Diabetes can increase the prevalence of EBV infection and worsen the prognosis of nasopharyngeal carcinoma.

Epstein‒Barr virus (EBV) infection is a primary oncogenic factor of nasopharyngeal carcinoma (NPC) that elicits epithelial-mesenchymal transition (EMT). Although diabetic patients are more susceptible to various infectious diseases, the pathological association with virus-related NPC has not yet been clarified. Herein, we evaluated the influence of diabetes on the clinicopathological changes of 70 patients with NPC. Disease-specific survival (DSS) modified by viral infection was also analysed. The proportion of NPC patients with diabetes was 32.9% (23/70 cases), and 91.3% (21/23 cases) were infected with EBV detected by EBER-I in situ hybridisation. NPC with diabetes showed an effect on EMT evaluated by immunostaining for E-cadherin and vimentin, which was correlated with HbA1c levels. Receiver operating characteristic (ROC) curve analysis determined a HbA1c level of 6.5% as the cut-off value for primary disease death at 2 years [area under the curve (AUC) 0.76; sensitivity 0.64; and specificity 0.81]. High HbA1c levels (≥6.5%) significantly increased the number of lymph node metastases in NPC compared to low HbA1c levels (<6.5%, p<0.01). Diabetic NPC patients had a significantly poorer prognosis than all non-diabetic patients (DSS, 72 months vs not reached, p<0.05). Diabetic EBV-positive NPC patients had a significantly poorer prognosis than non-diabetic EBV-positive patients (DSS, 35 months vs not reached, p<0.01). Multivariate analysis using the Cox proportional hazards model also suggested that HbA1c ≥6.5% was a significant factor in poor prognosis, with a hazard ratio of 6.84 (p<0.05). Collectively, our results revealed for the first time a high prevalence of EBV infection, poor prognosis and the importance of proper glycaemic control in diabetic NPC patients.

Post-menopausal ovarian fibroma associated with steroid hormone synthesis: A case report.

OBJECTIVE: Ovarian fibromas are benign, sex cord-stromal tumors occurring in both peri- and post-menopausal women. Generally, these tumors are non-functional and do not produce hormones. However, this case report proves the first case of steroid hormone synthesis in an ovarian fibroma by immunohistochemistry. CASE REPORT: A 77-year-old post-menopausal woman presented with a left ovarian tumor, abnormal endometrial thickness, and high levels of estradiol (E2). The tumor was found to be a fibroma, which was positive for alpha-inhibin. We examined estrogen-producing enzymes using immunohistochemistry. The tumor was positive for estrogen receptor, progesterone receptor, 17ß-hydroxysteroid dehydrogenase (HSD)-1, adrenal 4 binding protein/steroidogenic factor 1, 17ß-HSD-5, steroid sulfatase, and P450c17. CONCLUSION: This case study shows that E2 can be locally produced from circulating inactive steroids, by estrogen-producing enzymes. This is the first report of steroid hormone synthesis in an ovarian fibroma.

A case of metastatic endobronchial tumor from uterine leiomyosarcoma.

A 54-year-old woman presented with persistent productive cough, found to have an endobronchial tumor which obstructed the left upper lobe bronchus. Histopathological examination of a transbronchial biopsy of the endobronchial tumor suggested leiomyosarcoma. A positron emission tomography (PET)-CT revealed uterus tumor with moderate uptake of 18F-fluorodeoxyglucose, suggesting uterine malignancies. From the results of histological findings of the resected uterus and the biopsied bronchial specimen, she was diagnosed with uterine leiomyosarcoma and endobronchial metastasis. The systematic use of PET-CT could be useful for patients presenting with tumors that cause endobronchial metastasis of leiomyosarcomas.

Tumor Microenvironment in Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: Interaction between Tumors and Immune Cells, and Potential Effects of Neuroendocrine Differentiation on the Tumor Microenvironment.

The tumor microenvironment is considered to play a pivotal role in various human malignancies. Neuroendocrine and non-neuroendocrine neoplasms are considered to have different tumor microenvironments. However, owing to differences in the systemic and/or local immune statuses, tumor microenvironments in different patients may be difficult to compare. Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), although rare, could be useful for exploring the effects of neuroendocrine differentiation on the tumor microenvironment, because both neuroendocrine and non-neuroendocrine components are present in the same tumor. Here, we examined 33 cases of histologically confirmed MiNENs and evaluated the influence of neuroendocrine differentiation on the tumor microenvironment by comparing tumor-infiltrating lymphocytes, tumor-associated macrophages, and other relevant factors in the two components the same tumor. The immunoreactivity of those examined above was evaluated quantitatively. The values of vasohibin-1-positive density (p < 0.0001) and immunoreactivity (p < 0.0001) (representing the neoangiogenesis status) were significantly higher in neuroendocrine as compared to non-neuroendocrine areas of the same tumors. In addition, the Foxp3/CD8 (p = 0.0717) and the PD-1/CD8 ratios (p = 0.0176) (representing tumor immunity suppression) tend to increase in neuroendocrine carcinomas. Immunoreactivity of CD163, a marker of M2-like macrophages, was also higher in the neuroendocrine areas. Our findings indicate that neuroendocrine and non-neuroendocrine tumors differ from each other with respect to the characteristics of both tumor cells and the tumor microenvironment.

Herbal medicine-induced multiple pulmonary pseudotumors.

Japanese herbal medicines (HMs) cause adverse drug reactions (ADRs); however, solid nodule formation is uncommon. In this report, we aimed to show that ADRs with HM can mimic lung cancer. A 63-year-old man complained of back pain. His physician prescribed a traditional Japanese HM, Keishikajutsubuto, which alleviated his symptoms. After 4 weeks, a chest radiograph showed multiple lung nodules that were absent 6 months earlier; the patient did not have cough, fever, or dyspnea. Computed tomography (CT) showed multiple, bilateral lung nodules; however, blood tests and lung biopsy showed no abnormalities, ruling out interstitial pneumonia and lung cancer. Three months after the HM was discontinued, CT showed resolution of the lesions. Interstitial pneumonia was reported as a side effect of HM; however, no such side effect was reported for Keishikajutsubuto. When a patient presents with multiple lung nodules, a side effect of HM should be considered as a differential diagnosis.

Immune microenvironment in Barrett's esophagus adjacent to esophageal adenocarcinoma: possible influence of adjacent mucosa on cancer development and progression.

The immune microenvironment plays a pivotal role in cancer development and progression. Therefore, we studied the status of immune cells in esophageal adenocarcinoma (EAC) and adjacent Barrett's esophagus (BE) and their association with the clinical course of patients. We included 87 patients with EAC who underwent surgical resection or endoscopic submucosal dissection. CD3, CD8, Foxp3, p53, and Ki-67 were immunolocalized in EAC and adjacent BE (N = 87) and BE without EAC (N = 13). BE adjacent to EAC exhibited higher CD3+ lamina propria lymphocyte (LPL) numbers than BE without EAC. Abundant Foxp3+ LPLs in BE were associated with dysplasia and increased Ki-67 labeling index (LI) in BE glandular cells and tended to link to aberrant p53 expression. Abundant CD8+ LPLs in adjacent BE were associated with worse prognosis of EAC patients (P = 0.019). Results of our present study firstly revealed the potential influence of the tissue immune microenvironment of BE adjacent to EAC on cancer development and eventual clinical outcome of EAC patients. T cell infiltration could play pivotal roles in facilitating the dysplasia-adenocarcinoma sequence in BE. The number of Foxp3+ T cells is increased at the early stage of carcinogenesis and could help identify patients harboring dysplastic and highly proliferating cells. CD8+ T cells could reflect unfavorable inflammatory response in adjacent tissue microenvironment and help predict worse prognosis of EAC patients.

Glucocorticoid receptor and serum- and glucocorticoid-induced kinase-1 in esophageal adenocarcinoma and adjacent Barrett's esophagus.

Barrett's esophagus (BE) is a consequence of gastroesophageal reflux disease and is predisposed to esophageal adenocarcinoma (EAC). EAC is an exemplar model of inflammation-associated cancer. Glucocorticoids suppress inflammation through glucocorticoid receptor (GR) and serum- and glucocorticoid-induced kinase-1 (Sgk1) expressions. Therefore, we immunolocalized GR and Sgk1 in EAC and the adjacent BE tissues and studied their association with clinical disease course in 87 patients with EAC who underwent surgical resection (N = 58) or endoscopic submucosal dissection (N = 29). Low GR and Sgk1 expressions in adjacent BE tissues were associated with adverse clinical outcomes (P = 0.0008 and 0.034, respectively). Patients with low Sgk1 expression in EAC cells exhibited worse overall survival (P = 0.0018). In multivariate Cox regression analysis, low GR expression in the adjacent nonmalignant BE tissues was significantly associated with worse overall survival (P = 0.023). The present study indicated that evaluation of GR and Sgk1 expressions in both the EAC cells and adjacent nonmalignant BE tissues could help to predict clinical outcomes following endoscopic and surgical treatments. In particular, the GR status in BE tissues adjacent to EAC was an independent prognostic factor.

Spontaneous Regression of Recurrent Undifferentiated Carcinoma of the Endometrium.

We herein report a very rare case of spontaneous regression of recurrent undifferentiated carcinoma of the endometrium. An 80-year-old woman had undergone total hysterectomy with bilateral adnexectomy for undifferentiated carcinoma of the endometrium. The cancer recurred locally 10 months after surgery and then metastasized to the lung and liver. After she and her family elected to receive supportive care without active treatment, the local recurrences dramatically decreased, and the metastases of the lung, liver, and peritoneum also disappeared. This case showed that spontaneous regression can occur even with malignant tumors showing an extremely poor prognosis, such as undifferentiated carcinoma of the endometrium.

A case of intracystic papillary neoplasm of the gallbladder that exhibited findings similar to gallbladder adenomyomatosis with the formation of intramural cysts because of Rokitansky-Aschoff sinus infiltration.

A 74-year-old man underwent regular follow-up observations after being diagnosed with gallbladder adenomyomatosis based on findings, such as the thickening of the wall of the gallbladder fundus and the presence of intramural cysts. Over the course of 3 years, a papillary tumor located on the thickened wall of the gallbladder had increased in size and extended into the lumen. Consequently, the patient was diagnosed with gallbladder cancer and underwent extended cholecystectomy. The histological diagnosis was intracystic papillary neoplasm (ICPN) of the gallbladder. Although several Rokitansky-Aschoff sinuses that had increased in size because of tumor progression were observed, no adenomyomatosis of the gallbladder was detected. ICPN, a recently identified disease, is not widely known to present with imaging findings similar to adenomyomatosis. The primary treatment of ICPN is radical resection, whereas adenomyomatosis is generally conservatively managed with regular follow-up observations. As the treatment strategies for these two diseases greatly differ, differential diagnosis must be carefully performed.

[Molecular Investigation on the Presence of Hepatitis E Virus in Wild Game in Okazaki City, Japan between April 2010 and November 2014].

Cases of hepatitis E have been caused by infection with hepatitis E virus (HEV) due to consumption of raw or undercooked game meats and liver of wild boars or deer in various countries. We investigated HEV prevalence in wild boar and deer in Okazaki City and its outskirts, Aichi, Japan, using liver samples (439 boar; 185 deer) collected between April 2010 and November 2014. HEV RNA was detected in 49 (11.2%)of 439 and 0 of 185 samples of wild boar and deer, respectively. The positive rate (13.0%, 28/216) of HEV RNA from the wild boar with estimated body weight of less than 40 kg was significantly higher than that (2.7%, 3/111) in animals with estimated body weight of more than 40 kg. The 49 HEV strains were typed as genotype 4 (G4) by phylogenetic analysis. They clustered with Aichi/Shizuoka strains and 48 of the 49 strains subclustered together (Okazaki strains).