Genomic analysis of an aggressive hepatic leiomyosarcoma case following treatment for hepatocellular carcinoma.

A 70-year-old man undergoing treatment for immunoglobulin G4-related disease developed a liver mass on computed tomography during routine imaging examination. The tumor was located in the hepatic S1/4 region, was 38 mm in size, and showed arterial enhancement on dynamic contrast-enhanced computed tomography. We performed a liver biopsy and diagnosed moderately differentiated hepatocellular carcinoma. The patient underwent proton beam therapy. The tumor remained unchanged but enlarged after 4 years. The patient was diagnosed with hepatocellular carcinoma recurrence and received hepatic arterial chemoembolization. However, 1 year later, the patient developed jaundice, and the liver tumor grew in size. Unfortunately, the patient passed away. Autopsy revealed that the tumor consisted of spindle-shaped cells exhibiting nuclear atypia and a fission pattern and tested positive for α-smooth muscle actin and vimentin. No hepatocellular carcinoma components were observed, and the patient was pathologically diagnosed with hepatic leiomyosarcoma. Next-generation sequencing revealed somatic mutations in CACNA2D4, CTNNB1, DOCK5, IPO8, MTMR1, PABPC5, SEMA6D, and ZFP36L1. Based on the genetic mutation, sarcomatoid hepatocarcinoma was the most likely pathogenesis in this case. This mutation is indicative of the transition from sarcomatoid hepatocarcinoma to hepatic leiomyosarcoma.

A case of hepatocellular carcinoma with long-term survival by multidisciplinary treatment for cranial and skeletal muscle metastases.

We report a case in which multidisciplinary treatment was effective for hepatocellular carcinoma (HCC) with cranial and skeletal muscle metastases. A 55-year-old male with HCC received sorafenib for lung metastases. He was admitted to our hospital due to the skull metastasis detected by fluorodeoxyglucose positron emission tomography (FDG-PET). The patient underwent resection for skull metastasis. After the surgical treatment, he was treated with sorafenib again. Eight months after craniectomy, FDG-PET showed FDG uptake in the semimembranosus and semitendinosus muscles. Histopathological examination of the muscle biopsy revealed HCC muscle metastasis. Sorafenib treatment was discontinued. The investigational new drug (tegafur-gimeracil-oteracil) and tegafur-uracil were used for the treatment. These treatments proved to be ineffective as the lung metastases enlarged and new metastases appeared on the mediastinal lymph nodes and dura cava. The patient was unable to walk due to the enlarged thigh muscle metastases. Sorafenib was re-administered, which reduced the enlargement of the lung and mediastinal lymph nodes. Dural metastases were treated with resection and radiotherapy. Additional radiation therapy to the thigh muscles relieved the patient from pain experienced during walking. Sorafenib treatment was continued for the next 3 years. The patient survived for 4 years after the skull resection.

Sustained Eosinophilic Cholangitis Due to a Mite Allergy Mimicking Sclerosing Cholangitis.

Eosinophilic cholangiopathy (EC) presents with thickening and stenosis of the bile duct wall that is histologically characterized by eosinophil infiltration. The diagnosis is often difficult. We herein report a patient who had been followed up with a diagnosis of primary sclerosing cholangitis but had a final diagnosis of EC based on eosinophilia, histological findings of bile duct and liver biopsy specimens, and a review of a previous surgical specimen of the gallbladder. Antigen tests, isolation from her house, and accidental re-exposure to the antigen revealed that the causative antigen was the mite Dermatophagoides pteronyssinus.

Mixed neuroendocrine non-neuroendocrine neoplasm of the gallbladder complicated by a pancreaticobiliary maljunction of a non-dilated biliary duct: A case report.

RATIONALE: Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is a rare tumor. MiNEN of the gallbladder (GB) with pancreaticobiliary maljunction (PMJ) is extremely rare. The origin of MiNEN of the GB remains unknown; the biliary tract normally lacks neuroendocrine cells. MiNEN of the GB has a poor prognosis; because of its rarity, no treatment or management guidelines have been established yet. PATIENT CONCERNS: A 47-year-old male presenting with right hypochondrial pain and malaise for 3 months was referred to our hospital for further management. DIAGNOSIS: The neuron-specific enolase level was increased. Contrast-enhanced computed tomography revealed a mass of 70 mm in size with unclear boundaries in the liver. The GB was surrounded by this mass, narrowing the lumen of the GB. Many swollen lymph nodes were observed in the hepatoduodenal ligament. Endoscopic retrograde cholangiopancreatography revealed a PMJ with a non-dilated biliary duct. A percutaneous biopsy was performed on the liver mass, and the pathological findings were neuroendocrine carcinoma (NEC) (small cell type). We diagnosed a NEC of the GB, T3N1M0, stage IIIB (Union for International Cancer Control, 7th edition). INTERVENTIONS: Because of advanced lymph node metastasis, we considered this tumor difficult to cure solely by surgical intervention. After initial chemotherapy consisting of cisplatin and irinotecan, a marked reduction in both tumor and lymph node sizes enabled conversion surgery. The pathological diagnosis of the resected tumor was MiNEN consisting of NEC and adenocarcinoma. The primary lesion was the adenocarcinoma occupying the luminal side of the GB. As a postsurgical treatment, the patient received additional irradiation therapy to the common hepatic duct and liver stump because of positive surgical margins. OUTCOMES: At 13 months postoperatively, computed tomography findings revealed the appearance of a hypervascular liver tumor, and laboratory data showed increased serum neuron-specific enolase levels. Chemotherapy was unsuccessful, leading to the death of the patient 36 months from the date of diagnosis. LESSONS: There are several reports on the development of MiNEN of the GB. In our case, a PMJ-related adenocarcinoma of the GB transdifferentiated into NEC. Further accumulation of cases is necessary to establish a treatment strategy for MiNEN of the GB.

Association of the Low-density Lipoprotein Cholesterol/High-density Lipoprotein Cholesterol Ratio with Glecaprevir-pibrentasvir Treatment.

Objective The change in serum lipid levels by direct-acting antiviral (DAA) treatment for chronic hepatitis C varies depending on the type of DAA. How the lipid level changes induced by glecaprevir-pibrentasvir (G/P) treatment contribute to the clinical outcome remains unclear. We conducted a prospective observational study to evaluate the effectiveness of G/P treatment and the lipid level changes. Methods The primary endpoint was a sustained virologic response at 12 weeks (SVR12). The total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels and LDL-C/HDL-C (L/H) ratio were measured every two weeks. Patients This study included 101 patients. Seventeen cases of liver cirrhosis and nine cases of DAA retreatment were registered. The G/P treatment period was 8 weeks in 74 cases and 12 weeks in 27 cases. Results SVR12 was evaluated in 96 patients. The rate of achievement of SVR12 in the evaluable cases was 100%. We found significantly elevated TC and LDL-C levels over the observation period compared to baseline. The serum levels of HDL-C did not change during treatment but were significantly increased after treatment compared to baseline. The L/H ratio was significantly increased two weeks after the start of treatment but returned to the baseline after treatment. Conclusion The primary endpoint of the SVR12 achievement rate was 100%. G/P treatment changed the serum lipid levels. Specifically, the TC and LDL-C levels increased during and after treatment, and the HDL-C levels increased after treatment. G/P treatment may be associated with a reduced thrombotic risk. Therefore, validation in large trials is recommended.

Idiopathic retroperitoneal fibrosis diagnosed by endoscopic ultrasonography-guided fine-needle biopsy.

We demonstrate a case, in which endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) was useful for determining the diagnosis of lesions of retroperitoneal fibrosis. In our case, accessing the retroperitoneal lesions by conventional percutaneous biopsy procedures was not feasible due to the difficulty of avoiding the inferior vena cava and ureter. We believe that our case demonstrates a unique approach for performing histological analysis in a challenging case.

Artificial intelligence-assisted endoscopy changes the definition of mucosal healing in ulcerative colitis.

The relevance of endoscopic monitoring of ulcerative colitis (UC) has been translated into the new concept of "mucosal healing (MH)" as the therapeutic goal to achieve because a large amount of scientific data have revealed the favorable prognostic value of a healed mucosa in determining the clinical outcome of UC. Recent interest in MH has skewed toward not only endoscopic remission but also histological improvement (so called histological MH). However, we should recognize that there have been no prospectively validated endoscopic scoring systems of UC activity in previous clinical trials. Artificial intelligence (AI)-assisted endoscopy has been developed for gastrointestinal cancer surveillance. Recently, several AI-assisted endoscopic systems have been developed for assessment of MH in UC. In the future, the development of a new endoscopic scoring system based on AI might standardize the definition of MH. Therefore, "The road to an exact definition of MH in the treatment of UC has begun only now".

Autophagy and Autophagy-Related Diseases: A Review.

Autophagy refers to the process involving the decomposition of intracellular components via lysosomes. Autophagy plays an important role in maintaining and regulating cell homeostasis by degrading intracellular components and providing degradation products to cells. In vivo, autophagy has been shown to be involved in the starvation response, intracellular quality control, early development, and cell differentiation. Recent studies have revealed that autophagy dysfunction is implicated in neurodegenerative diseases and tumorigenesis. In addition to the discovery of certain disease-causing autophagy-related mutations and elucidation of the pathogenesis of conditions resulting from the abnormal degradation of selective autophagy substrates, the activation of autophagy is essential for prolonging life and suppressing aging. This article provides a comprehensive review of the role of autophagy in health, physiological function, and autophagy-related disease.

Immunological Mechanisms in Inflammation-Associated Colon Carcinogenesis.

Patients with chronic inflammatory bowel diseases are at an increased risk of developing colitis-associated cancer (CAC). Chronic inflammation positively correlates with tumorigenesis. Similarly, the cumulative rate of incidence of developing CAC increases with prolonged colon inflammation. Immune signaling pathways, such as nuclear factor (NF)-κB, prostaglandin E2 (PGE2)/cyclooxygenase-2 (COX-2), interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3), and IL-23/T helper 17 cell (Th17), have been shown to promote CAC tumorigenesis. In addition, gut microbiota contributes to the development and progression of CAC. This review summarizes the signaling pathways involved in the pathogenesis following colon inflammation to understand the underlying molecular mechanisms in CAC tumorigenesis.

Current Diagnostic and Therapeutic Approaches to Cytomegalovirus Infections in Ulcerative Colitis Patients Based on Clinical and Basic Research Data.

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus (the human herpesvirus 5) and an opportunistic pathogen that primarily infects HIV-positive and other immuno-compromised patients. Retrospective studies in the field of inflammatory bowel disease (IBD) have suggested a relationship between a concomitant colonic HCMV infection and poor outcomes in patients with an ulcerative colitis (UC) due to the presence of HCMV in surgical specimens of patients with a toxic megacolon or a steroid-resistant UC. Therefore, gastroenterologists have focused on the contribution of HCMV infections in the exacerbation of UC. Numerous studies have addressed the benefits of treating colonic HCMV reactivation in UC using an antiviral treatment. However, its clinical relevance remains uncertain as only a few prospective studies have assessed the direct relationship between clinical outcomes and the viral load of HCMV in colonic tissues. HCMV reactivation can be triggered by inflammation according to fundamental research studies. Thus, optimal control of intestinal inflammation is essential for preventing an HCMV reactivation in the intestinal mucosa. Indeed, several reports have indicated the effectiveness of an anti-tumor necrosis factor-alpha (TNFα) treatment in patients with an active UC and concomitant HCMV infections. In this review, we describe the mechanism of HCMV reactivation in UC cases and discuss the current issues regarding diagnosis and treatment of HCMV infections in UC patients.

Natural history of gastric cancer from a retrospective review of endoscopic images of older patients with interval gastric cancer.

AIM: Interval gastric cancers (IGC) are defined as those diagnosed after negative results of endoscopy carried out within the past 10 years. We aimed to investigate the characteristics of IGC and the natural history of gastric cancer (GC) from a retrospective view of endoscopic images of older patients with IGC. METHODS: We retrospectively reviewed endoscopic images of 240 patients with GC who were aged >60 years. We compared past endoscopic images with newer ones, in which GC was diagnosed. IGC were classified into two categories: missed cancers and new cancers. RESULTS: Of the 240 patients with GC, 32 had past endoscopic images that qualified for a precise review. A total of 14 cases involved new cancers, whereas 18 involved missed cancers. Most of the IGC were stage I for at least 2 years; however, a small subset was unresectable at >2 years after a negative endoscopy. Furthermore, the rate of endoscopic treatment was significantly higher for IGC compared with that for non-IGC. CONCLUSIONS: In people aged >60 years, most IGC remain in an early stage for at least 2 years; however, at >2 years after a negative endoscopy, some are unresectable. These results suggest that most early-stage GC will not develop into advanced cancers within 2 years; thus, a 2-year interval might be within the permissible range for patients with negative endoscopy results for any lesions. Geriatr Gerontol Int 2018; 18: 997-1002.

Endoscopic removal of an impacted barolith at the sigmoid colon: a rare case report.

A 45-year-old woman visited our hospital complaining of abdominal pain 1 week after undergoing an annual medical checkup. Her vital signs and blood test results were normal, but tenderness was found in the lower abdomen. A high-density round structure found at the midline of the lower abdomen on an abdominal radiograph was thought to be an accumulation of barium (a barolith) from upper gastrointestinal barium radiography. Two liters of an oral gastrointestinal cleaning agent was administered, but defecation did not occur. Lower gastrointestinal endoscopy revealed that the barolith was impacted at the sigmoid colon. We unsuccessfully attempted to move it using a pressurized water jet and forceps, but it was too large to be captured by the net. Therefore, we broke it down using a snare. After a successful endoscopic procedure, 120 mL of a glycerin enema solution was injected through the forceps opening, causing the barolith to be excreted. There is only one similar case of successful endoscopic treatment of a barolith in the literature.

Synthesis of water-soluble silicon-porphyrin: protolytic behaviour of axially coordinated hydroxy groups.

A new water-soluble silicon(IV)-tetra(4-carboxyphenyl)porphyrin (SiTCPP) with silicon(iv), the second most abundant element on Earth, in the center of porphyrin was synthesized. Fundamental properties including protolytic behaviour of axially coordinating hydroxy groups, and electrochemical behaviour were characterized. The properties were compared with those of silicon(IV)-tetra(2,4,6-trimethylphenyl)porphyrin (SiTMP) and silicon(IV)-tetra(4-trifluoromethylphenyl)porphyrin (SiTFMPP) and discussed in respect to the electron donating/withdrawing effect of the substituents. Two axially coordinating hydroxy groups of SiTCPP exhibit a four-step protolytic behaviour under the acidic conditions along with a single step protolysis of peripheral carboxyl groups. Though SiTCPP and SiTFMPP did not show any reactivity in the photochemical oxygenation of a substrate with K2PtCl6 as a sacrificial electron acceptor, the first oxidation wave in the electrochemical process of SiTCPP and SiTFMPP showed catalytic behaviour in aqueous acetonitrile solution at any pH condition, in contrast to SiTMP which has only a reversible oxidation wave under neutral and weakly acidic conditions. The criteria for the electrochemical oxidative activation of water and the photooxygenation of the substrate were obtained. The higher oxidation wave of Si-porphyrins than ∼0.86 volt vs. SHE is required for the electrochemical oxidation of water, while suitable protecting groups such as a methyl substituent is a requisite for the photochemical oxygenation with K2PtCl6 as a sacrificial electron acceptor.

CLCA2, a target of the p53 family, negatively regulates cancer cell migration and invasion.

The tumor suppressor p53 transcriptionally regulates a number of genes that are involved in cell-cycle inhibition, apoptosis and the maintenance of genetic stability. Recent studies suggest that p53 also contributes to the regulation of cell migration and invasion. Here, we show that human chloride channel accessory-2 (CLCA2) is a target gene of the p53 family (p53, p73 and p63). CLCA2 is induced by DNA damage in a p53-dependent manner. The p53 family proteins activate the CLCA2 promoter by binding directly to the conserved consensus p53-binding site present in the CLCA2 promoter. In terms of function, ectopic expression of CLCA2 inhibited cancer cell migration. In contrast, silencing CLCA2 with siRNA stimulated cancer cell migration and invasion. We also found that inactivation of CLCA2 enhanced the expression of focal adhesion kinase (FAK), as well as its promoter activation. A small-molecule FAK inhibitor reduced the effect of CLCA2 siRNA on cell migration and invasion, suggesting that CLCA2 inhibits cancer cell migration and invasion through suppression of the FAK signaling pathway. Furthermore, there was an inverse correlation between CLCA2 and FAK expression in 251 human breast cancer tissues. These results strongly suggest that CLCA2 is involved in the p53 tumor suppressor network and has a significant effect on cell migration and invasion.