A Case Report of Primary Neuroendocrine Carcinoma of the Anal Canal with Cancer Genome Profiling.

Primary neuroendocrine carcinoma (NEC) of the anal canal is a rare, highly malignant tumor with a poor prognosis. Despite the standard first-line treatment with etoposide or irinotecan combined with cisplatin, effective second-line therapies are lacking. In 2019, Japan approved cancer genome profiling (CGP) tests for solid tumors to enhance genomic understanding. We present the case of a 79-year-old woman with NEC of the anal canal, treated with etoposide, carboplatin, and amrubicin. Post-standard therapy, CGP suggested pemigatinib, a tyrosine kinase inhibitor; however, the patient died before receiving it. This case highlights the potential of personalized medicine to improve outcomes in such cases.

Severe Erythroderma Due to Adult-onset Still's Disease-like Disease Related to Graft-versus-host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

A 35-year-old woman was treated with chemotherapy for leukemia. One year later, allogeneic hematopoietic stem cell transplantation (HSCT) was performed with umbilical cord blood. After nine months, she developed a spiking fever, sore throat, arthralgia, pleural effusion, hyperferritinemia, and persistent generalized pruritic erythema. A skin biopsy showed dyskeratotic cells in the epidermis, neutrophil infiltration in the epidermis and upper dermis, and neutrophils in the parakeratotic layer. Treatment with tocilizumab was effective. Adult-onset Still's disease (AOSD)-like disease related to graft versus-host disease (GVHD) after HSCT was suspected. Abnormal immune states related to GVHD may cause AOSD-like disease with more severe skin lesions than usual.

Eosinophilic Cholangitis with Poor Prognosis after Corticosteroid- and Ursodeoxycholic Acid-Related Remission of Peripheral and Peribiliary Eosinophilia.

A 79-year-old man presented with high fever, marked eosinophilia, altered biochemical liver function tests (LFT) with predominance of biliary enzymes, and severe wall thickening of the gallbladder. Magnetic resonance cholangiopancreatography (MRCP) suggested cholecystitis, without signs of biliary strictures. Laparoscopic cholecystectomy and exploratory liver excision revealed eosinophilic cholangitis and cholecystitis, complicated with hepatitis and portal phlebitis. Prednisolone monotherapy rapidly improved peripheral eosinophilia, but not LFT. Liver biopsy showed that infiltrating eosinophils were replaced by lymphocytes and plasma cells. Treatment with ursodeoxycholic acid improved LFT abnormalities. Nevertheless, after 2 months, transaminase-dominant LFT abnormalities appeared. Transient prednisolone dose increase improved LFT, but biliary enzymes' levels re-elevated and jaundice progressed. The second and third MRCP within a 7-month interval showed rapid progression of biliary stricture. The repeated liver biopsy showed lymphocytic, not eosinophilic, peribiliary infiltration and hepatocellular reaction to cholestasis. Eighteen months after the first visit, the patient died of hepatic failure. Autopsy specimen of the liver showed lymphocyte-dominant peribiliary infiltration and bridging fibrosis due to cholestasis. Though eosinophil-induced biliary damage was an initial trigger, repeated biopsy suggested that lymphocytes played a key role in progression of the disease. Further studies are needed to elucidate the relationship between eosinophils and lymphocytes in eosinophilic cholangitis.

Greater age and hepatocellular aging are independent risk factors for hepatocellular carcinoma arising from non-B non-C non-alcoholic chronic liver disease.

We previously reported that hepatocellular aging can be assessed by measuring the nuclear size of hepatocytes. We attempted to elucidate whether this method is useful to identify the high risk group of hepatocellular carcinoma (HCC) in the patients with non-B non-C non-alcoholic liver injury. Fourteen patients with HCC and 78 without HCC, both of whom presented with non-B non-C non-alcoholic chronic liver injury and underwent liver biopsy, were selected. Twelve histologically normal liver tissues were selected as controls. The relative nuclear size (RNS) was calculated as the average nuclear size of the hepatocytes divided by that of lymphocytes. Multiple clinicopathological parameters were studied. The RNS values of normal livers ranged from 1.32 to 2.10, showing a gradual increase in an age-dependent manner. The RNS values of the injured livers without HCC increased after middle age. Univariate analysis identified greater age, existence of diabetes and RNS, as significantly positive contributors and ALT value and the degree of steatosis as negative contributors for the occurrence of HCC. Only age and RNS retained significance in multivariate analysis. All of the HCC patients were older than 50 and showed RNS values higher than 2.00. Therefore, such patients are classified as a high risk group of HCC.

The relation between health literacy, hypertension knowledge, and blood pressure among middle-aged Japanese adults.

BACKGROUND: With the growth in the popularity of the Internet, individuals' skills in finding and applying information about health issues [health literacy (HL)] are affecting their health behaviors. This study aimed to examine functional HL (FHL), critical HL (CHL), and hypertension knowledge (HK) among middle-aged Japanese adults. In addition, to measure health outcomes, we examined the relationship between HL, HK, and blood pressure (BP) level. METHODS: The study included middle-aged participants who received an annual health check-up at an urban clinic in Japan. FHL, CHL, and HK were assessed using structured questionnaires. In addition, BP was obtained from the electronic medical record. RESULTS: Participants included 139 women and 181 men with a mean age of 54.4 years (standard deviation = 0.69). Individuals with lower reading comprehension scores in FHL were more likely to have a history of hypertension (P = 0.003) and diabetes mellitus (P = 0.02). Individuals with lower CHL had significantly higher rates of current smoking (P = 0.03) and men with lower CHL had a significantly higher waist circumference (P = 0.03). There was a significant relationship between sex and HK (P = 0.03). Systolic BP in women with higher HL and HK was significantly lower than in men with higher FHL (P < 0.001), CHL (P = 0.01), and HK (P = 0.001). CONCLUSION: Lower HL and HK were associated with a poor health status and BP level in middle-aged participants. Further research is needed to examine the role of health management in improving outcomes and to address disparities between individuals with higher and lower HL.

Sofalcone, a gastric mucosa protective agent, increases vascular endothelial growth factor via the Nrf2-heme-oxygenase-1 dependent pathway in gastric epithelial cells.

Sofalcone, 2'-carboxymethoxy-4,4-bis(3-methyl-2-butenyloxy)chalcone, is an anti-ulcer agent that is classified as a gastric mucosa protective agent. Recent studies indicate heat shock proteins such as HSP32, also known as heme-oxygenase-1(HO-1), play important roles in protecting gastrointestinal tissues from several stresses. We have previously reported that sofalcone increases the expression of HO-1 in adipocytes and pre-adipocytes, although the effect of sofalcone on HO-1 induction in gastrointestinal tissues is not clear. In the current study, we investigated the effects of sofalcone on the expression of HO-1 and its functional role in rat gastric epithelial (RGM-1) cells. We found that sofalcone increased HO-1 expression in RGM-1 cells in both time- and concentration-dependent manners. The HO-1 induction was associated with the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in RGM-1 cells. We also observed that sofalcone increased vascular endothelial growth factor (VEGF) production in the culture medium. Treatment of RGM-1 cells with an HO-1 inhibitor (tin-protoporphyrin), or HO-1 siRNA inhibited sofalcone-induced VEGF production, suggesting that the effect of sofalcone on VEGF expression is mediated by the HO-1 pathway. These results suggest that the gastroprotective effects of sofalcone are partly exerted via Nrf2-HO-1 activation followed by VEGF production.