Creation and Validation of Patient-Derived Cancer Model Using Peritoneal and Pleural Effusion in Patients with Advanced Ovarian Cancer: An Early Experience.

Background: The application of personalized cancer treatment based on genetic information and surgical samples has begun in the field of cancer medicine. However, a biopsy may be painful for patients with advanced diseases that do not qualify for surgical resection. Patient-derived xenografts (PDXs) are cancer models in which patient samples are transplanted into immunodeficient mice. PDXs are expected to be useful for personalized medicine. The aim of this study was to establish a PDX from body fluid (PDX-BF), such as peritoneal and pleural effusion samples, to provide personalized medicine without surgery. Methods: PDXs-BF were created from patients with ovarian cancer who had positive cytology findings based on peritoneal and pleural effusion samples. PDXs were also prepared from each primary tumor. The pathological findings based on immunohistochemistry were compared between the primary tumor, PDX, and PDX-BF. Further, genomic profiles and gene expression were evaluated using DNA and RNA sequencing to compare primary tumors, PDXs, and PDX-BF. Results: Among the 15 patients, PDX-BF was established for 8 patients (5 high-grade serous carcinoma, 1 carcinosarcoma, 1 low-grade serous carcinoma, and 1 clear cell carcinoma); the success rate was 53%. Histologically, PDXs-BF have features similar to those of primary tumors and PDXs. In particular, PDXs-BF had similar gene mutations and expression patterns to primary tumors and PDXs. Conclusions: PDX-BF reproduced primary tumors in terms of pathological features and genomic profiles, including gene mutation and expression. Thus, PDX-BF may be a potential alternative to surgical resection for patients with advanced disease.

Consistency between Primary Uterine Corpus Malignancies and Their Corresponding Patient-Derived Xenograft Models.

Patient-derived xenograft (PDX) models retain the characteristics of tumors and are useful tools for personalized therapy and translational research. In this study, we aimed to establish PDX models for uterine corpus malignancies (UC-PDX) and analyze their similarities. Tissue fragments obtained from 92 patients with uterine corpus malignancies were transplanted subcutaneously into immunodeficient mice. Histological and immunohistochemical analyses were performed to compare tumors of patients with PDX tumors. DNA and RNA sequencing were performed to validate the genetic profile. Furthermore, the RNA in extracellular vesicles (EVs) extracted from primary and PDX tumors was analyzed. Among the 92 cases, 52 UC-PDX models were established, with a success rate of 56.5%. The success rate depended on tumor histology and staging. The pathological and immunohistochemical features of primary and PDX tumors were similar. DNA sequencing revealed similarities in gene mutations between the primary and PDX tumors. RNA sequencing showed similarities in gene expressions between primary and PDX tumors. Furthermore, the RNA profiles of the EVs obtained from primary and PDX tumors were similar. As UC-PDX retained the pathological and immunohistochemical features and gene profiles of primary tumors, they may provide a platform for developing personalized medicine and translational research.

Lymphatic Complications Following Sentinel Node Biopsy or Pelvic Lymphadenectomy for Endometrial Cancer.

Sentinel node biopsy (SNB) is performed worldwide in patients with endometrial cancer (EC). The aim of this study was to evaluate and compare the occurrence rate of lymphatic complications between SNB and pelvic lymphadenectomy (LND) for EC. The medical records of women who underwent SNB or pelvic LND for EC between September 2012 and April 2022 were assessed. A total of 388 patients were enrolled in the current study. Among them, 201 patients underwent SNB and 187 patients underwent pelvic LND. The occurrence rates of lower-extremity lymphedema (LEL) and pelvic lymphocele (PL) were compared between the patients who underwent SNB and those who underwent pelvic LND. The SNB group had a significantly lower occurrence rate of lower-extremity LEL than the pelvic LND group (2.0% vs. 21.3%, p < 0.01). There were no patients who had PL in the SNB group; however, 4 (2.1%) patients in the pelvic LND group had PL. The occurrence rates of lower-extremity LEL and PL were significantly lower in patients who underwent SNB than those who underwent pelvic LND. SNB for EC has a lower risk of lymphatic complications compared to systemic LND.

Cancer-Specific miRNAs Extracted from Tissue-Exudative Extracellular Vesicles in Ovarian Clear Cell Carcinoma.

Ovarian clear cell carcinomas (OCCs) arise from endometriotic cysts that many women develop. Biomarkers for early OCC detection need to be identified. Extracellular vesicles have attracted attention as biomarker carriers. This study aims to identify cancer-specific miRNAs as novel OCC biomarkers using tissue-exudative extracellular vesicles (Te-EVs). Te-EVs were collected from four patients with OCC on one side and a normal ovary on the other side. Microarray analysis was performed to identify cancer-specific miRNAs in Te-EVs. Serum samples obtained before and after surgery from patients with OCC and atypical endometrial hyperplasia (AEH) (controls) were compared using real-time PCR to examine changes in the detected EV miRNA levels. Thirty-seven miRNAs were >2-fold upregulated on the OCC side compared with the normal ovarian side. We selected 17 miRNAs and created specific primers for 12 of these miRNAs. The levels of six EV miRNAs were significantly decreased in postoperative OCC serum compared to those in preoperative OCC serum. In contrast, no significant change was observed between the pre and postoperative values in the control group. We identified OCC tissue-specific miRNAs in the EVs secreted by OCC tissues. These EV miRNAs have potential for use as biomarkers for the early diagnosis and detection of OCC.

A case of pyometra with a colouterine fistula due to rectal cancer presenting as acute abdomen.

Pyometra usually develops in elderly women, and it can be caused by various etiologies. We describe a rare case of pyometra with a colouterine fistula due to rectal cancer presenting as acute abdomen. A 67-year-old woman with purulent vaginal discharge and abdominal distension was referred to our hospital for suspected pyometra. Because the vaginal echogram showed pyometra at her initial medical examination, drainage was performed. Her symptoms subsequently disappeared temporarily, but 4 months later, she developed acute abdomen. The computed tomography scan showed a pelvic mass with expansion of the intestine. The patient underwent en bloc resection of the mass. Histopathologic analysis of the tumor showed rectal cancer with invasion of the uterus and ileum, and a colouterine fistula. Although pyometra due to a colouterine fistula is a very rare condition, the incidence of associated malignancy is considerable. Physicians should be aware of this potential presentation of colorectal cancer.