Phase 1 Study of Hypofractionated Proton Beam Radiation Therapy in Adjuvant Pancreatic Cancer (PROTON-PANC).

PURPOSE: Despite improvement in systemic therapy, patients with pancreatic ductal adenocarcinoma (PDAC) frequently experience local recurrence. We sought to determine the safety of hypofractionated proton beam radiation therapy (PBT) during adjuvant chemotherapy. METHODS AND MATERIALS: Nine patients were enrolled in a single-institution phase 1 trial (NCT03885284) between 2019 and 2022. Patients had PDAC of the pancreatic head and underwent R0 or R1 resection and adjuvant modified FOLFIRINOX (mFFX) chemotherapy. The primary endpoint was to determine the dosing schedule of adjuvant PBT (5 Gy × 5 fractions) using limited treatment volumes given between cycles 6 and 7 of mFFX. Patients received PBT on days 15 to 19 in a 28-day cycle before starting cycle 7 (dose level 1, DL1) or on days 8 to 12 in a 21-day cycle before starting cycle 7 (DL2). RESULTS: The median patient age was 66 years (range, 52-78), and the follow-up time from mFFX initiation was 12.5 months (range, 6.2-37.4 months). No patients received preoperative therapy. Four had R1 resections and 5 had node-positive disease. Three patients were enrolled on DL1 and 6 patients on DL2. One dose-limiting toxicity (DLT) occurred at DL2 (prolonged grade 3 neutropenia resulting in discontinuation of mFFX after cycle 7). No other DLTs were observed. Four patients completed 12 cycles of mFFX (range, 7-12; median, 11). No patients have had local recurrence. Five of 9 patients had recurrence: 3 in the liver, 1 in the peritoneum, and 1 in the bone. Six patients are still alive, 4 of whom are recurrence-free. The median time to recurrence was 12 months (95% CI, 4 to not reached [NR]), and median overall survival was NR (95% CI, 6 to NR; 2-year survival rate, 57%). CONCLUSIONS: PBT integrated within adjuvant mFFX was well tolerated, and no local recurrence was observed. These findings warrant further exploration in a phase 2 trial.

Factors associated with survival in patients operated on for hilar cholangiocarcinoma with curative intention.

OBJECTIVE: To determine the long-term survival and to analyze the factors associated with it in the patients operated on for hilar cholangiocarcinoma (HC) with curative intention. METHOD: Non concurrent cohort study. We included all patients who underwent surgery with curative intent for HC between 2002 and 2016. An analysis of factors associated with survival using Kaplan Meier, log-rank test and Cox regression was performed. A p-value less than 0.05 was considered significant. RESULTS: Thirty patients were operated on. The median age was 65.5 years (range: 33-84); 24 patients (80%) were male. The surgical margin was negative in 27 patients (90%). Twenty-one patients (70%) presented complications and three patients (10%) died postoperatively. Survival at the year, 5 years and 10 years were 65.7%, 37.3% and 16.6%, respectively. In multivariable analysis, the only factor associated with survival was the T stage (hazard ratio: 0.309; 95% confidence interval: 0.101-0.942; p = 0.03). DISCUSSION: Patients operated on for HC with curative intent in our center have adequate long-term survival, with high postoperative morbidity and mortality. The only factor that was associated with survival was T stage.

OBJETIVO: Determinar la sobrevida a largo plazo y analizar los factores asociados a esta en pacientes operados por colangiocarcinoma hiliar (CH) con intención curativa. MÉTODO: Estudio de cohorte no concurrente. Se incluyeron todos los pacientes sometidos a cirugía con intención curativa por CH entre 2002 y 2016. Se realizó un análisis de los factores asociados a la sobrevida mediante Kaplan Meier, test de log-rank y regresión de Cox. Se consideró significativo un valor de p < 0.05. RESULTADOS: Se operaron 30 pacientes. La mediana de edad fue de 65.5 años (rango: 33-84); 24 (80%) fueron de sexo masculino. El margen quirúrgico resultó negativo en 27 (90%) pacientes. Veintiún (70%) pacientes presentaron complicaciones y 3 (10%) fallecieron en el posoperatorio. Las sobrevidas al año, a 5 años y a 10 años fueron del 65.7%, el 37.3% y el 16.6%, respectivamente. En el análisis multivariable, el único factor asociado a la sobrevida fue el estadio T (hazard ratio: 0.309; intervalo de confianza del 95%: 0.101-0.942; p = 0.03). DISCUSIÓN: Los pacientes operados por CH con intención curativa en nuestro centro presentan una adecuada sobrevida a largo plazo, con una elevada morbimortalidad posoperatoria. El único factor que se asoció a la sobrevida fue el estadio T.

Factors associated with the survival of liver transplant patients due to hepatocellular carcinoma according to Milan criteria.

OBJECTIVE: To determine the overall survival of patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) following the Milan criteria (MC) and analyze factors associated with survival. METHOD: Non-concurrent cohort study. We analyzed patients undergoing LT for HCC between 2000 and 2016. An analysis of the factors associated with survival was carried out using Kaplan-Meier, log-rank test and Cox regression. A value of p < 0.05 was considered significant. RESULTS: A total of 50 LT were performed for HCC. The average age was 60.8 ± 6.1 years; 38 patients (76%) were male. In the multivariate analysis, the factors associated with survival were compliance with CM (hazard ratio [HR]: 0.104; 95% confidence interval [95%CI]: 0.017-0.637; p = 0.01) and absence of vascular invasion (HR: 0.050; 95%CI: 0.008-0.306; p < 0.01) in the explant biopsy. CONCLUSION: Survival of patients undergoing HT by HCC in our center is similar to that reported in the international literature, and is determined by the compliance of the CM and the absence of vascular invasion in the explant biopsy.

OBJETIVO: Determinar la sobrevida global de los pacientes sometidos a trasplante hepático (TH) por carcinoma hepatocelular (CHC) siguiendo los criterios de Milán (CM), y analizar los factores asociados a la sobrevida. MÉTODO: Estudio de cohorte no concurrente. Se analizaron los pacientes sometidos a TH por CHC entre los años 2000 y 2016. Se realizó un análisis de los factores asociados a la sobrevida mediante Kaplan-Meier, test de log-rank y regresión de Cox. Se consideró significativo un valor de p < 0.05. RESULTADOS: Se realizaron 50 TH por CHC. El promedio de edad fue de 60.8 ± 6.1 años; 38 pacientes (76%) fueron de sexo masculino. En el análisis multivariable, los factores asociados a la sobrevida fueron el cumplimiento de los CM (hazard ratio [HR]: 0.104; intervalo de confianza del 95% [IC 95%]: 0.017-0.637; p = 0.01) y la ausencia de invasión vascular (HR: 0.050; IC 95%: 0.008-0.306; p < 0.01) en la biopsia del explante. CONCLUSIÓN: La sobrevida de los pacientes sometidos a TH por CHC en nuestro centro es similar a lo reportado en la literatura internacional, y se encuentra determinada por el cumplimiento de los CM y la ausencia de invasión vascular en la biopsia del explante.

Laparoscopic Versus Open Distal Pancreatectomy: Comparative Analysis of Clinical Outcomes at a Single Institution.

PURPOSE: Undertake a comparison between laparoscopic distal pancreatectomy (LDP) and open distal pancreatectomy (ODP) for the management of benign and malignant lesions. METHODS: A case series study of 93 consecutive patients subjected to a distal pancreatectomy for pancreatic tumors between 2001 and 2015. In each patient, clinical and surgical characteristic, postoperative course, histopathologic examination, and survival were analyzed. RESULTS: LDP was associated with significantly less operative blood loss (50 mL vs. 300 mL; P<0.01), higher spleen preservation rate (52.6% vs. 19.2%; P<0.01) and shorter hospital stay (5 d vs. 8 d; P<0.01). In patients with adenocarcinoma, survival at 1 and 5 years were 63.5% and 15.9% in the ODP group versus 66.7% and 33.3% in the LDP group (P=0.43). CONCLUSIONS: LDP is a safe and feasible procedure for DP resections. LDP offers advantages over ODP in terms of reduction of operative blood loss, higher spleen preservation rate, and shorter hospital stay.

Gastrointestinal neuroendocrine tumor with unresectable liver metastases: an example of multimodal therapeutic approach.

Gastrointestinal neuroendocrine tumors (NET) frequently present with unresectable hepatic metastases, which poses a barrier for curative treatment. Resection of the primary tumor and subsequent orthotopic liver transplantation (OLT) has been proposed as a treatment approach but available data in this regard is limited. We present a clinical case of an otherwise asymptomatic 44-yo man complaining of abdominal pain and dyspepsia that was diagnosed of a 10 cm duodenal tumor with multiple hepatic metastases. A CT-guided biopsy confirmed a NET. He underwent first a Whipple's procedure, and then was listed for liver transplantation. During the waiting time a multimodal therapeutic approach was used including the use of radioactive 177lutetium-labeled somatostatin analogues, long-acting somastostatin analogues and antiangiogenic antibodies (bevacizumab) in order to keep neoplastic disease under control. Two years after Whipple's procedure and given disease stability he underwent OLT with an uneventful postoperative evolution. Patient condition and graft function are optimal after a 4-year follow-up period with no evidence of recurrence. This case report underscores how a multimodal approach involving careful patient selection, resective surgery as well as use of somatostatin analogues and antiangiogenic biological therapy followed by liver transplantation can achieve excellent long-term results in this difficult patient population.

¿Influye el medio de preservación del injerto en los resultados y costos del trasplante hepático de donante fallecido?: Comparación de dos soluciones de preservación / Outcomes using two preservation solutions (UW/HTK) in liver transplantation from brain death donors

Background: Preservation solutions are critical for organ transplantation. In liver transplant (LT), the solution developed by the University Of Wisconsin (UW) is the gold-standard to perfuse deceased brain death donor (DBD) grafts. Histidine-Tryptophan-Ketoglutarate (HTK), formerly a cardioplegic infusion, has been also used in solid organ transplantation. Aim: To compare the outcomes of LT in our center using either HTK or UW solution. Patients and Methods: Retrospective study including 93 LT DBD liver grafts in 89 patients transplanted between March 1994 and July 2010. Forty-eight grafts were preserved with UW and 45 with HTK. Donor and recipient demographics, total infused volume, cold ischemia time, post-reperfusion biopsy, liver function tests, incidence of biliary complications, acute rejection and 12-month graft and patient survival were assessed. Preservation solution costs per liver graft were also recorded. Results: Donor and recipient demographics were similar. When comparing UW and HTK, no differences were observed in cold ischemia time (9.6 ± 3 and 8.7 ± 2 h respectively, p = 0.23), biliary complications, the incidence of acute rejection, primary or delayed graft dysfunction. Histology on post-reperfusion biopsies revealed no differences between groups. The infused volume was significantly higher with HTK than with UW (9 (5-16) and 6 (3-11) l, p < 0.001). The cost per procurement was remarkably lower using HTK. Conclusions: Perfusion of DBD liver grafts with HTK is clinically equivalent to UW, with a significant cost reduction.

[Outcomes using two preservation solutions (UW/HTK) in liver transplantation from brain death donors]. / ¿Influye el medio de preservación del injerto en los resultados y costos del trasplante hepático de donante fallecido?: Comparación de dos soluciones de preservación.

BACKGROUND: Preservation solutions are critical for organ transplantation. In liver transplant (LT), the solution developed by the University Of Wisconsin (UW) is the gold-standard to perfuse deceased brain death donor (DBD) grafts. Histidine-Tryptophan-Ketoglutarate (HTK), formerly a cardioplegic infusion, has been also used in solid organ transplantation. AIM: To compare the outcomes of LT in our center using either HTK or UW solution. PATIENTS AND METHODS: Retrospective study including 93 LT DBD liver grafts in 89 patients transplanted between March 1994 and July 2010. Forty-eight grafts were preserved with UW and 45 with HTK. Donor and recipient demographics, total infused volume, cold ischemia time, post-reperfusion biopsy, liver function tests, incidence of biliary complications, acute rejection and 12-month graft and patient survival were assessed. Preservation solution costs per liver graft were also recorded. RESULTS: Donor and recipient demographics were similar. When comparing UW and HTK, no differences were observed in cold ischemia time (9.6 ± 3 and 8.7 ± 2 h respectively, p = 0.23), biliary complications, the incidence of acute rejection, primary or delayed graft dysfunction. Histology on post-reperfusion biopsies revealed no differences between groups. The infused volume was significantly higher with HTK than with UW (9 (5-16) and 6 (3-11) l, p < 0.001). The cost per procurement was remarkably lower using HTK. CONCLUSIONS: Perfusion of DBD liver grafts with HTK is clinically equivalent to UW, with a significant cost reduction.

Metástasis hepática de origen no colorrectal ni neuroendocrino: tratamiento quirúrgico / Surgical excision of non colorectal liver metastases

Background: The benefits of hepatic resections for colorectal liver metastases are well known. This is not the case for excisions in the treatment of non-colorectal, non neuroendocrine liver metastases. Aim: To assess the results of liver resection in the treatment of patients with non-colorectal, non neuroendocrine liver metastases. Material and Methods: Electronic database analysis of patients with noncolorectal non-endocrine liver metastases undergoing to hepatectomy between 2000-2009. Results: Seventeen patients aged 22 to 78 years, nine women, were operated. The most common primary tumors were stomach, liver, adrenal glands and uterus. In two cases, a synchronic primary tumor and metßstasis excision was performed. Anatomic seg-mentectomy was performed in 10 cases (58.8 percent) and a mayor surgical resection in 7 patients (41.2 percent). In 15 cases (88.2 percent) the tumor margins were negative. Three patients presented postoperative complications and three patients had hepatic tumor recurrence. No patient died in the peri-operative period. One, two and three years survival were 85, 51 and 51 percent respectively, after a follow-up ranging from 9 to 56 months. Conclusions: The surgical treatment of patients with non-colorectal non-endocrine liver metastases is safe and beneficial in selected patients, with a low rate of complications and good survival rates.

Introducción: Existe un claro beneficio en el tratamiento quirúrgico de las metástasis hepáticas de origen colorrectal y neuroendocrinas; sin embargo, todavía no está bien definida la efectividad de la resección quirúrgica en tumores de origen diferente a los anteriores. El objetivo del presente estudio es dar a conocer los resultados del tratamiento quirúrgico en este grupo de pacientes. Pacientes y Método: Análisis de la base de datos electrónica de los pacientes con metástasis hepáticas de origen no colorrectal ni neuroendocri-na que fueron sometidos a resección hepática en nuestro centro entre los años 2000-2009. Resultados: La serie estuvo constituida por 17 pacientes, nueve mujeres, mediana de edad de 51 años (rango, 22-78). Los principales sitios de origen del tumor primario fueron estómago, hígado, glándulas suprarrenales y útero. En dos casos se realizó cirugía sincrónica del primario y las metástasis; la técnica utilizada fue segmentectomía anatómica en 10 pacientes (58,8 por ciento) y resección anatómica mayor los siete restantes (41,2 por ciento). En 15 pacientes (88,2 por ciento) se logró borde quirúrgico libre de tumor, tres pacientes presentaron complicaciones postoperatorias y en tres hubo recidiva de la lesión hepática. No hubo mortalidad operatoria. Tras un seguimiento de 21 meses (rango, 9-56) la supervivencia al año, a los dos y a los tres años fue de 85 por ciento, 51 por ciento y 51 por ciento respectivamente. Discusión: El tratamiento quirúrgico de los pacientes con metástasis hepáticas de origen no colorrectal ni neuroendocrino es seguro y parece beneficioso en pacientes seleccionados, con baja tasa de complicaciones y con supervivencia favorable.

Empaquetamiento hepático permanente con malla de poliglactina en estallido hepático secundario a síndrome de Hellp / Permanent hepatic packing with polyglactin mesh in secondary ruptured liver to Hellp syndrome

El estallido hepático constituye una de las más graves complicaciones del síndrome de Hellp y es una de sus principales causas de muerte. Dada la presencia de falla hepática y trombocitopenia que constituyen la esencia del síndrome de Hellp, la hemostasia quirúrgica del hígado estallado es extremadamente difícil. Presentamos nuestra experiencia con dos casos de embarazos con síndrome de Hellp y complicados con estallido hepático, que debieron ser operados en nuestro servicio y que pudieron ser controlados mediante el empleo de un empaquetamiento hepático con malla de poliglactina. Los objetivos son discutir las alternativas técnicas para la resolución quirúrgica de esta grave complicación y mostrar los detalles de esta forma de empaquetamiento hepático permanente por nosotros empleado.

Barrett's esophagus complicated with stricture: correlation between classification and the results of the different therapeutic options.

Benign esophageal stricture is a serious complication of persistent gastroesophageal reflux in patients with esophagitis and Barrett's esophagus. A classification of the severity of the stricture is proposed, based on its internal diameter, its length, and the ease or difficulty in dilating it. Among 185 patients with esophageal strictures secondary to reflux esophagitis, 77 (41.6%) corresponded to type I or mild stricture, 73 (39.4%) to type II or moderate, and 35 (19.6%) to type III. Medical treatment was performed in only 15 cases, with 73% recurrence. Three types of surgical procedures were employed, always after dilatation, improvement of nutritional status, and a complete preoperative work-up: (1) conservative antireflux surgery, which had a high incidence of recurrence (41.1%); (2) acid suppression and duodenal diversion, in which 68 patients had a mortality rate of 2.9% and a recurrence rate of 4.4% (p <0.002); and (3) esophageal resection, which in 7 patients resulted in 1 death and no late recurrence. It is concluded that classification of the severity of the stricture is important to indicate the most appropriate treatment. Conservative antireflux surgery is followed by a high recurrence rate at late follow-up, whereas acid suppression and duodenal diversion seem to be an adequate procedure that is followed by a very low recurrence rate. Esophageal resection is indicated only for patients with severe or critical esophageal strictures.