W. H. Steup

Late Side Effects of Short-Course Preoperative Radiotherapy Combined With Total Mesorectal Excision for Rectal Cancer: Increased Bowel Dysfunction in Irradiated Patients—A Dutch Colorectal Cancer Group Study

PURPOSE Preoperative short-term radiotherapy improves local control in patients treated with total mesorectal excision (TME). This study was performed to assess the presence and magnitude of long-term side effects of preoperative 5 x 5 Gy radiotherapy and TME. Also, hospital treatment was recorded for diseases possibly related to late side effects of rectal cancer treatment. PATIENTS AND METHODS Long-term morbidity was assessed in patients from the prospective randomized TME trial, which investigated the efficacy of 5 x 5 Gy before TME surgery for mobile rectal cancer. Dutch patients without recurrent disease were sent a questionnaire. RESULTS Results were obtained from 597 patients, with a median follow-up of 5.1 years. Stoma function, urinary function, and hospital treatment rates did not differ significantly between the treatment arms. However, irradiated patients, compared with nonirradiated patients, reported increased rates of fecal incontinence (62% v 38%, respectively; P < .001), pad wearing as a result of incontinence (56% v 33%, respectively; P < .001), anal blood loss (11% v 3%, respectively; P = .004), and mucus loss (27% v 15%, respectively; P = .005). Satisfaction with bowel function was significantly lower and the impact of bowel dysfunction on daily activities was greater in irradiated patients compared with patients who underwent TME alone. CONCLUSION Although preoperative short-term radiotherapy for rectal cancer results in increased local control, there is more long-term bowel dysfunction in irradiated patients than in patients who undergo TME alone. Rectal cancer patients should be informed on late morbidity of both radiotherapy and TME. Future strategies should be aimed at selecting patients for radiotherapy who are at high risk for local failure.

Risk factors for anastomotic failure after total mesorectal excision of rectal cancer

Anastomotic leakage is a major complication of rectal cancer surgery. The aim of this study was to investigate risk factors associated with symptomatic anastomotic leakage after total mesorectal excision (TME).

Acute Side Effects and Complications After Short-Term Preoperative Radiotherapy Combined With Total Mesorectal Excision in Primary Rectal Cancer: Report of a Multicenter Randomized Trial

PURPOSE Total mesorectal excision (TME) surgery in the treatment of rectal cancer has been shown to result in a reduction in the number of local recurrences in retrospective studies. Reports on improved local control after preoperative, hypofractionated radiotherapy (RT) have led to the introduction of a prospective randomized multicenter trial, in which the effect of TME surgery with or without preoperative RT were evaluated. Any benefit in regard to a reduced local recurrence rate and possible improved survival must be weighed against potential adverse effects in both the short-term and the long-term. The present study was undertaken to assess the acute side effects of short-term, preoperative RT in rectal cancer patients and to study the influence of five doses of 5 Gy on surgical parameters, postoperative morbidity and mortality in patients randomized in the Dutch TME trial. PATIENTS AND METHODS We analyzed 1,530 Dutch patients entered onto a prospective randomized trial, comparing preoperative RT with five doses of 5 Gy followed by TME surgery with TME surgery alone, of which 1,414 patients were assessable. Toxicity from RT, surgery characteristics, and postoperative complications and mortality were compared. RESULTS Toxicity during RT hardly occurred. Irradiated patients had 100 mL more blood loss during the operation (P <.001) and showed more perineal complications (P =.008) in cases of abdominoperineal resection. The total number of complications was slightly increased in the irradiated group (P =.008). No difference was observed in postoperative mortality (4.0% v 3.3%) or in the number of reinterventions. CONCLUSION Preoperative hypofractionated RT is a safe procedure in patients treated with TME surgery, despite a slight increase in complications when compared with TME surgery only.

Total mesorectal excision (TME) with or without preoperative radiotherapy in the treatment of primary rectal cancer: Prospective randomised trial with standard operative and histopathological techniques

OBJECTIVE To document local recurrence in primary rectal cancer when standardised techniques of surgery, radiotherapy, and pathology are used, and to investigate whether the local recurrence rate after total mesorectal excision permits the omission of adjuvant short term preoperative radiotherapy. DESIGN Prospective randomised study. SETTING Dutch (n = 80), English (n = 1), German (n = 1), Swedish (n = 9), and Swiss (n = 1) hospitals. SUBJECTS The first 500 randomised Dutch patients with primary rectal cancer. MAIN OUTCOME MEASURES Local recurrence, survival, operation-related factors, specific pathological tumour characteristics, short and long term morbidity, and quality of life. RESULTS Between January 1996 and April 1998, 871 Dutch and 94 other patients were randomised. Our feasibility analysis shows that cooperation between and within the participating disciplines goes well. With regard to the surgical part, this can be confirmed by the large number of operations attended by consultant surgeons (58%). The number of abdominoperineal resections appeared to be low (30%), as did the percentage of lateral margins involved (13%). The rate of adverse effects of radiotherapy was acceptable. Apart from a larger operative blood loss and a higher infective complication rate in the irradiated group, no significant differences were found with regard to morbidity and mortality between the randomised groups. CONCLUSIONS The accrual of our trial is going well and it is feasible; short term preoperative radiotherapy is safe even in combination with TME.

Total mesorectal excision (TME) with or without preoperative radiotherapy in the treatment of primary rectal cancer. Prostpective randomsied trial with standard operative and histopathological techniques. Dutch Colorectal Cancer Group.

OBJECTIVE To document local recurrence in primary rectal cancer when standardised techniques of surgery, radiotherapy, and pathology are used, and to investigate whether the local recurrence rate after total mesorectal excision permits the omission of adjuvant short term preoperative radiotherapy. DESIGN Prospective randomised study. SETTING Dutch (n = 80), English (n = 1), German (n = 1), Swedish (n = 9), and Swiss (n = 1) hospitals. SUBJECTS The first 500 randomised Dutch patients with primary rectal cancer. MAIN OUTCOME MEASURES Local recurrence, survival, operation-related factors, specific pathological tumour characteristics, short and long term morbidity, and quality of life. RESULTS Between January 1996 and April 1998, 871 Dutch and 94 other patients were randomised. Our feasibility analysis shows that cooperation between and within the participating disciplines goes well. With regard to the surgical part, this can be confirmed by the large number of operations attended by consultant surgeons (58%). The number of abdominoperineal resections appeared to be low (30%), as did the percentage of lateral margins involved (13%). The rate of adverse effects of radiotherapy was acceptable. Apart from a larger operative blood loss and a higher infective complication rate in the irradiated group, no significant differences were found with regard to morbidity and mortality between the randomised groups. CONCLUSIONS The accrual of our trial is going well and it is feasible; short term preoperative radiotherapy is safe even in combination with TME.

Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial

BACKGROUND The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME). PATIENTS AND METHODS The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival. RESULTS Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39). CONCLUSION The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual. REGISTRATION NUMBER Dutch Colorectal Cancer group, CKTO 2003-16, ISRCTN36266738.

Total mesorectal excision (TME) with or without preoperative radiotherapy in the treatment of primary rectal cancer

OBJECTIVE To document local recurrence in primary rectal cancer when standardised techniques of surgery, radiotherapy, and pathology are used, and to investigate whether the local recurrence rate after total mesorectal excision permits the omission of adjuvant short term preoperative radiotherapy. DESIGN Prospective randomised study. SETTING Dutch (n = 80), English (n = 1), German (n = 1), Swedish (n = 9), and Swiss (n = 1) hospitals. SUBJECTS The first 500 randomised Dutch patients with primary rectal cancer. MAIN OUTCOME MEASURES Local recurrence, survival, operation-related factors, specific pathological tumour characteristics, short and long term morbidity, and quality of life. RESULTS Between January 1996 and April 1998, 871 Dutch and 94 other patients were randomised. Our feasibility analysis shows that cooperation between and within the participating disciplines goes well. With regard to the surgical part, this can be confirmed by the large number of operations attended by consultant surgeons (58%). The number of abdominoperineal resections appeared to be low (30%), as did the percentage of lateral margins involved (13%). The rate of adverse effects of radiotherapy was acceptable. Apart from a larger operative blood loss and a higher infective complication rate in the irradiated group, no significant differences were found with regard to morbidity and mortality between the randomised groups. CONCLUSIONS The accrual of our trial is going well and it is feasible; short term preoperative radiotherapy is safe even in combination with TME.

Patterns of lymphatic spread in rectal cancer. A topographical analysis on lymph node metastases

The presence of lymph node (LN) metastases is the most important prognostic factor in rectal cancer. The exact LN status can only be known when an extended lymph node dissection (LND) has been performed, a process not routinely performed. If the likelihood of LN metastases can be more accurately assessed preoperatively, then an optimal multimodality treatment plan can be established. 605 patients with primary rectal cancer operated upon with wide LND (D3 level) were analysed for LN metastases combining topographical localisation and morphological features of the tumour. More distal rectal tumours tend to more LN metastases and more lateral lymphatic spread. Tumours >or=3 cm show more LN metastases compared with those smaller than 3 cm. Depth of bowel wall invasion is strongly related to the presence of LN metastases. The peritoneal reflection has no discriminating role in the mode of spread. Intra-operative assessment by the surgeon for presence of LN metastases is not reliable. When localisation, depth of bowel wall invasion and diameter of a rectal tumour are known, a likelihood of LN metastases can be assessed pre-operatively, not intra-operatively.

Improved diagnosis and treatment of anastomotic leakage after colorectal surgery.

AIM This study aimed at testing feasibility of a standardised postoperative surveillance protocol to reduce delay in the diagnosis of anastomotic leakage (AL) and, subsequently, mortality. MATERIAL AND METHODS Patient files of patients operated between 1996 and 1999 were reviewed and used as historical controls (n=1066). As a result, a protocol for standardised post-operative surveillance was designed using easily accessible, clinical parameters. Between August 2004 and August 2006, all operated patients with a colorectal anastomosis (n=223) were prospectively subjected to this standardised surveillance. RESULTS AL was diagnosed in 7.0% of patients in the historical control group and 9.4% of patients in the standardised surveillance group. AL mortality decreased from 39% to 24% with standardised surveillance (n.s.). The delay in AL diagnosis was significantly reduced during standardised surveillance (4 versus 1.5 days, p=0.01), which was confirmed in the multivariate analysis. CONCLUSION With non-standardised postoperative monitoring, AL was associated with a high mortality rate. Patients were subjected to several additional tests, which were not primarily useful to diagnose AL. Standardised postoperative surveillance for AL was introduced successfully and resulted in a shorter delay between the first signs and symptoms to the confirmation of AL.

Influence of abdominal-wound closure technique on complications after surgery: a randomised study

BACKGROUND Wound complications that occur after closure of midline laparotomy remain challenging. A new continuous double-loop closure (CDLC) technique was developed to avoid wound rupture through resistance to high intra-abdominal pressure and continued approximation of wound edges. We investigated the efficacy of this technique. METHODS We randomly assigned 390 patients undergoing midline laparotomy-wound closure with the commonly used continuous running suture (CRS) technique (n=204) or with the CDLC technique (n=186). We assessed the influence of closure technique on the rate of wound and other complications, with emphasis on wound dehiscence, pulmonary complications, and death. FINDINGS The rate of wound complications did not differ significantly between groups. Pulmonary complications were seen in 11 patients (5.4%) in the CRS group, and in 32 patients (17.2%) in the CDLC group (p=0.0002). In the CRS group, 17 (8.3%) patients died, compared with 39 (21.0%) patients in the CDLC group (p=0.0004). INTERPRETATION The CDLC technique should not be used. The lessened compliance of the abdominal wall, which raises intra-abdominal pressure for long periods, may increase the risk of postoperative pulmonary complications and death. The ideal closure technique should combine strength to prevent wound rupture with elasticity to adapt to increased intra-abdominal pressure.