Efficacy and Safety of Full-thickness Resection Device (FTRD) for Colorectal Lesions Endoscopic Full-thickness Resection: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Endoscopic full-thickness resection (eFTR) is a field of increasing interest that offers a minimally invasive resection modality for lesions that are not amenable for resection by conventional methods. Full-thickness resection device (FTRD) is a new device that was developed for a single-step eFTR using an over-the scope-clip. In this meta-analysis, we aim to assess the efficacy and safety of FTRD for eFTR of colorectal lesions. METHODS: A Comprehensive literature review of different databases to identify studies reporting FTRD with outcomes of interest was performed. Studies with <10 cases were excluded. Rates of histologic complete resection (R0), technical success, and complications were extracted. Efficacy was assessed by using the technical and the R0 rates whereas safety was assessed by using the complications rates. Weighted pooled rates (WPRs) and the 95% confidence interval (CI) were calculated depending on the heterogeneity (I2 statistics). RESULTS: Nine studies including 551 patients with 555 lesions were included in this study. The WPR for overall R0 was 82.4% (95% CI: 79.0%-85.5%),with moderate heterogeneity (I2=34.8%). The WPR rate for technical success was 89.25% (95% CI: 86.4%-91.7%), with low heterogeneity (I2=23.7%). The WPR for total complications rate was 10.2% (7.8, 12.8%) with no heterogeneity. The pooled rate for minor bleeding, major bleeding, postpolypectomy syndrome, and perforation were 3.2%, 0.97%, 2.2%, and 1.2%, respectively. Of 44 periappendicular lesions, the pooled rate for acute appendicitis was 19.7%. CONCLUSIONS: FTRD seems to be effective and safe for eFTR of difficult colorectal lesions. Large prospective studies comparing FTRD with conventional resection techniques are warranted.

The adherence to the American Association for the Study of Liver Diseases 2018 guidelines in the management of hepatocellular carcinoma and its impact on survival.

Introduction: In two Korean and Italian studies, the adherence rate (AR) to ASSLD 2005 guidelines in the management of hepatocellular carcinoma (HCC) was 60%. In a US study, the AR to American Association for the Study of Liver Disease (AASLD) 2005 guidelines was 73.3%, 26.8%, 25.3%, and 58.8% for patients with Barcelona Clinic Liver Cancer (BCLC) Stage A, B, C, and D, respectively, and nonadherence to guidelines was associated with longer overall survival (OS) in patients with BCLC Stage D. Here, we explored the AR to AASLD 2018 guidelines and its impact on OS. Methods: Between 2017 and 2019, 148 unique treatment-naïve patients with HCC were identified. Patients were staged according to the BCLC staging system and their AR to AASLD 2018 guidelines was noted. OS was estimated using Kaplan-Meier method. Survivals among patients from different groups was compared using Log-rank test. Results: The overall AR to AASLD 2018 guidelines was 83%. The AR for BCLC Stages 0, A, B, C, and D were 100%, 97%, 77%, 77%, and 38%, respectively. In patients with BCLC Stage D, the OS of patients treated with modalities adherent versus nonadherent to AASLD 2018 guidelines was 0.03 vs. 5.2 months (P = 0.0005). Otherwise, adherence versus nonadherence to AASLD 2018 guidelines showed no statistically significant differences in OS for patients with BCLC Stages 0, A, B, and C. Conclusion: The overall AR to AASLD 2018 guidelines was 83%. Nonadherence to AASLD 2018 guidelines in patients with BCLC Stage D translated into better OS.

Efficacy and safety of endoscopic ultrasound-guided radiofrequency ablation for management of pancreatic lesions: a systematic review and meta-analysis.

Background: Radiofrequency ablation (RFA) has been used to treat various abdominal tumors including pancreatic tumors. Multiple approaches such as laparoscopic, open, and percutaneous have been used for pancreatic tissue ablation. More recently, endoscopic ultrasound (EUS)-guided RFA has emerged as a new technique for pancreatic tissue ablation. The role of EUS-RFA in management of pancreatic lesions is still not well-established. In this study, our aim is to assess efficacy and safety of EUS-RFA for management of pancreatic lesions. Methods: MEDLINE, Scopus, and Cochrane Library databases were searched to identify studies reporting EUS-RFA of pancreatic lesions with outcomes of interest. Studies with <5 patients were excluded. Clinical success was defined as symptom resolution, decrease in tumor size, and/or evidence of necrosis on radiologic imaging. Efficacy was assessed by the pooled clinical response rate whereas safety was assessed by the pooled adverse events rate. Heterogeneity was assessed using I2. Pooled estimates and the 95% CI were calculated using random-effect model. Results: Ten studies (5 retrospective and 5 prospective) involving 115 patients with 125 pancreatic lesions were included. 152 EUS-RFA procedures were performed. The lesions comprised of 37.6% non-functional neuroendocrine tumors (NFNETs), 15.4% were insulinomas, 26.5% were pancreatic cystic neoplasms (PCNs), and 19.7% were pancreatic adenocarcinomas. The majority were present in the pancreatic head (40.2%), 38.3% in the body, 11.2% in the tail, and 10.3% in the uncinate process. Pooled overall clinical response rate was 88.9% (95% CI: 82.4-93.7, I2=38.1%). Pooled overall adverse events rate was 6.7% (95% CI: 3.4-11.7, I2=34.0%). The most common complication was acute pancreatitis (3.3%) followed by pancreatic duct stenosis, peripancreatic fluid collection, and ascites (2.8%) each. Only one case of perforation was reported with pooled rate of (2.1%). Discussion: This study demonstrates that EUS-RFA is an effective treatment modality for pancreatic lesions, especially functional neuroendocrine tumors such as insulinomas.

Luminal-apposing stents for benign intraluminal strictures: a large United States multicenter study of clinical outcomes.

BACKGROUND: The use of fully covered lumen-apposing metal stents (LAMS) for benign short gastrointestinal (GI) strictures has been reported. This study aimed to evaluate the safety and efficacy of LAMS for refractory GI strictures. METHODS: A retrospective analysis was performed of patients who underwent LAMS placement for benign GI strictures in 8 United States centers. The primary outcomes were technical success and initial clinical response. Secondary outcomes were reintervention rate and adverse events. RESULTS: A total of 51 patients underwent 61 LAMS placement procedures; 33 (64.7%) had failed previous treatments. The most common stricture location was the pylorus (n=17 patients). Various sizes of stents were used, with 15-mm LAMS placed in 45 procedures, 20-mm LAMS in 14 procedures, and 10-mm LAMS in 2 procedures. The overall technical success, short-term clinical response and reintervention rate after stent removal were 100%, 91.8% and 31.1%, respectively. Adverse events were reported in 17 (27.9%) procedures, with stent migration being the most common (13.1%). In subgroup analysis, both 15 mm and 20 mm stents had comparable short-term clinical response and adverse event rates. However, stent migration (15.6%) was the most common adverse event with 15-mm LAMS while pain (14.3%) was the most common with 20-mm LAMS. The reintervention rate was 80% at 200-day follow up after stent removal. CONCLUSIONS: Using LAMS for treatment of short benign GI strictures is safe and effective. Larger LAMS, such as the new 20 mm in diameter, may have a lower stent migration rate compared to smaller diameter LAMS.

Life-Threatening Intrapulmonary Hemorrhage due to Vancomycin-Induced Thrombocytopenia: A Case Report.

Thrombocytopenia is a rare and sometimes life-threatening complication of Vancomycin. A 52-year-old male patient with acute kidney injury was treated with Vancomycin for ventilator-associated pneumonia. Three days later, his platelets decreased from 172 × 109/L to 3 × 109/L over a 36-hour period. The patient developed significant intrapulmonary bleeding leading to profound hypoxemia. Workup was negative for thrombotic thrombocytopenic purpura, disseminated intravascular coagulopathy, atypical hemolytic uremic syndrome, heparin-induced thrombocytopenia, and autoimmune diseases. All recently started medications were discontinued, and the patient was started empirically on methylprednisolone and intravenous immunoglobulin. The patient's platelets increased, and his airway bleeding stopped within 48 hours; his platelet count returned to normal by 18 days. Vancomycin-dependent anti-platelet antibodies were identified in the patient's serum by flow cytometry. Thrombocytopenia is an underrecognized complication of Vancomycin that can lead to life-threating bleeding. Stopping Vancomycin may be sufficient to reverse the thrombocytopenia in patients with normal renal function, but more aggressive measures such as steroids, IVIG, and dialysis may be required to stop bleeding and reverse thrombocytopenia in patients with underlying kidney injury who cannot effectively excrete Vancomycin.

Overcoming the Challenge of Full-Thickness Resection of Gastric Lesions Using a Colonic Full-Thickness Resection Device.

Endoscopic full-thickness resection device (FTRD) is a new and promising device for endoscopic full-thickness resection of gastrointestinal lesions. Limited data is available regarding its role in endoscopic full-thickness resection of upper gastrointestinal lesions compared with its well-studied role in colorectal lesions. Colonic FTRD is a preloaded device with a large cap which limits peroral insertion. A 49-year-old woman was referred to us for submucosal gastric lesion resection. Gradual dilatation of the upper esophagus was performed before successful advancement of the endoscope mounted with a FTRD system into the stomach. The lesion was successfully resected with no complications.

Piling Gold in the Prostate.

Radiation beams precisely directed at a tumor can attenuate the radiation to contiguous tissues. Image-guided radiation therapy using fiducials allows accurate delineation of tumor location. Traditionally, fiducials in the prostate have been placed by urologists or radiation oncologists. With the evolution of endoscopic ultrasound (EUS), fiducials have been successfully placed under the EUS guidance in different organs. In this case series, fiducials were placed in 3 patients with prostate cancer. All patients completed their radiation therapy, and no complications were reported except mild dysuria in one case. EUS-guided fiducial placement is safe and offers a new modality for fiducial placement in the prostate.

Usefulness of Restaging Pelvis Magnetic Resonance Imaging After Neoadjuvant Concurrent Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer.

INTRODUCTION: In patients with locally advanced rectal cancer, restaging pelvis magnetic resonance imaging (MRI) after neoadjuvant concurrent chemoradiotherapy is recommended despite its limited accuracy in predicting pathologic T (ypT) and N (ypN) stage. Neoadjuvant rectal (NAR) score is a novel short-term surrogate endpoint for disease-free survival (DFS) and overall survival (OS). We tested the agreement between restaging MRI T (yT) and N (yN) with ypT and ypN stages, respectively, and explored the prognostic significance of restaging MRI NAR (mNAR) score. PATIENTS AND METHODS: Between 2014 and 2018, 43 patients with locally advanced rectal cancer completed neoadjuvant concurrent chemoradiotherapy, had a restaging MRI, and underwent surgery. Weighted kappa was used to test the agreement between yT and yN with ypT and ypN, respectively. A kappa value of less than 0.5 was deemed unacceptable. Paired t test was used to compare NAR and mNAR mean scores. Survival was estimated by Kaplan-Meier curves. RESULTS: Restaging MRI could not predict ypT stage (slight agreement, κ = 0.111) or ypN stage (fair agreement, κ = 0.278). The mean mNAR score was higher than the mean NAR score (20 vs. 16, P = .0079). The median DFS for patients with low-intermediate NAR and high NAR was not reached vs. 30 months (P = .0063). The median OS for patients with low-intermediate NAR and high NAR was not reached vs. 40 months (P = .0056). There was a trend for longer DFS and OS in patients with low-intermediate mNAR scores (not reached in both groups, P = .058) compared to patients with high mNAR scores (not reached in both groups, P = .15). CONCLUSION: Restaging MRI could not predict ypT and ypN stage. The mean mNAR score was higher than the mean NAR score. There was a trend for longer DFS and OS in patients with low-intermediate mNAR scores compared to patients with high mNAR scores.

Vitamin B12 deficiency presenting as pseudo-thrombotic microangiopathy: a case report and literature review.

Pseudo-thrombotic microangiopathy (pseudo-TMA) is a recognized, yet uncommon, clinical presentation of vitamin B12 deficiency. Patients with pseudo-TMA present with microangiopathic hemolytic anemia (MAHA), thrombocytopenia and schistocytes. They are often misdiagnosed as thrombotic thrombocytopenia purpura (TTP) and receive unnecessary therapy. Here, we report a case of a 60-year-old male who presented with thrombocytopenia and normocytic normochromic anemia. Anemia work-up was remarkable for severe B12 deficiency (<60 pg/mL) and a positive non-immune hemolysis panel. Peripheral smear was reviewed and showed anisocytes, poikilocytes, schistocytes and hypersegmented neutrophils. Vitamin B12 replacement (1000 mcg IM daily) was started, ADAMTS13 activity was sent and daily plasmapheresis was initiated. Over the next 3 days, the patient's hemoglobin and platelets were stable and the hemolysis panel showed gradual improvement. On day 4, ADAMTS13 activity results came back normal at 61%. Accordingly, plasmapheresis was discontinued, parenteral B12 replacement was continued and that resulted in gradual improvement and eventually cessation of hemolysis and normalization of hemoglobin and platelets. In this patient, parietal cell autoantibodies were positive and so the diagnosis of pernicious anemia was made. Patients with severe vitamin B12 deficiency may present with features mimicking TTP such as MAHA, thrombocytopenia and schistocytosis. An early and accurate diagnosis of pseudo-TMA has a critical clinical impact with respect to administering the correct treatment with vitamin B12 replacement and avoiding, or shortening the duration of, unnecessary therapy with plasmapheresis.

Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern.

BACKGROUND: The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in colorectal cancer (CRC) differ among populations. The aim of this study was to assess mutation frequencies in the Arab population and determine their correlations with certain clinicopathological features. METHODS: Arab patients from the Arab Gulf region and a population of age- and sex-matched Western patients with CRC whose tumors were evaluated with next-generation sequencing (NGS) were identified and retrospectively reviewed. The mutation rates of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC were recorded, along with clinicopathological features. Other somatic mutation and their rates were also identified. Fisher's exact test was used to determine the association between mutation status and clinical features. RESULTS: A total of 198 cases were identified; 99 Arab patients and 99 Western patients. Fifty-two point seven percent of Arab patients had stage IV disease at initial presentation, 74.2% had left-sided tumors. Eighty-nine point two percent had tubular adenocarcinoma and 10.8% had mucinous adenocarcinoma. The prevalence rates of KRAS, NRAS, BRAF, PIK3CA, TP53, APC, SMAD, FBXW7 mutations in Arab population were 44.4%, 4%, 4%, 13.1%, 52.5%, 27.3%, 2% and 3% respectively. Compared to 48.4%, 4%, 4%, 12.1%, 47.5%, 24.2%, 11.1% and 0% respectively in matched Western population. Associations between these mutations and patient clinicopathological features were not statistically significant. CONCLUSIONS: This is the first study to report comprehensive hotspot mutations using NGS in Arab patients with CRC. The frequency of KRAS, NRAS, BRAF, TP53, APC and PIK3CA mutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency of FBXW7 mutation.

Continuation of trastuzumab beyond disease progression in HER2-positive metastatic gastric cancer: the MD Anderson experience.

BACKGROUND: Despite the wide spread use of trastuzumab in human epidermal growth factor receptor 2 (HER2) overexpressing metastatic gastric cancer patients, its optimal duration of administration beyond first-line disease progression is unknown. In HER2 overexpressing metastatic breast cancer, trastuzumab continuation beyond first-line disease progression has shown improvement in time to progression (TTP) without an increased risk of treatment related toxicity. METHODS: HER2-overexpressing metastatic gastric cancer patients were identified from our database between January 2010 and December 2014. We retrospectively reviewed the medical records of 43 patients who received trastuzumab in combination with chemotherapy as first-line and continued trastuzumab beyond disease progression. RESULTS: Forty-three cases were identified, 27 males (62.8%), median age of the patients was 58 years. Thirty-five (81.4%) presented with stage 4 as their initial presentation. Eighty one percent had 3+ HER2 overexpression by immunohistochemistry (IHC) and 18% had 2+ HER2 overexpression confirmed by fluorescence in situ hybridization (FISH). Thirteen (52%) were moderately differentiated, 16 (37.1%) were poorly differentiated. The most common sites of metastasis were liver 35 (81.4%) and lung 14 (32.5%). The most commonly used first-line regimen was oxaliplatin, 5-fluorouracil (5-FU), and trastuzumab in 22 (51.1%) patients. Twenty-five (58.1%) patients received irinotecan, 5-FU and trastuzumab in the second-line. Progression-free survival (PFS) was 5 months (95% CI: 4.01-5.99 months). Five patients are still alive and excluded from calculating the median overall survival (OS) which was 11 months (range, 5-53 months) for the remaining 20 subjects of this second-line group. Trastuzumab was not discontinued due to side effects in any of the study population. CONCLUSIONS: In conclusion, this retrospective analysis suggests that continuation of trastuzumab beyond disease progression in patients with HER2-overexpressing metastatic gastric cancer is feasible and safe. Randomized studies are warranted.