A multicentre comparison of a fast track or conventional postoperative protocol following laparoscopic or open elective surgery for colorectal cancer surgery.

AIM: The introduction of multimodal or fast track (FT) rehabilitation and laparoscopy in colorectal surgery has improved patient recovery and shortened hospital stay (HS). This study aimed to determine the influence of laparoscopic or open surgery on the postoperative recovery of colorectal cancer patients having a conventional care (CC) or FT protocol in the postoperative period. METHOD: A multicentre prospective study was controlled with a retrospective group. The prospective group included 300 patients having elective colorectal resection for cancer. The retrospective control group included 201 patients with the same characteristics who were treated before the introduction of the programme. The patients were divided into four groups including laparoscopy + FT, open surgery + FT, laparoscopy + CC, and open surgery + CC. The primary end-points were HS and morbidity. Secondary end-points included mortality and reoperation rates. RESULTS: The overall median HS was 7 days. The median HS for laparoscopy + FT was 5 days, open + FT 6 days, laparoscopy + CC 9 days and open + CC 10 days (P < 0.001). In the regression model the laparoscopy + FT group had the greatest reduction in HS (P < 0.001). A significant reduction in HS was observed in the laparoscopy + FT group compared with laparoscopy + CC (P < 0.001). The overall patient morbidity was 30.6%. The logistic regression model adjusted for propensity score showed no statistically significant differences between the study groups regarding all other end-points. CONCLUSION: Colorectal cancer patients who underwent laparoscopic surgery within a multimodal rehabilitation protocol experienced the shortest HS and the lowest morbidity.

Vascular endothelial growth factor gene polymorphisms in patients with colorectal cancer.

BACKGROUND: Angiogenesis plays an important role in tumor progression. The vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. In the present study we evaluated single nucleotide polymorphisms (SNPs) -2578C > A, -1154G > A, and +936C > T in the VEGF gene, and their prognostic value for patients operated on for colorectal cancer (CRC). PATIENTS AND METHOD: VEGF polymorphisms have been analyzed in 177 patients who had undergone surgical resection at Hospital Clínico San Carlos. The analysis of these polymorphisms was performed with specific probes for each nucleotide in a multiplex reaction using real-time PCR. RESULTS: We only found a statistically significant relationship for one of these three polymorphisms, +936C > T, with gender and tumor location; 10.7% of patients heterozygotes for this SNP had tumors located in proximal colon, 35.2% in distal segment and 54.1% in rectum (p = 0.03). Patients with the +936T/T genotype had 100% overall survival (OS). CONCLUSION: Patients with a +936T/T genotype showed increased survival, therefore the +936C > T SNP could be a useful marker in the follow-up and clinical management of patients with colorectal cancer.

Overexpression of c-myc and loss of heterozygosity on 2p, 3p, 5q, 17p and 18q in sporadic colorectal carcinoma.

AIM: The aim of the present study is to evaluate the prognostic influence of loss of heterozygosity on 2p, 3p, 5q, 17p and 18q, and c-myc overexpression on surgically treated sporadic colorectal carcinoma. METHODS: Tumor and non-tumor tissue samples from 153 patients were analyzed. Fifty-one percent of patients were male, and mean age in the series was 67 years. Tumors were located in the proximal colon in 37 cases, in the distal bowel in 37, and in the rectum in 79 patients. c-myc overexpression was studied by means of Northern blot analysis, and loss of heterozygosity through microsatellite analysis. RESULTS: c-myc overexpression was detected in 25% of cases, and loss of heterozygosity in at least one of the studied regions in 48%. There was no association between clinical and pathologic features, and genetic alterations. The disease-free interval was significantly shorter for patients with both genetic alterations; the presence of both events was an independent prognostic factor for poor outcome in the multivariate analysis (RR: 4.34, p < 0.0001). CONCLUSIONS: The presence of both loss of heterozygosity and overexpression of the c-myc oncogene separates a subset of colorectal carcinoma patients who have a shorter disease-free interval after curative-intent surgery.

Prognostic significance of the p185 protein in colorectal cancer.

The amplification and/or overexpression of the c-erbB-2/neu oncogene may play a role in tumor development and progression. The aim of this prospective study was to evaluate the prognostic value of p185 protein in colorectal cancer using immunohistochemical techniques. We analyzed 106 colorectal tumor tissue specimens from patients who had been operated on by the same surgeon and subjected to a median follow-up of 3 years. Thirty-three per cent of patients showed p185 overexpression related to an advanced stage of the disease. In patients with adenocarcinoma tumors of the colon without distant metastases, p185 detection was found to be of clinical prognostic relevance (p = 0.06).

N-acetyltransferase 2 (NAT2) genotype and colorectal carcinoma: risk variability according to tumour site?

BACKGROUND: Dietary heterocyclic aromatic amines (HAAs) are members of a family of chemicals that comprise highly mutagenic compounds related to colon cancer. The polymorphic N-acetyltransferase 2 enzyme (NAT2, E.C. 2.3.1.5) plays a key role in the transformation of HAAs to ultimate carcinogens. NAT2 enzyme activity is expressed in a genotype-dependent manner in colon epithelium. Therefore local activation of HAAs in colon, and hence increased risk to develop colon cancer, is likely to be related to high NAT2 enzyme activity. This study is aimed at analysing the association between genotypes leading to high NAT2 activity and colorectal cancer risk. METHODS: Genomic DNA from 120 colorectal cancer patients and 258 healthy individuals were analysed for enzyme-inactivating mutations at the coding region of the NAT2 gene by means of a mutation-specific polymerase chain reaction. RESULTS: Among patients with sigmoid colon cancer, a significant excess of individuals with genotypes leading to high NAT2 activity was observed as compared both to controls and to the rest of patients with colorectal cancer (P < 0.05). CONCLUSIONS: Our findings, which require independent confirmation, suggest that the NAT2 genotype constitutes a secondary risk factor to develop sigmoid colon cancer.

p53 exon 7 mutations as a predictor of poor prognosis in patients with colorectal cancer.

We have studied 61 resected colorectal adenocarcinomas in order to investigate p53 mutations as a prognostic factor for this pathology. Mutations in exons 5-9 of the p53 gene were analyzed by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique followed by sequencing. Our data indicate that p53 exon 7 mutations were prevalent in the latest stages of colorectal carcinogenesis and patients bearing this alteration had the worst prognosis. Therefore, according to our results, mutations affecting exon 7 of the p53 gene could be considered as a useful marker of biological aggressiveness for colorectal cancer.

Genetic abnormalities and microsatellite instability in colorectal cancer.

Our purpose was to investigate different genetic abnormalities, such as K-ras mutations, p53 alterations, and c-myc RNA overexpression, as well as microsatellite instability in 63 colorectal tumors obtained from patients that had undergone surgery. K-ras point mutations were analyzed by PCR-RFLP technique, followed by sequencing; p53 protein accumulation by immunohistochemistry; p53 gene mutations in exons 5-9 were studied by the SSCP and sequencing techniques, and c-myc overexpression by Northern blot. Microsatellite instability was performed at chromosomes 2p, 3p, and 11p by a PCR-based technique. Our data indicate a trend toward a poorer prognosis in patients who had K-ras transversions; besides, we have obtained a prevalence of c-myc RNA overexpression and p53 exon 7 mutations in the latest stages of tumor progression. In conclusion, our findings suggest that the recognition of molecular abnormalities might be used in colorectal cancer as a prognostic indicator or to determine the metastatic potential of colorectal adenocarcinomas.

[Colorectal cancer: has its diagnosis improved in the last decade?]. / Cáncer colorrectal: Ha mejorado su diagnóstico en la última década?

OBJECTIVE: To assess whether any shift in pathologic stage, tumor resectability and need of emergency surgery has been observed in colorectal carcinoma patients over the last ten years. EXPERIMENTAL DESIGN: Retrospective study. PATIENTS: We compare 201 patients treated in our Service from January 1981 to December 1983 (Group I) with 306 patients operated from January 1991 to December 1993 (Group II). RESULTS: No change has been noticed in any of the parameters analyzed. CONCLUSIONS: We think that the efforts in earlier detection of CCR should be increased to improve the prognosis of the disease.

[Treatment with sulindac of adenomatous polyps in familial polyposis]. / Tratamiento con Sulindac de los pólipos adenomatosos en la poliposis familiar.

BACKGROUND: The effect of sulindac, a nonsteroid antiinflammatory drug, has been reported to cause both regression and suppression of colon polyps in patients with familial adenomatous polyposis and Gardner's syndrome. We report our experience with seven patients with diffuse colonic polyposis treated with sulindac. PATIENTS AND METHODS: Seven patients with familiar adenomatous polyposis, four men and three women (mean age, 30 years; range 16 to 41 years) were included in this study. Two patients that underwent prior colectoctomy with ileorectal anastomosis and had polyps in the rectum were also included. The polyps ranged in size from 0.2 to 2.5 cm; most of them were less than 1 cm. Sulindac was given 150 mg. twice a day. Further colonoscopic examination was done at 6-month intervals during follow-up in all patients. RESULTS: A disappearance or a marked reduction in the number and size of polyps was observed in all patients after 24 months of treatment with sulindac. The drug was well tolerated and no side effects were observed during treatment. CONCLUSION: The authors conclude that sulindac is effective in inducing the regression of rectal polyps in familial, adenomatous polyposis.

[Appendiceal Crohn's disease]. / Enfermedad de Crohn apendicular.

Crohn's disease of the appendix is an uncommon process that is more frequent in young people. The most common preoperative diagnosis is acute appendicitis. At exploratory laparotomy the appendix is enlarged and malignancy may be suspected. The differential diagnosis may be difficult. Serologic tests and cultures should be performed to exclude Yersinia infections. Appendicectomy is a safe procedure when the disease is limited to the appendix. The postoperative course is usually uncomplicated with a low rate of complications and recurrence. Although it may be a different process than Crohn's disease and the recurrence rate is low, it is suggested that all the patients should be followed-up so that recurrences may be recognized and treated as early as possible. A new case is presented after two years of follow-up without recurrence.

[The prognostic value of common predictive variables in rectal cancer]. / Valor pronóstico de variables predictivas comunes en el cáncer de recto.

BACKGROUND: A study was undertaken to identify common clinical variables, easy to obtain in an out-patient office, that complement the prognostic estimation on survival offered by the staging classification in patients operated on for rectal cancer. PATIENTS AND METHODS: 236 patients were included. Twenty-one variables related to symptoms, examinations, type of operation, tumor stage, pathology and follow-up were evaluated, all of them were collected prospectively. The relative predictive value was analyzed by means of the Cox' proportional hazards progression model. RESULTS: Age, carcinoembryonic antigen (CEA), alcaline fosfatase (FA), deshidrogenase lactate (LDH), elective surgery, showed independent predictive value. The risk of death raised by 1.026 (CI 95%: 1.005-1.047) for each year of age at the moment of surgery, serum CEA over 5 ng/ml raises the risk by 2.32 (IC 95%: 1.385-3.893), LDH over 190 mU/ml by raises the risk by 1.64 (IC 95%: 1.026-2.639), FA over 250 U/ml raises the risk by 2.16 (IC 95%: 1.027-4.578), elective surgery reduces the risk by 0.32 (IC 95%: 0.106-0.965). CONCLUSIONS: Age, CEA, LDH, FA and elective surgery, complement the prediction on survival offered by the tumor stage in patients operated on for rectal cancer.

Prognostic significance of preoperative serum CA 19.9 assay in patients with colorectal carcinoma.

The prognostic information provided by preoperative serum CEA and CA 19.9 antigen assay on the postoperative outcome of 150 patients with colorectal cancer was analysed. The influence of both markers was studied by Cox's proportional-hazard regression analysis. In the univariate analysis, patients whose initial CA 19.9 level was higher than 37 U/ml had a 4.32-fold greater risk of death due to the cancer (95% CI: 1.72-10.84) (p < 0.001) than patients with lower values. The 36-month survival rate posttreatment was lower for patients with CA 19.9 serum levels over 37 U/ml (61% versus 90%) (p < 0.001). Patients whose initial CEA level was higher than 5 ng/ml had a 2.9-fold greater risk of death (95% CI: 1.05-7.99) (p = 0.04) than patients with lower values. The 36-month survival rate posttreatment was lower for patients with CEA serum levels over 5 ng/ml (84% versus 76%) (p = 0.04). After adjustment for Dukes' stage, CEA, CA 19.9, tumor site, sex and age, only Dukes' stage and CA 19.9 continued to provide independent predictive information on survival. The risk of death increases by 1.008 for every 10 U/ml rise in the level of the marker (95% CI: 1.002-1.014) (p = 0.009). With respect to analysis of disease-free survival, only Dukes' stage provided independent predictive value. CA 19.9 is an independent prognostic factor of survival in colorectal cancer. The authors suggest including CA 19.9 in a future multifactorial analysis of survival.

[The results after extensive radical resection of locally advanced colorectal carcinoma]. / Resultados tras resección radical ampliada por carcinoma colorrectal localmente avanzado.

The results of extended resections for locally advanced colorectal cancer and the factors influencing the long term survival and recurrence rate are analyzed in 69 patients. All of them underwent radical en-bloc resection including the primary tumor and the adjacent affected structures. The existence of tumoral invasion was confirmed in 42 cases (60%). In the remaining, inflammatory adhesions were presents. Overall 5 year survival did not show significant differences between the groups of patients with benign or malignant infiltration (71% y 51% respectively). Within the same tumor stage, the results were similar for the two types of infiltration. Significant differences were found when lymph nodes metastases were considered: 65% 5 year survival in patients with negative lymph nodes versus 35% in patients with positive nodes. The probability of metastases and tumor recurrence was significantly higher in the group with malignant infiltration. Patients with positive lymph nodes showed lower disease-free interval rate. These data show that long term control of the tumor in locally advanced colorectal carcinomas can be achieved by an aggressive surgical approach. The presence of lymph mode metastases is a more useful prognostic factor influencing survival and relapse rate that the local infiltration by it-self.

[Renal amyloidosis in a case of Crohn disease with colonic and rectal involvement]. / Amiloidosis renal en un caso de enfermedad de Crohn con afectación de colon y recto.

A clinical case characterized by renal amyloidosis, Crohn's disease of the colon and rectum, multiple chronic anal fistulae and ankylosing spondylitis is reported. This association has been infrequently recognized. In this patient Crohn's disease became manifest at 20 years of age and underwent a chronic and relapsing course. Proteinuria and renal amyloidosis were detected after eight years of evolution. Panproctocolectomy was performed. The patient progressed satisfactorily and six months later he remains asymptomatic, free from medication and with normal creatinine clearance. The authors recommend early surgical treatment on the diseased intestinal segment once the association has been diagnosed and before serious impairment of renal function has occurred.

Evaluation of serum CA 125 as a tumor marker in non-small cell lung cancer.

Serum CA 125 levels were evaluated in 130 healthy subjects and 133 patients with untreated pulmonary lesions. These were 33 patients with benign pulmonary conditions and 100 with lung cancer. The mean concentration of CA 125 was higher in patients with lung cancer (37 +/- 81 U/ml) than in those with nonmalignant disease (4.2 +/- 5.7 U/ml) (P less than 0.01). In the healthy control group CA 125 concentrations were significantly lower (0.63 +/- 1.5 U/ml) (P less than 0.001). In patients with lung cancer the concentration of this tumor marker was related to the tumor-node-metastasis (TNM) stage. At a cut-off value of 15 U/ml, CA 125 had a sensitivity of 44%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 65% with respect to healthy subjects; in patients with benign pulmonary conditions, these values were 44%, 94%, 94%, and 31%, respectively. At this cut-off value, a correlation between the respectability prognosis and the likelihood of survival 24 months posttreatment was observed. These findings suggest that CA 125 can be used as an adjunctive test in the management of patients with lung cancer patients.

Use of the copper/zinc ratio in the diagnosis of lung cancer.

Serum zinc (Zn), copper (Cu), and the Cu/Zn ratio were evaluated in 84 patients with pulmonary lesions before surgery and in 100 healthy normal controls. There were 20 patients with benign and 64 with malignant lung tumors. Only the mean (+/- SD) Cu/Zn ratio was significantly higher in malignant tumors (2.24 +/- 0.78) than in benign tissue (1.63 +/- 0.33) (P less than 0.001). In the normal group, the Cu/Zn ratio was significantly lower (1.43 +/- 0.29). Patients with advanced disease (Stage III) had higher Cu/Zn ratio than patients in Stages I and II (2.65 +/- 0.86 versus 1.9 +/- 0.27) (P less than 0.001). At a cutoff value of 1.72, Cu/Zn ratio had a sensitivity of 89%, specificity of 84%, positive predictive value of 78%, and negative predictive value of 92% between controls and lung cancer patients. Between lung cancer patients and patients with benign pulmonary lesions the aforementioned values were 89%, 70%, 90%, and 70% respectively. A correlation between increasing Cu/Zn ratio and tumor extension and postoperative survival was observed. These findings suggest that Cu/Zn ratio may be used as a diagnostic test in lung cancer patients.

Serum and tissue trace metal levels in lung cancer.

Copper, zinc, magnesium, calcium and iron were measured in serum and lung tissue - tumor mass and histologically nonneoplastic tissue - from lung cancer patients and compared with serum concentrations in healthy subjects and control lung tissue obtained from patients with nonmalignant lung disease. Lung cancer patients showed a significant increase in serum Cu and Cu/Zn ratio levels and decrease in serum Zn and Fe concentrations. These findings were correlated with TNM stage of the disease, but not with histologic type of tumor. Malignant lung tissue showed a higher level of Cu, Ca, Mg, and Cu/Zn ratio and lower Zn level than that found in control samples, as well as an increase in Cu, Mg and Cu/Zn ratio concentrations with regard to histologically nonneoplastic tissue samples from the same patient. Tissue concentration of trace metals was not significantly influenced either by histologic type of tumor or clinical TNM stage. Significant correlation coefficients between serum and tissue trace metal levels were not found.