Epidemiology and outcomes of gastrointestinal mucosal melanomas: a national database analysis.

AIM: Gastrointestinal malignant melanoma is a rare mucosal melanoma (MM). Other MM include the respiratory and the genitourinary tract. All mucosal melanomas have a poor prognosis when compared to cutaneous melanomas. Ano-rectal melanomas are by far the most common and most studied gastrointestinal MM. Large-scale clinical data is lacking due to the rarity of the disease. We aim to analyze epidemiology and survival of the Gastrointestinal (G.I.) MM over 45 years using a national database. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was queried to identify patients with biopsy-proven G.I. Melanomas. We selected tumor site, intervention, and survival information for oncology codes as per the international classification of diseases. Survival analysis was performed using the SPSS v 27 ® IBM software. RESULTS: Of the 1105 biopsy-proven confirmed cases of primary G.I. melanoma's, 191 (17.3%) received chemotherapy (C.T.), 202 (18.3%) received radiotherapy (R.T.), 63 (5.7%) received both C.T and R.T., while 684 (61.9%) of the population received surgery alone or combined with C.T. and/or R.T. Statistically significant improvement in survival was noted in all treatment strategies that utilized surgery and also when site-specific MM cohorts underwent a surgical approach with or without C.T and/or R.T. CONCLUSION: This is the most extensive study reporting epidemiological and survival data of treatment strategy outcomes of primary G.I. mucosal melanoma elucidating best overall survival with a management strategy involving surgical intervention.

Effects of triple-drug therapy with nitazoxanide, high-dose ribavirin and peginterferon-α-2a in patients with chronic hepatitis C.

AIM: The historical standard of care for patients with chronic hepatitis C virus (HCV) was peginterferon (PEG IFN) and ribavirin combination therapy, yielding sustained virological response (SVR) rates of 38-52% in HCV genotype 1 patients. This study evaluated a novel three-drug regimen of nitazoxanide and high-dose ribavirin as lead-in therapy, followed by PEG IFN-α-2a in triple therapy. METHODS: A prospective, open-label pilot study was conducted in treatment-naive patients with HCV genotype 1. Patients received nitazoxanide 500 mg twice a day for 2 weeks, then nitazoxanide plus ribavirin 1400 mg/day for 2 weeks, then nitazoxanide plus ribavirin plus PEG IFN-α-2a 180 µg weekly for 12 weeks, followed by ribavirin plus PEG IFN-α-2a for 12 weeks (48 weeks if HCV RNA negative after week 24). Primary outcome was SVR. Other outcomes included very rapid virological response (VRVR), rapid virological response (RVR), early virological response (EVR), end-of-treatment response (ETR), and safety and tolerability. RESULTS: Thirty-three patients with a mean age of 46 years, detectable HCV RNA (64% with <600 000 IU/mL), and METAVIR fibrosis scores (F1:F2:F3) of 15%:49%:36% were enrolled. Outcomes were as follows: SVR, 67% (22/33); VRVR, 39% (13/33); RVR, 48% (16/33); EVR, 70% (23/33); and ETR, 67% (22/33). Most patients required at least one growth factor. Two patients discontinued because of adverse events. CONCLUSION: This three-drug regimen was effective in achieving SVR in patients with HCV genotype 1. No patients relapsed, and the toxicity profile was favorable. Further studies on the role of nitazoxanide in the treatment of chronic HCV are warranted.

Endoscopic retrograde cholangiopancreatography-related early perforations: A study of effects of procedure duration, complexity, and endoscopist experience.

BACKGROUND: Perforations (Perf) during endoscopic retrograde cholangiopancreatography (ERCP) are rare (< 1%) but potentially fatal events (up to 20% mortality). Given its rarity, most data is through case series studies from centers or analysis of large databases. Although a meta-analysis has shown fewer adverse events as a composite (bleeding, pancreatitis, Perf) during ERCP performed at high-volume centers, there is very little real-world data on endoscopist and center procedural volumes, ERCP duration and complexity on the occurrence of Perf. AIM: To study the profile of Perf related to ERCP by center and endoscopist procedure volume, ERCP time, and complexity from a national endoscopic repository. METHODS: Patients from clinical outcomes research initiative-national endoscopic database (2000-2012) who underwent ERCP were stratified based on the endoscopist and center volume (quartiles), and total procedure duration and complexity grade of the ERCP based on procedure details. The effects of these variables on the Perf that occurred were studied. Continuous variables were compared between Perf and no perforations (NoPerf) using the Mann-Whitney U test as the data demonstrated significant skewness and kurtosis. RESULTS: A total of 14153 ERCPs were performed by 258 endoscopists, with 20 reported Perf (0.14%) among 16 endoscopists. Mean patient age in years 61.6 ± 14.8 vs 58.1 ± 18.8 (Perf vs. NoPerf, P = NS). The cannulation rate was 100% and 91.5% for Perf and NoPerf groups, respectively. 13/20 (65%) of endoscopists were high-volume performers in the 4th quartile, and 11/20 (55%) of Perf occurred in centers with the highest volumes (4th quartile). Total procedure duration in minutes was 60.1 ± 29.9 vs 40.33 ± 23.5 (Perf vs NoPerf, P < 0.001). Fluoroscopy duration in minutes was 3.3 ± 2.3 vs 3.3 ± 2.6 (Perf vs NoPerf P = NS). 50% of the procedures were complex and greater than grade 1 difficulty. 3/20 (15%) patients had prior biliary surgery. 13/20 (65%) had sphincterotomies performed with stent insertion. Peritonitis occurred in only 1/20 (0.5%). CONCLUSION: Overall adverse events as a composite during ERCP are known to occur at a lower rate with higher volume endoscopists and centers. However, Perf studied from the national database show prolonged and more complex procedures performed by high-volume endoscopists at high-volume centers contribute to Perf.

Fibrolamellar hepatocellular carcinoma: An epidemiologic and 5-year cancer survival assessment based off SEER data.

The fibrolamellar variant of hepatocellular carcinoma makes up a small percentage of liver tumors. Despite being a subset, it has been noted in the literature to have variations in terms of its epidemiology and intervention recommendations. Using the Surveillance, Epidemiology, and End Results database, 339 cases from 1988 to 2016 were studied. Favorable prognostic epidemiological factors included male sex, younger ages, and white race. Those who underwent any lymph node resection (combined with liver resection) did better than those without lymph node resection; chemotherapy proved beneficial for those where surgery was contraindicated. To our knowledge, this report is the largest conglomerate dataset analyzing prognostic profiles and treatment strategies for fibrolamellar hepatocellular carcinoma.

Demographic profile, management, and survival of primary Gastrointestinal Kaposi Sarcoma: A USA Nationwide SEER-based study.

Kaposi Sarcoma (KS) is a Human Herpes Virus-8 (HHV-8) associated angio-proliferative disorder commonly seen in patients with HIV. It most commonly involves the skin as classic purple lesions but occasionally involves the gastrointestinal (GI) tract. To date, published data is scarce on primary GI KS. Using a national database, this study analyzes the incidence, demographics, and survival of primary GI KS. We conducted a retrospective analysis (1975-2019) on biopsy-proven primary GI KS cases from 17 registries from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. A total of 685 patients with GI KS were identified. Female gender, Non-Hispanic Asian or Pacific Islander (NHAPI), married marital status, and large bowel site-specific primary KS to have better overall survival. Luminal gastrointestinal KS was more frequent (84.96%) than solid organ involvement (3.07% of all cases). This study is the most extensive population-based study about the epidemiological and survival data of patients with primary GI KS, revealing GI KS to be a young male disease with best outcomes in the large bowel and anal canal KS while inferior outcomes in extraintestinal GI KS.

A randomized study comparing levofloxacin, omeprazole, nitazoxanide, and doxycycline versus triple therapy for the eradication of Helicobacter pylori.

OBJECTIVES: Resistance to standard Helicobacter pylori (HP) treatment regimens has led to unsatisfactory cure rates in HP-infected patients. This study was designed to evaluate a novel four-drug regimen (three antibiotics and a proton pump inhibitor (PPI)) for eradication of HP infection in treatment-naive patients. METHODS: Patients with a diagnosis of HP gastritis or peptic ulcer disease confirmed using endoscopy and stool antigen testing were eligible for inclusion in this study. All patients underwent a washout period of 6 weeks from any prior antibiotic or PPI usage. Patients were then randomized to either levofloxacin, omeprazole, nitazoxanide, and doxycycline (LOAD) therapy for 7 days (LOAD-7) or 10 days (LOAD-10), including levofloxacin 250 mg with breakfast, omeprazole 40 mg before breakfast, nitazoxanide (Alina) 500 mg twice daily with meals and doxycycline 100 mg at dinner, or lansoprozole, amoxicillin, and clarithromycin (LAC) therapy for 10 days, which included lansoprozole 30 mg, amoxicillin 1 g with breakfast and dinner, and clarithromycin 500 mg with breakfast and dinner. HP eradication was confirmed by stool antigen testing at least 4 weeks after cessation of therapy. RESULTS: Intention-to-treat analysis revealed significant differences (P<0.05) in the respective eradication rates of the LOAD therapies (88.9% (80/90) LOAD-10, 90% (81/90) LOAD-7, 89.4% (161/180) for combined LOAD) compared with those receiving LAC, 73.3% (66/90). There were no differences in adverse effects between the groups. CONCLUSIONS: This open-label, prospective trial demonstrates that LOAD is a highly active regimen for the treatment of HP in treatment-naive patients. A large randomized controlled trial is warranted to further evaluate the efficacy of this regimen.

Advances in treatment and prevention of hepatitis B.

Chronic hepatitis B (CHB) continues to contribute to worldwide morbidity and mortality significantly. Scientists, clinicians, pharmaceutical companies, and health organizations have dedicated substantial Intellectual and monetary resources to finding a cure, increasing immunization rates, and reducing the global burden of CHB. National and international health-related organizations including the center for disease control, the national institute of health, the American Association for the study of liver disease (AASLD), The European association for the study of the Liver (EASL), The Asia Pacific association for the study of the Liver (APASL) and the world health organization release periodic recommendations for disease prevention and treatment. Our review of the most recent guidelines by EASL, AASLD, APASL, and Taiwan Association for the Study of the Liver revealed that an overwhelming majority of cited studies were published before 2018. We reviewed Hepatitis B-related literature published 2018 onwards to identify recent developments and current barriers that will likely direct future efforts towards eradicating hepatitis B. The breakthrough in our understanding of the hepatitis B virus life cycle and resulting drug development is encouraging with significant room for further progress. Data from high-risk populations, most vulnerable to the devastating effects of hepatitis B infection and reactivation remain sparse. Utilization of systems approach, optimization of experimental models, identification and validation of next-generation biomarkers, and precise modulation of the human immune response will be critical for future innovation. Within the foreseeable future, new treatments will likely complement conventional therapies rather than replace them. Most Importantly, pragmatic management of CHB related population health challenges must be prioritized to produce real-world results.

Is it time to rethink combined liver-kidney transplant in hepatitis C patients with advanced fibrosis?

AIM: To reduce hepatic and extrahepatic complications of chronic hepatitis C in kidney transplant recipients. METHODS: We conducted a systematic review of kidney only transplant in patients with hepatitis C and advanced fibrosis. RESULTS: The 5 year patient survival of kidney transplant recipients with and without hepatitis C cirrhosis ranged from 31% to 90% and 85% to 92%, respectively. Hepatitis C kidney transplant recipients had lower 10-year survival when compared to hepatitis B patients, 40% and 90% respectively. There were no studies that included patients with virologic cure prior to kidney transplant that reported post-kidney transplant outcomes. There were no studies of direct acting antiviral therapy and effect on patient or graft survival after kidney transplantation. CONCLUSION: Data on kidney transplant only in hepatitis C patients that reported inferior outcomes were prior to the development of potent direct acting antiviral. With the development of potent directing acting antiviral therapy for hepatitis C with high cure rates studies are needed to determine if patients with hepatitis C, including those with advanced fibrosis, can undergo kidney transplant alone with acceptable long term outcomes.

Clinical and Neurologic Manifestation of Minimal Hepatic Encephalopathy and Overt Hepatic Encephalopathy.

Hepatic encephalopathy (HE) shows a wide spectrum of neuropsychiatric manifestations. A combined effort with neuropsychological and psychometric evaluation has to be performed to recognize the syndrome, whereas minimal HE (MHE) is largely under-recognized. Subtle symptoms of MHE can only be diagnosed through specialized neuropsychiatric testing. Early diagnosis and treatment may drastically improve the quality of life for many cirrhotic patients. Further research to gain better insight into the pathophysiology and diagnostic accuracy of HE will help determine future management strategies.

Rifaximin therapy for metronidazole-unresponsive Clostridium difficile infection: a prospective pilot trial.

BACKGROUND: Clostridium difficile infection (CDI) is a recent epidemic in the United States, particularly in the hospital setting. Oral metronidazole is standard therapy for C. difficile infection, but resistance to metronidazole is becoming a clinical challenge. METHODS: We evaluated the efficacy of the nonsystemic oral antibiotic rifaximin for the treatment of metronidazole-resistant C. difficile infection. Twenty-five patients with C. difficile infection were enrolled in the study. All had mild-to-moderate C. difficile infection (5-10 bowel movements a day without sepsis) unresponsive to metronidazole (i.e. stools positive for toxins A and B after oral metronidazole 500 mg three times daily [t.i.d.] for 5 days). After discontinuation of metronidazole, rifaximin 400 mg t.i.d. for 14 days was prescribed. Patients were followed for 56 days and stool was tested for C. difficile using polymerase chain reaction (PCR) to assess the effect of treatment. A negative PCR test result was interpreted as a favorable response to rifaximin. RESULTS: Sixteen of 22 patients (73%) were eligible for study inclusion and completed rifaximin therapy experienced eradication of infection (stool negative for C. difficile) immediately after rifaximin therapy and 56 days post-treatment. Three patients (12%) discontinued therapy because of abdominal distention. Rifaximin was generally well tolerated. CONCLUSIONS: In conclusion, rifaximin may be considered for treatment of mild-to-moderate C. difficile infection that is resistant to metronidazole. Larger randomized trials are needed to confirm these positive findings.