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.

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.

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.

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.

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.

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.

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.

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.

Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis.

BACKGROUND: A comparison between atezolizumab plus bevacizumab (ATEZO/BEVA) and lenvatinib (LEN) for the treatment of hepatocellular carcinoma (HCC) remains unclear. OBJECTIVE: This study aimed to compare the therapeutic effects and safety of ATEZO/BEVA and LEN as first-line therapies for HCC. PATIENTS AND METHODS: This study was a retrospective analysis of 810 patients with HCC who underwent ATEZO/BEVA (n = 186) or LEN (n = 624) as first-line systemic therapy between March 2018 to March 2022 at 14 facilities. After propensity score matching, 304 patients (ATEZO/BEVA group: n = 152; LEN group: n = 152) were analyzed. RESULTS: After propensity score matching, although there was no significant difference in objective response rates (ORRs) between the ATEZO/BEVA and LEN groups (ORR 44.8% vs. 46.7%, p = 0.644), the median progression-free survival (PFS) and median overall survival (OS) in the ATEZO/BEVA group were significantly higher than those in the LEN group (median PFS: 8.3 months vs. 6.0 months, p = 0.005; median OS: not reached vs. 20.2 months, p = 0.039). The rates of appetite loss, fatigue, and proteinuria of grade 3 or higher in the ATEZO/BEVA group were lower than those in the LEN group. However, the rate of bleeding of grade 3 or higher in the ATEZO/BEVA group was higher than that in the LEN group. The conversion rate was higher in the ATEZO/BEVA group than that in the LEN group (8.6% vs. 1.9%, p = 0.007). CONCLUSIONS: ATEZO/BEVA showed superiority to LEN in terms of prognosis and conversion rate as first-line therapy. Moreover, ATEZO/BEVA had a lower rate of severe adverse events, except for bleeding, than LEN.

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.

Trends in hepatocellular carcinoma incident cases in Japan between 1996 and 2019.

We examined the epidemiological trends, including the distribution of sex, age, and disease etiology, in HCC incident cases, over 24 years. Data of 20,547 HCC patients (1996-2019) were analyzed in this prospective study. We divided the study period into four 6-yearly quarters. HCC etiology was categorized as hepatitis B virus (HBV) infection, HBV + hepatitis C virus (HCV) infection, HCV infection, and both negative (non-BC). The incident cases of HCC per quarter of the study period were 4311 (21.0%), 5505 (26.8%), 5776 (28.1%), and 4955 (24.1%), sequentially. Overall, 14,020 (68.2%) patients were male. The number of HCC cases in patients < 60 years, 60-69 years, 70-79 years, and ≥ 80 years were 3711 (18.1%), 6652 (32.4%), 7448 (36.2%), and 2736 (13.3%), respectively. The average age of newly-diagnosed patients increased in each quarter. HCC was associated with HBV, HBV + HCV, and HCV infections and non-BC in 2997 (14.6%), 187 (0.9%), and 12,019 (58.5%), and 5344 (26.0%) cases, respectively. The number of HCV-associated cases decreased in each quarter, while that of non-BC-associated cases increased. HCC incident cases tend to increase in the elderly and in non-BC patients; in contrast, HCC incident cases due to HCV tend to decrease.

Endoscopic injection sclerotherapy improves liver function compared with endoscopic variceal ligation.

Liver function is a most important prognostic factor in patients with liver cirrhosis. Also, portal hypertension is a fatal complication of liver cirrhosis and variceal treatment is indispensable. However, changes of liver functions after endoscopic variceal treatments are unknown. The aim of this study was to evaluate prognosis and liver functions after endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL). A total of liver cirrhotic 103 patients who underwent prophylactic EIS and EVL were enrolled. Overall survival rate was higher in EIS group than EVL group (p = 0.03). Multivariate analysis showed that EIS was a negative factor for death (HR: 0.46, 95% confidence interval: 0.24-0.88, p = 0.02). Liver functions were assessed by blood test taken at before and 3 months after treatment. In EIS group, albumin and prothrombin time improved (p < 0.01), leading to improvement of Child-Pugh score, ALBI score and MELD score (p < 0.05). However, these did not improve in EVL group. EIS was a significant factor related to the elevated value of albumin after treatment in linear regression analysis (estimated regression coefficient: 0.17, 95% confidence interval: 0.05-0.29, p = 0.005). These results revealed that EIS could improve liver functions and prognosis.

Airborne fine particulate matter in Japan induces lipid synthesis and inhibits autophagy in HepG2 cells.

Inhalation of particulate matter with a diameter less than 2.5 µm has been reported to exacerbates fatty liver disease. However, the components and mechanisms of particulate matter involved in hepatic lipid metabolism and autophagy have not been fully elucidated. We found that atmospheric particulate matter in Japan stimulated lipogenesis in hepatocytes even when its lipid component was removed. Furthermore, we demonstrated that particulate matter did not promote autophagosome formation but inhibited autophagic degradation in hepatocytes. In previous toxicity experiments, particulate matter collected from atmosphere often contained contaminants originating from filters. In this study, we exposed the powdery particulate matter with less contaminants collected using a cyclone and impactor system to HepG2 cells, human hepatocyte. This particulate matter induced lipogenesis and endoplasmic reticulum stress in HepG2 cells as well as previous reports of particulate matter in the USA and China. On the other hand, when autophagic flux were examined in detail, the particulate matter did not promote autophagosome formation, but inhibited autophagic degradation. Since these effects were similar to those of palmitate, a fatty acid, we prepared particulate matter in which lipid component was removed by acetone and compared the effects on HepG2 cells with those of untreated one. The particulate matter without lipid component induced lipid droplets as well as did the untreated one although it induced less endoplasmic reticulum stress. These results suggest that hepatic lipid synthesis is stimulated not only by the uptake of lipid but also by other components in the particulate matter.

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.

Impact of the Concomitant Use of Immunomodulator and a Lower Week 8 Partial Mayo Score on the Persistence of Adalimumab in Refractory Ulcerative Colitis.

Objective Real-world data of adalimumab (ADA) in the treatment of ulcerative colitis (UC) are scarce. We aimed to study the ADA response rates and predictors of response in UC treatment. Methods This observational, prospective and multi-center study assessed the clinical outcome of refractory UC patients treated with ADA who previously had an inadequate response to either conventional therapies or other anti-TNF antibodies or tacrolimus. The primary endpoint was the proportion of UC patients achieving a clinical response and remission at 8 and 52 weeks. We also evaluated the parameters which were associated with a clinical response at 8 and 52 weeks. Results A total of 35 patients were enrolled from 11 centers. The clinical responses at 8 and 52 weeks were 60.0% and 51.4%, respectively. The clinical remission rates at 8 and 52 weeks were 45.7% and 48.6%, respectively. Positive predictors for week 52 response were combination of ADA with immunomodulator (IM) (OR: 27.229; 95% CI; 1.897-390.76; p=0.015) and a week 8 lower partial Mayo score (OR: 0.406; 95% CI; 0.204-0.809; p=0.010). A receiver operation characteristic curve analysis revealed the optimal week 8 partial Mayo score to be 2.5, therefore a partial Mayo score of ≤2 was a positive predictor for the continuation of ADA. No malignancy or death occurred during this study. Conclusion ADA was effective for inducing and maintaining both a clinical response and remission in patients with refractory UC. It remains possible that the concomitant use of IM and a week 8 partial Mayo score of ≤2 may predict the long-term response of ADA.

CD169 Expression on Lymph Node Macrophages Predicts in Patients With Gastric Cancer.

The induction of an anti-cancer immune responses is potentially associated with the efficacy of anti-cancer therapy. Recent studies have indicated that sinus macrophages in regional lymph nodes are involved in anti-cancer immune responses in the cancer microenvironment. In the present study, we investigated the correlation between lymphocyte infiltration in cancer tissues and macrophage activation in regional lymph nodes. We retrospectively identified 294 patients with gastric cancer who underwent surgery from 2008 to 2012. Using immunohistochemistry, we evaluated CD169-expression on CD68-positive macrophages, and the density of CD8-postive lymphocytes in tumor microenvironment. We statistically examined the correlation between CD169 and CD8 expression, and performed Cox regression analysis of potential prognostic factors, including CD169 and CD8 expression, for cancer-specific survival (CSS) in patients with total and advanced gastric cancer. CD169 overexpression in lymph node sinus macrophages (LySMs) was positively correlated to the density of CD8-positive lymphocytes in primary cancer tissues (R = 0.367, p < 0.001). A high density of CD8-positive T lymphocytes in the primary site and a high level of CD169 expression in LySMs were independently associated with greater CSS in patients with total and advanced gastric cancer (p < 0.05 for all). The expression on CD169 in LySMs is a predictor of a favorable clinical course in patients with gastric cancer, and might be useful for evaluating anti-cancer immune responses.

Impact of sarcopenia on recurrent biliary obstruction after insertion of self-expandable metallic stent in patients with malignant biliary obstruction.

BACKGROUND/PURPOSE: Recurrent biliary obstruction (RBO) after self-expandable metallic stent (SEMS) insertion is a big problem in patients with unresectable malignant biliary obstruction (MBO). Sarcopenia is associated with poor prognosis in patients with malignancies. The purpose of this study is to clarify the relationship between RBO and sarcopenia. METHODS: Forty-six patients with normal psoas muscle mass index (PMI) and 55 with low PMI were enrolled, based on PMI cut-off values. We analyzed the cumulative incidences and predictors of RBO, considering death without RBO to be a competing risk. RESULTS: In the Kaplan-Meier analysis, the 60-, 180-, and 360-day cumulative incidence rates of RBO were 0.0%, 12.2%, and 22.0% in the normal PMI group, as compared to 4.0%, 31.1%, and 55.0% in the low PMI group, respectively (log-rank P = .003). In competing risk analysis, the incidences were 2.9%, 2.9%, and 7.1% in the normal PMI group, as compared to 13.7%, 34.8%, and 51.7% in the low PMI group, respectively (P < .001). In multivariate Cox regression and Fine-Gray's analyses, hazard ratios of low PMI for RBO were 4.593 (95% confidence interval 1.673-12.61, P = .003) and 4.980 (2.045-12.13, P < .001), respectively. CONCLUSIONS: Sarcopenia in MBO was an independent risk factor for RBO.

Rapidly Progressing Anaplastic Carcinoma of the Pancreas with Mucoepidermoid Carcinoma: An Autopsy Case Report.

A 75-year-old man visited our hospital for the examination of a tumor in the pancreas. Computed tomography showed an 85×85-mm low-density tumor in the pancreas. The tumor was pathologically diagnosed as poorly differentiated carcinoma by endoscopic ultrasound-guided fine-needle aspiration. Although we started chemotherapy, the patient died 84 days after the diagnosis. An autopsy demonstrated a ruptured anaplastic carcinoma with mucoepidermoid carcinoma of the pancreas. Anaplastic carcinoma with mucoepidermoid carcinoma is a very rare histologic subtype of pancreatic carcinoma, so pathological findings are important for predicting the patient's prognosis. Physicians should be aware of this rare but fatal disease.