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.

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.

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.

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.

A phase I/Ib study of trametinib (GSK1120212) alone and in combination with gemcitabine in Japanese patients with advanced solid tumors.

BACKGROUND: Trametinib is an inhibitor of MEK1/MEK2 activation and kinase activity. In order to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of single-agent trametinib (part 1) and trametinib in combination with gemcitabine (part 2), we undertook the first clinical study of this combination in Japanese patients with cancer and herein report our results. METHODS: In part 1, 13 patients with advanced solid tumors were enrolled into 3 dose cohorts, receiving trametinib once daily at a dose of 1.0, 2.0, or 3.0 mg. In part 2, 5 patients with pancreatic cancer received trametinib (2.0 mg once daily) in combination with gemcitabine (1000 mg/m(2)). RESULTS: In part 1, a dose-limiting toxicity was observed in a patient in the 2.0-mg dose cohort, but the maximum tolerated dose was not reached at doses up to 3.0 mg daily. The best overall response was a PR in 1 patient, and 6 patients had SD. In part 2, the combination of trametinib and gemcitabine was tolerated for a short period of time. However, serious interstitial lung disease (ILD) was observed in 3 of 5 patients 4 weeks or more after the start of the treatment, including 1 fatal case. Three patients achieved a PR, and 2 patients had SD. The most common adverse event was rash (85 % in part 1 and 100 % in part 2). CONCLUSIONS: Trametinib monotherapy was tolerable in Japanese patients with cancer. However, the combination of trametinib plus gemcitabine carried a higher risk as compared with monotherapy, during which no ILD was observed. (ClinicalTrials.gov number, NCT01324258.).

Retrospective analysis of fixed dose rate infusion of gemcitabine and S-1 combination therapy (FGS) as salvage chemotherapy in patients with gemcitabine-refractory advanced pancreatic cancer: inflammation-based prognostic score predicts survival.

PURPOSE: The purpose of this study was to assess the efficacy and safety of fixed dose rate infusion of gemcitabine and S-1 combination therapy (FGS) in patients with gemcitabine (GEM)-refractory pancreatic cancer (PC) and to explore independent variables associated with survival. METHODS: We retrospectively reviewed consecutive patients with GEM-refractory PC who received FGS at our institution from March 2009 to December 2013. GEM was administered by fixed dose rate intravenous infusion of 1,200 mg/m(2) as a 120-min infusion on day 1, and S-1 was administered orally twice a day at a dose of 40 mg/m(2) on days 1-7. Cycles were repeated every 14 days. RESULTS: Sixty-one patients with GEM-refractory PC received FGS. Sixteen patients received FGS as third-line treatment. Twenty-nine patients (48 %) had a history of S-1 administration. The objective response rate was 13 %, and the disease control rate was 49 %. The median progression-free survival time was 2.7 months, and the median overall survival time was 6.0 months. Major Grade 3 or 4 adverse events included neutropenia (15 %), diarrhea (3 %), anorexia (2 %), and fatigue (2 %). A high inflammation-based prognostic score (modified Glasgow prognostic score (mGPS), which incorporates C-reactive protein and albumin), a performance status >0, and serum carbohydrate antigen 19-9 level >2,000 IU/ml were independently associated with a poor outcome. CONCLUSIONS: FGS might be effective and well tolerated as salvage chemotherapy in a practical setting. The inflammation-based prognostic score is a simple and reliable indicator of survival in the setting of salvage chemotherapy.

Role of chemotherapy in treatments for biliary tract cancer.

The purpose of chemotherapy in patients with advanced solid cancers, including biliary tract cancer, is generally to improve the survival and quality of life of the patients. Also, adjuvant chemotherapy is expected to increase the curability of surgery in patients scheduled to undergo surgery. Most patients with unresectable biliary tract cancer develop obstructive jaundice, and biliary drainage is needed before any of the aforementioned treatments. Once jaundice is resolved by stenting of the bile duct or bilio-intestinal bypass, cholangitis often develops, leading to rapid deterioration of the patient's general condition. Therefore, the beneficial effect of chemotherapy in such patients remains controversial. A few randomized controlled trials have demonstrated the survival benefit of chemotherapy as compared with supportive care. In one of these trials, improvement of the quality of life was also confirmed. Recently, since the survival benefit of combined gemcitabine plus cisplatin therapy over gemcitabine alone has been demonstrated in randomized controlled clinical trials, this combined regimen has been recognized as a standard therapy for unresectable biliary tract cancer. A second-line regimen is now expected to be established for patients with gemcitabine-refractory biliary tract cancer, although the significance of second-line therapy remains unclear. One of the next issues in relation to chemotherapy for biliary tract cancer is the development of molecular-targeted agents; however, few large clinical trials of such agents have been conducted for biliary tract cancer. Various issues in chemotherapy for biliary tract cancer remain to be investigated, and global cooperation is necessary to conduct large clinical trials.

Rice transposable elements are characterized by various methylation environments in the genome.

BACKGROUND: Recent studies using high-throughput methods have revealed that transposable elements (TEs) are a comprehensive target for DNA methylation. However, the relationship between TEs and their genomic environment regarding methylation still remains unclear. The rice genome contains representatives of all known TE families with different characteristics of chromosomal distribution, structure, transposition, size, and copy number. Here we studied the DNA methylation state around 12 TEs in nine genomic DNAs from cultivated rice strains and their closely related wild strains. RESULTS: We employed a transposon display (TD) method to analyze the methylation environments in the genomes. The 12 TE families, consisting of four class I elements, seven class II elements, and one element of a different class, were differentially distributed in the rice chromosomes: some elements were concentrated in the centromeric or pericentromeric regions, but others were located in euchromatic regions. The TD analyses revealed that the TE families were embedded in flanking sequences with different methylation degrees. Each TE had flanking sequences with similar degrees of methylation among the nine rice strains. The class I elements tended to be present in highly methylated regions, while those of the class II elements showed widely varying degrees of methylation. In some TE families, the degrees of methylation were markedly lower than the average methylation state of the genome. In two families, dramatic changes of the methylation state occurred depending on the distance from the TE. CONCLUSION: Our results demonstrate that the TE families in the rice genomes can be characterized by the methylation states of their surroundings. The copy number and degree of conservation of the TE family are not likely to be correlated with the degree of methylation. We discuss possible relationships between the methylation state of TEs and their surroundings. This is the first report demonstrating that TEs in the genome are associated with a particular methylation environment that is a feature of a given TE.