Spatial distribution of tumor-resident macrophages as predictive biomarkers in endometrial cancer.

BACKGROUND: To investigate the role of CD47 expression and its relationship with tumor-resident macrophages, specifically at the tumor margin, in patients with type II endometrial cancer. This study aims to elucidate whether CD47 could serve as a prognostic marker and to understand the dynamics between CD47 and macrophages, which could inform new therapeutic strategies. METHODS: A retrospective cohort study was conducted involving 75 patients of type II endometrial. Immunohistochemical analysis was performed to assess CD47 expression and macrophage markers (CD68 and CD163). RESULTS: The study found no direct correlation between CD47 expression levels and overall survival (p = 0.32), challenging its role as an independent prognostic marker in type II endometrial cancer. The higher expression of CD47 had significantly less incidence of endometrioid carcinoma G3 (p = 0.047). The negative correlation between CD47 H-score and the density of CD68-positive macrophages at tumor margin was statistically significant (p = 0.049). A high density of CD68-positive macrophages at the tumor margin but a low density of CD163-positive macrophages at the tumor margin were associated with poorer prognosis (p = 0.036). CONCLUSIONS: The complex interaction between CD47 and macrophages, particularly at the tumor margin, suggests new avenues for targeted therapy in type II endometrial cancer.

Mean platelet volume as a potential biomarker for survival outcomes in ovarian clear cell carcinoma.

OBJECTIVE: This study aimed to explore the prognostic value of mean platelet volume (MPV) in patients with ovarian clear cell carcinoma (OCCC) and evaluate the predictive performance of a random forest model incorporating MPV and other key clinicopathological factors. METHODS: A total of 204 patients with OCCC treated between January 2004 and December 2019 were retrospectively analyzed. Clinicopathological characteristics and preoperative laboratory data were collected, and survival outcomes were evaluated using the Kaplan-Meier method and Cox proportional hazards models. An optimal MPV cutoff was determined by receiver operating characteristic (ROC) curve analysis. A random forest model was then constructed using the identified independent prognostic factors, and its predictive performance was evaluated. RESULTS: The ROC analysis identified 9.3 fL as the MPV cutoff value for predicting 2-year survival. The MPV-low group had lower 5-year overall survival and progression-free survival rates than the MPV-high group (p = 0.003 and p = 0.034, respectively). High MPV emerged as an independent prognostic factor (p = 0.006). The random forest model, incorporating the FIGO stage, residual tumors, peritoneal cytology, and MPV, demonstrated robust predictive performance (area under the curve: 0.905). CONCLUSION: MPV is a promising prognostic indicator in OCCC. Lower MPV correlated with worse survival rates, advocating its potential utility in refining patient management strategies. The commendable predictive performance of the random forest model, integrating MPV and other significant prognostic factors, suggests a pathway toward enhanced survival prediction, thereby warranting further research.

The prognostic significance of DDIT4 in endometrial cancer.

BACKGROUND: Despite extensive research on endometrial cancer and tumor hypoxic microenvironment, there are no reports exploring the role of DDIT4 in endometrial cancer. OBJECTIVE: This study aimed to elucidate the significance of DDIT4, as a prognostic biomarker for endometrial cancer by immunohistochemical staining and statistical analysis. METHODS: Four endometrial cancer cells were cultured under normoxia and hypoxia, and the differentially expressed genes were examined using RNA-seq. Immunohistochemical staining for DDIT4 and HIF1A was performed in 86 patients with type II endometrial cancer treated at our hospital, and their correlation with other clinicopathological factors and the prognostic role was analyzed using statistical methods. RESULTS: The expression analysis of hypoxia-inducible genes using four types of endometrial cancer cells revealed that DDIT4 was among the 28 genes that were upregulated in all cells. Based on our results of immunohistochemistry of DDIT4 expression in endometrial cancer tissues, univariate and multivariate analyses based on COX regression analysis showed that high DDIT4 expression significantly correlated to favorable prognosis in both progression-free survival and overall survival. Limited to recurrent cases, metastasis to only lymph nodes was significantly related to high DDIT4 expression, whereas metastasis to other parenchymal organs was significantly dominant in patients with low DDIT4 expression. CONCLUSIONS: The expression of DDIT4 enables to predict survival and recurrence in type II endometrial cancer.

Significance of Concurrent Chemoradiotherapy as Primary Treatment in Patients with Metastatic Cervical Cancer.

(1) This study investigated the prognostic impact of tumor size in patients with metastatic cervical cancer. (2) Methods: Seventy-three cervical cancer patients in our institute were stratified into two groups based on distant metastasis: para-aortic lymph node metastasis alone (IIIC2) or spread to distant visceral organs with or without para-aortic lymph node metastasis (IVB) to identify primary tumor size and concurrent chemoradiotherapy. (3) Results: The overall survival (OS) for patients with a tumor >6.9 cm in size was significantly poorer than that for patients with a tumor ≤6.9 cm in the IVB group (p = 0.0028); the corresponding five-year OS rates in patients with a tumor ≤6.9 and >6.9 cm were 53.3% and 13.4%, respectively. In the multivariate analysis, tumor size and primary treatment were significantly associated with survival in metastatic cervical cancer. (4) Conclusions: Tumor size ≤6.9 cm and concurrent chemoradiotherapy as the primary treatment were favorable prognostic factors for patients with metastatic cervical cancer.

The Prognostic Significance of Peritumoral Lymphocytes' Band-like Structure in Type II Endometrial Cancer.

BACKGROUND/AIM: Peritumoral ectopic lymphoid-like structures and tertiary lymphoid structures (TLS), have been identified in various cancers. However, evidence for the role of TLS in endometrial cancer (EC) is lacking. We found a cluster of peritumoral lymphocytes with band-like structures (PLB) in the forefront of EC and analyzed their association with the clinical outcome. MATERIALS AND METHODS: This was a single-center, retrospective cohort study. We evaluated peritumoral lymphoid cells using conventional hematoxylin-eosin and immunohistochemical staining by semi-quantitative digital analysis. RESULTS: A total of 85 cases were included and the presence of PLB was examined. A strong correlation was observed between the density of PLB and progression-free survival (very low, low vs. intermediate, high; HR=0.22; 95%CI=0.093-0.52; p<0.001) and overall survival (very low, low vs. intermediate, high; HR=0.259; 95%CI=0.091-0.73; p=0.011). CONCLUSION: PLB in type II EC show a strong association with fatal outcome.

Interleukin­33 expression in ovarian cancer and its possible suppression of peritoneal carcinomatosis.

Refractory peritoneal carcinomatosis is a common terminal feature of epithelial ovarian cancer (EOC). Previous reports have suggested that immunotherapy is a promising therapeutic strategy for EOC. Interleukin (IL)­33 is a member of the IL­1 superfamily of cytokines. The role of IL­33 in tissue inflammation and promoting type 2 immune responses has been established, and recently, there is accumulating evidence to suggest the involvement of IL­33 in carcinogenesis. In this study, we focused on the association between the tumor expression of IL­33 and ovarian peritoneal carcinomatosis. We used an immunosufficient murine model of peritoneal carcinomatosis and human EOC samples. The overexpression of IL­33 in the ID8 mouse EOC cell line tumors significantly prolonged the survival of immunocompetent mice in the peritoneal carcinomatosis setting, but not in the subcutaneous model. In addition, the silencing of IL­33 in ID8­T6 cells (subclone with high dissemination potential) significantly shortened the survival of the tumor­bearing mice. This was likely due to the intratumoral accumulation of CD8+ and CD4+ T cells, and a decrease in CD11b+Gr1+ cells. Furthermore, IL­33 induced the intraperitoneal microenvironment favoring tumor elimination through the inhibition of differentiation into CD11b+Gr1+ cells. On the whole, the findings of this study suggest IL­33 to be a cytokine that reflects antitumor peritoneal conditions. Further investigation of the antitumorigenic role of IL­33 may aid in the development of more effective therapeutic approaches for the treatment of EOC with peritoneal carcinomatosis.

Unique miRNA profiling of squamous cell carcinoma arising from ovarian mature teratoma: comprehensive miRNA sequence analysis of its molecular background.

Owing to its rarity, the carcinogenesis and molecular biological characteristics of squamous cell carcinoma arising from mature teratoma remain unclear. This study aims to elucidate the molecular background of malignant transformation from the aspects of microRNA (miRNA) profiling. We examined 7 patients with squamous cell carcinoma and 20 patients with mature teratoma and extracted their total RNA from formalin-fixed paraffin-embedded tissues. Then we prepared small RNA libraries and performed comprehensive miRNA sequencing. Heatmap and principal component analysis revealed markedly different miRNA profiling in cancer, normal ovarian and mature teratoma tissues. Then we narrowed down cancer-related miRNAs, comparing paired-cancer and normal ovaries. Comparisons of cancer and mature teratoma identified two markedly upregulated miRNAs (miR-151a-3p and miR-378a-3p) and two markedly downregulated miRNAs (miR-26a-5p and miR-99a-5p). In addition, these findings were validated in fresh cancer tissues of patient-derived xenograft (PDX) models. Moreover, several miRNAs, including miR-151a-3p and miR-378a-3p, were elevated in the murine plasma when tumor tissues were enlarged although miR-26a-5p and miR-99a-5p were not elucidated in the murine plasma. Finally, we performed target prediction and functional annotation analysis in silico and indicated that targets genes of these miRNAs markedly correlated with cancer-related pathways, including 'pathway in cancer' and 'cell cycle'. In conclusion, this is the first study on miRNA sequencing for squamous cell carcinoma arising from mature teratoma. The study identified four cancer-related miRNAs that were considered to be related to the feature of malignant transformation. Moreover, miRNAs circulating in the murine plasma of the PDX model could be novel diagnostic biomarkers.

Clinical characteristics of primary peritoneal carcinoma patients: a single-institution experience involving 8 patients.

Primary peritoneal carcinoma (PPC) is treated similarly to advanced epithelial ovarian carcinoma (aEOC); however, the standard approach for the management of PPC is controversial. The objective of this study was to evaluate the clinical features and prognosis of those patients. A retrospective analysis was performed of eight patients with PPC between January 2008 and December 2015. Clinicopathologic parameters, the diagnostic modality, treatment, and oncologic outcome were analyzed. The median age at the time of diagnosis was 72.5 years (range: 55-79), with a median follow-up of 26.5 months (range, 5-74). Most of the PPC developed with carcinomatosis peritonei involving ascites, while some cases developed sporadically in the peritoneal or extraperitoneal cavity without ascites. The most common initial symptom was abdominal fullness, and other symptoms were inguinal tumor, paralysis of the extremities, and respiratory disorder. The preoperative CA125 value was elevated in all patients. In four patients who did not undergo primary surgery, the final diagnoses were determined by the ascites cytology and radiological image. Initial or interval debulking surgery was performed in only two patients. All patients were treated with paclitaxel or docetaxel plus carboplatin. Five showed a complete response (CR), and one showed a partial response (PR). Among the five patients with CR, the median progression-free and overall survival periods were 15 (12-26) and 41.5 (32-74) months, respectively. Three patients without carcinomatosis peritonei showed a relatively favorable prognosis. The management of PPC is generally consistent with that of aEOC; however, in atypical cases, the treatment method should be considered individually.

Behçet's syndrome associated with acute myocardial infarction.

We report here a case of Behçet's syndrome. The patient was suddenly affected by chest pain during the clinical course of the disease and developed abdominal pain and melena after 5 weeks. The diagnosis of acute anteroseptal myocardial infarction was made on the basis of the electrocardiography findings, and many perforated ulcers were confirmed in specimens of the resected colon. Coronary angiography showed constriction by 50% of the left anterior descending artery. There were no atherosclerotic changes. Pulse therapy was performed using sodium methylprednisolone succinate at a dose of 1,000 mg for 3 days, followed by oral administration of prednisolone at a dose of 60 mg/day, leading to improvement of all the symptoms after 3 weeks. The electrocardiogram findings at that time were normal. Prompt resolution of the symptoms provided by corticosteroid therapy supports the conclusion of previous studies that myocardial infarction in Behçet's syndrome may possibly be due to vasculitis of the coronary arteries. In Behçet's syndrome, myocardial infarction is rare but should be considered as one of the most important lesions that determine the prognosis.

Creeping eruption caused by a larva of the suborder Spirurina type X.

We report a case of creeping eruption caused by a larva of the suborder Spirurina type X, which developed in a 46-year-old Japanese male. The patient ate small raw squids (Watasenia scintillans) 5 days before the onset of symptoms. On examination, an approximately 25-cm-long serpiginous red track with vesicles was observed from the right to the upper left side of the abdomen of the patient. Histological examination revealed the transverse section of a larval worm in the upper to middle dermis.The patient serum was positive only for the antibody against larvae of the suborder Spirurina type X in ELISA, and negative for all other anti-parasite antibodies. Because a considerable number of people are fond of eating raw or nearly-raw fish and shellfish in Japan, opportunities for developing creeping eruption cause by parasites present in raw fish and shellfish are relatively high.