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.

Pancreatolithiasis, or pancreatic calculi (PC), is a sequel of chronic pancreatitis (CP) and may occur in the main ducts, side branches or parenchyma. Calculi are the end result, irrespective of the etiology of CP. PC contains an inner nidus surrounded by successive layers of calcium carbonate. These calculi obstruct the pancreatic ducts and produce ductal hypertension, which leads to pain, the cardinal feature of CP. Both endoscopic therapy and surgery aim to clear these calculi and decrease ductal hypertension. In small PC, endoscopic retrograde cholangiopancreatography (ERCP) followed by sphincterotomy and extraction is the treatment of choice. Large calculi require fragmentation by extracorporeal shock wave lithotripsy (ESWL) prior to their extraction or spontaneous expulsion. In properly selected cases, ESWL followed by ERCP is the standard of care for the management of large PC. Long-term outcomes following ESWL have demonstrated good pain relief in approximately 60% of patients. However, ESWL has limitations. Per oral pancreatoscopy and intraductal lithotripsy represent techniques in evolution, and in current practice their use is limited to centers with considerable expertise. Surgery should be offered to all patients with extensive PC, associated multiple ductal strictures or following failed endotherapy.
Calcium Carbonate ; Calculi* ; Cholangiopancreatography, Endoscopic Retrograde ; Constriction, Pathologic ; Humans ; Hypertension ; Lithotripsy ; Pancreatic Ducts ; Pancreatitis, Chronic ; Shock ; Standard of Care

Pancreatolithiasis, or pancreatic calculi (PC), is a sequel of chronic pancreatitis (CP) and may occur in the main ducts, side branches or parenchyma. Calculi are the end result, irrespective of the etiology of CP. PC contains an inner nidus surrounded by successive layers of calcium carbonate. These calculi obstruct the pancreatic ducts and produce ductal hypertension, which leads to pain, the cardinal feature of CP. Both endoscopic therapy and surgery aim to clear these calculi and decrease ductal hypertension. In small PC, endoscopic retrograde cholangiopancreatography (ERCP) followed by sphincterotomy and extraction is the treatment of choice. Large calculi require fragmentation by extracorporeal shock wave lithotripsy (ESWL) prior to their extraction or spontaneous expulsion. In properly selected cases, ESWL followed by ERCP is the standard of care for the management of large PC. Long-term outcomes following ESWL have demonstrated good pain relief in approximately 60% of patients. However, ESWL has limitations. Per oral pancreatoscopy and intraductal lithotripsy represent techniques in evolution, and in current practice their use is limited to centers with considerable expertise. Surgery should be offered to all patients with extensive PC, associated multiple ductal strictures or following failed endotherapy.
Calcium Carbonate ; Calculi* ; Cholangiopancreatography, Endoscopic Retrograde ; Constriction, Pathologic ; Humans ; Hypertension ; Lithotripsy ; Pancreatic Ducts ; Pancreatitis, Chronic ; Shock ; Standard of Care

Gastrointestinal (GI) endoscopy plays an indispensable role in the diagnosis and management of various pediatric GI disorders. While the pace of development of pediatric GI endoscopy has increased over the years, it remains sluggish compared to the advancements in GI endoscopic interventions available in adults. The predominant reasons that explain this observation include lack of formal training courses in advanced pediatric GI interventions, economic constraints in establishing a pediatric endoscopy unit, and unavailability of pediatric-specific devices and accessories. However, the situation is changing and more pediatric GI specialists are now performing complex GI procedures such as endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography for various pancreatico-biliary diseases and more recently, per-oral endoscopic myotomy for achalasia cardia. Endoscopic procedures are associated with reduced morbidity and mortality compared to open surgery for GI disorders. Notable examples include chronic pancreatitis, pancreatic fluid collections, various biliary diseases, and achalasia cardia for which previously open surgery was the treatment modality of choice. A solid body of evidence supports the safety and efficacy of endoscopic management in adults. However, additions continue to be made to literature describing the pediatric population. An important consideration in children includes size of children, which in turn determines the selection of endoscopes and type of sedation that can be used for the procedure.
Adult ; Cardia ; Child* ; Cholangiopancreatography, Endoscopic Retrograde ; Diagnosis ; Endoscopes ; Endoscopy ; Endoscopy, Gastrointestinal* ; Endosonography ; Esophageal Achalasia ; Humans ; Mortality ; Pancreatic Diseases ; Pancreatitis, Chronic ; Specialization

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.

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.

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.

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.