Hemostatic spray (TC-325) vs. standard endoscopic therapy for non-variceal gastrointestinal bleeding: A meta-analysis of randomized controlled trials.

Background and study aims Hemospray (TC-325) is a mineral powder with adsorptive properties designed for use in various gastrointestinal bleeding (GIB) scenarios. We conducted a systematic review & meta-analysis of randomized controlled trials (RCTs) comparing TC-325 to standard endoscopic therapy (SET) for non-variceal GIB (NVGIB). Methods Multiple databases were searched through October 2022. Meta-analysis was performed using a random-effects model to determine pooled relative risk (RR) and proportions with 95 % confidence intervals (CI) for primary hemostasis, hemostasis failure, 30-day rebleeding, length of stay (LOS), and need for rescue interventions. Heterogeneity was assessed using I 2 %. Results Five RCTs with 362 patients (TC-325 178, SET 184) - 123 females and 239 males with a mean age 65 ±â€Š16 years). The most common etiologies were peptic ulcer disease (48 %), malignancies (35 %), and others (17 %). Bleeding was characterized as Forrest IA (7 %), IB (73 %), IIA (3 %), and IIB (1 %). SET included epinephrine injection, electrocautery, hemoclips, or a combination. No statistical difference in primary hemostasis between TC-325 compared to SET, RR 1.09 (CI 0.95-1.25; I 2 43), P =  0.2, including patients with oozing/spurting hemorrhage, RR 1.13 (CI 0.98-1.3; I 2 35), P =  0.08. Failure to achieve hemostasis was higher in SET compared to TC-325, RR 0.30 (CI 0.12-0.77, I 2 0), P =  0.01, including patients with oozing/spurting hemorrhage, RR 0.24 (CI 0.09 - 0.63, I 2 0), P =  0.004. We found no difference between the two interventions in terms of rebleeding, RR 1.13 (CI 0.62-2.07, I 2 26), P =  0.8 and LOS, standardized mean difference (SMD) 0.27 (CI, -0.20-0.74; I 2 62), P =  0.3. Finally, pooled rate of rescue interventions (angiography) was statistically higher in SET compared to TC-325, RR 0.68 (CI 0.5-0.94; I 2 0), P =  0.02. Conclusions Our analysis shows that for acute NV GIB, including oozing/spurting hemorrhage, TC-325 does not result in higher rates of primary hemostasis compared to SET. However, lower rates of failures were seen with TC-325 than SET. In addition, there was no difference in the two modalities when comparing rates of rebleeding and LOS.

Reply to Lissing et al. Comment on "Ramai et al. Risk of Hepatocellular Carcinoma in Patients with Porphyria: A Systematic Review. Cancers 2022, 14, 2947".

We thank Dr. Lissing and colleagues for providing us with these helpful comments [...].

Efficacy & safety of EUS-directed transgastric endoscopic retrograde cholangiopancreatography (EDGE) in Roux-en-Y gastric bypass anatomy: a systematic review & meta-analysis.

BACKGROUND: In patients with Roux-en-Y gastric bypass (RYGB) anatomy, laparoscopic endoscopic retrograde cholangiopancreatography (LA-ERCP) and enteroscopy-assisted ERCP (E-ERCP) have been utilized to achieve pancreaticobiliary access. Endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (EDGE) has recently emerged as an alternate and efficient approach. As data regarding EDGE continues to evolve, concerns about safety and efficacy remain, limiting wide adoptability. We performed a systematic review and meta-analysis to assess the safety and efficacy of EDGE and compare it to the current standard of care. METHODS: A comprehensive search of major databases (inception to Nov 2022) identified published studies on EDGE. A random-effects model was used to calculate the pooled rates and heterogeneity (I2). Risk ratio (RR) and standardized difference in means (SMD) were utilized for head-to-head comparison analysis between EDGE vs. LA-ERCP and EDGE vs. E-ERCP. Primary outcomes assessed pooled EDGE safety (adverse events) and efficacy (technical/clinical success). Secondary outcomes assessed efficacy and safety profiles via a comparative analysis of EDGE vs. LA-ERCP and EDGE vs. E-ERCP. RESULTS: A total of 16 studies (470 patients) were included. EDGE pooled technical success (TS) rate was 96% (95% CI 92-97.6, I2 = 0), and clinical success was 91% (85-95, I2 = 0). Pooled rate of all adverse events with EDGE was 17% (14-24.6, I2 = 32%). On sub-group analysis, these included failure of fistula closure 17% (10-25.5, I2 = 48%), stent migration 7% (4-12, I2 = 51%), bleeding 5% (3.2-7.9, I2 = 0), post-EDGE weight gain 4% (2-9, I2 = 0), perforation 4% (2.1-5.8, I2 = 0), and post-ERCP pancreatitis 2% (1-5, I2 = 0). EDGE TS was comparable to LA-ERCP (97% vs. 98%; RR, 1.00; CI, 0.85-1.17, p = 0.95) and E-ERCP (100% vs. 66%; RR, 1.26; CI, 0.99-1.6, p = 0.06). No statistical difference was noted in adverse events between EDGE and LA-ERCP (13% vs. 17.6%; RR, 0.61; CI, 0.28-1.35, p = 0.52) and E-ERCP (9.6% vs. 16%; RR, 0.61; CI, 0.28-1.35, p = 0.22). EDGE procedure time and hospital stay were shorter than LA-ERCP and E-ERCP (p < 0.001). CONCLUSION: Our analysis shows that EDGE is safe and efficacious to the current standard of care. Further head-to-head comparative trials are needed to validate our findings.

Early (<4 weeks) versus standard (≥4 weeks) endoscopic drainage of pancreatic walled-off fluid collections: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Previous studies have demonstrated that the ideal time for drainage of walled-off pancreatic fluid collections is 4 to 6 weeks after their development. However, some pancreatic collections, notably infected pancreatic fluid collections, require earlier drainage. Nevertheless, the optimal timing of the first intervention is unclear, and consensus data are sparse. The aim of this study was to evaluate the clinical efficacy and safety of EUS-guided drainage of pancreatic fluid collections <4 weeks after development compared with ≥4 weeks after development. METHODS: Search strategies were developed for PubMed, Embase, and Cochrane Library databases from inception. Outcomes of interest were technical success, defined as successful endoscopic placement of a lumen-apposing metal stent; clinical success, defined as a reduction in cystic collection size; and procedure-related adverse events. A random-effects model was used for analysis, and results are expressed as odds ratio (OR) with 95% confidence interval (CI). RESULTS: Six studies (630 patients) were included in our final analysis, in which 182 patients (28.9%) were enrolled in the early drainage cohort and 448 patients (71.1%) in the standard drainage cohort. The mean fluid collection size was 143.4 ± 18.8 mm for the early cohort versus 128 ± 19.7 mm for the standard cohort. Overall, technical success was equal in both cohorts. Clinical success did not favor either standard drainage or early drainage (OR, .39; 95% CI, .13-1.22; P = .11). No statistically significant differences were found in overall adverse events (OR, 1.67; 95% CI, .63-4.45; P = .31) or mortality (OR, 1.14; 95% CI, .29-4.48; P = .85). Hospital stay was longer for patients undergoing early drainage compared with standard drainage (23.7 vs 16.0 days, respectively). CONCLUSIONS: Both early (<4 weeks) and standard (≥4 weeks) drainage of walled-off pancreatic fluid collections offer similar technical and clinical outcomes. Patients requiring endoscopic drainage should not be delayed for 4 weeks.

The diagnostic performance of probe-based confocal laser endomicroscopy in the detection of gastric cancer: a systematic review and meta-analysis.

Background: Gastric cancer (GC) represents a significant global health burden with high morbidity and mortality, especially when diagnosed at advanced stages. Therefore, early detection of GC is critical. Probe-based confocal laser endomicroscopy (pCLE) is a new evolving technology that uses real-time, high-resolution imaging to inspect the mucosa at the cellular and microvascular level, using a confocal probe. Widespread studies using pCLE are limited at the current time. We aimed to investigate the diagnostic efficacy of this modality for the detection of GC. Methods: Multiple databases were searched from inception until November 2021. The diagnostic performance of pCLE was assessed by calculating its sensitivity, specificity and accuracy for the detection of GC, using pooled proportions and 95% confidence intervals (CI) with a random-effects model. Heterogeneity was assessed using I2. Results: Seven studies were included, with a total of 567 patients (mean age 61.7 years, 364 males). Pooled performance metrics of pCLE included a sensitivity of 87.9% (95%CI 81.4-92.4; P<0.001; I2=0%), specificity 96.5% (95%CI 91.5-98.6; P<0.001; I2=51.84%), and an accuracy of 94.7% (95%CI 89.5-97.4; P<0.001; I2=65.44%). Conclusions: pCLE is a highly effective diagnostic modality for detecting GC. Larger, randomized controlled studies are needed to determine its role in daily practice compared to conventional endoscopic practices.

Risk of Hepatocellular Carcinoma in Patients with Porphyria: A Systematic Review.

Acute porphyrias are a group of metabolic disorders resulting in defective porphyrin synthesis and reduced heme production, which carries a risk of malignancy. Porphyrias are inborn defects in the heme biosynthesis pathway resulting in neurovisceral manifestations and cutaneous photosensitivity attacks with multi-systemic involvement. Its estimated prevalence nears 5 per 100,000 patients worldwide. Subclinical liver disease is common, which can progress into transaminitis, fibrosis, cirrhosis, and malignancy. However, data on the incidence of primary liver cancer are lacking. We aim to determine the risk of hepatocellular carcinoma (HCC) in patients with porphyria. A systematic review and pooled analysis were conducted through 2021 on studies assessing blood tests, imaging, cancer development, liver transplant, surgical resection, and outcomes in porphyria. In total, 19 studies, which included 7381 patients with porphyria (3476 females), were considered for the final review. In eight studies, alpha-fetoprotein levels were elevated between 200 and 1000 IU/mL. Of the total cohort of patients with porphyria, primary liver cancer was diagnosed in 351 patients (4.8%), of whom 243 (3.3% of the total) were found to have HCC. A subset of patients was found to have cholangiocarcinoma (n = 18; 0.3% of the total). Interestingly, advanced liver disease or cirrhosis was not a prerequisite for the formation of HCC in a small group of patients. Of the total cohort, 30 patients underwent liver resection, 48 patients underwent liver transplantation, and 327 patients died. Patients with porphyria are at risk of developing primary liver malignancy. Further studies should aim to develop diagnostic and prognostic models aimed at the early detection of HCC in porphyria.

When Variants Collide: An Unusual Presentation of Metastatic Gastric Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm.

Gastrointestinal neuroendocrine neoplasms were recently reclassified into the 2019 World Health Organization schema into well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas, and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). Among these, gastric MiNENs are exceedingly rare and often metastasize quickly without diagnostic clues. We present a refractory gastric MiNEN with unique presenting features. This case highlights the clinical spectrum of these tumors, the importance of accurate histochemical interpretation, and clinical management in the absence of formalized guidelines. Future therapies looking at novel targets and palliative symptom relief are needed.

Blowing off steam-Identifying bowel perforation after routine colonoscopy.

Colonoscopy is an effective procedure for colorectal cancer (CRC) screening. Perforation is a rare yet the most severe complication, identified by landmarks-double dolphin, triangle, or double-wall sign signifying air and intracolonic contents leaking into the peritoneal space. Prompt recognition and surgical intervention are imperative to avoid high mortality.

Sarcoidosis Masquerading as Long-Standing Cholestasis.

Hepatic sarcoidosis is an exceedingly rare extrapulmonary manifestation of sarcoidosis, with the majority remaining stable for years without clinical clues, only displaying biochemical abnormalities. Amongst the literature, the timeline to cirrhosis has not been parsed out; hepatomegaly develops in 50% and cirrhosis in 33% of all hepatic sarcoidosis patients, making this an essential issue in this patient population. Interestingly, the risk for hepatocellular carcinoma remains high regardless of cirrhosis development. Corticosteroids and biologics remain the mainstay of therapy, although refractory cases may require deeper immunosuppression. Liver transplantation is seen in a handful of cases with promising results. We present an interesting case of cholestatic pattern livery injury in our outpatient setting that was eventually discovered to be hepatic sarcoidosis. Mild biochemical derangements or sole elevations in alkaline phosphatase are under-recognized, and patients often progress to cirrhosis and end-stage liver disease. This diagnostic miss has significant implications and represents an opportunity to treat liver disease with a reversible cause. Consensus guidelines recommend alkaline phosphatase screening in newly diagnosed cases of sarcoidosis.

Artificial intelligence (AI) real-time detection vs. routine colonoscopy for colorectal neoplasia: a meta-analysis and trial sequential analysis.

GOALS AND BACKGROUND: Studies analyzing artificial intelligence (AI) in colonoscopies have reported improvements in detecting colorectal cancer (CRC) lesions, however its utility in the realworld remains limited. In this systematic review and meta-analysis, we evaluate the efficacy of AI-assisted colonoscopies against routine colonoscopy (RC). STUDY: We performed an extensive search of major databases (through January 2021) for randomized controlled trials (RCTs) reporting adenoma and polyp detection rates. Odds ratio (OR) and standardized mean differences (SMD) with 95% confidence intervals (CIs) were reported. Additionally, trial sequential analysis (TSA) was performed to guard against errors. RESULTS: Six RCTs were included (4996 participants). The mean age (SD) was 51.99 (4.43) years, and 49% were females. Detection rates favored AI over RC for adenomas (OR 1.77; 95% CI: 1.570-2.08) and polyps (OR 1.91; 95% CI: 1.68-2.16). Secondary outcomes including mean number of adenomas (SMD 0.23; 95% CI: 0.18-0.29) and polyps (SMD 0.23; 95% CI: 0.17-0.29) detected per procedure favored AI. However, RC outperformed AI in detecting pedunculated polyps. Withdrawal times (WTs) favored AI when biopsies were included, while WTs without biopsies, cecal intubation times, and bowel preparation adequacy were similar. CONCLUSIONS: Colonoscopies equipped with AI detection algorithms could significantly detect previously missed adenomas and polyps while retaining the ability to self-assess and improve periodically. More effective clearance of diminutive adenomas may allow lengthening in surveillance intervals, reducing the burden of surveillance colonoscopies, and increasing its accessibility to those at higher risk. TSA ruled out the risk for false-positive results and confirmed a sufficient sample size to detect the observed effect. Currently, these findings suggest that AI-assisted colonoscopy can serve as a useful proxy to address critical gaps in CRC identification.

Black Esophagus in the Setting of Alcohol Abuse after External Beam Radiation.

Acute esophageal necrosis (AEN), black esophagus, or Gurvits syndrome is a rare clinical disorder characterized by a striking endoscopic appearance of necrotic esophageal mucosa, universally affecting the distal esophagus and ending abruptly at the gastroesophageal junction. It has been gaining traction as a demonstrable cause of upper gastrointestinal bleeding in the 21st century. Its pathophysiology is multifactorial affecting men and the elderly disproportionally, with a mortality rate nearing 36%. AEN has been associated with numerous conditions in the past, and we aim to present an unusual case of AEN on the setting of chronic alcohol use.

Severe primary refractory thrombotic thrombocytopenic purpura (TTP) in the post plasma exchange (PEX) and rituximab era.

Acute acquired thrombotic thrombocytopenic purpura (TTP) requires prompt recognition and initiation of plasma exchange (PEX) therapy and immunosuppression. When PEX fails, mortality nears 100%, making finding an effective treatment crucial. Primary refractory TTP occurs when initial therapies fail or if exacerbations occur during PEX therapy, both signifying the need for treatment intensification to achieve clinical remission. Rituximab helps treat most of the refractory TTP cases, except those that are severely refractory. A paucity of studies guiding severely refractory TTP makes management arbitrary and individualised, highlighting the value of isolated reports. We present an extremely rare case of primary refractory TTP with an insufficient platelet response to numerous types of treatments, including emerging therapies such as caplacizumab, on the background of repeated PEX and immunosuppressive therapies.