International consensus on the management of large (≥20 mm) colorectal laterally spreading tumors: World Endoscopy Organization Delphi study.

OBJECTIVES: There have been significant advances in the management of large (≥20 mm) laterally spreading tumors (LSTs) or nonpedunculated colorectal polyps; however, there is a lack of clear consensus on the management of these lesions with significant geographic variability especially between Eastern and Western paradigms. We aimed to provide an international consensus to better guide management and attempt to homogenize practices. METHODS: Two experts in interventional endoscopy spearheaded an evidence-based Delphi study on behalf of the World Endoscopy Organization Colorectal Cancer Screening Committee. A steering committee comprising six members devised 51 statements, and 43 experts from 18 countries on six continents participated in a three-round voting process. The Grading of Recommendations, Assessment, Development and Evaluations tool was used to assess evidence quality and recommendation strength. Consensus was defined as ≥80% agreement (strongly agree or agree) on a 5-point Likert scale. RESULTS: Forty-two statements reached consensus after three rounds of voting. Recommendations included: three statements on training and competency; 10 statements on preresection evaluation, including optical diagnosis, classification, and staging of LSTs; 14 statements on endoscopic resection indications and technique, including statements on en bloc and piecemeal resection decision-making; seven statements on postresection evaluation; and eight statements on postresection care. CONCLUSIONS: An international expert consensus based on the current available evidence has been developed to guide the evaluation, resection, and follow-up of LSTs. This may provide guiding principles for the global management of these lesions and standardize current practices.

Performance of endoscopic submucosal dissection for undifferentiated early gastric cancer: a multicenter retrospective cohort.

Background and study aims Undifferentiated early gastric cancer (UD-EGC) represents an extended indication for endoscopic submucosal dissection (ESD) based on the existing guidelines. This study evaluated the prevalence of UD-EGC recurrence after ESD, and potentially implicated risk factors. Patients and methods Data from 17 centers were collected retrospectively including demographics, endoscopic and pathological findings, and follow-up data from UD-EGC cases treated by ESD. Patients with incomplete resection or advanced disease were excluded. Descriptive statistics quantified variables and calculated the incidence of recurrence. Chi-square test was applied to assess any link between independent variables and relapse; significantly associated variables were inserted to a multivariable regression model. Results Seventy-one patients were eligible, with 2:1 female to male ratio and age of 65.8 ± 11.8 years. Mean lesion size was 33.5 ± 18.8 mm and the most frequent histological subtype was signet ring-cells UGC (2:1). Patients were followed-up every 5.6 ± 3.7 months with a mean surveillance period of 29.3 ± 15.3 months until data collection. Four patients (5.6%) developed local recurrence 8.8 ± 6.5 months post-ESD, with no lymph node or distal metastases been reported. Lesion size was not associated with recurrence ( P = 0.32), in contrast to lymphovascular and perineural invasion which were independently associated with local recurrence ( P = 0.006 and P < 0.001, respectively). Conclusions ESD could be considered as the initial step to manage UD-EGC, providing at least an "entire-lesion" biopsy to guide therapeutic strategy. When histology confirms absence of lymphovascular and perineural invasion, this modality could be therapeutic, providing low recurrence rates.

Cronkhite-Canada syndrome: First case report from Egypt and North Africa.

BACKGROUND: Gastrointestinal (GI) polyposis is a rare condition in GI diseases. To date about 500 cases of Cronkhite-Canada syndrome (CCS) have been reported worldwide. CASE SUMMARY: We report a 60-year-old female patient who presented with dyspepsia, abdominal pain, and weight loss of 1-year duration. Her physical examination showed alopecia and onychodystrophy. Upper endoscopy revealed diffuse markedly thickened gastric mucosa involving the whole stomach with thickened gastric rugae and numerous polypoidal lesions. Histopathological examination showed marked hyperplasia of the foveolar glands with inflammatory cell infiltration. Endoscopic ultrasound showed a significantly hypertrophic mucosa and muscularis mucosa, while the submucosa and the muscularis propria were spared, favouring its benign nature. Colonoscopy showed multiple sessile polyps scattered at different parts of the colon. Histopathological examination revealed tubular adenomatous polyps with low-grade dysplasia. Differential diagnoses included CCS, Menterier disease (MD), other polyposis syndromes, lymphoma, amyloidosis, and gastric malignancies. The presence of alopecia, nail dystrophy, GI polyposis, markedly thickened gastric mucosa and folds, abdominal pain, weight loss, and marked foveolar gland hyperplasia; all was in favour of CCS. Lymphoma was excluded due to sparing of the muscularis propria. The presence of colonic polyps and antral and duodenal infiltration, and the absence of hypoproteinaemia decreased the possibility for MD. CONCLUSION: The patient was diagnosed as having CCS.

Role of endoscopic ultrasound and cyst fluid tumor markers in diagnosis of pancreatic cystic lesions.

BACKGROUND: Pancreatic cystic lesions (PCLs) are common in clinical practice. The accurate classification and diagnosis of these lesions are crucial to avoid unnecessary treatment of benign lesions and missed opportunities for early treatment of potentially malignant lesions. AIM: To evaluate the role of cyst fluid analysis of different tumor markers such as cancer antigens [e.g., cancer antigen (CA)19-9, CA72-4], carcinoembryonic antigen (CEA), serine protease inhibitor Kazal-type 1 (SPINK1), interleukin 1 beta (IL1-ß), vascular endothelial growth factor A (VEGF-A), and prostaglandin E2 (PGE2)], amylase, and mucin stain in diagnosing pancreatic cysts and differentiating malignant from benign lesions. METHODS: This study included 76 patients diagnosed with PCLs using different imaging modalities. All patients underwent endoscopic ultrasound (EUS) and EUS-fine needle aspiration (EUS-FNA) for characterization and sampling of different PCLs. RESULTS: The mean age of studied patients was 47.4 ± 11.4 years, with a slight female predominance (59.2%). Mucin stain showed high statistical significance in predicting malignancy with a sensitivity of 87.1% and specificity of 95.56%. It also showed a positive predictive value and negative predictive value of 93.1% and 91.49%, respectively (P < 0.001). We found that positive mucin stain, cyst fluid glucose, SPINK1, amylase, and CEA levels had high statistical significance (P < 0.0001). In contrast, IL-1ß, CA 72-4, VEGF-A, VEGFR2, and PGE2 did not show any statistical significance. Univariate regression analysis for prediction of malignancy in PCLs showed a statistically significant positive correlation with mural nodules, lymph nodes, cyst diameter, mucin stain, and cyst fluid CEA. Meanwhile, logistic multivariable regression analysis proved that mural nodules, mucin stain, and SPINK1 were independent predictors of malignancy in cystic pancreatic lesions. CONCLUSION: EUS examination of cyst morphology with cytopathological analysis and cyst fluid analysis could improve the differentiation between malignant and benign pancreatic cysts. Also, CEA, glucose, and SPINK1 could be used as promising markers to predict malignant pancreatic cysts.

Influence of narrow-band ultraviolet B therapy on sirtuin 1 expression in lesional skin of patients with chronic plaque psoriasis: Relation to clinical improvement and interferon-γ expression.

BACKGROUND: Reduced sirtuin 1 (Sirt1) expression in psoriasis was previously reported, and its activation was associated with disease improvement. Narrow-band ultraviolet B (NB-UVB) downregulates several pro-inflammatory cytokines such as interferon-γ (IFN-γ) and influences keratinocyte differentiation in psoriasis. OBJECTIVES: The aim of this study was to study the in vivo influence NB-UVB treatment on Sirt1 expression in psoriatic skin in relation to disease improvement and IFN-γ expression. METHODS: Twenty-six patients with chronic plaque psoriasis were evaluated, and psoriasis area severity index (PASI) was calculated. Skin biopsies were taken from lesional skin of the patients before and after 3 months of treatment with NB-UVB and from 26 controls, where the distribution and immunohistochemistry (IHC) scores of Sirt1 and IFN-γ were determined. RESULTS: After 3 months of treatment, Sirt1 distribution and epidermal IHC score were significantly higher, whereas Sirt1 dermal IHC score and IFN-γ distribution, epidermal and dermal IHC scores were significantly lower than the pre-treatment values. Before and after 3 months of NB-UVB therapy, PASI showed a significant negative correlation with Sirt1 distribution and epidermal IHC score; and a significant positive correlation with interferon-γ distribution and epidermal IHC score. Moreover, Sirt1 distributions were negatively correlated with the corresponding interferon-γ distributions. Conclusions The detected upregulation of epidermal Sirt1 following NB-UVB therapy possibly represents another mechanism by which NB-UVB can act in psoriasis and also highlights the role of Sirt1 upregulation in psoriasis treatment.

Assessment of alteration in antiviral plasma concentration across dialysis days: computational and analytical study.

Aim: Protein-bound uremic toxins (PBUTs) may displace drugs from the plasma proteins and render them more liable to clearance. This study aims to investigate the possible interplay between PBUTs and directly acting antivirals (DAAs). Methods: PBUT plasma protein binding was compared to those of paritaprevir (PRT), ombitasivir (OMB) and ritonavir (RTV) in silico to assess the possible competitive displacement. The three drugs were LC-MS/MS determined in seven patients across dialysis and non-dialysis days and results were compared. Results & conclusion: Results showed that the PBUT exhibited a lower binding than DAA reducing the liability of their competitive displacement. This was echoed by an unaltered plasma concentration across dialysis days. Results may indicate that PBUT accumulation may have limited effect on disposition of DAA.

Peroral endoscopic myotomy (POEM) for the treatment of achalasia: A multicenter Middle Eastern experience.

BACKGROUND: Peroral endoscopic myotomy (POEM) was proposed in 2010 as a minimally invasive procedure for the treatment of achalasia. In this article, we describe the Middle Eastern experience with the procedure in terms of efficacy, length of admission, and short- and long-term complications. METHODS: A retrospective analysis of our prospectively collected data on patients who underwent a POEM procedure was conducted between March 2019 and May 2020. The primary outcome was clinical success rate, defined as a postprocedure Eckardt score ≤3 at ≥3 months. Secondary outcomes included the length of hospital stay, presence of reflux symptoms or need for proton pump inhibitors (PPIs) ≥3 months, and adverse events. RESULTS: During the study period, 67 patients (35 females) underwent the procedure for achalasia. The participants' ages ranged from 11 to 80 years (mean 41 ± 18 years). Eckardt scores before the treatment ranged between 4 and 12 (mean 8.85 ± 1.75). Sixty-four patients (95.5%) achieved Eckardt scores of ≤3 at ≥3 months after the procedure (95% confidence interval [CI]: 91%-100%). The difference between pre- and post-procedural Eckardt scores averaged around -8 points (95% CI: -7.5 to -8.5 P < 0.0001). Adverse events were reported in 24 patients (35.8%) and included pneumoperitoneum (32.8%), reflux symptoms at 3 months (29.9%), and surgical emphysema (3%). Six patients had adverse events that led to prolongation of admission; 3% of whom had aspiration pneumonia, 3% had pneumoperitoneum, 1.5% had both, and 1.5% had an esophageal tear. CONCLUSIONS: POEM is a promising procedure for the treatment of achalasia with a high clinical success rate, short hospital admission, and a reassuring safety profile.

Changes of Carotid Intima-Media Thickness After Sleeve Gastrectomy in High Cardiovascular Risk Patients: a Prospective Study.

PURPOSE: There are insufficient data showing the impact of laparoscopic sleeve gastrectomy (LSG) on carotid intima-media thickness (CIMT). Therefore, in the current work, we investigated the improvement of metabolic syndrome and CIMT in patients with obesity after LSG. METHODS: This study involved 120 consecutively selected Egyptian patients with a high cardiovascular risk who underwent LSG and were followed up for 12 months. RESULTS: CIMT declined from 0.95 ± 0.17 mm to 0.83 ± 0.12 (p < 0.001) after 12 months. In addition, the mean fasting blood glucose and fasting inulin level dropped significantly from 153.3 ± 63.6 to 108.8 ± 33.8 mg/dl and from 23.1 ± 7.1 mU/ml to 14.1 ± 6.4 respectively (p < 0.001). Furthermore, glycated hemoglobin (HbA1c) declined from 7.02 ± 1.7 to 5.5 ± 0.96 (p < 0.001). At the end of the follow-up period, metabolic parameters such as HOMA-IR, C-reactive protein (CRP), fibrinogen, total cholesterol, LDL cholesterol, triglycerides, AST, and ALT decreased significantly from their respective baselines (p value < 0.001). Moreover, the reduction in CIMT showed a strong positive correlation with the degree of weight loss at 6 months and 12 months of follow-up. CONCLUSION: LSG led to a substantial decrease in CIMT. Moreover, it significantly impacted cardiovascular risk factors such as obesity, hypertension, insulin resistance, lipid profile, and inflammatory markers.

Peroral endoscopic myotomy as treatment for Zenker's diverticulum (Z-POEM): a multi-center international study.

BACKGROUND: Peroral endoscopic myotomy for the treatment of Zenker's diverticulum (Z-POEM) is a novel technique that has been described in several recent reports. This method utilizes the third space (submucosal layer) to create a tunnel to facilitate complete visualization of the septum and hence cutting it entirely. Conventional endoscopic septotomy carries the risk of recurrence due to incomplete visualization of the septum. While surgical correction is a risky and lengthy procedure in old comorbid patients with Zenker's diverticulum. The aim of this study is to assess the efficacy and safety of Z-POEM. METHODS: The study enrolled 24 patients diagnosed with Zenker's diverticulum (ZD) who underwent Z-POEM at seven independent endoscopy centers in five different countries. RESULTS: Mean patient age ± standard deviation (SD) was 74.3 ± 11 years. Most of the patients were males (n = 20, 83.3%); four (16.7%) were females. More than 50% of the patients (n = 14, 58.3%) had associated comorbidities. The mean size of the diverticula was 4 cm (range 2-7 cm). The Kothari-Haber Score was used to assess clinical symptoms; values ranged from 6 to 14 (median = 9). We achieved 100% technical success with a median procedure time of 61 min and no adverse events. Median hospital stay was 1 day (range 1-5 days). There is a significant reduction in the Kothari-Haber Score after Z-POEM (P < 0.0001). Technical success was achieved in 100% of the patients. Clinical success was achieved in 23/24 (95.8%) of the patients with a median follow-up of 10 months (range 6-24 months). CONCLUSION: Z-POEM is a safe and effective modality for managing ZD.

Endoscopic intervention in a case proven latterly to be a COVID-19.

BACKGROUND: COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the newly developed worldwide outbreak of coronavirus disease with a high rate of mortality especially among elderly and multiple co-morbid personnel. Asymptomatic COVID-19-infected patients are a well-known source of transmission of infection. The risk of exposure to respiratory secretions and/or feces is hardly avoidable during the endoscopic procedure; also, the aerosol and droplets take up to an hour disperse, so they remain a risk to staff and other patients after they leave the room; therefore, strict infectious precautions should be taken by all health care workers to limit the virus spread. MAIN BODY: We present an endoscopic trial of duodenal stent insertion in non-operable gastric carcinoma that is proven 2 days later to be a COVID-19-positive case. Fortunately, no one of the health care workers that came in contact with the case becomes infected owing to the proper infection control measures. CONCLUSION: We recommended that the endoscopy examination and procedures should be strictly limited to urgent cases to minimize the risk of virus infection among health care workers.

Acceleration of Gastric Emptying and Improvement of GERD Outcome After Laparoscopic Sleeve Gastrectomy in Non-diabetic Obese Patients.

PURPOSE: Obesity has become a pandemic nowadays. Bariatric surgery is increasingly performed to manage obesity. Currently, laparoscopic sleeve gastrectomy (LSG) is a widely accepted procedure given its feasibility and efficacy. Previous studies revealed conflicting results regarding the change of gastric emptying following sleeve gastrectomy. The primary aim of the present study is to assess gastric motor function by gastric emptying scintigraphy in a cohort of non-diabetic patients undergoing laparoscopic sleeve gastrectomy (LSG) for treatment of severe obesity. METHODS: This prospective observational study included 100 obese, non-diabetic patients attending the surgery clinic at Cairo University Hospitals and Al Azhar University Hospitals. LSG was performed following a standardized protocol, with no complications observed. All patients had gastric emptying scintigraphy done through a standard semisolid meal (250 kcal), marked with 0.5 mCiTc 99, pre-operatively and 3 months after LSG. RESULTS: The mean age was 38.71 years (9.2) and males comprised 57% of the cohort. The body mass index, low-density lipoproteins, and glycated hemoglobin declined significantly at 3-month postsurgery. The scintigraphy study revealed a significantly reduced percent retention at equivalent time points 3 months after LSG. In addition, the percent of patients suffering from GERD decreased significantly after LSG. CONCLUSION: Gastric emptying becomes faster after LSG in morbidly obese non-diabetic patients. GERD symptoms improve after surgery.

Development and Validation of a New LC-MS/MS Analytical Method for Direct-Acting Antivirals and Its Application in End-Stage Renal Disease Patients.

BACKGROUND AND OBJECTIVE: The effectiveness of direct-acting antivirals (DAAs) is not well established in end-stage renal disease (ESRD) patients. Assessment of the plasma concentrations may support understanding of their therapeutic outcomes in this population. The aim of this study is to develop a direct, yet matrix-effect tolerant, analytical method for determining DAAs in the plasma of ESRD patients while maintaining a moderate cost per sample and with an improved analyte extraction recovery. METHODS: In this study, a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the analysis of ombitasvir (OMB), paritaprevir (PRT) and ritonavir (RIT) in plasma. Sample preparation was performed using the liquid-liquid extraction (LLE) method. Isocratic separation was performed using a mixture of methanol and 10 mM ammonium acetate (79:21, v/v) followed by MS/MS detection. The method was validated and applied to determine DAAs in the plasma of ESRD patients (n = 7). RESULTS: The developed method was linear (r2 > 0.995), accurate (89.4 ± 7.8 to 108.3 ± 3.0) and precise (% CV 0.9-15.0) and showed improved recovery (> 80) over previously published ones in the range 5-250, 30-1,500, 20-1,000 ng/mL for OMB, PRT and RIT, respectively. Relative matrix effect was absent, and the method accurately determined the three DAAs in real-life samples (n = 7). CONCLUSIONS: An efficient analytical method for the determination of DAAs is presented. The method overcomes the potential analytical response fluctuation in ESRD. The developed method show improved extraction recoveries and is suitable for routine application in developing economies where hepatitis C virus is most prevalent.

Risk index for early infections following living donor liver transplantation.

INTRODUCTION: Post-operative infections in patients undergoing living donor liver transplantation (LDLT) are a major cause of morbidity and mortality. This study aims to develop a practical and efficient prognostic index for early identification and possible prediction of post-transplant infections using risk factors identified by multivariate analysis. MATERIAL AND METHODS: One hundred patients with post-hepatitic cirrhosis, HCV positive, genotype 4, Child B/C or MELD score 13-25 undergoing LDLT were included. All potential predictors of infection were analyzed by backward logistic regression. Cut-off values were obtained from ROC curve analysis. Significant predictors were combined into a risk index, which was further tested and compared by ROC curve analysis. RESULTS: Post-operative infection was associated with a significantly higher mortality (50.7% vs. 33.3%). Total leucocyte count, total bilirubin, early biliary complications, fever and C-reactive protein were found to be independent predictors of early infectious complications after LDLT. The risk index predicted infection with the highest sensitivity and specificity as compared with each predictor on its own (AUC = 0.91, 95% CI: 0.830-0.955, p < 0.0001). CONCLUSIONS: The use of a combined risk index for early diagnosis of post-operative infections can efficiently identify high risk patients.

Gastric Peroral Endoscopic Myotomy (G-POEM) as a Treatment for Refractory Gastroparesis: Long-Term Outcomes.

Background and Aims: Gastric peroral endoscopic myotomy (G-POEM) has been regarded as a novel and minimally invasive therapy for refractory gastroparesis. This study reports the long-term outcomes and possible predictive factors for successful outcomes after G-POEM in an Asian population. Methods: This is a retrospective single-centre study of 16 patients who underwent G-POEM for refractory gastroparesis from August 2016 to October 2017. This study included 11 males and 5 females; in addition, 13 patients had postsurgical gastroparesis, and 3 patients had diabetes. The patients included had severe and refractory gastroparesis, as indicated by a Gastroparesis Cardinal Symptom Index (GCSI) score ≥20, and evidence of a delay on gastric emptying scintigraphy (GES). The primary outcome parameter was an assessment of the long-term clinical efficacy of the procedure. The secondary outcome parameter was the detection of possible predictive factors for success and the determination of cut-off values for such predictors. Results: Technical success was achieved in 100% of the patients, with a mean procedure time of 45.25±12.96 min. The long-term clinical response was assessed in all patients during a median follow-up of 14.5 months. Clinical success was achieved in 13 (81.25%) patients. There was a significant reduction in the GCSI scores and GES values after the procedure compared to the baseline values, with P values of <0.0001 and 0.012, respectively. Univariate regression analysis showed that the GCSI and GES had significant associations with the future clinical outcomes of the patients, but this finding was not confirmed in multivariate analysis. A GCSI cut-off score of ≤30 had a high sensitivity and a negative predictive value (NPV) of 100% for predicting a successful procedure. GES (half emptying time ≤221.6 min and 2-hour retention ≤78.6%) had a high specificity and a positive predictive value (PPV) of 100%. Conclusions: G-POEM is a safe and effective treatment option with a long-term efficacy of 81.6%. GCSI and GES could serve as good predictive measures.

Endoscopic ultrasound (EUS) elastography and strain ratio, could it help in differentiating malignant from benign pancreatic lesions?

Evaluating the role of endoscopic ultrasound (EUS) elastography and strain ratio in differentiation between malignant and benign pancreatic lesions.Three hundred twenty-five patients with solid pancreatic lesions were enrolled in this prospective study from 2014 to 2017. EUS real-time elastography scoring and strain ratio were done to all patients and compared to the final diagnosis to assess its sensitivity, specificity, positive and negative predictive values (PPV and NPV) in differentiating malignant from benign lesions.A cut-off value of 4.2 we had sensitivity of 95%, specificity of 63%, PPV of 89%, NPV of 81%, and accuracy of 87%. Another cut-off value of 10.9 showed a sensitivity of 75%, specificity of 88%, PPV of 95%, NPV of 54%, and accuracy of 79%. Adding the elastography to the better cut-off value gave a sensitivity of 97%, specificity of 63%, PPV of 89%, NPV of 88%, and accuracy of 89%.Real-time elastography and strain ration are valuable in differentiating malignant from pancreatic lesions.

Ultrasound, endoscopic ultrasound elastography, and the strain ratio in differentiating benign from malignant lymph nodes.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound elastography (EUS-elastography), or sono-elastography, has emerged in the past 2 decades as a qualitative method of estimating tissue stiffness. Strain elastography allows for semi-quantitative measurements of the average elasticity of a lesion, and previous studies have proposed the strain ratio (SR) for overcoming the limitations of the elasticity score. The main objective of this study is to assess the specificity, sensitivity and predictive values of the SR measured by EUS-elastography in differentiating benign from malignant lymph nodes (LNs). This study also aims to find significant ultrasonographic features other than the SR which could help in predicting LN malignancy. PATIENTS AND METHODS: This prospective study included 126 Egyptian patients with lymphadenopathy. US and EUS-elastography and the SR were assessed, in addition to detailed sonographic features, including size, longest diameter, shortest diameter, ratio of shortest/longest diameter, echotexture (echogenic or echo-poor) and hilum (lost or preserved). RESULTS: The SR cut-off value of 4.61 showed a sensitivity and specificity of 89.8% and 83.3%, respectively. This parameter had high positive and negative predictive values of 82.5% and 90.2%, respectively, for predicting malignant LNs. Univariate regression analysis showed that echogenicity, hilum preservation, elastography, the shortest dimension, the ratio of the shortest/longest dimension, ultrasound diagnosis and SR could be potential predictors of the final lymph node diagnosis. Sono-diagnosis depending on echogenicity, the shortest/longest diameter ratio and a preserved hilum in combination was the only predictive parameter in multivariate regression analysis. CONCLUSION: EUS-elastography and the SR could be excellent prognostic indices in differentiating benign from malignant lymph nodes if combined with other US features.