Genetic landscape and PD-L1 expression in Epstein-Barr virus-associated gastric cancer according to the histological pattern.

Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer. This study aims to investigate genomic and clinicopathological characteristics of EBVaGC according to the histological pattern. We retrospectively collected 18 specimens of surgically resected EBVaGCs. Whole-exome sequencing was performed for all cases. Moreover, PD-L1 expression and tumor-infiltrating lymphocyte (TIL) percentage were investigated. Among 18 EBVaGCs, 10 cases were of intestinal histology, 3 were of poorly cohesive histology, and the remaining 5 were of gastric carcinoma with lymphoid stroma histology. Whole-exome sequencing revealed that EBVaGCs with intestinal histology harbored pathogenic mutations known to frequently occur in tubular or papillary adenocarcinoma, including TP53, KRAS, FBXW7, MUC6, ERBB2, CTNNB1, and ERBB2 amplifications. One patient with poorly cohesive carcinoma histology harbored a CDH1 mutation. Patients with EBVaGCs with intestinal or poorly cohesive carcinoma histology frequently harbored driver mutations other than PIK3CA, whereas those with EBVaGCs with gastric carcinoma with lymphoid stroma histology lacked other driver mutations. Moreover, the histological pattern of EBVaGCs was significantly associated with the levels of TILs (P = 0.005) and combined positive score (P = 0.027). In conclusion, patients with EBVaGCs with different histological patterns exhibited distinct genetic alteration, PD-L1 expression, and degree of TILs.

Consensus Definition of Blood Samples from the Subcategorized Normal Controls in the Korea Biobank Network.

A control group is defined as a group of people used for comparison. Depending on the type of study, it can be a group of healthy people or a group not exposed to risk factors. It is important to allow researchers to select the appropriate control participants. The Korea Biobank Project-sponsored biobanks are affiliated with the Korea Biobank Network (KBN), for which the National Biobank of Korea plays a central coordinating role among KBN biobanks. KBN organized several working groups to address new challenges and needs in biobanking. The "Normal Healthy Control Working Group" developed standardized criteria for three defined control groups, namely, normal, normal-plus, and disease-specific controls. Based on the consensus on the definition of a normal control, we applied the criteria for normal control participants to retrospective data. The main reason for exclusion from the "Normal-plus" group was blood test results beyond 5% of the reference range, including hypercholesterolemia. Subclassification of samples of normal controls by detailed criteria will help researchers select optimal normal controls for their studies.

Comparison of diagnostic performances of slow-pull suction and standard suction in endoscopic ultrasound-guided fine needle biopsy for gastrointestinal subepithelial tumors.

BACKGROUND/AIMS: Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is integral to the diagnosis of gastrointestinal (GI) subepithelial tumors (SETs). The impact of different EUS-FNB tissue sampling techniques on specimen adequacy and diagnostic accuracy in SETs has not been fully evaluated. This study aimed to compare the diagnostic outcomes of slow-pull (SP) and standard suction (SS) in patients with GI SETs. METHODS: In this retrospective comparative study, 54 patients were enrolled. Medical records were reviewed for location and size of the target lesion, FNB needle type/size, technical order, specimen adequacy, diagnostic yield, and adverse events. The acquisition rate of adequate specimens and diagnostic accuracy were compared according to EUS-FNB techniques. RESULTS: The mean lesion size was 42.6±36.4 mm, and most patients were diagnosed with GI stromal tumor (75.9%). The overall diagnostic accuracies of the SP and SS techniques were 83.3% and 81.5%, respectively (p=0.800). The rates of obtaining adequate core tissue were 79.6% and 75.9%, respectively (p=0.799). No significant clinical factors affected the rate of obtaining adequate core tissue, including lesion location and size, FNB needle size, and final diagnosis. CONCLUSION: SP and SS had comparable diagnostic accuracies and adequate core tissue acquisition for GI SETs via EUS-FNB.

Regional lymph node recurrence without intragastric lesions after curative endoscopic resection of early gastric cancer meeting the absolute indications of endoscopic resection: A case report.

RATIONALE: With the increase of gastric cancer surveillance and endoscopic resection techniques, the number of endoscopic resections being performed for the treatment of early gastric cancer in East Asian countries has been increasing. Previously, endoscopic resection has been limited to only differentiated type intramucosal cancers which had a diameter ≤2.0 cm, provided there was no evidence of ulceration and lymphovascular invasion, known as absolute indications. And recently, indications for endoscopic resection have been expanded to include even more cases. PATIENT CONCERNS: A 57-year-old female, who had undergone curative endoscopic submucosal dissection for early gastric cancer under the absolute indications for endoscopic resection 5 years prior, was referred to the department of general surgery with metastatic perigastric lymph nodes without intragastric lesions. DIAGNOSIS: Computed tomography scan revealed the presence of a few enlarged lymph nodes at the distal part of the lesser curvature of the stomach. And positron emission tomography scan further revealed the presence of two hypermetabolic lymph nodes near the common hepatic artery, suggestive of metastatic lymph nodes. INTERVENTIONS: Laparoscopic distal gastrectomy and Roux-en-Y gastrojejunostomy with D2 lymph node dissection were performed. OUTCOMES: Final pathology report revealed the absence of any residual carcinoma in the stomach. However lymphovascular invasion of omental fat, and 3 out of 29 perigastric lymph nodes harvested had metastatic adenocarcinoma. LESSONS: The case demonstrates that regional lymph node recurrence without intragastric lesions after curative resection of early gastric cancer meeting the absolute indications for endoscopic resection is possible even 5 years after resection of the primary lesion.

Rebamipide for the Improvement of Gastric Atrophy and Intestinal Metaplasia: A Prospective, Randomized, Pilot Study.

BACKGROUND: The presence of atrophic gastritis (AG) and intestinal metaplasia (IM) is associated with an increased risk of gastric cancer (GC). Thus, the development of new strategies to improve AG/IM is essential for reducing the incidence of GC. AIMS: We aimed to evaluate the efficacy of rebamipide for improving AG/IM. METHODS: This was a prospective, randomized, pilot study from a single tertiary referral center. Fifty-three (rebamipide, n = 34 vs. placebo, n = 19) patients, who underwent endoscopic resection for gastric dysplasia or early GC, were analyzed. We obtained tissue samples from the antrum and corpus of the stomach, at the time of screening and 1-year later. The histologic grading of inflammation was performed by histopathologists RESULTS: The AG grade in the antrum improved significantly after rebamipide treatment (pre-administration, 1.870 ± 0.932 vs. post-administration, 1.430 ± 0.986; P = 0.013). Additionally, the severity of IM in the antrum was significantly improved (pre-administration, 1.750 ± 0.963 vs. post-administration, 1.370 ± 1.032; P = 0.038). The rebamipide subgroup analysis revealed that patients with no Helicobacter pylori (HP) infection showed significant improvements in AG in the antrum (pre-administration, 1.880 ± 1.040 vs. post-administration, 1.250 ± 0.894; P = 0.028) and IM in antrum (pre-administration, 1.840 ± 1.012 vs. post-administration, 1.180 ± 0.912; P = 0.020). CONCLUSIONS: This study demonstrated that the administration of rebamipide improves AG and IM in the antrum, especially in patients with HP non-infection (KCT0001915).

Case Report: Development of Type 1 Autoimmune Pancreatitis in an Adolescent With Ulcerative Colitis Mimicking Pancreatic Cancer.

Introduction: Autoimmune pancreatitis (AIP) is a rare extraintestinal manifestation of inflammatory bowel disease (IBD) which is typically responsive to corticosteroid treatment. Case Presentation: We report a case of a 17-year-old male diagnosed with ulcerative colitis who subsequently developed acute pancreatitis. Blood tests demonstrated elevated pancreatic enzyme levels of amylase (1319 U/L) and lipase (809 U/L). Abdominal computed tomography revealed peripancreatic fat stranding and the presence of a perisplenic pseudocyst. Azathioprine and mesalazine were stopped as possible causes of drug-induced pancreatitis. However, pancreatic enzymes remained elevated and corticosteroid treatment was started. Despite corticosteroid therapy, amylase and lipase levels continued to increase. Infliximab was started due to a flare in gastrointestinal symptoms of ulcerative colitis. Follow-up abdominal ultrasonography revealed a pancreatic tail mass. Tumor markers, including CA 19-9, were elevated and atypical cells were seen on histological examination of an endoscopic ultrasonography-guided fine needle aspiration biopsy. Surgical pancreaticosplenectomy was performed for suspected pancreatic neoplasm. Surprisingly, histology revealed chronic pancreatitis with storiform fibrosis and infiltration of IgG4-positive cells, compatible with AIP type 1. Thereafter, pancreatic enzymes gradually decreased to normal levels and the patient has been in remission for 9 months on infliximab monotherapy. Conclusion: Pediatric gastroenterologists should keep in mind that AIP may develop during the natural course of pediatric IBD. Moreover, the development of pancreatic fibrosis may be non-responsive to corticosteroid treatment and mimic pancreatic neoplasia.

Cytological, histological, and molecular characteristics of pure invasive micropapillary carcinoma of pancreas: A case report.

INTRODUCTION: Pure invasive micropapillary carcinoma (IMPC) is a rare histologic subtype of pancreatic cancer which has a high propensity for lymph node metastasis and poor prognosis. PATIENT CONCERNS: An 81-year-old woman was admitted to our institution with a 3-month history of back pain. Computed tomography of the abdomen and pelvis confirmed the presence of a low-density mass in the tail of the pancreas. DIAGNOSIS: Endoscopic ultrasound-guided fine needle aspiration cytology (FNAC) from the pancreatic mass showed small tumor cell clusters with three-dimensional aggregates and morula-like structures. The tumor was diagnosed as adenocarcinoma with micropapillary features. INTERVENTIONS: The patient underwent radical antegrade modular pancreatosplenectomy and regional lymph node dissection. Histological examination showed small clusters of tumor cells that were closely adhered to one another. The cells were located in empty stromal spaces mimicking lymphovascular channels. All tumor cells showed reverse polarity, resulting in an "inside-out" pattern. An extensive search was performed, and no typical ductal adenocarcinoma component was found. The tumor measured 1.5 × 1.3 cm and invaded into the peripancreatic fat tissue without adjacent organ invasion. One of the 12 regional lymph nodes showed metastasis. Ion Torrent next-generation sequencing identified missense mutations in KRAS, TP53, and SMAD4 using the Oncomine Comprehensive Panel version 1. OUTCOMES: Twelve months following surgical resection the patient remained healthy with no evidence of recurrence at clinical follow-up. LESSONS: This report highlights the diagnostic features and molecular characteristics of pure pancreatic IMPC and the challenges with diagnosis by FNAC. A centralized and collaborative accumulation of additional cases of pure IMPC could further elucidate its pathogenesis.

Clinical significance and prognostic role of hypoxia-induced microRNA 382 in gastric adenocarcinoma.

Hypoxia and angiogenesis are critical components in the progression of solid cancer, including gastric cancers (GCs). miR-382 has been identified as a hypoxia-induced miR (hypoxamiR), but the clinical significance in GCs has not been identified yet. To explore the clinical and prognostic importance of miR-382 in GCs, the surgical specimens of 398 patients with GCs in KNU hospital in Korea, the total of 183 patients was randomly selected using simple sampling methods and big data with 446 GCs and 45 normal tissues from the data portal (https://portal.gdc.cancer.gov/) were analysed. Expression of miR-382 as well as miR-210, as a positive control hypoxamiR by qRT-PCR in histologically malignant region of GCs showed significantly positive correlation (R = 0.516, p<0.001). High miR-210 and miR-382 expression was significantly correlated with unfavorable prognosis including advanced GCs (AGC), higher T category, N category, pathologic TNM stage, lymphovascular invasion, venous invasion, and perinueral invasion, respectively (all p<0.05). In univariate analysis, high miR-210 expression was significantly associated with worse overall survival (OS) (p = 0.036) but not high miR-382. In paired 60 gastric normal and cancer tissues, miR-382 expression in cancer tissues was significantly higher than normal counterpart (p = 0.003), but not miR-210 expression. However, by increasing the patient number from the big data analysis, miR-210 as well as miR-382 expression in tumor tissues was significantly higher than the normal tissues. Our results suggest that miR-382, as novel hypoxamiR, can be a prognostic marker for advanced GCs and might be correlated with metastatic potential. miR-382 might play important roles in the aggressiveness, progression and prognosis of GCs. In addition, miR-382 give a predictive marker for progression of GCs compared to the normal or preneoplastic lesion.

Early Gastric Adenosquamous Carcinoma Resected Using Endoscopic Submucosal Dissection.

Adenosquamous carcinoma (ASC) is characterized as a mixed neoplasia (adenocarcinoma with glandular architecture and squamous cell carcinoma [SqCC]). Because most ASCs are found in the advanced stage at the time of diagnosis, early gastric ASC is an extremely rare tumor. Here, we present the case of an incidental finding of early gastric ASC in a 61-year-old Korean man during a health screening. Histological biopsy through esophagogastroduodenoscopy revealed a moderately differentiated adenocarcinoma in the distal body. The patient underwent endoscopic submucosal dissection and was diagnosed with ASC. The SqCC components of this tumor were located adjacent to the adenocarcinoma components and occupied 40% of the tumor. Two individual tumor components had invaded into the submucosal layer with lymphovascular invasion. An abdominal computed tomography scan indicated no definite mass or wall thickening of the stomach and revealed neither lymph node enlargement nor distant metastasis. To the best of our knowledge, this is the 14th reported case of early gastric ASC, and all cases were reported in East Asians.

Exon 9 Mutation of PIK3CA Associated With Poor Survival in Patients With Epstein-Barr Virus-associated Gastric Cancer.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer (GC) is known to harbor a significant enrichment of of phosphatidylinositol 4, 5-biphosphate 3- kinase catalytic subunit alpha isoform (PIK3CA). Therefore, this study investigated the clinical relevance and prognostic role of PIK3CA mutations in patients with EBV-GC. MATERIALS AND METHODS: After reviewing 1,318 consecutive cases of surgically resected GC, 120 patients were identified as EBV-positive using EBV-encoded RNA in situ hybridization. PIK3CA mutations were identified in formalin-fixed and paraffin-embedded surgical specimens from 112 patients with EBV-GC with available tumor tissue samples. Real-time polymerase chain reaction was used to evaluate hot-spot mutations of exons 1, 4, 7, 9, and 20 of PIK3CA. RESULTS: Among the 112 patients, the frequency of PIK3CA mutations was 25.0% (n=28), and among the 28 patients harboring a PIK3CA mutation, most mutations were identified in exon 9 (n=21, 18.8%). The presence of PIK3CA mutation was also correlated with a higher T category (p<0.001) and N category (p<0.001), as well as the presence of perinueral invasion (p<0.001) and venous invasion (p<0.001). In a univariate analysis, PIK3CA mutation showed no association with overall survival (OS) (p=0.184) or disease-free survival (DFS) (p=0.150). Patients harboring exon 9 PIK3CA mutations exhibited a significantly shorter OS (p=0.023) and DFS (p=0.013) than the patients lacking an exon 9 PIK3CA mutation, yet without statistical significance in the multivariate analysis. Notably, exon 9 E542K mutation of PIK3CA was associated with the worst DFS (p=0.011). CONCLUSION: The current data show that PIK3CA mutations appear to play an important role in carcinogenesis and tumor aggressiveness in EBV-GC, and also support the concept that exon 9 mutation of PIK3CA is a prognostic indicator for predicting patient outcomes and a rationale for therapeutic targeting in EBV-GC.

Comparison of the Diagnostic Performances of Same-session Endoscopic Ultrasound- and Endoscopic Retrograde Cholangiopancreatography-guided Tissue Sampling for Suspected Biliary Strictures at Different Primary Tumor Sites.

BACKGROUND/AIMS: Determining the cause of suspected biliary stricture is often challenging in clinical practice. We aimed to compare the diagnostic yields of endoscopic ultrasound-guided tissue sampling (EUS-TS) and endoscopic retrograde cholangiopancreatography-guided tissue sampling (ERCP-TS) in patients with suspected biliary stricture at different primary lesions. METHODS: We enrolled patients who underwent same-session EUS- and ERCP-TS for the evaluation of suspected biliary stricture. Forceps biopsy and/or brush cytology of intraductal lesions and fine-needle aspiration for solid mass lesions were performed during ERCP and EUS, respectively. RESULTS: One hundred and twenty-five patients treated at our institution between January 2011 and September 2016, were initially considered for the study. However, 32 patients were excluded due to loss of follow-up (n=8) and ERCP-TS on the pancreatic duct (n=20) or periampullary lesions (n=4). Of the 93 patients included, 86 had a malignant tumor including cholangiocarcinoma (n=39), pancreatic cancer (n=37), and other malignancies (n=10). Seven patients had benign lesions. EUS-TS had higher rate of overall diagnostic accuracy than ERCP-TS (82.8% vs. 60.2%, p=0.001), and this was especially true for patients with a pancreatic lesion (84.4% vs. 51.1%, p=0.003). CONCLUSIONS: EUS-TS was found to be superior to ERCP-TS for evaluating suspected biliary strictures, especially those caused by pancreatic lesions.

An Extragastrointestinal Stromal Tumor Originating from the Pancreas.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract (GIT). In fewer than 5% of cases, GIST originates primarily from outside the GIT. The occurrence of GIST originating from the pancreas is rare. Sometimes, neuroendocrine tumors should be differentiated from GISTs because of their hyperenhancing nature in radiologic images. We report a case of GIST arising in the pancreas that was confirmed by surgical resection.

Elevated Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients with Advanced Gastric Cancer Treated with Trastuzumab Combination Chemotherapy.

BACKGROUND/AIM: This study investigated the clinical prognostic relevance of the neutrophil-to-lymphocyte ratio (NLR) in patients with human epidermal receptor 2 (HER2)-positive metastatic advanced gastric cancer (AGC) treated with combination chemotherapy including trastuzumab. PATIENTS AND METHODS: This is a retrospective analysis of 73 patients diagnosed with metastatic AGC who were treated with trastuzumab combination chemotherapy. NLR was calculated as the neutrophil count divided by the lymphocyte count. A cut-off value of 3 was selected, which classified patients into two categories, low (≤3.0) or high (>3.0). RESULTS: In the univariate analysis, the high-NLR patients showed a significantly shorter progression-free survival (PFS) and overall survival (OS) than the low-NLR patients (PFS, p=0.012, OS, p=0.047). In the multivariate analysis, the high NLR was independently associated with a shorter PFS (p=0.015) and OS (p=0.040). CONCLUSION: This study found that a high NLR was associated with a shorter PFS and OS in patients with HER2-positive gastric cancer treated with trastuzumab.

Factors to improve the interobserver agreement for gastric atrophy and intestinal metaplasia: consensus of definition and criteria.

AIMS: Intestinal metaplasia and atrophy of the gastric mucosa are associated with Helicobacter pylori infection and are considered premalignant lesions. The updated Sydney system is used for these parameters, but experienced pathologists and consensus processes are required for interobserver agreement. We sought to determine the influence of the consensus process on the assessment of intestinal metaplasia and atrophy. METHODS AND RESULTS: Two study sets were used: consensus and validation. The consensus set was circulated and five gastrointestinal pathologists evaluated them independently using the updated Sydney system. The consensus of the definitions was then determined at the first consensus meeting. The same set was recirculated to determine the effect of the consensus. The second consensus meeting was held to standardise the grading criteria and the validation set was circulated to determine the influence. Two additional circulations were performed to assess the maintainance of consensus and intraobserver variability. Interobserver agreement of intestinal metaplasia and atrophy was improved through the consensus process (intestinal metaplasia: baseline κ = 0.52 versus final κ = 0.68, P = 0.006; atrophy: baseline κ = 0.19 versus final κ = 0.43, P < 0.001). Higher interobserver agreement in atrophy was observed after consensus regarding the definition (pre-consensus: κ = 0.19 versus post-consensus: κ = 0.34, P = 0.001). There was improved interobserver agreement in intestinal metaplasia after standardisation of the grading criteria (pre-standardisation: κ = 0.56 versus post-standardisation: κ = 0.71, P = 0.010). CONCLUSIONS: This study suggests that interobserver variability regarding intestinal metaplasia and atrophy may result from lack of a precise definition and fine criteria, and can be reduced by consensus of definition and standardisation of grading criteria.

Intratumoural PD-L1 expression is associated with worse survival of patients with Epstein-Barr virus-associated gastric cancer.

BACKGROUND: This study investigated the clinical relevance and prognostic impact of the overall expression of programmed cell death protein ligand-1 (PD-L1) and programmed cell death protein ligand-2 (PD-L2), in patients with Epstein-Barr virus-associated gastric cancer (EBVaGC). METHODS: After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, the expression status of PD-L1 and PD-L2 in 120 patients with EBVaGC identified by EBV-encoded RNA in situ hybridisation was retrospectively analysed using immunohistochemistry (IHC). For each IHC marker, positivity was separately in intraepithelial tumour cells (iTu-) and immune cells in the tumour stroma area (str-). RESULTS: Among 116 eligible patients, 57 (49.1%) and 66 patients (56.9%) were determined as iTu-PD-L1-positive and str-PD-L1-positive, respectively, whereas 23 (21.6%) and 45 patients (38.8%) were determined as iTu-PD-L2 positive and str-PD-L2 positive, respectively. Intraepithelial tumour cell PD-L1 positivity was found to be significantly associated with lymph node (LN) metastasis (P=0.012) and a poor disease-free survival (DFS) (P=0.032), yet not overall survival (P=0.482). In a multivariate analysis, iTu-PD-L1 positivity was independently associated with a poor DFS (P=0.006, hazard ratio=12.085). In contrast, str-PD-L2-positivity was related to a lower T category (P=0.003), absence of LN metastasis (P=0.032) and perineural invasion (P=0.028). Intraepithelial tumour cell and str-PD-L2 positivity showed a trend towards an improved DFS, although not significant (P=0.060 and P=0.073, respectively). CONCLUSIONS: Intraepithelial tumour cells PD-L1 expression can be used to predict a poor outcome in patients with EBVaGC and can represent a rational approach for PD-1/PD-L pathway-targeted immunotherapy.

Clinical significance of tumor-infiltrating lymphocytes for gastric cancer in the era of immunology.

Immunotherapy has begun to revolutionize cancer treatment, by introducing therapies that target the host immune system instead of the tumor, therapies that possess unique adverse event profiles, and therapies that may cure certain types of cancer. The immune microenvironment of tumors is emerging as the most important means of understanding the relationship between a patient' immune system and their cancer, informing prognosis, and guiding immunotherapy, such as an antibody blockade of immune checkpoints. For some solid tumors, simple quantitation of lymphocyte infiltration would seem to have prognostic significance, suggesting that lymphocyte infiltration is not passive but may actively promote or inhibit tumor growth. For gastric cancers, several studies have provided strong evidence that immune cells contribute to determining prognosis. However, the exact role of immune cells in gastric cancer remains unclear. Therefore, this review focuses on the clinical significance of immune cells, especially tumor-infiltrating lymphocytes, in gastric cancer.

Early Diagnosis of ABCB11 Spectrum Liver Disorders by Next Generation Sequencing.

PURPOSE: The goal of this study was the early diagnosis of ABCB11 spectrum liver disorders, especially those focused on benign recurrent intrahepatic cholestasis and progressive familial intrahepatic cholestasis. METHODS: Fifty patients presenting neonatal cholestasis were evaluated to identify underlying etiologies. Genetic analysis was performed on patients suspected to have syndromic diseases or ABCB11 spectrum liver disorders. Two families with proven ABCB11 spectrum liver disorders were subjected to genetic analyses to confirm the diagnosis and were provided genetic counseling. Whole exome sequencing and Sanger sequencing were performed on the patients and the family members. RESULTS: Idiopathic or viral hepatitis was diagnosed in 34%, metabolic disease in 20%, total parenteral nutrition induced cholestasis in 16%, extrahepatic biliary atresia in 14%, genetic disease in 10%, neonatal lupus in 2%, congenital syphilis in 2%, and choledochal cyst in 2% of the patients. The patient with progressive familial intrahepatic cholestasis had novel heterozygous mutations of ABCB11 c.11C>G (p.Ser4*) and c.1543A>G (p.Asn515Asp). The patient with benign recurrent intrahepatic cholestasis had homozygous mutations of ABCB11 c.1331T>C (p.Val444Ala) and heterozygous, c.3084A>G (p.Ala1028Ala). Genetic confirmation of ABCB11 spectrum liver disorder led to early liver transplantation in the progressive familial intrahepatic cholestasis patient. In addition, the atypically severe benign recurrent intrahepatic cholestasis patient was able to avoid unnecessary liver transplantation after genetic analysis. CONCLUSION: ABCB11 spectrum liver disorders can be clinically indistinguishable as they share similar characteristics related to acute episodes. A comprehensive genetic analysis will facilitate optimal diagnosis and treatment.

Clinical Significance of p53 Protein Expression, Beta-catenin Expression and HER2 Expression for Epstein-Barr Virus-associated Gastric Cancer.

This study assessed the expression of the p53 protein, beta-catenin, and HER2 and their prognostic implications in patients with EBV-associated gastric cancer (EBVaGC). After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 117 patients were identified as EBV-positive using EBV-encoded RNA in-situ hybridization. The immunohistochemistry results were interpreted as follows: strong p53 nuclear expression in at least 50% of tumor nuclei was interpreted as a positive result, strong beta-catenin expression in at least 10% of cytoplasmic nuclei was interpreted as a positive result, and moderate or strong complete or basolateral membrane staining in 10% of tumor cells was interpreted as a positive result for HER2. Immunohistochemical staining for p53 was performed on tumor tissue from 105 patients, among whom 25 (23.8%) tested positive. Meanwhile, beta-catenin expression was positive in 10 patients (17.5%) and HER2 expression was positive in 8 patients (6.8%). The positive expression of p53 was significantly associated with a high T stage (p=0.006). More patients with lymph node metastasis were p53-positive (p=0.013). In the univariate analysis, the p53-positive patients showed significantly decreased disease-free survival (DFS) when compared with the p53-negative patients (p=0.022), although the p53 status was only marginally associated with overall survival (OS) (p=0.080). However, p53 expression showed no prognostic significance on DFS in the multivariate analysis. Moreover, beta-catenin and HER2 showed no association with DFS and OS in the survival analysis. The current study found a significant correlation between p53 expression and tumor progression and lymph node metastases in patients with EBVaGC.

Spontaneous Peripheral Ameloblastic Odontoma in a Male Sprague-Dawley Rat.

Peripheral ameloblastic odontoma is a rare variant of odontogenic tumor occurring in the extraosseous region. The present report describes a spontaneous tumor in male Sprague-Dawley (SD) rats. The clinically confirmed nodule in the right mandibular region was first observed when the rat was 42 weeks and remained until the terminal sacrifice date when the animal was 48 weeks of age. At necropsy, a well demarcated nodule, approximately 2.5 × 2.0 × 2.0 cm, protruded from the ventral area of the right mandible. The nodule was not attached to mandibular bone and was not continuous with the normal teeth. Histopathologically, the tumor was characterized by the simultaneous occurrence of an ameloblastomatous component and composite odontoma-like elements within the same tumor. The epithelial portion formed islands or cords resembling the follicle or plexiform pattern typical of ameloblastoma and was surrounded by mesenchymal tissue. Formation of eosinophilic and basophilic hard tissue matrix (dentin and enamel) resembling odontoma was observed in the center of the tumor. Mitotic figures were rare, and areas of cystic degeneration were present. Immunohistochemically, the epithelial component was positive for cytokeratin AE1/AE3 (CK AE1/AE3), and the mesenchymal component and odontoblast-like cells were positive for vimentin, in the same manner as in normal teeth. On the basis of these findings, the tumor was diagnosed as a peripheral ameloblastic odontoma in an extraosseous mandibular region in a SD rat. In the present study, we report the uncommon spontaneous peripheral ameloblastic odontoma in the SD rat. We also discuss here the morphological characteristics, origin, histochemical, and immunohistochemical features for the diagnosis of this tumor.

Coexistence of ulcerative colitis and Sjögren's syndrome in a patient with Takayasu's arteritis and Hashimoto's thyroiditis.

A 31-year-old woman with a 15-year history of Takayasu's arteritis (TA) and a 13-year history of Hashimoto's thyroiditis presented with hematochezia. She received a diagnosis of Sjögren's syndrome at 1 month before her visit to Kyungpook National University Medical Center. Her colonoscopic findings were compatible with a diagnosis of ulcerative colitis (UC). She was treated with oral mesalazine, and her hematochezia symptoms subsequently disappeared. The coexistence of UC and TA has been reported; however, reports on the coexistence of UC and Sjögren's syndrome, or of UC and Hashimoto's thyroiditis are rare. Although the precise etiologies of these diseases are unknown, their presence together suggests that they may have a common pathophysiologic background. Furthermore, in patients with autoimmune or vascular diseases, including TA, systemic manifestations should be assessed with consideration of inflammatory bowel diseases including UC in the presence of gastrointestinal symptoms such as diarrhea and hematochezia.