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H Harling

Publications and source records attributed to H Harling.

At least 19 recordsLinked to original sources
PubMed2007

Influence of caseload and surgical speciality on outcome following surgery for colorectal cancer: a review of evidence. Part 2: long-term outcome.

OBJECTIVE: We reviewed recent literature to assess the impact of hospital caseload, surgeon's caseload and education on long-term outcome following colorectal cancer surgery. METHOD: We searched the MEDLINE and Cochrane Library databases for relevant literature starting from 1992. We selected hospital caseload, surgeon's caseload and surgeon's education, type of hospital, and surgeon's experience as variables of interest. Measures of outcome were recurrence-free survival and overall survival, and for rectal cancer frequency of permanent stoma. We reviewed the 34 studies according to tumour location: colonic cancer, rectal cancer, or colorectal cancer. We described the studies individually and performed a meta-analysis whenever it was considered appropriate. RESULTS: For colonic cancer, overall survival improved with increasing hospital caseload, odds ratio (OR) 1.22 [95% confidence interval (CI) 1.16-1.28], and surgeon's education. For rectal cancer, overall survival improved with increasing hospital caseload, OR 1.38 (95% CI 1.19-1.60), and, possibly by surgeon' education and experience. Cancer-free survival was strongly influenced by surgeon's education. The colostomy rate was less in high caseload hospitals, OR 0.76 (95% CI 0.68-0.85). For colorectal cancer, overall survival improved with surgeon's education. CONCLUSION: The data have provided evidence that long-term survival following colorectal cancer surgery in general improved significantly with increasing hospital caseload and surgeon's education.

Colonic Neoplasms↗
PubMed2007

Influence of caseload and surgical speciality on outcome following surgery for colorectal cancer: a review of evidence. Part 1: short-term outcome.

OBJECTIVE: An association between caseload and outcome has been reported for complex surgical procedures. We systematically reviewed recent literature to determine whether caseload and surgical speciality are associated with short-term outcome following colorectal cancer surgery. METHOD: We searched the MEDLINE and Cochrane Library databases for relevant publications starting in 1992. We selected hospital caseload and type, and surgeon's caseload, education and experience as variables of interest. Measures of outcome were postoperative morbidity, in-hospital and 30-day mortality, and for rectal cancer anastomotic leak. We stratified the 35 reviewed studies by tumor location: colonic cancer, rectal cancer, or colorectal cancer and described the studies individually. A meta-analysis was performed only when it was considered appropriate. RESULTS: For colonic cancer, postoperative morbidity was associated with surgeon's caseload and education. Postoperative mortality was strongly associated with hospital caseload (OR 0.64, 95% CI 0.55-0.73), and surgeon's caseload (OR 0.50, 95% CI 0.39-0.64). It was also influenced by surgeon's education and experience. For rectal cancer, we found no evidence of an association between the selected variables and short-term outcome, including frequency of anastomotic leak. For colorectal cancer, there was evidence for an association between postoperative morbidity and hospital caseload. CONCLUSION: Our review offers evidence for a positive association between high hospital caseload, surgeon's caseload, sub-speciality and experience and improved short-term outcome in colonic cancer surgery. We failed to find evidence of a relationship for rectal cancer surgery, possibly owing to methodological artifacts. No study reported an inverse relation.

Clinical Competence↗
PubMed2006

Transanal stent in anterior resection does not prevent anastomotic leakage.

OBJECTIVE: A defunctioning transanal stent may theoretically reduce the leakage rate after anterior rectal resection. We present a randomized open study with the aim of comparing the leakage rate after anterior resection with a loop ileostomy, a transanal stent, both or neither. PATIENTS AND METHODS: Randomized open trial of 194 patients operated in 11 hospitals during September 2000 to September 2003 with anterior resection for a mobile rectal tumour, 115 men and 79 women, median age 68 years (range 37-90 years). The surgeon decided upon the use of a protective ileostomy, and after completion of the operation the patients were randomized in two groups with and without a transanal stent. RESULTS: A clinically significant leakage was diagnosed in 25 patients (13%). No significant difference was found 17 of 98 patients with a stent and 8 of 96 without (P = 0.09), or in 9 of 44 ileostomy patients with a stent and in 3 of 45 without (P = 0.07). Several leaks over a short time led to an interim analysis after inclusion of 194 of 448 planned patients. The analysis showed no significant protective effect of the stent, and more leakages in the stent group, although not statistically significant. On this basis it was decided to discontinue the study prematurely for ethical reasons. CONCLUSION: Decompression of the anastomosis with a transanal stent does not reduce the risk of anastomotic leakage after anterior resection.

Aged↗
PubMed2005

Hospital volume and outcome of rectal cancer surgery in Denmark 1994-99.

OBJECTIVE: The association between hospital volumen and outcome of major cancer surgery is being debated at present. We analysed the outcome of rectal cancer surgery in Denmark during the period 1994-99. METHODS: All patients with a first-time rectal cancer were registered in a national database during the 5-year period. In this observational cohort study, the influence of hospital case volume on resectional procedure, complications, 30-day mortality and 5-year mortality was analysed. RESULTS: The register comprised 5021 patients. Surgery was performed in 27 hospitals with <15 operations per year, 15 hospitals with 15-30 operations per year and 11 hospitals with >30 operations per year. In a multivariate model, the risk of permanent colostomy was significantly increased in the group of low-volume hospitals. On the contrary, volume did not influence the risk of anastomotic leakage, 30-day mortality and 5-year mortality. However, a large variation in 5-year mortality was observed particularly within the low-volume group of hospitals. CONCLUSIONS: In this study, only risk of having a permanent colostomy during surgery for rectal cancer was significantly related to hospital case volume. When individual hospitals were analysed, a large variation in 5-year mortality was observed within the low-volume group of hospitals.

Adult↗
PubMed2004

Survival of rectal cancer patients in Denmark during 1994-99.

OBJECTIVE: As survival from rectal cancer in Denmark is below the European average, we analysed survival during the period of 1994-99 focusing upon improvement strategies. METHOD: All patients with a first-time rectal cancer were registered in a national database during this 5-year period. In the observational cohort study, data on patient age and gender, tumour stage, surgical procedures, adjuvant radiotherapy, anastomotic leakage, 30-day mortality and long-term survival were evaluated. RESULTS: The database comprised 5021 patients. Sixty-four percent had a localized tumour. Less than a third of patients with fixed tumours had pre-operative radiotherapy and curative surgery was achieved in 70%. Anastomotic leakage occurred in 13%, and 30-day mortality was 4% following abdominoperineal or anterior resection and 11% following a Hartmann's procedure. The relative 5-year survival in the entire series was 39% in males and 47% in females, respectively. Following curative surgery the relative 5-year survival was 55% in males and 63% in females, respectively. Survival was 71% in the subset of patients receiving curative total mesorectal excision. CONCLUSION: The average tumour stage upon diagnosis was probably more advanced compared to the other Nordic countries and pre-operative radiotherapy was administered to a minority of patients with fixed tumours. The anastomotic leakage rate was relatively high, whereas the 30-day mortality was comparable to other studies. Survival from rectal cancer in Denmark is still less favourable compared to the other Nordic and several European countries but improved from 1996 and onwards.

Adenocarcinoma↗
PubMed2004

Blood loss and transfusion after total mesorectal excision and conventional rectal cancer surgery.

OBJECTIVES: A recent study showed less bleeding and need of transfusion after total mesorectal excision (TME) compared with conventional rectal cancer surgery. The aim of this study was to evaluate this result in more details. PATIENTS AND METHODS: Comparison of transfusion history in rectal cancer resections in two different multicentre-studies. Two hundred and forty-six patients were operated in the period 1991-93 with a conventional technique and 311 patients were operated with TME-technique in the period 1996-98. Peri-operative data, including blood transfusion from one month before until one month after the operation, was recorded prospectively. RESULTS: The median intra-operative blood loss was 1000 ml, range 50-6000 ml, before, and 550 ml, range 10-6000 ml (P < 0.001) after introduction of TME. The overall peri-operative transfusion rate was reduced from 73% to 43% (P < 0.001). When adjusted for blood loss, age, gender, weight, and type of resection, TME significantly reduced the risk of receiving intra or postoperative blood transfusion by 0.4 (CI: 0.3-0.6). The variability in blood loss among 12 TME-centres was more than 400% and not correlated with transfusion requirements within the centres. CONCLUSION: TME results in a reduced blood loss and a reduction of blood transfusion, but additional factors others than blood loss seems to influence the decision of transfusion.

Aged↗
PubMed2003

Recurrence and survival after mesorectal excision for rectal cancer.

BACKGROUND: 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. METHODS: Three hundred and eleven patients with a mobile rectal cancer had mesorectal excision with curative intent performed by certified surgeons and were followed for 3 years. Demographic, perioperative and follow-up data were recorded prospectively. A series of patients who had conventional operations for rectal cancer served as a control group. RESULTS: The cumulative 3-year local recurrence rate was 11 per cent after mesorectal excision compared with 30 per cent after conventional surgery (hazard ratio (HR) 0.33 (95 per cent confidence interval (c.i.) 0.21 to 0.52); P < 0.001). Multivariate regression analysis showed that only advanced age (HR 0.97 (95 per cent c.i. 0.94 to 1.00); P = 0.048) and tumour in the lower third of the rectum (HR 0.21 (95 per cent c.i. 0.04 to 1.97); P = 0.075) were marginal independent predictors of local recurrence after mesorectal excision. The cumulative crude 3-year survival rate was 77 per cent after mesorectal excision and 62 per cent after conventional surgery (HR 0.58 (95 per cent c.i. 0.43 to 0.77); P < 0.001). Age was the only independent predictor of death after mesorectal excision (HR 1.04 (95 per cent c.i. 1.02 to 1.07); P = 0.001). CONCLUSION: Mesorectal excision is associated with a considerably lower risk of local recurrence and a better survival rate than conventional surgery, and is the optimum method for rectal cancer resection.

Adenocarcinoma↗
PubMed1997

A plant cation-chloride co-transporter promoting auxin-independent tobacco protoplast division.

Although auxin plays a central role in plant development, little is known about the signal transduction pathways triggered by auxin regulating cell elongation, division and differentiation. We describe the molecular analysis of the mutant tobacco line axi 4/1, which was regenerated from an auxin-independent callus created by activation T-DNA tagging. Transcriptional enhancer-mediated deregulated expression of the tagged plant gene axi 4 uncouples division of axi 4/1 protoplasts from external auxin stimuli, whereas in untransformed protoplasts expression of axi 4 and cell division are auxin dependent. axi 4 encodes a 109 kDa protein with significant homology to a family of electroneutral cation-chloride co-transporters (CCCs). We show that overexpression of AXI 4 or another member of the CCC family, the Na+/K+/2Cl--co-transporter from shark, triggers auxin-independent growth of tobacco protoplasts. We suggest that Na+/K+/2Cl--co-transporters may play a role in signalling cell division and that this function is highly conserved between AXI 4 and the shark Na+/K+/2Cl--co-transporter. We also demonstrate that a C-terminal fragment of AXI 4 is sufficient to promote auxin-independent cell division, showing that the C-termini of CCCs are functional subunits triggering cell division. This may allow a molecular dissection of this process not only in plants but also in animal cells.

Amino Acid Sequence↗
PubMed1997

[Anastomotic leakage after low anterior resection for rectal cancer].

A series of 377 consecutive patients were operated upon with low anterior resection for rectal cancer in the nine Danish departments of surgical gastroenterology during 1992-1993. A retrospective analysis was carried out to calculate the frequency of anastomotic leakage and to evaluate factors of potential influence on the development of leakage according to the literature. Sixty-three patients (17%) developed leakage, which was followed by an increased mortality within the first three postoperative months. Only two variables significantly influenced the leakage rate: male gender was associated with a higher leakage rate (p = 0.02), whereas departments with a low number of rectal cancer surgeons had a low rate of anastomotic leakage (p = 0.02). In conclusion, the rather high frequency of anastomotic leakage calls for further clinical and pathogenetic research in this field. Until then, we recommend the routine use of a peroperative leakage test and selective use of prophylactic ostomy in cases of unsatisfactory anastomosis. Furthermore, it is recommended that low anterior resection for rectal cancer is limited to few surgeons in each department in order to ensure a uniform quality and hopefully also thereby reduce the rate of anastomotic leakage.

Adenocarcinoma↗
PubMed1997

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.

Animals↗
PubMed1997

Effect of omeprazole on the outcome of endoscopically treated bleeding peptic ulcers. Randomized double-blind placebo-controlled multicentre study.

BACKGROUND: Haemostasis is highly pH-dependent and severely impaired at low pH. However, there is no clear evidence that acid-suppressing drugs have beneficial effects in peptic ulcer haemorrhage. Endoscopic haemostatic treatment provides important reduction in morbidity and may be more efficient when a neutral intragastric pH is maintained. METHODS: We conducted a double-blind, placebo-controlled multicentre study of intravenous infusion of omeprazole (80 mg as bolus, followed by 8 mg/h) or placebo for 72 h. All patients received 20 mg omeprazole orally from day 3 until follow-up on day 21. Only patients with ulcer haemorrhage, endoscoped within 12 h after admission, and with a history or signs of circulatory failure and spurting bleeding, oozing bleeding, visible vessel, or clot, were included. Endoscopic intervention was aimed at when spurting bleeding, oozing bleeding, or a visible vessel was observed. The primary efficacy measure was the worst ranking on an overall outcome scale (5 = death, 4 = surgery, 3 = additional endoscopic treatment, 2 = more than 3 units of blood, and 1 = no more than 3 units of blood transfused). Base-line prognostic factors of treatment success by day 3 and of other binary outcomes were considered in a logistic regression model. RESULTS: Two hundred and seventy-four patients were randomly assigned to omeprazole (134 patients) or placebo (140 patients). The number of patients included in the 'intention-to-treat' analysis was 130 in the omeprazole group and 135 in the placebo group. The primary variable, the overall outcome at 72 h, showed a difference (P = 0.004) between the two treatments in favour of omeprazole. Treatment success by 72 h defined as no death, no operation, or no additional endoscopic treatment was 91.0% in the omeprazole group and 79.7% in the placebo group (therapeutic gain, 11.3 percentage units; 95% confidence interval, 2.3 to 20.4 percentage units). Significant differences in favour of omeprazole were also found for secondary variables such as number of blood transfusions, duration and degree of bleeding, and the need for surgery and additional endoscopic treatments on day 3 and day 21. However, the numbers of deaths by day 3, 21, or 35 were very similar. CONCLUSIONS: We found a beneficial effect of intravenous omeprazole in severe ulcer haemorrhage, with a reduction in the number of operations, in endoscopic treatments, and in the duration and severity of bleeding.

Aged↗
PubMed1994

[Treatment of radiation-induced vesicovaginal fistula].

The records of 23 patients with vesicovaginal fistulae (VVF) probably caused by irradiation treatment for cancer of the uterine cervix were analyzed. The median latency between irradiation and fistula formation was 17 years. Ten patients had histologically verified cancer recurrence besides a VVF. In addition, nine patients had a rectovaginal- and one an ileovaginal fistula. Twelve patients were treated primarily with ureteroileocutaneostomy a.m. Bricker. Six had bladder drainage, and four of these had ureteroileocutaneostomy performed at a later stage. Four patients initially underwent percutaneous nephrostomy. One patients had a unilateral ureteroileocutaneostomy performed. Eight patients are alive today (median observation time 2.5 years), and all of these had had ureteroileocutaneostomy performed. Three of these patients (38%) were completely relieved of symptoms while the rest occasionally experienced pain, vaginal discharge and bladder empyema. We conclude that ureteroilocutaneostomy a.m. Bricker is a satisfactory procedure for vesicovaginal fistulae because the socially incapacitating symptoms disappear or are considerably diminished.

Adult↗
PubMed1994

Activation tagging: a means of isolating genes implicated as playing a role in plant growth and development.

Activation T-DNA tagging has been used to generate a variety of tobacco cell lines selected by their ability to grow either in the absence of auxin or cytokinin in the culture media, or under selective levels of an inhibitor of polyamine biosynthesis. The majority of the cell lines studied in detail contain single T-DNA inserts genetically co-segregating with the selected phenotype. While most of the plants regenerated from the mutant cell lines appear phenotypically normal, several display phenotypes which could be inferred to result from disturbances in the content, or the metabolism, of auxins and cytokinins, or polyamines. The tagging vector is designed to allow the isolation of tagged plant genes by plasmid rescue. Confirmation that the genomic sequence responsible for the selected phenotype has indeed been isolated is provided by PEG-mediated protoplast DNA uptake of rescued plasmids followed by selection for protoplast growth under the original selective conditions. Several plasmids have been rescued from the mutant lines which confer on transfected protoplasts the ability to grow either in the absence of auxin or cytokinin in the culture media, or under selective levels of an inhibitor of polyamine biosynthesis. This review describes the background to activation tagging and our progress in characterizing the genes that have been tagged in the mutant lines we have generated.

Cytokinins↗
PubMed1993

On the effects of human galanin in man.

Human galanin was recently isolated and sequenced and was found to differ from porcine galanin, hitherto used for studies in humans, in several important respects. We therefore synthesized and purified human galanin and infused it i.v. at a rate of 74 pmol.kg-1.min-1 into six healthy volunteers for 60 min during a hyperglycaemic clamp. The clamp was achieved by i.v. infusion of glucose at a rate which in a control experiment had been demonstrated to maintain the plasma glucose level at 12-13 mmol/l for 90 min. Galanin concentrations reached a plateau of approximately 1500 pmol/l throughout the infusion as opposed to pre-infusion and control levels of 20-30 pmol/l. The glucose levels obtained in the two experiments were indistinguishable. Plasma levels of C-peptide and insulin increased significantly in both experiments and the dynamic concentration curves were almost identical. Glucagon concentrations in plasma decreased significantly and similarly. Growth hormone levels, however, increased eight-fold during galanin infusions. Galanin was eliminated from plasma with a half-life of 3.7 +/- 0.4 min, similar to that of porcine galanin. It is concluded that human galanin powerfully stimulates growth hormone secretion in man, but has no effect on pancreatic endocrine secretion or glucose metabolism in the concentrations obtained in this study.

Adult↗
PubMed1993

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.

Animals↗