Gene expression differences in primary colorectal tumors and matched liver metastases: chemotherapy related or tumoral heterogeneity?

Background: Treatment of metastatic colorectal cancer (mCRC) is generally based on genetic testing performed in primary tumor biopsies, but whether the genomic status of primary tumors is identical to that of metastases is not well known. We compared the gene expression profiles of formalin-fixed paraffin-embedded (FFPE) biopsies of colorectal primary tumors and matched liver metastases. Patients and methods: We compared the expression of 18 genes in FFPE CRC tumors and their matched liver metastases from 32 patients. The expression of each gene in CRC primary tumors and their matched liver metastases was tested using Student’s t test for paired samples. Pairwise correlations of each gene in the primary tumors and matched liver metastases were evaluated by Pearson’s correlation coefficient. Results: The expression of six genes was significantly different in primary tumors compared with their matched liver metastases [CXCR4 (p < 0.001), THBS1 (p = 0.007), MMP 9 (p = 0.048), GST Pi (p = 0.050), TYMP(p = 0.042) and DPYD (p < 0.001)]. For the remaining genes, where no significant differences were observed, only SMAD4 (r s = 0.447, p = 0.010), ERCC1 (r s = 0.423, p = 0.016) and VEGF A (r s = 0.453, p = 0.009) showed significant correlation in expression between the two tissues. Therefore, we only detected similar gene expression levels between the tumor and the metastases in these three markers. Conclusions: We only found similar gene expression levels between the tumor and the metastases in three genes (SMAD4, ERCC1, and VEGF A). However, our study could not assess whether the differences in gene expression were secondary to tumoral heterogeneity or to molecular changes induced by previous chemotherapy (AU)

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SMAD4 and TS expression might predict the risk of recurrence after resection of colorectal liver metastases

Purpose. Colorectal liver metastases (CLM) have significant molecular heterogeneity, which contributes to the risk of recurrence following surgery. Most of the traditional scores intended to predict recurrence is based on clinicopathological variables and it is unclear whether incorporating molecular biomarkers might improve our assessment of the risk of recurrence. Our aim was to determine if molecular biomarkers might be associated with the risk of recurrence after surgery of CLM. Patients and methods. A total of 121 patients diagnosed with colorectal cancer (CRC) with resected liver metastases were included. The role of several clinicopathological variables to predict patient’s outcome after resection of liver metastases was analyzed. Eighteen genes related to CRC pathogenesis were also included in the analyses. Univariate and multivariate stepwise Cox regression analyses were performed to identify factors associated with recurrence and the risk of death. Results. Eight prognostic factors for progression-free survival and nine factors for overall survival were identified in the univariate analyses. After adjusting for other risk factors, only the expression of two molecular factors was associated with the risk of recurrence: TS (HR 0.631, 95 % CI 0.422–0.944) and SMAD4 (HR 1.680, 95 % CI 1.047–2.695). None of the variables was significantly associated with the risk of death in the multivariate analyses. Conclusions. The prognostic significance of most traditional clinicopathological variables might be insufficient to define patients at risk for recurrence after liver metastases resection. Molecular biomarkers might improve the identification of patients with higher risk of recurrence (AU)

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Gene expression differences in primary colorectal tumors and matched liver metastases: chemotherapy related or tumoral heterogeneity?

BACKGROUND: Treatment of metastatic colorectal cancer (mCRC) is generally based on genetic testing performed in primary tumor biopsies, but whether the genomic status of primary tumors is identical to that of metastases is not well known. We compared the gene expression profiles of formalin-fixed paraffin-embedded (FFPE) biopsies of colorectal primary tumors and matched liver metastases. PATIENTS AND METHODS: We compared the expression of 18 genes in FFPE CRC tumors and their matched liver metastases from 32 patients. The expression of each gene in CRC primary tumors and their matched liver metastases was tested using Student's t test for paired samples. Pairwise correlations of each gene in the primary tumors and matched liver metastases were evaluated by Pearson's correlation coefficient. RESULTS: The expression of six genes was significantly different in primary tumors compared with their matched liver metastases [CXCR4 (p < 0.001), THBS1 (p = 0.007), MMP 9 (p = 0.048), GST Pi (p = 0.050), TYMP (p = 0.042) and DPYD (p < 0.001)]. For the remaining genes, where no significant differences were observed, only SMAD4 (r s = 0.447, p = 0.010), ERCC1 (r s = 0.423, p = 0.016) and VEGF A (r s = 0.453, p = 0.009) showed significant correlation in expression between the two tissues. Therefore, we only detected similar gene expression levels between the tumor and the metastases in these three markers. CONCLUSIONS: We only found similar gene expression levels between the tumor and the metastases in three genes (SMAD4, ERCC1, and VEGF A). However, our study could not assess whether the differences in gene expression were secondary to tumoral heterogeneity or to molecular changes induced by previous chemotherapy.

SMAD4 and TS expression might predict the risk of recurrence after resection of colorectal liver metastases.

PURPOSE: Colorectal liver metastases (CLM) have significant molecular heterogeneity, which contributes to the risk of recurrence following surgery. Most of the traditional scores intended to predict recurrence is based on clinicopathological variables and it is unclear whether incorporating molecular biomarkers might improve our assessment of the risk of recurrence. Our aim was to determine if molecular biomarkers might be associated with the risk of recurrence after surgery of CLM. PATIENTS AND METHODS: A total of 121 patients diagnosed with colorectal cancer (CRC) with resected liver metastases were included. The role of several clinicopathological variables to predict patient's outcome after resection of liver metastases was analyzed. Eighteen genes related to CRC pathogenesis were also included in the analyses. Univariate and multivariate stepwise Cox regression analyses were performed to identify factors associated with recurrence and the risk of death. RESULTS: Eight prognostic factors for progression-free survival and nine factors for overall survival were identified in the univariate analyses. After adjusting for other risk factors, only the expression of two molecular factors was associated with the risk of recurrence: TS (HR 0.631, 95 % CI 0.422-0.944) and SMAD4 (HR 1.680, 95 % CI 1.047-2.695). None of the variables was significantly associated with the risk of death in the multivariate analyses. CONCLUSIONS: The prognostic significance of most traditional clinicopathological variables might be insufficient to define patients at risk for recurrence after liver metastases resection. Molecular biomarkers might improve the identification of patients with higher risk of recurrence.

Management of colorectal cancer patients after resection of liver metastases: can we offer a tailored treatment?

Surgical resection remains the only option of cure for patients with colorectal liver metastases, and no patient should be precluded from surgery. There is much controversy not only regarding the most appropriate therapeutic approach in the neoadjuvant setting but also after surgery is performed. Many patients will experience early relapses but others will be long survivors. We need to establish reliable prognostic and predictive factors to offer a tailored treatment. Several prognostic factors after metastasectomy have been identified: high C-reactive protein levels, a high neutrophil-lymphocyte ratio, elevated neutrophil count and low serum albumin are related to a worst outcome. Elevated CEA and Ki 67 levels, intrahepatic and perihepatic lymph node invasion are also some of the markers related to a worst outcome. In contrast, the administration of preoperative chemotherapy has been associated with a better prognosis after hepatectomy. The administration of adjuvant chemotherapy should be done taking in consideration these factors. Regarding predictive factors, determination of ERCC1, TS, TP and DPD and UGT1 polymorphisms assessment could be considered prior to chemotherapy administration. This would avoid treatment related toxicities and increase this population quality of life (AU)

Injury patterns from major urban terrorist bombings in trains: the Madrid experience.

BACKGROUND: Terrorist urban mass casualty incidents (MCI) in the last 3 years have targeted commuter trains at rush hour, producing large numbers of casualties. Civilian care providers are usually not familiar with the types of blast injuries sustained by victims of these MCI. METHODS: We focus on the injury patterns sustained by casualties of the Madrid, 11 March 2004, terrorist bombings, at the seven hospitals that received most victims. Data were gathered of casualties who had injuries other than superficial bruises, transient hearing loss from barotrauma without eardrum perforation, and/or emotional shock. The degree of severity in critical patients was assessed with the ISS. RESULTS: The bombings resulted in 177 immediate fatalities, 9 early deaths, and 5 late deaths. Most survivors had noncritical injuries, but 72 (14%) of 512 casualties assessed had an Injury Severity Score (ISS) >15. The critical mortality rate was of 19.5%. The most frequently injured body regions were the head-neck and face. Almost 50% of casualties had ear-drum perforation, and 60% of them were bilateral. There were 43 documented cases of blast lung injury, with a survival rate of 88.3%. Maxillofacial and open long-bone fractures were most prevalent. Gustillo's grade III of severity predominated in tibia-fibular and humeral fractures. Upper thoracic fractures (D1-6 segment) represented 65% of all vertebral fractures and were associated with severe blast to the torso. Severe burns were uncommon. Eye injuries were frequent, although most were of a mild-to-moderate severity. Abdominal visceral lesions were present in 25 (5%) patients. A multidisciplinary approach was necessary in most operated patients, and orthopedic trauma procedures accounted for 50% of the caseload in the first 24 h. CONCLUSIONS: Ninety-three percent of the fatalities of the Madrid trains terrorist bombings were immediate, and most survivors had noncritical injuries. Closed doors increased the immediate fatality rate in the trains. Severely wounded casualties presented specific patterns of injuries, some of them life-threatening and unusual in other types of trauma mechanisms. Ear-lobe amputations and upper thoracic spine fractures were markers of critical injuries.

Morbilidad atribuible a los cálculos abandonados en la cavidad abdominal tras la colecistectomía laparoscópica / Morbidity attributable to calculi left in the abdominal cavity after laparoscopic cholecystectomy

Objetivo. Analizar la morbilidad postoperatoria atribuible a los cálculos abandonados en la cavidad abdominal tras colecistectomía laparoscópica. Diseño. Estudio retrospectivo de cohortes. Pacientes y métodos. Se revisaron las colecistectomías laparoscópicas realizadas en el Hospital Universitario de Getafe entre 1991 y 1997. Se excluyeron los pacientes con signos de colecistitis aguda, hidropesía vesicular o vesícula escleroatrófica. En 22 casos hubo rotura de la pared vesicular con abandono de uno o más cálculos en la cavidad peritoneal al finalizar la intervención (cohorte de cálculos libres), mientras que en 277 casos la vesícula biliar tenía la pared íntegra. Entre estos últimos, se extrajo una muestra de 22 casos operados por los mismos cirujanos (cohorte control). El seguimiento ambulatorio fue de 42 meses. El análisis estadístico se realizó con el programa SPSS. Resultados. No se registró ninguna complicación pulmonar o intraabdominal, ni tampoco hubo reintervenciones. En la cohorte de cálculos libres, la duración de la cirugía fue 25 min más larga (p < 0,02) y la estancia media postoperatoria fue 0,6 días mayor (p < 0,04). Conclusiones. En ausencia de enfermedad inflamatoria, el abandono de cálculos en la cavidad peritoneal prolonga el tiempo quirúrgico y la estancia hospitalaria, pero no aumenta la morbilidad postoperatoria (AU)

Antiemetic efficacy of ondansetron in laparoscopic cholecystectomy. A randomized, double-blind, placebo-controlled study.

OBJECTIVE: to assess the effectiveness of ondansetron in preventing postoperative nausea and vomiting after elective laparoscopic cholecystectomy, and the effect of this anesthetic on hospital stay. METHODS: this randomized, double-blind, placebo-controlled study was done in the General Surgery Service of the Getafe University Hospital. Patients who were scheduled for laparoscopic cholecystectomy to treat uncomplicated cholelithiasis, and who had an ASA status of I-II, were recruited. Before surgery the patients received either ondansetron 4 mg or placebo intravenously. This study was approved by the local ethics committee. RESULTS: 56 patients were included, 29 in the ondansetron group and 27 in the placebo group. In the latter, 4 patients were later excluded because of conversion to open surgery. Postoperative nausea and emetic episodes were experienced by 7% of the patients in the ondansetron group and 47% in the placebo group (p = 0.0007). Oral intake started 7 h after surgery in the ondansetron group and 11 h after surgery in the placebo group (p = 0.04), with a mean difference of 4 h. Hospital stay was 30 h and 48 h respectively (p = 0.01), with a mean difference of 18 h. CONCLUSION: ondansetron given prior to surgery at a dose of 4 mg prevents postoperative nausea and vomiting after laparoscopic cholecystectomy, and reduces hospital stay.