Safety/efficacy of atezolizumab + bevacizumab during anti-platelet/anticoagulation therapy in unresectable hepatocellular carcinoma.

BACKGROUND AND AIMS: This study aimed to determine the safety and efficacy of atezolizumab + bevacizumab therapy in hepatocellular carcinoma patients receiving anti-platelet agents or anticoagulants. METHODS: Patients were divided into those using (IM out) and those not using (IM in) anti-platelet agents or anticoagulants, who violated the exclusion criteria of the IMbrave150 trial, and were retrospectively examined. RESULTS: The study included 185 patients (IM in: 157; IM out: 28). For first-line treatment, progression-free survival was 184 days for IM in and 266 days for IM out (p = .136). Overall survival was 603 days for IM in and not reached for IM out (p = .265), with no significant between-group difference. Similarly, there were no significant between-group differences in progression-free survival or overall survival for later-line treatment. Haemorrhagic adverse events of ≥grade 3 were observed in 11 IM in patients and 3 IM out patients. No significant factors associated with haemorrhagic adverse events of ≥grade 3 were identified in the multivariate analysis including IM out classification, whose p value was .547. Regarding thrombotic/embolic adverse events in the IM out group, one case of exacerbation of portal vein thrombosis was observed. No deaths were directly attributable to bleeding events or exacerbations of thrombosis. CONCLUSION: Atezolizumab + bevacizumab therapy shows similar safety and efficacy in patients receiving and those not receiving anti-platelet agents or anticoagulants; therefore, it can be considered for patients with hepatocellular carcinoma receiving anti-platelet agents or anticoagulants.

[A Case of Duodenal Tumor Accompanied by Liver and Lymph Node Metastases after Ten Years of Observation].

A 67-year-old woman presented with a history of upper abdominal pain and weight loss. Physical examination revealed a lump in the right lower quadrant. She had undergone esophagogastroduodenoscopy at another hospital ten years ago, which showed a 15-mm elevated lesion in the duodenal bulb. The patient had not undergone further examinations or received treatment during the 10 years. Esophagogastroduodenoscopy conducted in our hospital revealed an enlarged tumor that was difficult to assess on the whole image. The tumor was diagnosed as a well-differentiated adenocarcinoma based on a biopsy specimen. Enhanced computed tomography revealed a hypervascular duodenal tumor with liver and lymph node metastases. The patient was treated with capecitabine plus oxaliplatin for the duodenal cancer. Lymph node metastases increased markedly after 2 courses of chemotherapy. The patient died 3 months after the initiation of chemotherapy. The natural history of sporadic non-ampullary duodenal epithelial tumors remains to be fully elucidated due to the low incidence rate. This case suggests that sporadic non-ampullary duodenal epithelial tumors have a biological potential for invasive malignancy.

Red dichromatic imaging improves visibility of bleeding during gastric endoscopic submucosal dissection.

Bleeding frequently occurs during gastric endoscopic submucosal dissection (ESD) and bleeding points are sometimes difficult to detect. Red dichromatic imaging (RDI) was recently developed to improve the visibility of bleeding. Our study aimed at examining the efficacy of RDI in improving the visibility of bleeding during gastric ESD. We retrospectively evaluated the visibility score and color difference of bleeding spot during gastric ESD during September 2020-January 2021. The visibility score was evaluated as four numeric values by operators, and the color difference between the bleeding spot and surroundings was evaluated using RDI and white light imaging (WLI). A further analysis to evaluate bleeding characteristics was performed to evaluate the possible beneficial effects of RDI. Twenty patients with a total of 85 bleedings were analyzed. The mean visibility score in RDI was significantly higher than that in WLI (3.69 ± 0.60 vs 3.20 ± 0.84, p < 0.01). The color difference with RDI was also significantly higher than that with WLI (19.51 ± 15.18 vs 14.80 ± 7.41, p < 0.01). Furthermore, in the bleedings with a higher visibility score in RDI, the color difference in RDI was significantly higher than that in WLI (23.99 ± 19.29 vs 14.33 ± 7.08, p < 0.01). The multivariate analysis of visibility scores revealed that submergence of bleeding points was independently associated with the superiority of RDI (odds ratio 10.35, 95% confidence interval: 2.76-38.81, p < 0.01). Our study demonstrates that RDI can improve the visibility of bleeding during gastric ESD.

Predictors of response to anamorelin in gastrointestinal cancer patients with cachexia: a retrospective study.

PURPOSE: Anamorelin, a ghrelin receptor agonist, has recently been approved for gastric, pancreatic, and colorectal cancer patients with cachexia in Japan. However, only few studies have investigated the predictors of response to anamorelin in clinical settings. Thus, our study aimed to investigate the predictors of the response, in addition to its efficacy and safety. METHODS: The clinical outcomes of 20 patients were evaluated during administration. They were divided into two groups based on lean body mass, responders and non-responders, and their clinical characteristics were compared. RESULTS: The mean ± standard error (SE) variations at 12 weeks in lean body mass and handgrip strength were 2.63 ± 0.79 kg and - 1.53 ± 1.20 kg, respectively. The mean ± SE variations at 8 weeks in fasting blood glucose and hemoglobin A1c were 32.88 ± 13.77 mg/dL and 0.90 ± 0.18%, respectively. Total protein, albumin, transferrin, and prognostic nutritional index at baseline were significantly higher in responders (n = 8) than in non-responders (n = 12), whereas the neutrophil/lymphocyte and C-reactive protein/albumin ratios at baseline were significantly higher in non-responders than in responders. CONCLUSION: The study confirmed the efficacy and safety of anamorelin and identified nutritional or systemic inflammatory markers as predictors of anamorelin response in advanced gastrointestinal cancer patients.

Rectal administration of low-dose diclofenac does not reduce post-endoscopic retrograde cholangiopancreatography pancreatitis: a propensity score matching analysis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a popular technique; however, post-ERCP pancreatitis (PEP) remains a major adverse event. The administration of rectal nonsteroidal anti-inflammatory drugs (NSAIDs) is reportedly effective in preventing PEP. However, the recommended dose varies and the efficacy of low-dose rectal NSAIDs remains unclear. Therefore, we decided to investigate the effectiveness of low-dose rectal diclofenac on PEP prevention, using propensity score matching. METHODS: This single-center retrospective study included 401 patients who underwent ERCP between July 2015 and March 2020. After December 2016, we administered rectal diclofenac within 30 min before the ERCP procedure as widely as possible. Patients were divided into those who did (diclofenac group) and did not (control group) receive rectal diclofenac. Patients weighing ≥ 50 kg were administered a 50 mg dose, while those weighing < 50 kg were administered a 25 mg dose. The incidence and severity of PEP in the two groups were assessed by propensity score matching analysis. RESULTS: Among 401 patients undergoing ERCP, 367 fulfilled the inclusion criteria. Overall, 187 patients received rectal diclofenac (diclofenac group) and 180 did not (control group). After propensity score matching, 105 pairs were selected for evaluation. Overall, seven (6.7%) patients in the diclofenac group and 10 (9.5%) in the control group developed PEP (P = 0.45). Moderate or severe PEP occurred in four (3.8%) patients in the diclofenac group and six (5.7%) in the control group (P = 0.52). CONCLUSIONS: The administration of low-dose rectal diclofenac could not reduce the incidence and severity of PEP.

Interstitial Lung Disease Associated with Agaricus blazei Murill in a Patient with Pancreatic Ductal Adenocarcinoma Receiving Gemcitabine-Based Therapy.

A male in his sixties with locally advanced pancreatic ductal adenocarcinoma (PDAC) was administered gemcitabine plus nab-paclitaxel therapy. Computed tomography (CT) scans after five courses revealed nonspecific interstitial pneumonitis in addition to PDAC aggravation. No evidence of respiratory infection was detected, and his condition was stable and asymptomatic at diagnosis. Sputum test and interferon-gamma release assay revealed no evidence of tuberculosis. Through careful history taking, the patient was found to be taking dietary supplementation with Agaricus blazei Murill extract for approximately 1 month. Drug-induced lymphocyte stimulation tests for gemcitabine and nab-paclitaxel were negative, whereas those for Agaricus blazei Murill were positive. CT scans after withdrawal showed improved pneumonitis. These findings suggest a possibility that the dietary supplementation may lead to drug-induced interstitial lung disease (ILD). This patient indicates that pertinent diagnostic interviews are essential for the identification of drug-induced ILD.

Microbiological analysis of patients with first and recurrent episodes of acute cholangitis in a middle-sized hospital: A single-center retrospective study in rural North Kyoto, Japan.

BACKGROUND: Knowledge of the bacterial spectrum involved in acute cholangitis is essential for adequate empiric antibiotic treatment. There is a lack of published data comparative data between patients with first and recurrent episodes of acute cholangitis. This study aimed to analyze the microbial spectrum in patients with first and second episodes of acute cholangitis. METHODS: We retrospectively assessed 251 patients with first episodes of acute cholangitis between January 2014 to September 2020. RESULTS: At the first episode of acute cholangitis, the predominant strains belonged to Escherichia coli (17.9%), followed by Klebsiella spp. (15.5%), Enterobacter spp. (6.4%), and Enterococcus spp. (5.6%). During follow-up, acute cholangitis recurred in 109 patients; at the second episode, the predominant strains belonged to Enterococcus spp. (35.8%), followed by Klebsiella spp. (27.5%), Enterobacter spp. (22.9%), and Escherichia coli (15.6%). Enterococcus spp. were the most common pathogen in patients with second episode of acute cholangitis, regardless of whether the cholangitis was caused by a malignant tumor or a benign disease. CONCLUSIONS: Unlike in patients with a first episode of acute cholangitis, clinicians should consider empirical treatment with anti-enterococcal antibiotics in patients with recurrent episodes of acute cholangitis.

Depletion of Psoas Muscle Mass after Systemic Chemotherapy Is Associated with Poor Prognosis in Patients with Unresectable Pancreatic Cancer.

The impact of the psoas muscle mass index (PMI) on survival is still poorly understood in unresectable pancreatic cancer. Thus, we aimed to investigate whether the PMI at diagnosis or its decrease during chemotherapy can influence the prognosis of unresectable pancreatic cancer. The data of 100 patients were analyzed, and they were divided into two groups according to the median PMI in each sex. Subsequently, 72 patients undergoing computed tomography (CT) within 30-100 days from CT at diagnosis were evaluated in terms of PMI change rate, and divided into two groups based on the median. We evaluated the clinical characteristics and outcomes in terms of the PMI at diagnosis or its decrease during chemotherapy. The median PMI was 5.00 in males, and 3.66 in females. The median overall survival (OS) was 278.0 days in the high-PMI group and 221.0 days in the low-PMI group (p = 0.329). The median PMI change rate was -2.4%. The median OS was 347.0 days in the group without PMI decrease and 172.0 days in the group with PMI decrease (p = 0.001). We determined that a pivotal prognostic factor was not the PMI at diagnosis, but rather PMI decrease during chemotherapy in unresectable pancreatic cancer.

Unusual abscess formation in colon cancer with mucinous components.

Colon cancer with mucinous components was accompanied by bacterial infection and abscess formation.

Clinical Features of False-Negative Early Gastric Cancers: A Retrospective Study of Endoscopic Submucosal Dissection Cases.

BACKGROUND: We frequently encounter early gastric cancer (EGC) that could not be detected in the previous esophagogastroduodenoscopy even if the procedure was annually performed. However, little evidence exists regarding the characteristics of false-negative EGCs. Our aim was to reveal the clinical features of false-negative EGCs. METHODS: We retrospectively reviewed cases of endoscopic submucosal dissection (ESD) for EGCs in Fukuchiyama City Hospital between January 2013 and May 2019. False-negative EGCs were defined as EGCs within 3 years of negative endoscopy. We evaluated the clinical characteristics of false-negative and initially detected EGCs and the difference in the detected and last missed endoscopy in false-negative EGCs. The miss rates of false-negative EGCs were compared between trainees (nonboard-certified endoscopists) and experienced endoscopists (board-certified endoscopists); thereafter, the characteristics of false-negative EGCs missed by trainees were investigated. RESULTS: Of 219 cases, 119 were classified as false-negative EGCs. False-negative EGCs were characterized as smaller lesions, which presented with normal color or gastritis-like appearance, and were diagnosed after ESD and H. pylori eradication (P < 0.01). The rate of trainees in the last missed endoscopy was significantly higher than that in the detected endoscopy. The miss rate of false-negative EGC by trainees was higher than that of experienced endoscopists but not significantly different (0.70% vs. 0.57%, P = 0.08). The false-negative EGCs missed by trainees were characterized as reddish or well-differentiated lesions, which were located in the lower or lesser curvature of the stomach (P < 0.05). CONCLUSION: The characteristics of false-negative EGCs were similar to those of H. pylori-eradicated EGC. Procedures with shortened examination time and those performed by trainees were risk factors of missing false-negative EGCs. Trainees should pay attention to reddish or well-differentiated EGCs located in the lower or lesser curvature of the stomach.

Severe Liver Injury Associated with Glecaprevir Plus Pibrentasvir Therapy in a Patient with Treatment-naïve Hepatitis C Virus Infection.

A 49-year-old man underwent treatment with glecaprevir plus pibrentasvir (G/P) for chronic hepatitis C infection. Six weeks later, he was admitted to our hospital because of jaundice and fatigue with no accompanying skin rash. A laboratory examination and evaluation of the patient's history resulted in a diagnosis of acute liver injury. Discontinuation of G/P and a rigorous medical protocol, including plasma exchange and hemodiafiltration, successfully mitigated the liver damage. The patient was also found to be allergic to two drugs other than the G/P therapy. In such cases with a history of drug allergy, careful observation may be required to detect serious adverse events.

Hepatitis B Virus Reactivation 55 Months Following Chemotherapy Including Rituximab and Autologous Peripheral Blood Stem Cell Transplantation for Malignant Lymphoma.

A 54-year-old woman underwent chemotherapy including rituximab and autologous peripheral blood stem cell transplantation (auto-PBSCT) for diffuse large B-cell lymphoma. Before the treatment, she exhibited a resolved hepatitis B virus (HBV) infection. She was diagnosed with HBV reactivation based on positive serum HBV-DNA test results, 55 months after her last treatment. Subsequently, he was treated with tenofovir alafenamide fumarate (TAF) therapy and her liver function improved. Patients undergoing chemotherapy including rituximab and auto-PBSCT are at a high risk of HBV reactivation. In such cases, careful and long-term observations may be required to detect HBV reactivation.

Tiny capillary hemangioma of the ileum as the cause of chronic anemia.

A 70-year-old male was diagnosed with tiny capillary hemangioma of the ileum using double-balloon endoscopy. Capillary hemangiomas should be included in the differential diagnoses of OGIB.

Development of Hepatocellular Carcinoma in a Patient with Chronic Hepatitis C 21 Years after Achieving a Sustained Virological Response to Interferon Therapy.

A 77-year-old man with chronic hepatitis C (CH-C) infection, who achieved a sustained virological response (SVR) to interferon (IFN) therapy, was followed up regularly. Before IFN therapy, he did not have metabolic diseases, and the histological diagnosis of his chronic hepatitis was stage-3 fibrosis. After achieving SVR, the fibrosis-4 (FIB-4) index level dropped once but gradually increased. 21 years after SVR, hepatocellular carcinoma (HCC) was diagnosed by dynamic computed tomography. The HCC was 12 mm in diameter. The HCC was treated with radiofrequency ablation. CH-C patients with advanced fibrosis require long-term follow-up, even after achieving SVR.

Neutrophil to lymphocyte ratio predicts prognosis in unresectable pancreatic cancer.

Inflammation-based prognostic indicators have been developed to predict the prognosis in patients with pancreatic cancer. However, prognostic indices have not been established in patients with unresectable pancreatic cancer, including those without indication for chemotherapy at diagnosis. This study aimed to identify the predictors in all patients with unresectable pancreatic cancer. We retrospectively analyzed data of 119 patients with unresectable pancreatic cancer from June 2006 to September 2018. The following laboratory parameters were evaluated: the Glasgow Prognostic Score (GPS), modified GPS, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein albumin (CRP/Alb) ratio, and prognostic nutritional index (PNI). We performed time-dependent receiver operating characteristic analysis, overall survival (OS) analysis, and univariate and multivariate analyses to determine the prognostic factors in patients with unresectable pancreatic cancer. The cut-off value for NLR was determined to be 3.74. The 6-month OS rates in low and high NLR groups were 75.5% and 18.8% (P < 0.001). In the univariate analysis, advanced age (P = 0.003), metastatic pancreatic cancer (P = 0.037), no treatment (P < 0.001), worse Eastern Cooperative Oncology Group Performance Status (ECOG-PS) (P < 0.001), high GPS (P < 0.001), high modified GPS (P < 0.001), high NLR (P < 0.001), high PLR (P = 0.002), high CRP/Alb ratio (P < 0.001), and low PNI (P < 0.001) were identified as the prognostic factors. The multivariate analysis revealed that metastatic pancreatic cancer (P = 0.046), no treatment (P < 0.001), worse ECOG-PS (P = 0.002), and high NLR (P < 0.001) were independently associated with OS. We revealed that the high NLR could be an independent indicator of poor prognosis in patients with unresectable pancreatic cancer.

Gastric Metastasis from Colorectal Cancer Mimicking a Submucosal Tumor.

Signet-ring cell carcinoma, a colorectal cancer (CRC) subtype, sometimes shows metastases to uncommon metastatic sites. However, gastric metastasis is extremely rare. Here, we describe a case of gastric metastasis from colonic cancer. A 76-year-old woman presented with anemia. Colonoscopic biopsy revealed a CRC on the transverse colon showing a poorly differentiated adenocarcinoma with a partial component of the signet-ring carcinoma. Computed tomography revealed multiple subcutaneous nodules on her chest and back, and a tumor in the left lower lobe of her lung. Esophagogastroduodenoscopy showed a submucosal tumor-like lesion in the upper gastric body, and endoscopic biopsy revealed the poorly differentiated adenocarcinoma along with the partial component of the signet-ring carcinoma as well as the colonic, subcutaneous, and pulmonary lesion. The findings of endoscopic and microscopic examinations revealed gastric metastasis from CRC on the transverse colon. A systemic chemotherapy was given, and the biopsy conducted 1 year after the initial chemotherapy revealed no evidence of the residual tumor tissue in the gastric lesion. However, best supportive care was recommended depending on metastasis to the rectum. Our case suggests that gastric metastases from CRC should be considered in patients with lesions resembling a submucosal tumor accompanied by central depression and erosion.

Surveillance of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is sufficient epidemiological cohort data to recommend the surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association (AGA) expert review published in 2020 recommends that NAFLD patients with cirrhosis or advanced fibrosis estimated by non-invasive tests (NITs) consider HCC surveillance. NITs include the fibrosis-4 (FIB-4) index, the enhanced liver fibrosis (ELF) test, FibroScan, and MR elastography. The recommended surveillance modality is abdominal ultrasound (US), which is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with NAFLD. In NAFLD patients with a high likelihood of having an inadequate US, or if an US is attempted but inadequate, CT or MRI may be utilized. The GALAD score, consisting of age, gender, AFP, the lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and the protein induced by the absence of vitamin K or antagonist-II (PIVKA-II), can help identify a high risk of HCC in NAFLD patients. Innovative parameters, including a Mac-2 binding protein glycated isomer, type IV collagen 7S, free apoptosis inhibitor of the macrophage, and a combination of single nucleoside polymorphisms, are expected to be established. Considering the large size of the NAFLD population, optimal screening tests must meet several criteria, including high sensitivity, cost effectiveness, and availability.

Cervical squamous cell carcinoma coexisting with ectopic gastric mucosa treated by endoscopic submucosal dissection: A case report.

A 69-year-old Japanese man underwent an endoscopic submucosal dissection (ESD) for early gastric cancer 2 years prior to admission at Fukuchiyama City Hospital. A follow-up esophagogastroduodenoscopy (EGD) revealed a butterfly-shaped brownish area in the cervical esophagus. A successful endoscopic submucosal dissection of the esophageal lesion was performed for total biopsy. Histopathological analysis of the resected specimen revealed moderately differentiated squamous cell carcinoma of the esophagus, cervical esophagus tumor type 0-IIb, a tumor diameter of 14x8 mm, T1b pathological findings (invading into submucosa), infiltrative growth α, lymphatic invasion (-), venous invasion (-), a horizontal tumor free margin and a vertical tumor free margin. The results demonstrated that the squamous cell carcinoma had invaded into the submucosal layer under the ectopic gastric mucosa. After endoscopic treatment, chemoradiation therapy was administered to the patient.