Indirect comparison of various lumen apposing metal stents for EUS-guided biliary and gallbladder drainage: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Studies assessing endoscopic ultrasound guided biliary drainage (EUS-BD) or gallbladder drainage (EUS-GB) using lumen apposing metal stents (LAMS) have shown variable results based on the type of LAMS. We performed a meta-analysis of the available data. METHODS: Multiple online databases were searched for studies using LAMS (AXIOS or SPAXUS) for EUS-BD and EUS-GB. The outcomes of interest were technical success, clinical success and adverse events. Pooled proportions along with 95% confidence intervals (CI) were calculated. RESULTS: A total of 18 observational studies were included: 11 for AXIOS stent (433 patients with mean age 72 years and 54% males) and 7 for SPAXUS stent (242 patients with mean age 74 years and 50% males). The respective pooled outcomes for AXIOS stent (EUS-BD and EUS-GB) were: technical success (96.2% and 96.2%), clinical success (92.8% and 92.7%), total adverse events (10.1% and 23.6%), and bleeding (3.7% and 4.8%). The respective pooled outcomes for SPAXUS stent (EUS-BD and EUS-GB) were: technical success (93.8% and 95.9%), clinical success (90.1% and 94.2%), total adverse events (12.6% and 9.5%), and bleeding (3.1% and 1.8%). CONCLUSION: AXIOS and SPAXUS stents demonstrate similar pooled technical and clinical success rates. Adverse events occurred in 23.6% patients (AXIOS stent) and 9.5% patients (SPAXUS stent) during EUS-GB.

Safety and efficacy of thalidomide in treatment of gastrointestinal bleeding secondary to angioectasias: a systematic review and meta-analysis.

BACKGROUND: Thalidomide has been used for angioectasia-associated refractory gastrointestinal bleeding (GIB), with studies showing variable efficacy and side effects profile. We conducted a meta-analysis to reconcile the data. METHODS: Online databases were searched for studies evaluating thalidomide in patients with refractory/recurrent GIB due to angioectasias. The outcomes of interest were cessation of bleeding, rebleeding, need for blood transfusion, hospitalization and adverse events. Pooled proportions for incidence, and odds ratios (OR) for comparison with control were calculated along with 95% confidence interval (CI). RESULTS: A total of seven studies with 346 patients (n = 269 thalidomide, n = 77 control) were included. Thalidomide dose was usually started at 50-100mg/day. The mean age was 65 years, 45% patients were men, and mean follow-up was 1.8 years. The pooled clinical outcomes with thalidomide were: cessation of bleeding 42.2% (95% CI 36.02 to 48.41), rebleeding 30%, need for blood transfusion 20.1%, hospitalization 40% and adverse events 55.9%. When compared with the control group in 2 studies, patients on thalidomide had significantly higher odds of cessation of bleeding (OR 21.40, 95% CI 5.78 to 79.29, p < 0.00001) and adverse events, with lower need for blood transfusion and hospitalization. DISCUSSION: In patients with angioectasias-related refractory/recurrent GIB, the use of thalidomide results in significantly decreased bleeding risk and may play a role in the management of such patients.

Meta-Analysis of Endoscopic Full-Thickness Resection Versus Endoscopic Submucosal Dissection for Complex Colorectal Lesions.

BACKGROUND: Studies evaluating endoscopic full-thickness resection (EFTR) and endoscopic submucosal dissection (ESD) for complex colorectal lesions have shown variable results. We conducted a meta-analysis of the available data. METHODS: Online databases were searched for studies comparing EFTR versus ESD for complex colorectal lesions. The outcomes of interest were resection rates, procedure time (min), and complications. Pooled odds ratios (OR) and standardized mean difference (SMD) along with 95% CI were calculated. RESULTS: A total of 4 studies with 530 patients (n=215 EFTR, n=315 ESD) were included. The mean follow-up duration was 5 months. The mean age of the patients was 68 years and 64% were men. The EFTR and ESD groups had similar rates of en bloc resection (OR: 1.73, 95% CI: 0.60-4.97, P=0.31) and R0 resection (OR: 1.52, 95% CI: 0.55-4.14, P=0.42). The EFTR group had significantly reduced procedure time (SMD -1.87, 95% CI: -3.13 to -0.61, P=0.004), total complications (OR: 0.24, 95% CI: 0.13-0.44, P<0.00001), perforation (OR: 0.12, 95% CI: 0.03-0.39, P=0.0005) and postresection electrocoagulation syndrome (OR: 0.06, 95% CI: 0.01-0.48, P=0.008). Delayed bleeding was similar in the 2 groups (OR: 0.80, 95% CI: 0.30-2.12, P=0.66). Residual/recurrent lesions were significantly higher in the EFTR group (OR: 4.67, 95% CI: 1.39-15.66, P=0.01). DISCUSSION: This meta-analysis of small studies with high heterogeneity showed that EFTR and ESD have comparable resection rates for complex colorectal lesions. EFTR is faster and has fewer complications, but it increases residual or recurrent lesions.

Conventional Versus Traction Endoscopic Submucosal Dissection for Colorectal Tumors: A Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: Compared with conventional endoscopic submucosal dissection (C-ESD) for colorectal lesions, the traction method (T-ESD) allows the lesion to be stabilized with easier dissection. However, randomized controlled trials (RCTs) have reported conflicting results on the clinical outcomes of T-ESD as compared with C-ESD. We conducted a meta-analysis to compile the data. METHODS: Multiple databases were searched for RCTs evaluating C-ESD versus T-ESD for colorectal tumors. The end points of interest were procedure time (min), resection speed (mm²/min), R0 resection, en bloc resection, delayed bleeding, and perforation. Standard meta-analysis methods were employed using the random-effects model. RESULTS: Six RCTs with a total of 566 patients (C-ESD n=284, T-ESD n=282) were included. The mean age was 67±10 y and 60% were men. As compared with the T-ESD technique, the C-ESD group was associated with longer procedure time (SMD 0.91, 95% CI 0.58 to 1.23, P<0.00001) and lesser resection speed (SMD -1.03, 95% CI -2.01 to -0.06, P=0.04). No significant difference was found in the 2 groups with respect to R0 resection rate (RR 1.00, 95% CI 0.94 to 1.06, P=0.87), en bloc resection (RR 0.99, 95% CI 0.97 to 1.01, P=0.35), delayed bleeding (RR 0.66, 95% CI 0.17 to 2.59, P=0.55) and perforation (RR 2.16, 95% CI 0.75 to 6.27, P=0.16). DISCUSSION: On meta-analysis, pooled procedure time was significantly faster with T-ESD compared with C-ESD. The clinical outcomes, however, were comparable.

Prevalence of Gastrointestinal Symptoms, Hepatic Dysfunction, and Outcomes in Hospitalized Patients With COVID-19 Infection: An Early Experience.

Background and objective Coronavirus disease 2019 (COVID-19) was first reported in China two years ago as primarily a lung infection associated with cough and fever. It spread rapidly across the world and was declared a pandemic in early 2020, with 131 million people infected and 2.85 million deaths worldwide. To date, approximately 550,000 deaths have occurred due to COVID-19 in the United States and the numbers continue to rise. The extrapulmonary manifestations of this disease such as acute kidney injury (AKI), cardiovascular events, and gastrointestinal (GI) indications were not emphasized initially. However, subsequent studies from the United States and Canada have noted GI involvement in this disease in a large number of cases. Our group, taking care of these patients during the early phase of the pandemic in 2020, observed the frequent presentations of GI symptoms such as diarrhea and hepatic dysfunction and this study examines the same. Methods We undertook a retrospective study of 184 consecutive adult patients who were hospitalized at our center with confirmed COVID-19 infection, with a view to further elucidate the GI and hepatic involvement during the early breakout (March 17-May 17, 2020) of this illness. Results Major comorbidities associated with this illness in our cohort of patients included hypertension (HTN, 66%), diabetes mellitus (DM, 44%), obesity (41%), and chronic kidney disease (CKD, 17%). The most common GI manifestation was diarrhea (25%) and, interestingly, more than two-thirds of the patients had at least one liver function abnormality. The most common liver function abnormality was elevated serum aspartate aminotransferase (AST). Elevated AST was significantly correlated (p<0.05) with inflammatory markers such as D-dimer, lactate dehydrogenase (LDH), and ferritin, as well as AKI by bi-variate analysis. Salient observations from our study include higher mortality, frequent AKI, and cardiovascular events in male patients (p<0.05).  The liver injury in our cohort was suspected to be multifactorial, involving excessive cytokine release, viral infiltration of the hepatocytes, and cholangiocytes playing a role in transaminitis. The mean (±SD) duration of hospital stay was 13.5 ±15 days with 33% admissions to the ICU. The overall mortality was around 27%, with no significant difference between African Americans and Caucasians. However, patients admitted to the ICU had a very high mortality rate (54%) compared to those admitted to intermediate care (IMC)/acute care who had less severity of illness and associated pulmonary complications. Conclusions This study evaluates the presence of comorbidities such as DM, HTN, and obesity in patients hospitalized with COVID-19 at a community hospital in the Mid-Atlantic region of the United States. Statistical analysis of the data obtained for this cohort revealed a high frequency of GI symptoms, with diarrhea as the predominant common initial manifestation of the disease. Serum AST elevations were common and correlated with inflammatory markers and AKI. Male gender was also significantly associated with the development of AKI, higher frequency of cardiovascular events, and increased mortality. Overall mortality was noted to be 27%, with higher mortality in patients admitted to the ICU (54%) as compared to the IMC/floor (13%). These observations should spur future investigations into the role of these comorbidities, development of diarrhea, and hepatic dysfunction in COVID-19.

Identification and engraftment of new bacterial strains by shotgun metagenomic sequence analysis in patients with recurrent Clostridioides difficile infection before and after fecal microbiota transplantation and in healthy human subjects.

BACKGROUND: Recurrent Clostridioides diffícile infection (RCDI) is associated with major bacterial dysbiosis and colitis. Fecal microbiota transplantation (FMT) is a highly effective therapeutic modality for RCDI. While several studies have identified bacterial species associated with resolution of symptoms in patients, characterization of the fecal microbiome at the bacterial strain level in RCDI patients before and after FMT and healthy donors, has been lacking. The aim of this study was to examine the ability of bacterial strains from healthy donors to engraft in the gastrointestinal tract of patients with RCDI following FMT. METHODS: Fecal samples were collected from 22 patients with RCDI before and after FMT and their corresponding healthy donors. Total DNA was extracted from each sample and analyzed by shotgun metagenomic sequencing. The Cosmos-ID analysis platform was used for taxonomic assignment of sequences and calculation of the relative abundance (RA) of bacterial species and strains. From these data, the total number of bacterial strains (BSI), Shannon diversity index, dysbiosis index (DI), and bacterial engraftment factor, were calculated for each strain. FINDINGS: A marked reduction (p<0·0001) in the RA of total and specific bacterial strains, especially from phylum Firmicutes, was observed in RCDI patients prior to FMT. This change was associated with an increase in the DI (p<0·0001) and in pathobiont bacterial strains from phylum Proteobacteria, such as Escherichia coli O157:H7 and Klebsiella pneumoniae UCI 34. BSI was significantly lower in this group of patients as compared to healthy donors and correlated with the Shannon Index. (p<0·0001). Identification and engraftment of bacterial strains from healthy donors revealed a greater diversity and higher relative abundance of short-chain fatty acid (SCFA)-producing bacterial strains, including Lachnospiraceae bacterium 5_1_63FAA_u_t, Dorea formicigenerans ATCC 27755, Anaerostipes hadrusand others, in RCDI patients after FMT. INTERPRETATION: These observations identify a group of SCFA-producing bacterial strains from healthy donors that engraft well in patients with RCDI following FMT and are associated with complete resolution of clinical symptoms and bacterial dysbiosis.

Superiority of Higher-Volume Fresh Feces Compared to Lower-Volume Frozen Feces in Fecal Microbiota Transplantation for Recurrent Clostridioides Difficile Colitis.

GOALS: To compare the clinical outcomes of different protocols for fecal microbiota transplantation (FMT) in two community hospitals with similar patient demographics. BACKGROUND: FMT is commonly performed for recurrent or refractory Clostridioides difficile infection (rCDI). The clinical efficacy of FMT for this indication has been well established. However, there has been no standardization or optimization of the amount of fecal material, method of feces preparation, or route of delivery for FMT. STUDY: In this retrospective study, patients with rCDI received FMT using commercially available frozen fecal preparation (22.7 g) at Center A and locally prepared fresh fecal filtrate (30-50 g) at Center B. The primary outcome was defined as complete resolution of clinical symptoms related to rCDI after at least 8 weeks of follow-up. RESULTS: Fifty patients from each center were included in the study. Clinical success after initial FMT with lower-volume frozen fecal preparation at Center A was 32/50 (64.0%) compared to 49/50 (98.0%) with higher-volume fresh fecal filtrate at Center B (p < 0.0001). Seventeen patients in Center A and 1 patient in Center B underwent at least one repeat FMT. Overall clinical success was achieved in 43/50 (86%) of patients in Center A and 50/50 (100%) in Center B (p = 0.012). CONCLUSIONS: Our results suggest superior clinical efficacy of a larger amount of fresh fecal filtrate over a smaller amount of commercially available frozen fecal preparation. Further studies are needed to examine the effect of varying amounts of feces and the optimal protocol for FMT in patients with rCDI.

Parkinson's Disease: The Emerging Role of Gut Dysbiosis, Antibiotics, Probiotics, and Fecal Microbiota Transplantation.

The role of the microbiome in health and human disease has emerged at the forefront of medicine in the 21st century. Over the last 2 decades evidence has emerged to suggest that inflammation-derived oxidative damage and cytokine induced toxicity may play a significant role in the neuronal damage associated with Parkinson's disease (PD). Presence of pro-inflammatory cytokines and T cell infiltration has been observed in the brain parenchyma of patients with PD. Furthermore, evidence for inflammatory changes has been reported in the enteric nervous system, the vagus nerve branches and glial cells. The presence of α-synuclein deposits in the post-mortem brain biopsy in patients with PD has further substantiated the role of inflammation in PD. It has been suggested that the α-synuclein misfolding might begin in the gut and spread "prion like" via the vagus nerve into lower brainstem and ultimately to the midbrain; this is known as the Braak hypothesis. It is noteworthy that the presence of gastrointestinal symptoms (constipation, dysphagia, and hypersalivation), altered gut microbiota and leaky gut have been observed in PD patients several years prior to the clinical onset of the disease. These clinical observations have been supported by in vitro studies in mice as well, demonstrating the role of genetic (α-synuclein overexpression) and environmental (gut dysbiosis) factors in the pathogenesis of PD. The restoration of the gut microbiome in patients with PD may alter the clinical progression of PD and this alteration can be accomplished by carefully designed studies using customized probiotics and fecal microbiota transplantation.

Pancreatic Extramedullary Plasmacytoma Presenting as a Pancreatic Mass.

Extramedullary plasmacytomas (EMP) are a subcategory of plasma cell neoplasm that involves organs outside the bone marrow. Involvement of the pancreas is relatively rare, reported in only 2.3% of autopsies. Radiologic findings in plasmacytoma are nonspecific, but endoscopic ultrasound fine-needle aspiration is a fast and reliable technique to acquire a histologic sample for initial diagnosis. Recently, the use of fluorine-18 fluorodeoxyglucose PET/CT has been recommended in patients with active multiple myeloma and solitary plasmacytoma. We present an interesting case of primary EMP in the pancreatic body encasing the portal vein as well as the celiac artery, which was detected before the patient was diagnosed of multiple myeloma.

A Case of Acute Severe Hepatotoxicity and Mild Constriction of Common Bile Duct Associated With Ingestion of Green Tea Extract: A Clinical Challenge.

Consumption of herbal and dietary supplements (HDS) has increased worldwide as potential treatment for weight reduction and metabolic enhancement. However, it has been reported that HDS can cause liver injury which accounts for 20% of hepatotoxicity in the United States. Prevention of HDS induced liver injury remains a challenge due to difficulties in identifying the hepatotoxins in these preparations and lack of federal regulations for dietary supplements. We report a case of acute severe hepatic necrosis presumably due to consumption of nutritional supplement advertised to boost vitality and stem cells in human body.

Unexplained Portal Gas in a Patient with an Esophageal Ulcer.

Emphysematous gastritis is the infection of gastric mucosa by gas producing microorganisms. It is a rare infection with less than 100 cases reported in the literature. The association of portal venous gas along with emphysematous gastritis is a rare entity. The concomitant portal venous gas worsens the outcome and warrant for surgical treatment. Our case has portal venous gas on CT scan along with suspicion of emphysematous gastritis and an esophageal ulcer on upper GI endoscopy. Medical treatment was given in our case of portal venous gas with the esophageal ulcer. Our case is unique because our patient responded to the conservative management. The patient presented with past history of polysubstance abuse and chronic kidney disease presented with symptoms of acute abdomen. CT scan revealed portal venous gas and suspicion of gastric emphysema. In addition, few foci of gas are seen along the vessels traversing between the stomach and liver. Endoscopy with gastric mucosa biopsy showed Candida albicans. Subsequently, antifungals were started. There was improvement in clinical condition of the patient. We, hereby, also summarize all the reported cases of emphysematous gastritis with treatment and outcome in each case. There has been change in trend from surgical to medical treatment.

Grading of EUS-FNA cytologic specimens from patients with pancreatic neuroendocrine neoplasms: it is time move to tissue core biopsy?

Pancreatic neuroendocrine neoplasms (p-NENs) are rare and characterized by an indolent course, with a much better prognosis than non-neuroendocrine tumors of the pancreas. In the non-functional class of p-NENS, surgery remains the only curative treatment for early localized disease, but there are few therapeutic options for advanced disease. The prognosis of non-functional p-NENs is determined by many clinical criteria. In 2010, however, the World Health Organization (WHO) introduced a grading system in which determination of the Ki-67 proliferative index has become essential with key role in determining therapeutic decision in both advanced and early diseases. Conventionally, Ki-67 has been assessed on surgical specimens. In last decade, however, the availability of EUS-guided fine needle aspiration (EUS-FNA) has provided the opportunity to sample pancreatic lesions and to assess the value of this parameter pre-operatively. The few studies reporting the use of EUS-FNA cytological specimens for Ki-67 measurement showed promising results. As shown by Weynand and colleagues FNA-cytology may underestimate the staging and caution in using this method to classify tumors as low-grade (G1) should be adopted. Thus, Ki-67 expression on cytological specimens remains unsatisfactory and the need for tissue biopsy specimens has been strongly advocated. Based on a recent study that has reported a high concordance of EUS-guided core biopsy for histologic examination and surgical specimens, especially when a cut-off of 5% is used to differentiate G1 and G2 tumors, EUS tissue acquisition by core biopsy is ready for prime time and should be adopted as a standard of practice.

Endoscopic therapy with 2-octyl-cyanoacrylate for the treatment of gastric varices.

BACKGROUND: Gastric variceal bleeding is associated with significant morbidity and mortality and limited endoscopic therapeutic options. AIM: The aim of this study was to evaluate the short- and long-term efficacy and safety of endoscopic therapy with 2-octyl-cyanoacrylate in patients with gastric variceal bleeding. METHODS: A single-center retrospective review of patients receiving endoscopic therapy for gastric variceal hemorrhage. Patient demographics, laboratory, and procedural data were collected. Patients were followed to death, liver transplantation, or last follow-up. Success rates were defined as immediate control of bleeding; early re-bleeding (1-7 days), short-term re-bleeding (1-12 weeks), overall survival, and serious procedure complications. RESULTS: A total of 41 patients (39 with cirrhosis) underwent 54 cyanoacrylate injections during study period. Mean age was 57 and 73 % were males. Twenty-four (58.5 %) patients had failed or were deemed ineligible for transjugular intra-hepatic portosystemic shunt, and 5 % were done for primary prophylaxis. Immediate hemostasis was achieved in five active bleeders. During a median survival time of 117 days, early re-bleeding was seen in 1 (2.4 %), short-term re-bleeding in five patients (12 %), and varices were eradicated in 15 (46.8 %) patients on follow-up. Mean MELD score at the time of the first injection was 17.1 ± 7.8. Mean volume injected was 3.4 cc and median number of varices injected per session was one. Eight patients died during the long-term follow-up: metastatic cancer (2), infections (3), liver failure (1), and re-bleeding (2). There were no serious procedure-related complications. CONCLUSIONS: Endoscopic cyanoacrylate therapy appears effective and safe for treatment of patients with bleeding from gastric varices or high-risk stigmata.

Efficacy of combined jejunal and colonic fecal microbiota transplantation for recurrent Clostridium difficile Infection.

The prevalence of recurrent Clostridium difficile infection (RCDI) is increasing; fecal microbiota transplantation (FMT) is an effective therapy. However, there have been no studies of the efficacy of a single session of combined enteral and colonic FMT or characterizations of changes in the microbiota between donors and recipients. We performed a study of 27 patients with RCDI who were given a fixed volume of processed fecal filtrate via enteroscopy and colonoscopy in a single session. Patients were closely monitored, and fecal samples were collected from 2 patient-donor pairs for 16S rRNA analysis. All patients had reduced stool frequency, abdominal pain, white blood cell counts, and elimination of fecal C difficile toxin (P < .05). FMT increased microbial diversity, increasing proportions of Lachnospiraceae (phylum Firmicutes) and reducing proportions of Enterobacteriaceae. FMT was associated with marked changes in the composition of fecal microbiota in 2 patients with RCDI.

The therapeutic approaches for hepatitis C virus: protease inhibitors and polymerase inhibitors.

The current standard of care for hepatitis C infection is peginterferon/ribavirin (PegIFN/RBV). We are entering the era where direct-acting antiviral agents (DAAs) will be added to PegIFN/RBV, leading to higher sustained response rates in genotype 1 infected individuals. Currently DAAs are directed toward specific proteins involved in hepatitis C replication with NS3/NS4A protease inhibitors furthest in development. Telaprevir and boceprevir are both NS3/NS4a inhibitors that significantly improve sustained response when added to PegIFN and RBV. The hepatitis C virus (HCV) polymerase inhibitors are another promising DAA class. These molecules are divided into nucleoside/nucleotide polymerase inhibitors and nonnucleotide/nucleoside polymerase inhibitors. Nucleoside/nucleotide polymerase inhibitors have a high barrier to resistance and appear to be effective across a broad range of genotypes. Nonnucleoside polymerase inhibitors have a lower barrier of resistance and appear to be genotype specific. Preliminary data with these compounds are also promising. A third class, NS5A inhibitors, has also shown potent HCV RNA suppression in preliminary studies as monotherapy and with PegIFN and RBV. Combinations of these agents are also entering clinical trials and indeed a preliminary report has demonstrated that the combination of an NS3/4A protease inhibitor and NS5B polymerase inhibitor can effectively suppress virus in genotype 1 individuals. Future studies will concentrate on combinations of direct-acting antiviral agents without and with PegIFN and RBV. Clinicians will need to be familiar with managing side effects as well as resistance as we enter this new era.