Cáncer de vesícula biliar ¿la contaminación por bilis afecta el pronóstico? / Gallbladder Cancer: does bile contamination affect the prognosis?

Resumen 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. Materiales 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 ésta. 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 incluyó edad, género, 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.

Background: Incidental gallbladder cancer is observed in up to 3.5% of patients undergoing laparoscopic cholecystectomy. To study the role of wall perforation on the prognosis, we evaluated a series of patients in whom perforation occurred during the cholecystectomy. Materials and Method: 109 patients who underwent a laparoscopic cholecystectomy in whom final diagnosis was gallbladder cancer were the focus of the study. We divided the patients according the occurrence of spillage. Furthermore, patients with spillage were divided into two categories according the spillage magnitude. Results: Of the patients, spillage was documented in 32 (29.3%). In 13 patients spillage was considered major. The median follow-up of patients was 36 months, while 35 (32.1%) patients died during the follow-up. Five-year survival of all patients with spillage was not statistically different from the group without spillage. However, the group with major spillage had a statistically worse survival than the rest. A Cox regression analysis including age, gender, level of invasion and spillage category showed that major spillage was independently associated with a worse prognosis.

Técnica de linfadenectomía y resección del lecho vesicular laparoscópica por cáncer vesícula biliar incidental / Lymphadenectomy technique and laparoscopic vesicular bed resection for incidental gallbladder cancer

Resumen 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 neoplasia. Presentamos 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.

Gallbladder cancer is considered an infrequent disease but in Chile has a higher incidence. Prognostic is considered dismal except in those patients in whom the diagnosis is performed after the cholecystectomy specimen study. Reoperation with gallbladder bed resection and lymphadenectomy is considered the treatment in patients with incidental cases. We show the way this operation is performed in Clinica Alemana of Santiago and in the Air Force Hospital. The laparoscopic approach is an alternative to those patients in whom the diagnosis was done after the cholecystectomy. Laparoscopy allows to accomplish same objectives and to obtain identical results that the open approach. The technical standardization should contribute to spread its employment and to improve the results.

Resección hepática extendida con vena cava inferior por colangiocarcinoma intrahepático: presentación de 2 casos / Extended hepatic resection with inferior cava vein for intrahepatic cholangiocarcinoma: presentation of two cases

Resumen 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 Clínica 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 período desde el posoperatorio hasta el alta, fue de 13 y 23 días respectivamente. Discusión: 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.

Introduction: Intrahepatic cholangiocarcinoma is the second most common primary liver tumor and surgical resection the only valid curative treatment. Case reports: We describe two patients harboring an intrahepatic cholangiocarcinoma with cava vein involvement who underwent resection at Clinica Alemana of Santiago. Both patients were females with ages of 39 and 47 years old. Both patients underwent left liver resection, associated to resection of segment I and of a portion of cava vein. Reconstruction of resected portion of the cava vein was performed by using a pericardium bovine patch and primary closure respectively. Postoperative period was uneventfully being discharged at 13 and 23 days respectively. Discussion: Although surgical resection is the only way to get curativeness, frequent involvement of large vascular structures make treatment unfeasible. A multidisciplinary approach associated with a meticulous technique performed by an experienced surgical team make possible to accomplish the above objective.

[Natural history of gallbladder cancer. Analysis of biopsy specimens]. / Desde la displasia hasta el cáncer de la vesícula biliar.

BACKGROUND: There is scarcity of knowledge about the development of gallbladder cancer. AIM: To study the features of development and progression of gallbladder cancer. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: From a morphological standpoint, the period in which a dysplasia becomes a carcinoma is approximately 10 years.

[Immunohistochemical expression of Ki-67 as a marker of proliferation in gallbladder mucosa samples with or without cancer]. / Proliferación celular en la mucosa de la vesícula biliar no tumoral en colecistitis crónicas litiásicas. Expresión de Ki-67 en matrices de tejidos.

BACKGROUND: There is paucity of knowledge on the proliferative features of normal or chronically inflamed gallbladder and the mechanisms of development of gallbladder cancer. AIM: To study the proliferation features of non tumoral gallbladder mucosa through the expression of Ki-67 antigen in tissue micro array analysis. MATERIAL AND METHODS: 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). RESULTS: 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 (p <0.01). 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. CONCLUSIONS: 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.

Aspectos quirúrgicos del cáncer de vesícula biliar / Strategies for the surgical treatment of gallbladder cancer

There is controversy in some aspects of the surgical treatment of non-mucosal gallbladder carcinoma. An accurate staging based on T (wall) involvement is crucial, otherwise understanding may yield falsely pessimistic results. The decision about the type of resection to be performed should be based on patient status (age, performance, comorbidities, etc) and tumor characteristics (histological type, vascular, neural or lymphatic spread, cell differentiation, tumor involvement of surgical margins in cystic duct, etc). For muscular (T1b) involvement, there is a great controversy about performing a simple cholecystectomy or en-block radical resection. For T2 there is consensus that an en-block radical surgery including liver resection (IVb - V) and lymphonodal clearance should be performed, since this approach has a great impact in survival. The role of surgical excision for tumors with serosal or liver involvement is controversial, due to the poor survival of these patients. However we have observed a 13% actuarial survival at 5 years, in this subset of patients.

Mutación del gen K-ras en el cáncer de la vesícula biliar / K-ras gene mutation in gallbladder carcinoma

Background: Different K-ras mutation frequencies in gallbladder cancer have been reported. Aim: To study the frequency of K-ras gene mutations in advanced gallbladder carcinoma not associated to anomalous junction of pancreatic-biliary duct (AJPBD). Material and methods: 33 formalin fixed paraffin embedded samples of gallbladder carcinoma (30 women, age range 32-86 years) were selected. Pancreatic cancer tissue with K-ras mutations was used as control. DNA was extracted from the histological section by mean of microdissection and K-ras mutations in codon 12 were detected by polymerase chain reaction and restriction fragment length polymorphism (RFLP), using previously reported technique. Results: Most cases were poorly differentiated adenocarcinomas. K-ras mutation was detected in 10 cases (30%) samples. No differences in K-ras mutation frequency between subserous and serous tumors were detected and no relation between histological features and the mutation was observed. Conclusions: K-ras mutation in codon 12 is present in 30% in our advanced gallbladder carcinomas. The study of K-ras mutation in preneoplastic lesions and early carcinomas will be important to determine the role of this gene in the gallbladder carcinogenesis in Chile (Rev Méd Chile 2004; 132: 955-60).

Contenido de ADN y sobrevida en el carcinoma subseroso de la vesícula biliar / DNA content and survival in subserous gallbladder carcinoma

Background: The clinical and morphological characterization of the subserous gallbladder carcinomas is controversial. Aim: To study the prognostic importance of DNA content of subserous gallbladder carcinoma. Material and methods: We studied 104 females aged 60±12 years old and 16 men aged 70±13 years old. In all of them diagnosis was established after mapping of cholecystectomy sample and had a complete clinical follow up. DNA content was measured by flow cytometry. Results: All tumors were adenocarcinoma, and only 16 percent were well differentiated. Aneuploidy was observed in 29 cases (26 perceeeent) with DNA index fluctuating between 1.1 and 1.8. Lymphatic vessel tumor involvement was present in 16 of 22 cases with aneuploidy and in 22 of 46 diploid tumors (p= 0.05). Eighty nine percent of aneuploid tumors were detected macroscopically and 11 percent were unapparent. Five years survival was non significantly better among patients with diploid tumors than in patients with aneuploid tumors (45 and 28 percent, respectively, p= 0.2). The histological differentiation was the only variable significantly associated with survival. Conclusions: Aneuploidy is present in 26 percent of subserous gallbladder carcinoma. It is not related with any of the morphological or clinical variables studied in this series of patients.

Pólipos y adenomas de la vesícula biliar: consideraciones clínico-patológicas / Clinicopathological features of gallbladder polyps and adenomas

Background: Chile has a high frequency of gallbladder cancer. Polyps are common lesions of gallbladder mucosa but there is little information about their morphological features. Aim: To report the clinical and pathological features of 219 gallbladder polyps. Material and methods: Cholecystectomies samples in which a polypoid lesion was diagnosed microscopically. In all cases, complete clinical information and digitalized images of the complete surgical specimens was reviewed. Results: In a period of 10 years, 21.412 gallbladders were processed. Among these, 884 carcinomas were diagnosed and in 219 cases (1 percent) a polyp was found. One hundred and eighty three patients were females (mean age 49.3 years) and 36 males (mean age 53.4 years). The preoperative diagnosis of gallbladder polyp was done only in 26 cases (12 percent). Eighty five percent of polyps were non-neoplastic (metaplastic in 32 percent, cholesterol in 29 percent, hyperplastic in 22 percent and inflammatory in 2 percent). The remaining 15 percent were adenomas. Seventy five percent of non-neoplastic polyps were located in the proximal half of the gallbladder and 88 percent of adenomas in the distal half. Ninety five percent of non-neoplastic polyps measured less than 10 mm. Among adenomas, 47 percent measured less than 5 mm and 28 percent more than 10 mm. Smaller polyps were of cholesterol and larger polyps were adenomas. Eight adenomas were associated with an adenocarcinoma, two had less than 5 mm lenght. Mean age of patients with adenomas associated to cancer was higher than patients with pure adenomas (64.6 and 44.3 years respectively, p >0.001). Conclusions: There are size and location differences between non neoplastic polyps and adenomas. Adenomas associated to cancer may measure less than 5 mm. Therefore the polyp size criteria to decide surgical behavior in symptomatic gallstone patients may be misleading (Rev Méd Chile 2004; 132: 673-9).

Quimiorradioterapia de neoadyuvancia en cáncer de vesícula biliar / Neoadjuvant chemoradiotherapy in gallbladder cancer

Background: Gallbladder cancer is generally associated with a poor prognosis, being local recurrence the main pattern of failure. Aim: To evaluate neoadjuvant chemoradiation as a means to improve the prognosis in gallbladder cancer. Patients and methods: Twenty three gallbladder cancer patients were prospectively treated between June 1993 and September 1999 in the Temuco Regional Hospital. Eighteen (82 percent) patients had subserosal infiltration, while three (13 percent) had serosal and two (9 percent) adipose tissue infiltration. Chemotherapy was done with 5-fluorouracil in continuous infusion during 5 days at day 1 and 28 of treatment. Radiotherapy consisted in a total dose of 4500 cGy, divided in 25 sessions. Patients' survival was compared with a series of 19 patients not subjected to chemoradiation, formerly treated at the institution. Results: Twenty patients had hematological problems secondary to the therapy. Leucopenia and thrombocytopenia were the most common toxic effects and eight had leucopenia under 2.0 x 10 during the treatment course. Chemoradiation delayed surgical treatment in eight patients. After the chemoradiation protocol, seven patients were excluded from surgical treatment and 14 patients underwent resection. Three of the latter (11 percent) had liver involvement and four (14 percent) had lymph node involvement. Among the patients who underwent resection, five are still alive with a follow up of 43.8 months. Treated patients had a worst actuarial survival than subjects not treated with chemoradiation. Conclusions: In this series of patients chemoradiation had no positive effect and a potentially detrimental effect in patients with gallbladder cancer (Rev Méd Chile 2004; 132: 51-7).

Patrón de ADN y pronóstico en cáncer gástrico / DNA pattern and pronostic in gastric cancer

Con el fin de conocer la capacidad predictiva pronóstica del contenido de ADN en relación con el grado de profundidad en la pared, estudiamos 149 pacientes intervenidos por un cáncer gástrico. El total de pacientes tenía un seguimiento mínimo de 5 años. En aquellos pacientes con compromiso de submucosa, muscular propia o subserosa, la presencia de anormalidades en el contenido de ADN fue asociado con un peor pronóstico. Por otro lado, en aquellos con invasión de la serosa no apreciamos relación entre las variables estudiadas. Como conclusión, podemos decir que el estudio del contenido de ADN es útil solamente en pacientes sin invasión de la serosa