EUS-guided versus percutaneous liver biopsy: A prospective randomized clinical trial.

Background and Objectives: Prospective studies comparing EUS-guided liver biopsy (EUS-LB) to percutaneous LB (PC-LB) are scarce. We compared the efficacy and safety of EUS-LB with those of PC-LB in a prospective randomized clinical trial. Methods: Between 2020 and 2021, patients were enrolled and randomized (1:1 ratio). The primary outcome was defined as the proportion of patients with ≥11 complete portal tracts (CPTs). The sample size (n = 80) was calculated based on the assumption that 60% of those in the EUS-LB and 90% of those in the PC-LB group will have LB with ≥11 CPTs. The secondary outcomes included proportion of patients in whom a diagnosis was established, number of CPTs, pain severity (Numeric Rating Scale-Pain Intensity), duration of hospital stay, and adverse events. Results: Eighty patients were enrolled (median age, 53 years); 67.5% were female. Sixty percent of those in the EUS-LB and 75.0% of those in the PC-LB group met the primary outcome (P = 0.232). The median number of CPTs was higher in the PC-LB (17 vs 13; P = 0.031). The proportion of patients in whom a diagnosis was established was similar between the groups (92.5% [EUS-LB] vs 95.0% [PC-LB]; P = 1.0). Patients in the EUS-LB group had less pain severity (median Numeric Rating Scale-Pain Intensity, 2.0 vs 3.0; P = 0.003) and shorter hospital stay (2.0 vs 4.0 hours; P < 0.0001) compared with the PC-LB group. No patient experienced a serious adverse event. Conclusions: EUS-guided liver biopsy was safe, effective, better tolerated, and associated with a shorter hospital stay.

Co-Presentation of Lupus Nephritis with Autoimmune Hepatitis.

BACKGROUND Systemic lupus erythematosus (SLE) is a multiorgan immunologic disease which commonly results in systemic manifestations by involving joints, kidneys, skin, heart, hematologic cell lines, pulmonary and central nervous systems. The hepatic involvement of lupus is relatively less common, which creates diagnostic challenges, as the clinical presentations of lupus hepatitis and autoimmune hepatitis (AIH) are similar. CASE REPORT A 51-year-old woman presented for multiple joint pain that began 2 years ago. Her work-up, including kidney biopsy, was consistent with a diagnosis of class V lupus nephritis. Subsequently, within a few months, she was admitted with acute elevation of liver enzymes and high immunoglobulin IgG level, and a liver biopsy demonstrated impressive interface hepatitis with many plasma cells and lymphocytes, suggestive of chronic hepatitis with high histological activity. This case illustrates the co-presentation of lupus nephritis and AIH, which is a rare association. The patient was managed with a tapering dose of prednisone, hydroxychloroquine initially, and later with mycophenolate mofetil, with complete resolution of liver enzyme abnormalities by 4-month follow-up. CONCLUSIONS Lupus hepatitis is hepatic involvement of SLE, which should be distinguished from AIH. Accurate diagnosis is important, as management and prognosis of these immunologic conditions can differ. Although both entities share clinical and biochemical markers, the presence of anti-ribosomal P antibodies and liver histology features of predominant lymphoid infiltrates with lobular inflammation favor lupus hepatitis. A multidisciplinary approach involving rheumatologists, hepatologists, and pathologists can improve disease outcomes by properly differentiating the 2 entities and guiding the selection of appropriate immunosuppressive therapy.

Tumoral Intraductal Neoplasms of the Bile Ducts Comprise Morphologically and Genetically Distinct Entities.

CONTEXT.­: Tumoral (grossly visible) intraductal neoplasms of the bile ducts are still being characterized. OBJECTIVE.­: To investigate their morphologic, immunohistochemical, and molecular features. DESIGN.­: Forty-one cases were classified as gastric-, intestinal-, pancreatobiliary-type intraductal papillary neoplasm (IPN), intraductal oncocytic papillary neoplasm (IOPN), or intraductal tubulopapillary neoplasm (ITPN) on the basis of histology. All neoplasms were subjected to targeted next-generation sequencing. RESULTS.­: The mean age at diagnosis was 69 years (42-81 years); male to female ratio was 1.3. Most neoplasms (n = 23, 56%) were extrahepatic/large (mean size, 4.6 cm). The majority (n = 32, 78%) contained high-grade dysplasia, and 68% (n = 28) revealed invasion. All gastric-type IPNs (n = 9) and most ITPNs/IOPNs showed consistent colabeling for CK7/MUC6, which was less common among others (P = .004). Intestinal-type IPNs (n = 5) showed higher rates of CK20 expression than others (P < .001). Overall, the most commonly mutated genes included TP53 and APC, while copy number variants affected ELF3 and CDKN2A/B. All gastric-type IPNs contained an alteration affecting the Wnt signaling pathway; 7 of 9 (78%) showed aberrations in the MAPK pathway. Mutations in APC and KRAS were common in gastric-type IPNs as compared with others (P = .01 for both). SMAD4 was more frequently mutated in intestinal-type IPNs (P = .02). Pancreatobiliary-type IPNs (n = 14) exhibited frequent alterations in tumor suppressor genes including TP53, CDKN2A/B, and ARID2 (P = .04, P = .01 and P = .002, respectively). Of 6 IOPNs analyzed, 3 (50%) revealed ATP1B1-PRKACB fusion. ITPNs (n = 6) showed relatively few recurrent genetic aberrations. Follow-up information was available for 38 patients (median, 58.5 months). The ratio of disease-related deaths was higher for the cases with invasion (56% versus 10%). CONCLUSIONS.­: Tumoral intraductal neoplasms of the bile ducts, similar to their counterparts in the pancreas, are morphologically and genetically heterogeneous.

A Case Series of Gastric Metastatic Growths.

Gastric cancer is one of the gastrointestinal malignancies that can be quite devastating with high morbidity and mortality. Unfortunately, it is a malignancy that is encountered all across the world and is often brought into suspicion based on symptoms of the patient. The presentation differs based on the symptomatology and can be quite variable in each and every case. Malignant lesions in the stomach discovered endoscopically can represent as primary gastric growths or can be secondary as a consequence of metastatic spread from a distant primary site. It is important to recognize the different patterns of presentation of metastatic disease and to be aware of the primary tumor sites. The treatment and ultimately the prognosis changes drastically when dealing with a metastatic disease as opposed to a primary localized source with limited spread. The aim of our study is to present a mini series of cases that manifest as metastatic gastric growths. Their clinical, endoscopic and histological appearance is depicted to provide an understanding of each case. The primary sites of origin for our patients were the lungs, skin, lymphoid tissue and kidneys. Their overall clinical course is presented including the approach to the management in each case as well as their outcomes.

Kratom (Mitragyna speciosa)-Induced Hepatitis.

Kratom is a plant with opioid-like properties known to produce stimulant and analgesic effects. Although there are numerous studies on the psychoactive components of kratom, less is known about the toxicity. Specifically, few reports describe kratom-induced hepatotoxicity and demonstrate histological features. We provide a case report detailing the clinicopathologic findings of drug-induced liver injury caused by kratom. The laboratory workup included significant elevation of total bilirubin and alkaline phosphatase. Liver biopsy demonstrated a prominent canalicular cholestatic pattern, mixed portal inflammation, and newly described perivenular necrosis. This report provides additional information on kratom toxicity because its use continues to rise.

Cystic dystrophy of the duodenal wall: case report and literature review.

Cystic dystrophy of the duodenal wall (CDDW) is an uncommon pathological condition that may be a cause of symptomatic duodenal mass in some patients. CDDW and closely related conditions that involve the duodenal wall and the pancreatoduodenal groove have gone by a variety names in the literature. Though their pathophysiology is not fully understood, they are thought to be due to the presence of heterotopic pancreatic tissue that undergoes a degenerative process. A multimodal imaging approach paired with biopsy is often employed to rule out malignancy in these patients. This case report provides an account of the radiological and pathological findings that helped lead to the diagnosis of CDDW. A review of relevant literature and a discussion of the presented case are provided.

High-grade appendiceal mucinous neoplasm presenting as a giant appendiceal mucocele.

Appendiceal mucinous neoplasms are rare findings defined by an accumulation of mucus within the vermiform appendix, and can be caused by a variety of conditions. Appendiceal mucinous neoplasms are important to consider because they can develop into pseudomyxoma peritonei as a consequence of perforation. We report a case of a 55-year-old man who initially presented with increasing abdominal girth, constipation, anorexia, and unintentional weight loss. Computed tomography examination of the abdomen and pelvis demonstrated a huge thin-walled cystic mass causing significant displacement of the surrounding abdominal and pelvic structures. The mass was amenable to resection and removed without perforation. Gross pathologic examination demonstrated a 44.0 × 40.0 × 23.0 cm unilocular cystic mass with a section of attached bowel. Microscopic examination revealed high-grade appendiceal mucinous neoplasm arising in a background of low-grade appendiceal mucinous neoplasm. This case report provides an evidence to include appendiceal mucinous neoplasms in the differential diagnosis of large abdominal cystic masses.

Histologic diagnosis of a case of anal duct carcinoma with cytological correlation and differential diagnoses.

Anal duct carcinoma is an uncommon malignancy of the glands of the anal duct. This entity poses a diagnostic challenge, both clinically and histologically. This article describes histopathologic findings in a case of anal duct carcinoma, including the initial diagnosis on biopsy and subsequent cytology specimens. Additionally, differential diagnoses of this neoplasm are discussed. With a high index of suspicion, and attention to histological and immunohistochemical features, anal duct carcinoma can be accurately diagnosed both on biopsy and on cytology.

The efficacy and safety of endoscopic ultrasound-guided liver biopsy versus percutaneous liver biopsy in patients with chronic liver disease: a retrospective single-center study.

BACKGROUND AND AIMS: There is limited literature on endoscopic ultrasound-guided liver biopsy (EUS-LB), a new method of obtaining liver biopsy (LB). METHODS: We conducted a retrospective study of the efficacy and safety of EUS-LB compared to percutaneous liver biopsy (PC-LB) in patients with chronic liver disease at our center between January 2018 and August 2019. RESULTS: Thirty patients underwent EUS-LB and 60 patients underwent PC-LB were identified (median follow-up post-LB was 8 days; interquartile range (IQR), 3-5 days). The median number of portal tracts was significantly higher in the PC-LB group (13 vs. 5; P < 0.0001). A histologic diagnosis was established in 93% of the EUS-LB group, compared to 100% in the PC-LB group (P = 0.841). Patients in EUS-LB group had significantly shorter hospital stay (median time of hospital stay was 3 vs. 4.2 h in the EUS-LB vs. PC-LB group, respectively; P = 0.004) and reported less pain compared to PC-LB group (median pain score was 0 vs. 3.5; P = 0.0009). EUS-LB were performed using a 19-gauge (n = 27) or 22-gauge (n = 3); there was a tendency towards higher number of portal tracts in the 22- vs. the 19-gauge needle group (6 vs. 5; P = 0.501). No patient in either group had significant adverse events such as bleeding or death. CONCLUSION: EUS-LB is safe and is associated with less pain, shorter hospital stay, and high diagnostic yield (93%) compared to PC-LB. Randomized trials are needed to standardize the utility of EUS-LB.

Portal Cavernoma Cholangiopathy: Histologic Features and Differential Diagnosis.

Objectives: Portal cavernoma cholangiopathy (formerly portal biliopathy) is a type of biliary injury that occurs in association with a portal vein thrombus or cavernoma. Although the radiographic features of portal cavernoma cholangiopathy have been enumerated in the literature, its histologic features have not been described in detail. Methods: We describe the histologic findings in liver specimens from three patients with radiologically confirmed portal cavernoma cholangiopathy. Results: Of the three patients, one underwent surgical resection due to a clinical suspicion for cholangiocarcinoma, one had a liver biopsy sample obtained for evaluation of possible cirrhosis, and one had a clinically suspicious "hilar mass" at the time of orthotopic liver transplant. Histologic features common among the three liver specimens included portal venous abnormalities, where the portal veins were obliterated or small relative to the portal tract size, and obstructive biliary changes, such as ductular reaction and reactive epithelial atypia accompanied by a mixed inflammatory cell infiltrate with neutrophils. Conclusions: This case series provides clinicopathologic characteristics of portal cavernoma cholangiopathy. Histologic changes are reminiscent of hepatoportal sclerosis and/or bile duct obstruction. Attention to portal veins can provide helpful diagnostic clues, especially when biopsy samples are obtained from patients with a known portal vein thrombus or cavernoma.

Limited role of Chromogranin A as clinical biomarker for pancreatic neuroendocrine tumors.

BACKGROUND: Serum Chromogranin A (CgA) is widely used as a biomarker for pancreatic neuroendocrine tumors (PanNETs). The aim of this study was to investigate the value of CgA as a diagnostic and prognostic marker for well-differentiated PanNETs. METHODS: Patients with well-differentiated PanNET and a baseline CgA measurement, between 2011 and 2016 were reviewed. The diagnostic value was determined by comparing CgA values from patients with PanNETs to those with other pancreatic neoplasms and healthy controls. The Kaplan-Meier method was used to investigate the CgA prognostic significance. RESULTS: Ninety-nine patients met inclusion criteria. As a diagnostic marker, CgA had a sensitivity of 66%, specificity of 95%, and overall accuracy of 71%. The use of PPIs was associated with a higher CgA level (p = 0.015). When excluding patients on PPIs, CgA accuracy in distinguishing PanNETs from other pancreatic neoplasms was 66%, the sensitivity and specificity were 60% and 75% respectively. Elevated CgA (p = 0.004), Ki67% (p < 0.001), tumor grade (p < 0.001) and stage of disease (p = 0.036) were associated with disease-specific survival. CONCLUSION: CgA has a limited role as a diagnostic biomarker for well-differentiated PanNETs. An elevated CgA level may have prognostic value but its role should be further investigated with respect to other known pathological factors.

Evaluation of Natural Tooth Color Space of the Indian Population and Its Comparison to Manufacturer's Shade Systems.

PURPOSE: This study evaluated the natural tooth color space of the Indian population and compared it with the manufacturer's shade systems. MATERIALS AND METHODS: Maxillary central incisors of individuals aged 18-30 years and shade tabs of Vita Lumin vaccum (VL), Vitapan 3D master (V3D), and Shofu's Vintage Halo (SVH) shade guide were digitally photographed under standardized conditions. L*a*b* values from middle part of tooth and shade tab were attained using Adobe Photoshop 7.0 software. Comparative evaluation between the natural teeth and shade tabs was done, and color differences were noted and analyzed using appropriate software. RESULTS: The L*a*b* values of the Indian population displayed a broader range than the shade guides. The mean Δ E* for VL shade guide was 7.22, 7.99 for SVH, and 8.39 for V3D, which was statistically significant. Color space of the Indian population on displayed an elongated cone with an irregular base. The plots of all the three shade guides were narrower and shorter and deficient in the blue-green region as compared to the population. CONCLUSIONS: Within the limitations of this study, the mean color difference between the Indian population and the three shade guides was above the acceptability thresholds (ΔE* = 2.7-6.8). VL, V3D, and SVH shade guides were deficient in their coverage and therefore can be considered inconsistent.

A prototype of a novel cell phone application for tracking the vaccination coverage of children in rural communities.

Immunization saves millions of lives against vaccine-preventable diseases. Yet, 24 million children born every year do not receive proper immunization during their first year. UNICEF and WHO have emphasized the need to strengthen the immunization surveillance and monitoring in developing countries to reduce childhood deaths. In this regard, we present a software application called Jeev to track the vaccination coverage of children in rural communities. Jeev synergistically combines the power of smartphones and the ubiquity of cellular infrastructure, QR codes, and national identification cards. We present the design of Jeev and highlight its unique features along with a detailed evaluation of its performance and power consumption using the National Immunization Survey datasets. We are in discussion with a non-profit organization in Haiti to pilot test Jeev in order to study its effectiveness and identify socio-cultural issues that may arise in a large-scale deployment.

Comparison of the adherence to the american diabetes association guidelines of diabetes care in primary care and subspecialty clinics.

BACKGROUND: Diabetes mellitus is a major public health problem with significant morbidity and mortality. Evidence based guidelines have been proposed to reduce the micro and macrovascular complications, but studies have shown that these goals are not being met. We sought to compare the adherence to the American Diabetes Association guidelines for measurement and control of glycohemoglobin (A1c), blood pressure (BP), lipids (LDL) and microalbuminuria (MA) by subspecialty and primary care clinics in an academic medical center. METHODS: 390 random charts of patients with diabetes from Family Practice (FP), Internal Medicine (IM) and Diabetes (DM) clinics at Michigan State University were reviewed. RESULTS: We reviewed 131, 134 and 125 charts from the FP, IM and DM clinics, respectively. DM clinic had a higher percentage of patients with type 1 diabetes 43/125 (34.4%) compared with 7/131 (5.3%) in FP and 7/134 (5.2%) in IM clinics. A1c was measured in 99%, 97.8% and 100% subjects in FP, IM and DM clinics respectively. B.P. was measured in all subjects in all three clinics. Lipids were checked in 97.7%, 95.5% and 92% patients in FP, IM and DM clinics respectively. MA was measured at least once during the year preceding the office visit in 85.5%, 82.8% and 76.8% patients in FP, IM and DM clinics respectively. A1C was controlled (<7%) in 38.9, 43.3, 28.8% of patients in the FP, IM and DM clinics, respectively (p = 0.034). LDL was controlled (<100 mg/dl or 2.586 mmol/l) in 71.8, 64.9, 64% of patients in the FP, IM and DM clinics, respectively. MA was controlled (<30 mg/gm creatinine) in 60.3%, 51.5% and 60% patients in FP, IM and DM clinics respectively (P = 0.032). BP was controlled (<130/80) in 59.5, 67.2 and 52.8% patients in the FP, IM and DM clinics, respectively. CONCLUSION: Testing rates for A1C, LDL, and MA were high, in both subspecialty and primary care clinics. However, the degree of control was not optimal. Significantly fewer patients in the DM clinic had A1c <7%, the cause of which may be multifactorial.

Transgelin: a potentially useful diagnostic marker differentially expressed in triple-negative and non-triple-negative breast cancers.

Triple negative (TN) (estrogen receptor [ER], progesterone receptor [PR] and HER2-) are highly aggressive, rapidly growing, hormone-unresponsive tumors diagnosed at later stage that affect younger women with shorter overall survival. Most TN tumors are of the basal type. For the remainder, identification of target markers for effective treatment strategies remains a challenge. Transgelin (TGLN) is a 22-kd actin-binding protein of the calponin family. It is one of the earliest markers of smooth muscle differentiation. TGLN has been shown to have important biologic activities including regulating muscle fiber contractility, cell migration, and tumor suppression. We examined TGLN expression in the different molecular subtypes of breast cancer. TGLN expression was examined as a function of tumor size, grade, histologic type, lymph node status, patients' age and overall survival, ER, PR, HER2, and Ki-67 in 101 tumors that included 35 luminal A, 28 luminal B, 4 HER2, and 34 TN types. TGLN positivity (defined as 2+ or 3+) was associated with more aggressive tumors (10% of grade I/II tumors were TGLN+ versus 53% of grade III tumors; P < .001), high Ki-67 count, and low ER and PR expression (P < .001) but not with tumor size, age, or lymph node metastasis. TN (n = 34) tumors were 7.7 times more likely to be TGLN+ than non-TN (n = 67) tumors (77% versus 10%, respectively; P < .001). TGLN may be an excellent diagnostic marker of TN tumors and could be useful in stratification of patients. TGLN may also prove a potential target for future treatment strategies.

High-Risk Microgranular Acute Promyelocytic Leukemia with a Five-Way Complex Translocation Involving PML-RARA.

Acute promyelocytic leukemia (APL) is classically characterized by chromosomal translocation (15;17), resulting in the PML-RARA fusion protein leading to disease. Here, we present a case of a 50-year-old man who presented with signs and symptoms of acute leukemia with concern for APL. Therapy was immediately initiated with all-trans retinoic acid. The morphology of his leukemic blasts was consistent with the hypogranular variant of APL. Subsequent FISH and cytogenetic analysis revealed a unique translocation involving five chromosomal regions: 9q34, 17q21, 15q24, 12q13, and 15q26.1. Molecular testing demonstrated PML/RARA fusion transcripts. Treatment with conventional chemotherapy was added and he went into a complete remission. Given his elevated white blood cell count at presentation, intrathecal chemotherapy for central nervous system prophylaxis was also given. The patient remains on maintenance therapy and remains in remission. This is the first such report of a 5-way chromosomal translocation leading to APL. Similar to APL with chromosomal translocations other than classical t(15;17) which result in the typical PML-RARA fusion, our patient responded promptly to an ATRA-containing regimen and remains in complete remission.

Community gastroenterologists can learn diminutive colon polyp histology characterization with narrow band imaging by a computer-based teaching module.

BACKGROUND AND AIM: The aim of the present study was to evaluate the impact of a computer-based teaching module on the performance of community gastroenterologists for characterization of diminutive polyps (≤5 mm) using narrow band imaging video clips. METHODS: Eighty videos were distributed in pre- and post-test DVD along with a 20-min audiovisual teaching presentation detailing endoscopic features differentiating adenomas from hyperplastic polyps using narrow band imaging. Each participant first reviewed pretest video clips and entered their responses for polyp histology and their confidence in diagnosis: high: ≥90% or low: <90%. Following this, they reviewed the teaching module and assessed the post-test videos. Performance characteristics were calculated for pre- and post-test videos by comparing predicted histology with actual histology. Fisher's exact test was used for analysis and the kappa statistic was calculated for interobserver agreement. RESULTS: Fifteen gastroenterologists in community practice completed the study. Sensitivity, specificity, accuracy and negative predictive value in characterization of polyp histology improved significantly post-test compared to pretest. In post-test, accuracy was 92% for high-confidence diagnoses and the proportion of these increased with training from 46% (pretest) to 64% (post-test); P < 0.001. Interobserver agreement for diagnosis improved from fair (kappa = 0.23) in pretest to moderate (kappa = 0.56) in post-test. CONCLUSIONS: A teaching module using video clips can be used to teach community gastroenterologists polyp histology characterization by narrow band imaging. Whether this translates into real-time high accuracy in polyp detection needs to be further evaluated.

Trainee participation and adenoma detection rates during screening colonoscopies.

GOAL: To evaluate whether participation of a gastroenterology trainee had an impact on adenoma detection rate (ADR) during screening colonoscopies performed with standard-definition colonoscopes (SD-C) versus high-definition colonoscopes (HD-C). BACKGROUND: ADR is an established quality indicator of colonoscopy and efforts to improve ADR have led to technological advancements including HD-C that have a greater angle of view and produce an image with higher pixel density compared with SD-C. Moreover, other factors like trainee participation have been shown to improve adenoma detection. METHODS: This is a retrospective review of screening colonoscopies performed during 2 different time periods by 4 experienced endoscopists with or without trainee participation. There are 2 arms of this study, based on whether screening colonoscopy was performed using SD-C or HD-C. Detailed review of endoscopy and histopathologic reports was conducted. Statistical analysis was performed and odds ratio and incidence rate ratios were calculated to adjust for numerous factors. RESULTS: No significant differences were seen with trainee participation in the SD-C arm of the study. In the HD-C arm, the total number, and the proportion of subjects with: adenomas, diminutive adenomas, and right-sided adenomas were significantly higher with trainee participation. CONCLUSIONS: Trainee participation significantly improved the overall adenoma detection, specifically diminutive adenoma and right-sided adenoma detection, but only when colonoscopies were performed with HD-C. The improved image quality and resolution provided by HD-C, coupled with enhanced visual scanning an additional pair of eyes provides, may account for the differential impact of trainee participation on ADR.