From conventional two-stage hepatectomy to ALPPS: Fifteen years of experience in a hepatobiliary surgery unit.

BACKGROUND: Hepatectomy in patients with large tumor load may result in postoperative liver failure and associated complications due to excessive liver parenchyma removal. Conventional two-stage hepatectomy (TSH) and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique are possible solutions to this problem. Colorectal liver metastases (CRLM) is the most frequent indication, and there is a need to assess outcomes for both techniques to improve surgical and long-term oncological outcomes in these patients. METHODS: A single-center retrospective study was designed to compare TSH with ALPPS in patients with initially unresectable bilateral liver tumors between January 2005 and January 2020. ALPPS was performed from January 2012 onwards as the technique of choice. Long-term overall survival (OS) and disease-free survival (DFS) were evaluated as primary outcome in CRLM patients. Postoperative morbidity, mortality and liver growth in all patients were also evaluated. RESULTS: A total of 38 staged hepatectomies were performed: 17 TSH and 21 ALPPS. Complete resection rate was 76.5% (n = 13) in the TSH group and 85.7% (n = 18) in the ALPPS group (P = 0.426). Overall major morbidity (Clavien-Dindo ≥ 3a) (stage 1 + stage 2) was 41.2% (n = 7) in TSH and 33.3% (n = 7) in ALPPS patients (P = 0.389), and perioperative 90-day mortalities were 11.8% (n = 2) vs. 19.0% (n = 4) in each group, respectively (P = 0.654). Intention-to-treat OS rates at 1 and 5 years in CRLM patients for TSH (n = 15) were 80% and 33%, and for ALPPS (n = 17) 76% and 35%, respectively. DFS rates at 1 and 5 years were 36% and 27% in the TSH group vs. 33% and 27% in the ALPPS group, respectively. CONCLUSIONS: ALPPS is an effective alternative to TSH in bilateral affecting liver tumors, allowing higher resection rate, but patients must be carefully selected. In CRLM patients similar long-term OS and DFS can be achieved with both techniques.

Efficacy of hydrodynamic interleukin 10 gene transfer in human liver segments with interest in transplantation.

Different diseases lead, during their advanced stages, to chronic or acute liver failure, whose unique treatment consists in organ transplantation. The success of intervention is limited by host immune response and graft rejection. The use of immunosuppressant drugs generally improve organ transplantation, but they cannot completely solve the problem. Also, their management is delicate, especially during the early stages of treatment. Thus, new tools to set an efficient modulation of immune response are required. The local expression of interleukin (IL) 10 protein in transplanted livers mediated by hydrodynamic gene transfer could improve the organ acceptance by the host because it presents the natural ability to modulate the immune response at different levels. In the organ transplantation scenario, IL10 has already demonstrated positive effects on graft tolerance. Hydrodynamic gene transfer has been proven to be safe and therapeutically efficient in animal models and could be easily moved to the clinic. In the present work, we evaluated efficacy of human IL10 gene transfer in human liver segments and the tissue natural barriers for gene entry into the cell, employing gold nanoparticles. In conclusion, the present work shows for the first time that hydrodynamic IL10 gene transfer to human liver segments ex vivo efficiently delivers a human gene into the cells. Indexes of tissue protein expression achieved could mediate local pharmacological effects with interest in controlling the immune response triggered after liver transplantation. On the other hand, the ultrastructural study suggests that the solubilized plasmid could access the hepatocyte in a passive manner mediated by the hydric flow and that an active mechanism of transportation could facilitate its entry into the nucleus. Liver Transplantation 23:50-62 2017 AASLD.

Management of pancreatic gastrinoma associated with Von Hippel-Lindau disease: a case report.

BACKGROUND: Pancreatic neuroendocrine tumors (PNET) are a heterogeneous group and constitute 1.3% of all pancreatic tumors. Approximately 10% of these occur in the context of hereditary syndromes, such as VHL disease. CASE REPORT: We report a case of a female patient of 37 years diagnosed VHL and intervened on several occasions by cerebral hemangioblastoma and renal carcinomas. During its follow-up she was diagnosed 2 gastrinomas functioning under 2 cm were enucleated. Later developed new PNET and underwent a total duodenopancreatectomy without pyloric preservation. DISCUSSION: The management of PNET in VHL is difficult due to the association of multiple tumors in different organs and the morbidity and mortality associated with the surgery of the pancreas. Management must be individualized for each patient, based on the ability to produce hormones and present symptoms, the size and location, and in the context of other tumors that usually present in these patients.

Monosegment ALPPS: A new variant of the techniques for rapid hepatic regeneration. Critical review of the initial results of our series.

Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is a novel surgical technique that provides fast and effective growth of liver remnant volume, allowing surgical resection of hepatic lesions initially considered unresectable. Short and long-term results and the convenience of carrying out this technique are issues that still remain under debate while waiting for the final outcomes of the multicenter registries with larger number of cases. The aim of this paper is to describe, from a critical point of view, the outcomes of the cases performed at our center (n=8). On the other hand, it is possible to leave only one hepatic segment as a liver remnant and we illustrate this new surgical procedure (ALPPS monosegment) performed in one patient.

Two stage hepatectomy (TSH) versus ALPPS for initially unresectable colorectal liver metastases: A systematic review and meta-analysis.

BACKGROUND: Although numerous comparisons between conventional Two Stage Hepatectomy (TSH) and Associating Liver Partition and Portal Vein Ligation for staged hepatectomy (ALPPS) have been reported, the heterogeneity of malignancies previously compared represents an important source of selection bias. This systematic review and meta-analysis aimed to compare perioperative and oncological outcomes between TSH and ALPPS to treat patients with initially unresectable colorectal liver metastases (CRLM). METHODS: Main electronic databases were searched using medical subject headings for CRLM surgically treated with TSH or ALPPS. Patients treated for primary or secondary liver malignancies other than CRLM were excluded. RESULTS: A total of 335 patients from 5 studies were included. Postoperative major complications were higher in the ALPPS group (relative risk [RR] 1.46, 95% confidence interval [CI] 1.04-2.06, I2 = 0%), while no differences were observed in terms of perioperative mortality (RR 1.53, 95% CI 0.64-3.62, I2 = 0%). ALPPS was associated with higher completion of hepatectomy rates (RR 1.32, 95% CI 1.09-1.61, I2 = 85%), as well as R0 resection rates (RR 1.61, 95% CI 1.13-2.30, I2 = 40%). Nevertheless, no significant differences were achieved between groups in terms of overall survival (OS) (RR 0.93, 95% CI 0.68-1.27, I2 = 52%) and disease-free survival (DFS) (RR 1.08, 95% CI 0.47-2.49, I2 = 54%), respectively. CONCLUSION: ALPPS and TSH to treat CRLM seem to have comparable operative risks in terms of mortality rates. No definitive conclusions regarding OS and DFS can be drawn from the results.

Manejo del gastrinoma pancreático asociado a la enfermedad de Von Hippel-Lindau. A propósito de un caso / Management of pancreatic gastrinoma associated with Von Hippel-Lindau disease: a case report

Introducción: los tumores neuroendocrinos de páncreas (TNEP) son un grupo heterogéneo y constituyen el 1,3% de todos los tumores pancreáticos. Aproximadamente el 10% aparecen en el contexto de síndromes familiares como el Von Hippel-Lindau (VHL). Caso clínico: presentamos el caso de una paciente mujer de 37 años diagnosticada de VHL e intervenida en varias ocasiones por hemangioblastomas cerebrales y carcinomas renales. Durante su seguimiento se diagnostica de 2 gastrinomas funcionantes menores de 2 cm que se enuclearon. Posteriormente desarrolló nuevo TNEP y se le realizó una duodenopancreatectomía total sin preservación pilórica. Discusión: el manejo de los TNEP en el VHL es difícil debido a la asociación de múltiples tumores en diferentes órganos y a la morbi-mortalidad asociada a la cirugía del páncreas. Su tratamiento hay que individualizarlo en cada paciente, basándonos en su capacidad de producción de hormonas y, por tanto de dar sintomatología, en su tamaño y localización y, además debe ser contextualizado con el resto de tumores que suelen presentar estos pacientes (AU)

Background: Pancreatic neuroendocrine tumors (PNET) are a heterogeneous group and constitute 1.3% of all pancreatic tumors. Approximately 10% of these occur in the context of hereditary syndromes, such as VHL disease. Case report: We report a case of a female patient of 37 years diagnosed VHL and intervened on several occasions by cerebral hemangioblastoma and renal carcinomas. During its follow-up she was diagnosed 2 gastrinomas functioning under 2 cm were enucleated. Later developed new PNET and underwent a total duodenopancreatectomy without pyloric preservation. Discussion: The management of PNET in VHL is difficult due to the association of multiple tumors in different organs and the morbidity and mortality associated with the surgery of the pancreas. Management must be individualized for each patient, based on the ability to produce hormones and present symptoms, the size and location, and in the context of other tumors that usually present in these patients (AU)

ALPPS monosegmento: una nueva variante de las técnicas de regeneración hepática rápida. Revisión crítica de los resultados iniciales de nuestra serie / Monosegment ALPPS: A new variant of the techniques for rapid hepatic regeneration. Critical review of the initial results of our series

La hepatectomía secuencial, descrita en la literatura anglosajona con el acrónimo ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) es una técnica novedosa que ofrece un crecimiento rápido y efectivo del volumen remanente hepático, y que permite la resección quirúrgica de lesiones hepáticas consideradas inicialmente irresecables. Los resultados a corto y largo plazo y la conveniencia de realizar esta técnica son cuestiones que permanecen en discusión a la espera de los resultados finales de los registros multicéntricos. El objetivo del presente trabajo es la revisión crítica de los resultados de la serie de casos realizados en nuestro centro (n = 8). Por otra parte, es posible con esta técnica dejar un único segmento hepático como remanente y realizamos una descripción de esta variante técnica novedosa (ALPPS monosegmento), llevada a cabo en uno de los casos

Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is a novel surgical technique that provides fast and effective growth of liver remnant volume, allowing surgical resection of hepatic lesions initially considered unresectable. Short and long-term results and the convenience of carrying out this technique are issues that still remain under debate while waiting for the final outcomes of the multicenter registries with larger number of cases. The aim of this paper is to describe, from a critical point of view, the outcomes of the cases performed at our center (n = 8). On the other hand, it is possible to leave only one hepatic segment as a liver remnant and we illustrate this new surgical procedure (ALPPS monosegment) performed in one patient

Endometrioma hepático. Actualización y nuevos abordajes / Hepatic endometrioma. An update and new approaches

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