Insight on ALPPS - Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy - mechanisms: activation of mTOR pathway.

BACKGROUND: ALPPS procedure has been introduced to increase the volume of future liver remnant. The mechanisms underlying the accelerated regeneration observed with ALPPS are unknown. It was hypothesized that AMPK/mTOR is activated as an integrating pathway for metabolic signals leading to proliferation and cell growth. Our aim was to analyze increase in liver volume, proliferation parameters and expression of AMPK/mTOR pathway-related molecules in patients undergoing ALPPS. METHODS: A single center prospective study of patients undergoing ALPPS was performed from 2013 to 2015. Liver and serum samples, clinical laboratory results and CT-scan data were obtained. ELISA, Ki-67 immunostaining and qRT-PCR were performed in deportalized and remnant liver tissue in both stages of the procedure. RESULTS: 11 patients were enrolled. Remnant liver volume increased 112 ± 63% (p < 0.05) in 9.1 ± 1.6 days. Proliferation-related cytokines IL-6, TNF-α, HGF and EGF significantly increased, while higher Ki-67 immunostaining and cyclin D expression were observed in remnant livers after ALPPS. mTOR, S6K1, 4E-BP1, TSC1 and TSC2 expression were significantly increased in remnant livers at second stage, while AMPK and Akt increased only in deportalized liver samples. CONCLUSION: Rapid liver regeneration with ALPPS might be associated with hepatocyte proliferation induced by mTOR pathway activation.

LAPAROSCOPIC REDO FUNDOPLICATION ALONE, REDO NISSEN FUNDOPLICATION, OR TOUPET FUNDOPLICATION COMBINED WITH ROUX-EN-Y DISTAL GASTRECTOMY FOR TREATMENT OF FAILED NISSEN FUNDOPLICATION.

BACKGROUND: Laparoscopic Nissen fundoplication fails to control the gastroesophageal reflux in almost 15% of patients, and most of them must be reoperated due to postoperative symptoms. Different surgical options have been suggested. AIMS: This study aimed to present the postoperative outcomes of patients submitted to three different procedures: redo laparoscopic Nissen fundoplication alone (Group A), redo laparoscopic Nissen fundoplication combined with distal gastrectomy (Group B), or conversion to laparoscopic Toupet combined with distal gastrectomy with Roux-en-Y gastrojejunostomy (Group C). METHODS: This is a prospective study involving 77 patients who were submitted initially to laparoscopic Nissen fundoplication and presented recurrence of gastroesophageal reflux after the operation. They were evaluated before and after the reoperation with clinical questionnaire and objective functional studies. After reestablishing the anatomy of the esophagogastric junction, a surgery was performed. None of the patients were lost during follow-up. RESULTS: Persistent symptoms were observed more frequently in Group A or B patients, including wrap stricture, intrathoracic wrap, or twisted fundoplication. In Group C, recurrent symptoms associated with this anatomic alteration were infrequently observed. Incompetent lower esophageal sphincter was confirmed in 57.7% of patients included in Group A, compared to 17.2% after Nissen and distal gastrectomy and 26% after Toupet procedure plus distal gastrectomy. In Group C, despite the high percentage of patients with incompetent lower esophageal sphincter, 8.7% had abnormal acid reflux after surgery. CONCLUSIONS: Nissen and Toupet procedures combined with Roux-en-Y distal gastrectomy are safe and effective for the management of failed Nissen fundoplication. However, Toupet technique is preferable for patients suffering from mainly dysphagia and pain.

Laparoscopic redo fundoplication alone, redo nissen fundoplication, or toupet fundoplication combined with roux-en-y distal gastrectomy for treatment of failed nissen fundoplication / Refazer fundoplicatura laparoscópica, refazer fundoplicatura a nissen ou toupet combinada com gastrectomia distal em y-roux para tratamento de recidiva após fundoplicatura a nissen

ABSTRACT BACKGROUND: Laparoscopic Nissen fundoplication fails to control the gastroesophageal reflux in almost 15% of patients, and most of them must be reoperated due to postoperative symptoms. Different surgical options have been suggested. AIMS: This study aimed to present the postoperative outcomes of patients submitted to three different procedures: redo laparoscopic Nissen fundoplication alone (Group A), redo laparoscopic Nissen fundoplication combined with distal gastrectomy (Group B), or conversion to laparoscopic Toupet combined with distal gastrectomy with Roux-en-Y gastrojejunostomy (Group C). METHODS: This is a prospective study involving 77 patients who were submitted initially to laparoscopic Nissen fundoplication and presented recurrence of gastroesophageal reflux after the operation. They were evaluated before and after the reoperation with clinical questionnaire and objective functional studies. After reestablishing the anatomy of the esophagogastric junction, a surgery was performed. None of the patients were lost during follow-up. RESULTS: Persistent symptoms were observed more frequently in Group A or B patients, including wrap stricture, intrathoracic wrap, or twisted fundoplication. In Group C, recurrent symptoms associated with this anatomic alteration were infrequently observed. Incompetent lower esophageal sphincter was confirmed in 57.7% of patients included in Group A, compared to 17.2% after Nissen and distal gastrectomy and 26% after Toupet procedure plus distal gastrectomy. In Group C, despite the high percentage of patients with incompetent lower esophageal sphincter, 8.7% had abnormal acid reflux after surgery. CONCLUSIONS: Nissen and Toupet procedures combined with Roux-en-Y distal gastrectomy are safe and effective for the management of failed Nissen fundoplication. However, Toupet technique is preferable for patients suffering from mainly dysphagia and pain.

RESUMO RACIONAL: A fundoplicatura de Nissen laparoscópica falha em controlar o refluxo gastroesofágico em quase 15% dos pacientes e a maioria deles deve ser reoperada devido aos sintomas. Diferentes técnicas cirúrgicas têm sido sugeridas. OBJETIVOS: Apresentar os resultados pós-operatórios de pacientes submetidos a 3 procedimentos diferentes: Reoperação e fundoplicatura de Nissen laparoscópica apenas (Grupo A), reoperação e fundoplicatura de Nissen laparoscópica combinado com gastrectomia distal (Grupo B) ou reoperação e conversão para Toupet laparoscópico combinado com gastrectomia distal e reconstrução em Y-Roux (Grupo C). MÉTODOS: estudo prospectivo incluindo 77 pacientes submetidos inicialmente a fundoplicatura de Nissen laparoscópica que apresentaram recidiva do refluxo gastroesofágico após a operação. Eles foram avaliados antes e após a reoperação com questionário clínico e estudos funcionais específicos. Reestabelecida a anatomia da junção esôfago-gástrica, procedeu-se às referidas cirurgias. Nenhum paciente perdeu seguimento. RESULTADOS: Os sintomas persistentes foram observados com maior frequência nos pacientes dos Grupos A ou B, associados à estenose da fundoplicatura, fundoplicatura intratorácico ou fundoplicatura torcida. No Grupo C, os sintomas recorrentes associados a essa alteração anatômica foram observados com pouca frequência. Esfincter esofágico inferior incompetente foi confirmado em 57,7% dos pacientes pertencentes ao Grupo A em comparação com 17,2% após fundoplicatura de Nissen laparoscópica combinado com gastrectomia distal, e 26% após a Toupet laparoscópico combinado com gastrectomia distal e reconstrução em Y-Roux. Nesse grupo, apesar do alto percentual de pacientes com esfincter esofágico inferior incompetente, 8,7% apresentaram refluxo ácido anormal após a cirurgia. CONCLUSÕES: As técnicas de Nissen ou Toupet combinados com a gastrectomia distal em Y de Roux são seguras e eficazes para o manejo da falha da fundoplicatura a Nissen. A técnica de Toupet é preferível para pacientes que sofrem principalmente com disfagia e dor.