Result of the implementation of multidisciplinary teams in rectal cancer.

AIM: In 2003 colorectal multidisciplinary teams (MDTs) were established in all major Danish hospitals treating colorectal cancer. The aim was to improve the prognosis by multidisciplinary evaluation and decision about surgical and oncological treatment, based on medical history, clinical examination, imaging, histology and comorbidity. The present study evaluates the effect of the introduction of colorectal MDTs on 1 August 2004 in two Danish hospitals. METHOD: A retrospective cohort study was conducted comparing the outcome during the last 3 years before introduction of MDTs with the first 2 years after (the MDT cohort). The national colorectal cancer database, with follow-up recorded by the National Patient Registry in September 2010 was used. The end-points included the incidence of preoperative radiochemotherapy offered according to the national guidelines, R0/R1/R2 resection, postoperative mortality, local recurrence, distant recurrence and over-all and disease-free survival. RESULTS: Eight hundred and eleven patients were diagnosed with primary rectal cancer in Hvidovre and Bispebjerg hospitals between 1 May 2001 and 31 August 2006. The frequency of preoperative MRI scans increased in the MDT cohort and perioperative mortality decreased. More metachronous distant metastases were found in the MDT cohort but there was no difference in overall survival. CONCLUSION: There was an improved postoperative mortality but no other potential benefits for the patients were seen after the implementation of colorectal MDTs.

Length of stay after laparoscopic colonic surgery - an 11-year nationwide Danish survey.

AIM: The use of laparoscopic colonic surgery in Denmark was analysed with particular reference to the length of stay. METHOD: Data were obtained from the Danish National Patient Registry to assess duration of hospital stay after laparoscopic colonic surgery in Denmark within the 11-year period from 2000 to 2010. RESULTS: There were 4582 laparoscopic colonic resections performed, reaching about 1000 operations/year in the last 2 years (2009-2010). Length of stay decreased from a median of 7 to 4 days, while mean length of stay only decreased from 9 to 7 days. CONCLUSION: The use of laparoscopic colonic resection has increased in Denmark over the last 11 years and with a concomitant decrease in postoperative length of stay. However, there is a need for further improvement by combining the laparoscopic technique with fast-track recovery.

A nationwide study on anastomotic leakage after colonic cancer surgery.

AIM: Anastomotic leakage (AL) is a major challenge in colorectal cancer surgery due to increased morbidity and mortality. Possible risk factors should be investigated differentially, distinguishing between rectal and colonic surgery in large-scale studies to avoid selection bias and confounding. METHOD: The incidence and risk factors associated with AL were analysed in an unselected nationwide prospective cohort of patient subjected to curative colonic cancer surgery with primary anastomosis and entered into The Danish Colorectal Cancer Group database between May 2001 and December 2008. RESULTS: AL occurred in 593 (6.4%) of 9333 patients. Laparoscopic surgery [odds ratio (OR) 1.34; 95% confidence interval (CI) 1.05-1.70; P=0.03); left hemicolectomy (OR 2.02; 95% CI 1.50-2.72; P=0.01) or sigmoid colectomy (OR 1.69; 95% CI 1.32-2.17; P=0.01); intra-operative blood loss (OR 1.04; 95% CI 1.01-1.07; P=0.03); blood transfusion (OR 10.27; 95% CI 6.82-15.45; P<0.001) and male gender (OR 1.41; 95% CI 1.12-1.75; P=0.02) were associated with AL in the multivariate analysis. CONCLUSION: The main finding that a laparoscopic approach was associated with an increased risk of AL should prompt close future monitoring. There was no evidence that centralization of surgery to high-volume hospitals reduced the rate of AL.

Postoperative morbidity after fast-track laparoscopic resection of rectal cancer.

AIM: Analysis was carried out of the nature and chronological order of early complications after fast-track laparoscopic rectal surgery with a view to optimizing the short-time outcome of rectal cancer surgery. METHOD: A total of 102 consecutive patients who underwent elective fast-track laparoscopic rectal cancer surgery were analysed prospectively from the Danish Colorectal Cancer Database supplemented by data from the medical records. We studied in detail the nature and chronological order of postoperative morbidity and reason for prolonged stay (> 5 days). RESULTS: Twenty-five patients (25%) had one or more complications. Surgical complications occurred in 19 patients, while six patients had medical complications as the primary event. Fifteen patients underwent reoperation, three died, and eight were readmitted within 30 days. The median length of stay was 5 days (range 2-42). CONCLUSION: Postoperative morbidity remains a significant problem in the fast-track era, even in experienced surgical hands. Our results suggest that besides improvement of surgical technique further improvement of outcome lies in early recognition and proper treatment of complications and the perioperative optimization of organ function.

Intra-operative perforation is an important predictor of local recurrence and impaired survival after abdominoperineal resection for rectal cancer.

AIM: Abdominoperineal resection for rectal cancer is associated with higher rates of local recurrence and poorer survival than anterior resection. The aim of this study was to evaluate the outcome of conventional abdominoperineal resection in a large national series. METHOD: The study was based on the Danish National Colorectal Cancer Database and included patients treated with abdominoperineal resection between 1 May 2001 and 31 December 2006. Follow up in the departments was supplemented with vital status in the Civil Registration System. The analysis included actuarial local and distant recurrence, and overall and cancer-specific survival. Risk factors for local recurrence, distant metastases, overall survival and cancer-specific survival were identified using multivariate analyses. RESULTS: A total of 1125 patients were followed up for a median of 57 (25-93) months. Intra-operative perforation was reported in 108 (10%) patients. The cumulative 5-year local recurrence rate was 11% [95% confidence interval (CI), 7-13)], overall survival was 56% (95% CI, 53-60) and cancer-specific survival was 68% (95% CI, 65-71). Multivariate analysis showed that perforation, tumour stage and nonradical surgery were independent risk factors for local recurrence; tumour fixation to other organs, perforation and tumour stage were independent risk factors for distant metastases; and risk factors for impaired overall survival and cancer-specific survival were age, tumour perforation, tumour stage, lymph node metastases and nonradical surgery. CONCLUSION: Intra-operative perforation is a major risk factor for local and distant recurrence and survival and therefore should be avoided.

Pathogenesis of morbidity after fast-track laparoscopic colonic cancer surgery.

AIM: Analysis of the nature and time course of early complications after laparoscopic colonic surgery is required to allow rational strategies for their prevention and management. METHOD: One hundred and four consecutive patients who underwent elective fast-track laparoscopic colonic cancer surgery were analysed prospectively from the Danish Colorectal Cancer Database, supplemented by data from the medical records. We studied in detail the time course of morbidity and reasons for prolonged stay (> 3 days). RESULTS: Seventeen (16.3%) patients had one or more complications. Surgical complications occurred in 14 patients, of which four were preceded by medical complications. Three patients had only medical complications. Median length of stay was 3 days (range 1-44). CONCLUSION: Further improvement of outcomes after fast-track laparoscopic colonic surgery might be obtained by improved surgical performance.

Anastomotic leakage after curative anterior resection for rectal cancer: short and long-term outcome.

OBJECTIVE: The influence of symptomatic anastomotic leakage (AL) after anterior resection (AR) for rectal cancer on short and long-term mortality and local and distant recurrence was analysed. METHOD: All patients with a first diagnosis of rectal carcinoma were prospectively registered in a national database. This comprised 1494 Danish citizens who had had a curative AR between May 2001 and December 2004. Data on survival and recurrence were obtained from the National Patient Register. Multivariate analyses were performed. RESULTS: Anastomotic leakage increased the 30-day mortality [odds ratio (OR) 4.01 (95% CI 2.24-7.17)]. Of other possible risk factors, only age had a significant interaction with leakage, as the risk of death within 30 days of AR decreased with increasing age. Long-term survival decreased significantly after AL [hazard ratio (HR) of 1.63, CI 1.21-2.19]. A total of 97 (6.7%) and 258 (18.0%) patients had local and distant recurrence respectively in the follow-up period. The risk of local and distant recurrence after AL was not different with HR of 1.50 (CI 0.84-2.69) and 1.13 (CI 0.76-1.69) respectively. No other factors influenced the risk of recurrence due to AL. CONCLUSION: Anastomotic leakage after AR for rectal cancer increases the 30-day and long-term mortality, but AL did not increase the risk of local and distant recurrence.

Improved survival after rectal cancer in Denmark.

OBJECTIVE: In 1995, an analysis showed an inferior prognosis after rectal cancer in Denmark compared with the other Scandinavian countries. The Danish Colorectal Cancer Group (DCCG) was established with the aim of improving the prognosis, and in this study we present a survival analysis of patients treated from 1994 to 2006. METHOD: The study was based on the National Rectal Cancer Registry and the National Colorectal Cancer Database, supplemented with data from the Central Population Registry. The analysis included actuarial overall and relative survival. RESULTS: A total of 10 632 patients were operated on. The overall 5-year survival increased from 0.37 in 1994 to 0.51% in 2006; the improvement was greater in men (20% points) than in women (10% points), and greatest in stage III (20% points). The relative 5-year survival increased from 0.46 to 0.62, including an improvement of 23% points in men and 9% points in women and the greatest in stage III (22% points). CONCLUSIONS: The prognosis has improved substantially, probably mainly because of initiatives taken by the DCCG, among which implementation of total mesorectal excision, improved staging and centralized treatment are considered most important.

Anastomotic leakage after anterior resection for rectal cancer: risk factors.

OBJECTIVE: The study aimed to identify risk factors for clinical anastomotic leakage (AL) after anterior resection for rectal cancer in a consecutive national cohort. METHOD: All patients with an initial first diagnosis of colorectal adenocarcinoma were prospectively registered in a national database. The register included 1495 patients who had had a curative anterior resection between May 2001 and December 2004. The association of a number of patient- and procedure-related factors with clinical AL after anterior resection was analysed in a cohort design. RESULTS: Anastomotic leakages occurred in 163 (11%) patients. In a multivariate analysis, the risk of AL was significantly increased in patients with tumours located below 10 cm from the anal verge if no faecal diversion was undertaken (OR 5.37 5 cm (tumour level from anal verge), 95% CI 2.10-13.7, OR 3.57 7 cm, CI 1.81-7.07 and OR 1.96 10 cm, CI 1.22-3.10), in male patients (OR 2.36, CI 1.18-4.71), in smokers (OR 1.88, CI 1.02-3.46), and perioperative bleeding (OR 1.05 for intervals of 100 ml blood loss, CI 1.02-1.07). CONCLUSION: Anastomotic leakage after anterior resection for low rectal tumours is related to the level, male gender, smoking and perioperative bleeding. Faecal diversion is advisable after total mesorectal excision of low rectal tumours in order to prevent AL.

Seasonal variation in short-term mortality after surgery for colorectal cancer?

OBJECTIVE: Comorbidity has a major impact on short-term and long-term survival of colorectal cancer (CRC) and many CRC patients suffer from comorbidities. Mortality rates for comorbidities like cardio-respiratory diseases exhibit distinct seasonal variations with highest rates in the winter. Therefore, we hypothesized some seasonal variation in 30-day mortality after surgery for CRC as well. METHOD: In a nationwide study, we examined the seasonal pattern in 30-day mortality after surgery for CRC from 1996 to 2006. We identified 33 556 CRC patients in the Danish hospital discharge registries. Monthly 30-day mortality rates were calculated and we constructed a fitted curve of the monthly mortality rates using a periodic regression model. We stratified the analyses for tumour site, urgency of surgery for colon cancer and the level of comorbidity based on American Society of Anaesthesiologists (ASA) score. RESULTS: The overall 30-day mortality was 8.7% [95% confidence interval 8.4-9.0%). Significant seasonal variation in monthly 30-day mortality could not be identified. For colon cancer, a nonsignificant increase was seen in July. An even higher increase in July was observed for CRC patients with moderate or severe comorbidity (ASA score >or= III), but was also nonsignificant. CONCLUSION: Although comorbidity is a well-known negative predictor of short-term survival of CRC, monthly 30-day mortality after surgery for CRC did not exhibit seasonal variation like that observed for comorbid conditions such as cardio-respiratory diseases.

A national cohort study of long-course preoperative radiotherapy in primary fixed rectal cancer in Denmark.

OBJECTIVE: Preoperative radiotherapy has been shown to enable a fixed rectal cancer to become resectable which in turn may result in long-time survival. In this study, we analysed the outcome of long-course preoperative radiotherapy in fixed rectal cancer in a national cohort including all Danish patients registered with primary inoperable rectal cancer and treated in the period May 2001 to December 2005. METHOD: The study was based on surgical and demographic data from a continuously updated and validated national database. In addition, retrospective data were retrieved from all departments of radiotherapy concerning technique of radiotherapy, dose and fractionation and use of concomitant chemotherapy. Outcome was determined by actuarial analysis of local control, disease-free survival and overall survival. RESULTS: A total of 258 patients with fixed rectal cancer received long-course radiotherapy (> 45 Gy). The median age at diagnosis was 66 years (range: 32-85) and 185 (72%) patients were male. The resectability rate was 80%, and a R0 resection was obtained in 148 patients (57% of all patients and 61% of those operated). The 5-year local recurrence rate for all patients was 5% (95% CI: 3-7%), and the actuarial distant recurrence rate was 41% (95% CI: 35-47%). The cumulative 5-year disease-free survival was 27% (95% CI: 22-32%) and overall 5-year survival was 34% (95% CI: 29-39%). CONCLUSIONS: This study is the first population-based report on outcome of preoperative long-course radiotherapy in a large unselected patient group with clinically fixed rectal cancer. Most patients could be resected with the intention of cure and one in three was alive after 5 years.

Postoperative medical complications are the main cause of early death after emergency surgery for colonic cancer.

BACKGROUND: Only a few small studies have evaluated risk factors related to early death following emergency surgery for colonic cancer. The aim of this study was to identify risk factors for death within 30 days after such surgery. METHODS: Some 2157 patients who underwent emergency treatment for colonic cancer from May 2001 to December 2005 were identified from the national colorectal cancer registry. Thirty-day mortality rates were calculated and risk factors for early death were identified using logistic regression analysis. RESULTS: The overall 30-day mortality rate was 22.1 per cent. The strongest risk factor for early death was postoperative medical complications (cardiopulmonary, renal, thromboembolic and infectious), with an odds ratio of 11.7 (95 per cent confidence interval 8.8 to 15.5). Such complications occurred in 24.4 per cent of patients, of whom 57.8 per cent died. Other independent risk factors were age at least 71 years, male sex, American Society of Anesthesiologists grade III or more, palliative outcome, tumour perforation, splenectomy and adverse intraoperative surgical events. Postoperative surgical complications were noted in 20.4 per cent of the patients but had no statistically significant influence on mortality. CONCLUSION: Emergency surgery for colonic cancer is still associated with an increased risk of death. There is a need for a system providing increased safety in the perioperative period.

Implementation of the scientific evidence into daily practice--example from fast-track colonic cancer surgery.

OBJECTIVE: To report the implementation and results of fast-track surgery for colonic cancer in the daily routine. METHOD: A total of 131 consecutive patients scheduled for elective colonic cancer resections entered a fast-track perioperative course after thorough information. The regimen contained: no preoperative bowel cleansing, transverse and small abdominal incisions, no drains nor tubes, mobilization and normal meal the evening on the day of surgery, epidural analgesia, oral laxatives, and a planned discharge on postoperative day 3. RESULTS: Median number of days postoperative in hospital were 4 days (range 1-46). Eighty-nine per cent experienced an uncomplicated course, 3% were readmitted within 30 days, and the 30-day mortality was 3.8%. CONCLUSION: Fast-track surgery is feasible in an unselected patient population scheduled for elective colon cancer resections without compromising quality.

Enhanced recovery after giant ventral hernia repair.

PURPOSE: Giant ventral hernia repair is associated with a high risk of postoperative morbidity and prolonged length of stay (LOS). Enhanced recovery (ERAS) measures have proved to lead to decreased morbidity and LOS after various surgical procedures, but never after giant hernia repair. The current study prospectively examined the results of implementation of an ERAS pathway including high-dose preoperative glucocorticoid, and compared the outcome with patients previously treated according to standard care (SC). METHODS: Consecutive patients who underwent giant ventral hernia repair were included. Pain, nausea and fatigue were registered prospectively in all patients treated according to ERAS, as well as continuous measurement of transcutaneous capillary oxygen saturation. Postoperative morbidity and LOS were compared between patients treated according to ERAS and a historic group treated with SC. RESULTS: A total of 32 patients were included. Postoperative LOS was decreased after the introduction of the ERAS pathway compared with SC (median 3.0 vs. 5.5 days, P = 0.003). Scores of pain, nausea and fatigue were low, while mean oxygen saturation during the first three postoperative days was 0.92. There were no differences when comparing readmission (5 vs. 2, P = 0.394), postoperative complications (7 vs. 4, P = 0. 458), or reoperation (5 vs. 1, P = 0.172) in ERAS versus controls. CONCLUSIONS: The current study suggests that an ERAS pathway including preoperative high-dose glucocorticoid may lead to low scores of pain, fatigue and nausea after giant ventral hernia repair with reduced LOS compared with patients treated according to SC.

Extrinsic control of the release of galanin and VIP from intrinsic nerves of isolated, perfused, porcine ileum.

By immunohistochemistry galanin-like immunoreactivity and vasoactive intestinal polypeptide (VIP)-like immunoreactivity were found in nerve cell bodies mostly in the submucous plexus and in nerve fibres in the mucosa, submucosa and muscularis including the myenteric plexus of the porcine ileum and were found to co-exist in most of these structures. Using isolated, perfused porcine ileum we studied the release of galanin and VIP in response to electrical stimulation of the mixed periarterial nerves or to intraarterial infusions of different neuroactive agents. Nerve stimulation (4-10 Hz) inhibited the basal release of galanin and VIP from the ileum (to 69 +/- 6 and 62 +/- 6% of basal release). After infusion of the alpha-adrenergic blocker, phentolamine, (10(-6) M) electrical stimulation increased the release of both galanin and VIP (to 140 +/- 12 and 133 +/- 13% of basal output). This increase was abolished by atropine (10(-6) M) and by hexamethonium (3.10(-5) M). Infusion of norepinephrine (10(-6) M) inhibited, whereas acetylcholine (10(-6) M) stimulated the release of both peptides. The effect of the latter was abolished by atropine. The inhibitory effect of nerve stimulation was not influenced by atropine. Our results suggest that the galanin- and VIP-producing intrinsic neurons receive inhibitory signals by noradrenergic nerve fibers and stimulatory signals mediated by cholinergic nerves, possibly via a cholinergic interneuron.

Galanin in the porcine pancreas.

Galanin, a 29 amino acid neuropeptide, was recently isolated from pig intestine. We studied the localization, nature and effect of galanin in pig pancreas. Galanin immunoreactive nerve fibers were regularly found in the pancreas. A peptide chromatographically similar to synthetic galanin was identified in pancreas extracts. The effect of galanin on the endocrine and exocrine secretion was studied in isolated pancreases, perfused with a synthetic medium containing 3.5, 5 or 8 mmol/l glucose and synthetic galanin (10(-10)-10(-8) mol/l). There was no effect on the basal exocrine secretion. The output of insulin, glucagon, somatostatin and pancreatic polypeptide (PP) was measured in the effluent. There was no effect on PP secretion. At a perfusate glucose concentration of 5 mmol/l, galanin at 10(-9) mol/l increased insulin secretion by 55 +/- 14% (mean +/- S.E.M., n = 5) of basal secretion, and at 10(-8) mol/l by 58 +/- 27% (n = 6). At 8 mmol/l glucose, insulin secretion increased by 25 +/- 10% (n = 6) and 62 +/- 17% (n = 8). At 5 mmol/l glucose glucagon secretion was increased by 15 +/- 3% (n = 5) by galanin at 10(-9) mol/l and by 29 +/- 11% (n = 5) by galanin at 10(-8) mol/l, and at 8 mmol/l glucose by 66 +/- 27% and 41 +/- 25%. Somatostatin secretion was inhibited to 72 +/- 2% (n = 5) of basal secretion by galanin at 10(-9) mol/l and to 65 +/- 7% (n = 7) at galanin at 10(-8) mol/l, both at 5 mmol/l glucose. At 8 mmol/l the figures were 83 +/- 6% and 70 +/- 10%. Insulin secretion in response to square wave increases in glucose concentration from 3.5 to 11 mmol/l (n = 5) increased 2-fold during simultaneous perfusion with galanin (10(-8) mol/l).

Calcitonin gene-related peptide (CGRP), a potent regulator of biliary flow.

This study was designed to investigate the effect of porcine calcitonin gene-related peptide (CGRP) on the motility of the porcine biliary tract in vivo. We measured the pressure in the gallbladder and sphincter of Oddi and, in separate experiments, the biliary flow into the duodenum during local intraarterial infusions of CGRP. To determine if the observed effect could be caused by release of cholecystokinin (CCK), we measured the CCK release. The basal pressure in the sphincter of Oddi increased dose-dependently from 5.9 +/- 0.5 mmHg to 11.5 +/- 2.1 mmHg and the motility index of phasic contractions (amplitude x frequency) from 47 +/- 8 to 347 +/- 64 mmHg s-1, at an infusion rate of 32.6 pmol kg-1 min-1. No effect was observed on the gallbladder pressure. CGRP at 6.5 pmol kg-1 min-1 significantly reduced the biliary flow into the duodenum to 47.7 +/- 6% of the basal level. Atropine, injected intravenously, completely abolished the contractile effect of CGRP. CGRP had no effect on the release of CCK. We conclude that CGRP increases biliary motility and hereby reduces bile flow, an effect which involves cholinergic but not cholecystokininergic mechanisms.

Effect of intestinal inhibitory peptides on vagally induced secretion from isolated perfused porcine pancreas.

Several gastrointestinal peptides inhibit pancreatic secretion in intact animals, but fail to do so in isolated pancreas preparations. Using isolated perfused porcine pancreas with intact innervation, we studied the influence of such peptides (somatostatin, peptide YY, glucagon-like peptide-1, oxyntomodulin, neuropeptide Y, galanin, and calcitonin gene-related peptide) on vagally induced secretion and on release of vasoactive intestinal polypeptide (VIP), a neuropeptide involved in fluid and bicarbonate secretion. In control experiments electrical vagus stimulation increased flow of juice from 0.9 +/- 0.1 to 37.3 +/- 5.6 ml/h and protein output from 43 +/- 5 to 1,244 +/- 336 mg/h (mean +/- SD). With somatostatin-14 at 10(-10) mol/L, the fluid response was reduced to 64 +/- 11% of controls, protein concentration to 78 +/- 3.8%, and protein output to 50 +/- 5% (p < 0.05). At 10(-8) M the response was almost abolished. VIP release, which in control experiments increased from 0.2 +/- 0.05 to 2.1 +/- 0.4 pmol/min, was similarly reduced (p < 0.01). Galanin at 10(-8) M inhibited the fluid response to 54 +/- 7% of controls, protein output to 51.7 +/- 11%, and VIP release to 54 +/- 6% (p < 0.01). None of the other inhibitory peptides affected vagus responses. It is concluded that somatostatin and galanin inhibit pancreatic secretion through interaction with intrapancreatic ganglia. The other peptides act on extrapancreatic, possibly central sites.

Long-term prognosis of patients with severe radiation enteritis.

One hundred thirty-six patients (median age 59 years) presented with intestinal complications of previous radiotherapy. Seventy-eight had bleeding or stricture and 58 had perforation or fistula. One hundred twenty-four patients survived for more than 3 months and were followed for a median of 4.5 years. Sixty-eight patients were free of symptoms, whereas 16 experienced operation-related complications. Twelve patients had continuing symptoms of radiation enteritis, and new radiation-induced complications developed in 28. Sixteen of 51 patients with perforation or fistula had new complications compared with 12 of 73 patients with bleeding of stricture (p = 0.05). Overall, 57 patients died during the study. Thirteen died from radiation-induced complications and 27, from recurrent malignancy. Radiation deaths occurred in the postoperative period but had no impact on long-term survival. Life expectancy was poorer in patients presenting with perforation or fistula compared with bleeding or stricture, the main reason being significantly more recurrences among patients with fistulas (p less than 0.05).

[Combined nitroglycerin-heparin infusion in mesenteric venous thrombosis]. / Kombineret nitroglycerin-heparininfusion ved venøs mesenteriel trombose.

Surgical treatment of venous mesenterial thrombosis (VMT) may result in a short bowel-syndrome. We report the successful outcome of combined intravenous heparin and nitroglycerine in a case of VMT followed by a limited resection of small bowel.