Correlation of bone marrow 2-deoxy-2-[ 18 F]fluoro-D-glucose uptake with systemic inflammation in patients with newly diagnosed endometrial cancer.

OBJECTIVE: To clarify the relationship between 2-deoxy-2-[ 18 F]fluoro-D-glucose (FDG) uptake of bone marrow and systemic inflammation in patients with newly diagnosed endometrial cancer. METHODS: A total of 119 patients with untreated endometrial cancer underwent FDG PET/computed tomography (CT). For bone marrow FDG uptake, the mean standardized uptake value (SUVmean) of the five vertebrae (T11-12 and L3-L5) was measured and averaged (bone marrow SUV). The bone marrow-to-liver ratio (BLR) was calculated by dividing the bone marrow SUV by the SUVmean of the normal liver. FDG PET parameters were correlated with white blood cell count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and C-reactive protein (CRP), albumin, and hemoglobin levels. They were also correlated with FIGO stage. RESULTS: Bone marrow SUV and BLR showed significant positive correlations with white blood cell count, NLR, and CRP level and significant negative correlations with albumin level. BLR also showed a significant positive correlation with PLR. No significant differences in bone marrow SUV and BLR were apparent according to FIGO stage. CONCLUSION: Pretreatment FDG PET/CT in patients with newly diagnosed endometrial cancer may provide information on host systemic inflammation as assessed by bone marrow FDG uptake.

Initial screening by immunohistochemistry is effective in universal screening for Lynch syndrome in endometrial cancer patients: a prospective observational study.

BACKGROUND: Few prospective reports of universal screening for Lynch syndrome exist for patients with endometrial cancer. In this study, we performed immunohistochemical staining for DNA mismatch repair-related genes (MLH1, MSH2, MSH6 and PMS2), to determine the extent to which Lynch syndrome can be diagnosed in endometrial cancer patients through universal screening. METHODS: We recruited 116 consecutive patients assumed to have uterine corpus malignancy from October 2019 to February 2021 in a prospective observational study. We performed immunohistochemical for mismatch repair-related proteins on samples from 100 patients who had surgicopathologically confirmed diagnoses of endometrial cancer. Samples with missing immunohistochemical results for any of the proteins had subsequent universal screening tests for microsatellite instability, DNA methylation of the MLH1 promoter region and mismatch repair genetics. RESULTS: We identified 19 (19.0%) patients with lost results for any of the proteins. All 19 patient samples had subsequent screening tests. We identified the microsatellite instability-high phenotype in 84.2% (16/19) of these patients and MLH1 methylation in 57.9% (11/19). Mismatch repair genetic testing detected two pathological variants, in MSH2 and MSH6, which indicated that the prevalence of Lynch syndrome was 2.0% in our cohort. Two cases of unclassified variant (MSH6) and one case of benign variant (PMS2) were also detected. CONCLUSIONS: Initial screening by immunohistochemical is an effective method in universal screening for Lynch syndrome in endometrial cancer patients.

Clinical relevance of addition of conventional treatment to concurrent chemoradiotherapy in patients with FIGO stage III-IV cervical cancer: a retrospective analysis of a Japanese cohort.

BACKGROUND: Concurrent chemoradiotherapy has limited therapeutic efficacy for stage III-IV cervical cancer. We aimed to identify a subgroup of patients with stage III-IV cervical cancer who benefit from concurrent chemoradiotherapy with additional treatment. METHODS: We retrospectively reviewed 120 patients with stage III-IV cervical cancer who were treated with concurrent chemoradiotherapy from 2002 to 2018. We compared overall survival between patients treated with concurrent chemoradiotherapy alone and those who received concurrent chemoradiotherapy with additional conventional treatments (systemic chemotherapy before and/or after concurrent chemoradiotherapy and/or extended-field radiation). Prognostic factors were statistically analysed. RESULTS: Overall, 44 (36.7%) and 21 (17.5%) patients were radiologically diagnosed with pelvic and para-aortic lymph node enlargement, respectively. The median tumour diameter was 5.7 cm. A total of 69 (57.5%) patients received no additional treatment, and 51 (42.5%) received additional treatment. Cox regression analysis identified the following prognostic factors: histological non-squamous cell carcinoma (hazard ratio, 3.9; 95% confidence interval, 1.8-8.2), tumour diameter of ≥6 cm (hazard ratio, 2.1; 95% confidence interval, 1.2-3.7), radiological pelvic lymph node enlargement (hazard ratio, 2.1; 95% confidence interval, 1.1-4.0) and radiological para-aortic lymph node enlargement (hazard ratio, 2.1; 95% confidence interval, 1.1-4.1). Even in the lowest risk group (no risk factors), the 5-year overall survival rate was lower in the additional treatment group than in the concurrent chemoradiotherapy alone group (78.7% vs. 80.9%, respectively; log-rank test, P = 0.79). CONCLUSIONS: Addition of conventional treatments to concurrent chemoradiotherapy might not improve survival in patients with advanced cervical cancer. Novel treatment strategies including immune checkpoint inhibitors should be considered for such patients.

Validity of skeletal muscle mass index measurements for assessing sarcopenia in patients with gynecological cancer.

BACKGROUND: The current study investigated an optimal method for using CT scan in detection of low skeletal muscle mass quantity (SMQ). METHODS: In total, 82 consecutive patients with gynecological cancers were examined using computed tomography (CT) and dual-energy X-ray absorptiometry (DEXA) before treatment. Low SMQ was defined as a DEXA-based skeletal muscle mass index (SMI) of <5.40 kg/m2. Furthermore, CT-based SMI values were measured by six evaluators, and each evaluator measured SMI values two times for each subject. The first SMI value and the average SMI value were used for analyses. Receiver operating characteristic (ROC) analyses were performed to evaluate the performance of CT-based SMI measurements for detecting low SMQ. Interobserver agreement was assessed using the intraclass correlation coefficient (ICC). RESULTS: In total, 23 patients (28.0%) were diagnosed with low skeletal muscle mass. All areas under the curve (AUC) values from twelve (six evaluators × two measurements) ROC curves were within the range of 0.8-0.9. AUC values based on a single measurement and those based on two measurements were almost the same. The ICC was 0.828 (95% CI 0.777-0.874, P < 0.001) when using a single measurement value and increased to 0.959 (95% CI 0.944-0.971, P < 0.001) when using the average of the two measurements. CONCLUSIONS: A single measurement CT-based SMI efficiently identified patients with low SMQ in a daily clinical setting. The reliability of SMI measurements might be further improved by using a mean value of two measurements compared with the use of a single measurement value.

A BMI-category distribution pattern of intrinsic and treatment-related prognostic factors in endometrial cancer.

OBJECTIVE: In patients with endometrial cancer, obesity is associated with favorable prognostic characteristics but not with prolonged survival. The aim of this study was to elucidate the reason for this clinical paradox. METHODS: We retrospectively reviewed 1173 patients with endometrial cancer. Patients were divided into a non-obese group [body mass index (BMI) < 30 kg/m2], class I obesity group (BMI 30-35 kg/m2) and class II obesity group (BMI ≥ 35 kg/m2). The relationship between clinicopathological factors and disease-specific survival (DSS) was analyzed by Cox regression analysis. To correct for three-time significance testing, we used the Bonferroni method, giving the level of probability at which findings were considered significant as P < 0.0167. RESULTS: Three disease-intrinsic variables-older age, advanced stage and high-risk histology-and three treatment-related variables-no hysterectomy, no lymphadenectomy and no chemotherapy-were independently associated with poor DSS. DSS was similar among the three groups of patients even though the proportion of patients with plural pretreatment-related unfavorable risk factors significantly decreased with increment of BMI category (40.1 vs. 27.5 vs. 17.6%, P = 0.0003). The proportion of patients with plural treatment-related unfavorable prognostic factors significantly increased with increment of BMI category (21.3 vs. 26.7 vs. 39.3%, P = 0.0072). CONCLUSIONS: Poor-quality surgical staging in obese women may result in worse than expected survival outcomes.

Clinical implication of psoas muscle mass measurement for predicting death within 3 months in patients with incurable uterine cervical or corpus malignancy.

OBJECTIVE: The aim of this study was to find a clinical marker for identifying refractory cancer cachexia. METHODS: We analyzed computed tomography imaging data, which included the third lumbar vertebra, from 94 patients who died of uterine cervix or corpus malignancy. The time between the date of examination and date of death was the most important attribute for this study, and the computed tomography images were classified into >3 months before death and ≤ 3 months before death. Psoas muscle mass index was defined as the left-right sum of the psoas muscle areas (cm2) at the level of third lumbar vertebra, divided by height squared (m2). RESULTS: A data set of 94 computed tomography images was obtained at baseline hospital visit, and a data set of 603 images was obtained at other times. One hundred (16.6%) of the 603 non-baseline images were scanned ≤3 months before death. Mean psoas muscle mass index change rates at >3 months before death and ≤3 months before death were -1.3 and -20.1%, respectively (P < 0.001). Receiver operating characteristic curve analysis yielded a cutoff value of -13.0%. The area under the curve reached a moderate accuracy level (0.777, 95% confidence interval 0.715-0.838). When we used the cutoff value to predict death within 3 months, sensitivity and specificity were 74.0 and 82.1%, respectively. CONCLUSIONS: Measuring change in psoas muscle mass index might be useful for predicting cancer mortality within 3 months. It could become a potential tool for identifying refractory cancer cachexia.

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.

Validity of measuring psoas muscle mass index for assessing sarcopenia in patients with gynecological cancer.

OBJECTIVE: The current study evaluated the performance of psoas muscle mass measurement for detecting low skeletal muscle mass quantity. METHODS: A sample of 82 consecutive patients with gynecological cancers was examined using computed tomography and dual energy X-ray absorptiometric scan before treatment. Skeletal muscle mass index was measured by dual energy X-ray absorptiometric scan and its cut-off value was set at 5.40 kg/m2 for detecting low skeletal muscle mass. Psoas muscle mass index was manually measured with cross-sectional computed tomography imaging at the level of L3 by six evaluators. RESULTS: Low skeletal muscle mass index was identified in 23 (28.0%) patients. Two-way analysis of variance confirmed a significant main effect of skeletal muscle mass index on mean psoas muscle mass index values (P < 0.0001). A receiver operating characteristic curve obtained from a total of 492 psoas muscle mass index data points gathered from six evaluators produced an area under the curve value of 0.697 (95% confidence interval 0.649-0.744) and a cut-off value of 3.52 cm2/m2, with sensitivity of 79.0% and specificity of 59.6%. Using the cut-off value, the kappa coefficient for evaluating diagnostic agreement between skeletal muscle mass index (low vs. normal) and psoas muscle mass index (low vs. normal) was 0.308 (95% confidence interval 0.225-0.392), suggesting poor agreement. Fleiss' kappa produced a coefficient of 0.418 (95% confidence interval 0.362-0.473), suggesting moderate agreement. CONCLUSIONS: Although relevance between skeletal muscle mass index and psoas muscle mass index was confirmed, intensity of relevance between them was weak. Psoas muscle mass index measurement should be subordinated to skeletal muscle mass index measurement for detection of low skeletal muscle mass.

Diagnostic criteria of sentinel lymph node micrometastasis or macrometastasis based on tissue rinse liquid-based cytology in gynecological cancer.

OBJECTIVE: This study aimed to establish intraoperative diagnostic criteria of sentinel lymph node (SLN) micro-/macrometastasis on the basis of tissue rinse liquid-based cytology (TRLBC) in gynecological cancer. METHODS: We enrolled 214 patients with gynecological cancer who underwent rapid diagnosis of SLN metastasis on the basis of TRLBC from a total of 490 SLNs. For slides that were classified as positive for atypical cells on cytological inspection, we counted the number of clusters (an atypical cell mass consisted of three or more cells) and the number of single cells (an atypical cell other than clusters). Receiver operating characteristic (ROC) analysis was applied to determine the efficiency of predicting SLN micro-/macrometastasis. RESULTS: On cytological inspection, 36 slides were classified as positive for atypical cells, while 21 slides (4.3%) were true positive, 15 (3.1%) were false positive, and 454 (92.6%) were true negative. There were no false negative results in this study. The area under the ROC curve for the number of cluster was superior to that for the number of single cells for distinguishing micro-/macrometastasis from negative/isolated tumor cells (0.86 vs. 0.67, P = 0.032). The optimum cut-off value of the number of clusters was 5 for distinguishing these two categories. CONCLUSIONS: TRLBC is a highly sensitive alternative for detecting SLN metastasis as a rapid intraoperative diagnosis. Counting the number of atypical cell clusters might be useful for distinguishing micro-/macrometastasis from isolated tumor cells.

Imaging-based definition of lower uterine segment carcinoma to improve the detection sensitivity of probable Lynch syndrome.

OBJECTIVE: The aim of this study was to investigate a magnetic resonance imaging-based definition of lower uterine segment carcinoma. METHODS: We retrospectively reviewed 587 consecutive patients with endometrial cancer who underwent hysterectomy. Lower uterine segment carcinoma was determined through pathological examination and magnetic resonance imaging assessment. For imaging assessment, the location of the inner lining of the uterus was classified into four equal parts on a sagittal section image. A tumor was defined as lower uterine segment carcinoma when its thickest part was located in the second or the third part from the uterine fundus. Lower uterine segment carcinoma was further divided into lower uterine segment in a narrow sense, upon which diagnosis was exclusively based on pathological findings, and lower uterine segment in a broad sense that were the remaining lower uterine segment carcinomas except lower uterine segment carcinomas in a narrow sense. The relationship between lower uterine segment carcinoma and probable Lynch syndrome was investigated. Patients with loss of MSH2, MSH6, and PMS2 expression or those with tumors with loss of MLH1 and absence of MLH1 promoter methylation were diagnosed as probable Lynch syndrome. RESULTS: Lower uterine segment carcinoma was identified in 59 (10.2%) patients. Twenty-eight (47.5%) patients were categorized as lower uterine segment in a narrow sense and 31 (52.5%) as lower uterine segment in a broad sense. Among them, probable Lynch syndrome was identified in 12 (20.3%) cases. There was no difference in clinical profiles, including the prevalence of probable Lynch syndrome between the two categories. CONCLUSIONS: A magnetic resonance imaging-based expanded definition of lower uterine segment carcinoma is likely to secure characteristics equivalent to a conventional pathology-based definition of lower uterine segment carcinoma. The novel definition of lower uterine segment carcinoma might improve the detection of probable Lynch syndrome.

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.

A case of retroperitoneal desmoid-type fibromatosis that involved the unilateral ureter after gynaecologic surgery.

INTRODUCTION: Desmoid-type fibromatosis represents a rare, benign, soft tissue tumour that is locally invasive with high recurrence potential. PRESENTATION OF CASE: We encountered a case of retroperitoneal desmoid-type fibromatosis in a 45-year-old woman who presented with chief complaints of stomach ache and vomiting. She underwent total abdominal hysterectomy and left salpingo-oophorectomy due to uterine myoma and a paroophoritic cyst at 42 years of age. Abdominal computed tomography showed a 5-cm left retroperitoneal tumour and severe hydronephrosis of the left kidney. Multiple imaging studies failed to provide a definitive diagnosis. Therefore, we performed tumour resection, right salpingo-oophorectomy, ureterectomy, and ureterocystostomy. The tumour surrounded the left ureter and adhered to the left internal/external iliac artery, rectum, bladder, and the edge of the vagina. Histopathologic examination yielded a diagnosis of retroperitoneal desmoid-type fibromatosis. One month after the operation, transvaginal sonography showed a 2-cm mass in the pelvis. We suspected tumour recurrence and commenced pharmacotherapy with tranilast (300mg/day, three times per day). Four months after the operation, the mass disappeared. DISCUSSION: There are minimal reports of postoperative intra-abdominal desmoid-type fibromatosis and preoperative diagnosis is difficult. To the best of our knowledge, there are no reported cases of desmoid-type fibromatosis that involved the ureter with severe hydronephrosis following a gynaecologic operation. CONCLUSION: We experienced a case of retroperitoneal desmoid-type fibromatosis that involved a unilateral ureter after gynaecologic surgery.

[Comparison between Primary Debulking Surgery and Neo-Adjuvant Chemotherapy Followed by Interval Debulking Surgery for Patients with Stage III-IV Ovarian Cancer].

The current standard treatment for advanced ovarian cancer is primary debulking surgery(PDS). We may expect a good prognosis if complete debulking(no visible residual tumor)is possible. However, if complete surgery is not possible owing to the location of the tumor or poor performance status, neo-adjuvant chemotherapy(NAC)could be an alternative option. Interval debulking surgery(IDS)can be planned after NAC to try and achieve complete debulking surgery. We reviewed stage III and IV epithelial ovarian cancers treated at Kansai Rosai Hospital between January 2012 and January 2016. Fifty-one cases (PDS: 22 cases, NAC-IDS: 29 cases)were enrolled in our analysis. Progression-free survival(PFS), overall survival(OS), the successful complete surgery rate, and the contents and complications of the surgery were compared between the PDS and NAC-IDS groups. There was no significant difference in PFS and OS between the 2 groups(PFS: p=0.467, OS: p=0.685). Blood loss was larger in the PDS group(p=0.013). Patients in the NAC-IDS group were likely to be able to eventually achieve complete surgery(p=0.016). NAC followed by IDS is one of the effective treatment options for advanced ovarian cancers.

[A Retrospective Analysis of Systematic Lymphadenectomy for Loco-Regional(pT1)Epithelial Ovarian Cancer].

BACKGROUND: The incidence of lymph node metastasis in pT1 epithelial ovarian cancer is between 5% and 21%. Most cases with lymph node metastasis are those of serous carcinoma; it is relatively rare in mucinous carcinoma. Therefore, there is a recent trend to omit systematic lymphadenectomy in early stage mucinous carcinoma. The purpose of this study was to verify whether the omission of systematic lymphadenectomy in mucinous carcinoma is oncologically safe. METHODS: We reviewed all pT1 epithelial ovarian cancer cases that were treated in our hospital between January 2002 and December 2015. RESULTS: Fiftynine cases of pT1 epithelial ovarian cancer were included. The overall rate of lymph node metastasis was 6.8%(4 in 59). It was 6.5%(2 in 31)in clear cell carcinoma and 22.2%(2 in 9)in mucinous carcinoma. CONCLUSION: According to our study, lymph node metastasis in pT1 mucinous carcinoma has a rate of 22.2% and some affected cases were not detected by presurgery imaging studies. Therefore, we need to be careful about the omission of systematic lymphadenectomy in mucinous carcinoma.

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.

[A Retrospective Case Study of Combination Chemotherapy with Bevacizumab for Recurrent Ovarian Cancer].

OBJECTIVES: Treatment for ovarian cancer with bevacizumab(Bmab)has been covered by public medical insurance in Japan since November 2013. It is recommended that the use of Bmab is limited to the first treatment for FIGO stage III or IV ovarian cancer. The OCEAN trial for platinum sensitivity in relapsed patients and the AURELIA trial for platinum-resistance in relapsed patients were performed, and both significantly improved progression-free survival. METHOD: We retrospectively studied patients receiving Bmab with an anticancer agent for recurrent ovarian cancer. Written informed consent was obtained from all patients. RESULTS: Between November 2013 and September 2015, Bmab at 15mg/kg/3-4 week was administered to 20 patients with recurrent ovarian cancer. The median age was 58 years(range 32-81)and the median performance status was 0-2. Platinum-sensitive recurrence occurred in 6 patients. The response rate and disease control rate of combination chemotherapy with Bmab was 50.0% and 57.1%. However, 11 patients stopped treatment with Bmab due to serious adverse events. CONCLUSION: Combination chemotherapy with Bmab for recurrent ovarian cancer may be feasible.

[A Case of Bilateral Pneumothorax after Chemotherapy for Uterine Leiomyosarcoma with Multiple Lung Metastases].

We encountered a case of uterine leiomyosarcoma with multiple lung metastases. The patient was a 52-year-old woman who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by chemotherapy with gemcitabine and docetaxel. After 1 cycle of chemotherapy, the lung metastasis was reduced, but at the same time, she developed bilateral pneumothorax. Chemical pleurodesis using talc was performed. The lungs were expanded and stabilized in 7 days. After 5 cycles of chemotherapy were administered, no recurrence of pneumothorax and adverse effects were observed.

[A Case of Pneumocystis Pneumonia during Chemotherapy for Recurrent Ovarian Cancer].

A 53-year-old patient with recurrent ovarian clear cell adenocarcinoma developed fever (39°C) and cough on day 28 of liposomal doxorubicin chemotherapy, the 4th cycle of the 4th regimen since initial treatment. Drug-induced interstitial pneumonia was suspected from a chest CT image showing diffuse ground-glass opacities; however, we deduced pneumocystis pneumonia from the elevated serum beta-D-glucan levels. After effective treatment with sulfamethoxazole and amphotericin B, the patient's symptoms and radiological findings improved. Pneumocystis pneumonia is an opportunistic infection that poses a risk not only for patients undergoing aggressive immunosuppressive therapy, those infected with HIV, and those with transplants, but also for patients undergoing chemotherapy. When pneumonia is diagnosed during chemotherapy, it is essential to consider the possibility of pneumocystis pneumonia.

Family history and BRCA1/BRCA2 status among Japanese ovarian cancer patients and occult cancer in a BRCA1 mutant case.

BACKGROUND: This study aimed to examine family history among Japanese ovarian cancer patients and to investigate the TP53 status of fallopian tube epithelial and ovarian cancer cells in a Japanese BRCA1 mutant case that may be associated with the transformed state in hereditary ovarian cancer. METHODS: One hundred and two primary ovarian cancer patients were retrospectively evaluated in this cross-sectional study. The family history of cancer was determined in probands. In a BRCA1 mutant case, p53 immunostaining and direct sequencing, followed by laser-capture microdissection, were performed for the fallopian tube, considered the origin of ovarian cancer. RESULTS: Nine of 102 (8.8%) families were regarded as having hereditary breast-ovarian cancer syndrome, two families (2.0%) were diagnosed with Lynch syndrome and six patients harbored BRCA1 or BRCA2 mutations. One case underwent risk-reductive salpingo-oophorectomy as a BRCA1 mutant carrier was retrospectively diagnosed as occult cancer. Common TP53 mutations were detected in cancer and fallopian tube epithelial cells in the case. CONCLUSIONS: Here, we integrate family cancer history and histology in ovarian cancer cases as well as TP53 status in a BRCA1 mutant case into a discussion regarding carcinogenesis in a Japanese population. The TP53 status for the BRCA1 mutant case examined here supports the recently proposed theory that ovarian cancer develops because of BRCA1 or BRCA2 inactivation and/or TP53 mutations.

Experience of risk-reducing salpingo-oophorectomy for a BRCA1 mutation carrier and establishment of a system performing a preventive surgery for hereditary breast and ovarian cancer syndrome in Japan: our challenges for the future.

BACKGROUND: Risk-reducing salpingo-oophorectomy is currently regarded as the most certain primary method for preventing ovarian cancer among BRCA1/2 mutation carriers with hereditary breast and ovarian cancer syndrome. However, risk-reducing salpingo-oophorectomy has rarely been performed in Japan. METHODS: We developed the first system in Japan for performing risk-reducing salpingo-oophorectomy for BRCA1/2 mutation carriers at our university hospital in 2008. RESULTS: The indication for risk-reducing salpingo-oophorectomy for patients with hereditary breast/ovarian cancer syndrome is currently limited in Japan. This situation may be because of the limited number of genetic counseling units, the limited number of facilities that can perform BRCA1/2 genetic testing and the fact that prophylactic surgery is not covered by health insurance in Japan. CONCLUSIONS: Recent treatment guidelines for breast cancer in Japan recommended risk-reducing salpingo-oophorectomy for BRCA1/2 mutation carriers. Risk-reducing salpingo-oophorectomy should be performed in the framework of the standard therapeutic modality for BRCA1/2 mutation carriers in the near future.