Henrik Harling

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.

Recurrence and survival after mesorectal excision for rectal cancer

Mesorectal excision for rectal cancer has resulted in local recurrence rates of 3–11 per cent compared with up to 38 per cent after conventional methods. The results of a prospective Danish study with a historical control group are presented.

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.

Anastomotic leak increases distant recurrence and long-term mortality after curative resection for colonic cancer: a nationwide cohort study.

Objective:To investigate the impact of anastomotic leak (AL) on disease recurrence and long-term mortality in patients alive 120 days after curative resection for colonic cancer. Background:There is no solid data as to whether AL after colonic cancer surgery increases the risk of disease recurrence. Methods:This was a nationwide cohort study of 9333 patients, prospectively registered in the database of the Danish Colorectal Cancer Group and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable Cox regression analysis was used to adjust for confounding. Results:The incidence of AL was 6.4%, 744 patients died within 120 days. Of the remaining 8589 patients, 861 (10.0%) developed local recurrence with no association to AL [adjusted hazard ratio (HR) = 0.78; 95% confidence interval (CI): 0.55–1.12; P = 0.184]. Distant recurrence developed in 1281 (14.9%) patients and more frequently after AL (adjusted HR = 1.42; 95% CI: 1.13–1.78; P = 0.003). AL was also associated with increased long-term mortality (adjusted HR = 1.20; 95% CI: 1.01–1.44; P = 0.042). In 2841 patients with stage III cancer, AL was associated with both decreased likelihood of receiving adjuvant chemotherapy (adjusted HR = 0.58; 95% CI: 0.45–0.74; P < 0.001) and a delay to initial administration (16 days; 95% CI: 12–20 days; P < 0.001). Conclusions:AL was significantly associated with increased rates of distant recurrence and long-term all-cause mortality. Cancelled or delayed administration of adjuvant chemotherapy may partly account for these findings.

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

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.

Do patient characteristics, disease, or treatment explain social inequality in survival from colorectal cancer? ☆

This paper investigates the association between individually measured socioeconomic status (SES) and all-cause survival in colorectal cancer patients, and explores whether factors related to the patient, the disease, or the surgical treatment mediate the observed social gradient. The data were derived from a nationwide clinical database of all adenocarcinomas of the colon or rectum diagnosed in Denmark between 2001 and 2004 (inclusive). These data were linked to those from several central registries providing information on income, education, and housing status, as well as to data on comorbidity from previous hospitalizations and use of medication. Only patients with colorectal cancer as their first primary tumour and those born after 1920 were included. A total of 8763 patients were included in the study. Cox proportional hazard regression models revealed a positive social gradient in survival for increasing levels of education and income, and in owners versus renters of housing. A series of regression analyses were used to test potential mediators of the association between the socioeconomic indicators and survival by stepwise inclusion of lifestyle factors (smoking, alcohol intake, body mass index), comorbidity, stage of disease, mode of admission, type of operation, specialization of the surgeon, and curative versus palliative resection. A causal diagram guided the analyses. Inclusion of comorbidity, and to a lesser extent lifestyle, reduced the variation associated with SES, while no evidence of a mediating effect was found for disease or surgical treatment factors. This indicates that the difference in survival among colorectal cancer patients from different social groups was probably not caused by unintentional differences in treatment factors related to surgery, and suggests that primary prevention of chronic diseases among the socially deprived might be one way to reduce social differences in prognosis.

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.

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).

Adenocarcinoma of the anal ducts

The records of 21 patients treated for adenocarcinoma of the anal ducts between 1943 and 1982 were reviewed. The patients were followed until death or current status in April 1987. The median follow-up period was eight months (range, 3 to 144 months). Fifteen patients had an erroneous diagnosis made at first physician visit resulting in a media doctors delay of 14 months (range, 3 to 24 months) before correct treatment was carried out. Nine of the tumors were localized perianally (ischiorectal space), seven anally, and five in a fistula-in-ano. Tumors localized anally were significantly smaller and had a significantly shorter history than perianally or fistula-in-ano localized tumors (P<.05 for each localization). Three patients with anal tumors had their diagnosis made accidentally by routine histologic examination of an excised hemorrhoid. First examination revealed distant metastases in 13 patients and follow-up examination revealed regional or distant metastases in seven patients. Modes of treatment were wide local excision (N=3), abdominoperineal resection (N=3), colostomy (N=9), and radiotherapy (N=2). Twenty of the 21 patients died within 18 months due to the cancer. One long-term survivor was observed; the patient was alive 12 years after local excision of the tumor without evidence of recurrent disease. The crude five- and 10-year survival was only 4.8 percent.

Management of Anastomotic Leakage in a Nationwide Cohort of Colonic Cancer Patients

BACKGROUND The mortality associated with anastomotic leakage (AL) after colonic cancer surgery is high and management often results in permanent fecal diversion. Preservation of bowel continuity in combination with proximal loop diversion (salvage) may reduce the number of permanent ostomies without jeopardizing safety. STUDY DESIGN This nationwide study used prospective data from the database of the Danish Colorectal Cancer Group, the National Patient Registry, and patient files. Patients with AL requiring surgery (grade C) were categorized according to the type of surgical treatment as anastomotic takedown with an end-ostomy or salvage. Thirty-day mortality, long-term mortality, and permanent ostomy rates were analyzed using multivariable logistic and Cox regression analyses. RESULTS Anastomotic leakage occurred in 593 of 9,333 patients (6.4%), of whom 507 with grade C were included. Takedown and salvage were undertaken in 433 (85.4%) and 74 (14.6%) patients, respectively. Salvage was performed more frequently for Hinchey I-II or minor anastomotic defects and resulted in increased likelihood of stoma reversal (adjusted hazard ratio 3.24, 95% CI 2.04 to 5.16, p < 0.001), corresponding to a risk of permanent fecal diversion of 16.8%, compared with 54.5% after takedown. Adjusted mortality rates were comparable between the groups. A second episode of AL after stoma reversal occurred more frequently in patients with end-ileostomies (10 of 64) than in patients with end-colostomies (1 of 64) or loop-ileostomies (3 of 36), p = 0.017. CONCLUSIONS Patients with Hinchey I-II and small anastomotic defect were safely managed by anastomotic salvage, which reduced the risk of permanent fecal diversion. Anastomotic salvage is a viable option for this subset of patients.