Helicobacter pylori Status May Differentiate Two Distinct Pathways of Gastric Adenocarcinoma Carcinogenesis.

BACKGROUND: We evaluated the phenotype of sporadic gastric cancer based on HP status and binding of a tumor risk marker monoclonal, Adnab-9. METHODS: We compared a familial GC kindred with an extremely aggressive phenotype to HP-positive (HP+) and -negative (HP-) sporadic gastric adenocarcinoma (GC) patients in the same community to determine if similar phenotypes exist. This might facilitate gene discovery to understand the pathogenesis of aggressive GC phenotypes, particularly with publications implicating immune-related gene-based signatures, and the development of techniques to gauge the stance of the innate immune system (InImS), such as the FERAD ratio (blood ferritin:fecal Adnab-9 binding OD-background binding). Resection specimens for the sporadic and familial group were stained for HP and examined for intestinal metaplasia (IM) and immunostaining for Adnab-9. Familial kindred specimens were also tested for the E-cadherin mutation and APC (adenomatous polyposis coli). Survival was evaluated. RESULTS: Of 40 GC patients, 25% were HP+ with a greater proportion of intestinal metaplasia (IM) and gastric atrophy than the HP- group. The proband of the familial GC kindred, a 32-year-old mother with fatal GC, was survived by 13-year-old identical twins. Twin #1 was HP- with IM and Twin #2 was HP+. Both twins subsequently died of GC within two years. The twins did not have APC or E-cadherin mutations. The mean overall survival in the HP+ sporadic GC group was 2.47 ± 2.58 years and was 0.57 ± 0.60 years in the HP- group (p = 0.01). Survival in the kindred was 0.22 ± 0.24 years. Adnab-9 labeling was positive in fixed tissues of 50% of non-familial GC patients and in gastric tissue extract from Twin #2. The FERAD ratio was determined separately in six prospectively followed patient groups (n = 458) and was significantly lower in the gastric cancer patients (n = 10) and patients with stomach conditions predisposing them to GC (n = 214), compared to controls (n = 234 patients at increased risk for colorectal cancer but without cancer), suggesting a failure of the InImS. CONCLUSION: The HP+ sporadic GC group appears to proceed through a sequence of HP infection, IM and atrophy before cancer supervenes, and the HP- phenotype appear to omit this sequence. The familial cases may represent a subset with both features, but the natural history strongly resembles that of the HP- group. Two different paths of carcinogenesis may exist locally for sporadic GC. The InImS may also be implicated in prognosis. Identifying these patients will allow for treatment stratification and early diagnosis to improve GC survival.

Quality analysis of publicly available information about hypoplastic left heart syndrome.

PURPOSE: Publicly available health information is increasingly important for patients and their families. While the average US citizen reads at an 8th-grade level, electronic educational materials for patients and families are often advanced. We assessed the quality and readability of publicly available resources regarding hypoplastic left heart syndrome (HLHS). METHODS: We queried four search engines for "hypoplastic left heart syndrome", "HLHS", and "hypoplastic left ventricle". The top 30 websites from searches on Google, Yahoo!, Bing, and Dogpile were combined into a single list. Duplicates, commercial websites, physician-oriented resources, disability websites, and broken links were removed. Websites were graded for accountability, content, interactivity, and structure using a two-reviewer system. Nonparametric analysis of variance was performed. RESULTS: Fifty-two websites were analysed. Inter-rater agreement was high (Kappa = 0.874). Website types included 35 hospital/healthcare organisation (67.3%), 12 open access (23.1%), 4 governmental agency (7.7%), and 1 professional medical society (1.9%). Median total score was 19 of 39 (interquartile range = 15.8-25.3): accountability 5.5 of 17 (interquartile range = 2.0-9.3), content 8 of 12 (interquartile range = 6.4-10.0), interactivity 2 of 6 (interquartile range = 2.0-3.0), and structure 3 of 4 (interquartile range = 2.8-4.0). Accountability was low with 32.7% (n = 17) of sites disclosing authorship and 26.9% (n = 14) citing sources. Forty-two percent (n = 22) of websites were available in Spanish. Total score varied by website type (p = 0.03), with open access sites scoring highest (median = 26.5; interquartile range = 20.5-28.6) and hospital/healthcare organisation websites scoring lowest (median = 17.5; interquartile range = 13.5-21.5). Score differences were driven by differences in accountability (p = 0.001) - content scores were similar between groups (p = 0.25). Overall readability was low, with median Flesch-Kincaid Grade Level of 11th grade (interquartile range = 10th-12th grade). CONCLUSIONS: Our evaluation of popular websites about HLHS identifies multiple opportunities for improvement, including increasing accountability by disclosing authorship and citing sources, enhancing readability by providing material that is understandable to readers with the full spectrum of educational background, and providing information in languages besides English, all of which would enhance health equity.

Never too early: the impact of a shadowing programme in paediatric and congenital cardiac surgery for undergraduate college students.

PURPOSE: Diversification of the medical and cardiothoracic surgical workforce represents an ongoing need. A congenital cardiac surgery shadowing programme for undergraduate students was implemented at the University of Florida Congenital Heart Center. METHODS: Students shadowing in the Congenital Heart Center from 17 December 2020 through 20 July 2021 were sent a survey through Qualtrics to evaluate the impact of their shadowing experience. The main objectives of the survey were to determine the personal relationship(s) of the students to physicians prior to shadowing, how the presence or absence of physicians in the family of a given student related to the exposure of the student to a medical setting prior to shadowing, and the interest of the students in medicine and cardiothoracic surgery prior to and after the shadowing experience. Survey responses included "Yes/No" questions, scaled responses using a Likert scale, selection lists, and free text responses. When applicable, t-tests were utilised to assess differences between student groups. RESULTS: Of the 37 students who shadowed during the study period, 26 (70%) responded. Most students were female (58%, n = 15), and the mean age was 20.9 ± 2.4 years. Students spent a mean duration of 95 ± 138 hours shadowing providers as part of the shadowing programme. Likert scale ratings of interest in the professions of medicine, surgery, and cardiothoracic surgery all increased after the shadowing experience (p < 0.01). Students with a family member in medicine had more clinical exposure prior to the shadowing programme (p < 0.01). CONCLUSION: A surgical shadowing programme at a Congenital Heart Center may have an important formative impact on the views of undergraduate students regarding potential careers in surgery and medicine. Additionally, students without family members in medicine tend to have less prior exposure to medicine and could likely benefit more from this type of shadowing programme.

Prospective markers for early diagnosis and prognosis of sporadic pancreatic ductal adenocarcinoma.

BACKGROUND AND AIM: Sporadic pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer. No proven screening strategies are available and frequent cross-sectional imaging studies (CT/MRI) are impractical even in patients thought to be at higher risk than the general population. Few PDA biomarkers have been studied prospectively for screening. Here, we prospectively evaluated the Adnab-9 monoclonal antibody in stool, pancreaticobiliary secretions, and tissue for screening and prognostic value in sporadic PDA. We also evaluated the prognostic value of characterized early biomarkers in pancreaticobiliary secretions. METHODS: Adnab-9 diagnostic ability was tested in stool in 249 and 1,132 patients from China and the US, respectively. Immunohistochemistry was performed in 22 tissue samples with Adnab-9 antibody and anti-Defensin 5, a constituent of Paneth cells. Pancreatobiliary secretions were collected from 12 PDA patients and 9 controls. The enriched PCR method was performed to detect K-ras mutations. ELISA was performed with Adnab-9, anti-Her-2/neu, and monoclonal antibody D4 (anti-Reg I). RESULTS: Adnab-9 alone was diagnostic and prognostic when measured in pancreatic secretions, feces, and tissues of PDA patients compared to controls (p < 0.05). Significantly, Adnab-9 fecal binding can precede the clinical diagnosis by 2.3 years, potentially allowing earlier clinical intervention. In pancreatic secretions, a combination of K-ras and Her-2/neu when appropriately standardized can be diagnostic in 75 % of PDA. CONCLUSIONS: Our study suggests that Adnab-9 may be an effective marker for diagnosis and prognosis of PDA. Adnab-9 may be reflective of the presence of Paneth cells confirmed by Defensin-5 staining. These cells may modulate the biological activity of the cancer and confer a better prognosis.

SlimQuick™ - associated hepatotoxicity in a woman with alpha-1 antitrypsin heterozygosity.

Green tea (Camellia sinensis)-associated hepatotoxicity is reported. However, the presence of alpha-1 antitrypsin MZ phenotype as a predisposing factor to green tea-associated drug-induced liver injury (DILI) is unknown. A previously healthy woman with alpha-1 antitrypsin MZ phenotype who took SlimQuick™, an herbal supplement containing green tea extract, developed severe hepatotoxicity requiring corticosteroid treatment. Green tea-associated hepatotoxicity is reviewed and alpha-1 antitrypsin MZ phenotype as a predisposing factor to green tea-associated DILI is discussed. Liver biopsy demonstrated marked inflammation with necrosis suggestive of toxic injury with diffuse alpha-1 antitrypsin globule deposition on immunostaining. Corticosteroid therapy resulted in rapid clinical improvement. Alpha-1 antitrypsin MZ phenotype may increase vulnerability to herbal hepatotoxicity.

Managing anticoagulation and antiplatelet medications in GI endoscopy: a survey comparing the East and the West.

BACKGROUND: Anticoagulation and antiplatelet medications may potentiate GI bleeding, and their use may lead to an increased need for a GI endoscopy. We hypothesized that there might be different practice patterns among international endoscopists. OBJECTIVE: To explore the differences in management practices for patients who receive anticoagulation and antiplatelet medications from Eastern and Western endoscopists. DESIGN: International survey study. SETTING: Academic medical centers and private clinics. SUBJECTS: Members of the American Society for Gastrointestinal Endoscopy (ASGE) in Eastern (Korea, Japan, China, India, Thailand, Singapore, Malaysia, and Philippines) and Western (United States and Canada) countries were invited to complete a Web-site-based questionnaire. In addition, the questionnaire was sent to university hospitals in South Korea and academic institutions in the United States. METHODS: A survey was administered that contained detailed questions about the use of an endoscopy in patients on anticoagulation and antiplatelet medications. MAIN OUTCOME MEASUREMENTS: Different opinions and clinical practice patterns regarding the use of anticoagulation and antiplatelet medications by Eastern and Western endoscopists. RESULTS: A total of 105 Eastern and 106 Western endoscopists completed the survey. Western endoscopists experienced more instances of procedure-related bleeding (P = .003) and thromboembolism after withdrawal of medications (P = .016). Eastern endoscopists restarted medications later (1-3 days) than Western endoscopists after a biopsy (same day) (P < .001). Eastern endoscopists withdrew aspirin for more than 7 days before a polypectomy and then restarted it 1 to 3 days after a polypectomy, whereas Western endoscopists performed a polypectomy without withdrawing aspirin (P < .001). ASGE guidelines were followed less often by Eastern than by Western endoscopists (P < .001). LIMITATIONS: Low response rate, heterogeneity of the sample, and recall bias. CONCLUSIONS: The opinions and clinical practice patterns for the management of anticoagulation and antiplatelet medications differed significantly between Eastern and Western endoscopists. The lack of uniformity in practice patterns suggests that more data and better education are required in the area of GI endoscopy for patients on anticoagulation and antiplatelet medications, particularly given that individual patient characteristics may be associated with unique types of complications.

The presentation of contralateral axillary lymph node metastases from breast carcinoma: a clinical management dilemma.

Metastases to the contralateral axillary lymph nodes in breast cancer patients are uncommon. Involvement of the contralateral axilla is a manifestation of systemic disease (stage IV) or a regional metastasis from a new occult primary (T0N1, stage II). The uncertain laterality of the cancer responsible for these metastases complicates overall disease staging and is a management dilemma for clinicians. Seven women who developed contralateral axillary metastases (CAM), but did not have evidence of systemic disease were identified. Patient demographics, histopathologic tumor characteristics, treatment and outcome were examined. The median age was 49 years. A family history of breast cancer was present in six (86%). The initial breast cancers were located in all quadrants. They were generally hormone receptor negative, HER-2/neu overexpressing and associated with lymphovascular invasion. There was a median interval of 71 months between initial breast cancer diagnosis and CAM presentation. Surgical management of the CAM included simple excision in one (14%) and axillary lymph node dissection in five (71%). Adjuvant treatment consisted of chemotherapy in seven (100%) and hormonal therapy in one (14%). The median follow-up from the diagnosis of CAM was 35 months and three women were alive without disease, two were alive with disease and two had died of disease. With surgical treatment, there were no axillary recurrences in this series. When patients present with CAM and no evidence of systemic disease or a new primary in the contralateral breast, surgical treatment should be considered for local control and possibly improved relapse-free survival.

Differentiating true versus pseudo left ventricular aneurysm: a case report and review of diagnostic strategies.

The differentiation of left ventricular pseudoaneurysm from true aneurysm is sometimes difficult. Given the propensity for pseudoaneurysms to rupture leading to cardiac tamponade, shock, and death, compared with a more benign natural history for true aneurysms, accurate diagnosis of these conditions is clinically important. Clinical symptoms, physical examination findings, electrocardiograms, and routine x-rays are not sensitive or specific for diagnosing left ventricular aneurysms nor for distinguishing true from pseudoaneurysm once detected. Our aim is to present a case report demonstrating these difficulties and to review the use of various cardiac imaging modalities in differentiating between these 2 entities.