse even 40 years after operation.

A case of radiologically identified molar invasion into extensive arteriovenous shunts (AVSs) is described. CT and MRI revealed a large uterine mass, accompanied by multiple AVSs. Dynamic MRI and pelvic angiography demonstrated multiple trophoblastic cysts invading into the AVSs. Resected specimen confirmed the diagnosis of invasive mole. Dynamic MRI was very useful in determining the etiology of AVS.

Tumor angiogenesis has been shown to play an important role in tumor growth and metastasis. This study examines the prognostic significance of two histological markers of angiogenesis, i.e., vascular cuffing (VC), a bead-like arrangement of microvessels closely surrounding microscopic tumor nests, and microvessel density (MVD), the number of microvessels in a unit area, in cervical squamous cell carcinoma.One hundred twenty-two specimens from surgically resected uteri with cervical squamous cell carcinoma were histologically reviewed and immunostained for CD34. VC was graded into "none," "incomplete," and "complete." The MVD was determined by counting the microvessels with a light microscope within a x200 field area where neovascularization occurred most actively. Stromal inflammation was also split into three grades. The relationship of VC or MVD to clinicopathological prognostic factors such as FIGO stage, cervical stromal invasion, lymph-vascular space invasion, pelvic lymph node metastasis, and parametrial invasion was evaluated using univariate and multivariate analyses.The patients with a complete VC pattern showed a significantly worse prognosis compared to those with a pattern graded as either none or incomplete (P0.011 and P0.0001, respectively). The Cox regression analysis revealed the complete VC pattern, together with parametrial invasion, to be an independent prognostic indicator for overall survival. MVD and the grading of stromal inflammation showed no significant relationship with VC or overall survival.The complete VC pattern may therefore be a useful prognostic indicator in cervical squamous cell carcinoma.

Objective. Many studies have demonstrated that clinically evident tumor cells already carry multiple genetic alterations and further accumulation of genetic alteration causes tumor progression which plays a role in metastasis. Therefore, it could be expected that malignant potential in the metastatic site is more aggressive than that in the primary site. Using several immunohistochemical markers (p53, Ki-67, and CD44v6), we investigated an alteration of malignant potential. Methods. We immunohistochemically examined expression of p53, Ki-67, and CD44 in primary and metastatic lesions of ovarian cancer. Fifty-six samples of primary lesions and matched metastatic sites from 56 patients with primary epithelial ovarian cancers were included in this study. Results. In 16 cases (28%), the histological grade of the metastatic lesion increased. This difference was statistically significant ( P = 0.0232). In 16 cases (28%), the expression of p53 increased in the metastatic lesions, in 5 pairs from negative to positive, whereas the case decrease in the metastatic lesions was only 1. This difference was statistically significant ( P = 0.0046). There was no significant difference in Ki-67 labeling indices and expression of CD44v6 between the primary and matched metastatic lesions. The degree of p53 expression in the metastatic lesions significantly correlated with disease-free survival ( P = 0.0482), whereas that in the primary lesions did not. Moreover, high p53 expression in the metastatic lesions significantly correlated with disease-free survival in multivariate analysis. Conclusions. The p53 expression in metastatic lesions may reflect an aggressive biologic behavior in ovarian cancer.

Few studies have examined the accuracy of preoperative endometrial cytology in diagnosing low- and high-risk histology in women with endometrial cancer (EC). This single-institutional retrospective study compared the accuracy of endometrial cytology and biopsy in preoperatively predicting low-risk and high-risk histology of EC.Between January 2006 and March 2013, 198 women with EC were examined by endometrial cytology, endometrial biopsy and hysterectomy specimen in National Kyushu Cancer Center. Among these women, 110 had endometrial cytology samples available to compare with endometrial biopsy, and were enrolled in our study (mean age ± standard deviation: 59.57 ± 10.32 years). Single-use plastic endometrial suction curettes were used in 12 of the 110 cases and thin metallic curettes for the rest.For type 2 EC, which includes grade 3 endometrioid adenocarcinoma and non-endometrioid histology, biopsy was 67.6% sensitive (25/37) and 84.9% specific (62/73); whereas cytology was 70.3% sensitive (26/37) and 91.8% specific (67/73). Cytology precisely diagnosed only one of 14 cases of serous carcinoma, but it diagnosed 11 of the 14 cases as type 2 EC, and its accuracy in distinguishing EC types was not inferior to endometrial biopsy (10/14). For EC, 9.1% (10/110) were unevaluable using biopsy, significantly more than the 0% (0/110) by cytology (P = 0.002).Although preoperative prediction of serous carcinoma was difficult, endometrial cytology had a higher evaluable rate for EC types. Endometrial cytology may complement endometrial biopsy in preoperative women with EC.

The activity and synergy for the combination treatment of cisplatin and gemcitabine has been identified in a variety of human tumor cells, including ovarian cancer cells, and has been widely approved for the treatment of non-small cell lung cancer, pancreatic cancer and biliary tract cancer. As the gastrointestinal symptoms with cisplatin therapy are commonly considered to negatively affect the quality of life of patients more than those experienced with carboplatin therapy, carboplatin is generally preferred over cisplatin in combination therapy. This study evaluated the safety and efficacy of cisplatin plus gemcitabine in patients with recurrent ovarian cancer.Patients with recurrent ovarian, peritoneal or fallopian tube cancer, who had failed with multiple other chemotherapy agents, including platinum, received cisplatin (30 mg/m(2)) plus gemcitabine (750 mg/m(2)) on days 1 and 8 of every 28 days for between 1 and 4 cycles.In total, 18 patients were treated with cisplatin and gemcitabine between 2006 and 2011. There were 1 complete and 5 partial responses, producing an overall response rate of 33.4 %. Median overall survival was 11.0 months. Grade 4 neutropenia and thrombocytopenia were seen in 11.1 and 22.2 % of patients, respectively. Non-hematological toxicity was less than Grade 1.Non-hematological toxicity with combined cisplatin and gemcitabine therapy was considered tolerable and did not impede patient quality of life. However, this drug combination should be monitored for hematologic toxicity.

We report the case of 31-year-old patient with an inhibin B-secreting granulosa cell tumor of the left ovary who presented with secondary amenorrhea. Preoperative serum hormonal levels were as follows: follicle-stimulating hormone (FSH) 0.3 mIU/mL, luteinizing hormone (LH) 9.81 mIU/mL, estradiol 142.0 pg/mL and inhibin B 2429 pg/mL. Gonadotropin-releasing hormone (GnRH) test revealed no FSH response and a normal LH response. After removal of the tumor, the levels of FSH and inhibin B returned to within the normal range, and regular menses resumed 27 days postoperatively. In premenopausal women, secondary amenorrhea may be the initial manifestation of granulosa cell tumor. A low FSH level coupled with normal levels of E2 and LH, the inhibition of the FSH response to GnRH and an elevated inhibin level suggest the presence of an inhibin-secreting ovarian tumor and also rule out the possibility of isolated FSH deficiency.

We recently treated a 21-year-old woman with leiomyomas arising from the bilateral ovaries, a very rare condition. On magnetic resonance imaging, more than half of the left adnexal mass showed low signal intensity on T2-weighted images and good enhancement by gadolinium-DTPA, and the remaining part showed high signal intensity on T2-weighted images and no enhancement. The right adnexal mass showed homogeneously low signal intensity on T2-weighted images, so the lesions initially were diagnosed as ovarian fibromas or as the-comas with a certain degree of degeneration. Pathologic examination of the excised tumors proved that they were bilateral ovarian leiomyomas; in addition, the tumor from the left side showed hemorrhagic and myxoid changes with torsion of 180 degrees.

Objective. The purpose of this study was to demonstrate the incidence, the histopathological characteristics, and the proliferation activity of endometriosis and atypical endometriosis associated with ovarian carcinoma. Methods. Microscopic slides of primary lesions from 127 patients with primary ovarian carcinoma were reviewed. The presence or absence of endometriosis and the transitions from typical endometriosis to atypical endometriosis and from atypical endometriosis to carcinoma were also histologically evaluated. Ki-67 immunoreactivity of typical and atypical endometriosis and carcinoma was examined. In addition, endometrial metaplasias were also evaluated. Results. Of the 127 patients, 37 had endometriosis: 70% (30/43) had clear cell adenocarcinoma, 43% (3/7) had endometrioid adenocarcinoma, 7% (4/60) had serous adenocarcinoma, and none (0/17) had mucinous adenocarcinoma. Thirty-three cases showed typical endometriosis and 29 cases had atypical endometriosis (25 cases had both). Tufting and the stratification of the lining epithelium were observed in 25 and 23 cases, respectively. The transition from typical endometriosis to atypical endometriosis was observed in 22 cases, and the transition from atypical endometriosis to carcinoma, in 23 cases. Only one case showed a direct transition from typical endometriosis to carcinoma. The mean Ki-67 indices were as follows: ovarian carcinoma, 23.1; atypical endometriosis, 9.9; typical endometriosis, 2.7. In 18 cases with metaplasia in endometriosis, eosinophilic metaplasia and ciliated metaplasia were the most common types. Five cases had two types of metaplasia. Conclusions. Ovarian carcinomas, especially clear cell and endometrioid adenocarcinomas, are highly associated with endometriosis. Atypical endometriosis shows proliferation activity intermediate to those of typical endometriosis and ovarian carcinoma, suggesting it is a precancerous status.

BACKGROUND Angiogenesis is essential for tumor growth, progression, and metastases. Microvessel density (MVD), a measure of tumor angiogenesis, has been found to have prognostic significance in many tumor types for predicting metastasis and survival. METHODS Between 1979-1989, 56 cases of FIGO Clinical Stage I and II adenocarcinoma of the uterine cervix treated by hysterectomy were reviewed histologically. All hysterectomy specimens were stained immunohistologically for factor VIII-related antigen. MVD was counted in a x200 field ( 0.785 mm2 per field) in the most active area of neovascularization. Results were expressed as the highest number of microvessels identified within any single x200 field. MVD and several other prognostic parameters were examined for correlation with progression free survival (PFS) and overall survival (OS) by a multivariate analysis according to the Cox proportional hazards model. RESULTS In early adenocarcinoma of the uterine cervix, MVD was increased significantly in invasive areas compared with adjacent nonneoplastic areas (median: 62.5 [range, 30-105] vs. median: 36.5 [range, 23-47]; P = 0.0003). MVD also was significantly correlated with ascites cytology (P = 0.0377). There was no correlation between microvessel count and lymph node status, depth of invasion, disease stage, lymph-vascular space invasion, grade, or parametrial involvement. Patients with high MVD (≥ 75) had significantly worse PFS and OS than those with low MVD (< 75) (log rank test, P = 0.0180 and 0.0199, respectively). Multivariate analysis showed that MVD correlated significantly and independently with PFS and OS. CONCLUSIONS In adenocarcinoma of the cervix, MVD is an independent prognostic factor for PFS and OS. Cancer 1998;83:1384-1390. © 1998 American Cancer Society.

Objective The purpose of this study was to improve the reliability of frozen section with the use of tumor diameter (TD) as an additional factor and intraoperatively to identify a subgroup of early endometrial cancers that would not require lymphadenectomy. Study Design Data for 228 patients who underwent surgery with frozen section were analyzed retrospectively. Lymphadenectomy was performed in 86% of patients; the nodes were positive in 8%. Results The accuracy of frozen section for myometrial invasion, grade, and low-risk prediction significantly increased with decreasing TD ( P = .036) and was 98%, 95%, and 95%, respectively, when the TD was ≤3 cm. Patients with a TD of ≤2 cm and patients with a TD of 2-3 cm who had low-risk predictors had no nodal metastasis; patients with a TD of 2-3 cm who had intermediate-high risk predictors and a TD of >3 cm with any level of risk predictors were at risk of nodal metastases. Conclusion When the TD was ≤3 cm, the low-risk group that is defined by frozen section can be predicted accurately and safely to remain lymph-node metastasis free.