Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision.

BACKGROUND: Hereditary adenomatous polyposis syndromes, including familial adenomatous polyposis and other rare adenomatous polyposis syndromes, increase the lifetime risk of colorectal and other cancers. METHODS: A team of 38 experts convened to update the 2008 European recommendations for the clinical management of patients with adenomatous polyposis syndromes. Additionally, other rare monogenic adenomatous polyposis syndromes were reviewed and added. Eighty-nine clinically relevant questions were answered after a systematic review of the existing literature with grading of the evidence according to Grading of Recommendations, Assessment, Development, and Evaluation methodology. Two levels of consensus were identified: consensus threshold (≥67% of voting guideline committee members voting either 'Strongly agree' or 'Agree' during the Delphi rounds) and high threshold (consensus ≥ 80%). RESULTS: One hundred and forty statements reached a high level of consensus concerning the management of hereditary adenomatous polyposis syndromes. CONCLUSION: These updated guidelines provide current, comprehensive, and evidence-based practical recommendations for the management of surveillance and treatment of familial adenomatous polyposis patients, encompassing additionally MUTYH-associated polyposis, gastric adenocarcinoma and proximal polyposis of the stomach and other recently identified polyposis syndromes based on pathogenic variants in other genes than APC or MUTYH. Due to the rarity of these diseases, patients should be managed at specialized centres.

Fibrosis-related transcriptome unveils a distinctive remodeling matrix pattern in penetrating ileal Crohn's disease.

BACKGROUND AND AIMS: Stricturing (B2) and penetrating (B3) ileal Crohn's disease have been reported to present similar levels of histopathological transmural fibrosis. This study aimed to compare the fibrosis-related transcriptomic profiles of penetrating and stricturing ileal Crohn's disease. METHODS: Using Nanostring technology and comparative bioinformatics, we analyzed the expression of 787 fibrosis-related genes in 36 ileal surgical specimens, 12 B2 and 24 B3, the latter including 12 cases with associated stricture(s) (B3s) and 12 without (B3o). Quality control of extracted RNA was performed according to Nanostring parameters and principal component analysis for the distribution analysis. For the selection of the differentially expressed genes a p-adjusted <0.05 and Fold Change ≤-1.5 or ≥ 1.5 was adopted. qPCR and immunohistochemistry analyses were used to validate selected differentially expressed genes. RESULTS: We included 34 patients with B2 and B3 phenotypes, balanced for age at diagnosis, age at surgery, gender, Crohn's disease localization, perianal disease and therapy. Inflammation and fibrosis histopathological scoring were similar in all cases. B2 and B3 groups showed a very good clustering regarding 30 significantly differentially expressed genes, all being remarkably upregulated in B3. More than half of these genes were involved in Crohn's disease fibrogenesis, while eight differentially expressed genes were so in other organs. The most significantly active biologic processes and pathways in penetrating disease were response to TGFßand matrix organization and degradation, as validated by immunohistochemistry. CONCLUSIONS: Despite the histopathological similarities in fibrosis between stricturing and penetrating ileal Crohn's disease, their fibrosis-related transcriptomic profiles are distinct. Penetrating disease exhibits a distinctive transcriptomic landscape related to enhanced matrix remodeling.

International consensus on the management of metastatic gastric cancer: step by step in the foggy landscape : Bertinoro Workshop, November 2022.

BACKGROUND: Many gastric cancer patients in Western countries are diagnosed as metastatic with a median overall survival of less than twelve months using standard chemotherapy. Innovative treatments, like targeted therapy or immunotherapy, have recently proved to ameliorate prognosis, but a general agreement on managing oligometastatic disease has yet to be achieved. An international multi-disciplinary workshop was held in Bertinoro, Italy, in November 2022 to verify whether achieving a consensus on at least some topics was possible. METHODS: A two-round Delphi process was carried out, where participants were asked to answer 32 multiple-choice questions about CT, laparoscopic staging and biomarkers, systemic treatment for different localization, role and indication of palliative care. Consensus was established with at least a 67% agreement. RESULTS: The assembly agreed to define oligometastases as a "dynamic" disease which either regresses or remains stable in response to systemic treatment. In addition, the definition of oligometastases was restricted to the following sites: para-aortic nodal stations, liver, lung, and peritoneum, excluding bones. In detail, the following conditions should be considered as oligometastases: involvement of para-aortic stations, in particular 16a2 or 16b1; up to three technically resectable liver metastases; three unilateral or two bilateral lung metastases; peritoneal carcinomatosis with PCI ≤ 6. No consensus was achieved on how to classify positive cytology, which was considered as oligometastatic by 55% of participants only if converted to negative after chemotherapy. CONCLUSION: As assessed at the time of diagnosis, surgical treatment of oligometastases should aim at R0 curativity on the entire disease volume, including both the primary tumor and its metastases. Conversion surgery was defined as surgery on the residual volume of disease, which was initially not resectable for technical and/or oncological reasons but nevertheless responded to first-line treatment.

HER2 and PD-L1 Expression in Gastric and Gastroesophageal Junction Cancer: Insights for Combinatorial Targeting Approaches.

Gastric and gastroesophageal junction adenocarcinomas (GA/GEJA) are associated with a poor prognosis, primarily due to late disease diagnosis. Human Epidermal Growth Factor Receptor 2 (HER2) overexpression and programmed death-ligand 1 (PD-L1) expression are important biomarkers for treatment selection in locally advanced unresectable and metastatic GA/GEJA, and there is increasing interest in their role in earlier stages of disease. In this study, we aimed to evaluate HER2 and PD-L1 expression in a curative-intent GA/GEJA cohort to describe their expression patterns and analyze the association between HER2 expression and clinicopathological features. HER2 expression was evaluated in surgical and endoscopic submucosal dissection tumor samples, and PD-L1 was evaluated in HER2-positive cases. The clinical cohort included 107 patients, with 8.4% testing positive for HER2 (seven of whom also exhibited a PD-L1 combined positive score of ≥1. HER2 status was not significantly associated with survival outcomes. A pathologist-guided, region-specific analysis revealed that PD-L1 expression rarely overlaps with HER2-positive tumor areas. While the therapeutic implications of these observations remain unknown, these findings suggest that combination strategies targeting HER2 and PD-L1 might be directed toward distinct tumor subclones. The herein disclosed region-specific biomarker expression patterns may have important therapeutic and prognostic impacts, warranting further evaluation.

Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs. METHODS: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment. RESULTS: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed. CONCLUSION: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.

Disseminated Mycobacterium bovis Infection: A Rare Complication of Bacillus Calmette-Guérin Immunotherapy.

Intravesical instillation of bacillus Calmette-Guérin (BCG) is a crucial adjunctive therapy in the treatment of bladder carcinoma. Its systemic complications are rare but include disseminated Mycobacterium bovis (M. bovis) infections, the diagnosis of which is a challenging task that requires keen clinical awareness. We report the case of an adult male treated with BCG who presented with fever, nonspecific constitutional symptoms, hepatic cytolysis, and cholestasis. After a detailed workup, the diagnosis was made of disseminated M. bovis infection with hepatic, pulmonary, renal, and ureteral involvement. Prompt anti-tuberculosis treatment resulted in clinical and analytical improvement. This case highlights the importance of early recognition of this serious complication in patients with BCG exposure, as well as the difficulty in confirming the diagnosis for proper treatment.

Clinical Features of Gastric Signet Ring Cell Cancer: Results from a Systematic Review and Meta-Analysis.

BACKGROUND: Conflicting results about the prognostic relevance of signet ring cell histology in gastric cancer have been reported. We aimed to perform a meta-analysis focusing on the clinicopathological features and prognosis of this subgroup of cancer compared with other histologies. METHODS: A systematic literature search in the PubMed database was conducted, including all publications up to 1 October 2021. A meta-analysis comparing the results of the studies was performed. RESULTS: A total of 2062 studies referring to gastric cancer with signet ring cell histology were identified, of which 262 studies reported on its relationship with clinical information. Of these, 74 were suitable to be included in the meta-analysis. A slightly lower risk of developing nodal metastases in signet ring cell tumours compared to other histotypes was found (especially to undifferentiated/poorly differentiated/mucinous and mixed histotypes); the lower risk was more evident in early and slightly increased in advanced gastric cancer. Survival tended to be better in early stage signet ring cell cancer compared to other histotypes; no differences were shown in advanced stages, and survival was poorer in metastatic patients. In the subgroup analysis, survival in signet ring cell cancer was slightly worse compared to non-signet ring cell cancer and differentiated/well-to-moderately differentiated adenocarcinoma. CONCLUSIONS: Most of the conflicting results in signet ring cell gastric cancer literature could be derived from the lack of standardisation in their classification and the comparison with the different subtypes of gastric cancer. There is a critical need to strive for a standardised classification system for gastric cancer, fostering clarity and coherence in the forthcoming research and clinical applications.

The ECM and tissue architecture are major determinants of early invasion mediated by E-cadherin dysfunction.

Germline mutations of E-cadherin cause Hereditary Diffuse Gastric Cancer (HDGC), a highly invasive cancer syndrome characterised by the occurrence of diffuse-type gastric carcinoma and lobular breast cancer. In this disease, E-cadherin-defective cells are detected invading the adjacent stroma since very early stages. Although E-cadherin loss is well established as a triggering event, other determinants of the invasive process persist largely unknown. Herein, we develop an experimental strategy that comprises in vitro extrusion assays using E-cadherin mutants associated to HDGC, as well as mathematical models epitomising epithelial dynamics and its interaction with the extracellular matrix (ECM). In vitro, we verify that E-cadherin dysfunctional cells detach from the epithelial monolayer and extrude basally into the ECM. Through phase-field modelling we demonstrate that, aside from loss of cell-cell adhesion, increased ECM attachment further raises basal extrusion efficiency. Importantly, by combining phase-field and vertex model simulations, we show that the cylindrical structure of gastric glands strongly promotes the cell's invasive ability. Moreover, we validate our findings using a dissipative particle dynamics simulation of epithelial extrusion. Overall, we provide the first evidence that cancer cell invasion is the outcome of defective cell-cell linkages, abnormal interplay with the ECM, and a favourable 3D tissue structure.

Gastric polyps in Familial Adenomatous Polyposis Portuguese patients: the first Western cohort with Asian features.

INTRODUCTION: Chronic atrophic gastritis may contribute to gastric polyps (GP) phenotype in familial adenomatous polyposis (FAP). Considering the high prevalence of Helicobacter-pylori (HP) infection in Portugal, we aim to characterise GP in a series of Portuguese patients. METHODS: In a retrospectively-selected series of 53 FAP patients, clinical data and histopathological features of GP and background gastric mucosa were studied. SPSS (27.0) was used for statistical analysis. RESULTS: Thirteen patients (24.5%) developed fundic gland polyps (FGP), seven (13.2%) gastric adenomas (GA) and ten (18.9%) both FGP and GA. Out of 100 GP, four were hyperplastic polyps, 58 FGP (24 with dysplasia), 35 intestinal-type GA (intGA) and three foveolar-type GA (fovGA). IntGA were larger (60% >7mm, p=0.03), occurred predominantly in the distal stomach (66.7%, p=0.024), in patients harbouring gastric intestinal metaplasia (IM) (86.7%, p<0.001) and duodenal adenomas (86.7%, p<0.001) Conclusion: This is the first Western series showing high prevalence of intGA in FAP patients, comparable to Asian cohorts. HP infection and chronic atrophic gastritis/intestinal metaplasia are likely responsible for this difference, with risk of neoplastic transformation and management implications. Biopsy/excision of GP >7mm, in the distal stomach, and in patients harbouring gastric intestinal metaplasia/duodenal adenomas should be considered.

Predicting residual neoplasia after a non-curative gastric ESD: validation and modification of the eCura system in the Western setting: the W-eCura score.

OBJECTIVE: To evaluate the risk factors for lymph node metastasis (LNM) after a non-curative (NC) gastric endoscopic submucosal dissection (ESD) and to validate and eventually refine the eCura scoring system in the Western setting. Also, to assess the rate and risk factors for parietal residual disease. DESIGN: Retrospective multicentre multinational study of prospectively collected registries from 19 Western centres. Patients who had been submitted to surgery or had at least one follow-up endoscopy were included. The eCura system was applied to assess its accuracy in the Western setting, and a modified version was created according to the results (W-eCura score). The discriminative capacities of the eCura and W-eCura scores to predict LNM were assessed and compared. RESULTS: A total of 314 NC gastric ESDs were analysed (72% high-risk resection (HRR); 28% local-risk resection). Among HRR patients submitted to surgery, 25% had parietal disease and 15% had LNM in the surgical specimen. The risk of LNM was significantly different across the eCura groups (areas under the receiver operating characteristic curve (AUC-ROC) of 0.900 (95% CI 0.852 to 0.949)). The AUC-ROC of the W-eCura for LNM (0.916, 95% CI 0.870 to 0.961; p=0.012) was significantly higher compared with the original eCura. Positive vertical margin, lymphatic invasion and younger age were associated with a higher risk of parietal residual lesion in the surgical specimen. CONCLUSION: The eCura scoring system may be applied in Western countries to stratify the risk of LNM after a gastric HRR. A new score is proposed that may further decrease the number of unnecessary surgeries.

Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders beyond Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic Gastrointestinal Disorders beyond Eosinophilic Esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs. METHODS: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment. RESULTS: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed. CONCLUSION: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.

Performance of Immunohistochemical and Molecular Methods in Detecting Microsatellite Instability in Gastric Cancer: A Multicenter Study.

INTRODUCTION: Microsatellite instability (MSI) is an important prognostic molecular biomarker for gastric cancer (GC). MSI status may be detected by immunohistochemistry (IHC) for mismatch repair (MMR) proteins and polymerase chain reaction (PCR). Idylla™ MSI assay has not been validated for GC but may prove to be a valid alternative. METHODS: In a series of 140 GC cases, MSI status was evaluated by IHC for MLH1, PMS2, MSH2, and MSH6; gold-standard pentaplex PCR panel (PPP) (BAT-25, BAT-26, NR-21, NR-24, and NR-27); and Idylla. Statistical analysis was performed using SPSS 27.0. RESULTS: PPP identified 102 microsatellite stable (MSS) cases and 38 MSI-high cases. Only 3 cases showed discordant results. Compared with PPP, the sensitivity was 100% for IHC and 94.7% for Idylla. Specificity was 99% for IHC and 100% for Idylla. MLH1 IHC alone showed sensitivity and specificity of 97.4% and 98.0%, respectively. IHC identified three indeterminate cases; all were MSS according to PPP and Idylla. CONCLUSION: IHC for MMR proteins represents an optimal screening tool for MSI status in GC. If resources are limited, isolated MLH1 evaluation may constitute a valuable option for preliminary screening. Idylla may help detect rare MSS cases with MMR-loss and define MSI status in indeterminate cases.

Role of Endoscopic Biopsies and Morphologic Features in Predicting Microsatellite Instability Status in Gastric Cancer: A Multicenter Comparative Study of Endoscopic Biopsies and Surgical Specimens.

Evaluation of mismatch repair (MMR) protein and microsatellite instability (MSI) status plays a pivotal role in the management of gastric cancer (GC) patients. In this study, we aimed to evaluate the accuracy of gastric endoscopic biopsies (EBs) in predicting MMR/MSI status and to uncover histopathologic features associated with MSI. A multicentric series of 140 GCs was collected retrospectively, in which EB and matched surgical specimens (SSs) were available. Laurén and WHO classifications were applied and detailed morphologic characterization was performed. EB/SS were analyzed by immunohistochemistry (IHC) for MMR status and by multiplex polymerase chain reaction (mPCR) for MSI status. IHC allowed accurate evaluation of MMR status in EB (sensitivity: 97.3%; specificity: 98.0%) and high concordance rates between EB and SS (Cohen κ=94.5%). By contrast, mPCR (Idylla MSI Test) showed lower sensitivity in evaluating MSI status (91.3% vs. 97.3%), while maintaining maximal specificity (100.0%). These results suggest a role of IHC as a screening method for MMR status in EB and the use of mPCR as a confirmatory test. Although Laurén/WHO classifications were not able to discriminate GC cases with MSI, we identified specific histopathologic features that are significantly associated with MMR/MSI status in GC, despite the morphologic heterogeneity of GC cases harboring this molecular phenotype. In SS, these features included the presence of mucinous and/or solid components ( P =0.034 and <0.001) and the presence of neutrophil-rich stroma, distant from tumor ulceration/perforation ( P <0.001). In EB, both solid areas and extracellular mucin lakes were also discriminating features for the identification of MSI-high cases ( P =0.002 and 0.045).

3D Chromatin Architecture Re-Wiring at the CDH3/CDH1 Loci Contributes to E-Cadherin to P-Cadherin Expression Switch in Gastric Cancer.

Cadherins are cell-cell adhesion molecules, fundamental for cell architecture and polarity. E-cadherin to P-cadherin switch can rescue adherens junctions in epithelial tumours. Herein, we disclose a mechanism for E-cadherin to P-cadherin switch in gastric cancers. CDH1 and CDH3 mRNA expression was obtained from 42 gastric tumours' RNA-seq data. CRISPR-Cas9 was used to knock out CDH1 and a putative regulatory element. CDH1-depleted and parental cells were submitted to proteomics and enrichment GO terms analysis; ATAC-seq/4C-seq with a CDH1 promoter viewpoint to assess chromatin accessibility and conformation; and RT-PCR/flow cytometry to assess CDH1/E-cadherin and CDH3/P-cadherin expression. In 42% of gastric tumours analysed, CDH1 to CDH3 switch was observed. CDH1 knockout triggered CDH1/E-cadherin complete loss and CDH3/P-cadherin expression increase at plasma membrane. This switch, likely rescuing adherens junctions, increased cell migration/proliferation, commonly observed in aggressive tumours. E- to P-cadherin switch accompanied increased CDH1 promoter interactions with CDH3-eQTL, absent in normal stomach and parental cells. CDH3-eQTL deletion promotes CDH3/CDH1 reduced expression. These data provide evidence that loss of CDH1/E-cadherin expression alters the CDH3 locus chromatin conformation, allowing a CDH1 promoter interaction with a CDH3-eQTL, and promoting CDH3/P-cadherin expression. These data highlight a novel mechanism triggering E- to P-cadherin switch in gastric cancer.

Autoimmune hepatitis and eosinophilia: A rare case report.

BACKGROUND: Autoimmune hepatitis consists of a chronic liver disease whose etiology is unknown. It is comprised of relevant immunological aspects and of immune-mediated liver injury. Eosinophilia may be a considerable feature, particularly happening in male patients. CASE SUMMARY: We report here a Crohn´s disease patient presenting with de novo hypergammaglobulinemia, circulating autoantibodies and elevated transaminase levels. He also had significant peripheral eosinophilia and elevated immunoglobulin E levels at diagnosis. The pathology findings from liver biopsy were compatible with autoimmune hepatitis with eosinophilic infiltration. CONCLUSION: This is the first report of autoimmune hepatitis with exuberant eosinophilic infiltration in the liver and bone marrow, described in a patient with Crohn's disease.

Engaging European society at the forefront of cancer research and care: How discussions at the 5th Gago Conference on European Science policy led to the Heidelberg Manifesto

European cancer research stakeholders met in October 2022 in Heidelberg, Germany, at the 5th Gago conference on European Cancer Policy, to discuss the current cancer research and cancer care policy landscape in Europe. Meeting participants highlighted gaps in the existing European programmes focusing on cancer research, including Europe's Beating Cancer Plan (EBCP), the Mission on Cancer (MoC), Understanding Cancer (UNCAN.eu), and the joint action CRANE, and put forward the next priorities, in the form of the Heidelberg Manifesto for cancer research. This meeting report presents all discussions that shed light on how infrastructures can be effectively shaped for translational, prevention, clinical and outcomes cancer research, with a focus on implementation and sustainability and while engaging patients and the public. In addition, we summarize recommendations on how to introduce frameworks for the digitalization of European cancer research. Finally, we discuss what structures, commitment, and resources are needed to establish a collaborative cancer research environment in Europe to achieve the scale required for innovation.

Primary gastric choriocarcinoma: a rare and aggressive gastrointestinal malignancy.

A 40-year-old male with no previous medical history presented to emergency department with a 2-week history of progressive dyspnea. He also described night sweats and weight loss (15 kg) during the last 3 months. Thoraco-abdominal computed tomography showed multiple bilateral lung nodules associated with supra-clavicular, hilar and peri-esophageal lymphadenopathies and gastric parietal thickening. These imaging features were suggestive of primary gastric cancer with lung and lymph node metastases. Therefore, he undergone upper digestive endoscopy that showed a large ulcerated protruding lesion at the greater curvature of the body suggestive of malignancy. Gastric biopsies of the lesion confirmed a solid neoplasia constituted by solid nests and sheets of highly pleomorphic, bizarre cells with cytotrophoblastic and syncytiotrophoblastic differentiation that, on immunohistochemistry, stained positive for ß-HCG, SALL-4 and glypican-3. CT-guided biopsy of lung nodules revealed malignant cells with similar histopathological and immunohistochemical features. Elevated serum alpha-fetoprotein and ß-HCG were also detected. Clinical and ultrasound examination were negative for testicular masses. These findings were consistent with a primary gastric choriocarcinoma presenting with lung and lymph node metastases (stage IV). Although chemotherapy was started, the patient evolved unfavorably and died after 9 months. Primary gastric choriocarcinoma is a rare and aggressive gastrointestinal malignancy. This case demonstrates its rapid growth rate and high metastatic potential that may lead to symptoms from secondary involvement of distant organs.

Liver biopsy in inflammatory bowel disease patients with sustained abnormal liver function tests: a retrospective single-center study.

Background: Inflammatory bowel disease (IBD) may be associated with a wide range of hepatobiliary manifestations. This study aimed to characterize the spectrum of hepatobiliary disorders in patients with IBD who underwent liver biopsy for sustained abnormal liver function tests (LFT). Method: A retrospective study was performed of all patients with IBD who underwent liver biopsy between January 2010 and December 2020 for sustained abnormal LFT (at least 6-month duration). Results: A total of 101 patients were included, mostly male (62.4%), with a mean age of 44.4±13.3 years. The most common IBD type was Crohn's disease (61.4%). Median time interval between abnormal LFT and biopsy was 14 (7-36) months. Abnormal LFT was predominantly hepatocellular in 40 patients (39.6%), cholestatic in 26 (25.7%) and mixed in 35 (34.7%). The most frequent diseases were nonalcoholic fatty liver disease (NAFLD) in 33 patients (32.7%), drug-induced liver disease (DILI) in 30 (29.7%), autoimmune hepatitis (AIH) in 13 (12.9%) and primary sclerosing cholangitis (PSC) in 13 (12.9%). Three patients had primary biliary cholangitis. Remarkably, 70 patients (69.3%) already had fibrosis by the time of liver biopsy and in 6 (5.9%) liver disease was already detected in the stage of cirrhosis. Conclusions: Abnormal LFT in IBD patients had a wide range of etiologies and histology was often essential for reaching a correct diagnosis. NAFLD, DILI, AIH and PSC were the most common diagnoses and patients often presented in cirrhotic stage. Therefore, liver biopsy must be considered early in IBD patients with unexplained sustained abnormal LFT.

Histologic Features of Syphilitic Gastritis: A Rare but Resurging Imitator of Common Diseases.

OBJECTIVES: The range of histopathologic features of gastric syphilis is not well described. Here we describe the clinicopathologic findings of eight patients with syphilitic gastritis. METHODS: A search of our Pathology Data System (2003-2022) and multiple other institutions identified eight patients with syphilitic gastritis. Clinical information, pathology reports, and available slides were reviewed. RESULTS: Lesions predominated in middle-aged adults (mean age, 47.2 years; range, 23-61 years) with a propensity for men (n = 7). Three patients had a documented history of human immunodeficiency virus. Clinical presentations included weight loss, abdominal pain, hematochezia, fever, dyspepsia, nausea and vomiting, hematemesis, anemia, and early satiety. Endoscopic findings included ulcerations, erosions, abnormal mucosa, and nodularity. All specimens shared an active chronic gastritis pattern with intense lymphohistiocytic infiltrates, variable plasma cells, and gland loss. Prominent lymphoid aggregates were seen in four specimens. The diagnosis was confirmed either by immunostain for Treponema pallidum (n = 7) or by direct immunofluorescence staining and real-time polymerase chain reaction (n = 1). All patients with available follow-up data showed resolution of symptoms after antibiotic therapy (n = 4). CONCLUSIONS: Recognition of the histologic pattern of syphilitic gastritis facilitates timely treatment, prevents further transmission, and avoids unnecessarily aggressive treatment.