1.Downstaging with atezolizumab-bevacizumab: a case series
Anand V. KULKARNI ; Parthasarathy KUMARASWAMY ; Balachandran MENON ; Anuradha SEKARAN ; Anuhya RAMBHATLA ; Sowmya IYENGAR ; Manasa ALLA ; Shantan VENISHETTY ; Sumana Kolar RAMACHANDRA ; Giri V. PREMKUMAR ; Mithun SHARMA ; P. Nagaraja RAO ; Duvvur Nageshwar REDDY ; Amit G. SINGAL
Journal of Liver Cancer 2024;24(2):224-233
Background:
s/Aims: Hepatocellular carcinoma (HCC) is generally diagnosed at an advanced stage, which limits curative treatment options for these patients. Locoregional therapy (LRT) is the standard approach to bridge and downstage unresectable HCC for liver transplantation (LT). Atezolizumab-bevacizumab (atezo-bev) can induce objective responses in nearly one-third of patients; however, the role and outcomes of downstaging using atezo-bev remains unknown.
Methods:
In this retrospective single-center study, we included consecutive patients between November 2020 and August 2023, who received atezo-bev with or without LRT and were subsequently considered for resection/LT after downstaging.
Results:
Of the 115 patients who received atezo-bev, 12 patients (10.4%) achieved complete or partial response and were willing to undergo LT; they (age, 58.5 years; women, 17%; Barcelona Clinic Liver Cancer stage system B/C, 5/7) had received 3-12 cycles of atezo- bev, and four of them had received prior LRT. Three patients died before LT, while three were awaiting LT. Six patients underwent curative therapies: four underwent living donor LT after a median of 79.5 days (range, 54-114) following the last atezo-bev dose, one underwent deceased donor LT 38 days after the last dose, and one underwent resection. All but one patient had complete pathologic response with no viable HCC. Three patients experienced wound healing complications, and one required re-exploration and succumbed to sepsis. After a median follow-up of 10 months (range, 4-30), none of the alive patients developed HCC recurrence or graft rejection.
Conclusions
Surgical therapy, including LT, is possible after atezo-bev therapy in well-selected patients after downstaging.
2.Submucosal endoscopy: the present and future
Zaheer NABI ; Duvvur Nageshwar REDDY
Clinical Endoscopy 2023;56(1):23-37
Submucosal endoscopy or third-space endoscopy utilizes the potential space between the mucosal and muscularis layers of the gastrointestinal tract to execute therapeutic interventions for various diseases. Over the last decade, endoscopic access to the submucosal space has revolutionized the field of therapeutic endoscopy. Submucosal endoscopy was originally used to perform endoscopic myotomy in patients with achalasia cardia, and its use has grown exponentially since. Currently, submucosal endoscopy is widely used to resect subepithelial tumors and to manage refractory gastroparesis and Zenker’s diverticulum. While the utility of submucosal endoscopy has stood the test of time in esophageal motility disorders and subepithelial tumors, its durability remains to be established in conditions such as Zenker’s diverticulum and refractory gastroparesis. Other emerging indications for submucosal endoscopy include esophageal epiphrenic diverticulum, Hirschsprung’s disease, and esophageal strictures not amenable to conventional endoscopic treatment. The potential of submucosal endoscopy to provide easy and safe access to the mediastinum and peritoneal spaces may open doors to novel indications and rejuvenate the interest of endoscopists in natural orifice transluminal endoscopic surgery in the future. This review focuses on the current spectrum, recent updates, and future direction of submucosal endoscopy in the gastrointestinal tract.
3.Proposal of novel staging system CNM (Crohn’s primary site, nodes, mesentery) to predict postoperative recurrence of Crohn’s disease
Guduru Venkat RAO ; Partha PAL ; Anuradha SEKARAN ; Pradeep REBALA ; Manu TANDAN ; D. Nageshwar REDDY
Intestinal Research 2023;21(2):196-204
After oncologic resection, histological grading and staging of the tumor give important prognostic information about the future risk of recurrence and hence influence the subsequent management plan. Several studies and their meta-analysis have shown that various histological features (e.g., microscopic positive resection margins, plexitis, granuloma, mesenteric inflammatory activity) can predict postoperative clinical/endoscopic/surgical recurrence after resection in Crohn’s disease (CD). Inclusion of mesentery in surgical resection specimens has been shown to reduce surgical recurrence after ileocolonic resection in CD. However, there is no uniform histopathological staging system for risk stratification in postoperative CD to systematically predict postoperative recurrence. This is because the prediction to date is based on clinical characteristics (smoking status, disease phenotype, surgical history). Histopathological predictors are still not adopted in routine clinical practice due to the lack of a uniform staging system, heterogeneity of published studies and lack of standardized definition of histological features. In this article, we attempted to incorporate all such histological features in a single histological staging system CNM (Crohn’s primary site [resection margin positivity, plexitis, granuloma, depth of infiltration], nodes [presence of granuloma], mesentery [involved or not]) in surgical resection specimen in CD. The proposed CNM classification would help to enable systematic reporting, design future clinical trials, stratify postoperative recurrence risk and choose appropriate postoperative prophylaxis.
4.Outcomes of Endoscopic Drainage in Children with Pancreatic Fluid Collections: A Systematic Review and Meta-Analysis
Zaheer NABI ; Rupjyoti TALUKDAR ; Sundeep LAKHTAKIA ; D. Nageshwar REDDY
Pediatric Gastroenterology, Hepatology & Nutrition 2022;25(3):251-262
Purpose:
Endoscopic drainage is an established treatment modality for adult patients with pancreatic fluid collections (PFCs). Available data regarding the efficacy and safety of endoscopic drainage in pediatric patients are limited. In this systematic review and metaanalysis, we aimed to analyze the outcomes of endoscopic drainage in children with PFCs.
Methods:
A literature search was performed in Embase, PubMed, and Google Scholar for studies on the outcomes of endoscopic drainage with or without endoscopic ultrasonography (EUS) guidance in pediatric patients with PFCs from inception to May 2021. The study’s primary objective was clinical success, defined as resolution of PFCs. The secondary outcomes included technical success, adverse events, and recurrence rates.
Results:
Fourteen studies (187 children, 70.3% male) were included in this review. The subtypes of fluid collection included pseudocysts (60.3%) and walled-off necrosis (39.7%).The pooled technical success rates in studies where drainage of PFCs were performed with and without EUS guidance were 95.3% (95% confidence interval [CI], 89.6–98%; I2 =0) and 93.9% (95% CI, 82.6–98%; I2 =0), respectively. The pooled clinical success after one and two endoscopic interventions were 88.7% (95% CI, 82.7–92.9%; I2 =0) and 92.3% (95% CI, 87.4–95.4%; I2 =0), respectively. The pooled rate of major adverse events was 6.3% (95% CI, 3.3–11.4%; I2 =0). The pooled rate of recurrent PFCs after endoscopic drainage was 10.4% (95% CI, 6.1–17.1%; I2 =0).
Conclusion
Endoscopic drainage is safe and effective in children with PFCs. However, future studies are required to compare endoscopic and EUS-guided drainage of PFCs in children.
5.Comparison of Short Versus Long Esophageal Myotomy in Cases With Idiopathic Achalasia:A Randomized Controlled Trial
Zaheer NABI ; Mohan RAMCHANDANI ; Mahiboob SAYYED ; Radhika CHAVAN ; Santosh DARISETTY ; Rajesh GOUD ; H V V MURTHY ; D Nageshwar REDDY
Journal of Neurogastroenterology and Motility 2021;27(1):63-70
Background/Aims:
Per-oral endoscopic myotomy (POEM) is an established treatment for achalasia. The technique of POEM is still evolving and the impact of length of esophageal myotomy on the outcomes of POEM is not known. In this study, we aim to compare the outcomes of short (3 cm) versus long (6 cm and above) esophageal myotomy in patients undergoing POEM for achalasia cardia.
Methods:
Consecutive patients with idiopathic achalasia (type I and II) were randomized to receive short (3 cm) or long esophageal myotomy (≥ 6 cm).Both groups were compared for clinical success, operative time, adverse events, and gastroesophageal reflux disease (GERD).
Results:
Seventy-one consecutive patients with type I and II achalasia underwent POEM with short (n = 34) or long (n = 37) esophageal myotomy techniques. Mean length of esophageal myotomy in short and long groups was 2.76 ± 0.41 and 7.97 ± 2.40, respectively (P < 0.001). Mean operative time was significantly shorter in short myotomy group (44.03 ± 13.78 minutes and 72.43 ± 27.28 minutes, P < 0.001). Clinical success was comparable in both arms at 1-year (Eckardt score 0.935 ± 0.929 vs 0.818 ± 0.983, P = 0.627).Improvement in objective parameters including integrated relaxation pressure and barium column height at 5 minutes was similar in both groups. GERD was detected in 50.88% patients with no significant difference in short and long myotomy groups (44.44% vs 56.67%, P = 0.431).
Conclusions
A short esophageal myotomy is non-inferior to long myotomy with regards to clinical success, adverse events, and GERD in cases with type I and II achalasia. Reduced operating duration favors short esophageal myotomy in these patients.
6.Very early onset inflammatory bowel disease in a South Asian country where inflammatory bowel disease is emerging: a distinct clinical phenotype from later onset disease
Rupa BANERJEE ; Partha PAL ; Zaheer NABI ; Upender SHAVA ; Girish GANESH ; D. Nageshwar REDDY
Intestinal Research 2021;19(4):398-407
Background/Aims:
Information on pediatric inflammatory bowel disease (PIBD) and very early onset IBD (VEOIBD) are sparse in India, where IBD is emerging. We aimed to evaluate characteristics of VEOIBD and later onset PIBD (LO-PIBD) in India.
Methods:
We performed retrospective analysis of a large, prospectively maintained IBD registry. PIBD was divided in to VEOIBD ( < 6 years) and LO-PIBD (6–17 years). Demographic data, disease characteristics and treatment were compared between the PIBD groups and with other Asian/Western studies as well as the adult patients of the registry.
Results:
Of 3,752 IBD patients, 292 (7.8%) had PIBD (0–17 years) (175 Crohn’s disease [CD], 113 ulcerative colitis [UC], 4 IBD-undifferentiated; 22 VEOIBD [7.5%], and 270 LO-PIBD [92.5%]). VEOIBD patients had more severe disease compared to LO-PIBD in both UC (P= 0.003) and CD (P< 0.001). Familial IBD was more common in VEOIBD (13.6%) compared to LO-PIBD (9.2%). Ileal disease (L1) was an independent risk factor for diagnostic delay in pediatric CD. Diagnostic delay ( > 6 months) was significantly lower in VEOIBD (40.9%) than in LO-PIBD (78.8%) (P< 0.001). Compared to other Asian and Western studies, extensive UC (72.5%) and complicated CD (stricturing/penetrating: 42.7%) were relatively more common. Perianal CD was relatively less frequent (7.4%). PIBD had a significantly higher number of complicated and ileal CD and extensive UC comparison to adult cohort of the registry.
Conclusions
VEOIBD has more aggressive phenotype than LO-PIBD. Disease appears distinct from other Asian and Western studies and adult onset disease, with more complicated CD and extensive UC.
7.Assessment of Pyloric Sphincter Physiology Using Functional Luminal Imaging Probe in Healthy Volunteers
Nitin JAGTAP ; Rakesh KALAPALA ; D Nageshwar REDDY
Journal of Neurogastroenterology and Motility 2020;26(3):391-396
Background/Aims:
The functional luminal imaging probe (FLIP) can measure tissue distensibility and geometric changes through volumetric distention. The esophagogastric junction has been well studied using EndoFLIP, studies on pylorus are lacking. We aim to study biomechanical properties of pylorus using EndoFLIP to create normative data.
Methods:
We performed a prospective study of 20 healthy volunteers (ages, 18-54 years; 10 men) who underwent pylorus evaluation using 12- cm FLIP placed across the pyloric sphincter. FLIP data were analyzed using FLIP planimetry plots at baseline and after administration of hyoscine butyl bromide injection.
Results:
The median pylorus distensibility index (P-DI) was 8.37 mm2/mmHg (interquartile range, 4.22-13.04 mm2/mmHg) at 40 mL balloon volume. The 90th percentile at 40 mL balloon for P-DI was 14.89 mm2/mmHg, for cross-sectional area was 244.20 mm2/mmHg, and diameter and pressure were 17.58 mm and 48.84 mmHg, respectively. There was significant increase in P-DI after administration of hyoscine butyl bromide injection (P < 0.05).
Conclusion
The normative values can be used as reference values for pyloric distensibility. This reference can be used in studies of related to pyloric diseases such as gastroparesis.
9.Endoscopic Management of Combined Biliary and Duodenal Obstruction
Zaheer NABI ; D Nageshwar REDDY
Clinical Endoscopy 2019;52(1):40-46
Combined obstruction of the bile duct and duodenum is a common occurrence in periampullary malignancies. The obstruction of gastric outlet or duodenum can follow, occur simultaneously, or precede biliary obstruction. The prognosis in patients with combined obstruction is particularly poor. Therefore, minimally invasive palliation is preferred in these patients to avoid morbidity associated with surgery. Endoscopic palliation is preferred to surgical bypass due to similar efficacy, less morbidity, and shorter hospital stay. The success of endoscopic palliation depends on the type of bilioduodenal stenosis and the presence of previously placed duodenal metal stents. Biliary cannulation is difficult in type II bilioduodenal strictures where the duodenal stenosis is located at the level of the papilla. Consequentially, technical and clinical success is lower in these patients than in those with type I and III bilioduodenal strictures. However, in cases with failure of endoscopic retrograde cholangiopancreatography, with the introduction of endoscopic ultrasound for biliary drainage, the success of endoscopic bilioduodenal bypass is likely to increase further. The safety and efficacy of endoscopic ultrasound-guided drainage has been documented in multiple studies. With the development of dedicated accessories and standardization of drainage techniques, the role of endoscopic ultrasound is likely to expand further in cases with double obstruction.
Bile Ducts
;
Catheterization
;
Cholangiopancreatography, Endoscopic Retrograde
;
Constriction, Pathologic
;
Drainage
;
Duodenal Obstruction
;
Duodenum
;
Endoscopy
;
Gastric Outlet Obstruction
;
Humans
;
Jaundice, Obstructive
;
Length of Stay
;
Prognosis
;
Stents
;
Ultrasonography
10.Endoscopic Palliation for Biliary and Pancreatic Malignancies: Recent Advances
Zaheer NABI ; D Nageshwar REDDY
Clinical Endoscopy 2019;52(3):226-234
Malignancies of the pancreatobiliary system are usually unresectable at the time of diagnosis. As a consequence, a majority of these cases are candidates for palliative care. With advances in chemotherapeutic agents and multidisciplinary care, the survival rate in pancreatobiliary malignancies has improved. Therefore, there is a need to provide an effective and long-lasting palliative care for these patients. Endoscopic palliation is preferred to surgery as the former is associated with equal efficacy and reduced morbidity. The main role of endoscopic palliation in the vast majority of pancreatobiliary malignancies includes biliary and enteral stenting for malignant obstructive jaundice and gastric outlet obstruction, respectively. Recent advances in endoscopic palliation appear promising in imparting long-lasting relief of symptoms. Use of radiofrequency ablation and photodynamic therapy in malignant biliary obstruction has been shown to improve the survival rates as well as the patency of biliary stents. The emergence of endoscopic ultrasound (EUS) as a therapeutic tool has enhanced the capability of minimally invasive palliation in pancreatobiliary cancers. EUS is a valuable alternative to endoscopic retrograde cholangiopancreatography for the palliation of obstructive jaundice. More recently, EUS is emerging as an effective primary modality for biliary and gastric bypass.
Catheter Ablation
;
Cholangiopancreatography, Endoscopic Retrograde
;
Diagnosis
;
Gastric Bypass
;
Gastric Outlet Obstruction
;
Humans
;
Jaundice, Obstructive
;
Palliative Care
;
Pancreatic Neoplasms
;
Photochemotherapy
;
Stents
;
Survival Rate
;
Ultrasonography

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