ObjectiveHeyde’s syndrome (HS), a rare condition characterised by a unique relationship between severe aortic stenosis and angiodysplasia, is often diagnosed late increasing the risk for a prolonged hospital course and mortality in the elderly. The leading hypothesis explaining the aetiology of HS is acquired von Willebrand syndrome (AVWS) but not all studies support this claim. While individual cases of HS have been reported, here we present the first systematic review of case reports and focus on the prevalence of AVWS.DesignA systematic search was conducted through PubMed/MEDLINE, CINAHL-EBSCO, Web of Science and Google Scholar since inception. The resulting articles were screened by two independent reviewers based on inclusion criteria that the article must be a case report/series or a letter to the editor in English describing HS in an adult patient.ResultsSeventy-four articles encompassing 77 cases met the inclusion criteria. The average age was 74.3±9.3 years old with a slight female predominance. The small intestine, especially the jejunum, was the most common location for bleeding origin. Capsule endoscopy and double balloon enteroscopy were superior at identifying bleeding sources than colonoscopy (p=0.0027 and p=0.0095, respectively) and oesophagogastroduodenoscopy (p=0.0006 and p=0.0036, respectively). The mean duration from symptom onset to diagnosis/treatment of HS was 23.8±39 months. Only 27/77 cases provided evidence for AVWS. Surgical and transcutaneous aortic valve replacement (AVR) were superior at preventing rebleeding than non-AVR modalities (p<0.0001).ConclusionFurther research is warranted for a stronger understanding and increased awareness of HS, which may hasten diagnosis and optimal management.

Immunoglobulin G4 (IgG4)‐positive marginal zone lymphoma (MZL) is rare and undefined. It is unclear whether IgG4‐positive MZLs have as favorable an outcome as MZLs in general. Also, correlation with IgG4‐related disease (IgG4‐RD) and IgG4‐positive MZLs is unknown. Following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses extension for scoping reviews, we searched MEDLINE and EMBASE for all peer‐reviewed articles using keywords including“IgG4” and “marginal zone lymphoma” from their inception to February 20, 2022. Twenty‐two articles, including six observational studies and 24 cases from 16 case reports and case series, were included. Only one study had a comparative group, and the other five were exploratory observational studies. IgG4‐positive MZLs commonly occurred in males (83.3%). It primarily involved ocular adnexa (41.7%) and skin (29.2%). Only 29.2% had concurrent IgG4‐RD, and no expiration was noted. While most cases were treated with excision, resection, or clinical observation, 21.7% received rituximab‐cyclophosphamide, doxorubicin, vincristine, and prednisone as a first‐line treatment. This systematic review summarizes the current understanding of the characteristics of IgG4‐positive MZLs. While there seems to be IgG4‐RD‐related and de novo IgG4‐positive MZLs, future research needs to clearly define MZL with polyclonal IgG4‐positive cells and IgG4‐producing lymphoma. Further studies are critical to clarifying long‐term prognosis and optimal surveillance planning.

BACKGROUND Combined hepatocellular and cholangiocarcinoma (HCC/CC) is a rare primary hepatic malignancy which carries a poor prognosis due to its aggressive nature. Few centers have enough cases to draw definitive conclusions and there is limited understanding of prognosis. Given the rarity of HCC/CC, an analysis of large national cancer database was needed to obtain larger number of HCC/CC cases. AIM To identify associated factors for 5-year survival of HCC/CC. METHODS We conducted a retrospective study of The Surveillance, Epidemiology, and End Results (SEER) database obtained from SEER*Stat 8.3.6 software. Previously defined histology code 8180 for the International Classification of Disease for Oncology, 3rd edition was used to identify HCC/CC cases from 2004 to 2015. We collected demographics, American Joint Committee on Cancer (AJCC) stage, treatment, tumor size, and survival data. These data were converted to categorical variables. The Shapiro-Wilk normality test was used to assess normal distribution. Mann-Whitney U test was used to compare continuous variables without normal distribution, and t -test was used to compare continuous variables with a normal distribution. The Kaplan-Meier survival curve analyzed 5-year survival. Univariate and multivariate logistic regression model was used to analyze factors associated with 5-year survival. Multivariate Cox proportional hazard regression was done on 5-year survival. We defined P < 0.05 was statistically significant. RESULTS We identified 497 patients with the following characteristics: Mean age 62.4 years (SD: 11.3), 149 (30.0%) were female, racial distribution was: 276 (55.5%) white, 53 (10.7%) black, 84 (16.9%) Asian and Pacific Islander (API), 77 (15.5%) Hispanic, and 7 (1.4%) others or unknown. Stage I/II disease occurred in 41.5% and tumor size < 50 mm was seen in 35.6% of patients. Twenty-four (4.8%) received locoregional therapy (LRT), 119 (23.9%) underwent resection, and 50 (10.1%) underwent liver transplantation. The overall median survival was 6 mo [Interquartile range (IQR): 1-22]. After multivariate logistic regression, tumor size < 50 mm [Odds ratios (OR): 2.415, P = 0.05], resection (OR: 12.849, P < 0.01), and transplant (OR: 27.129, P < 0.01) showed significance for 5-year survival. Age > 60, sex, race, AJCC stages, metastasis, and LRT were not significant. However, API vs white showed significant OR of 2.793 (CI: 1.120-6.967). Cox proportional hazard regression showed AJCC stages, tumor size < 50 mm, LRT, resection, and transplant showed significant hazard ratio. CONCLUSION HCC/CC patients with tumor size < 50 mm, resection, and transplant were associated with an increase in 5-year survival. API showed advantageous OR and haz...

Among immune-related adverse events associated with immune checkpoint inhibitors, immune-mediated gastritis (IMG) has been rarely described in the literature and has not yet been well characterized. This scoping review aimed to characterize IMG in terms of precipitating agents, clinical presentations, and prognosis. After the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including "gastritis," "immune checkpoint inhibitor," and "immune-related adverse event" from their inception to December 28, 2021. Twenty-two articles, including 5 observational studies and 17 case reports and case series, were included. Nivolumab, pembrolizumab, and combination therapy with those and cytotoxic T-lymphocyte-associated antigen-4 inhibitor (ipilimumab) were commonly used in those with IMG. 59.8% had epigastric pain, and 50% had erosive gastritis. 87.5% had Common Terminology Criteria for Adverse Events (CTCAE) grade 3 gastritis, and 91.2% received corticosteroids. Recurrence was noted in 16.7%, and only 1 expiration was noted. 4.3% had positive helicobacter pylori and cytomegalovirus from the gastric specimen. Similar to immunerelated colitis, patients with IMG may have a favorable prognosis with a better response to immune checkpoint inhibitors if treated appropriately. The diagnosis of IMG is made by exclusion, and a thorough workup is necessary to rule out concurrent helicobacter pylori and cytomegalovirus involvement. Further studies are critical for a better understanding of this complication.

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