Outcomes of immune checkpoint inhibitor-induced liver toxicity managed by hepatologists in a multidisciplinary toxicity team.

AIM: To detect immune-related adverse events (irAEs) early and treat them appropriately, our institute established an irAE-focused multidisciplinary toxicity team in cooperation with various departments. This study aimed to evaluate a consultation system involving a team of hepatologists in terms of its utility for the management of severe immune checkpoint inhibitor (ICI)-induced liver toxicity. METHODS: To analyze the diagnosis and treatment of severe ICI-induced liver toxicity (Grade 2 requiring corticosteroid therapy and Grade 3 or higher), we examined patients' clinical courses before and after the hepatologist consultation system was established (pre-period, September 2014 to February 2019; post-period, March 2019 to March 2023). RESULTS: The median follow-up period was 392 days. Of the 1247 patients with advanced malignancies treated with ICIs, 66 developed severe ICI-induced liver toxicity (n = 22 and 44 in the pre- and post-periods, respectively). In the pre-period, hepatologist consultations were sought for 15/22 patients, whereas in the post-period, 42/44 patients were referred to and treated by hepatologists. The time from the onset of liver toxicity to the consultation was significantly shorter in the post-period than in the pre-period (mean 1.9 vs. 6.5 days, respectively; p = 0.012). The number of patients with a biopsy-confirmed diagnosis of ICI-induced liver toxicity was significantly higher in the post-period than in the pre-period (n = 22 vs. n = 3, respectively; p = 0.006). Finally, there were no cases of immune-related cholangitis in the pre-period, compared to five cases in the post-period. CONCLUSION: A hepatologist consultation system in an irAE-focused multidisciplinary toxicity team is useful for managing severe ICI-induced liver toxicity.

Identification of the Microbiome Associated with Prognosis in Patients with Chronic Liver Disease.

We investigated the prognostic role of the gut microbiome and clinical factors in chronic liver disease (hepatitis, cirrhosis, and hepatocellular carcinoma [HCC]). Utilizing data from 227 patients whose stool samples were collected over the prior 3 years and a Cox proportional hazards model, we integrated clinical attributes and microbiome composition based on 16S ribosomal RNA sequencing. HCC was the primary cause of mortality, with the Barcelona Clinic Liver Cancer staging system-derived B/C significantly increasing the mortality risk (hazard ratio [HR] = 8.060; 95% confidence interval [CI]: 3.6509-17.793; p < 0.001). Cholesterol levels < 140 mg/dL were associated with higher mortality rates (HR = 4.411; 95% CI: 2.0151-9.6555; p < 0.001). Incertae sedis from Ruminococcaceae showed a protective effect, reducing mortality risk (HR = 0.289; 95% CI: 0.1282 to 0.6538; p = 0.002), whereas increased Veillonella presence was associated with a higher risk (HR = 2.733; 95% CI: 1.1922-6.2664; p = 0.017). The potential of specific bacterial taxa as independent prognostic factors suggests that integrating microbiome data could improve the prognosis and treatment of chronic liver disease. These microbiome-derived markers have prognostic significance independently and in conjunction with clinical factors, suggesting their utility in improving a patient's prognosis.

An image-based metal artifact reduction technique utilizing forward projection in computed tomography.

The projection data generated via the forward projection of a computed tomography (CT) image (FP-data) have useful potentials in cases where only image data are available. However, there is a question of whether the FP-data generated from an image severely corrupted by metal artifacts can be used for the metal artifact reduction (MAR). The aim of this study was to investigate the feasibility of a MAR technique using FP-data by comparing its performance with that of a conventional robust MAR using projection data normalization (NMARconv). The NMARconv was modified to make use of FP-data (FPNMAR). A graphics processing unit was used to reduce the time required to generate FP-data and subsequent processes. The performances of FPNMAR and NMARconv were quantitatively compared using a normalized artifact index (AIn) for two cases each of hip prosthesis and dental fillings. Several clinical CT images with metal artifacts were processed by FPNMAR. The AIn values of FPNMAR and NMARconv were not significantly different from each other, showing almost the same performance between these two techniques. For all the clinical cases tested, FPNMAR significantly reduced the metal artifacts; thereby, the images of the soft tissues and bones obscured by the artifacts were notably recovered. The computation time per image was ~ 56 ms. FPNMAR, which can be applied to CT images without accessing the projection data, exhibited almost the same performance as that of NMARconv, while consuming significantly shorter processing time. This capability testifies the potential of FPNMAR for wider use in clinical settings.

Extensive Hepatic Infarction due to Polycythemia Vera.

Polycythemia vera (PV) is one of the three BCR-ABL1-negative myeloproliferative neoplasms characterized by activating mutations in JAK2, which clinically presents as erythrocytosis and has an increased risk of both thromboembolic events and progression to myelofibrosis and acute myeloid leukemia. Splanchnic vein thrombosis is a rare manifestation of venous thromboembolism involving one or more abdominal vessels and is strongly associated with PV. We herein report a case in which hepatic infarction due to PV was saved by conservative treatment.

Artificial intelligence-based diagnostic imaging system with virtual enteroscopy and virtual unfolded views to evaluate small bowel lesions in Crohn's disease.

Since even subtle mucosal changes may be depicted using virtual endoscopy created by the three-dimensional reconstruction of MDCT images, we developed a novel diagnostic imaging system that integrates and displays virtual enteroscopy, curved planar reconstruction, and a virtual unfolded view, the width of which changes with increases/decreases in the inner luminal diameter. The system is also equipped with artificial intelligence that superimposes and displays depressed areas, generates an automatic small bowel centerline that connects fragmented small bowel regions, and performs electronic cleansing. We retrospectively evaluated the diagnostic performance of this system for small bowel lesions in Crohn's disease, which were divided into two groups: endoscopically-observable and endoscopically-unobservable. Lesion detection rates for stenoses, longitudinal ulcers with a cobblestone appearance, and scars were excellent in both groups. This system, when used in combination with endoscopy, shows slight mucosal changes in areas in which an endoscope cannot reach due to strictures, thereby extending the range of observation of the small bowel. This system is a useful diagnostic modality that has the capacity to assess mucosal healing and provide extraluminal information.

Gastric ectopic pancreas with a pseudocyst.

Ectopic pancreas (EP) is defined as pancreatic tissue that lacks anatomical or vascular connections to the normal pancreas. EP is generally asymptomatic and is detected incidentally during endoscopy. However, due to pseudocyst formation, inflammation, or malignant transformation, it may cause non-specific gastrointestinal symptoms, such as abdominal pain, abdominal discomfort, nausea, vomiting, and bleeding. Pseudocyst formation in EP may result from the retention of exocrine secretions in the absence of connections between the glandular epithelium and gastric lumen. We herein report a case of EP with a pseudocyst associated with epigastric pain. EP with a pseudocyst, although rare, needs to be considered in a differential diagnosis of cystic lesions of the stomach.

Characteristics of microbiomes of the saliva, duodenal bulb, and descending portion of superficial nonampullary duodenal epithelial tumors.

INTRODUCTION: Nonampullary duodenal epithelial tumors are rare, but their prevalence is increasing. Various gastrointestinal cancers have been associated with microbiomes. We evaluated the characteristics of the salivary and duodenal microbiomes of patients with nonampullary duodenal epithelial tumors. METHODS: Saliva and biopsy samples from the duodenal bulb and descending portion were obtained from 15 patients with nonampullary duodenal epithelial tumors and 10 controls. Next-generation sequencing was performed to identify bacteria for comparison. RESULTS: Saliva samples had higher Amplicon Sequence Variants (ASVs) and more observed species than duodenal samples. Saliva samples from patients with nonampullary duodenal epithelial tumor were dominated by Bacteroidetes and Prevotella, whereas Proteobacteria and Neisseria were dominant in the control samples. The relative abundance of bacteria was higher in patients with nonampullary duodenal epithelial tumors. Most bacteria were classified as bacteria of oral origin. Oribacterium and Stomatobaculum were significantly higher in the saliva, duodenal bulb, and descending portion of patients with nonampullary duodenal epithelial tumors. CONCLUSION: Patients with nonampullary duodenal epithelial tumors had different salivary and duodenal microbiomes than controls. Bacteria types differed between groups at each site, and most bacteria of oral origin were more abundant in patients with nonampullary duodenal epithelial tumors.

Validating computer applications for calculating spatial resolution and noise property in CT using simulated images with known properties.

The purpose of this study was to evaluate, using simulated images with known property values, how accurately some computer applications for calculating modulation transfer function (MTF), task transfer function (TTF), or noise power spectrum (NPS) in computed tomography (CT) based on widely known techniques produce their results. Specifically, they were three applications applicable to the wire method for MTF calculation, two applications corresponding to the circular edge (CE) and linear edge (LE) methods for TTF, and one application using a two-dimensional Fourier transform for NPS, which are collectively integrated with the software 'CTmeasure' provided by the Japanese Society of CT Technology. Images for the calculation with radial symmetry were generated based on a roll-off type filter function. The accuracy of each application was evaluated by comparing the calculated property with the true one. The calculated MTFs for the wire method accurately matched the true ones with percentage errors of smaller than 1.0%. In contrast, the CE and LE methods presented relatively large errors of up to 50% at high frequencies, whereas the NPS's errors were up to 30%. A closer investigation revealed, however, that these errors were attributable not to the applications but to the insufficiencies in the measurement techniques commonly employed. By improving the measurement conditions to minimize the effects of the insufficiencies, the errors notably decreased, whichvalidated the calculation techniques in the applications we used.

An atypical case of isolated immunoglobulin G4-related sclerosing cholangitis with a cholangiogram resembling primary sclerosing cholangitis.

An asymptomatic 77-year-old man with intrahepatic bile duct dilation was referred to our hospital. Cholangiography revealed alternations between strictures and dilated segments from the right and left hepatic ducts to the lower bile ducts, with findings of a pruned tree, beaded, shaggy appearance, and diverticulum-like outpouching. Histopathology revealed abundant immunoglobulin G4 (IgG4)-positive plasma cells (> 10 per high-power field) with an IgG4/IgG-positive cell ratio of 40-50%. After 2 weeks of steroid therapy, the cholangiography markedly improved. Because the cholangiographic findings resembled those of primary sclerosing cholangitis, steroid therapy proved useful in differentiating IgG4-related sclerosing cholangitis from primary sclerosing cholangitis.

Successful Treatment with Steroids in a Patient with Vanishing Bile Duct Syndrome and Acute Tubular Necrosis.

Vanishing bile duct syndrome (VBDS) is a rare but potentially serious cholestatic liver disease caused by various etiologies, including drugs. We herein report a complicated case of VBDS with acute tubular necrosis (ATN) that improved significantly with steroid treatment. An Asian man in his 30s was admitted with the acute onset of severe jaundice and a decline in the renal function. Although initial treatment with ursodeoxycholic acid did not reduce jaundice or renal dysfunction, steroid treatment remarkably improved the VBDS and ATN to within the respective normal ranges. Steroid treatment can be considered in cases of VBDS that appear to have an immune-mediated cause.

Impact of sarcopenia on biliary drainage during neoadjuvant therapy for pancreatic cancer.

BACKGROUND/AIMS: Since the usefulness of neoadjuvant chemo(radiation) therapy (NAT) for pancreatic cancer has been demonstrated, recurrent biliary obstruction (RBO) in patients with pancreatic cancer with a fully covered self-expandable metal stent (FCSEMS) during NAT is expected to increase. This study investigated the impact of sarcopenia on RBO in this setting. METHODS: Patients were divided into normal and low skeletal muscle index (SMI) groups and retrospectively analyzed. Patient characteristics, overall survival, time to RBO (TRBO), stent-related adverse events, and postoperative complications were compared between the two groups. A Cox proportional hazard model was used to identify the risk factors for short TRBO. RESULTS: A few significant differences were observed in patient characteristics, overall survival, stent-related adverse events, and postoperative complications between 38 patients in the normal SMI group and 17 in the low SMI group. The median TRBO was not reached in the normal SMI group and was 112 days in the low SMI group (p=0.004). In multivariate analysis, low SMI was the only risk factor for short TRBO, with a hazard ratio of 5.707 (95% confidence interval, 1.148-28.381; p=0.033). CONCLUSION: Sarcopenia was identified as an independent risk factor for RBO in patients with pancreatic cancer with FCSEMS during NAT.

Risk factors for rebleeding in gastroduodenal ulcers.

BACKGROUND: Rebleeding after hemostasis of the gastroduodenal ulcer (GDU) is one of the indicators associated with death among GDU patients. However, there are few studies on risk score that contribute to rebleeding after endoscopic hemostasis of bleeding peptic ulcers. AIMS: The aim of this study was to identify factors associated with rebleeding, including patient factors, after endoscopic hemostasis of bleeding gastroduodenal ulcers and to stratify the risk of rebleeding. METHODS: We retrospectively enrolled 587 consecutive patients who were treated for Forrest Ia to IIa bleeding gastroduodenal ulcers with endoscopic hemostasis at three institutions. Risk factors associated with rebleeding were assessed using univariate and multivariate logistic regression analyses. The Rebleeding Nagoya University (Rebleeding-N) scoring system was developed based on the extracted factors. The Rebleeding-N score was internally validated using bootstrap resampling methods. RESULTS: Sixty-four patients (11%) had rebleeding after hemostasis of gastroduodenal ulcers. Multivariate logistic regression analysis revealed four independent rebleeding risk factors: blood transfusion, albumin <2.5, duodenal ulcer, and diameter of the exposed vessel ≧2 mm. Patients with 4 risk factors in the Rebleeding-N score had a 54% rebleeding rate, and patients with 3 risk factors had 44% and 25% rebleeding rates. In the internal validation, the mean area under the curve of the Rebleeding-N score was 0.830 (95% CI = 0.786-0.870). CONCLUSIONS: Rebleeding after clip hemostasis of bleeding gastroduodenal ulcers was associated with blood transfusion, albumin <2.5, diameter of the exposed vessel ≧2 mm, and duodenal ulcer. The Rebleeding-N score was able to stratify the risk of rebleeding.

Outcomes of endoscopic papillectomy of ampullary carcinoma and factors affecting additional surgery.

BACKGROUND/PURPOSE: Data on the prognosis of endoscopic papillectomy (EP) for ampullary carcinoma (AC) is limited; therefore, we aimed to identify the factors associated with endoscopically controlled AC. METHODS: Between January 2003 and October 2022, 75 patients underwent EP for ampullary tumors and were diagnosed with AC based on the pathological features of the resected tissue. The factors associated with additional surgery after EP were also evaluated. RESULTS: A total of 67 patients had ACs ranging from carcinoma in situ to tumors limited to the mucosa (M group), and eight patients had ACs ranging from those limited to the sphincter of Oddi to those invading the duodenal muscularis propria (OD group). The 3-year endoscopic tumor control (condition not requiring additional surgery) rates in the M and OD groups were 90.8% and 84.6% (p = .033), respectively. In the M group, the presence of tumor components in the resection margins was the only significant factor associated with additional surgeries (p = .010) in the univariate analysis. The 3-year endoscopic tumor control rates were 100% for negative and uncertain resection margins and 76.6% for positive margins (p = .009). CONCLUSIONS: If the AC is confined to the mucosa and the resection margins are negative or uncertain, the tumor can be well-controlled endoscopically.

Effects of 1-kestose on microbiome changes caused by vonoprazan: a randomized, double-blind, placebo-controlled pilot study.

BACKGROUND AND AIM: Potassium-competitive acid blockers more strongly suppress the gastric acid barrier than proton pump inhibitors and cause dysbiosis. However, preventive measures in this regard have not been established. We aimed to evaluate whether 1-kestose, a known prebiotic, was effective at alleviating dysbiosis caused by potassium-competitive acid blockers. METHODS: Patients scheduled to undergo endoscopic resection for superficial gastroduodenal tumors were enrolled and randomized 1:1 to receive either 1-kestose or placebo. All patients were started on potassium-competitive acid blocker (vonoprazan 20 mg/day) and took 1-kestose 10 g/day or placebo (maltose) 5 g/day for 8 weeks. The primary outcome was the effect of 1-kestose on potassium-competitive acid blocker-induced alterations in the microbiome. The fecal microbiome was analyzed before and after potassium-competitive acid blocker treatment via MiSeq (16S rRNA gene V3-V4 region). RESULTS: Forty patients were enrolled, and 16 in each group were analyzed. In the placebo group, the Simpson index, an alpha diversity, was significantly decreased and relative abundance of Streptococcus was significantly increased by 1.9-fold. In the kestose group, the Simpson index did not change significantly and relative abundance of Streptococcus increased 1.3-fold, but this was not a significant change. In both groups, no adverse events occurred, ulcers were well healed, and pretreatment and posttreatment short-chain fatty acid levels did not differ. CONCLUSIONS: The potassium-competitive acid blocker caused dysbiosis in the placebo group; this effect was prevented by 1-kestose. Thus, 1-kestose may be useful in dysbiosis treatment.

Endoscopic submucosal dissection using a novel thin-therapeutic endoscope for superficial esophageal squamous cell carcinoma with severe stricture at the pharyngoesophageal junction.

When performing endoscopic submucosal dissection (ESD) beyond stenoses, there have only been two choices: balloon dilation until a conventional therapeutic endoscope passes through or the use of an ultrathin endoscope. However, balloon dilation has a risk of perforation and an ultrathin endoscope limits the devices that may be used. The novel thin-therapeutic endoscope has an outer diameter of 7.9 mm and instrument channel diameter of 3.2 mm; therefore, there are no restrictions on the ESD device that may be used, and the procedure may be performed in the same manner as regular ESD. We herein report a case in which the thin-therapeutic endoscope was useful for esophageal ESD beyond a stenosis.