Role of tumour location and surgical extent on prognosis in T2 gallbladder cancer: an international multicentre study.

BACKGROUND: In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection. METHODS: Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted. RESULTS: Data from 937 patients were available for evaluation. The overall 5-year disease-free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5-year disease-free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5-year disease-free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five-year disease-free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic. CONCLUSION: Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection.

ANTECEDENTES: En el cáncer de vesícula biliar, la ubicación del tumor subdivide el estadio T2 en tumores con invasión del lado peritoneal y del lado del hígado (T2a y T2b). Para los tumores que invaden el lado peritoneal (T2a) se sugiere que se puede obviar la resección hepática sin que ello comprometa el pronóstico. Sin embargo, este argumento no ha sido validado. El estudio tuvo como objetivo investigar el valor pronóstico de la localización del tumor en el cáncer de vesícula biliar T2 y establecer la extensión adecuada de la resección quirúrgica. MÉTODOS: Se recogieron los datos clínicos de pacientes que se sometieron a cirugía por cáncer de vesícula biliar en 14 hospitales de Corea, Japón, Chile y Estados Unidos. Se realizaron análisis de la supervivencia y de los factores de riesgo. RESULTADOS: Se dispuso de datos de 937 pacientes para ser evaluados. La tasa de supervivencia global libre de enfermedad a los 5 años fue del 70,6%, y las de T2a y T2b del 74,5% y 65,5% (P = 0,028). Con respecto a la resección hepática, la colecistectomía extendida presentó una tasa mejor de supervivencia libre de enfermedad a los 5 años que la colecistectomía simple (73,0% versus 61,5%, P = 0,012). La tasa de supervivencia libre de enfermedad a los 5 años fue marginalmente mejor para la colecistectomía extendida que para la colecistectomía simple tanto en T2a (76,5% versus 66,1%, P = 0,094) como en T2b (68,2% versus 56,2%, P = 0,084). Las tasas de supervivencia libre de enfermedad a los 5 años no fueron diferentes entre la resección hepática en cuña y la segmentectomía S4b+S5 (74,1% versus 71,5%, P = 0,720). En el análisis multivariable, los factores de riesgo independientes para la recidiva fueron la presencia de síntomas (cociente de riesgos instantáneos, hazard ratio, HR 1,52, P = 0,002), la resección R1 (HR 1,96, P = 0,004) y el estadio N1/N2 (N1 HR 3,40, P < 0,001; N2 HR 9,56, P < 0,001). El 70,8% de las recidivas eran metastásicas. CONCLUSIÓN: La localización del tumor no fue un factor pronóstico independiente en el cáncer de vesícula biliar T2. La colecistectomía extendida fue marginalmente superior que la colecistectomía simple. La cirugía radical debe incluir una resección hepática y una linfadenectomía adecuada.

Adjuvant concurrent chemoradiation therapy in patients with microscopic residual tumor after curative resection for extrahepatic cholangiocarcinoma.

PURPOSE: We investigated the role of adjuvant concurrent chemoradiation therapy (CCRT) in patients with a microscopically positive resection margin (R1) after curative resection for extrahepatic cholangiocarcinoma (EHCC). METHODS/PATIENTS: A total of 84 patients treated with curative resection for EHCC were included. Fifty-two patients with negative resection margins did not receive any adjuvant treatments (R0 + S group). The remaining 32 patients with microscopically positive resection margins received either adjuvant CCRT (R1 + CCRT group, n = 19) or adjuvant radiation therapy (RT) alone (R1 + RT group, n = 13). RESULTS: During the median follow-up period of 26 months, the 2-year locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival rates (OS) were: 81.8, 62.6, and 61.5% for R0 + S group; 71.8, 57.8, and 57.9% for R1 + CCRT group; and 16.8, 9.6, and 15.4% for R1 + RT group, respectively. Multivariate analysis revealed that the R1 + CCRT group did not show any significant difference in survival rates compared with the R0 + S group. The R1 + RT group had lower LRRFS [hazard ratio (HR) 3.008; p = 0.044], DFS (HR 2.364; p = 0.022), and OS (HR 2.417; p = 0.011) when compared with the R0 + S and R1 + CCRT group. CONCLUSIONS: A lack of significant survival difference between R0 + S group and R1 + CCRT group suggests that adjuvant CCRT ameliorates the negative effect of microscopic positive resection margin. In contrast, adjuvant RT alone is appeared to be inadequate for controlling microscopically residual tumor.

Is c-Met oncoprotein expression an adverse prognosticator in extrahepatic bile duct cancer treated with curative resection followed by adjuvant chemoradiotherapy?

PURPOSE: To analyze the expression of c-Met, and to investigate correlations between the expression of c-Met, clinicopathologic variables, and survival in patients undergoing curative surgery followed by adjuvant chemoradiotherapy for extrahepatic bile duct (EHBD) cancer. METHODS: Ninety EHBD cancer patients who underwent curative resection followed by adjuvant chemoradiotherapy were enrolled. Expression of c-Met was assessed with immunohistochemical staining on tissue microarray. The correlation between clinicopathologic variables and survival outcomes was evaluated using Kaplan-Meier method and Cox proportional hazard model. RESULTS: On univariate analysis, 66 patients (76.7 %) showed c-Met expression. c-Met expression had a significant impact on 5-year overall survival (OS) (43.0 % in c-Met(+) vs. 25.0 % in c-Met(-), p = 0.0324), but not on loco-regional relapse-free survival or distant metastasis-free survival (DMFS). However, on multivariate analysis incorporating tumor location and nodal involvement, survival difference was not maintained (p = 0.2940). Tumor location was the only independent prognostic factor predicting OS (p = 0.0089). Hilar location tumors, nodal involvement, and poorly differentiated tumors were all identified as independent prognostic factors predicting inferior DMFS (p = 0.0030, 0.0013, and 0.0037, respectively). CONCLUSIONS: This study showed that c-Met expression was not associated with survival outcomes in EHBD cancer patients undergoing curative resection followed by adjuvant chemoradiotherapy. Further studies are needed to fully elucidate the prognostic value of c-Met expression in these patients.

Stellar physics. Observing the onset of outflow collimation in a massive protostar.

The current paradigm of star formation through accretion disks, and magnetohydrodynamically driven gas ejections, predicts the development of collimated outflows, rather than expansion without any preferential direction. We present radio continuum observations of the massive protostar W75N(B)-VLA 2, showing that it is a thermal, collimated ionized wind and that it has evolved in 18 years from a compact source into an elongated one. This is consistent with the evolution of the associated expanding water-vapor maser shell, which changed from a nearly circular morphology, tracing an almost isotropic outflow, to an elliptical one outlining collimated motions. We model this behavior in terms of an episodic, short-lived, originally isotropic ionized wind whose morphology evolves as it moves within a toroidal density stratification.

Phosphorus requirements for 60- to 100-kg pigs selected for high lean deposition under different thermal environments.

Two experiments were conducted to determine the requirement of available P (aP) of pigs selected for high lean deposition during summer (maximum and minimum temperatures of 29.8 ± 3.6 and 21.3 ± 1.1°C, respectively; Exp. 1) and winter (maximum and minimum temperatures of 24.7 ± 2.1 and 9.1 ± 1.6°C, respectively; Exp. 2). Pigs (66.5 ± 2.8 kg, Exp. 1; and 61.1 ± 0.6 kg, Exp. 2) were randomly allotted to 5 dietary treatments. Exp. 1 had 5 pens/treatment and Exp. 2 had 6 pens/treatment, and all pens had 2 pigs. Treatments were composed of a corn-soybean meal basal diet and 4 diets with additional dicalcium phosphate to obtain 5 aP concentrations (0.122, 0.187, 0.252, 0.317, and 0.382% in Exp. 1, and 0.135, 0.200, 0.265, 0.330, and 0.395% in Exp. 2). Pigs were allowed ad libitum access to their respective diets for 30 d. In Exp. 1, increasing aP improved ADFI and ADG (quadratic, P < 0.05), with maximum responses obtained at 0.226 and 0.256% of aP, respectively. Increasing aP improved (P < 0.05) G:F. A broken-line analysis indicated that G:F was maximized (P < 0.05) at 0.295% of aP or 9.04 g of aP/d. Increasing aP also increased (quadratic, P < 0.05) P and Ca (g/kg) in the metacarpals with maximum responses obtained at 0.314 and 0.272% of aP, respectively. The percentage of ash in the metacarpals continued to increase (linear, P < 0.05) with increasing aP. In Exp. 2, ADG and G:F improved (linear and quadratic, P < 0.05) as aP increased in the diet. A broken-line analysis indicated that G:F was maximized (P < 0.05) at 0.316% of aP or 10.58 g of aP per day. However, increasing aP had no effect on ADFI. Percentages of ash, P, and Ca in the metacarpals increased (linear, P < 0.05) with increasing aP. In conclusion, results of this experiment indicated that finishing pigs (60 to 100 kg) kept in a thermoneutral environment require 0.316% aP in the diet (10.58 g/d) to maximize G:F, but the requirement is only 0.295% aP (9.04 g/d) when pigs are under heat stress.

Selenium levels and glutathione peroxidase activities in blood in an andean high-altitude population.

Selenium (Se) levels in blood (whole blood, erythrocytes and serum) and blood glutathione peroxidase (GSH-Px) activity were investigated in people living at high altitude in Bolivia (4,000 m above sea level). These parameters were compared to those of people living at low altitude (300 m above sea level). The Se levels in whole blood of the high-altitude subjects did not differ significantly from those of the low-altitude subjects. However, the Se levels in erythrocytes were significantly lower in the high-altitude subjects than in the low-altitude subjects, whereas serum Se levels were higher in the high-altitude subjects than in the low-altitude subjects. GSH-Px activity (Unit/g Hb) was significantly lower in the high-altitude subjects than in the low-altitude subjects. The mean corpuscular Hb concentration (MCHC), an indicator of the age of erythrocytes, in the high-altitude subjects was significantly higher than in the low-altitude subjects. These results show that the GSH-Px activity in the blood of the high-altitude subjects is relatively low. This may be due to their aged erythrocytes and/or to relatively low Se intake in the high-altitude population compared with low-altitude population.

Physical growth of Aymara children in a herding community of the Bolivian Altiplano.

In a small agropastoral Aymara community called Wariscata in the Andean Altiplano of Bolivia, anthropometric measurements were made in 1988. In comparison with those of published data for the other rural and urban Andean populations (Aymara, Quechua and Mestizo at high and low altitudes), the Aymara children of Wariscata were taller and heavier than other rural high altitude native children, but similar in height to urban high altitude children. This is possibly due to secular change of growth accompanied with nutritional improvement that has taken place in recent years. Chest width and depth had similar values to those in other Aymara children. But, Aymara children in Wariscata of both sexes had smaller chest dimensions (depth and width) than those of Quechua children. However, these ethnic differences in chest dimensions were not reflected in the adult Aymara and Quechua, suggesting different process of chest growth in Aymara and Quechua populations.