Role of Biliary Stent in Recurrence of Biliary Stones and Complications After Stone Clearance in Patients Awaiting Cholecystectomy: A Randomized Trial.

INTRODUCTION: The role of prophylactic biliary stenting after clearance of choledocholithiasis in patients awaiting cholecystectomy for concomitant cholelithiasis is controversial. We planned a randomized controlled trial to study the effect of prophylactic biliary stenting after achieving biliary clearance in reducing recurrence of choledocholithiasis and biliary complications in patients awaiting cholecystectomy. METHODS: Patients with concomitant cholelithiasis and choledocholithiasis were included, and those who had evidence of clearance of choledocholithaisis (documented on occlusion cholangiogram during endoscopic retrograde cholangiography [ERC]) were randomized to prophylactic biliary stenting or no stenting. Choledocholithaisis recurrence rate (primary outcome), biliary complications and need for repeat/emergency ERC (secondary outcomes) were compared till 3 months after clearance. RESULTS: Between September 2021 and July 2022, 70 patients were randomized into group A, stenting (n = 35), and group B, no stenting (n = 35). Sixty-six patients were included in the final analysis. Baseline characteristics were comparable between the 2 groups. Ten (15.2%) patients had recurrence of choledocholithiasis, and it was comparable between the 2 groups (7/34 [20.6%] and 3/34 [9.4%], P = 0.306). Five patients (2 cholecystitis and 3 post-ERC pancreatitis) from the stent group while none from the no stent group developed complications, and this difference was statistically significant ( P = 0.024). None of the patients in both the groups needed emergency ERC during the follow-up. DISCUSSION: This randomized trial shows a higher complication rate with prophylactic stenting, while there is no benefit in preventing choledocholithiasis recurrence in patients waiting for cholecystectomy after biliary clearance (CTRI registration number: CTRI/2021/09/036538).

Multiparametric MR imaging with diffusion-weighted, intravoxel incoherent motion, diffusion tensor, and dynamic contrast-enhanced perfusion sequences to assess gallbladder wall thickening: a prospective study based on surgical histopathology.

OBJECTIVE: To investigate the diagnostic performance of a multiparametric magnetic resonance imaging (MRI) protocol comprising quantitative MRI (diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI), and dynamic contrast-enhanced (DCE) perfusion MRI) and conventional MRI in the characterization of gallbladder wall thickening (GWT). METHODS: This prospective study comprised consecutive adults with GWT who underwent multiparametric MRI between July 2020 and April 2022. Two radiologists evaluated the MRI independently. The final diagnosis was based on surgical histopathology. The association of MRI parameters with malignant GWT was evaluated. The area under the curve (AUC) for the quantitative MRI parameters and diagnostic performance of conventional, and multiparametric MRI were compared. The interobserver agreement between two radiologists was calculated. RESULTS: Thirty-five patients (mean age, 56 years, 23 females) with GWT (25 benign and ten malignant) were evaluated. The quantitative MRI parameters significantly associated with malignant GWT were apparent diffusion coefficient on DWI (p = 0.007) and mean diffusivity (MD) on DTI (p = 0.013), perfusion fraction (f) on IVIM (p = 0.033), time to peak enhancement (TTP, p = 0.008), and wash in rate (p = 0.049) on DCE-MRI. TTP had the highest AUC of 0.790, followed by MD (0.782) and f (0.742) (p = 0.213) for predicting malignant GWT. Multiparametric MRI had significantly higher sensitivity (90% vs. 80%, p = 0.045) than conventional MRI for diagnosing malignant GWT. The two radiologists' reading had substantial to near-perfect agreement (kappa = 0.639-1) and moderate to strong correlation (interclass correlation coefficient = 0.5-0.88). CONCLUSION: Multiparametric protocol incorporating advanced sequences improved the diagnostic performance of MRI for differentiating benign and malignant GWT. KEY POINTS: • Multiparametric MRI had 90% sensitivity and 88% specificity for diagnosing malignant GWT, compared to 80% sensitivity and 88% specificity for conventional CE-MRI. • Among the quantitative MRI parameters, TTP (perfusion-MRI) had the highest AUC of 0.790, followed by MD (0.782) and IVIM-f (0.742). • For most quantitative MRI parameters, there was moderate to strong agreement (ICC = 0.5-0.88).

Differentiating gastrointestinal tuberculosis and Crohn's disease- a comprehensive review.

Gastrointestinal Tuberculosis (GITB) and Crohn's disease (CD) are both chronic granulomatous diseases with a predilection to involve primarily the terminal ileum. GITB is often considered a disease of the developing world, while CD and inflammatory bowel disease are considered a disease of the developed world. But in recent times, the epidemiology of both diseases has changed. Differentiating GITB from CD is of immense clinical importance as the management of both diseases differs. While GITB needs anti-tubercular therapy (ATT), CD needs immunosuppressive therapy. Misdiagnosis or a delay in diagnosis can lead to catastrophic consequences. Most of the clinical features, endoscopic findings, and imaging features are not pathognomonic for either of these two conditions. The definitive diagnosis of GITB can be clinched only in a fraction of cases with microbiological positivity (acid-fast bacilli, mycobacterial culture, or PCR-based tests). In most cases, the diagnosis is often based on consistent clinical, endoscopic, imaging, and histological findings. Similarly, no single finding can conclusively diagnose CD. Multiparametric-based predictive models incorporating clinical, endoscopy findings, histology, radiology, and serology have been used to differentiate GITB from CD with varied results. However, it is limited by the lack of validation studies for most such models. Many patients, especially in TB endemic regions, are initiated on a trial of ATT to see for an objective response to therapy. Early mucosal response assessed at two months is an objective marker of response to ATT. Prolonged ATT in CD is recognized to have a fibrotic effect. Therefore, early discrimination may be vital in preventing the delay in the diagnosis of CD and avoiding a complicated course.

Frequency, outcomes, and need for intervention in stricturing gastrointestinal tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Gastrointestinal strictures impact clinical presentation in abdominal tuberculosis and are associated with significant morbidity. AIM: To conduct a systematic review of the prevalence of stricturing disease in abdominal and gastrointestinal tuberculosis and response to antitubercular therapy (ATT). METHODS: We searched Pubmed and Embase on 13th January 2022, for papers reporting on the frequency and outcomes of stricturing gastrointestinal tuberculosis. The data were extracted, and pooled prevalence of stricturing disease was estimated in abdominal tuberculosis and gastrointestinal (intestinal) tuberculosis. The pooled clinical response and stricture resolution (endoscopic or radiologic) rates were also estimated. Publication bias was assessed using the Funnel plot and Egger test. The risk of bias assessment was done using a modified Newcastle Ottawa Scale. RESULTS: Thirty-three studies reporting about 1969 patients were included. The pooled prevalence of intestinal strictures in abdominal tuberculosis and gastrointestinal TB was 0.12 (95%CI 0.07-0.20, I2 = 89%) and 0.27 (95% CI 0.21-0.33, I2 = 85%), respectively. The pooled clinical response of stricturing gastrointestinal tuberculosis to antitubercular therapy was 0.77 (95%CI 0.65-0.86, I2 = 74%). The pooled stricture response rate (endoscopic or radiological) was 0.66 (95%CI 0.40-0.85, I2 = 91%). The pooled rate of need for surgical intervention was 0.21 (95%CI 0.13-0.32, I2 = 70%), while endoscopic dilatation was 0.14 (95%CI 0.09-0.21, I2 = 0%). CONCLUSION: Stricturing gastrointestinal tuberculosis occurs in around a quarter of patients with gastrointestinal tuberculosis, and around two-thirds of patients have a clinical response with antitubercular therapy. A subset of patients may need endoscopic or surgical intervention. The estimates for the pooled prevalence of stricturing disease and response to ATT had significant heterogeneity.

Factors contributing to flares of ulcerative colitis in North India- a case-control study.

BACKGROUND: Ulcerative colitis is a relapsing and remitting disease that may be associated with flares. The causes of flares in the Indian setting are not well recognized. METHODS: The present prospective case-control study was conducted at a single center in North India. Cases were defined as patients admitted for flare of ulcerative colitis, while controls were patients in remission enrolled from the outpatient department. The basis of the diagnosis of flare was a simple clinical colitis activity index (SCCAI) of ≥ 5 and endoscopic activity, while remission was based on SCCAI < 4 and a normal fecal calprotectin. A questionnaire evaluating recent infections, stress, drug intake (antibiotics, pain medication), adherence to therapy, and use of complementary and alternative therapy (CAM) was administered. RESULTS: We included 84 patients (51 with flare and 33 in remission) with a median age of 38 years, of whom 47 (55.9%) were males. The two groups were similar for baseline parameters, including age (38, 23-50 and 38, 25.5-48.5 years), male gender (52.9% and 60.6%), extent of disease, extraintestinal manifestations (21.6% and 12.1%), use of 5-aminosalicylates (76.5% and 90.9%). The thiopurine use was lower in those having a flare (15.7% and 36.4%). Amongst the predictors of flare, the recent infections (39.2% and 30.3%), recent travel (31.4 and 27.3%), eating outside food (47.1% and 39.4%), consumption of milk products (88.2% and 75.8%), use of pain medication (43.1% and 33.3%) and recent stress (62.7% and 60.6%) were similar between cases and controls. The rates of antibiotic use (29.4% and 6.1%), lack of adherence (50.9% and 15.2%), and intake of CAM (70.6% and 33.3%) were higher in those with flare. Patients attributed a lack of adherence to the cost of therapy, presumed cure (due to lack of symptoms), and fear of adverse effects. CONCLUSION: Lack of adherence to inflammatory bowel disease therapies and recent CAM and antibiotic intake was higher in patients with flares of UC. The study makes ground for educational intervention(s) promoting knowledge and adherence to IBD therapies.

Pancreatic Dysfunction and Reduction in Quality of Life Is Common After Pancreaticoduodenectomy.

BACKGROUND: Improvements in survival after pancreaticoduodenectomy has increased the number of patients potentially at risk of pancreatic insufficiency. AIMS: We studied long-term (> 1 year) pancreatic functions (endocrine and exocrine) after pancreaticoduodenectomy and aimed to recognize the impact of various clinicopathological factors and postoperative complications on pancreatic functions. METHODS: All patients who underwent pancreaticoduodenectomy at least 1 year prior were recruited from July 2020 to December 2021. Endocrine function was assessed using HbA1c, fasting blood sugar and postprandial blood sugar levels. Pancreatic exocrine function was assessed clinically with history of steatorrhea and objectively with quantitative estimation of fecal elastase-1 levels in stool samples. Volume of remnant pancreas, parenchymal thickness and duct diameter were assessed by computed tomography. Quality of life assessment was done using SF-36 questionnaire. RESULTS: Of the 106 patients assessed, 64 patients met the inclusion criteria. Endocrine insufficiency was noted in 51.6%, and 34.3% had new onset diabetes mellitus. The incidence of pancreatic exocrine insufficiency was 87.5% and severe insufficiency was found in 62.5% of patients. Twenty-nine (45.3%) patients had both exocrine and endocrine insufficiency. Patients with CRPOPF had higher risk of severe exocrine insufficiency (5 vs. 2, OR 1.57(0.28-8.81) p = 0.6). The SF-36 scores were lower than general population especially in role limitation due to physical health, role limitation due to emotional problems, energy/fatigue, general health perception and health change domains. CONCLUSION: Post-pancreaticoduodenectomy patients have a high frequency of pancreatic insufficiency and should be screened for same. The post-operative pancreatic fistula increases the risk of pancreatic exocrine insufficiency.

Genotoxic and mutagenic potential of 7-methylxanthine: an investigational drug molecule for the treatment of myopia.

7-Methylxanthine (7-MX, CAS No. 552-62-5, purity 99.46%) is the first orally administered drug candidate, which showed anti-myopic activity in different pre-clinical studies. In the present study, we investigated the in-vivo genotoxic and mutagenic toxicity of 7-MX in Wistar rats using comet/single-cell gel electrophoresis, chromosomal aberration and micronucleus assays after oral administration. For the single-dose study (72 h), two doses of 7-MX 300 and 2000 mg/kg body weight were selected. For a repeated dose 28 d study, three doses (250, 500, and 1000 mg/kg) of 7-MX were selected. The doses were administered via oral gavage in the suspension form. Blood and major vital organs such as bone marrow, lung and liver were used to perform comet/single cell gel electrophoresis, chromosomal aberration, and micronucleus assays. The in-vitro Ames test was performed on TA98 and TA100 strains. In the chromosomal aberration study, a non-significant increase in deformities such as stickiness, ring chromosome, and endoreduplication was observed in bone marrow cells of 7-MX treated groups. These chromosomal alterations were observed upon treatment with doses of 2000 mg/kg single dose for 72 h and 1000 mg/kg repeated dose for 28 d. At a dose of 500 mg/kg, DNA damage in terms of tail length, tail moment, % tail DNA and the olive tail moment was also found to be non-significant in 7-MX treated groups. The Ames test showed the non-mutagenic nature of 7-MX in both strains of TA98 and TA100 of Salmonella typhimurium with or without metabolic activation. Thus, the present work is interesting in view of the non- genotoxicity and non-mutagenicity of repeated doses of 7-MX.

Contrast-enhanced ultrasound of solid pancreatic head lesions: a prospective study.

OBJECTIVE: To evaluate the role of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of solid pancreatic head lesions (SPHL). METHODS: This prospective study comprised consecutive patients with SPHL who underwent CEUS evaluation of the pancreas. Findings recorded at CEUS were enhancement patterns (degree, completeness, centripetal enhancement, and percentage enhancement) and presence of central vessels. In addition, time to peak (TTP) and washout time (WT) were recorded. The final diagnosis was based on histopathology or cytology. Multivariate analysis was performed to identify parameters that were significantly associated with pancreatic ductal adenocarcinoma (PDAC). RESULTS: Ninety-eight patients (median age 53.8 years, 59 males) were evaluated. The final diagnosis was PDAC (n = 64, 65.3%), inflammatory mass (n = 16, 16.3%), neuroendocrine tumor (NET, n = 14, 14.3%), and other tumors (n = 4, 4.1%). Hypoenhancement, incomplete enhancement, and centripetal enhancement were significantly more common in PDAC than non-PDAC lesions (p = 0.001, p = 0.031, and p = 0.002, respectively). Central vessels were present in a significantly greater number of non-PDAC lesions (p = 0.0001). Hypoenhancement with < 30% enhancement at CEUS had sensitivity and specificity of 80.6% and 67.7%, respectively, for PDAC. There was no significant difference in the TTP and WT between PDAC and non - PDAC lesions. However, the WT was significantly shorter in PDAC compared to NET (p = 0.011). In multivariate analysis, lack of central vessels was significantly associated with a PDAC diagnosis. CONCLUSION: CEUS is a useful tool for the evaluation of SPHL. CEUS can be incorporated into the diagnostic algorithm to differentiate PDAC from non-PDAC lesions. KEY POINTS: • Hypoenhancement and incomplete enhancement at CEUS were significantly more common in PDAC than in non-PDAC. • Central vessels at CEUS were significantly associated with PDAC. • There was no difference in TTP and WT between PDAC and non-PDAC lesions.

Safety and efficacy of non-fluoroscopic endoscopic dilatation of gastrointestinal tuberculosis related strictures.

INTRODUCTION: Stricturing gastrointestinal tuberculosis (GITB) may result in persistent symptoms even after antitubercular therapy (ATT) and may require surgical intervention. Data on efficacy and safety of endoscopic dilatation for management GITB related strictures is scarce. METHODS: A retrospective analysis of database of patients who underwent endoscopic balloon dilatation for suspected or proven gastrointestinal tuberculosis was performed. The analysis included the site of involvement, technical success, clinical success (response), relapse and requirement of surgery in these patients. RESULTS: Out of 34 patients (47.1% males, mean age 31.9 ± 12.9 years), eventually four patients were diagnosed to have Crohn's disease while the rest had GITB. Initial technical success was achieved in 30 (88.2%) patients. Initial clinical success was achieved in 28 (82.3%) patients. Median number of dilatation sessions required to obtain symptomatic relief were 2.5 (1-5) per patient. Two patients with initial clinical success had recurrence of symptoms over follow up of 1 year, out of which one patient was managed with repeat endoscopic balloon dilatation successfully. Of 30 patients with technical success, 16 (53.4%) were on ATT when they underwent dilatation while two were in intestinal obstruction. Eventually 7 patients required surgical intervention for various reasons. CONCLUSION: Non-fluoroscopic endoscopic balloon dilatation is an acceptable and fairly safe modality for symptomatic tuberculous strictures of gastrointestinal tract.

Oesophageal Tuberculosis: A Systematic Review Focusing on Clinical Management.

Oesophageal tuberculosis, an uncommon form of extrapulmonary tuberculosis, has been reported mainly as small case series and the literature is heterogeneous. A systematic review to characterize the clinical presentation, evaluation and management of oesophageal tuberculosis was performed. Electronic databases were searched with keywords: esophagus OR esophageal AND tuberculosis. We included original papers and case series (> 4 patients) with oesophageal tuberculosis. Twenty-two studies reporting 311 patients were included. Mean age in most of the studies was 31-51 years and male gender constituted 50.5% patients. Dysphagia (72.3%), odynophagia (22.4%) and chest pain (31.3%) were predominant symptoms. Mid-oesophagus was the commonest site of involvement (88%). Endoscopic findings included ulcers (59.9%), submucosal bulge (31.7%), extrinsic compression (24.8%) and pseudotumour (5.8%). On endoscopic ultrasound, presence of hypoechoic (69.5%), heteroechoic (47.6%) and matted (86.3%) mediastinal lymph nodes and oesophageal wall involvement (67.3%) were common findings. Computed tomography showed mediastinal lymphadenopathy (76.5%) and oesophageal thickening (52.1%). Diagnosis was confirmed by granuloma (72.3%) and acid fast bacilli positivity (32.5%) in mots patients. Response to antitubercular therapy was excellent; 97.7% patients recovered and 2.3% patients died. Surgery (14.5%) and oesophageal stenting (11.4%) were required infrequently. Oesophageal tuberculosis should be considered in endemic regions as a cause of dysphagia because early treatment is associated with excellent outcomes.

Per Oral Endoscopic Myotomy for the Management of Large Esophageal Diverticula (D-POEM): Safe and Effective Modality for Complete Septotomy.

With the advent of the technique of sub-mucosal tunnelling, peroral endoscopic myotomy (POEM) has been used for the treatment of esophageal diverticulum, which otherwise is a recurring problem with conventional flexible endoscopic treatment due to incompleteness of septotomy. This study reports our experience of the use of diverticular POEM (D-POEM) technique in the management of large esophageal diverticulum. This is a retrospective study of prospectively maintained database including all consecutive patients with symptomatic esophageal diverticulum presenting at a tertiary care academic center. D-POEM was performed using the technique of submucosal tunnelling and septotomy. Besides baseline parameters, technical success, clinical success, size of diverticula, procedure time, complications and symptom recurrence on follow up were noted. A total of five patients (4 males; median age 72) were included with an average Charlson comorbidity index of 3.2 ± 0.8. Of them, three had Zenker's while two had epiphrenic diverticulum. The median symptom duration was 12 months with a mean diverticulum size of 68.8 ± 1.9 mm. The mean procedure time was 64.80 ± 12.6 min. with a mean septotomy/myotomy length of 79.44 ± 12.2 mm. Minor adverse events were noted intra-procedure in two cases. Clinical success achieved in all cases with a significant mean dysphagia score reduction from 2.20 to 0.20 post procedure (p = 0.011). On a median follow up of 280 days (range 98-330), none had recurrence of symptoms. Our data highlighted that complete septotomy by D-POEM technique can be achieved for the management of large esophageal diverticulum and is safe and effective.

Sub-chronic and chronic toxicity evaluation of 7-methylxanthine: a new molecule for the treatment of myopia.

Myopia (nearsightedness) is a vision disorder with a blurring of far objects, affect millions worldwide. 7-methylxanthine (7-MX) is a molecule that is presently under clinical investigation for the treatment of myopia. In the present study, we have investigated sub-chronic and chronic toxicity of 7-MX in comparison to other clinically used methylxanthines i.e., caffeine and theobromine as per OECD guidelines 408 and 452. 7-MX was administered orally for 90 days at three different doses of 250, 500, and 1000 mg/kg for sub-chronic toxicity evaluation, and at a limit dose of 1000 mg/kg in 180 days chronic toxicity evaluation in rats. In sub-chronic treatment, 7-MX showed no mortality and signs for toxicity in any group, whereas 10% and 40% mortality with signs for toxicity were observed in caffeine and theobromine treated groups, respectively. A similar, safety profile was observed with 7-MX in 180 days of chronic toxicity study. Further, to confirm any morphological changes in organs; ultrasound and X-rays analysis were performed and no changes in the size of organs, cyst formation, fluid retention, or crystal formation was observed. Thus, the repeated dose study of 7-MX for 180 days may augment the possibility of using 7-MX clinically for the safe and effective treatment of myopia.

Per oral endoscopic myotomy with fundoplication is a technically feasible NOTES for achalasia cardia.

BACKGROUND: Per-oral endoscopic myotomy (POEM) has become the standard of care for the endoscopic management of achalasia but its major long-term adverse effect has been the development of reflux-associated symptoms and sequelae. AIM: This study was conducted to assess the feasibility and reproducibility of the technique of POEM with fundoplication (POEM + F), a pure Natural Orifice Transluminal Endoscopic Surgery (NOTES) procedure in achalasia. MATERIAL AND METHODS: Between November 2019 and January 2020, three patients with achalasia cardia were subjected to POEM + F. Various parameters such as technical feasibility, procedure time, adverse events and post-procedure follow-up were noted. RESULTS: POEM + F was successfully completed in all three patients. Other than intra-operative capno-peritoneum, no major adverse events were noted. On follow-up at one month, maintenance of wrap was noted. CONCLUSION: POEM + F is a technically feasible and a reproducible pure NOTES procedure.

Differentiating benign and malignant pancreatic masses: Ga-68 PSMA PET/CT as a new diagnostic avenue.

OBJECTIVE: Differentiation of malignant and benign pancreatic lesions on anatomical imaging is difficult in some cases with overlapping features. Prostate-specific membrane antigen (PSMA) is overexpressed during angioneogenesis in many tumors. We aimed to evaluate the PSMA expression in pancreatic lesions to differentiate these lesions and explore the performance of Ga-68 PSMA-PET/CT vis-a-vis F-18 FDG-PET/CT. METHODS: Patients with pancreatic lesions on conventional imaging were prospectively recruited. All the patients underwent a whole-body F-18 FDG-PET/CT and a regional abdominal Ga-68 PSMA-PET/CT. Focal tracer uptake (FDG or PSMA) on PET images was considered positive. Histopathology and/or cytopathology were considered the reference standard. RESULTS: A total of forty patients (27 males, mean age 55.3 ± 9.8, range 37-71 years) were enrolled. Of these, 19 were diagnosed as malignant on histopathology/cytology. Patients with benign lesions showed no worsening of symptoms for at least 6 months on follow-up. FDG-PET/CT revealed 17 true-positive (TP), 9 false-positive (FP), 12 true-negative (TN), and 2 false-negative (FN) findings, whereas PSMA-PET/CT had 18 TP, 2 FP, 19 TN, and 1 FN finding. The sensitivity, specificity, PPV, NPV, and accuracy for FDG-PET/CT were 89.5%, 57.1%, 65.4%, 85.7%, and 72.5%, respectively, while for PSMA-PET/CT were 94.7%, 90.5%, 90%, 95%, and 92.5%, respectively. ROC curve analysis showed that the SUVmax value of 4.8 on PSMA-PET/CT could predict the malignant potential of a lesion with a specificity of 90.5% and a sensitivity of 84.2%. CONCLUSIONS: Ga-68 PSMA-PET/CT imaging helped in establishing a non-invasive pre-operative diagnosis of primary pancreatic malignancy with a higher degree of specificity and accuracy compared with FDG-PET/CT. KEY POINTS: • Conventional imaging such as CT and MRI are unable to reliably differentiate localized malignant pancreatic lesion from benign lesions mimicking malignancy such as mass-forming pancreatitis. • FDG PET/CT helps in detecting malignant foci in view of their increased glucose metabolism. However, it may be falsely positive in inflammatory lesions which may occasionally hinder its ability to differentiate between benign and malignant lesions. • Apart from prostatic malignancy, PSMA is overexpressed in neovasculature of many non-prostatic malignancies. The present study highlights that Ga68 PSMA PET/CT performed better in diagnosing malignancy non-invasively than FDG-PET/CT with a higher PPV (90.5% vs. 65.4%) and accuracy (92.5% vs. 72.5%).

'Rollover' abdominal paracentesis versus standard technique: protocol of a crossover randomized comparative trial.

The sensitivity of single abdominal paracentesis for diagnosis of peritoneal carcinomatosis in patients with malignant ascites is 40-70%. Tumor cells shed from the peritoneum settle preferentially in certain recesses of the peritoneum. We aim to compare the standard technique of abdominal paracentesis versus a rollover technique in a randomized crossover study to assess the cytological yield in patients suspected to have peritoneal carcinomatosis. Each patient will serve as their own control and the outcome assessor (cytopathologist) will be blinded to the method of paracentesis performed. The primary objective will be to compare the tumor cell positivity between the standard paracentesis group and the rollover group among enrolled patients. Clinical Trial registration: CTRI/2020/06/025887 and NCT04232384.

Lay abstract Existing methods of diagnosing cancer-related ascites are dependent on microscopic evaluation of fluid obtained from the ascites. However, this may not diagnose all such cases because the fluid may not contain many tumor cells. This may be due to the settling of tumor cells in certain inaccessible locations of the peritoneum (the lining of the abdominal cavity). This trial will look at whether rolling the patient from side to side could be helpful in increasing the chances of finding tumor cells in the ascites.

FDG-PET-CT Enterography Helps Determine Clinical Significance of Suspected Ileocecal Thickening: A Prospective Study.

BACKGROUND: Ileocecal thickening (ICT) on imaging could result from diverse etiologies but may also be clinically insignificant. AIM: Evaluation of role of combined 2-deoxy-2-fluorine-18-fluoro-D-glucose(18F-FDG)-positron emission tomography and computed tomographic enterography (PET-CTE) for determination of clinical significance of suspected ICT. METHODS: This prospective study enrolled consecutive patients with suspected ICT on ultrasound. Patients were evaluated with PET-CTE and colonoscopy. The patients were divided into: Group A (clinically significant diagnosis) or Group B (clinically insignificant diagnosis) and compared for various clinical and radiological findings. The two groups were compared for maximum standardized uptake values of terminal ileum, ileo-cecal valve, cecum and overall. RESULTS: Of 34 patients included (23 males, mean age: 40.44 ± 15.40 years), 12 (35.3%) had intestinal tuberculosis, 11 (32.4%) Crohn's disease, 3 (8.8%) other infections, 1 (2.9%) malignancy, 4 (11.8%) non-specific terminal ileitis while 3 (8.8%) had normal colonoscopy and histology. The maximum standardized uptake value of the ileocecal area overall (SUVmax-ICT-overall) was significantly higher in Group A (7.16 ± 4.38) when compared to Group B (3.62 ± 9.50, P = 0.003). A cut-off of 4.50 for SUVmax-ICT-overall had a sensitivity of 70.37% and a specificity of 100% for prediction of clinically significant diagnosis. Using decision tree model, the SUVmax-ICT with a cut-off of 4.75 was considered appropriate for initial decision followed by the presence of mural thickening in the next node. CONCLUSION: PET-CTE can help in discrimination of clinically significant and insignificant diagnosis. It may help guide the need for colonoscopy in patients suspected to have ICT on CT.

Prophylactic ligation of the opacified thoracic duct in minimally invasive esophagectomy - feasibility and safety.

BACKGROUND: Chyle leak is a rare but morbid complication of esophagectomy. We assessed the feasibility of visualization and prophylactic ligation of the opacified thoracic duct (TD) after administration of 50 ml of olive oil. METHODS: This prospective single center study considered all patients with carcinoma of the middle and lower thirds of the thoracic esophagus including the gastroesophageal junction (GEJ), managed from January 2018 to December 2019, for inclusion. All patients underwent McKeown minimally invasive esophagectomy. After anesthesia and endotracheal intubation, 50 ml of olive oil was administered through a nasogastric (NG) tube. During thoracoscopic esophageal mobilization, the opacified thoracic duct was identified and ligated using Weck Hem-o-lok clips immediately above the diaphragmatic hiatus. Postoperatively, the nature, volume, and triglyceride levels of the fluid from the chest drain were recorded. RESULTS: Forty-three patients with carcinoma of the esophagus were assessed for inclusion and eventually, 33 were enrolled. The median age of the study population was 55 years, and there were 20 males. The tumor site was the lower esophagus in 24 (72.7%) patients. The most common histolopathological finding was squamous cell carcinoma (97%). The opacified thoracic duct could be identified and ligated in 31 (93.9%) patients. The median duration from the administration of olive oil to the ligation of the thoracic duct was 100 min. The median chest drain output and triglyceride levels on postoperative day (POD) one were 250 ml and 48 mg% respectively. No patient developed postoperative chylothorax. CONCLUSION: Opacification and visualization of the thoracic duct during thoracoscopy can be aided by administering olive oil. Ligation of this opacified duct is feasible and safe.

Scientific validation of the antimicrobial and antiproliferative potential of Clerodendrum serratum (L.) Moon, its phytoconstituents and their biosafety by acute oral toxicity study.

The screening of aqueous extract of Clerodendrum serratum revealed its broad-spectrum antimicrobial potential against Gram positive, Gram negative bacteria, and yeast. Optimizing the extraction strategies, revealed 15% concentration of aqueous extract prepared at 40 °C by extracting for 40 min, as optimum parameters and its statistical optimization by Box-Behnken design led to 1.16-1.35 folds enhancement in activity. Organic solvent extraction further improved the activity where methanol proved to be the best organic extractant which was effective against all the 13 pathogens tested with inhibition zone ranging from 14 to 32 mm. Minimum Inhibitory Concentration (MIC) study endorsed the methanolic extract to be the best organic extractant, as it showed the lowest MIC (0.5-10 mg/ml) in comparison to aqueous extract (1-10 mg/ml) as well as Partially Purified Phytoconstituents i.e., flavonoids (1-5 mg/ml), diterpenes (5-10 mg/ml) and cardiac glycosides (5-10 mg/ml). All these were found to be biosafe in both In-vitro (Ames and MTT assay) and In-vivo toxicity studies. Acute oral toxicity testing of flavonoids (2000 mg/ml) on Wistar rats did not reveal any significant change in relative organ weight, biochemical, hematological parameters and organs' architecture in comparison to control. Antiproliferative potential of flavonoids against human cancerous cell lines i.e., HeLa, HCT-15, and U87-MG, further increase the importance of this plant as a promising candidate for drug development. The overall study justified the medicinal importance of this plant.

Pre-clinical and cellular toxicity evaluation of 7-methylxanthine: an investigational drug for the treatment of myopia.

The present study entails the toxicity evaluation of 7-methyl xanthine (7-MX), first of its kind molecule found effective in phase II clinical trials for the treatment of myopia, in comparison to other clinically used xanthines i.e., caffeine and theobromine. For acute toxicity evaluation, 7-MX was administered orally in two rodent species (rat and mice) at the doses of 300 mg/kg and 2000 mg/kg and for repeated dose 28-d oral toxicity, at 250, 500, and 1000 mg/kg in rats. Further, cellular toxicity was evaluated in normal breast epithelial (fR2), rat brain C6 glioma (C6 glioma) and human colorectal (Caco-2) cell lines. Also, the cell uptake assay to determine the intestinal permeability of drug was performed in Caco-2 cells. In acute toxicity, 7-MX treatment showed no mortality and toxicity, whereas 66.6% (mice) and 33.3% (rat) mortality was observed in both caffeine and theobromine treatment groups. In repeated dose 28-d oral toxicity, 7-MX treatment was found to have no-observed-adverse-effect level up to the dose of 1000 mg/kg in the present study conducted as per OECD guidelines 407. Also, very high IC50 value of 305.5 and 721 µg/mL was observed for 7-MX in fR2 and C6 glioma cells, respectively. In Caco-2 cells, linear bioavailability and high % cell viability was observed. Thus, 7-MX may be classified as Globally Harmonized System (GHS) category 5 drug with LD50 >2000-5000 mg/kg. Also, the repeated dose 28-d oral toxicity study demonstrated 7-MX to be nontoxic in nature, with cell line toxicity results further endorsing its nontoxic nature.

Novel Vitamin E TPGS based docetaxel nanovesicle formulation for its safe and effective parenteral delivery: Toxicological, pharmacokinetic and pharmacodynamic evaluation.

Docetaxel (DTX) is a highly lipophilic, BCS class IV drug with poor aqueous solubility (12.7 µg/mL). Presently, only injectable formulation is available in the market which uses a large amount of surfactant (Tween 80) and dehydrated alcohol as a solubilizer. High concentrations of Tween 80 in injectable formulations are associated with severe consequences i.e. nephrotoxicity, fluid retention, and hypersensitivity reactions. The present study aims to eliminate Tween 80, thus novel biocompatible surfactant Vitamin E TPGS based nanovesicle formulation of DTX (20 mg/mL) was developed and evaluated for different quality control parameters. Optimized nanovesicular formulation (NV-TPGS-3) showed nanometric size (102.9 ± 2.9 nm), spherical vesicular shape, high drug encapsulation efficiency (95.2 ± 0.5%), sustained-release profile and high dilution integrity with normal saline. In vitro cytotoxicity assay, showed threefold elevation in the IC50 value of the optimized formulation in comparison to the commercial formulation. Further, no mortality and toxicity were observed during 28 days repeated dose sub-acute toxicity studies in Swiss albino mice up to the dose of 138 mg/kg, whereas, commercial formulation showed toxicity at 40 mg/kg. In addition, in vivo anticancer activity on Ehrlich Ascites Carcinoma induced mice showed a significant tumour growth inhibition of 76.3 ± 5.3% with the NV-TPGS-3 treatment when compared to Ehrlich Ascites Carcinoma control. Results demonstrated that the developed Vitamin E TPGS based nanovesicular formulation of DTX could be a better alternative to increase its clinical uses with improved therapeutic efficacy, reduced toxicity and dosing frequency, and sustained drug release behaviour.