Mismatch repair status in the prediction of benefit from adjuvant fluorouracil chemotherapy in colorectal cancer.

AIM: Some retrospective studies have shown a lack of benefit of 5-fluorouracil (5-FU) adjuvant chemotherapy in patients with mismatch repair (MMR) deficient colorectal cancer. Our aim was to assess if this molecular marker can predict benefit from 5-FU adjuvant chemotherapy. A second objective was to determine if MMR status influences short term survival. METHODS: We included 754 patients with a median follow up of 728.5 days (range 1-1097). A total of 260 patients with stage II or III tumours received 5-FU adjuvant chemotherapy, according to standard clinical criteria and irrespective of their MMR status. A tumour was considered MMR deficient when either BAT-26 showed instability or there was loss of MLH1 or MSH2 protein expression. RESULTS: At the end of the follow up period, 206 patients died and 120 presented with tumour recurrence. Sixty six (8.8%) patients had MMR deficient tumours. There were no significant differences in overall survival (MMR competent 72.1%; MMR deficient 78.8%; p = 0.3) or disease free survival (MMR competent 61.3%; MMR deficient 72.3%; p = 0.08). In patients with stage II and III tumours, benefit from 5-FU adjuvant chemotherapy was restricted to patients with MMR competent tumours (overall survival: chemotherapy 87.1%; non-chemotherapy 73.5%; log rank, p = 0.00001). Patients with MMR deficient tumours did not benefit from adjuvant chemotherapy (overall survival: chemotherapy 89.5%; non-chemotherapy 82.4%; log rank, p = 0.4). CONCLUSIONS: Benefit from 5-FU adjuvant chemotherapy depends on the MMR status of tumours in patients with colorectal cancer. 5-FU adjuvant chemotherapy improves survival in patients with MMR competent tumours but this benefit from chemotherapy cannot be extended to patients with MMR deficient tumours.

[Evaluation of the efficacy and efficiency of a multidisciplinary unit for the treatment of patients with colorectal cancer]. / Evaluación de la eficacia y eficiencia de una unidad multidisciplinaria para la atención de pacientes con cáncer colorrectal.

INTRODUCTION: Because of the increased complexity of the diagnostic-therapeutic approach to colorectal cancer (CRC), these patients should be managed in specialized multidisciplinary units. The aim of this study was to evaluate the efficacy and efficiency of a CRC unit (CRCU) in the diagnostic-therapeutic management of these patients. PATIENTS AND METHODS: Two groups of 50 patients with colon cancer treated in our center before and after the implementation of the CRCU were selected. Fulfillment with the protocol in terms of tumoral staging, surgical and adjuvant treatment, follow-up, interval until treatment, hospital stay, morbidity and early mortality, and the overall duration of the diagnostic-therapeutic process was analyzed. In addition, clinical workload was evaluated and a cost-minimization analysis was performed. RESULTS: The CRCU reduced the interval until surgery (20.3 12.0 vs 28.0 20.4 days; p = 0.05), hospital stay (9.8 7.7 vs 14.5 9.3 days: p = 0.01), the time to the start of adjuvant treatment (29.4 10.2 vs 39.7 19.8 days; p = 0.03) and the overall duration of the process (60.4 23,8 vs 82.1 46.1 days; p = 0.05), representing a saving of 978.85 E per patient. This improvement took place despite an increase in clinical workload (24% in 5 years in relation to the number of admissions) and had no effect on morbidity (26 vs 24%; NS) or immediate mortality (6 vs 4%; NS). CONCLUSION: Specialized multidisciplinary units increase the efficacy and efficiency of the management of patients with CRC.

Laparoscopic-assisted vs. open colectomy for colorectal cancer: influence on neoplastic cell mobilization.

Laparoscopic surgery for treatment of colorectal cancer has been suggested to enhance tumor dissemination. Recently, molecular techniques have been developed to detect micrometastatic disease in patients with solid tumors, with a higher accuracy than cytologic or immunohistochemical approaches. This study was undertaken to investigate the potential harmful effects of laparoscopic-assisted colectomy on neoplastic cell mobilization in patients with resectable colorectal cancer. Fifty patients with nonmetastatic colorectal cancer were randomly assigned to laparoscopic-assisted (LAC, n = 26) or open (OC, n = 24) colectomy. Peripheral venous blood samples were obtained preoperatively, immediately after tumor removal, and 24 hours later. In 10 patients from each treatment group, portal blood and peritoneal fluid samples were also obtained before and after resection. Neoplastic cells were detected by means of reverse transcriptase-polymerase chain reaction targeted to carcinoembryonic antigen (CEA) transcription. CEA mRNA was detected in peripheral venous blood samples from 35 of 50 colorectal cancer patients preoperatively. Among those 15 baseline-negative patients, four experienced conversion 24 hours after tumor resection (2 [33%] of 6 in the LAC group vs. 2 [22%] of 9 in the OC group; NS). At that time point, clearance of CEA mRNA expression was observed in 14 of the 35 baseline-positive patients (9 [45%] of 20 in the LAC group vs. 5 [33%] of 15 in the OC group; NS). In addition, only one patient in the LAC group with baseline-negative CEA mRNA expression experienced portal blood conversion after tumor removal, although his peripheral blood level remained negative. Finally, baseline peritoneal fluid CEA mRNA expression was never detected, but one patient in each group became positive postoperatively. These results confirm that preoperative and perioperative mobilization of neoplastic cells is a frequent occurrence in patients with colorectal cancer, but the surgical approach (LAC vs. OC) does not seem to be a determining factor.

Lack of prognostic influence of circulating tumor cells in peripheral blood of patients with colorectal cancer.

BACKGROUND AND AIMS: Circulating tumor cells in peripheral blood may be detected using high-sensitivity molecular techniques in several types of solid neoplasms, but their significance in colorectal cancer is controversial. The aim of this study was to assess the prognostic value of carcinoembryonic antigen (CEA) messenger RNA (mRNA) detection in peripheral blood samples from patients with colorectal cancer. METHODS: Peripheral vein blood samples from 95 consecutive patients with histologically confirmed colorectal carcinoma were obtained immediately before surgery to determine the presence of circulating tumor cells by use of a reverse-transcription polymerase chain reaction targeting CEA mRNA. Endpoints of the study were disease-free and overall survival. Results are referred to the whole series and, more importantly, to the 68 patients who underwent surgery for cure. RESULTS: After a median follow-up of 42 months, 19 of 68 patients (28%) operated on for cure had tumor relapse. In addition, 50 of 68 patients (73%) were alive. The probability of disease-free and overall survival was dependent on lymph node metastases and degree of differentiation, but not on the presence of circulating tumor cells (disease-free survival: relative risk, 1.00; 95% confidence interval [CI], 0.39-2.22, P = 0.99; overall survival: relative risk, 0.91, 95% CI, 0.34-2.43; P = 0.84). Similar results were obtained when all 95 patients with colorectal cancer were analyzed (disease-free survival: relative risk, 1.11; 95% CI, 0.63-1.95; P = 0.71; overall survival: relative risk, 1.21; 95% CI, 0.63-2.30, P = 0.55). CONCLUSIONS: Preoperative detection of blood circulating tumor cells by means of reverse-transcription polymerase chain reaction of CEA does not have prognostic significance in patients with colorectal cancer.

La detección precoz del cáncer colorrectal

El avance en el conocimiento de los mecanismos fisiopatológicos implicados y de la historia natural del cáncer colorrectal ha propiciado la implementación de programas de cribado y vigilancia. Estos programas, dirigidos al diagnóstico precoz de esta neoplasia, incluyen diversos procedimientos, entre los que destacan las pruebas de detección de sangre oculta en heces, las exploraciones endoscópicas o radiológicas y, más recientemente, determinados análisis genéticos (AU)

[Autoimmune hepatitis associated with thyroiditis and hypophysitis. A case report]. / Hepatitis autoinmune asociada a tiroiditis e hipofisitis. Presentación de un caso.

Autoimmune hepatitis primarily affects women and 40% of cases are associated with extrahepatic autoimmune dysfunction. Thyroiditis, ulcerative colitis and rheumatoid arthritis are the most commonly implicated entities. We present a 46-year-old woman with type-II autoimmune hepatitis and Graves disease who presented deterioration in level of consciousness, her symptoms mimicking severe liver failure. Hormone studies and nuclear magnetic resonance imaging revealed hypophysitis, which led to hypothyroidism and metabolic encephalopathy. The syndrome was resolved with hormone replacement therapy.

[Steatosis and nonalcoholic steatohepatitis. A comparative analysis]. / Esteatosis y esteatohepatitis no alcohólica. Análisis comparativo.

Liver biopsies with a main histological diagnosis of steatosis were selected from 3,422 liver biopsies carried out in our department between January 1995 and December 1998. Patients with known risk factors for steatosis, such as excessive alcohol consumption, hepatitis C infection, treatment with amiodarone, perhexiline maleate, tamoxifen, antiviral drugs (didanosine, zidovudine) methotrexate, sodium valproate or total parenteral nutrition, Wilson's disease and organ transplant were subsequently excluded. Of the 43 liver biopsies finally included in the study, 23 showed simple steatosis and 20 steatohepatitis. Eighty-one per cent of the patients were male (mean age of 44 years) and the majority were asymptomatic. The most frequent indication for liver biopsy was hypertransaminasemia. No differences were observed between the two groups in terms of frequency and severity of classical risk factors for steatosis (diabetes mellitus, dyslipemia and obesity). Thirty-five percent of patients with steatohepatitis and 26% of those with simple steatosis had none of these risk factors. Patients with steatohepatitis were older than those with simple steatosis. They presented more severe symptomatology, the degree of steatosis was more intense and laboratory investigations showed greater alterations. These results suggest that simple steatosis and nonalcoholic steatohepatitis are two different phases of the same disease. The difficulty in clinical differentiation justifies carrying out liver biopsy, especially in patients with more severe symptomatology whose laboratory results show greater alterations, since these patients present more marked histological lesions, are at risk of developing liver cirrhosis and require therapy.