Differences in branched-chain amino acid to tyrosine ratio (BTR) among etiologies of chronic liver disease progression compared to healthy adults.

BACKGROUND: The branched-chain amino acids (BCAAs) to tyrosine (Tyr) ratio (BTR) test is used to evaluate the progression of chronic liver disease (CLD). However, the differences across sex, age, body mass index (BMI) and etiologies are still unclear. METHODS: We retrospectively reviewed data from 2,529 CLD cases with free amino acids (FAAs) in peripheral blood from four hospitals and 16,421 general adults with FAAs data from a biobank database. In total, 1,326 patients with CLD (covering seven etiologies) and 8,086 healthy controls (HCs) were analyzed after exclusion criteria. We investigated the change of BTR in HCs by sex, age and BMI and then compared these to patients divided by modified ALBI (mALBI) grade after propensity score matching. RESULTS: BTR is significantly higher in males than females regardless of age or BMI and decreases with aging in HCs. In 20 types of FAAs, 7 FAAs including BCAAs were significantly decreased, and 11 FAAs including Tyr were significantly increased by mALBI grade in total CLD. The decreasing timings of BTR were at mALBI grade 2b in all CLD etiologies compared to HCs, however in chronic hepatitis C (CHC), chronic hepatitis B (CHB) and alcoholic liver disease (ALD), BTR started to decrease at 2a. There was a positive correlation between BCAAs and albumin among parameters in BTR and mALBI. The correlation coefficients in PBC, ALD and MASLD were higher than those of other etiologies. CONCLUSIONS: BTR varies by sex and age even among healthy adults, and decreasing process and timing of BTR during disease progression is different among CLD etiologies.

Detection Rates of Non-Cavitary Epithelioid Cell Granuloma by Gastrointestinal Biopsy in Patients with Treatment-Naïve Crohn's Disease.

Introduction: Detecting non-cavitary epithelioid cell granuloma by gastrointestinal biopsy is important in the initial diagnosis of Crohn's disease (CD). In the present study, we aimed to determine the rate of granuloma detection by gastrointestinal biopsy according to the number of biopsies performed. Methods: The present study included patients newly diagnosed with CD at our hospital between April 2017 and March 2023. During endoscopic examinations, biopsy specimens were taken from affected lesions. Initially, one section per biopsy was examined to detect granuloma. In cases where no granulomas were detected, step sections were additionally prepared and examined. The rate of granuloma detection by gastrointestinal biopsy was retrospectively examined. Results: A total of 30 patients with a new diagnosis of CD were included in this study. In total, 284 gastrointestinal biopsies were performed in 29 cases. The rate of granuloma detection by gastrointestinal biopsy per case was 58.6% (17 out of 29 cases). The rate of granuloma detection by gastrointestinal biopsy per biopsy was 6.0% (17 out of 284 biopsies) on initial histological examination and 11.6% (33 out of 284 biopsies) following examination of step sections. The rate of granuloma detection was significantly improved by performing histological examination of step sections compared with initial examinations (p < 0.05). Conclusion: The rate of granuloma detection per biopsy was 11.6%, even after histological examination of step sections. These results indicate that performing multiple intestinal biopsies and assessing for the presence of granuloma using multiple section examinations are required in the initial diagnosis of CD.

Diffuse pancreatic parenchymal atrophy, an imaging finding predictive of the development of pancreatic ductal adenocarcinoma: A case-control study.

Background and Aim: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer, partly because its early detection is difficult. This study aimed to identify computed tomography (CT) findings associated with PDAC prior to diagnosis. Methods: Past CT images were retrospectively collected from the PDAC group (n = 54) and the control group (n = 90). The following imaging findings were compared: pancreatic mass, main pancreatic duct (MPD) dilatation with or without cutoff, cyst, chronic pancreatitis with calcification, partial parenchymal atrophy (PPA), and diffuse parenchymal atrophy (DPA). In the PDAC group, CT findings were examined during the pre-diagnostic period and 6-36 months and 36-60 months before diagnosis. Multivariate analyses were performed using logistic regression. Results: MPD dilatation with cutoff (P < 0.0001) and PPA (P = 0.023) were identified as significant imaging findings 6-36 months before diagnosis. DPA was identified as a novel imaging finding at 6-36 months (P = 0.003) and 36-60 months (P = 0.009) before diagnosis. Conclusion: DPA, MPD dilatation with cutoff, and PPA were identified as imaging findings associated with pre-diagnostic PDAC.

Direct peroral cholangioscopy with red dichromatic imaging 3 detected the perihilar margin of superficial papillary extension in a patient with intraductal papillary neoplasm of the bile duct.

Intraductal papillary neoplasms of the bile duct (IPNB) are a tumor derived from bile duct epithelium that tends to spread laterally and non-invasively. Surgery is the first-choice treatment for IPNB. It is extremely important to accurately diagnose the extent of lateral tumor extension. Although peroral cholangioscopy (POCS) is a potentially useful modality for detecting tumor range with direct observation, poor image quality is a limitation of POCS. Recently, a new-generation endoscopy system (EVIS X1) was equipped with functions such as red dichromatic imaging to improve image quality. A 75-year-old man with cholangitis was referred to our department. Various imaging studies showed a mass in the middle to lower bile duct and dilatation of the common bile duct and the intrahepatic bile duct. Endoscopic retrograde cholangiopancreatography was performed. A biopsy of the main tumor in the lower common bile duct revealed IPNB. It was difficult to determine the extent of superficial tumor extension with modalities such as contrast-enhanced computed tomography, magnetic resonance imaging, and endoscopic ultrasonography but the detailed evaluation was possible using POCS with red dichromatic imaging 3. The patient underwent hepatopancreatoduodenectomy. This case suggests the usefulness of direct observation using POCS with red dichromatic imaging 3 to determine the range of IPNB.

Practical dosimetry procedure of air kerma for kilovoltage X-ray imaging in radiation oncology using a 0.6-cc cylindrical ionization chamber with a cobalt absorbed dose-to-water calibration coefficient.

In this study, we implemented a practical dosimetry procedure of air kerma for kilovoltage X-ray beams using a 0.6-cc cylindrical ionization chamber, and validated the procedure with the accuracy of the measurements using the 0.6-cc chamber compared to the measurements using a 6-cc chamber and a semiconductor device. In addition, the kerma area products (KAPs) were compared with the dose reference levels of radiology. A modified air kerma formalism using a 0.6-cc cylindrical ionization chamber air kerma formalism with a cobalt absorbed dose-to-water calibration coefficient was implemented. Validation of the formalism showed good agreement between the 0.6-cc chamber and the 6-cc chamber (< 5%), and between the 0.6-cc chamber and the semiconductor device (< 2%) in the 60-120 kV range. The KAPs for four RO machines had difference factors of 0.04-15.4 and 0.01-4.1 from their median and maximum dose reference levels in radiology, respectively.

Self-expandable metal stents have longer patency and less cholangitis than inside stents in malignant perihilar biliary obstruction.

Background and Aim: Outcomes of an inside stent (IS, a plastic stent placed above the sphincter of Oddi) versusa self-expandable metal stent (SEMS) for the drainage of malignant perihilar biliary obstruction has not been fully studied. The drainage strategy for perihilar biliary obstruction is difficult and should be clarified. Methods: Clinical data of patients who underwent biliary drainage for malignant perihilar biliary obstruction with IS or SEMS between April 2016 and September 2021 at our institution were retrospectively examined. Outcomes, including the time to recurrent biliary obstruction (TRBO), survival, and incidence of recurrent biliary obstruction with concomitant cholangitis (RBOC), were retrospectively evaluated. Results: Median TRBO was 280 (95% confidence interval [CI], 110-not available) days in the SEMS group (n = 24) and 113 (95% CI, 74-192) days in the IS group (n = 25) (P = 0.043). Among the patients with perihilar cholangiocarcinoma, the median survival of the two groups was comparable, namely 330 days in the SEMS group and 359 days in the IS group (P = 0.46). The incidence of RBOC at re-intervention was significantly higher in patients with ISs (83.9%) than in those with SEMSs (0%) (P = 0.00004). Conclusions: TRBO was significantly longer in the SEMS group. Regardless of whether SEMSs or ISs were placed during the first intervention, patient survival was similar. Using easily removable ISs first might be a reasonable option because TRBO with SEMSs was shorter than patient survival. Cholangitis is a problem associated with the placement of IS.

Neutrophil Infiltration and Acinar-ductal Metaplasia Are the Main Pathological Findings in Pembrolizumab-induced Pancreatitis.

The histopathological findings of immune checkpoint inhibitor (ICI)-induced pancreatitis have rarely been reported. A 56-year-old man with squamous cell carcinoma of the lung with bone metastasis was being treated with pembrolizumab, an anti-programmed cell death protein-1 antibody. After 13 doses, he was referred to our department due to pancreatitis. Despite characteristic symptoms of acute pancreatitis, imaging findings were similar to those of autoimmune pancreatitis. However, a histological examination showed neutrophil-based inflammatory cell infiltration and acinar-ductal metaplasia. Immunostaining showed CD8-positive T lymphocyte infiltration. This case revealed the characteristic histopathology of pembrolizumab-induced pancreatitis, which was previously poorly understood.

Hypereosinophilia with Hepatic Nodule Formation Caused by Ganoderma lucidum.

A 61-year-old man who underwent surgery for rectal adenocarcinoma developed multiple hepatic nodules. The nodules were 1-3 cm without a capsular structure or contrast enhancement on computed tomography/magnetic resonance imaging, findings that were atypical for adenocarcinoma metastases. A biopsy showed the aggregation of eosinophils without larval bodies, ova, or granulomas. Laboratory tests showed a marked increase in eosinophils and a slight liver enzyme elevation. He had been taking the commercial herbal medicine Ganoderma lucidum for his liver function. After discontinuing G. lucidum, the eosinophil counts and liver enzyme levels rapidly resolved, and the nodules disappeared completely. This is a rare case of hypereosinophilia with hepatic nodules reactive to herbal medicine rather than a parasitic infection.

A Gas-forming Liver Abscess with Massive Bleeding into the Abscess Cavity Due to a Ruptured Inferior Phrenic Artery.

An 88-year-old woman developed a huge abscess, forming an air-fluid level in the right lobe of the liver. A pigtail catheter was placed and drained thick pus with putrid odor from the abscess cavity. Gram-positive rods were detected in the pus, which were subsequently determined to be Clostridium perfringens by culture. She developed hemorrhaging in the abscess cavity when the right inferior phrenic artery was damaged by inflammation that had spread from the abscess. Emergency transarterial embolization with gelatin sponges was performed, and the bleeding ceased. We herein report a rare case of liver abscess that caused inferior phrenic artery injury, resulting in bleeding.

Nasopancreatic Drainage for 4 Patients during the Early Phase of Acute Pancreatitis.

We encountered 4 patients with acute pancreatitis (AP) of various etiologies and coexisting acute cholangitis who underwent endoscopic biliary stenting (EBS) and nasopancreatic drainage (NPD) via endoscopic retrograde cholangiopancreatography (ERCP) during the early phase of AP. ERCP is performed to treat acute cholangitis even in the context of AP. However, in difficult cases, accidental contrast media injection or guidewire insertion into the pancreatic duct can happen during ERCP for the purpose of EBS. It is concerned that cannulation injury and increased pancreatic duct pressure can exacerbate existing AP. Because pancreatic guidewire-associated techniques were required for all of them due to difficult biliary cannulation, we performed a NPD catheter placement using the pancreatic guidewire to decompress the pancreatic duct to prevent further exacerbating AP. Surprisingly, all patients dramatically improved without systemic or local complications. NPD could be performed without any adverse events and did not worsen the course of AP. Early decompression of a pancreatic duct using NPD may rather improve AP that had already developed. Further prospective research is needed to confirm our observations.

Immunoglobulin G4-Related Hepatic Inflammatory Pseudotumor Diagnosed with Endoscopic Ultrasound-Guided Fine-Needle Biopsy.

A 71-year-old man with obstructive jaundice was referred to our department. He underwent cholangiojejunostomy 15 years ago for palliative drainage. At that time, he had obstructive jaundice caused by an unresectable pancreatic head tumor. Contrast-enhanced computed tomography (CE-CT) now revealed a mass with low enhancement in the hepatic hilum that occluded the hilar bile duct and infiltrated extensively along the portal vein and hepatic artery. CE-CT also showed marked atrophy of the left hepatic lobe. No swelling or tumors were observed in the pancreas. Serum immunoglobulin G4 (IgG4) levels were as high as 465 mg/dL. Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) was performed targeting the hepatic hilar lesion. Immunohistological results of the biopsy specimens suggested that the lesion was an IgG4-related hepatic inflammatory pseudotumor (IPT) with no atypical cells. Steroid treatment resulted in rapid clinical improvement. This case suggested the usefulness of EUS-FNB for diagnosing IgG4-related hepatic hilar IPT.

BEX2 is required for maintaining dormant cancer stem cell in hepatocellular carcinoma.

Cancer stem cells (CSCs) are responsible for therapy resistance and share several properties with normal stem cells. Here, we show that brain-expressed X-linked gene 2 (BEX2), which is essential for dormant CSCs in cholangiocarcinoma, is highly expressed in human hepatocellular carcinoma (HCC) lesions compared with the adjacent normal lesions and that in 41 HCC cases the BEX2high expression group is correlated with a poor prognosis. BEX2 localizes to Ki67-negative (nonproliferative) cancer cells in HCC tissues and is highly expressed in the dormant fraction of HCC cell lines. Knockdown of BEX2 attenuates CSC phenotypes, including sphere formation ability and aldefluor activity, and BEX2 overexpression enhances these phenotypes. Moreover, BEX2 knockdown increases cisplatin sensitivity, and BEX2 expression is induced by cisplatin treatment. Taken together, these data suggest that BEX2 induces dormant CSC properties and affects the prognosis of patients with HCC.

Suggestive Diagnostic Process in a Case of Multiple Myeloma with Gastrointestinal Immunoglobulin Light-Chain Amyloidosis Accompanied by Protein-Losing Enteropathy.

Multiple myeloma is a type of plasma cell neoplasm that produces monoclonal immunoglobulin. Multiple myeloma is known to cause immunoglobulin light-chain (AL) amyloidosis, which frequently involves the kidney and heart. Bone pain or fractures caused by osteolytic lesions and physical disorders related to renal or cardiac AL amyloidosis are major initial symptoms in multiple myeloma. Multiple myeloma diagnosed from the gastrointestinal symptoms is rare. We report a case of an 80-year-old man with multiple myeloma accompanied by gastrointestinal AL amyloidosis and secondary protein-losing enteropathy. The diagnostic process was suggestive, in that diarrhea and refractory leg edema related to protein-losing enteropathy were the primary symptoms and the trigger for making a sequential diagnosis of gastrointestinal AL amyloidosis and underlying multiple myeloma. This case is highly suggestive, in that multiple myeloma with gastrointestinal AL amyloidosis should be considered one of the background diseases of protein-losing enteropathy.

Unusual imaging findings of pancreatobiliary-type intraductal papillary mucinous neoplasm.

We experienced a rare case of main duct intraductal papillary mucinous neoplasm (MD-IPMN) without overt mucin production. Histological findings classified the tumor as high-grade dysplasia of pancreatobiliary-type IPMN that has been reported to show high malignant potential with a property to disseminate extensively into pancreatic ducts.

Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Noninvasive Predictors of the Therapeutic Outcomes of Systemic Corticosteroid Therapy in Ulcerative Colitis.

INTRODUCTION: Predictive biomarkers for the therapeutic outcome of induction therapy with systemic corticosteroid for active ulcerative colitis (UC) have not been established. This study aimed to investigate whether neutrophil-to-lymphocyte ratio (NLR) and/or platelet-to-lymphocyte ratio (PLR) can be predictive biomarkers for the therapeutic outcomes of systemic corticosteroid therapy in UC. METHODS: This was a single-center retrospective cohort study. In total, 48 patients with UC who received induction therapy with systemic corticosteroid were enrolled. Based on the achievement of clinical remission after 8 weeks of treatment, the patients were divided into the remission group (n = 28) and the nonremission group (n = 20). Clinical characteristics, NLR, and PLR at baseline between the remission and nonremission groups were compared via a univariate analysis. The independent risk factors of nonremission were identified via a multivariate analysis. RESULTS: The baseline Mayo score, platelet count, lymphocyte count, C-reactive protein (CRP) levels, NLR, and PLR between the 2 groups significantly differed. The nonremission group had higher NLR and PLR than the remission group (4.70 [3.04-11.3] vs. 3.10 [1.36-16.42]; p < 0.05, and 353.6 [220.3-499.8] vs. 207.2 [174.4-243.6]; p < 0.001, respectively). A multivariate analysis revealed that a Mayo score of ≥9, CRP level of ≥1.26 mg/dL, and PLR of ≥262 (hazard ratio: 23.1, 95% confidence interval: 1.29-413.7, p = 0.033) were considered independent risk factors for nonremission. CONCLUSION: This report first identified the efficacy of NLR and PLR as candidate biomarkers for predicting the therapeutic outcomes of systemic corticosteroid therapy in UC.

Presymptomatic Crohn's Disease in a Young Patient Diagnosed Just After the Onset of Idiopathic Acute Pancreatitis.

Acute pancreatitis is an extraintestinal manifestation of inflammatory bowel disease. There have been few reports describing acute pancreatitis preceding a diagnosis of inflammatory bowel disease. We herein report a rare case of a 16-year-old boy with presymptomatic Crohn's disease that was newly diagnosed just after the onset of idiopathic acute pancreatitis. Crohn's disease of any stage, much less in the presymptomatic stage, is rarely diagnosed just after the development of acute pancreatitis. The present case suggests that acute pancreatitis without an apparent cause in young or pediatric population can precede a diagnosis of presymptomatic Crohn's disease.

A case of jejunal solitary Peutz-Jeghers polyp with intussusception identified by double-balloon enteroscopy.

Solitary Peutz-Jeghers polyp is a rare hamartomatous polyp that has similar histologic characteristics with those of polyps in Peutz-Jeghers syndrome, without associated mucocutaneous hyperpigmentation and a family history. Previous reports indicated that solitary Peutz-Jeghers polyp is rarely found in the small intestine. We experienced a rare case of jejunal solitary Peutz-Jeghers polyp. A 29-year-old man was admitted to our hospital with a 6-month history of upper abdominal pain. He had no hyperpigmentation or a family history of Peutz-Jeghers syndrome. Abdominal computed tomography showed a 3-cm tumor-like structure at the tip of a mildly intussuscepted jejunum. Per oral double-balloon enteroscopy revealed a 3-cm pedunculated polyp in the jejunum. The patient underwent partial jejunal resection under laparotomy. Macroscopically, the surgical specimen showed a pedunculated polyp, measuring 30 × 15 × 10 mm in size, with lobulated head. Histopathologic examination revealed irregular aggregation of hyperplastic crypts with branching muscular bundles originating from the muscularis mucosae. Based on these histologic findings, we finally diagnosed the patient as a solitary Peutz-Jeghers polyp in the jejunum. The present case indicated that solitary Peutz-Jeghers polyp should be considered in a patient with solitary hamartomatous polyp in the gastrointestinal tract.

A Biliary Mucinous Cystic Neoplasm with Intrahepatic and Lymph Node Metastases.

A 51-year-old woman who presented with a large cystic liver tumor with mural nodules in the lateral segment developed Trousseau's syndrome. A mural nodule directly invaded her liver parenchyma. Metastatic nodules were detected in the right lobe and portal/paraaortic lymph nodes. The pathological findings showed mucin-producing adenocarcinoma cells to have invaded the fibrous stroma forming a micropapillary cluster. She developed obstructive jaundice due to tumor progression and subsequently died of hepatic failure. Invasive biliary mucinous cystic neoplasm (MCN) is a rare form of a malignant tumor with a relatively favorable prognosis. This is a very rare case biliary MCN with invasive carcinoma that showed intrahepatic and lymph node metastases.

Effect of viral DNA methylation on expression of hepatitis B virus proteins depends on the virus genotype.

The frequency of HBV genomic methylation in the liver was reported to vary among patients, but the detailed mechanism is still unknown. In this study, the effects of HBV genome methylation on HBV replication were investigated in vitro. A total of 6 plasmids containing 1.24-fold the HBV genome of different genotypes (subgenotypes A1, A2, B1, and C2) were purified after in vitro methylation with CpG methyltransferase (M.SssI) and transfected into HepG2 cells. In genotype B and C strains, methylation markedly decreased the amount of hepatitis B e antigen (HBeAg) in the culture supernatant. A reduction of hepatitis B surface antigen (HBsAg) was found in some HBV strains but the reduction was smaller than that of HBeAg. There was no significant difference in particle-associated HBV DNA in the culture supernatant. These findings suggest that HBV genomic methylation might be involved in the HBeAg decline in genotype B and C, in part, and that the reduction of HBsAg was less than that of HBeAg. In conclusion, this study showed that the effect of HBV genomic methylation differs among HBV genotypes, suggesting a potential explanation for the different clinical outcomes of genotypes A, B, and C.