Low skeletal muscle mass and high visceral adiposity are associated with recurrence of acute cholecystitis after conservative management: A propensity score-matched cohort study.

BACKGROUND: Recurrent acute cholecystitis (RAC) can occur after non-surgical treatment for acute cholecystitis (AC), and can be more severe in comparison to the first episode of AC. Low skeletal muscle mass or adiposity have various effects in several diseases. We aimed to clarify the relationship between RAC and body parameters. METHODS: Patients with AC who were treated at our hospital between January 2011 and March 2022 were enrolled. The psoas muscle mass and adipose tissue area at the third lumbar level were measured using computed tomography at the first episode of AC. The areas were divided by height to obtain the psoas muscle mass index (PMI) and subcutaneous/visceral adipose tissue index (SATI/VATI). According to median VATI, SATI and PMI values by sex, patients were divided into the high and low PMI groups. We performed propensity score matching to eliminate the baseline differences between the high PMI and low PMI groups and analyzed the cumulative incidence and predictors of RAC. RESULTS: The entire cohort was divided into the high PMI (n = 81) and low PMI (n = 80) groups. In the propensity score-matched cohort there were 57 patients in each group. In Kaplan-Meier analysis, the low PMI group and the high VATI group had a significantly higher cumulative incidence of RAC than their counterparts (log-rank P = 0.001 and 0.015, respectively). In a multivariate Cox regression analysis, the hazard ratios of low PMI and low VATI for RAC were 5.250 (95% confidence interval 1.083-25.450, P = 0.039) and 0.158 (95% confidence interval: 0.026-0.937, P = 0.042), respectively. CONCLUSIONS: Low skeletal muscle mass and high visceral adiposity were independent risk factors for RAC.

Impact of Interferon-Free Direct-Acting Antivirals on the Incidence of Extrahepatic Malignancies in Patients with Chronic Hepatitis C.

BACKGROUND: The incidence of extrahepatic malignancies (EHMs) after hepatitis C virus (HCV) eradication by interferon (IFN)-based and IFN-free direct-acting antivirals (DAAs) treatment remains unclear. AIMS: The aim was to evaluate the cumulative incidence of EHMs diagnosed for the first time after the antiviral treatments. METHODS: We analyzed a total 527 patients with chronic HCV infection and without prior history of any malignancies who achieved sustained virological response by antiviral treatments, including IFN-based (n = 242) or IFN-free DAAs (n = 285). The baseline predictors for EHM occurrence were analyzed using Cox regression analysis. RESULTS: Thirty-two patients were diagnosed with EHMs, 14 in IFN-based and 18 in IFN-free DAAs, respectively. The total duration of follow-up was 1,796 person-years in IFN-based and 823 person-years in IFN-free DAAs. The incidence of EHMs in IFN-based and IFN-free DAAs was 7.8 and 21.9 per 1,000 person-years, respectively. The cumulative incidence of EHMs was significantly higher in IFN-free DAAs than IFN-based (p = 0.002). IFN-free DAAs was a single independent predictor for incidence of EHMs (p = 0.012). As for gender, the incidence of EHMs was significantly higher in IFN-free DAAs only in the female cohort (p = 0.002). After propensity score matching, IFN-free DAAs was a single independent predictor for incidence of EHMs in the female patients (p = 0.045). CONCLUSIONS: The incidence of EHMs after HCV eradication is higher in IFN-free DAAs than IFN-based regimens, especially in female patients. We should carefully follow-up not only HCC but also EHMs after IFN-free DAAs regimens.

A Case of Successful Endoscopic Extraction of Common Bile Duct Stones After Closing a Duodenal Perforation Using Over-The-Scope Clip.

A 57-year-old man visited our hospital for acute cholangitis due to common bile duct (CBD) stones in March 2021. Biliary stenting was performed without any complications. The cholangitis improved rapidly. He was re-hospitalized to treat the CBD stones in May 2021. Although endoscopic retrograde cholangiopancreatography was performed, endoscopy caused a perforation of the duodenal bulb. We successfully performed endoscopic closure of the duodenal defect using an over-the-scope clip (OTSC®). Considering that mild CBD dilatation of 10 mm can carry an increased risk of stenosis after surgery, we decided to avoid surgery and perform a follow-up endoscopic treatment. He was re-hospitalized in July 2021. The endoscopy revealed OTSC® in the anterior wall of the duodenal bulb and complete healing of the perforation. We carefully advanced the scope to the second portion of the duodenum while avoiding OTSC®, and the ampulla of Vater was identified. We were then able to remove the stones without any complications. OTSC® was effective in closing a duodenal perforation and enabled us to carry out the retreatment safely and successfully.

Hepatic Cyst Infection Following Recurrent Biliary Obstruction in Polycystic Liver Disease.

An 89-year-old man with polycystic liver disease (PCLD) received uncovered self-expandable metallic stent (SEMS) placement above the papilla for malignant biliary obstruction caused by cholangiocarcinoma. He developed cholangitis ten months later due to SEMS occlusion caused by tumor ingrowth, and 2 plastic biliary stents were placed inside the SEMS across the papilla. Fever and right costal pain appeared two weeks after reintervention. Suspecting hepatic cyst infection based on imaging studies, percutaneous transhepatic cyst drainage was performed. Increased inflammatory cells and the presence of pathogens in the cyst fluid led to a definitive diagnosis of hepatic cyst infection. Following drainage, the hepatic cyst shrank with resolution of the symptoms. SEMS occlusive-related cholangitis or retrograde infection due to duodenal-biliary reflux after reintervention was considered as the cause of the hepatic cyst infection. Careful clinical and imaging evaluation should be performed in patients with PCLD undergone biliary stenting, because cyst infection may occur following stent occlusion or subsequent biliary reintervention.

A Case of Pancreatic Neuroendocrine Tumor G3 Which Responded Remarkably to Chemotherapy.

Pancreatic neuroendocrine carcinoma (NEC) as classified in the World Health Organization (WHO) 2010 was reclassified in the WHO 2017 as either neuroendocrine tumor (NET) G3 or NEC. An accurate diagnosis based on the WHO 2017 classification is important in order treating this disease appropriately. We report a case diagnosed as NET G3 that responded remarkably well to treatment with streptozocin. The patient would likely not have received the streptozocin treatment if she had been diagnosed with NEC. The WHO 2017 classification is reasonable for the treatment of advanced pancreatic neuroendocrine neoplasms.

Influence of gastroesophageal flap valve on esophageal variceal bleeding in patients with liver cirrhosis.

OBJECTIVES: Esophageal variceal bleeding can be fatal in patients with liver cirrhosis. The aim of this study was to investigate the relationship between gastroesophageal flap valve (GEFV) and esophageal variceal bleeding. METHODS: Subjects were cirrhotic patients with endoscopically diagnosed esophageal varices treated at our hospital between 2005 and 2019, excluding those with F3 form and red color (RC) signs at first endoscopy. Sixty-five patients with normal GEFV (Hill grade I or II) and 42 with abnormal GEFV (Hill grade III or IV) were enrolled. Propensity score matching eliminated the baseline differences, resulting in a sample size of 30 patients per cohort. The primary endpoint was esophageal variceal bleeding, and the secondary endpoint was variceal bleeding or appearance of RC sign. We analyzed the cumulative incidences and predictors of each endpoint. RESULTS: The 3-, 5-, and 10-year cumulative incidences of the primary endpoints were all 3.4% in the normal GEFV group, and 19.0%, 24.6% and 34.0% in the abnormal GEFV group, respectively (log-rank P = 0.011). Cumulative incidence of the secondary endpoint was 13.8%, 33.1% and 39.2% in the normal GEFV group, and 42.2%, 54.6% and 84.9% in the abnormal GEFV group, respectively (log-rank P = 0.001). In multivariate Cox regression analyses, hazard ratios of abnormal GEFV of the primary and secondary endpoints were 12.79 (95% confidence interval 1.331-122.8) and 3.600 (1.653-7.840), respectively. CONCLUSIONS: Abnormal GEFV was an independent risk factor for esophageal variceal bleeding and appearance of RC sign.

Type 4B hereditary hemochromatosis due to heterozygous p.D157A mutation in SLC40A1 complicated with hypopituitarism.

Hemochromatosis is a clinical syndrome characterized by iron overload in various organs. We present here a case of type 4 hereditary hemochromatosis due to heterozygous mutation in SLC40A1 gene (p.D157A). SLC40A1 encodes ferroportin, a macromolecule only known as iron exporter from mammalian cells. He first presented symptoms correlated with hypopituitarism. Furthermore, marked hyperferritinemia and high transferrin saturation were revealed in combination with the findings of iron overload in the liver, spleen and pituitary gland by computed tomography and magnetic resonance imaging. Liver biopsy revealed iron deposition in both hepatocytes and Kupffer cells. SLC40A1 mutations are considered to cause wide heterogeneity by various ferroportin mutations. Thus, clinicopathological examinations seem to be very important for diagnosing phenotype of type 4 hemochromatosis in addition to the gene analysis. We diagnosed him as type 4B hereditary hemochromatosis (ferroportin-associated hemochromatosis) by the findings of high transferrin saturation and iron deposition in hepatocytes, and then started iron chelating treatment. We should suspect the possibility of hereditary hemochromatosis even in Japanese with severe iron overload. Although the same mutation in SLC40A1 gene (p.D157A) had been reported to cause "loss of function" phenotype, we considered that the mutation of our case caused "gain of function" phenotype.

Hepatocyte Growth Factor and Primary Systemic Amyloidosis.

A 75-year-old-man experienced liver dysfunction and was diagnosed with decompensated liver cirrhosis. His serum hepatocyte growth factor (HGF) was very high (16.24 ng/ml). Because the etiology was unclear, we considered the possibility of amyloidosis. Biopsy of the mucosa of the stomach, duodenum and rectum demonstrated amyloid deposition. From the findings of Congo red staining and immunohistochemical analyses, we made a diagnosis of systemic amyloid light-chain amyloidosis. Unfortunately, the patient died one month after the diagnosis. We considered that serum HGF was useful for the diagnosis and prediction of prognosis of primary systemic amyloidosis.

Idiopathic copper toxicosis: is abnormal copper metabolism a primary cause of this disease?

Idiopathic copper toxicosis (ICT) is characterized by marked copper deposition, Mallory-Denk body (MDB) formation and severe hepatic injury. Although the characteristics are apparently different from Wilson disease, large amounts of copper accumulate in the liver of the patients. We extensively treated a patient with ICT to reduce the body copper, however, the patient needed liver transplantation. Previous liver biopsy revealed high copper content. But extirpated liver contained an extremely small amount of copper, although MDBs and severe inflammation remained. These phenomena suggest abnormal copper metabolism is not the principle cause of ICT but some other abnormality must exist.

Effect of direct-acting antivirals on platelet-associated immunoglobulin G and thrombocytopenia in hepatitis C virus-related chronic liver disease.

BACKGROUND & AIMS: Hepatitis C virus (HCV) infection has been known to cause various extrahepatic autoimmune disorders. The prevalence of platelet-associated immunoglobulin G (PA-IgG) has been high in patients with HCV infection. Because thrombocytopenia in HCV-related liver diseases is a notable problem, we performed prospective study on the effect of direct-acting antivirals (DAAs) treatment on PA-IgG and platelet count. METHODS: A total of 215 patients with HCV-related liver disease were enrolled in this study. The patients who discontinued DAAs or did not undergo adequate laboratory examinations and who did not achieve sustained virologic response were excluded and finally a total of 187 patients were investigated. RESULTS: A total of 171 patients (91.4%) were PA-IgG positive (>46 ng/107 cells) before starting DAAs (baseline). The PA-IgG level elevation was significantly correlated with higher liver inflammation and fibrosis markers (P < 0.05) and lower platelet count (P = 0.000019). The platelet count of the patients with low PA-IgG titer tended to be higher at baseline, end of treatment (EOT), and at 12 and 24 weeks after EOT. The platelet count increased at EOT (P < 0.05) and 24 weeks after EOT (P < 0.01). The PA-IgG levels were significantly decreased at EOT, 12 and 24 weeks after EOT (P < 0.01). Multiple regression analysis found that only platelet count at baseline was closely associated with negative conversion of PA-IgG at 24 weeks after EOT (P = 0.004). CONCLUSIONS: Eradication of HCV by DAAs treatment successfully decreased PA-IgG level and increased platelet count.

Secondary sclerosing cholangitis with hemobilia induced by pembrolizumab: Case report and review of published work.

A 66-year-old man was admitted to our department due to cholestatic liver injury. He had received five cycles of pembrolizumab for small-cell lung cancer. Imaging showed the possibility of sclerosing cholangitis (SC) with hemobilia. Histologically, CD8+ T cells had infiltrated the biliary epithelium of the extrahepatic bile duct. We reached the diagnosis of secondary SC induced by pembrolizumab. Although we treated him with high-dose corticosteroids, laboratory data showed only a moderate response. Clinicians should recognize that immune checkpoint inhibitors can sometimes cause severe and irreversible SC.

Impact of examining additional deeper sections on the pathological diagnosis of endoscopically resected early gastric cancer.

OBJECTIVES: The pathological diagnosis of endoscopically resected early gastric cancer (EGC) is performed by evaluating a few representative sections from the specimen. We aimed to determine whether evaluating twice as many sections as usual by essentially cutting the original sections in half could improve the pathological diagnosis of EGC. METHODS: We retrospectively investigated 85 EGC in 82 patients who had undergone endoscopic resection at our hospital from August 2008 to October 2012. EGC without indications of curative resection were excluded. We re-examined the original paraffin blocks after shaving away approximately half their original thickness, and evaluated whether the pathological diagnoses were affected. This technique essentially doubled the number of sections examined. RESULTS: Ten pathological diagnoses of 68 EGC (14.7%) were changed from curative resection to non-curative resection when we evaluated twice as many sections as in the standard method. The median tumor size was 25 mm in the changed diagnosis group versus 14.5 mm in the no change group (P = 0.03). The univariate analysis also showed that tumor size was a significant predictor of changed diagnosis (P = 0.015). Both the changed diagnosis group and no change group had no recurrence during follow up. CONCLUSIONS: Histological evaluation of twice as many sections as usual changed the initial pathological diagnosis of EGC, although the clinical implication of an additional deeper section was controversial because there was no recurrence. Our analysis also emphasized the importance of detailed histological evaluation to confirm a radical cure in endoscopic resection, especially in the case of larger EGC.

Recognition of infection, status of outpatient treatment, and treatment history before carcinogenesis in patients with viral hepatitis-associated liver cancer.

We conducted a survey on the recognition of infection, status of outpatient treatment, and treatment history in hepatitis virus-associated hepatocellular carcinoma patients admitted to our department between 2005 and 2014. We compared these parameters in 75 patients with primary hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and 307 patients with hepatitis C virus-associated hepatocellular carcinoma (HCV-HCC). Based on the presence or absence of outpatient treatment in medical institutions at the time of HCC diagnosis, the patients were divided into an outpatient treatment-free group or an outpatient treated group. In addition, the latter group was divided into three subgroups depending on the department consulted:the Department of Internal Medicine group, the Department of Gastroenterology group, and a hepatologist-treated group. Patients in the outpatient treatment-free group accounted for 40.0% of patients with HBV-HCC. In the outpatient treated group (60.0%), 21.3% were treated in the Department of Internal Medicine, 22.7% in the Department of Gastroenterology, and 16.0% were treated by a hepatologist. The percentage of HBV-HCC patients in the outpatient treatment-free group was 1.9 times higher than that in the HCV-HCC group and 0.6-fold higher in the hepatologist-treated group. Of the HBV-HCC patients, non-recognizers who were not diagnosed with a viral infection accounted for 21.3%, and non-outpatients who had not consulted a hospital despite the recognition of infection accounted for 33.3%. These percentages were approximately 2 times higher than in HCV-HCC patients. Of the HBV-HCC patients, 66.7% in the hepatologist-treated group had received nucleic acid analogue preparations. On the other hand, one patient in each of the Department of Internal Medicine and Department of Gastroenterology groups (approximately 6.0%) had received a nucleic acid analogue, lamivudine, despite the appearance of a resistant strain. In the HBV-HCC patients, the proportions of "non-recognizers" and "non-outpatients" were higher than in the HCV-HCC patients, suggesting a lack of appropriate treatment.

A case of idiopathic gastroesophageal submucosal hematoma and its disappearance observed by endoscopy.

A 74-year-old man was hospitalized due to hematemesis. Upper gastrointestinal endoscopy revealed a very large and dark red mass in the cardiac region of the stomach that extended from the upper esophagus. A biopsy specimen showed hemorrhagic tissue and no malignant cells. The tumor-like region ulcerated at 5 days after the administration of intravenous lansoprazole at a dose of 30 mg twice a day and resolved with scar formation at 2 months after a change to oral rabeprazole at a dose of 10 mg/day.We diagnosed the patient with gastroesophageal submucosal hematoma. Gastroesophageal submucosal hematoma is a rare complication. In this case, we could follow the process of its disappearance by endoscopy.

Child-Pugh grade deterioration stratified by the etiology after transcatheter arterial chemoembolization as initial treatment for hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, TACE can cause deterioration of liver functions. We aimed to identify the factors that influence deterioration of liver function after TACE. We retrospectively analyzed 262 patients who underwent TACE as initial treatment for HCC with Child-Pugh grade A. We divided them into three groups stratified by the etiology of underlying liver disease. Patients were classified into hepatitis B virus (HBV) group, hepatitis C virus (HCV) group, and non-HBV / non-HCV (NBNC) group. Liver functions at one month after TACE and time to Child-Pugh grade B or C were compared between the three groups. The HBV, HCV and NBNC groups contained 23, 123 and 116 patients, respectively. The decline in albumin level after TACE was significantly higher in NBNC group than other groups (p = 0.02). NBNC group showed a shorter time to Child-Pugh grade deterioration compared with HBV group and HCV group (p < 0.001). Multivariate Cox regression analysis showed that NBNC group was a significant factor for Child-Pugh grade deterioration (Hazard ratio 3.74, 95% confidence interval 1.89-7.40, p < 0.001). These results revealed that liver functions worsened most remarkably in NBNC group after TACE.

An Unusual Abscess Associated with Gallbladder Perforation Successfully Treated with Percutaneous Transhepatic Gallbladder Drainage and Endoscopic Ultrasound-guided Abscess Drainage.

Abscesses associated with gallbladder perforation are often confined to the peri-gallbladder region. We herein report a rare case of gallbladder perforation in which the abscess cavity extended into the left upper quadrant. A 79-year-old woman developed gallbladder perforation secondary to acalculous cholecystitis. Computed tomography revealed fluid collection extending from the peri-gallbladder to the dorsal left hepatic lobe in contact with the stomach. We successfully treated percutaneous transhepatic gallbladder drainage and simultaneous endoscopic ultrasound-guided transgastric internal and external abscess drainage. This minimally invasive approach is considered safe and feasible for managing such a rare case.

A case of adrenal metastasis of hepatocellular carcinoma diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

An 82-year-old man had been treated for lung adenocarcinoma and hepatocellular carcinoma (HCC). Contrast-enhanced computed tomography examination showed swelling of the left adrenal gland, suggesting metastasis of lung adenocarcinoma, HCC, or primary adrenal tumor. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed for the pathological diagnosis, and adrenal metastasis of HCC was diagnosed. No notable complications due to EUS-FNA were found. There have been reports of adrenal metastasis due to various cancers, but there are few reports that can confirm the diagnosis of adrenal metastasis of HCC using EUS-FNA. Adrenal metastasis of HCC is not a rare condition, but it may be difficult to diagnose in the case of multiple cancer complications. We experienced a case in which EUS-FNA was useful for the diagnosis of adrenal metastasis of HCC.

Two Cases with Isolated Splenic Sarcoidosis Diagnosed by an Ultrasound-guided Fine-needle Aspiration Biopsy.

Asymptomatic splenic nodules were detected incidentally in two middle-aged women at an annual checkup. They showed no abnormalities on laboratory tests, but imaging studies revealed splenic nodules. No other localized lesions were found. Splenic nodules were hypoechoic on ultrasonography (US), hypovascular on contrast-enhanced computed tomography, and showed a low intensity on T2-weighted magnetic resonance imaging. We performed US-guided percutaneous aspiration biopsies using 21-gauge needles without complications, including bleeding. Pathological specimens showed noncaseating granulomas, so both patients were diagnosed with isolated splenic sarcoidosis. A US-guided fine-needle aspiration biopsy is a safe and useful method for diagnosing splenic nodules.

Autoimmune hepatitis complicated by adult-onset Still's disease during treatment with tocilizumab: A case report from acute onset to recurrence.

The characteristics of liver dysfunction due to adult-onset Still's disease are not specific. Differentiating from autoimmune hepatitis is important in deciding whether to continue corticosteroid therapy, and also in terms of management of cirrhosis and surveillance of hepatocellular carcinoma. Liver biopsy is thought to be the most important determinant for differential diagnosis.