Tratamiento del cáncer colorrectal con metástasis irresecables con quimioterapia sin resección del primario: análisis de las complicaciones relacionadas con el tumor / Treatment of colorectal cancer with unresectable metastasis with chemotherapy without primary tumor resection: Analysis of tumor-related complications

INTRODUCCIÓN: Aunque el tratamiento convencional de los pacientes con cáncer colorrectal en estadio IV ha consistido en la resección del tumor primario seguida de quimioterapia, varios estudios defienden que en pacientes poco sintomáticos el primer y único tratamiento debe ser quimioterapia. El objetivo es analizar las complicaciones relacionadas con el tumor primario en una serie consecutiva de pacientes con cáncer colorrectal y metástasis irresecables tratados con quimioterapia sin cirugía. MATERIAL Y MÉTODOS: Estudio descriptivo retrospectivo. Se ha incluido a todos los pacientes con cáncer colorrectal y metástasis irresecables en los que se decidió realizar quimioterapia sin resección del tumor primario durante el periodo enero 2007-febrero 2011. RESULTADOS: La edad media de los 61 pacientes analizados era de 67 ± 13 años. Veinte (33%) pacientes presentaron alguna complicación durante el seguimiento. La complicación más frecuente fue la obstrucción intestinal en 15 (25%) seguida de la perforación. Las complicaciones precisaron cirugía en 6 (10%). No hemos encontrado diferencias estadísticamente significativas en las características de los pacientes entre aquellos que presentaron una complicación y los que no, aunque el porcentaje de complicaciones entre los portadores de prótesis colónica (53%) dobló el del resto de pacientes (26%). CONCLUSIONES: La quimioterapia sin cirugía es una buena opción en la mayoría de los pacientes con cáncer colorrectal y metástasis irresecables. Sin embargo, aunque el porcentaje de pacientes que precisan cirugía es bajo, el número de complicaciones relacionadas con el tumor primario no es despreciable. Se necesitan estudios que permitan identificar a aquellos pacientes en los que estaría indicada una colectomía profiláctica

INTRODUCTION: Although the conventional treatment of patients with stage IV colorectal cancer involves resection of the primary tumor followed by chemotherapy, several studies suggest that in patients with few symptoms the first and only treatment should be chemotherapy. The objective of this study is to analyze the complications related to the primary tumor in a series of patients with unresectable metastatic colorectal cancer treated with chemotherapy without surgery. MATERIAL AND METHODS: Retrospective descriptive study. The study included all patients with unresectable metastatic colorectal cancer treated with chemotherapy without resection of the primary tumor (January 2007-February 2011). RESULTS: The mean age of the 61 patients analyzed was 67 ± 13 years and the performance status was 0-1 in 53 (87%). Twenty (33%) patients developed complications during follow-up. The most common complication was intestinal obstruction in 15 (25%) patients followed by perforation. Complications required surgery in 6 (10%) cases. We did not find differences in patient characteristics between those who had a complication and those without, although the complication rate in patients with a colonic stent (53%) was twice that of other patients (26%). CONCLUSIONS: Chemotherapy without surgery is a good option in most patients with unresectable metastatic colorectal cancer. However, although the percentage of patients requiring surgery is low, the total number of complications related to the primary tumor is not negligible. Studies are needed to identify those patients in whom a prophylactic colectomy could be indicated

[Treatment of colorectal cancer with unresectable metastasis with chemotherapy without primary tumor resection: analysis of tumor-related complications]. / Tratamiento del cáncer colorrectal con metástasis irresecables con quimioterapia sin resección del primario: análisis de las complicaciones relacionadas con el tumor.

INTRODUCTION: Although the conventional treatment of patients with stage iv colorectal cancer involves resection of the primary tumor followed by chemotherapy, several studies suggest that in patients with few symptoms the first and only treatment should be chemotherapy. The objective of this study is to analyze the complications related to the primary tumor in a series of patients with unresectable metastatic colorectal cancer treated with chemotherapy without surgery. MATERIAL AND METHODS: Retrospective descriptive study. The study included all patients with unresectable metastatic colorectal cancer treated with chemotherapy without resection of the primary tumor (January 2007-February 2011). RESULTS: The mean age of the 61 patients analyzed was 67±13 years and the performance status was 0-1 in 53 (87%). Twenty (33%) patients developed complications during follow-up. The most common complication was intestinal obstruction in 15 (25%) patients followed by perforation. Complications required surgery in 6 (10%) cases. We did not find differences in patient characteristics between those who had a complication and those without, although the complication rate in patients with a colonic stent (53%) was twice that of other patients (26%). CONCLUSIONS: Chemotherapy without surgery is a good option in most patients with unresectable metastatic colorectal cancer. However, although the percentage of patients requiring surgery is low, the total number of complications related to the primary tumor is not negligible. Studies are needed to identify those patients in whom a prophylactic colectomy could be indicated.

Phase II study of preoperative radiotherapy and concomitant weekly intravenous oxaliplatin combined with oral capecitabine for stages II-III rectal cancer.

INTRODUCTION: A prospective phase II study was conducted to assess the clinical activity and tolerability of oxaliplatin, capecitabine, and radiotherapy (RT) for neoadjuvant therapy of stages II-III rectal cancer. MATERIALS AND METHODS: Patients with histologically confirmed stages II-III (T3-T4 and/or N+) resectable rectal adenocarcinoma were eligible. Capecitabine was administered at 825 mg/m(2) twice daily for 5 days/week and oxaliplatin at 50 mg/m(2) on day 1 weekly for 5 weeks starting the first day of RT (before RT). RT consisted of a total dose of 45 Gy delivered in 25 fractions of 1.8 Gy, 5 days per week, for 5 weeks. RESULTS: A total of 46 patients were included (35 male, 10 female, median age 62 years). TNM Stage was T3 in 43 patients and T4 in 2. Twenty-eight patients had suspected nodal involvement. The intended chemoradiation treatment was completed in 94 % patients. Grade 3/4 toxicity included lymphocytopenia (6 patients), diarrhea (4 patients), emesis (2 patients), asthenia (3 patients), anorexia (1 patient), and hepatic toxicity (1 patient). Grade 1 neurotoxicity occurred in 18 patients, Grade 2 neurotoxicity in 3, and Grade 1 palmoplantar erythrodysesthesia in 2. Forty-two patients underwent surgery (complete resection 95 %, sphincter-saving operation 55 %). The overall pathologic response rate was 83 %, with a pathologic complete response (pCR) rate of 11.9 % (95 % CI 4.0-25.6). CONCLUSIONS: The pCR rate observed with oxaliplatin plus capecitabine and RT did not reach the pre-specified criteria of efficacy in this trial, which is in line with recent results of randomized phase III trials.

Snail1 protein in the stroma as a new putative prognosis marker for colon tumours.

Over-expression of Snail1 gene transcriptional repressor promotes an epithelial-to-mesenchymal transition in epithelial tumour cell lines. Expression of Snail1 RNA has been associated to the pathogenesis of a number of malignancies; however, the lack of good monoclonal antibodies against this protein has precluded a definitive analysis of Snail1 protein. In this study, we aimed to determine the expression of this transcriptional factor in colorectal tumours. Using a Snail1 well-characterized monoclonal antibody developed in our laboratories we have analyzed by immunohistochemistry a cohort of 162 human colorectal tumours. Ninety tumours (56%) showed nuclear expression in the tumoral tissue and the adjacent stroma; in 34 (21%), Snail1 was detected just in the stroma, whereas in only 4 the expression of Snail1 was detected in the tumoral tissue and the stroma was negative. No correlation was found between the presence of Snail1 in the tumour and tumour stage; however, a trend (p = 0.054) was detected when the expression of this factor in the stroma was considered. Snail1 immunoreactivity in this compartment was associated with presence of distant metastasis (p = 0.006). Moreover, expression of Snail1 in the tumor stroma correlated with lower specific survival of cancer patients (p = 0.011). Interestingly, this correlation was also detected in stage I and II tumors. Therefore, our results indicate that the presence of nuclear Snail1 immunoreactive cells in the stroma may be an informative indicator of prognosis of colon tumours especially useful in those corresponding to lower stages and identify a new marker suitable to label activated stroma in colon tumours.

A Phase II study of preoperative radiotherapy and concomitant weekly irinotecan in combination with protracted venous infusion 5-fluorouracil, for resectable locally advanced rectal cancer.

PURPOSE: The aim of this study was to evaluate the efficacy and tolerance of preoperative chemoradiotherapy (CRT) with irinotecan (CPT-11) and 5-fluorouracil (5-FU) in patients with resectable rectal cancer. METHODS AND MATERIALS: Patients with resectable T3-T4 rectal cancer and Eastern Cooperative Oncology Group performance status <2 were included. CPT-11 (50 mg/m(2) weekly) and 5-FU (225 mg/m(2)/day continuous infusion, 5 days/week) were concurrently administered with radiation therapy (RT) (45 Gy, 1.8 Gy/day, 5 days/week), during 5 weeks. RESULTS: A total of 74 patients were enrolled: mean age, 59 years (20-74 years; SD, 11.7). Planned treatment was delivered to most patients (median relative dose intensity for both drugs was 100%). Grade 3/4 lymphocytopenia occurred in 35 patients (47%), neutropenia in 5 (7%), and anemia in 2 (3%). Main Grade 3 nonhematologic toxicities were diarrhea (14%), asthenia (9%), rectal mucositis (8%), and abdominal pain (8%). Of the 73 resected specimens, 13.7% (95% confidence interval [CI], 6.8-23.7) had a pathologic complete response and 49.3% (95% CI, 37.4-61.3) were downstaged. Additionally, 66.7% (95% CI, 51.1-80.0) of patients with ultrasound staged N1/N2 disease had no pathologic evidence of nodal involvement after CRT. CONCLUSIONS: This preoperative CRT schedule has been shown to be effective and feasible in a large population of patients with resectable rectal cancer.

Cofactors associated with liver disease mortality in an HBsAg-positive Mediterranean cohort: 20 years of follow-up.

The risk of developing liver cancer in hepatitis B virus (HBV) carriers differs across geographical areas, suggesting that exposure to other risk factors may contribute to HBV-linked cancer risk. Our study estimates the mortality due to liver disease and the role of other risk factors in a Spanish HBV cohort. 2,352 hepatitis B surface antigen (HBsAg)-positive and 15,504 HBsAg-negative subjects were identified among blood donors during 1972-1985 and were followed until December 2000 through the Mortality Registry. Clinical examination and an epidemiological questionnaire were performed on 1,000 HBsAg-positive survivors during 1994-1996. In subjects deceased from liver disease, medical records were revised and relatives were interviewed. A nested case-control analysis was conducted comparing both groups. In HBsAg-positive men, an excess mortality from liver cancer [standardized mortality ratio (SMR): 14.1; 7.7-23.6], cirrhosis (SMR: 10.5; 7.0-15.1), haematological neoplasms (SMR: 3.2; 1.2-6.9) and AIDS was detected (SMR: 5.5; 2.2-11.4). In women, an excess was found for cirrhosis (SMR: 7.2; 1.4-21.1). Progression factors to liver disease were alcohol intake [odds ratio (OR): 6.3; 3.1-12.8], diabetes (OR: 3.6; 1.3-9.6), HBV replication (OR: 50.0; 14.9-167.3) and hepatitis C virus (HCV) infection (OR: 27.4; 7.1-107.7). In conclusion, in Spain after 20 years of follow-up, chronic HBV exposure appears as a major risk factor for liver cancer among men and for cirrhosis in both sexes. The risk of death from liver disease among HBV carriers with the presence of HBV replication, HCV, alcohol consumption and diabetes was significantly increased and suggests synergism among these exposures and HBV. Mortality from haematological neoplasms was detected and could be associated to HIV coinfection. These results support screening and adequate follow-up among HBsAg-positive subjects at high risk to develop liver disease, particularly when these risk cofactors are present.