Survival In Rectal Cancer Research Articles

Expression of carbonic anhydrase IX suggests poor outcome in rectal cancer

The aim of the study is to assess the value of carbonic anhydrase isozyme IX (CA IX) expression as a predictor of disease-free survival (DFS) and disease-specific survival (DSS) in rectal cancer treated by preoperative radio- or chemoradiotherapy or surgery only. Archival tumour samples from 166 patients were analysed for CA IX expression by three different evaluations: positive/negative, proportion of positivity and staining intensity. The results of immunohistochemical analysis were confirmed by demonstrating CA IX protein in western blotting analysis. Forty-four percent of the operative samples were CA IX positive, of these 34% had weak and 66% moderate/strong staining intensity. In univariate survival analysis, intensity of CA IX expression was a predictor of DFS (P=0.003) and DSS (P=0.034), both being markedly longer in tumours with negative or weakly positive staining. In multivariate Cox model, number of metastatic lymph nodes and CA IX intensity were the only independent predictors of DFS. Carbonic anhydrase isozyme IX intensity was the only independent predictor of DSS, with HR=9.2 for dying of disease with moderate-intense CA IX expression as compared with CA IX-negative/weak cases. Negative/weak CA IX staining intensity is an independent predictor of longer DFS and DSS in rectal cancer.

Phosphorylated Caveolin-1 Regulates Rho/ROCK-Dependent Focal Adhesion Dynamics and Tumor Cell Migration and Invasion

Rho/ROCK signaling and caveolin-1 (Cav1) are implicated in tumor cell migration and metastasis; however, the underlying molecular mechanisms remain poorly defined. Cav1 was found here to be an independent predictor of decreased survival in breast and rectal cancer and significantly associated with the presence of distant metastasis for colon cancer patients. Rho/ROCK signaling promotes tumor cell migration by regulating focal adhesion (FA) dynamics through tyrosine (Y14) phosphorylation of Cav1. Phosphorylated Cav1 is localized to protrusive domains of tumor cells and Cav1 tyrosine phosphorylation is dependent on Src kinase and Rho/ROCK signaling. Increased levels of phosphorylated Cav1 were associated with elevated GTP-RhoA levels in metastatic tumor cells of various tissue origins. Stable expression and knockdown studies of Cav1 in tumor cells showed that phosphorylated Cav1 expression stimulates Rho activation, stabilizes FAK association with FAs, and promotes cell migration and invasion in a ROCK-dependent and Src-dependent manner. Tyrosine-phosphorylated Cav1, therefore, functions as an effector of Rho/ROCK signaling in the regulation of FA turnover and, thereby, tumor cell migration and invasion. These studies define a feedback loop between Rho/ROCK, Src, and phosphorylated Cav1 in tumor cell protrusions, identifying a novel function for Cav1 in tumor metastasis that may contribute to the poor prognosis of some Cav1-expressing tumors.

The Metastatic Lymph Node Ratio (Lnr) Is a Powerful Predictor of Survival and Recurrence in Colon and Rectal Cancer

The Metastatic Lymph Node Ratio (Lnr) Is a Powerful Predictor of Survival and Recurrence in Colon and Rectal Cancer

Lymph node harvest and survival in rectal cancer

4048 Background: The NCCN recommends that at least 12 nodes be identified in a colon cancer specimen to ensure adequate staging. This standard is applied to rectal cancer despite anatomic and treatment differences. The factors that predict adequate nodal harvest and the relationship between harvest and survival in rectal cancer patients, with or without preop xrt are unknown. Methods: We performed a retrospective cohort study of 8,580 patients with stage I-III rectal cancer undergoing proctectomy from 1996–2004 using SEER-Medicare. Multivariate logistic regression was performed to identify patient and hospital variables associated with adequate LN harvest. Kaplan-Meier curves and Cox regression compared survival among patients who had ≥12, 1–11, or no nodes harvested, adjusting for patient and hospital characteristics. Results: 28% of patients had ≥12 nodes and 14% had no nodes harvested. Patients who were older, had more comorbidities or underwent preop XRT or emergent surgery were less likely to have ≥12 nodes harvested. High surgical volume and teaching status were positively associated with having ≥12 nodes harvested. Median survival by nodal harvest by stage and treatment are shown in table 1. After multivariate adjustment, node status remained significantly associated with mortality (p<0.001). Compared to patients with no nodes harvested, patients with 1–11 nodes were 27% (HR 0.73) and patients with ≥12 nodes 40% (HR 0.63) less likely to die. The effect of node harvest varied by stage and treatment, with the weakest association with survival in patients with stage III disease and stage I patients who received preop XRT or postop therapy. Conclusion: Nodal harvest is associated with survival following proctectomy for rectal cancer, primarily in Stage I and II patients. Further research is needed to understand the contribution of treatment and quality measures to this finding and to determine whether number of nodes is an appropriate quality measure for patients who undergo preop XRT. Median Survival (Years) # Nodes Surgery Only Preop XRT, Surgery Surgery, Postop Tx I II III I II III I II III 0 5.9 1.4 5.1 3.9 4.4 3.3 1–11 7.6 3.6 1.8 7.7 5.4 3.4 6.0 6.1 4.9 ≥12 9.3 4.8 2.1 6.3 7.2 3.1 6.1 8.4 4.9 P-value <.001 <.001 .08 .02 .005 .49 .04 <.001 .78 No significant financial relationships to disclose.

Comparison of rectal and colon cancer outcomes: A population based analysis

4040 Background: Rectal cancer has previously been associated with inferior five year survival in comparison to colon cancer. Total mesorectal excision (TME) and adjuvant therapy have reduced locoregional recurrence and, in some studies, improved rectal cancer survival. Therapy and outcomes of colon and rectal cancer were compared among 3 patient cohorts referred to the British Columbia Cancer Agency (BCCA) between 1990 and 2002. Methods: Patients with resected, pathological stage II or III colorectal cancer referred to BCCA in 1990, 1995/96, and 2001/02 were included. For those patients receiving long-course preoperative radiation, the higher of clinical or pathological stage was used. Kaplan Meier method was used for survival analysis. Results: 1,851 patients were included with a median age range of 64–69 and follow up time of 15.7 [1990], 10.8 [1995/96] and 5.3 [2001/02] years. Between 1990 and 2001/02 the use of adjuvant chemotherapy increased significantly for rectal cancer from 14.7% to 68.5% (p<0.001) and for colon cancer from 32.9% to 54% (p<0.001). The use of preoperative radiation therapy (RT) (p<0.001) and total mesorectal excision (TME) (p<0.001) in rectal cancer also significantly increased. 5 year overall survival (OS) was numerically inferior for rectal compared to colon cancer in 1990 and similar to colon cancer in the later cohorts (Table). The analysis was limited by small sample size and an expanded cohort will be presented. 5 year OS significantly improved for both rectal (p<0.001) and colon cancer (p=0.025) between 1990 and 2001/02. Conclusions: In this population based study, 5 year OS for stage II/III rectal and colon cancer significantly improved between 1990 and 2001/02, with similar outcomes now apparent for both sites. With respect to rectal cancer, improved outcomes are likely related to increased use of TME technique, preoperative RT and adjuvant chemotherapy. Improved outcomes for colon cancer likely reflect increased use of adjuvant chemotherapy. 5 year overall survival for colon and rectal cancer Year N 5 Y Overall Survival (%) Rectal Cancer 5 Y Overall Survival (%) Colon Cancer P-Value 1990 236 43.8 [34.9, 54.9] 53.7 [46.0, 62.7] 0.0969 Stage II 83 55.2 [39.7, 76.6] 63.6 [51.8, 78.2] 0.3954 Stage III 153 38.8 [28.7, 52.4] 47.7 [38.2, 59.5] 0.2088 1995–96 563 59.3 [53.1, 66.3] 61.7 [56.7, 67.2] 0.5607 Stage II 233 68 [58.3, 79.2] 72.3 [65.3, 80] 0.4675 Stage III 330 54.4 [46.6, 63.4] 53.5 [46.8, 61.2] 0.8654 2001–02 1052 63.7 [58.5, 69.4] 66.2 [62.4, 70.1] 0.4543 Stage II 430 70.6 [63.1, 78.9] 77.1 [71.9, 82.7] 0.158 Stage III 622 58.4 [51.4, 66.4] 59.1 [54.2, 64.4] 0.8818 No significant financial relationships to disclose.

Misclassification of colorectal cancer stage and area variation in survival

We previously investigated the impact of health area of residence on colon and rectal cancer survival by estimating area-specific relative excess risk of death (RER), stratified by stage at diagnosis. The aims of this study were to quantify errors in colorectal cancer stage obtained from an Australian population-based cancer registry and assess the potential impact of errors in stage on these estimates. For a subset of cases, we compared the cancer registry stage with that from a survey of treating surgeons. We then randomly reallocated all cases to a simulated "corrected" stage according to the estimated misclassification probabilities and repeated the analysis of area variation stratified by simulated stage 1,000 times. We found 70% agreement between the Registry and Survey stage. This reallocation of the Registry cases by stage resulted in substantial variation in area-specific RERs across the simulated samples. Area variation in survival for localized colon and localized rectal cancer, which were previously statistically significant when classified using Registry stage, appeared no longer to be so. Misclassification of cancer registry stage can have an important impact on estimates of spatial variation in stage-specific colon and rectal cancer survival. If population-based cancer registry data are to be effectively used in evaluating and improving cancer care, the quality of the stage data may need to be improved.

Survival and treatment trends of rectal cancer patients in a population with suboptimal local control

Aim To explore trends in rectal cancer survival in Manitoba, particularly in patients where local control was an issue. Method Patients diagnosed with rectal or rectosigmoid adenocarcinoma from 1985 to 1999 were included. Demographic, treatment and mortality information were abstracted from the registry. Relative survival was examined for all patients for the periods 1985–1989, 1990–1994 and 1995–1999, and subsequently limited to those who underwent major surgery (Hartmann's, anterior, and abdominal perineal resection). Results Of the 2925 patients identified, 2163 (74%) had undergone a major surgery. Five-year relative survival was 46%, 54% and 53% for all patients for the three periods, respectively; major surgery results were 53%, 59% and 60%. Radiotherapy was used in 32% of cases in 1985–1989 and in 40% of cases in 1995–1999. Chemotherapy was used in 13% of cases in 1985–1989 and in 37% of cases in 1995–1999. Conclusion Consistent with other studies, overall rectal cancer survival in Manitoba has improved since 1985. Better local control, as suggested in other studies, does not appear to be a major factor in that improvement. Future work should include review of the local control strategy in Manitoba and factors to explain the improved survival.

A prospective randomized study with a 5-year minimum follow-up evaluation of transanal endoscopic microsurgery versus laparoscopic total mesorectal excision after neoadjuvant therapy

This study aimed to compare the oncologic results for local excision via transanal endoscopic microsurgery (TEM) and those for laparoscopic resection (LR) via total mesorectal excision in the treatment of T(2) N(0), G(1-2 )rectal cancer after neoadjuvant therapy with both treatments, incorporating a 5-year minimum follow-up period. The study enrolled 70 patients whose malignancy was staged at admission as T(2) N(0), G(1-2 )rectal cancer located within 6 cm of the anal verge with a tumor diameter less than 3 cm. Of these patients, 35 were randomized to TEM and 35 to LR. The patients in both groups previously had undergone high-dose radiotherapy (5,040 cGy in 28 fractions over 5 weeks) combined with continuous infusion of 5-flurouracil (200 mg/m(2)/day). The median follow-up period was 84 months (range, 72-96 months). Two local recurrences (5.7%) were observed after TEM and 1 (2.8%) after LR. Distant metastases (2.8%) occurred in one case each after TEM and LR. The probability of survival for rectal cancer was 94% for TEM and 94% for LR. The study shows similar results between the two treatments in terms of local recurrences, distant metastases, and probability of survival for rectal cancer.

Association of demographic and treatment variables in longterm rectal cancer survival

Association of demographic and treatment variables in longterm rectal cancer survival

Retroperitoneal margin involvement by adenocarcinoma of the caecum and ascending colon: what does it mean?

Circumferential margin involvement (CRM) is a powerful predictor of local recurrence, distant metastasis and patient survival in rectal cancer. In this study, we aimed to determine the frequency of retroperitoneal margin involvement in right colon cancer and describe its relationship to tumour stage and outcome of surgical treatment. Two hundred and twenty-eight consecutive resections for adenocarcinoma of the ascending colon and caecum were identified between 1998 and 2006. Tumour involvement of the posterior retroperitoneal surgical resection margin (RSRM) was recorded and correlated with tumour stage, grade and clinical outcome. RSRM positive patients were compared with CRM positive rectal tumours resected in the same surgical unit. Nineteen of 228 right hemicolectomies (8.4%) showed tumour involvement of the RSRM (defined as < or = 1 mm). Approximately half of the RSRM positive patients underwent palliative resections because of synchronous distant metastases. Out of nine 'potentially curative' resections where the RSRM was involved, five patients subsequently developed metastatic recurrence and two isolated local recurrence. RSRM positivity was associated with advanced tumour stage and more extensive extramural spread than CRM positive rectal cancers. Retroperitoneal surgical resection margin involvement by caecal and ascending colon carcinoma is a marker of advanced tumour stage and associated with a high incidence of synchronous and metachronous distant metastasis. More aggressive surgery to obtain a clear margin or postoperative radiotherapy to the tumour bed is likely to benefit only a minority of patients.

Ratio of metastatic to examined lymph nodes is a powerful predictor of overall survival in rectal cancer: An analysis of Intergroup 0114

4006 Background: Lymph node (LN) metastasis is associated with decreased survival in rectal cancer. It has been suggested that at least 14 LN be evaluated for adequate staging. However, a large percentage of patients have fewer than the recommended number of LN examined. We hypothesized that LN ratio would be predictive of overall survival in rectal cancer. Methods: Data was analyzed from Intergroup 0114, a mature trial of postoperative adjuvant chemotherapy and radiation in T3/4 and/or LN positive rectal cancer. Survival was the same for all arms allowing the entire group to be considered as one. The primary endpoint evaluated was overall survival. A proportional hazards model was used to determine the relative prognostic impact of LN ratio compared to number of LN examined, number of positive LN, number of negative LN and AJCC nodal stage. LN ratio was defined as the number of positive LN divided by the total number of LN examined. Four groups were analyzed based on proportion of positive LN: =0.25, &gt;0.25–0.50, &gt;0.50–0.75 and &gt;0.75. Results: 1,648 patients were evaluable. There were 251 T1/2, 1,251 T3 and 146 T4 tumors. 513 patients were N0, 743 N1 and 392 N2. Median number of LN was 9. LN ratio was predictive of 5-year overall survival with rates of 0.71, 0.56, 0.50 and 0.43 respectively when analyzed by quartile (p&lt;0.0001). LN ratio remained significant when overall survival was analyzed by number of LN examined and grouped into &lt;10, &lt;15 and &gt;15 nodes evaluated (p&lt;0.0001 for all). LN ratio also predicted overall survival in N1 (p=0.04) and N2 (p=0.0002) disease. When comparing LN ratio (χ2=79.5, p&lt;0.0001) to number of LN examined (χ2=4.7, p=0.03), number of positive LN (χ2=38, p&lt;0.0001), number of negative LN (χ2=32, p&lt;0.0001) and AJCC nodal stage (χ2=55.5, p&lt;0.0001), LN ratio appears to be the strongest predictor of overall survival. Conclusion: LN ratio predicts overall survival in patients with resected rectal cancer. Importantly, this is true in patients who have had a small number of LN evaluated, in addition to those with a large number of LN examined. LN ratio also appears to be a stronger predictor of overall survival than other described LN prognostic factors. LN ratio may be a useful variable to stratify outcome in patients with node-positive rectal cancer. No significant financial relationships to disclose.

Quality of life after transanal endoscopic microsurgery and total mesorectal excision in early rectal cancer

Total mesorectal excision (TME) is the gold standard in rectal cancer, if curation is intended. Transanal endoscopic microsurgery (TEM) is a much safer technique and seems to have comparable survival in early rectal cancer. The impact of both procedures on quality of life has never been compared. In this study we compared quality of life after TEM and TME. Fifty-four patients underwent TEM for a T1 carcinoma. Only patients without known locoregional or distant recurrences were included, resulting in 36 eligible patients in whom quality of life after TEM was studied. The questionnaires used included the EuroQol EQ-5D, EQ-VAS, EORTC QLQ-C30 and EORTC QLQ-CR38. The results were compared with a sex-and age-matched sample of T+N0 rectal cancer patients who had undergone sphincter saving surgery by TME and a sex- and age matched community-based sample of healthy persons. Thirty-one patients after TEM returned completed questionnaires (overall response rate 86%). Quality of life was compared with 31 TME patients and 31 healthy controls. From the patients' and social perspective quality of life did not differ between the three groups. Compared with TEM, significant defecation problems were seen after TME (P < 0.05). A trend towards better sexual functioning after TEM, compared with TME, was seen, especially in male patients, although it did not reach statistical significance. Transanal endoscopic microsurgery and TME do not seem to differ in quality of life postoperatively, but defecation disorders are more frequently encountered after TME. This difference could play a role in the choice of surgical therapy in (early) rectal cancer. Further prospective studies are needed to confirm our conclusions.

A 30-Year Analysis of Colorectal Adenocarcinoma in Transplant Recipients and Proposal for Altered Screening

PurposeThe risk of malignancy after solid-organ transplantation is well documented. However, the incidence and specific risk for colorectal adenocarcinoma, although previously proposed, has been difficult to calculate. We reviewed the University of Wisconsin transplant database for all cases of colorectal adenocarcinoma to assess the risk of this malignancy, as well as the need for improved screening in this population. MethodsThe transplant database was queried using diagnosis codes for colorectal adenocarcinoma to configure a list of eligible patients. Exclusion criteria included: age less than 18 years at the time of transplant, diagnosis of colorectal cancer or patient death less than 12 months posttransplant, and pretransplant history of colorectal cancer or proctocolectomy. Statistical analysis determined overall incidence, age-specific incidence, and survival for this population. ResultsA total of 5,603 kidney, liver, or combination transplants were eligible for analysis from 1966 through 2004. The mean follow-up was 9.3 years. We identified 40 cases of colorectal adenocarcinoma. Twenty-five of these cases (62%) occurred in kidney transplant recipients, 13 after liver transplant, and two after kidney–pancreas combination. Twenty-seven patients (68%) diagnosed with cancer have died, 12 of metastatic disease. The median survival postcancer diagnosis was 2.3 years. These results were compared to the National Cancer Institute Survival, Epidemiology, and End Results (SEER) database for colon and rectal cancer. The current age-adjusted annual incidence based on year 2000 census data is 0.053% (52.9/100,000), and the extrapolated 10-year incidence is 0.27%. The 10-year incidence in the transplanted cohort is 0.71% (incidence ratio = 2.6). The 5-year survival postcancer diagnosis is 63.5% in the general population (SEER), vs. 30.7% in the transplant cohort. The SEER median age at diagnosis of colorectal adenocarcinoma is 72.0 years. Of the transplant recipients who developed cancer, the median age at diagnosis was 58.7 years (32.4 to 78.2), and 11 patients (27%) were diagnosed at or before age 50. In the U.S. population, the annual incidence of colorectal adenocarcinoma below the age of 50 is 0.0055% (5.52/100,000) and the 10-year extrapolated incidence is 0.11%. The 10-year incidence in the under-50 transplant cohort is 0.33% (incidence ratio = 3.0). In this under-50 cohort, median time from transplant to cancer diagnosis was 7.8 years. ConclusionThe incidence of and 5-year survival after diagnosis of colorectal adenocarcinoma in transplant recipients is markedly different than the general population. Patients are often diagnosed at a younger age. With current screening guidelines, over 25% of at-risk patients would not be screened. We propose modifying these guidelines to allow earlier detection of colorectal cancer in this population.

Telomerase Activity is a Prognostic Factor for Recurrence and Survival in Rectal Cancer

This study was designed to determine whether telomerase activity measured in samples of tumoral tissue, transitional mucosa, and normal mucosa from patients with sporadic colorectal cancer is a prognostic factor for recurrence and overall survival. Telomerase activity was determined by fluorescence-based telomeric repeat amplification in tissue samples from 108 patients with sporadic colorectal cancer. A telomerase index was determined by using the formula log (telomerase activity of cancer tissue - telomerase activity of normal mucosa). Mean telomerase activity in tumoral tissue was 11.49 (total product generated), in transitional mucosa it was 1.51, and in normal mucosa it was 1.09 (P < 0.001). Telomerase activity and telomerase index were not correlated with clinicopathologic factors. Rectal cancer patients' recurrence-free survival was related to N classification (P = 0.004) and to tumor-node-metastases stage classification (P = 0.023) and telomerase index 0.85 (P = 0.023). Overall survival was associated with N classification (positive/negative) and telomerase index (</=0.85 or >0.85; P = 0.018 and P = 0.011, respectively). Measurement of telomerase activity has a diagnostic value in colorectal patients. In rectal cancer, telomerase index is an independent prognostic factor for disease progression. A telomerase index</=0.85 and negative nodes can be used to predict disease progression.

Long-term Result for Rectal Cancer in Cases of a Curative Resection after Preoperative Chemoradiotherapy

Purpose: Preoperative chemoradiation is the recommended standard therapy for locally advanced rectal cancer and is associated with sphincter preservation and improved survival. Our study was performed to determine the surgical outcomes and the prognostic factors for rectal cancer with preoperative chemoradiotherapy (PCRT) followed by a relative curative resection. Methods: We retrospectively reviewed the cases of 251 advanced rectal cancer patients who underwent a PCRT, between Jan 1995 and Dec 2002. All patients a received 25 days RTX (total dose: 4,500∼5,040 cGy) and intravenous 5-FU (425 mg/m2/ day) plus leucovorin (20 mg/day) for 24 hrs. Surgery was performed about 4∼6 weeks after completion of RTX. The median follow up was 79 months (range 1-142). Results: All patients were comfortable with PCRT. Postoperative mortality was 1.1%. After PCRT, 92.2% of the patients and, especially, 82.2% of the low rectal cancer patients had sphincter preserving surgery. Complete remission of the tumor was stenin 15.1% of the cases, but was not significantly associated with recurrence. The overall recurrence and the local recurrence rates were 15.1% and 4.4%, respectively. Cell differentiation, circumferential margin, and lymphovascular invasion were independent risk factors for local recurrence in the multivariate analysis. Prognostic factors for overall and disease-free survival were cell differentiation, circumferential margin, lymphovascular invasion, and lymph node metastasis in the multivariate analysis. The 5-year disease-free survival rates for stages I, II, and III, and for no-residual tumor were 96.1%, 83.4%, 69.0%, and 89.1%, respectively (P＜0.05). Conclusions: Advanced rectal cancer treated using preoperative chemoradiation resulted in excellent sphincter preservation. Our long-term follow-up results showed good local control and improved survival for rectal cancer.

370 POSTER Risk factors for non radical resection, local recurrence, disease free survival and overall survival for rectal cancer in EORTC 22921 trial

370 POSTER Risk factors for non radical resection, local recurrence, disease free survival and overall survival for rectal cancer in EORTC 22921 trial

Total pelvic exenteration for primary locally advanced and locally recurrent rectal cancer

Aims To report the role of total pelvic exenteration in a series of locally advanced and recurrent rectal cancers. Methods In the period 1994–2004, TPE was performed in 35 of 296 patients with primary locally advanced and recurrent rectal cancer treated in the Daniel den Hoed Cancer Center; 23 of 176 with primary locally advanced and 12 of 120 with recurrent rectal cancer. All but one patient received pre-operative External Beam Radiation Therapy (EBRT). After 1997, Intra Operative Radiotherapy (IORT) was performed in case of a resection margin less than 2 mm. Results Overall major complication rates were not significantly different between patients with primary and recurrent rectal cancer (26% vs. 50%, p = 0.94). The hospital mortality rate was 3%. The 5-year local control and overall survival of patients with primary locally advanced rectal cancer were 88% and 52%, respectively. In patients with recurrent rectal cancer 3-year local control and survival rates were 60% and 32%, respectively. An incomplete resection, preoperative pain and advanced Wanebo stage for recurrent cancer were negative prognostic factors for both local control and overall survival. Conclusion TPE in primary locally advanced rectal cancer enables good local control and acceptable overall survival, thereby justifying the use of the procedure. Patients with recurrent rectal cancer showed a high rate of major complications, a high distant metastasis rate, and a poor overall survival.

Late adverse effects of short-course preoperative radiotherapy in rectal cancer

Preoperative radiotherapy improves local control and survival in rectal cancer, but there are few reports on long-term morbidity. The aims of this study were to compare long-term morbidity and quality of life in patients undergoing rectal cancer surgery with or without preoperative radiotherapy. A total of 252 patients, randomized within the two Stockholm trials on preoperative radiotherapy in rectal cancer, were alive at a mean of 15 years after surgery. Some 139 of these patients were available for follow-up by questionnaires and clinical examination. Questionnaires regarding medical history and quality of life were completed by all patients. All patients had a clinical examination, and those without a stoma underwent rigid sigmoidoscopy. Overall, patients who had preoperative radiotherapy experienced significantly more late complications than those who did not (69 versus 43 per cent; P = 0.002). This morbidity consisted mainly of cardiovascular disease (35 versus 19 per cent; P = 0.032), faecal incontinence (12 of 21 versus 11 of 42 patients having anterior resection; P = 0.013) and urinary incontinence (45 versus 27 per cent; P = 0.023). No significant differences between groups were found for hip or pelvic fractures, small bowel obstruction or global quality of life. Preoperative short-course, high-dose radiotherapy in patients with rectal cancer increases the risk of anal and urinary dysfunction, and may lead to increased cardiovascular morbidity, at long-term follow-up.

Long-term results of intraoperative presacral electron boost radiotherapy (IOERT) in combination with total mesorectal excision (TME) and chemoradiation in patients with locally advanced rectal cancer

We analyzed the long-term results of patients with locally advanced rectal cancer using a multimodal approach consisting of total mesorectal excision (TME), intraoperative electron-beam radiation therapy (IOERT), and pre- or postoperative chemoradiation (CRT). Between 1991 and 2003, 210 patients with locally advanced rectal cancer (65 International Union Against Cancer [UICC] Stage II, 116 UICC Stage III, and 29 UICC Stage IV cancers) were treated with TME, IOERT, and preoperative or postoperative CHT. A total of 122 patients were treated postoperatively; 88 patients preoperatively. Preoperative or postoperative fluoropyrimidine-based CRT was applied in 93% of these patients. Median age was 61 years (range, 26-81). Median follow-up was 61 months. The 5-year actuarial overall survival (OS), disease-free survival (DFS), local control rate (LC), and distant relapse free survival (DRS) of all patients was 69%, 66%, 93%, and 67%, respectively. Multivariate analysis revealed that UICC stage and resection status were the most important independent prognostic factors for OS, DFS, and DRS. The resection status was the only significant factor for local control. T-stage, tumor localization, type of resection, and type of chemotherapy had no significant impact on OS, DFS, DRS, and LC. Acute and late complications > or =Grade 3 were seen in 17% and 13% of patients, respectively. Multimodality treatment with TME and IOERT boost in combination with moderate dose pre- or postoperative CRT is feasible and results in excellent long-term local control rates in patients with intermediate to high-risk locally advanced rectal cancer.

Predictive poor prognostic factors in colonic carcinoma

Five-year survival in rectal cancer has been steadily improving since the introduction of neoadjuvant chemoradiation and total mesorectal excision surgery. In contrast, 5-year survival rates and management of colonic carcinoma remain relatively unchanged. This study aims to identify poor prognostic factors in colonic cancer patients that could potentially be predicted pre-operatively to identify a subset of patients amenable to neoadjuvant treatment strategies. Database compilation of all operable rectal and colonic cancer patients presenting to a single district general hospital over 5 years. Data were documented on presentation and site of tumour, TNM staging, differentiation and extramural venous invasion. There was no significant difference in 4-year survival between rectal (57.5%) and right (57%) or left sided (52.5%) colonic cancers (p=0.4689). On multivariate analysis, N2-stage, T4-stage and emergency presentation were identified as independent prognostic factors. On univariate analysis, in addition to the above factors, presence of venous invasion (p=0.001) and poor differentiation (p=0.0003) of tumour also predicted for poor 5-year survival. T4-stage and N2-stage and extramural venous invasion are poor prognostic factors that could be identified pre-operatively with suitably accurate imaging. Such patients could then be considered for a pre-operative treatment strategy.