Intensified surveillance after surgery for colorectal cancer significantly improves survival.

BACKGROUND: Postoperative surveillance after curative resection for colorectal cancer has been demonstrated to improve survival. It remains unknown however, whether intensified surveillance provides a significant benefit regarding outcome and survival. This study was aimed at comparing different surveillance strategies regarding their effect on long-term outcome. METHODS: Between 1990 and 2006, all curative resections for colorectal cancer were selected from our prospective colorectal cancer database. All patients were offered to follow our institution's surveillance program according to the ASCO guidelines. We defined surveillance as "intensive" in cases where >70% appointments were attended and the program was completed. As "minimal" we defined surveillance with <70% of the appointments attended and an incomplete program. As "none" we defined the group which did not take part in any surveillance. RESULTS: Out of 1469 patients 858 patients underwent "intensive", 297 "minimal" and 314 "none" surveillance. The three groups were well balanced regarding biographical data and tumor characteristics. The 5-year survival rates were 79% (intensive), 76% (minimal) and 54% (none) (OR 1.480, (95% CI 1.135-1.929); p <0.0001), respectively. The 10-year survival rates were 65% (intensive), 50% (minimal) and 31% (none) (p <0.0001), respectively. With a median follow-up of 70 months the median time of survival was 191 months (intensive), 116 months (minimal) and 66 months (none) (p <0.0001). After recurrence, the 5-year survival rates were 32% (intensive, p = 0.034), 13% (minimal, p = 0.001) and 19% (none, p = 0.614). The median time of survival after recurrence was 31 months (intensive, p <0.0001), 21 months (minimal, p <0.0001) and 16 month (none, p <0.0001) respectively. CONCLUSION: Intensive surveillance after curative resection of colorectal cancer improves survival. In cases of recurrent disease, intensive surveillance has a positive impact on patients' prognosis. Large randomized, multicenter trials are needed to substantiate these results.

Influence of thymidylate synthase and p53 protein expression on clinical outcome in patients with colorectal cancer.

AIMS: Thymidylate synthase (TS) and tumor suppressor p53 are two proteins with an influence on tumor resistance to radio-chemotherapy that is well known. For this reason we tested the effect of TS and p53 expression on clinical outcome (tumor recurrence and survival) in patients after curative tumor resection, especially in patients who received adjuvant radio-chemotherapy. PATIENTS AND METHODS: A total of 120 patients with colorectal cancer were included in the study. A curative resection was possible in 83 patients, and 30 of this group received adjuvant therapy. For the immunohistochemical staining of tumor specimens, monoclonal antibody (mAb) TS 106 against TS and mAb DO-1 against p53 protein were used. TS positivity was defined as a moderate to high staining intensity in the cytoplasma of cells and p53 positivity as nuclear staining of tumor cells in >10% of these cells. RESULTS: Thymidylate synthase immunoreactivity was found in 59% of all cases and p53 staining in 51%. No relation between clinicopathological features and p53 expression was found in contrast to TS expression, where a highly significant association of TS-positive cases with tumor invasion (pT) was observed. Curatively resected patients with a TS-positive tumor developed tumor recurrence/distant metastases significantly more often than TS negative tumors. The same result was found when comparing p53-positive with p53-negative tumors and TS+/p53+ with TS-/p53- tumors. TS expression was highly significantly associated with poor survival and was the strongest independent prognostic factor in multivariate analysis, followed by lymph node status. CONCLUSION: Thymidylate synthase expression seems to be an independent prognostic factor and a possible predictor of tumor recurrence in patients with colorectal cancer.

p53 autoantibodies in sera of patients with a colorectal cancer and their association to p53 protein concentration and p53 immunohistochemistry in tumor tissue.

We evaluated p53 autoantibodies (p53-Ab) as a preoperative tumor marker and as a prognosis marker. We also investigated whether p53-Ab production is dependent on p53 protein overexpression in tumor tissue or on tumor volume. Serum samples of patients with a colorectal cancer (n = 130) and of healthy controls (n = 44) were examined for p53-Ab using an ELISA kit. P53 protein expression in tumor tissue was demonstrated immunohistochemically and quantified by ELISA. Tumor volume was calculated and patients' survival computed using the Kaplan-Meier method. p53-Ab were detected in the serum from 15% of patients; all controls were negative. There was a significant correlation between p53-Ab production and positive immunostaining or p53 protein concentration in tumor tissue. p53-Ab were detected at a higher percentage of patients with a tumor volume of 10 cm3 or greater than in those with a smaller tumor. No difference in patients' prognosis was found between the p53-Ab positive and negative groups. Because of their low sensitivity (15%) p53-Ab are not suitable as a preoperative tumor marker. However, their high specificity (100%) and their potential for early diagnosis of a tumor relapse makes them valuable for postoperative monitoring during follow-up in p53-Ab positive patients. Furthermore, their detection can be used as a simple serological test for early detection of p53 alterations.

Vascular endothelial growth factor (VEGF)--a valuable serum tumour marker in patients with colorectal cancer?

INTRODUCTION: Neo-angiogenesis, of great importance for tumour growth and nutrition, is preferentially mediated by the cytokine vascular endothelial growth factor (VEGF), which has a direct effect on vascular endothelial cell proliferation and migration. This study was designed to clarify whether VEGF is a suitable tumour marker in sera of patients with a colorectal cancer, and whether VEGF concentrations in sera and tumour tissues are correlated with tumour extension (pTNM) and especially with tumour volume or size. Furthermore, the influence of VEGF levels on patients >> prognosis was examined. METHODS: VEGF serum concentrations of 122 patients with colorectal cancer and 65 controls were determined with an ELISA kit. Additionally, VEGF concentrations of tumour and normal tissue were measured in 38 patients using the same ELISA. RESULTS: Our results demonstrate that VEGF is not a suitable diagnostic tumour marker in patients with colorectal cancer due to its low sensitivity (36%). However, a combination of the serum tumour markers CEA and VEGF can significantly increase the pre-operative diagnostic sensitivity to 62%. VEGF serum levels differed significantly between patients (mean 438 pg/ml) and controls (mean 203 pg/ml), and also between tumour and normal tissue (984 vs 89 pg/mg protein). Serum concentration showed a significant correlation to tumour volume and size. Patients with VEGF serum levels greater than cut-off had a poorer prognosis than those less than or equal to cut-off. For this reason VEGF could be used as a predictor of patients >> outcome.

Ordinary colorectal adenocarcinoma vs. primary colorectal signet-ring cell carcinoma: study matched for age, gender, grade, and stage.

PURPOSE: This study contributes to the characterization of primary colorectal signet-ring cell cancer in contrast to ordinary colorectal carcinoma. Primary colorectal signet-ring cell cancer is a rare but distinctive primary neoplasm of the large bowel with still-controversial clinicopathologic features. METHODS: Clinicopathologic features and survival data are evaluated in comparison with those of the ordinary colorectal adenocarcinoma (non-signet colorectal carcinoma) in a retrospective study matched for age, gender, grade, and stage. RESULTS: In a series of 1,600 consecutive colorectal cancer patients since 1979, 14 patients (0.88 percent) with a signet-ring cell cancer were identified. Gender ratio was balanced, and mean age was 67.5 years. The majority of patients had an advanced tumor stage at the time of diagnosis (57.1 percent Stage IV and 35.7 percent Stage III). Median survival time was only 16 months. In a study matched for age, gender, grade, and stage, a lower survival rate was found for patients with signet-ring cell cancer, but the difference did not reach statistical significance. In contrast to non-signet colorectal carcinoma, signet-ring cell cancer was characterized by a significantly higher incidence of peritoneal tumor spread (64.3 percent) and a lower incidence of hepatic metastases (14.3 percent). CONCLUSIONS: Signet-ring cell cancer represents a rare but distinctive primary neoplasm of the large bowel. It is frequently diagnosed in an advanced tumor stage, thus showing an overall poorer prognosis than nonsignet colorectal carcinoma. Usually only palliative surgery is possible. A high incidence of peritoneal seeding and a low incidence of hepatic metastasis is characteristic of signet-ring cell cancer.

Blood selenium and glutathione peroxidase status in patients with colorectal cancer.

PURPOSE: It is still controversial whether a low selenium level and a reduced activity of the selenium-dependent enzyme, glutathione peroxidase, in blood are associated with an increased risk and poor prognosis of cancer in humans. This study evaluates whether colorectal cancer patients have lower serum selenium and glutathione peroxidase levels than a gender-matched and age-matched control group and whether there is a correlation to clinical data and prognosis. METHODS: In a retrospective study, serum selenium and glutathione peroxidase activity of 106 patients with colorectal cancer were determined. Clinical data were provided by our long-term follow-up program for colorectal cancer patients. RESULTS: Patients with a selenium level <70 microg/l had a significantly lower mean survival time and a lower cumulative cancer-related survival rate than patients with a selenium level >70 microg/l (P = 0.0009). When considering the different tumor stages, a decline of the mean selenium level in the T4 carcinoma group was found in the analysis of variance (P < 0.05). The lowest selenium level was found for patients with advanced tumor disease and in a preoperative situation, ie., high tumor burden. In comparison with the control group, the cancer group showed a significant reduction of serum glutathione peroxidase activity (P < 0.01) but no significant difference in selenium level. CONCLUSIONS: These results support the hypothesis of an association between low selenium level and advanced tumor disease. From our data, it cannot be decided whether this phenomenon is more likely to be a consequence or a causative factor for development and course of the disease.

Flow-cytometric analysis of the DNA-content in paraffin-embedded tissue from colorectal carcinomas and its prognostic significance.

The nuclear DNA content of 163 colorectal carcinomas was determined by flow-cytometry (FCM) on formalin-fixed, paraffin-embedded tissue. DNA-aneuploidy was found in 97 cases (59.5%), in which no statistically significant correlations with sex, mean age, tumour stage (Dukes and pTNM) and tumour grade were noted. The frequency of aneuploidy was significantly higher in patients less than 70 years of age (p less than 0.01) and in tumours localized in the left colon and rectum (p less than 0.002), irrespective of their stage. The tumours in which different areas could be analysed (n = 80) showed a heterogeneous DNA-ploidy pattern in 18%. Comparison of the DNA content in primary tumours and in lymph node metastases (n = 49) showed a difference in DNA-ploidy in 38% of the DNA-aneuploid tumours, but in only 6% of the DNA-diploid carcinomas (p less than 0.02). DNA-aneuploid carcinomas tended to show a higher rate of local recurrence and were associated with an unfavourable prognosis (p = 0.04) in those patients in which complete resection of their tumours was possible (n = 72). The significantly higher mortality of patients with DNA-aneuploid carcinomas of stage pT3, as well as those with Dukes stage A and B tumours indicates that DNA-aneuploidy may be a stage-independent additional risk factor in colorectal cancer.

[Retrospective flow-cytometric analysis of the DNA content in colorectal carcinomas and the test of the prognostic significance of DNA ploidy]. / Retrospektive Durchflusszytophotometrische Untersuchung des DNS-Gehaltes kolorektaler Karzinome und Uberprüfung der prognostischen Bedeutung der DNS-Ploidie.

The nuclear DNA content of 163 colorectal carcinomas was determined by flow-cytometry (FCM) on formalin-fixed and paraffin-embedded tissue. DNA-aneuploidy was found in 97 cases (59.5%), without correlation to sex, mean age, tumor-stage (DUKES and pTNM) and grading. The frequency of aneuploidy was statistically significantly higher in patients younger than 70 years of age (p less than 0.01) and in tumors localized in the left colon and rectum (p less than 0.002). The tumors in which different areas could be analyzed (n = 80) showed a heterogeneous DNA-ploidy pattern in 18%. The comparison of DNA-content in primaries and in lymph-node metastases (n = 49) resulted in a difference of DNA-ploidy in 38% of the DNA-aneuploid tumors, but only in 6% of the DNA-diploid carcinomas (p less than 0.02). Carcinomas with DNA-aneuploidy showed a trend to a higher rate of loco-regional recurrences, a higher S-phase fraction (13.5% +/- 5.9 vs. 8.1 +/- 7.0), and proved to be associated with a poorer prognosis (p = 0.04). The statistically significantly higher mortality of patients with DNA-aneuploid carcinomas in DUKES A and B stages indicates that DNA-aneuploidy could perhaps be regarded as a stage-independent additional risk factor.

[Anastomotic recurrence following colorectal cancer]. / Anastomosenrezidiv nach kolorektalem Karzinom.

Reported in this paper are 22 patients with recurrence of anastomosis, following curative resection of colorectal carcinoma. Recurrence in all cases was diagnosed by colonoscopy. Seventy-five per cent of all patients under follow-up care were without symptoms, and 83 per cent underwent intended radical surgery to cope with their recurrence. Curative re-operations were followed by mean survival of 39.4 months, while the five year survival rate amounted to 44 per cent. Hence, the prognosis of recurrence at the suture line appeared to be better than that of colorectal carcinoma recurrences localised elsewhere.