Low anterior resection syndrome in a Scandinavian population of patients with rectal cancer: a longitudinal follow-up within the QoLiRECT study.

AIM: Low anterior resection syndrome (LARS) is common after low anterior resection. Our aim was to evaluate the prevalence and 'bother' (subjective, symptom-associated distress) of major LARS after 1 and 2 years, identify possible risk factors and relate the bowel function to a reference population. METHOD: The QoLiRECT (Quality of Life in RECTal cancer) study is a Scandinavian prospective multicentre study including 1248 patients with rectal cancer, of whom 552 had an anterior resection. Patient questionnaires were distributed at diagnosis and after 1, 2 and 5 years. Data from the baseline and at 1- and 2-year follow-up were included in this study. RESULTS: The LARS score was calculated for 309 patients at 1 year and 334 patients at 2 years. Prevalence was assessed by a generalized linear mixed effects model. Major LARS was found in 63% at 1 year and 56% at 2 years. Bother was evident in 55% at 1 year, decreasing to 46% at 2 years. Major LARS was most common among younger women (69%). Among younger patients, only marginal improvement was seen over time (63-59%), for older patients there was more improvement (62-52%). In the reference population, the highest prevalence of major LARS-like symptoms was noted in older women (12%). Preoperative radiotherapy, defunctioning stoma and tumour height were found to be associated with major LARS. CONCLUSION: Major LARS is common and possibly persistent over time. Younger patients, especially women, are more affected, and perhaps these patients should be prioritized for early stoma closure to improve the chance of a more normal bowel function.

Better survival for patients with colon cancer operated on by specialized colorectal surgeons - a nationwide population-based study in Sweden 2007-2010.

AIM: Mortality and complication rates after surgery for colon cancer are high, especially after emergency procedures. The aim of the present study was to evaluate the importance of the formal competence of surgeons for survival and morbidity. METHOD: The Swedish Colorectal Cancer Registry prospectively records data on patients diagnosed with cancer within the colon and rectum. A cohort of patients operated on for colon cancer between 2007 and 2010 were followed 5 years after surgery. Data on postoperative morbidity, mortality and long-term survival were compared with regard to formal competency of the most senior surgeon attending the procedure. RESULTS: This analysis includes 13 365 patients operated on for colon cancer, including 10 434 elective procedures and 2931 emergency cases. The overall 5-year survival was higher for those operated on by subspecialist colorectal surgeons compared with general surgeons (60% vs 48%; P < 0.001). Five-year survival after elective surgery was 63% vs 55% (P < 0.001) and 35% vs 31% (P < 0.05) after emergency procedures when performed by colorectal surgeons compared with general surgeons. Postoperative 30-day mortality was 3% after surgery performed by colorectal surgeons compared with 7% when performed by general surgeons. Mortality at 90 days was 6% after surgery performed by colorectal surgeons compared with 11% for patients operated on by general surgeons (P < 0.001). CONCLUSION: Subspecialization in colorectal surgery is associated with better outcome for patients operated on for colon cancer, and effort should be made to increase the availability of colorectal surgeons for both acute and elective colon cancer surgery.

Two-year results of the randomized clinical trial DILALA comparing laparoscopic lavage with resection as treatment for perforated diverticulitis.

BACKGROUND: Traditionally, perforated diverticulitis with purulent peritonitis was treated with resection and colostomy (Hartmann's procedure), with inherent complications and risk of a permanent stoma. The DILALA (DIverticulitis - LAparoscopic LAvage versus resection (Hartmann's procedure) for acute diverticulitis with peritonitis) and other randomized trials found laparoscopic lavage to be a feasible and safe alternative. The medium-term follow-up results of DILALA are reported here. METHODS: Patients were randomized during surgery after being diagnosed with Hinchey grade III perforated diverticulitis at diagnostic laparoscopy. The primary outcome was the proportion of patients with one or more secondary operations from 0 to 24 months after the index procedure in the laparoscopic lavage versus Hartmann's procedure groups. The trial was registered as ISRCTN82208287. RESULTS: Forty-three patients were randomized to laparoscopic lavage and 40 to Hartmann's procedure. Patients in the lavage group had a 45 per cent reduced risk of undergoing one or more operations within 24 months (relative risk 0·55, 95 per cent c.i. 0·36 to 0·84; P = 0·012) and had fewer operations (ratio 0·51, 95 per cent c.i. 0·31 to 0·87; P = 0·024) compared with those in the Hartmann's group. No difference was found in mean number of readmissions (1·37 versus 1·50; P = 0·221) or mortality between patients randomized to laparoscopic lavage or Hartmann's procedure. Three patients in the lavage group and nine in the Hartmann's group had a colostomy at 24 months. CONCLUSION: Laparoscopic lavage is a better option for perforated diverticulitis with purulent peritonitis than open resection and colostomy.

Quality of life in a randomized trial of early closure of temporary ileostomy after rectal resection for cancer (EASY trial).

BACKGROUND: A temporary ileostomy may reduce symptoms from anastomotic leakage after rectal cancer resection. Earlier results of the EASY trial showed that early closure of the temporary ileostomy was associated with significantly fewer postoperative complications. The aim of the present study was to compare health-related quality of life (HRQOL) following early versus late closure of a temporary ileostomy. METHODS: Early closure of a temporary ileostomy (at 8-13 days) was compared with late closure (at more than 12 weeks) in a multicentre RCT (EASY) that included patients who underwent rectal resection for cancer. Inclusion of participants was made after index surgery. Exclusion criteria were signs of anastomotic leakage, diabetes mellitus, steroid treatment, and signs of postoperative complications at clinical evaluation 1-4 days after rectal resection. HRQOL was evaluated at 3, 6 and 12 months after resection using the European Organisation for Research and Treatment of Cancer (EORTC) questionnaires QLQ-C30 and QLQ-CR29 and Short Form 36 (SF-36®). RESULTS: There were 112 patients available for analysis. Response rates of the questionnaires were 82-95 per cent, except for EORTC QLQ-C30 at 12 months, to which only 54-55 per cent of the patients responded owing to an error in questionnaire distribution. There were no clinically significant differences in any questionnaire scores between the groups at 3, 6 or 12 months. CONCLUSION: Although the randomized study found that early closure of the temporary ileostomy was associated with significantly fewer complications, this clinical advantage had no effect on the patients' HRQOL. Registration number: NCT01287637 (https://www.clinicaltrials.gov).

Time trends, improvements and national auditing of rectal cancer management over an 18-year period.

AIM: The main aims were to explore time trends in the management and outcome of patients with rectal cancer in a national cohort and to evaluate the possible impact of national auditing on overall outcomes. A secondary aim was to provide population-based data for appraisal of external validity in selected patient series. METHOD: Data from the Swedish ColoRectal Cancer Registry with virtually complete national coverage were utilized in this cohort study on 29 925 patients with rectal cancer diagnosed between 1995 and 2012. Of eligible patients, nine were excluded. RESULTS: During the study period, overall, relative and disease-free survival increased. Postoperative mortality after 30 and 90 days decreased to 1.7% and 2.9%. The 5-year local recurrence rate dropped to 5.0%. Resection margins improved, as did peri-operative blood loss despite more multivisceral resections being performed. Fewer patients underwent palliative resection and the proportion of non-operated patients increased. The proportions of temporary and permanent stoma formation increased. Preoperative radiotherapy and chemoradiotherapy became more common as did multidisciplinary team conferences. Variability in rectal cancer management between healthcare regions diminished over time when new aspects of patient care were audited. CONCLUSION: There have been substantial changes over time in the management of patients with rectal cancer, reflected in improved outcome. Much indirect evidence indicates that auditing matters, but without a control group it is not possible to draw firm conclusions regarding the possible impact of a quality control registry on faster shifts in time trends, decreased variability and improvements. Registry data were made available for reference.

COLOR II. A randomized clinical trial comparing laparoscopic and open surgery for rectal cancer.

INTRODUCTION: Laparoscopic resection of rectal cancer has been proven efficacious but morbidity and oncological outcome need to be investigated in a randomized clinical trial. TRIAL DESIGN: Non-inferiority randomized clinical trial. METHODS: The COLOR II trial is an ongoing international randomized clinical trial. Currently 27 hospitals from Europe, South Korea and Canada are including patients. The primary endpoint is loco-regional recurrence rate three years post-operatively. Secondary endpoints cover quality of life, overall and disease free survival, post-operative morbidity and health economy analysis. RESULTS: By July 2008, 27 hospitals from the Netherlands, Belgium, Germany, Sweden, Spain, Denmark, South Korea and Canada had included 739 patients. The intra-operative conversion rate in the laparoscopic group was 17%. Distribution of age, location of the tumor and radiotherapy were equal in both treatment groups. Most tumors are located in the mid-rectum (41%). CONCLUSION: Laparoscopic surgery in the treatment of rectal cancer is feasible. The results and safety of laparoscopic surgery in the treatment of rectal cancer remain unknown, but are subject of interim analysis within the COLOR II trial. Completion of inclusion is expected by the end of 2009. TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT00297791 (www.clinicaltrials.gov).

Fibrin glue for securing the mesh in laparoscopic totally extraperitoneal inguinal hernia repair: a study with a 40-month prospective follow-up period.

BACKGROUND: Anchoring the mesh in laparoscopic totally extraperitoneal groin hernia repair (TEP) with human fibrin glue has theoretical advantages. However, these have been supported and reported previously only in animal studies. Before the initiation of large patient trials, the authors wanted to confirm the feasibility, assess the costs, and rule out any flagrant short- and long-term adverse effects of fibrin glue usage in a small series of patients. METHODS: Nine consecutive TEP repairs with fibrin glue mesh fixation were performed. The perioperative and postoperative outcomes at 1, 16, and 40 months were compared with those for a control group of 96 stapled repairs. RESULTS: Gluing was easy and is less expensive than stapling. No fibrin glue-related adverse effects were found. The overall outcome was similar to that for stapled repairs, with no indication that the glued repairs were inferior. CONCLUSIONS: Fibrin glue seems to be a reasonable, feasible, and maybe even competitive alternative to the standard tissue-penetrating mesh fixation. The results of this study justify launching larger trials.

Laparoscopy reduces unnecessary appendicectomies and improves diagnosis in fertile women. A randomized study.

BACKGROUND: The aim of this study was to study the value of diagnostic laparoscopy prospectively in fertile women scheduled for acute appendectomy. METHODS: For this study, 110 women, with acute abdominal pain ages 15 to 47 years, in whom the surgeon had decided to perform an appendectomy, were randomized to either open appendectomy or diagnostic laparoscopy, then open appendectomy if necessary. RESULTS: Appendicitis was diagnosed in 66% of the women after open surgery, and in 73% after laparoscopy. During laparoscopy, was appendicitis misdiagnosed in only 7% of the women, from whom the appendix unnecessarily removed, whereas 34% in the open surgery group had a healthy appendix removed. No appendicitis was missed in the laparoscopic group. The relative risk of removing a healthy appendix in open surgery was 6.6 relative risk (range, 2-21 C.I.) as compared with laparoscopy. Among the women with a healthy appendix, a gynecologic diagnosis was found in 73% after laparoscopy, as compared with 17% after open surgery. CONCLUSIONS: Laparoscopy reduces unnecessary appendectomies and improves diagnosis in fertile women.

Laparoscopic bowel mobilization combined with intraoperative colonoscopic polypectomy in patients with an inaccessible polyp of the colon.

BACKGROUND: The purpose of this report was to describe a simple technique suitable for polyps where circumstances of the bowel anatomy prevent complete access and control of the colonoscopic procedure. METHODS: By combining laparoscopic mobilization of the bowel with colonoscopic polypectomy, previously inaccessible polyps could be snared in two patients. RESULTS: Both patients had 3-cm large sessile adenomas in the sigmoid colon safely removed, and they returned home within a day. CONCLUSIONS: The described procedure increases the safety of the otherwise difficult polypectomy and also avoids laparotomy with enterotomy or bowel resection as the alternative.

No differences in mucosal adaptive growth one week after intestinal resection in rats given enteral glutamine supplementation or deprived of glutamine.

OBJECTIVE: To evaluate the effects of intraluminal glutamine on the adaptation of intestinal mucosa after resection compared with transsection and un-operated on control animals. DESIGN: Open, controlled, experimental study. SETTING: University hospital, Sweden. SUBJECTS: 123 Sprague-Dawley rats. INTERVENTION: Daily isonitrogenous oral diet was given either free of glutamine or supplemented with 4% glutamine for 2 or 7 days to rats subjected to intestinal resection, transection or no operation. MAIN OUTCOME MEASURES: Body weight and protein content, DNA content, and thymidine incorporation in jejunal and ileal mucosa. RESULTS: Resection resulted in a significant growth stimulation evaluated by weight/body weight, protein, and DNA content (p < 0.05-0.001). Glutamine supplementation did not significantly influence this growth response. Thymidine incorporation in jejunum was stimulated by glutamine on day 3 (p < 0.05-0.001). CONCLUSION: The glutamine fortified diet had no growth stimulating effects compared with a glutamine free diet one week after 60% intestinal resection. An early increase in thymidine incorporation indicated that glutamine had a transient proliferative effect.

Effects of graded glutamine intake on liver protein metabolism following partial hepatectomy.

OBJECTIVE: To elucidate whether glutamine can influence the rate of regeneration and protein metabolism in regenerating liver. DESIGN: Liver regeneration rate, protein content and synthesis were measured in rats 7 days after a liver resection or sham operation. After the operation, the rats were fed three elementary isonitrogenous diets, one without and two including different levels of glutamine. METHODS: Fifty-six rats were randomly assigned to either sham operation or liver resection. After the operation, they received an isonitrogenous, isocaloric elementary diet with a glutamine content of 0, 2 or 4%. The resected part of the liver was weighed and analysed for DNA and protein content. Seven days later, hepatic protein synthesis was measured by the flooding method using L-[3H]-phenylalanine, and the liver was analysed for DNA, RNA and protein content. RESULTS: The regeneration rate was higher in the group receiving 2% glutamine but not in the group receiving 4% glutamine than in the 0% group. Total protein content was increased in regenerating liver in the 2 and 4% glutamine groups compared with the 0% group. Protein synthesis was higher 7 days after liver resection than in sham-operated rats. In the 2% group there was a tendency towards increased protein synthesis compared with the 0% group. CONCLUSION: A diet with normal glutamine content improved liver regeneration rate, total protein content and protein synthesis in regenerating liver, but an excess of glutamine did not enhance this effect.

Interobserver variation of colonoileoscopic findings in Crohn's disease.

BACKGROUND: Colonoileoscopy is increasingly used to evaluate Crohn's disease, but the reproducibility of endoscopic findings is not clear. METHODS: The interobserver variation of endoscopic findings and the influence of experience on assessments were investigated in 82 colonoileoscopies in Crohn's disease. RESULTS: In colonic assessment there was excellent agreement for most endoscopic features (kappa values > 0.75; p < 0.001). In ileal assessment agreement was excellent with regard to detection of large ulcers and strictures and endoscopic staging on the basis of ulcer size and stricture (kappa > 0.76; p < 0.001). Observer experience was an important factor in ileal assessments: agreement was excellent for 13 features within experienced pairs, compared with 3 when only 1 of a pair was experienced. In colonic assessment experience was less important. CONCLUSION: The study showed that acceptable agreement can be obtained on some well-defined inflammatory lesions in Crohn's disease even when investigator experience is limited. Endoscopic staging on the basis of ulcer size and stricture, being excellently reproducible, can serve as a simple summarizing assessment.

Protein synthesis in regenerating rat liver during malnutrition.

To examine the effect of malnutrition on liver protein metabolism and synthesis during liver regeneration, 104 rats were allocated to semi-starvation or ordinary food intake for 1 week. Half of each group was sham operated and the other half was partially hepatectomized. Specimens were taken from the liver at the time of liver resection and from animals killed 24, 48 and 72 h after the primary operation. Liver samples were analysed for DNA and protein, and in the 48-h groups RNA and protein synthesis were also analysed. Protein synthesis was measured by the flooding method using L[4-3H] phenylalanine. The liver weight during regeneration increased very rapidly in the well-nourished animals, but when expressed as percent of body weight or as proportional increases, the difference between well-nourished and malnourished animals disappeared. The fractional rate of protein synthesis was not changed in sham-operated malnourished or well-nourished animals. During regeneration, protein synthesis in well-nourished animals was elevated compared to sham-operated controls, but a lesser stimulation was seen in malnourished rats. It was concluded that the mechanism of liver regeneration depends on nutritional state, involving an increase in protein synthesis in well-nourished animals, but relying more on a decrease in protein degradation or cessation of secretory protein synthesis in malnourished animals.

The impact of leucine infusion on skeletal muscle amino acid and energy metabolism in severely traumatized patients.

The response to trauma is associated with increased energy requirements and net protein breakdown. The branched chain aminoacids, especially leucine, are considered to act by serving as a fuel for muscle tissue and by stimulating synthesis of proteins and controlling protein breakdown. Such results have been obtained mainly from in vitro studies. The present study was designed to evaluate the pharmacological effect of leucine infusion on muscle energy/amino acid metabolism in man after severe multiple trauma. 16 patients were studied and randomly allocated into 2 groups. Group 1 was given fat and 20% glucose while group 2 received 6 g N in form of leucine dissolved in 10% glucose solution and fat. The patients received 40 kcal/kg/24 h over an 8 day period after trauma. Biochemical analyses, muscle biopsies (energy substrates, electrolytes, amino acids), nitrogen balance and 3-methyl histidine excretion in urine were evaluated. Biochemical data revealed a significant increase (p < 0.05) of serum urea in group 2 day 4 and 8 after trauma. Muscle intracellular electrolytes (K(+), Mg(2+)) and energy substrates (ATP, phosphocreatine) showed a similar decrease in both groups. The intracellular muscle amino acids displayed a pattern known to be related to trauma without differences between the groups. The cumulative nitrogen balance 8 days after the injury was -93.5 g N +/- 10.1 (SEM) in group 1 and -73 g N +/- 7.5 in group 2. The 3-methylhistidine excretion was markedly increased similar in both groups. The present study demonstrated no significant pharmacological effect of leucine administration on muscle metabolism, nitrogen balance or 3-methylhistidine excretion in severely traumatized patients. Conventional balanced amino acid solutions are probably optimal to meet the patients actual requirements.

Effect of pancreaticobiliary diversion on liver regeneration.

To ascertain whether the increase in cholecystokinin (CCK) level associated with pancreaticobiliary diversion has a cytoproliferative effect on the liver similar to that on the pancreas, we studied three groups of rats: group I (n = 19) had a pancreaticobiliary diversion and 4 weeks later a 70% liver resection, group II (n = 13) had a liver resection only, and group III (n = 6) underwent a sham liver operation. Tissue samples were taken from the liver and pancreas 48 h after the liver operation. Liver regeneration was evaluated on the basis of continuous incorporation of tritiated thymidine into hepatocytes, liver weight, and DNA content. For confirmation of the increase in CCK levels the effects on the pancreas was studied by measuring wet weight, total protein, and total DNA content. The results showed trophic effects on the pancreas, as expected, but no effects whatsoever on liver regeneration. CCK does not seem to have any role in the regulation of liver regeneration.

Availability of energy substrates during liver regeneration in malnourished rats.

A retarded liver regeneration rate during malnutrition has previously been reported. To explore the mechanisms, some energy substrates were studied during liver regeneration and malnutrition. Forty-one rats were allocated to one of three groups (G): GI were normally nourished rats, which were partially hepatectomized; GII were semistarved rats, which were partially hepatectomized; and GIII were normally nourished rats, which were sham-operated. Biopsy specimens were taken from the liver at the time of partial hepatectomy and when they were killed after 48 h of regeneration. The samples were analysed for adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), glycogen, lactate, and pyruvate, and energy charge potential (ECP) was calculated. ATP, ECP, and glycogen levels were decreased in the malnourished group before the resection. After 48 h of regeneration all values were unchanged in the normally nourished group, whereas ATP, ADP, and ECP were increased in the malnourished group compared with the initial values. The lactate/pyruvate quotient was increased in malnourished rats compared with normal rats. The results suggest that the energy supply is not a limiting factor for the reduced regeneration rate seen in malnourished animals.