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Critical care air transport has played an important role during the coronavirus disease 2019 (COVID-19) pandemic. The goal of this article is to analyze results and lessons learned from the evacuation of the first 100 COVID-19 patients transported between medical facilities in Chile.We reviewed prospective data of patients who were referred for air transport between March 27, 2020, and July 9, 2020.Of 115 referred patients, 100 were transported by air. All patients were intubated and mechanically ventilated. Hypertension, diabetes, and obesity were the most commonly observed comorbidities. Our service did not experience any major problems in patient care en route or among the crewmembers. We did not observe any severe acute respiratory syndrome coronavirus 2 infections among our flight team members during the study period. Twelve (12%) patients died at their destination intensive care unit, whereas the remaining 88 patients (88%) returned to their primary hospitals after recovery.Air transport of mechanically ventilated patients with COVID-19 infection has been shown to be a safe way of transport, with no in-flight deaths and an in-hospital mortality of 12%, which compares favorably with the in-hospital mortality of similar patients who did not undergo air transport.

Background Although gallbladder cancer (GBCA) is characterized by a dismal prognosis, there is a proportion of patients who are cured. The aim of this study was to analyze the profile of these patients. Methods A database was queried for patients who underwent curative resection with a follow-up of at least 5 years. Patients were prospectively treated and registered by the same surgical team. A multivariate regression analysis was used to identify factors associated with long-term survival. Results From 1988 to 2013, 461 patients were evaluated and 112 who underwent resection were analyzed. Among the patients, five year survival was 57% while lymph node and liver compromise were the only independent factors associated with survival. On the other hand, the elapsed time between the cholecystectomy and the resection, the differentiation grade and the level of wall invasion did not have an independent effect on the prognosis. Conclusion Despite its poor prognosis, a subset of patients can be cured of GBCA. R0 resection of patients without lymph and liver infiltration are key to GBCA survival.

Introducción: En algunas áreas el cáncer de la vesícula biliar se detecta en hasta el 3,5% de los pacientes intervenidos por colelitiasis. Con el objetivo de evaluar el rol de la ruptura de la vesícula y la consiguiente contaminación por bilis, se evaluó una serie de pacientes portadores de cáncer de vesícula diagnosticado posterior a la colecistectomía. Material y Método: El estudio se efectuó en 109 pacientes en quienes se diagnosticó un cáncer de vesícula posterior a la colecistectomía. El grupo a estudiar se dividió de acuerdo a la ocurrencia o no de contaminación por bilis al momento de la colecistectomía, como también de acuerdo a la magnitud de esta. Resultados: De los pacientes estudiados, en 32 se documentó la ocurrencia de contaminación por bilis al momento de la colecistectomía. De estos, en 13 la contaminación fue considerada mayor. El tiempo promedio de seguimiento fue de 33 meses, 35 pacientes (32,1%) fallecieron durante el seguimiento. La sobrevida media de la totalidad de la serie que tuvo contaminación por bilis no se diferenció de los pacientes sin contaminación. Sin embargo el grupo que tuvo una contaminación catalogada como mayor, presentó una sobrevida estadísticamente inferior al resto de los pacientes. Finalmente se realizó un análisis mediante el modelo de regresión de COX que incluyo edad, genero, nivel de invasión y tipo de contaminación, resultando la existencia de contaminación mayor por bilis un factor independientemente asociado al pronóstico.Conclusión: La presencia de ruptura vesicular y contaminación mayor por bilis debiera considerarse un factor pronóstico.

El cáncer de vesícula es infrecuente a nivel mundial, a diferencia de su alta incidencia en Chile. Su pronóstico es malo en general, y dependerá de su forma de presentación, siendo mejor en los casos diagnosticados después de una colecistectomía laparoscópica por patología benigna. La reintervención, que incluye la resección hepática y linfadenectomía, es el pilar de la terapia curativa en esta neoplasiaPresentamos la descripción de la técnica quirúrgica realizada en los pacientes con cáncer de vesícula de diagnóstico incidental, en el Servicio de Cirugía de Clínica Alemana de Santiago y en el Hospital de la Fuerza Aérea de Chile.El abordaje laparoscópico representa una alternativa quirúrgica válida en el tratamiento de pacientes con cáncer de vesícula biliar diagnosticados después de la colecistectomía.La estandarización de la técnica debiera contribuir a su mayor empleo y a la obtención de buenos resultados desde un punto de vista oncológico

Data to guide surveillance following oncologic extended resection (OER) for gallbladder cancer (GBC) are lacking. Conditional recurrence-free survival (C-RFS) can inform surveillance. We aimed to estimate C-RFS and identify factors affecting conditional RFS after OER for GBC. Patients with ≥ T1b GBC who underwent curative-intent surgery in 2000–2018 at four countries were identified. Risk factors for recurrence and RFS were evaluated at initial resection in all patients and at 12 and 24 months after resection in patients remaining recurrence-free. Of the 1071 patients who underwent OER, 484 met the inclusion criteria; 290 (60%) were recurrence-free at 12 months, and 199 (41%) were recurrence-free at 24 months. Median follow-up was 24.5 months for all patients and 47.21 months in survivors at analysis. Five-year RFS rates were 47% for the overall population, 71% for patients recurrence-free at 12 months, and 87% for the patients without recurrence at 24 months. In the entire cohort, the risk of recurrence peaked at 8 months. T3–T4 disease was independently associated with recurrence in all groups: entire cohort [hazard ratio (HR) 2.16, 95% confidence interval (CI) 1.49–3.13, P

Objective To test the degree of agreement in selecting therapeutic options for patients suffering from colorectal liver metastasis (CRLM) among surgical experts around the globe. Summary/background Only few areas in medicine have seen so many novel therapeutic options over the past decades as for liver tumors. Significant variations may therefore exist regarding the choices of treatment, even among experts, which may confuse both the medical community and patients. Methods Ten cases of CRLM with different levels of complexity were presented to 43 expert liver surgeons from 23 countries and 4 continents. Experts were defined as experienced surgeons with academic contributions to the field of liver tumors. Experts provided information on their medical education and current practice in liver surgery and transplantation. Using an online platform, they chose their strategy in treating each case from defined multiple choices with added comments. Inter-rater agreement among experts and cases was calculated using free-marginal multirater kappa methodology. A similar, but adjusted survey was presented to 60 general surgeons from Asia, Europe, and North America to test their attitude in treating or referring complex patients to expert centers. Results Thirty-eight (88%) experts completed the evaluation. Most of them are in leading positions (92%) with a median clinical experience of 25 years. Agreement on therapeutic strategies among them was none to minimal in more than half of the cases with kappa varying from 0.00 to 0.39. Many general surgeons may not refer the complex cases to expert centers, including in Europe, where they also engage in complex liver surgeries. Conclusions Considerable inconsistencies of decision-making exist among expert surgeons when choosing a therapeutic strategy for CRLM. This might confuse both patients and referring physicians and indicate that an international high-level consensus statements and widely accepted guidelines are needed.

Gallbladder cancer (GBC) is a rare malignancy of biliary tract cancer (BTC), characterized by late presentation and poor prognosis. It exhibits wide geographical as well as ethnical variations. So, diverse epidemiology along with etiological factors have been discussed in the current article. Present review unravels the germ line polymorphisms contributing to GBC susceptibility through candidate gene approach and GWAS. GBC is enriched with multiple mutations consisting of both passenger and driver mutations. The identification of the hotspot driver mutations which are involved in the etiopathogenesis of this cancer is necessary, before targeted therapies could be implemented clinically. Thus, this review sheds lights on both traditional low throughput methods along with high throughput NGS used to determine somatic mutations in cancer. With the advent of GWAS and high throughput sequencing methods, it is possible to comprehend the mutational landscape of this enigmatic disease. This article is the first one to provide insights into the genetic heterogeneity of GBC along with somatic mutational data from Catalogue of Somatic Mutations in Cancer (COSMIC) database. In addition, management of tumor heterogeneity as a therapeutic challenge has been discussed. Future goals involve liquid biopsy based research for better clinical management of the disease. Therefore, research efforts involving discovery of non- invasive markers for early stage cancer detection along with novel therapies should be directed.

Residual disease (RD) has been described as one of the most relevant prognostic factors after radical surgical resection for incidental gallbladder cancer (IGC). The purpose of the present study was to analyze patterns of RD and determinant prognostic factors in patients undergoing re-resection for IGC. Patients undergoing re-exploration due to IGC between 1990 and 2014 were identified in two referral centers from different South-American countries. Patients submitted to a radical definitive operation were included in the study. Demographics and tumor-treated related variables were analyzed in correlation with RD and survival. The site of RD, local (gallbladder bed) or regional (lymph nodes and bile duct) was correlated with disease-specific survival (DSS). Of 265 patients with IGC submitted to surgery, 168 underwent a radical re-resection and RD was found in 58 (34.5%). Demographic, clinical and surgical variables were compared between both centers showing differences in type of resection, laparoscopic approach, T stages and disease stage. Location of RD was regional in 34 (20.2%) and local in 24 (14.3%), and no residual disease was found in 110 (65.5%) patients. T stage (T1b = 20%, T2 = 23.8%, T3 = 71.7%, p

ResumenObjetivoAnalizar datos relacionados con el programa «Colecistectomía como prevención del cáncer de vesícula biliar».MétodoSe analizan los resultados obtenidos de la página web del DEIS del Ministerio de Salud chileno.ResultadosEl año 2006, fecha de inicio del programa, fueron egresados 42.780 pacientes entre 20 y 64 años con diagnósticos correspondientes a los códigos CIE-10, K80-K83. El año 2012, el número de egresos fue de 58.818, lo que significó que desde el año 2006 fueron egresados 39.419 pacientes más que si se hubiesen mantenido los números del año 2006. Por otra parte, desde antes de la puesta en práctica del programa, se aprecia una disminución de la mortalidad ajustada por edad del cáncer de vesícula.ConclusiónAunque desde la puesta en marcha del programa de prevención del cáncer de vesícula se observa un aumento en el número de casos intervenidos, especialmente durante los años 2011 y 2012, la caída de la tasa de mortalidad parece deberse a factores diferentes al aumento de las colecistectomías.AbstractGoalTo evaluate published data related to the program ‘Cholecystectomy as prevention of Gallbladder Cancer’.MethodAnalysis of the results obtained from the DEIS web page (Ministry of Health of Chile).ResultsSince 2006, The Chile Ministry of Health began a program to reduce the number of gallbladder cancer cases in Chile. To accomplish the above, Chile Government has guarantied the execution of a cholecystectomy program under parameters of quality, opportunity and financial support between the ages of 35 and 49 years old. During 2006, 42,780 patients corresponding to the ICD 10 codes, K80-K83 between 20 and 64 years old were discharged from Chilean Hospitals. In 2012, six years after the beginning of the program, 58,818 were discharged. The program would make done possible to discharge approximately 39,419 extra patients.On the other hand, during the last ten years, a decrease in the mortality rate of gallbladder cancer has been observed in Chile.ConclusionAlthough since the beginning of the program an increase in the number of patients discharged is observed, the decrease in the gallbladder cancer mortality seems not to have relation with the program.

Introducción: El colangiocarcinoma intrahepático (CIH) corresponde al segundo tumor hepático primario y la resección quirúrgica es la única alternativa válida para el tratamiento curativo de esta enfermedad.Reporte de casos: Describimos 2 paciente portadores de CIH con compromiso de vena cava inferior (VCI) que fueron sometidos a resección en Clinica Alemana de Santiago (CAS). Ambas pacientes son de género femenino de 39 y 47 años de edad. Ambas fueron sometidas a resección mayor hepática izquierda, asociada a resección del segmento I y extendida a VCI. La reconstrucción de la VCI fue realizada con parche pericárdico bovino y cierre primario respectivamente. El periodo desde el pos operatorio hasta el alta, fue de 13 y 23 días respectivamenteDiscusión: Aunque la reseccion quirúrgica es la única vía para la curación en el CIH, el compromiso de estructuras vasculares hacen que esto no sea posible. El manejo multidisciplinario asociado a una técnica meticulosa realizada por un equipo quirúrgico experimentado, hacen posible lograr buenos resultados.

Gallbladder cancer is considered a rare disease associated with a dismal prognosis (1-3). However, since the irruption of laparoscopic cholecystectomy, incidental cases have increased and prognosis improved. The main reason for this improvement is the detection of unapparent tumors corresponding to mucosal and muscular lesions. Although laparoscopy has been associated with faster recovery and shorter hospital stay, the effect that gallbladder rupture and subsequent bile spillage on the prognosis of patients harboring an incidental gallbladder cancer is not completely understood (4,5).

Gallbladder cancer (GBC) is the second-leading cause of death from malignant tumors in Chilean women. The phosphatidylinositol 3-kinase (PI3K) pathway is involved in proliferation, cell survival, and growth. We investigated mutations in exons 9 and 20 of the PI3K gene in GBC. Mutations in exons 9 (E542K, E545G, E545K) and 20 (H1047L and H1047R) of PI3K were determined by direct sequencing in 130 cases of GBC. The patient group consisted of 110 women and 20 men, and mutations were found in 22 cases (16.9%). Of these, 14 cases had mutations in exon 9 (63.6%) (E542K, 64%; E545K, 29%; and E545G, 7%) and 8 in exon 20 (37.4%; H1047L, 50%; H1047R, 50%). No differences were noted in the frequency and type of mutations analyzed by sex, age, or histologic features. We observed mutations in 22% of the early-stage GBC and 14.6% of the advanced cases. In this series of GBC, 17% of cases were noted as having mutations in either exons 9 or 20 of PI3K. These results suggest that therapeutic testing of inhibitors of the PI3K/AKT pathway may be of benefit in advanced GBC patients.

Background Equipoise exists regarding the benefit of adjuvant therapy (AT) in patients with gallbladder cancer (GBC). The aim of this study was to critically review the available evidence for the effectiveness of AT in patients with GBC following surgery with curative intent. Methods A systematic review was performed. Relevant studies were identified from Trip Database, BIREME-BVS, SciELO, Cochrane Central Register, WoS, MEDLINE, EMBASE and SCOPUS. Adjuvant therapies considered included chemotherapy, chemoradiotherapy, and radiotherapy. The primary outcome was overall survival (OS). Subgorup analysis of patients with positive lymph node disease (PLND), positive surgical margin (PSM), or advanced stage (AS) were performed. Results 748 related articles were identified; 27 met the selection criteria (3 systematic reviews and 24 observational studies). Evidence provided was moderate, poor and very poor for chemotherapy, chemoradiotherapy, and radiotherapy. Existing evidence is not robust, but suggests certain benefits with AT in improving OS, especially in patients with PLND, PSM and AS. Conclusion Results do not provide strong evidence that AT is effective in patients who undergo resection for GBC. Subgroups of PLND and PSM may have a survival advantage. Future studies with appropriate internal validity and adequate number of patients are required to better answer this question.

Gallbladder cancer (GBC) should be considered an orphan disease in oncology and represent a unique carcinogenetic model. This review will analyse some of the current aspects of GBC.Chile has the highest incidence and mortality of GBC in the world. Most patients are diagnosed in advanced stages with few treatment options. During the last two decades, little progress has been made in early diagnosis and treatment. At the molecular level, recent access to next-generation sequencing and other techniques for detecting the mutations of multiple genes have made advances in this area.The use of therapies targeted according to the detection of specific molecular alterations is in the early stages of evaluation and could represent a significant advance in the treatment of a large number of patients from developing countries.

To determine the prognostic impact of tumor location in gallbladder cancer.Depth of tumor is a strong predictor of survival after curative resection of gallbladder cancer. However, the gallbladder has a unique anatomical relationship with the liver, and the clinical significance of tumor location remains unclear.For 437 patients with gallbladder cancer who underwent resection at 4 international institutions, clinicopathologic characteristics and their association with survival were analyzed. Tumor location was defined as "hepatic side" or "peritoneal side," and the prognostic significance of tumor location was evaluated.Among the 252 patients with T2 disease, patients with tumors on the hepatic side (T2h, n = 99) had higher rates of vascular invasion, neural invasion, and nodal metastasis than patients with tumors on the peritoneal side (T2p, n = 153) (51% vs 19%, 33% vs 8%, and 40% vs 17%, respectively; P0.01 for all). After a median follow-up of 58.9 months, 3-year and 5-year survival rates were 52.1% and 42.6%, respectively, for T2h tumors and 73.7% and 64.7%, respectively, for T2p tumors (P = 0.0006). No such differences were observed in T1 or T3 tumors. Multivariate analysis confirmed the independent association of hepatic-side location with survival in T2 tumors (hazard ratio, 2.7; 95% confidence interval, 1.7-4.2; P0.001). This subclassification of T2 tumors predicted recurrence in the liver (23% vs 3%; P = 0.003) and distant lymph nodes (16% vs 3%; P = 0.019) even after radical resection.After curative resection of T2 gallbladder cancer, tumor location predicts the pattern of recurrence and survival.

The laparoscopic cholecystectomy has allowed the detection of an increasing number of incidental gallbladder cancers (IGBC). Although laparoscopy is employed in the management of a variety of abdominal tumors, its use in gallbladder cancer is reduced and controversial. This study analyzes the role of laparoscopy in gallbladder cancer with the focus in IGBC. We evaluated our prospective series of 51 patients with an IGBC who were treated by laparoscopy between 2006 and 2016 at the Clinica Alemana in Santiago, Chile. The series comprised 7 men and 44 women. Age ranged from 43 to 76 years (mean age 60). Regarding wall involvement, 29 patients had a T2 tumor, which was the most common. 8 and 14 patients had T1b and T3 tumors, respectively. Of the patients, 17 underwent only laparoscopic exploration. This was due to the presence tumor dissemination not being observed in the preoperative staging. 10 patients had to be converted to complete the resection, whereas 24 patients were laparoscopically resected. The quality of the resected material was not different between those who were converted and those who were treated by laparoscopy. In the laparoscopic group, the average number of harvested lymph nodes was 7.9, not statistically different from the converted group. The mean of hospital stay in the laparoscopic group (4.3 days) was significantly lower than the converted group. Laparoscopy has been shown to be a safe and feasible method for the management of IGBC. This method not only allows for a complete exploration, identifying a previously unseen residual tumor, but also makes it possible to accomplish the same oncology objectives as the open procedure. Therefore, laparoscopy should be considered a valid alternative in the management of IGBC.

Gallbladder cancer is now considered a distinct clinical entity, allowing for a separate analysis from that of other malignancies of the biliary tree. Symptoms related to a malignant tumor of the gallbladder include jaundice and abdominal pain, or a palpable abdominal mass that occurs in a late stage of the disease. The majority of patients with operable gallbladder cancer are diagnosed by cholecystectomy performed for presumed benign disease, mostly cholelithiasis, a clinical entity known as incidental gallbladder cancer. Given the poor prognosis if tumor invasion beyond the muscular layer and/or nodal metastasis is found, adjuvant treatments have been implemented, but few data are available to guide treatment decisions in this setting. For advanced disease, a multidisciplinary treatment approach including biliary drainage procedures and palliative support is needed in the management of this aggressive disease. Palliative chemotherapy with a combination of gemcitabine and cisplatin or oxaliplatin is the standard treatment based on the findings of two phase III trials that showed improved overall survival compared to single-agent chemotherapy and best supportive care. Several phase II studies have been reported investigating the role of targeted agents against EGFR, VEGF, HER2, and MEK. International collaboration to enhance our knowledge of gallbladder cancer should be encouraged.

Objectives To explore gallbladder cancer (GBC), the second leading cause of cancer-related death in women in Chile. Methods Analysis of macroscopic and microscopic variables, morphometry, and survival in 1,366 patients with GBC. Results Patients comprised 1,138 women and 228 men; diagnoses included 213 (15.6%) cases of mucosal carcinoma, 132 (9.7%) cases of muscular carcinoma, 316 (23.1%) cases of subserosal carcinoma, 382 (28.0%) cases of serosal carcinoma, and 323 (23.6%) cases beyond the serosa. Women older than 55 years with a gallbladder length greater than 9.5 cm had a five-times-greater relative risk of cancer. Those with a gallbladder wall thickness less than 7 mm had a better 5-year survival rate than those with a gallbladder wall thickness greater than 10 mm ( P = .0001). Patients who had cholesterolosis of the gallbladder had 9.2 times less probability of having cancer. The infiltration level of the gallbladder wall was the most important independent prognostic factor ( P < .001), followed by differentiation and lymphatic involvement ( P < .001 and P = .05, respectively). Vascular infiltration had a mortality rate of 100%. Conclusions Morphologic features are strongly associated with the prognosis of GBC and must be taken into consideration when supplementary treatment is recommended.

Resumen es: A pesar de la disminucion observada en las cifras de mortalidad de la pancreatoduodenectomia, continua siendo una intervencion asociada a una alta tasa d...

Gallbladder cancer is a rare disease in Western developed countries, but it is a highly prevalent and lethal disease in Chile and other countries in Latin America. No randomized controlled trials have been performed in gallbladder cancer to establish standard treatments. We therefore performed the first Latin American consensus meeting for the management of gallbladder cancer. In this article we present the conclusions of the panel of experts for the palliative treatment of unresectable or metastatic gallbladder cancer based on a review of the literature, the discussion of the participating experts and the opinion of the assistants. The topics reviewed included: (1) Gallbladder cancer and cholangiocarcinoma--are they the same disease?; (2) Palliative chemotherapy: indications, drugs and schedules; (3) Palliative radiotherapy; (4) Palliative Surgery; (5) Management of malignant biliary obstruction.

The different bariatric surgery techniques that alter the digestive anatomy also modify the gastric absorption surface. Since alcohol is a substance that is mainly metabolized in the stomach, the goal of this study was to determine alcohol absorption before and after a laparoscopic sleeve gastrectomy (LSG) in the same patients.Studies were carried out on 12 morbidly obese patients who underwent a LSG (eight men and four women). Each patient was given 3.6 ml of red wine to drink at 14% for each liter of body water mass. Alcotest values (Alcoscan Alcomate AL-6000) were measured 10 min after the wine dose had been consumed. Measurements were then repeated every 5 min until the alcohol had been completely eliminated from the bloodstream. During the postoperatory period (median of 2.3 months), the measurement was repeated with the total dose per kg adjusted to the new water body mass. The results were measured with a nonparametric analysis for repeated samples.The maximum average peak of the Alcotest was 2.02 g/l during the postoperative period compared to 0.87 g/l during the preoperative period (p = 0.001 Wilcoxon). At 175 min, the blood alcohol level value reaches zero (0) in all pre-operatory patients, while after surgery, an average value of 0.26 g/l was observed (p = 0.027 Wilcoxon). After 4 h, an Alcotest average of 0.20 g/l was observed in these patients.Alcohol absorption was considerably modified after LSG with higher and longer blood alcohol values for equivalent amounts of alcohol.

The aim of this study was to evaluate the role that laparoscopy plays in the management of gallbladder cancer.From August 2005 to March 2009, 23 patients affected by gallbladder cancer detected after the study of a cholecystectomy specimen underwent laparoscopy as part of their management.Among the patients, 5 underwent only an exploratory laparoscopy, while 11 were converted due to the existence of dense adhesions that precluded a complete exploration. Of the patients with adhesions who underwent conversion, three were unresectable. The remainder underwent a lymphadenectomy and liver resection after conversion. Of the seven who underwent a complete laparoscopic exploration, five had a lymphadenectomy and liver resection done completely by laparoscopy while conversion was needed for two. Conversion was required due to lymphatic metastasis at the hepatic pedicle and the presence of a bile leak. Postoperative time was uneventful, with patients discharged within 3 days of the operation.Laparoscopy may be employed in the management of patients with early forms of gallbladder cancer undergoing reoperation. Although the presence of adhesions may result in inadequate exploration, there is a subset of patients for whom it is possible to perform a complete exam. Furthermore, laparoscopic lymphadenectomy and gallbladder bed resection is a promising technique in well-selected patients.

Background and Objectives: The goal of this study was to evaluate a series of patients with early gallbladder cancer, focusing on the selection of treatment and the role of Rokitansky Aschoff sinus infiltration. Methods: We performed a retrospective analysis of a prospective series of 371 patients with gallbladder cancer. Specimens were reviewed by an independent pathologist to confirm the diagnosis and depth of infiltration and to evaluate the presence of Rokitansky Aschoff sinus involvement. Results: Forty-nine and 45 patients with muscular (pT1b) and mucosal (pT1a) infiltration gallbladder cancer tumors were studied respectively. Simple cholecystectomy was the treatment in all patients, with the exception of 11 patients who underwent further surgery. Rokitansky Aschoff sinus invasion was seen in seven patients with mucosa (pT1a) and three with muscular (pT1b) compromise. The 5-year survival rates of patients with muscular (pT1b) and mucosal (pT1a) infiltration were 87.6% and 86.4%, respectively. Patients with Rokitansky Aschoff involvement had a lower survival rate than those with no involvement in both categories. Conclusions: Early gallbladder cancer is associated with a favorable prognosis and cholecystectomy should be the standard treatment. Despite some patients having a worse prognosis, there are no data to support more aggressive treatment. J. Surg. Oncol. 2009 Wiley-Liss, Inc.

Gallbladder cancer (GBC) is the second-leading cause of death from malignant tumors in Chilean women. The phosphatidylinositol 3-kinase (PI3K) pathway is involved in proliferation, cell survival, and growth. We investigated mutations in exons 9 and 20 of the PI3K gene in GBC. Mutations in exons 9 (E542K, E545G, E545K) and 20 (H1047L and H1047R) of PI3K were determined by direct sequencing in 130 cases of GBC. The patient group consisted of 110 women and 20 men, and mutations were found in 22 cases (16.9%). Of these, 14 cases had mutations in exon 9 (63.6%) (E542K, 64%; E545K, 29%; and E545G, 7%) and 8 in exon 20 (37.4%; H1047L, 50%; H1047R, 50%). No differences were noted in the frequency and type of mutations analyzed by sex, age, or histologic features. We observed mutations in 22% of the early-stage GBC and 14.6% of the advanced cases. In this series of GBC, 17% of cases were noted as having mutations in either exons 9 or 20 of PI3K. These results suggest that therapeutic testing of inhibitors of the PI3K/AKT pathway may be of benefit in advanced GBC patients.

Gallbladder cancer (GC) is considered a rare disease associated with a poor prognosis. Unfortunately, the low number of cases makes the performance of trials addressing the role of adjuvant, neoadjuvant, and/or palliative therapy difficult. For a long time, the majority of trials were 5-fluorouracil (5 FU)-based, and results were uniformly poor. Since the introduction of Gemcitabine, response rates of approximately 30% have been observed through the use of this drug and new approaches have been tested. In this sense, drugs such as Cisplatin and Capecitabine have been employed concurrently with gemcitabine and/or radiation. Since a recurrence pattern is both distant and local, chernoradiation seems a logical option to deal with the disease. However, at the present time, the lack of valid and scientific evidence means that most of the recommendations originate from trials dealing with other tumors, such as pancreas cancer and biliary tract cancer (BTC). The aforementioned treatment alternatives warrant further evaluation focusing on GC.

To explore gallbladder cancer (GBC), the second leading cause of cancer-related death in women in Chile.Analysis of macroscopic and microscopic variables, morphometry, and survival in 1,366 patients with GBC.Patients comprised 1,138 women and 228 men; diagnoses included 213 (15.6%) cases of mucosal carcinoma, 132 (9.7%) cases of muscular carcinoma, 316 (23.1%) cases of subserosal carcinoma, 382 (28.0%) cases of serosal carcinoma, and 323 (23.6%) cases beyond the serosa. Women older than 55 years with a gallbladder length greater than 9.5 cm had a five-times-greater relative risk of cancer. Those with a gallbladder wall thickness less than 7 mm had a better 5-year survival rate than those with a gallbladder wall thickness greater than 10 mm (P = .0001). Patients who had cholesterolosis of the gallbladder had 9.2 times less probability of having cancer. The infiltration level of the gallbladder wall was the most important independent prognostic factor (P.001), followed by differentiation and lymphatic involvement (P.001 and P = .05, respectively). Vascular infiltration had a mortality rate of 100%.Morphologic features are strongly associated with the prognosis of GBC and must be taken into consideration when supplementary treatment is recommended.

Mujer de 58 anos con antecedentes de hiperten-sion arterial, hipotiroidismo en tratamiento y mela-noma maligno (MM) cutaneo dorsal operado el ano 2010 cuyo informe histopatologico revelo un MM de 1,25 mm de espesor segun Breslow y nivel IV de Clark con estudio de bordes quirurgicos negativos. El estudio de diseminacion no demostro lesiones secundarias.La paciente evoluciona asintomatica pesquisan-dose en ecotomografia abdominal de 2013 un engro-samiento parietal vesicular de aproximadamente 3,1 cm de diametro mayor con senal al

Background: The quality of the archival samples stored at pathology services could be a limiting factor for molecular biology studies. Aim: To determine the quality of DNA extracted from gallbladder cancer samples at different institutions. Material and Methods: One hundred ninety four samples coming from fve medical centers in Chile, were analyzed. DNA extraction was quantifed determining genomic DNA concentration. The integrity of DNA was determined by polymerase chain reaction amplification of different length fragments of a constitutive gene (β-globin products of 110, 268 and 501 base pairs). Results: The mean DNA concentration obtained in 194 gallbladder cancer samples was 48 ± 43.1 ng/µl. In 22% of samples, no amplification was achieved despite obtaining a mean DNA concentration of 58.3 ng/ul. In 81, 67 and 22% of samples, a DNA amplification of at least 110, 268 or 501 base pairs was obtained, respectively. No differences in DNA concentration according to the source of the samples were demonstrated. However, there were marked differences in DNA integrity among participating centers. Samples from public hospitals were of lower quality than those from private clinics. Conclusions: Despite some limitations, in 80% of cases, the integrity of DNA in archival samples from pathology services in our country would allow the use of molecular biology techniques.

Background: Overexpression/amplification of the HER2 gene in advanced gastric cancer is a predictor of response to adjuvant therapy with monoclonal antibodies. Aim: To determine the frequency of HER2 gene overexpression and amplification in advanced gastric cancer. Material and Methods: One hundred nine advanced gastric cancer biopsy specimens, from 76 men and 33 women aged 67 ± 14 and 62 ± 12 years respectively, were selected. Three histological patterns (diffuse, intestinal and mixed) were recognized. Automated immunohistochemistry was performed with monoclonal c-erbB-2 (NCL-356) Novocastra. Fluorescent in situ hybridiza- tion (FISH) for HER2 was performed in positive cases. Results: In 39% of cases, immunohistochemical staining was negative. It was 1+, 2+ and 3+ positive in 15, 36 and 11% of cases, respectively. It was positive in 16% and 3% of intestinal type and mixed carcinomas, respectively. It was negative in all diffuse carcinomas. FISH was performed in 39 (2 +) cases and in 11 (3 +) cases. The gene amplification was positive in two (2 +) and 11 (3 +) cases (11.9%). The overall concordance between immunohistochemical staining and in situ hybridization was 85%. Conclusions: In advanced gastric cancer, HER2 gene overexpression or amplification was observed in 11% and 12% of cases, respectively. (Rev Med Chile 2013; 141: 1411-1419)

The HER2/neu gene is a proto-oncogene that can predict the response to treatment with trastuzumab, pertuzumab, and lapatinib. This study was conducted to determine the frequency of HER2/neu overexpression and to identify a subgroup of patients with gallbladder cancer who would benefit from targeted therapy.Patients with gallbladder cancer (n = 187; 165 women and 22 men) with a recorded follow-up of at least 5 years were included, along with control subjects (n = 75). An automated immunohistochemical technique was used with an anti-ErbB2 antibody. Scoring was conducted according to the CAP/ASCO (College of American Pathologists/American Society of Clinical Oncology) criteria for breast cancer.Overexpression of HER2/neu was observed in 12.8% of the cases. Of those, 0% were mucosal, 14.3% muscular, 12.8% subserosal, and 10.6% serosal. In 20% of the cases, equivocal staining was observed. Overexpression was more frequent in the advanced cancers and in the better differentiated tumors (13.8% and 17.4%, respectively), but the difference was nonsignificant. The patients with overexpression of HER2/neu had a worse overall survival, when compared with those who had no expression at 5 years (34% vs. 41%).This is the single largest study of HER2/neu expression in gallbladder cancer to use commonly accepted scoring criteria. The results indicate that HER2/neu overexpression occurred in 14% of the advanced gallbladder cancer cases. This subgroup may benefit from inhibitors of the HER2/neu pathway.

Overexpression/amplification of the HER2 gene in advanced gastric cancer is a predictor of response to adjuvant therapy with monoclonal antibodies.To determine the frequency of HER2 gene overexpression and amplification in advanced gastric cancer.One hundred nine advanced gastric cancer biopsy specimens, from 76 men and 33 women aged 67 ± 14 and 62 ± 12 years respectively, were selected. Three histological patterns (diffuse, intestinal and mixed) were recognized. Automated immunohistochemistry was performed with monoclonal c-erbB-2 (NCL-356) Novocastra. Fluorescent in situ hybridization (FISH) for HER2 was performed in positive cases.In 39% of cases, immunohistochemical staining was negative. It was 1+, 2+ and 3+ positive in 15, 36 and 11% of cases, respectively. It was positive in 16% and 3% of intestinal type and mixed carcinomas, respectively. It was negative in all diffuse carcinomas. FISH was performed in 39 (2 +) cases and in 11 (3 +) cases. The gene amplification was positive in two (2 +) and 11 (3 +) cases (11.9%). The overall concordance between immunohistochemical staining and in situ hybridization was 85%.In advanced gastric cancer, HER2 gene overexpression or amplification was observed in 11% and 12% of cases, respectively.

The quality of the archival samples stored at pathology services could be a limiting factor for molecular biology studies.To determine the quality of DNA extracted from gallbladder cancer samples at different institutions.One hundred ninety four samples coming from five medical centers in Chile, were analyzed. DNA extraction was quantified determining genomic DNA concentration. The integrity of DNA was determined by polymerase chain reaction amplification of different length fragments of a constitutive gene (β-globin products of 110, 268 and 501 base pairs).The mean DNA concentration obtained in 194 gallbladder cancer samples was 48 ± 43.1 ng/µl. In 22% of samples, no amplification was achieved despite obtaining a mean DNA concentration of 58.3 ng/ul. In 81, 67 and 22% of samples, a DNA amplification of at least 110, 268 or 501 base pairs was obtained, respectively. No differences in DNA concentration according to the source of the samples were demonstrated. However, there were marked differences in DNA integrity among participating centers. Samples from public hospitals were of lower quality than those from private clinics.Despite some limitations, in 80% of cases, the integrity of DNA in archival samples from pathology services in our country would allow the use of molecular biology techniques.

Gallbladder cancer is a rare disease in Western developed countries, but it is a highly prevalent and lethal disease in Chile and other countries in Latin America. No randomized controlled trials have been performed in gallbladder cancer to establish standard treatments. We therefore performed the first Latin American consensus meeting for the management of gallbladder cancer. In this article we present the conclusions of the panel of experts for the palliative treatment of unresectable or metastatic gallbladder cancer based on a review of the literature, the discussion of the participating experts and the opinion of the assistants. The topics reviewed included: (1) Gallbladder cancer and cholangiocarcinoma--are they the same disease?; (2) Palliative chemotherapy: indications, drugs and schedules; (3) Palliative radiotherapy; (4) Palliative Surgery; (5) Management of malignant biliary obstruction.

Bariatric surgery is increasingly being performed and sleeve gastrectomy (SG) has proved to be effective and safe. Among its complications, leaks are the most serious and life threatening. The focus of the study is nine patients who underwent a SG and developed a gastric leak after surgery. Our data were obtained from the clinical charts of the patients and through interviews with the surgeon who performed the index surgery. Eight patients underwent SG at outside institutions while one was operated at Clinica Alemana. Three patients developed symptoms within 5 days after surgery, while the rest were diagnosed after 10 days from the surgery. A CT scan was the method used to confirm the diagnosis in all patients. The three patients who had a leak detected during the immediate postoperative period underwent laparoscopic reoperation. Among the rest of the patients, percutaneous drainage was employed in one patient as the primary procedure while the other underwent surgical drainage. An esophageal endoluminal stent was employed in four patients. The leak closed in all patients with the healing time ranging from 21 to 240 days. Diagnosis of a leak after a SG required a greater index of suspicion in order to perform an early diagnosis. Sepsis control and nutritional support are the cornerstones of this treatment. Evolution is characterized by longer periods of time that are necessary in order to wait until the leak closes. Management must be tailored to each patient.

Gallbladder cancer (GBC) is the main cause of death by malignant tumour in women in Chile. There is no information regarding the role of excision repair cross-complementing group 1 (ERCC1) in GBC. Our aim is to determine the expression and significance of ERCC1 as a prognostic factor in GBC. Tissue microarrays were prepared using 200 surgically resected GBCs and 50 non-malignant gallbladders as controls. In 190 cases, ERCC1 was determined by immunohistochemistry. The correlation between ERCC1 expression and GBC pathological characteristics and patient survival were analysed. Ninety-five percent of the non-malignant gallbladder epithelia showed intense and diffuse ERCC1 expression. GBC cases showed ERCC1 expression in the tumour cells in 100/190 (53%) cases. The best differentiated tumours showed significantly greater expression than the less differentiated (p0.05). Patients with ERCC1-positive status with subserosal carcinomas (pT2) had significantly better survival than ERCC1-negative patients at 20 and 60 months of follow-up (p=0.005), and the probability of dying was 6 times lower for ERCC1-positive than for ERCC1-negative patients. Our preliminary results show that chole-cystectomised patients with GBC in stage pT2 and with ERCC1 expression have significantly better survival than patients at the same stage that did not present ERCC1 expression.

Introducción: La Gastrectomía Vertical ha reemplazado a la banda gástrica en el manejo de un importante número de pacientes portadores de obesidad. El objetivo de este trabajo es mostrar los resultados de una serie de pacientes, en los que se realizó una Gastrectomía Vertical posterior a la extracción de una banda gástrica en un mismo tiempo operatorio. Método: La serie incluye a 10 pacientes operados entre Mayo de 2008 y Noviembre de 2009. La principal indicación de la Gastrectomía Vertical fue el fracaso de la banda como tratamiento de la obesidad. Resultados: En los 10 pacientes estudiados, la gastrectomía se pudo efectuar sin mayores dificultades ni diferencias con respecto al procedimiento habitual. No existieron complicaciones post operatorias, siendo la totalidad de los pacientes dados de alta dentro de las 72 horas. Conclusión: La Gastrectomía Vertical representa una alternativa de manejo en pacientes portadores de una banda gástrica con indicación de extracción de esta, ya sea por fracaso o por síntomas asociados a su presencia. El procedimiento puede efectuarse de manera segura en el mismo acto operatorio y sus resultados son comparables a los observados cuando la técnica se efectúa en pacientes que no han sido intervenidos previamente.

Cholesterolosis is frequently observed in cholecystectomies performed for lithiasis or chronic cholecystitis.To determine the degree of association between cholesterolosis and gallbladder cancer.In a prospective study of gallbladder cancer, all gallbladders obtained during cholecystectomies were processed for pathological study, following a special protocol. As part of this study, 23,304 surgical samples obtained between 1993 and 2002 were studied, looking for a relationship between cholesterolosis and chronic cholecystitis, adenomas, dysplasia and gallbladder cancer.Seventy nine percent of patients were women. Cholesterolosis was observed in 3123 cases (13.4%). Cholesterolosis was more common in women (14.2%) than in men (10.2%9) (p0.001). In the same period, 29 patients were diagnosed with adenomas (0.12%), 179 cases with dysplasia not associated with gallbladder cancer (0.8%) and 739 gallbladder cancer (3.2%). The frequency of cholesterolosis was 13.8% in chronic cholecystitis, 13.7% in adenomas, 12.1% in dysplasias and 1.35% in patients with gallbladder cancer (p0.01). Of the thirteen cases with gallbladder cancer and cholesterolosis, 10 were early gallbladder carcinomas. Patients with cholesterolosis were 9.2 times less likely td have cancer than those who did not have cholesterolosis.Cholesterolosis has a strong negative association with gallbladder cancer.

Subserosal carcinoma is the stage that presents the greatest difficulty in the diagnosis therapeutic handling and prognosis evaluation.To study the expression of p53 and p27 genes in subserosal gallbladder cancer.One hundred twenty seven tissue samples of subserosal gallbladder cancer (coming from 112 females aged 62+/-13 years and 15 men aged 67+/-17 years) and 50 control samples were selected to construct tissue arrays. p53 and p27 genes were determined by immunohistochemistry.Thirty eight percent of tumors were not detected at the macroscopic examination, 52% and 17% had lymph node and blood vessel involvement, respectively. Fifty six and 46% were positive for p53 and p27, respectively. No association between the expression of both genes and gender, degree of differentiation, lymph node or blood vessel involvement, was observed. Overall five years actuarial survival was 32%. Patients with positive or negative p53 expression had a 22% and 53% survival, respectively (p=0.05). No association between survival and p27 expression was observed.p53 gene expression is a prognostic factor for subserosal gallbladder cancer.

There is paucity of knowledge on the proliferative features of normal or chronically inflamed gallbladder and the mechanisms of development of gallbladder cancer.To study the proliferation features of non tumoral gallbladder mucosa through the expression of Ki-67 antigen in tissue micro array analysis.The immunohystochemical expression of Ki-67 in tissue micro array was studied in 96 samples of non tumoral gallbladder mucosa (coming from 74 females aged 45+/-16 years and 22 males aged 53+/-16 years) and 102 samples of gallbladder cancer (coming from 84 females aged 62+/- 14 years and 18 males aged 70+/- 13 years).The staining index of Ki-67 expression was 19+/-25% (range 096-8996) in samples of non tumoral mucosa and 46+/-29% (range 396-9896) in gallbladder cancer (p0.01). Ki-67 was expressed in less than 10% of epithelial cells in 55% of non tumoral mucosa samples and 6% of gallbladder cancer samples. Seventy five percent of gallbladder cancer samples had a staining index of more than 20%. An expression of Ki-67 over 20% or 50% was observed in 25% and 15% of non tumoral mucosa samples, respectively.Non tumoral gallbladder mucosa samples have a high proliferation index, measured using Ki-67 immunohystochemical expression. There is a group of samples with cellular hyper-proliferation that maybe related to the pathogenesis of gallbladder cancer.

There is scarcity of knowledge about the development of gallbladder cancer.To study the features of development and progression of gallbladder cancer.Review of histopathological studies of gallbladder obtained in 25,971 cholecytectomies performed in patients aged 45+/- 16 years, 79% females, between 1993 and 2004. Among these, 210 had a dysplasia not associated to cancer and 1,039 had a gallbladder cancer Clinical and morphological parameters of preneoplastic and neoplastic lesions were analyzed. Ninety five percent of patients were followed.All cases of dysplasia were incidental findings. Metaplasia, dysplasia and carcinoma in situ were present in the adjacent mucosa in 66%, 81% y 69% of gallbladder carcinomas, respectively. Twenty five percent of gallbladders studied were carcinomas (mucous carcinoma in 18% and muscular carcinoma in 7%). Ninety two percent of cases had chronic inflammation in the gallbladder wall. Seventy two percent of mucous carcinomas were not detected macroscopically Five years survival of mucous carcinoma was 92%. There was an association between the intensity of the lesion and the age of the patients. The age difference between chronic cholecystitis and gallbladder cancer was 11 years for women and nine for men.From a morphological standpoint, the period in which a dysplasia becomes a carcinoma is approximately 10 years.

The goal of this study was to evaluate a series of patients with early gallbladder cancer, focusing on the selection of treatment and the role of Rokitansky Aschoff sinus infiltration.We performed a retrospective analysis of a prospective series of 371 patients with gallbladder cancer. Specimens were reviewed by an independent pathologist to confirm the diagnosis and depth of infiltration and to evaluate the presence of Rokitansky Aschoff sinus involvement.Forty-nine and 45 patients with muscular (pT1b) and mucosal (pT1a) infiltration gallbladder cancer tumors were studied respectively. Simple cholecystectomy was the treatment in all patients, with the exception of 11 patients who underwent further surgery. Rokitansky Aschoff sinus invasion was seen in seven patients with mucosa (pT1a) and three with muscular (pT1b) compromise. The 5-year survival rates of patients with muscular (pT1b) and mucosal (pT1a) infiltration were 87.6% and 86.4%, respectively. Patients with Rokitansky Aschoff involvement had a lower survival rate than those with no involvement in both categories.Early gallbladder cancer is associated with a favorable prognosis and cholecystectomy should be the standard treatment. Despite some patients having a worse prognosis, there are no data to support more aggressive treatment.