Changes in Gastric Pathology after H. pylori Treatment in Community-Driven Research Aimed at Gastric Cancer Prevention.

Community-driven projects have characterized Helicobacter pylori (Hp) infection in Indigenous communities in the Northwest Territories (NT) and Yukon (YT), Canada. These projects address concerns about the frequent diagnosis of Hp infection among community members and its relation to gastric cancer deaths, perceived to occur with alarming frequency in this region. Projects included breath-test screening for Hp infection, gastroscopy with gastric biopsies, and treatment to eliminate Hp infection. Previous project results showed a high prevalence of stomach pathologies associated with increased cancer risk among Hp-positive participants at baseline. This analysis describes changes in precancerous gastric pathologies in project participants who had gastroscopy before baseline treatment during 2008-2013 and again in 2017. Throughout the study period, the same pathologist graded Hp density, active gastritis, chronic gastritis, atrophic gastritis, and intestinal metaplasia using the updated Sydney System. Of 310 participants from three communities with baseline pathology data, 69 had follow-up pathology data. Relative to baseline, the prevalence of Hp infection and precancerous gastric pathology was substantially lower at follow-up; most participants who were Hp-positive at baseline and Hp-negative at follow-up had reduced severity of active, chronic, and/or atrophic gastritis at follow-up. Though follow-up numbers are small, these results yield evidence that successful Hp treatment has the potential to reduce the risk of gastric cancer in Arctic Indigenous communities.

Acute hepatitis following mRNA BNT162b2 COVID-19 vaccination.

BACKGROUND: Widespread administration of COVID-19 vaccinations have led to reports of rare but potentially serious side effects. METHODS: We present two cases of acute hepatitis following mRNA BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccination. RESULTS: A 25-year-old male presented to hospital with progressive jaundice 5 days following his second dose of Comirnaty. Initial bloodwork revealed severe hepatocellular enzyme elevation and conjugated hyperbilirubinemia with preserved INR. Extensive serologic workup was negative, with normal imaging. Percutaneous liver biopsy was performed and revealed acute cholestatic hepatitis possibly related to drug-induced liver injury. He was started on prednisone 40 mg daily with good initial response but had a second flare; a biopsy was repeated which showed near-identical findings. Steroids were discontinued given non-response and the patient had gradual near complete resolution of liver enzymes and hyperbilirubinemia. A 32-year-old male presented with a 4-week history of nausea followed by progressive choluria, jaundice, and pruritis. He received his second dose of Comirnaty vaccination two weeks prior to presentation. Initial bloodwork showed mixed enzyme elevation with hyperbilirubinemia. Serological workup and imaging were unrevealing. He underwent liver biopsy which showed severe intrahepatic cholestasis, with drug-induced liver injury being suggested as most likely cause. His course was self-limited with resolution of serological abnormalities and symptoms. CONCLUSIONS: While overwhelmingly safe on a population level, our case series illustrate two cases of acute icteric hepatitis following mRNA BNT162b2 vaccination. Clinicians should be aware of this association with hepatic inflammation and consider vaccine history an important component of evaluating patients with acute liver injury.

Epidemiological and Clinical Characteristics of Alveolar Echinococcosis: An Emerging Infectious Disease in Alberta, Canada.

Human alveolar echinococcosis (AE) is a zoonotic cestode infection which is usually fatal in the absence of treatment. Treatment involves major surgery or indefinite antiparasitic therapy. The incidence is rising in Europe and Asia, with an increased risk observed in immunocompromised individuals. Previously, AE acquisition in North America was extremely rare, except for one remote Alaskan Island. Recent studies have demonstrated a new European-like strain of Echinococcus multilocularis (Em) in wildlife and in human AE in western Canada. We report the experience of all AE patients diagnosed in Alberta. Each was diagnosed by histopathology, serology, and PCR-confirmed by a reference laboratory. Seventeen cases of human AE, aged 19-78 years, nine females, were diagnosed between 2013 and 2020: all definitely or probably acquired in Alberta. Six lived in urban areas, and 14 had kept dogs. In eight, the lesions were found incidentally on abdominal imaging performed for other indications. Six were immunocompromised to varying degrees. Six were first diagnosed at surgery. All have been recommended benzimidazole therapy. One died of surgical complications. Clinicians should be aware of this diagnostic possibility in patients presenting with focal nonmalignant hepatic mass lesions. Greater urbanization of coyotes, the predominant definitive host of Em in Alberta, and growing numbers of immune suppressed individuals in the human population may lead to increasing recognition of AE in North America.

Community-driven research in the canadian arctic: dietary exposure to methylmercury and gastric health outcomes.

Indigenous Arctic Canadians have a higher prevalence of gastric neoplasms relative to North Americans of European ancestry. We investigated the hypothesis that low-dose methylmercury exposure from eating fish/whale increases the risk of gastric cancer in Arctic communities. We used intermediate endpoints from an established model of gastric carcinogenesis: intestinal metaplasia, atrophy, and severe chronic gastritis. During 2008-2012, we obtained gastric biopsies from participants of community-driven projects in 3 communities. In 2016, we collected hair samples to measure methylmercury levels and interviewed them about diet. In cross-sectional analysis, logistic regression estimated odds ratios for the estimated effect of hair-methylmercury concentration on the prevalence of each pathology outcome stratified by selenium intake. Among 80 participants, prevalence of intestinal metaplasia, atrophy and severe chronic gastritis was 17, 29 and 38%, respectively. Adjusted Odds of severe chronic gastritis and atrophy were highest at hair-methylmercury concentrations ≥1µg/g when estimated selenium intake was 0, and approached 0 for all methylmercury levels as estimated selenium intake increased. Gastric pathology increased with methylmercury exposure when selenium intake was low. Though limited by small numbers, these findings suggest selenium ingested by eating fish/whale may counter harmful effects of methylmercury exposure in Arctic populations.

Case report: progressive familial intrahepatic cholestasis type 3 with compound heterozygous ABCB4 variants diagnosed 15 years after liver transplantation.

BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) type 3 is an autosomal recessive disorder arising from mutations in the ATP-binding cassette subfamily B member 4 (ABCB4) gene. This gene encodes multidrug resistance protein-3 (MDR3) that acts as a hepatocanalicular floppase that transports phosphatidylcholine from the inner to the outer canalicular membrane. In the absence of phosphatidylcholine, the detergent activity of bile salts is amplified and this leads to cholangiopathy, bile duct loss and biliary cirrhosis. Patients usually present in infancy or childhood and often progress to end-stage liver disease before adulthood. CASE PRESENTATION: We report a 32-year-old female who required cadaveric liver transplantation at the age of 17 for cryptogenic cirrhosis. When the patient developed chronic ductopenia in the allograft 15 years later, we hypothesized that the patient's original disease was due to a deficiency of a biliary transport protein and the ductopenia could be explained by an autoimmune response to neoantigen that was not previously encountered by the immune system. We therefore performed genetic analyses and immunohistochemistry of the native liver, which led to a diagnosis of PFIC3. However, there was no evidence of humoral immune response to the MDR3 and therefore, we assumed that the ductopenia observed in the allograft was likely due to chronic rejection rather than autoimmune disease in the allograft. CONCLUSIONS: Teenage patients referred for liver transplantation with cryptogenic liver disease should undergo work up for PFIC3. An accurate diagnosis of PFIC 3 is key for optimal management, therapeutic intervention, and avoidance of complications before the onset of end-stage liver disease.

Patterns of fish and whale consumption in relation to methylmercury in hair among residents of Western Canadian Arctic communities.

BACKGROUND: Methylmercury contamination of the environment represents a substantial environmental health concern. Human exposure to methylmercury occurs primarily through consumption of fish and marine mammals. Heavily exposed subgroups include sport or subsistence fishers residing in Arctic communities. We aimed to estimate the association of fish/whale consumption patterns of Canadian Arctic subsistence fishers with the internal dose of methylmercury as measured in hair. METHODS: This research was conducted within ongoing community projects led by the CANHelp Working Group in Aklavik and Fort McPherson, Northwest Territories and Old Crow, Yukon. We interviewed each participant using a fish-focused food-frequency questionnaire during September-November 2016 and collected hair samples concurrently. Methylmercury was measured in the full-length of each hair sample using gas chromatography inductively-coupled plasma-mass spectrometry. Multivariable linear regression estimated beta-coefficients and 95% confidence intervals (CIs) for the effect of fish/whale consumption on hair-methylmercury concentrations. RESULTS: Among 101 participants who provided hair samples and diet data, the mean number of fish/whale species eaten was 3.5 (SD:1.9). The mean hair-methylmercury concentration was 0.60 µg/g (SD:0.47). Fish/whale consumption was positively associated with hair-methylmercury concentration, after adjusting for sex, hair length and use of permanent hair treatments. Hair-methylmercury concentrations among participants who consumed the most fish/whale in each season ranged from 0.30-0.50 µg/g higher than those who consumed < 1 meal/week. CONCLUSIONS: In this population of Canadian Arctic subsistence fishers, hair-methylmercury concentration increased with fish/whale consumption, but the maximum concentrations were below Health Canada's 6.0 µg/g threshold for safe exposure.

Phlebosclerotic Colitis - An Enigma Among Ischemic Colitis.

Phlebosclerotic Colitis is a rare, potentially life-threatening condition of unclear etio-pathogenesis seen almost exclusively in Asians and people of Asian descent. The condition predominantly affects the right hemicolon and imaging plays a crucial role in its diagnosis. Here we report the only second documented case of phlebosclerotic colitis in North America in a 60-year-old Canadian resident of Vietnamese descent with a history of consuming herbal medication (sanshishi) in soup for 2-3 decades.

Burden of disease from Helicobacter pylori infection in western Canadian Arctic communities.

BACKGROUND: Indigenous communities across the circumpolar north have elevated H. pylori (Hp) prevalence and stomach cancer incidence. We aimed to describe the Hp-associated disease burden among western Canadian Arctic participants in community-driven projects that address concerns about health risks from Hp infection. METHODS: During 2008-2013, participants underwent Hp screening by urea breath test and gastroscopy with gastric biopsies. We estimated Hp prevalence and prevalence by Hp status of endoscopic and histopathologic diagnoses. RESULTS: Among 878 participants with Hp status data, Hp prevalence was: 62% overall; 66% in 740 Indigenous participants; 22% in 77 non-Indigenous participants (61 participants did not disclose ethnicity); 45% at 0-14 years old, 69% at 15-34 years old, and 61% at 35-96 years old. Among 309 participants examined endoscopically, visible mucosal lesions were more frequent in the stomach than the duodenum: the gastric to duodenal ratio was 2 for inflammation, 8 for erosions, and 3 for ulcers. Pathological examination in 308 participants with gastric biopsies revealed normal gastric mucosa in 1 of 224 Hp-positive participants and 77% (65/84) of Hp-negative participants with sharp contrasts in the prevalence of abnormalities between Hp-positive and Hp-negative participants, respectively: moderate-severe active gastritis in 50 and 0%; moderate-severe chronic gastritis in 91 and 1%; atrophic gastritis in 43 and 0%; intestinal metaplasia in 17 and 5%. CONCLUSIONS: The observed pattern of disease is consistent with increased risk of stomach cancer and reflects substantial inequity in the Hp-associated disease burden in western Arctic Canadian hamlets relative to most North American settings. This research adds to evidence that demonstrates the need for interventions aimed at reducing health risks from Hp infection in Indigenous Arctic communities.

Malignant transformation of hepatic adenoma complicated by rupture and hemorrhage: An extremely rare clinical entity.

Hepatic adenomas (HAs) are rare benign tumors of the liver and comprise 2% of all liver tumors with an annual incidence of 3-4/100,000 per year in Europe and North America. These tumors may be clinically silent or present with abdominal pain. Although rare, the most important complications associated with this tumor is haemorrhage and malignant transformation to hepatocellular carcinoma. The reported risk of malignant transformation is believed to be 4.2%. We present an extremely rare case report of a young woman on the oral contraceptive pill (OCP) with malignant transformation of a hepatic adenoma complicated additionally by tumor rupture and intraperitoneal bleed. This article therefore highlights the need to carefully evaluate any liver lesion in a young female on the OCP to be a possible adenoma and if confirmed to be so, to consider the potential risks associated with it as well as the need for follow-up imaging in order to avoid life threatening complications.

Acute Liver Failure from Tumor Necrosis Factor-α Antagonists: Report of Four Cases and Literature Review.

BACKGROUND: Tumor necrosis factor-α antagonists (anti-TNF-α) have been associated with drug-induced liver injury. However, cases of anti-TNF-α-associated acute liver failure have only been rarely reported. AIMS: To identify cases of anti-TNF-α-associated acute liver failure and evaluate patterns of liver injury and common characteristics to the cases. METHODS: The United States Acute Liver Failure Study Group database was searched from 1998 to 2014. Four subjects were identified. A PubMed search for articles that reported anti-TNF-α-associated acute liver failure identified five additional cases. RESULTS: The majority of individuals affected were female (eight of nine cases). Age of individual ranged from 20 to 53 years. The most common anti-TNF-α agent associated with acute liver failure was infliximab (n = 8). The latency between initial drug exposure and acute liver failure ranged from 3 days to over a year. Of the nine cases, six required emergency LT. Liver biopsy was obtained in seven cases with a preponderance toward cholestatic-hepatitic features; none showed clear autoimmune features. CONCLUSIONS: Anti-TNF-α-associated acute liver failure displays somewhat different characteristics compared with anti-TNF-α-induced drug-induced liver injury. Infliximab was implicated in the majority of cases. Cholestatic-hepatitic features were frequently found on pre-transplant and explant histology.

Insulinoma or non-insulinoma pancreatogenous hypoglycemia? A diagnostic dilemma.

Insulinoma is the most common cause of endogenous hyperinsulinemic hypoglycemia in adults. An alternate etiology, non-insulinoma pancreatogenous hypoglycemia (NIPH), is rare. Clinically, NIPH is characterized by postprandial hyperinsulinemic hypoglycemia, negative 72-h fasts, negative preoperative localization studies for insulinoma and positive selective arterial calcium infusion tests. Histologically, diffuse islet hyperplasia with increased number and size of islet cells is present and confirms the diagnosis. Differentiating NIPH from occult insulinoma preoperatively is challenging. Partial pancreatectomy is the procedure of choice; however, recurrence of symptoms, although less debilitating, occurs commonly. Medical management with diazoxide, verapamil and octreotide can be used for persistent symptoms. Ultimately, near-total or total pancreatectomy may be necessary. We report a case of a 67-year-old male with hypoglycemia in whom preoperative workup, including computerized tomography abdomen, suggested insulinoma, but whose final diagnosis on pathology was NIPH instead.

Case 235: Hepatic Adenomatosis Due to Inflammatory Adenomas.

History An asymptomatic 33-year-old woman was referred to the Hepatology Department in 2013 for work-up of indeterminate multifocal liver masses. These lesions were discovered incidentally at multiphase contrast material-enhanced multidetector computed tomography (CT) performed in 2004 to investigate right lower quadrant pain. Imaging surveillance at sporadic intervals revealed slow progressive growth of the lesions over time; however, the number of lesions remained constant. There was no history of cancer, nor were there predisposing factors for chronic liver disease or cirrhosis. The patient had a history of menorrhagia, which was managed with oral contraceptive use for 20 years; this was stopped in 2013 after hysterectomy. The patient's γ-glutamyl transferase (77 U/L [1.28 µkat/L]; normal level, <55 U/L [<0.92 µkat/L]) and C-reactive protein (97.1 mg/L [924.8 nmol/L]; normal level, <8 mg/L [<76.2 nmol/L]]) levels were chronically elevated at serum testing. In 2013, 9 years after the initial CT examination, magnetic resonance (MR) imaging with gadoxetic acid (Primovist; Bayer Healthcare, Whippany, NJ) was performed. Finally, ultrasonography (US)-guided biopsy of one of the lesions (in segment 5/6) was performed a year after MR imaging.

Review of renal cell carcinoma and its common subtypes in radiology.

Representing 2%-3% of adult cancers, renal cell carcinoma (RCC) accounts for 90% of renal malignancies and is the most lethal neoplasm of the urologic system. Over the last 65 years, the incidence of RCC has increased at a rate of 2% per year. The increased incidence is at least partly due to improved tumor detection secondary to greater availability of high-resolution cross-sectional imaging modalities over the last few decades. Most RCCs are asymptomatic at discovery and are detected as unexpected findings on imaging performed for unrelated clinical indications. The 2004 World Health Organization Classification of adult renal tumors stratifies RCC into several distinct histologic subtypes of which clear cell, papillary and chromophobe tumors account for 70%, 10%-15%, and 5%, respectively. Knowledge of the RCC subtype is important because the various subtypes are associated with different biologic behavior, prognosis and treatment options. Furthermore, the common RCC subtypes can often be discriminated non-invasively based on gross morphologic imaging appearances, signal intensity on T2-weighted magnetic resonance images, and the degree of tumor enhancement on dynamic contrast-enhanced computed tomography or magnetic resonance imaging examinations. In this article, we review the incidence and survival data, risk factors, clinical and biochemical findings, imaging findings, staging, differential diagnosis, management options and post-treatment follow-up of RCC, with attention focused on the common subtypes.

Neuroinflammation Preceding and Accompanying Primary Central Nervous System Lymphoma: Case Study and Literature Review.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an aggressive lymphoma confined to the CNS. Although the pathogenesis of PCNSL in immunocompetent individuals remains unclear, there have been several case studies demonstrating the "sentinel" inflammatory lesions months before the manifestation of PCNSL. However, the pathologic relationship between the inflammatory lesions and subsequent PCNSL is still unknown. CASE DESCRIPTION: We present the case of a 44-year-old immunocompetent woman who developed several cerebral and cerebellar lesions on magnetic resonance imaging (MRI). A partial resection of the cerebellar contrast-enhancing lesion showed active inflammation with large destructive process but no evidence of B-cell lymphoma. Her disease was in a relapsing-remitting course for 28 months and progressed with new MRI findings of more contrast-enhancing lesions. She died at 33 months after the initial presentation. Postmortem examination revealed B-cell PCNSL with extensive involvement but sparing a few brain regions, including the previous resection site, with only an inflammatory destructive process. CONCLUSIONS: PCNSL may be preceded and accompanied by an inflammatory process that is pathologically distinct from PCNSL. Our case study, in combination with a review of previously published similar cases, supports the hypothesis that the "sentinel" inflammatory lesions may be the first immune response against PCNSL.

Intra-abdominal desmoplastic small round cell tumour: staging and surveillance with 18F-FDG PET/CT following peritonectomy and HIPEC.

Intra-abdominal desmoplastic small round cell tumours are rare aggressive tumours of mesothelial origin with less than 60 cases reported in the literature. They are difficult to treat and the role of 18F-fludeoxyglucose positron emission tomography (PET)/CT scan in their management has not been established. A 41-year-old male presented with a 21-cm desmoplastic small round cell tumour and was managed with radiotherapy, surgery and chemotherapy, with each treatment monitored and guided by 18F-fludeoxyglucose PET/CT scan. We present the imaging findings of the serial PET/CT scans of this patient and their impact on management.

Multimodality Imaging Characteristics of the Common Renal Cell Carcinoma Subtypes: An Analysis of 544 Pathologically Proven Tumors.

OBJECTIVES: The objective of this study was to define the characteristic imaging appearances of the common renal cell carcinoma (RCC) subtypes. MATERIALS AND METHODS: The Institutional Review Board approval was obtained for this HIPAA-compliant retrospective study, and informed consent was waived. 520 patients (336 men, 184 women; age range, 22-88 years) underwent preoperative cross-sectional imaging of 544 RCCs from 2008 to 2013. The imaging appearances of the RCCs and clinical information were reviewed. Data analysis was performed using parametric and nonparametric statistics, descriptive statistics, and receiver operating characteristic analysis. RESULTS: The RCC subtypes showed significant differences (P < 0.001) in several imaging parameters such as tumor margins, tumor consistency, tumor homogeneity, the presence of a central stellate scar, T2 signal intensity, and the degree of tumor enhancement. Low T2 signal intensity on magnetic resonance imaging (MRI) allowed differentiation of papillary RCC from clear cell and chromophobe RCCs with 90.9% sensitivity and 93.1% specificity. A tumor-to-cortex ratio ≥1 on the corticomedullary phase had 98% specificity for clear cell RCC. CONCLUSION: The T2 signal intensity of the tumor on MRI and its degree of enhancement are useful imaging parameters for discriminating between the RCC subtypes while gross morphological findings offer additional value in RCC profiling.

Percutaneous transhepatic cholangioscopy for indeterminate biliary strictures using the SpyGlass system: a case series.

Peroral cholangioscopy is useful in differentiating benign from malignant biliary strictures. However, when conventional biliary access via endoscopic retrograde cholangiopancreatography (ERCP) fails, percutaneous transhepatic cholangioscopy (PTCS) via the SpyGlass cholangioscopy system can be used to achieve a diagnosis. Four patients with biliary strictures in whom conventional ERCP was not possible and percutaneous brushings were either nondiagnostic or unsatisfactory were investigated with PTCS. The technique of PTCS involves insertion of the SpyGlass cholangioscope through a percutaneous transhepatic sheath, placed just prior to the procedure, to visualize the stricture and obtain biopsies with the SpyBite forceps. On the basis of our early observations, we conclude that PTCS using the SpyGlass cholangioscopy system for the assessment of biliary strictures is feasible, safe, and provides high diagnostic accuracy.

Impact of combination antiretroviral therapy in the NOD.c3c4 mouse model of autoimmune biliary disease.

BACKGROUND & AIMS: The NOD.c3c4 mouse model develops autoimmune biliary disease characterized by spontaneous granulomatous cholangitis, antimitochondrial antibodies and liver failure. This model for primary biliary cirrhosis (PBC) has evidence of biliary infection with mouse mammary tumour virus (MMTV), suggesting that the virus may have a role in cholangitis development and progression of liver disease in this mouse model. We tested the hypothesis that MMTV infection is associated with cholangitis in the NOD.c3c4 mouse model by investigating whether antiretroviral therapy impacts on viral levels and liver disease. METHODS: NOD.c3c4 mice were treated with combination antiretroviral therapy. Response to treatment was studied by measuring MMTV RNA in the liver, liver enzyme levels in serum and liver histology using a modified Ishak score. RESULTS: Combination therapy with the reverse transcriptase inhibitors, tenofovir and emtricitabine, resulted in a significant reduction in serum liver enzyme levels, attenuation of cholangitis and decreased MMTV levels in the livers of NOD.c3c4 mice. Furthermore, treatment with the retroviral protease inhibitors, lopinavir and ritonavir, in addition to the reverse transcriptase inhibitors, resulted in further decrease in MMTV levels and attenuation of liver disease in this model. CONCLUSIONS: The attenuation of cholangitis with regimens containing the reverse transcriptase inhibitors, tenofovir and emtricitabine, and the protease inhibitors, lopinavir and ritonavir, suggests that retroviral infection may play a role in the development of cholangitis in this model.