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Background: Although carbon-ion radiotherapy (C-ion RT) with concurrent chemotherapy (chemo-C-ion RT) is a promising treatment for adenocarcinoma (AC) of the uterine cervix, its long-term efficacy remains unclear. We evaluated the long-term significance of concurrent weekly cisplatin and C-ion RT for locally advanced AC of the uterine cervix., Methods: We performed a pooled analysis of patients with stage IIB-IVA AC of the uterine cervix who underwent C-ion RT alone or chemo-C-ion RT between September 2007 and December 2018 at our institution. Patients received 74.4 Gy (relative biological effectiveness) with or without cisplatin (40 mg/m 2 per week for up to 5 weeks), underwent no prior pelvic RT or systemic therapy, and had a performance status of 0-2. Propensity score matching was based on the year of diagnosis, regional lymph node metastasis, and stage., Results: The matched cohort contained 26 patients who underwent C-ion RT and 26 who underwent chemo-C-ion RT. The median age and follow-up period were 57 (range, 28-79) years and 34 (range, 2-126) months, respectively. The 5-year overall survival rate was significantly better in the chemo-C-ion RT group (72%) than in the C-ion RT group (46%; P = .041). The 5-year distant metastatic-free rate was also significantly better in the chemo-C-ion RT group (66%) than in the C-ion RT group (41%; P = .048). The incidence of grade ≥ 3 late toxicities was comparable between the two groups., Conclusions: Chemo-C-ion RT for locally advanced AC of the uterine cervix is associated with a long-term survival benefit., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

We herein reported a rare case of an occult fallopian tube carcinoma first detected from the diaphragm metastasis. An 83-year-old woman who had a 30-mm tumor on the right diaphragm underwent radical resection. Pathologically, the tumor was diagnosed as a high-grade serous adenocarcinoma, suggesting metastasis from the pelvic visceral carcinoma. Although the primary site could not be detected by imaging examinations, laparoscopy revealed multiple peritoneal disseminations; therefore, total hysterectomy was performed. Finally, microscopic tumor invasion into the right fimbriae of the fallopian tube was found. A precise and detailed pathological and immunohistochemical examinations of the resected metastatic diaphragm tumor helped us obtain a proper diagnosis of the primary lesion and treat the patient appropriately. Since it is difficult to diagnose diaphragm tumors before surgery based on the anatomy, surgical options have played an important role in their treatment and diagnosis clinically.

Objectives: It has been established that concurrent chemoradiotherapy (CCRT) is efficacious for cervical cancer, but adherence is unsatisfactory among elderly patients. To improve adherence, we have developed and initiated a daily low-dose cisplatin-based CCRT regimen. Here, we retrospectively evaluated the use of CCRT, especially for elderly patients., Methods: The study included a total of 53 patients who were 70 years or older, had stage IB-IVA cervical cancer, and were initially treated with daily CCRT. The daily CCRT comprised pelvic external beam radiotherapy (2 Gy/d × 25) with daily low-dose cisplatin (8.0 mg/m(2) per day) and either low- or high-dose-rate intracavitary brachytherapy., Results: The median age was 72 years (range, 70-85 years). The median follow-up duration was 32 months (range, 2-104 months). The 3-year overall survival rate was 79.0%. Daily cisplatin chemotherapy was successfully completed in 32 (60.4%) of the 53 patients. Grade 3 or 4 neutropenia was observed in 19 patients (36%). A late complication of grade 3 rectal hemorrhage occurred in 3 patients who received high-dose-rate brachytherapy. All primary tumors responded to daily CCRT; complete response was observed in 43 patients (91.5%) and partial response was observed in 4 patients (8.5%)., Conclusions: Daily CCRT in patients 70 years and older had acceptable compliance and safety. Daily CCRT is suggested to be a good treatment option for elderly patients who have advanced cervical cancer and require concurrent cisplatin.

We investigated the first site of distant failure after carbon ion radiotherapy (C-ion RT) for locally advanced cervical cancer in three clinical trials. A total of 91 cases were enrolled in the three trials (Protocol 9702, 9704 and 9902). Histologically, 36 cases had squamous cell carcinoma (SqCC) and 55 cases had adenocarcinoma (AC), including 13 with adenosquamous cell carcinoma. The number of cases with Stage IIB, IIIB and IVA disease was 21, 59 and 11, respectively. Of the 91 cases, 42 had positive pelvic lymph nodes (PLNs). The median tumor size was 6.0 cm (range, 3.0–12.0 cm). The median follow-up duration for all cases was 40 months (range, 7–181 months). A total of 40 cases developed distant failure as the first site of failure: 13 of 36 (36.1%) SqCC cases had distant failure, with 9 of them with para-aortic lymph node (PALN) failure; 27 of 55 (44.0%) AC cases had distant failure, and 23 of them had distant failure excluding PALN metastasis. Distant failure rates of SqCC cases who had positive and negative PLNs before C-ion RT were 61.1% and 11.1%, respectively (P = 0.0045). Those of AC cases were 54.2% and 45.2%, respectively (P = 0.507). In conclusion, there were high rates of distant failure after C-ion RT in AC cases regardless of PLN status, and there were high rates of distant failure after C-ion RT, especially PALN failure, in SqCC cases with positive PLNs.

Background: This study sought to evaluate the toxicity and efficacy of carbon ion radiotherapy (C-ion RT) for locally advanced adenocarcinoma of the uterine cervix in a phase 1/2 clinical trial., Methods: The treatment consisted of whole-pelvic irradiation of 36.0 gray equivalents (GyE) in 12 fractions and local boost with dose escalation from 26.4 to 38.4 GyE in 8 fractions. The dose escalation was performed with careful observation of acute normal tissue responses. Total dose to the cervical tumor was 62.4 to 74.4 GyE in 20 fractions., Results: Between April 1998 and February 2010, 58 patients were treated with C-ion RT in this clinical trial. The number of patients with stage IIB, IIIB, and IVA disease were 20, 35, and 3, respectively. Median tumor size was 5.5 cm (range, 3.0-11.8 cm). Twenty-seven patients had pelvic lymph node metastases. The median follow-up period was 38 months. All patients completed the treatment schedule. Grade 2 or higher late toxicity was found in 8 patients: 5 with bladder and 2 with small intestine grade 2 toxicities, and 1 patient had grade 4 rectal complication, which was surgically salvaged. The 5-year local control rate, local control rate including salvage surgery, and overall survival rate in all cases were 54.5%, 68.2%, and 38.1%, respectively., Conclusions: Dose escalation of C-ion RT for adenocarcinoma of the uterine cervix was accomplished without severe toxicities except in 1 case. Although the number of patients in this study was small, the results support continued investigation and analysis to confirm therapeutic efficacy., (© 2014 American Cancer Society.)

Background: The current study examined the clinical usefulness of YKL-40 in detection and prognosis of uterine cervical cancer., Patients and Methods: Serum levels of YKL-40, cancer antigen 125 (CA 125), carbohydrate antigen 19-9 (CA19-9), and squamous cell carcinoma (SCC) antigen were determined by enzyme-linked immunosorbent assay in women with benign gynecologic disease (n=24), cervical malignancy (SCC, n=104; adenocarcinoma, n=37), and age-matched healthy controls (n=45). Immunohistochemical analysis for local YKL-40 expression was carried out on 28 adenocarcinomas., Results: Receiver operating characteristic curve analysis showed that YKL-40 [area under the curve (AUC)=0.882] was significantly better at discriminating adenocarcinoma from healthy control than SCC antigen, CA 125, and CA19-9. For SCC, YKL-40 (AUC=0.898) carried out similarly to SCC antigen and was better than CA 125 and CA19-9. Using a cut-off YKL-40 value of 92.2 ng/ml, sensitivity of YKL-40 in stage I adenocarcinoma (68%) was higher than that of the other three markers (11%-21%). Tumor-associated macrophages showed immunoreactivity for YKL-40 in 2 of 28 adenocarcinoma tissue samples, but adenocarcinoma cells themselves were nonimmunoreactive in all samples. Multivariate Cox regression analysis revealed that elevated pretreatment YKL-40 levels predicted unfavorable prognosis, independent of International Federation of Gynecology and Obstetrics stage and age at diagnosis., Conclusions: Pretreatment serum YKL-40 level is a possible prognosticator of cervical adenocarcinoma.

Objective: The purpose of this study was to investigate the diagnostic impact of preoperative serum p53 antibody (S-p53 Ab) in patients with endometrial cancer., Study Design: A hospital-based series of 67 patients, comprising 58 endometrioid adenocarcinomas (EA) and 9 serous adenocarcinomas (SA) between 1998-2002 were included. First, preoperative pathology was compared with final pathology in terms of histologic classification and tumor grade. Second, S-p53 Ab and CA125 were measured using preoperative serum samples, and immunohistochemical staining for p53 protein was assessed using hysterectomy specimens., Results: There were discrepancies between preoperative and final pathology in terms of histologic classification (7%) and tumor grade in EAs (30%); other objective tests, therefore, were needed to minimize the diagnostic problems. S-p53 Ab titers varied from 0.27-786 (mean, 124) in SAs and from 0.1-7.47 (mean, 0.46) U/mL in EAs, respectively, and were positive in 6 (67%) SAs and in 3 (6%) EAs using 1.3 U/mL as cut-off. S-p53 Ab-positive rate was significantly correlated with SA histology and grade 3 EA tumor (odds ratio, 40; P = .005; 95% confidence interval, 3.04-525.43) with higher sensitivity and higher specificity than p53 staining and CA125, respectively., Conclusion: S-p53 Ab could conveniently and specifically identify high-risk endometrial cancer.

Background: There are therapeutic dilemmas regarding conservative management of endometrial cancer in young women., Methods: We planned a prospective study to conservatively treat women aged under 40 years with clinical stage 1A, grade 1 endometrioid adenocarcinoma from 1999 to 2005. There were nine women (aged 28-40) who fulfilled the criteria, and medroxyprogesterone acetate (400 mg/day) was continued for 6 months. Curettage materials were pathologically evaluated according to our criteria including partial response (PR) (a small amount of cancer tissue with remarkable hormonal effects or atypical hyperplasia). To predict complete response (CR) to progestin, immunohistochemical staining for insulin-like growth factor type 1 receptor, phosphatase and tensin homolog deleted on chromosome ten, progesterone receptor (PgR), estrogen receptor and Ki67 were assessed., Results: Seven (78%) and two cases presented complete and PRs, respectively. Two patients developed recurrent disease 10 and 22 months after the last dilatation and curettage, and both had synchronous ovarian cancer. However, all nine patients were alive and disease-free for a mean of 39 months. Of eight married patients, four (50%) conceived and three delivered full-term singletons. CR was related to positive expression of PgR (P=0.008)., Conclusions: Patients with an initial PR can obtain CR after further treatment, and the PgR may be useful in predicting CR to fertility-preserving treatment in young women with endometrial cancer.

Background: Malignant transformation of adenomyosis is a very rare event. Only about 30 cases of this occurrence have been documented till now., Case Presentation: The patient was a 57-year-old woman with a slightly enlarged uterus, who underwent total hysterectomy and unilateral adnexectomy. On gross inspection, the uterine wall displayed a single nodule measuring 5 cm and several small gelatinous lesions. Microscopic examination revealed a common leiomyoma and multiple adenomyotic foci. A few of these glands were transformed into a moderately differentiated adenocarcinoma. The endometrium was completely examined and tumor free. The carcinoma was, therefore, considered to be an endometrioid adenocarcinoma arising from adenomyosis. Four months later, an ultrasound scan revealed enlarged pelvic lymph nodes: a cytological diagnosis of metastatic adenocarcinoma was made. Immunohistochemical studies showed an enhanced positivity of the tumor site together with the neighbouring adenomyotic foci for estrogen receptors, aromatase, p53 and COX-2 expression when compared to the distant adenomyotic glands and the endometrium. We therefore postulate that the neoplastic transformation of adenomyosis implies an early carcinogenic event involving p53 and COX-2; further tumor growth is sustained by an autocrine-paracrine loop, based on a modulation of hormone receptors as well as aromatase and COX-2 local expression., Conclusion: Adenocarcinoma in adenomyosis may be affected by local hormonal influence and, despite its small size, may metastasize.