Local recurrence rate in a national Danish patient cohort after curative treatment for rectal cancer.

AIM: Several trials have shown that preoperative (chemo)radiotherapy (CRT) reduces local recurrence rates (LRRs) in rectal cancer (RC). The use of CRT varies greatly between countries. It is unknown whether the restrictive use of CRT in Denmark results in a higher LRR relative to other countries. The aim was to evaluate the LRR in a national Danish consecutive cohort of patients with RC. METHODS: All data from patients with RC in Denmark in 2009-2010 who were operated on with curative intent were retrieved from the Danish Colorectal Cancer Group database. Patients with metastases at the time of diagnosis, patients with synchronous colon cancer, and patients, in whom only local surgical procedures were performed, were excluded. In total, 1633 patients met the inclusion criteria. Clinical follow-up was at least five years with a cut-off date of 31 December 2015. RESULTS: Clinical follow-up was 5.4 years (median) with an interquartile range of 4.5-6.1 years. Of all included patients, 479 (29%) were treated with preoperative long-course CRT. Local recurrence was found in 68 patients, resulting in an LRR of 4.2%, and 182 (11%) patients developed distant metastases. Five-year overall survival was 74% (95% CI: 71.64-75.91). CONCLUSIONS: Five-year follow-up of curatively treated patients with RC in Denmark revealed a low LRR. This figure is identical to those reported in other Nordic countries, despite Denmark's considerably stricter guidelines for CRT. The obtained results justify the currently adopted restrictive use of preoperative CRT in Denmark.

Inflammatory bowel disease meta-evidence and its challenges: is it time to restructure surgical research?

AIM: The aim of this study was to compare the methodological quality and input paper characteristics of systematic reviews and meta-analyses reported in the medical and surgical literature by performing a systematic 'overview of reviews'. Ulcerative colitis (UC) and Crohn's disease (CD) were used as the framework for this comparison as they are relatively common serious conditions, with both medical and surgical options for therapy. METHOD: Medline, Embase, CINHAL and the Cochrane Database were searched to November 2013. Eligible papers were systematic reviews or meta-analyses that considered a question of therapy in CD or UC. Two independent reviewers selected the papers, extracted the data and scored their methodology using the AMSTAR scoring system. The papers were categorized into medical therapy (M), surgical therapy (S) or medical and surgical therapy (MS) groups. Following retrieval of the sample of meta-evidence papers, the original input studies used in their creation were identified and a search of Medline, Embase, CINHAL and the Cochrane Database was performed. A team of researchers then examined the collection of papers for bibliographic and financial information. RESULTS: Five hundred papers were identified in the meta-evidence search, of which 118 were deemed eligible. There was a difference in the AMSTAR-rated average quality of the papers between the S and M group (S 7.36 vs M 8.75, P = 0.01). On average S papers were published in journals with a lower impact factor (S 3.26, M 5.04, MS 5.30, P < 0.001). S papers also showed more heterogeneity (I(2) ; S 37%, M 24%, MS 10%, P < 0.001). Some 25% of S meta-analyses used data-sets with significant heterogeneity (I(2) > 75%), compared with 8% of M meta-analyses and 3% of the MS meta-analyses. Some 5% of S papers were done on data sets that had I(2) values > 90%. There was no difference in the average number of papers assessed in each group, the average number of patients per meta-paper, the average time covered by the reviews, the average number of papers considered within each meta-analysis, or the average number of patients considered within each meta-analysis. Considering the conclusions of each meta-analysis, S meta-evidence was 50% more likely than M meta-evidence to be unable to make recommendations for practice. A total of 1499 original input papers were identified, of which 283 were used in more than one review. Within the non-repeated papers (n = 1023) the average impact factor within the S group was lower than that of the M and the MS groups (3.720 vs 11.230 vs 7.563, respectively; ANOVAP < 0.001). M papers had higher rates of pharmaceutical sponsorship than S papers (M 56% vs S 1%) and twice the level of government support (M 16% vs S 8%). Of note, 21% of M papers had corporate sponsorship but did not list any conflict of interest. CONCLUSION: Compared with M meta-analyses, S meta-analyses in the UC and CD domain are more likely to be of poorer methodological quality, are of a greater degree of heterogeneity and less often offer a positive conclusion. The papers used to generate meta-evidence in M papers have a greater degree of corporate and government sponsorship, and are more likely to come from journals with higher impact factors.

National and international guidelines for rectal cancer.

AIM: Rectal cancer is a common malignancy. Differences in daily practice may influence the morbidity and mortality, and many national and international organizations have created guidelines for staging and treatment of rectal cancer. Even though consensus is reached within individual guidelines, this might not be the case between guidelines. No formal evaluation of the contrasting guidance has been reported. METHOD: A systematic search for national and international guidelines on rectal cancer was performed. Eleven guidelines were identified for further analysis. RESULTS: There was no consensus concerning the definition of rectal cancer. Ten of the 11 guidelines use the TNM staging system and there was general agreement regarding the recommendation of MRI and CT in rectal cancer. There was consensus concerning a multidisciplinary approach, preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME). There was no consensus concerning local treatment of T1 tumours and adjuvant therapy, and not all guidelines included metastatic disease and recurrence. There was no consensus on the protocol for follow up. The guidelines had different approaches to evidence. All referred to evidence but not all considered the level of evidence. CONCLUSION: The intention of the study was to provide an overview of international guidelines for rectal cancer based on the underlying evidence, but despite hard evidence it was very difficult to reach general conclusions. Despite much knowledge, there is no international consensus on guidelines for the staging and treatment of rectal cancer.

Pelvic floor reconstruction with a biological mesh after extralevator abdominoperineal excision leads to few perineal hernias and acceptable wound complication rates with minor movement limitations: single-centre experience including clinical examination and interview.

AIM: The aim of the study was to describe long-term subjective and objective results of pelvic floor reconstruction using an absorbable biological mesh after extralevator abdominoperineal excision (ELAPE) for low rectal cancer. METHOD: Records of 53 patients who had an ELAPE with reconstruction of the pelvic floor with a Permacol® mesh between August 2007 and August 2011 were reviewed. Thirty-one of the patients were called for interview and clinical examination. RESULTS: Three (6%) patients developed perineal hernia, 11 had fistulae (nine of which were treated successfully), four patients had a perineal abscess and four patients had superficial wound infections. Removal of the mesh was necessary in one case, while another patient needed implantation of a new mesh. In 13 of the 31 interviewed patients, long-term pain was present, but resolved after a median of 8 months (3-56). No major sitting or movement disabilities were encountered. Three-year survival was 82%, and no local recurrences were found. CONCLUSION: Pelvic floor reconstruction with a biological mesh is a feasible solution when performing ELAPE for low rectal cancer, although long-term pain is a frequent complication.

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.

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.

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.

Strict follow-up programme including CT and ¹8F-FDG-PET after curative surgery for colorectal cancer.

AIM: The risk of local recurrence following curative surgery for colorectal cancer (CRC) is up to 50%. A rigorous follow-up program may increase survival. Guidelines on suitable methods for scheduled follow up examinations are needed. This study evaluates a strict follow-up program including carcinogenic embryonic antigen (CEA), chest X-ray, abdominal ultrasound (US), computed tomography (CT) and (18)F-FDG positron emission tomography (FDG-PET). METHOD: A cohort of 132 patients, treated by surgery with curative intent for CRC, was included. Patients were followed prospectively with scheduled controls at 3, 6, 12 and 24 months after curative surgery. CEA, chest X-ray, US, CT and FDG-PET supplemented by clinical examination. The end-point was recurrence. Sensitivity and specificity was estimated 2 years after surgery. RESULTS: Of the 132 patients included in the study, 25 experienced recurrence, detected at scheduled controls (n = 18) and at intervals between them (n = 7). The results of CT and FDG-PET were correlated with recurrence. CT combined with FDG-PET had the highest specificity and sensitivity. CONCLUSION: A total of 72% of recurrences were detected at scheduled controls. The findings supported a strict follow-up program following curative surgery for colorectal cancer. FDG-PET combined with CT should be included in control programs.

Staged or simultaneous resection of synchronous liver metastases from colorectal cancer--a systematic review.

OBJECTIVE: A systematic review of the literature was undertaken to estimate the differences in length of hospital stay, morbidity, mortality and long-term survival between staged and simultaneous resection of synchronous liver metastases from colorectal cancer to determine the level of evidence for recommendations of a treatment strategy. METHOD: A Pub-med search was undertaken for studies comparing patients with synchronous liver metastases, who either had a combined or staged resection of metastases. Twenty-six were considered and 16 were included based on Newcastle Ottawa Quality Assessment Scale. All studies were retrospective and had a general bias, because the staged procedure was significantly more often undertaken in patients with left-sided primary tumours and larger, more numerous and bi-lobar metastases. Analyses of primary outcomes were performed using the random effects model. RESULTS: For the reason of the heterogeneity of the observational studies, no odds ratios were calculated. In 11 studies, there was a tendency towards a shorter hospital stay in the synchronous resection group. Fourteen studies compared total perioperative morbidity and lower morbidity was observed in favour of a combined resection. Fifteen studies compared perioperative mortality, which seemed to be lower with the staged approach. Eleven studies compared 5-year survival, which seemed to be similar in the two groups. CONCLUSION: No randomized controlled trials were identified, and hence a meta-analysis was not performed. The evidence level is II to III with grade C recommendations. Synchronous resections can be undertaken in selected patients, provided that surgeons specialized in colorectal and hepatobiliary surgery are available.

An interim analysis of recruitment to the COLOFOL trial.

OBJECTIVE: To analyse the ongoing process of recruiting patients into a multicenter randomized trial on follow-up after curative surgery for colorectal cancer. The trial is registered in Clinical Trials Registration. METHOD: Prospective registration of all operated patients as well as inclusions (curative resection, stage II or III disease,

Transanal endoscopic microsurgery in 143 consecutive patients with rectal adenocarcinoma: results from a Danish multicenter study.

OBJECTIVE: The long-term results are presented on total survival, cancer-specific survival and recurrence in 143 consecutive patients treated with transanal endoscopic microsurgery (TEM) for adenocarcinoma of the rectum. METHOD: Four Danish centres established in 1995 a database for registration of all TEM procedures. Data were supplemented from pathology reports and death certificates were checked in the Danish patient registry. Data were analysed with multivariance regression and survival analysis. RESULTS: The T stage was as follows: T1 50%, T2 33%, T3 14%, and stage unknown 3%. TEM was performed with curative intent in 43%, for compromise in 52% and for palliation in 5%. Five-year total survival was 66% and 5-year cancer-specific survival 87%. Cancer-specific survival for T1 was 94%. The significant predictors for total survival were age and tumour size. For cancer-specific survival T stage, radical resection, tumour size and recurrence were significant predictors. Eighteen per cent had recurrence and 15% had immediate reoperation. CONCLUSION: The TEM provides good long-term results for pT1 cancers. In old patients and patients with co-morbidity TEM may provide acceptable long-term results for T2 cancers. Tumours larger than 3 cm should not be treated with TEM for cure.

Systematic reviews and meta-analyses in coloproctology: interpretation and potential pitfalls.

A systematic review (SR) is the unbiased appraisal of systematically identified relevant studies. Implicit in its definition is a robust and scientifically valid process, and when performed as such, SR is an important clinical research tool and influence in health policy decision-making. This educational paper outlines that, from the original prototype based on randomized trials, there are now many other types of SRs including those based on: nonrandomized comparative studies, observational studies, prognostic studies, and studies of diagnostic and screening tools. While each of these has a similar 'anatomy' or format, at an individual class level, there are principles specific to each SR type. Several examples from the coloproctology literature are used as case-studies to illustrate potential pitfalls, and upon re-analysis, often reverse or attenuate the conclusions stated in the original publication. These examples serve to emphasize the need for health professionals to understand the process of SR and meta-analysis so that we all arrive at appropriate interpretations to the benefit of our patients.

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.

Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study.

BACKGROUND: Patients undergoing major abdominal surgery carry a high risk of venous thromboembolism (VTE), but the optimal duration of postoperative thromboprophylaxis is unknown. OBJECTIVES: To evaluate the efficacy and safety of thromboprophylaxis with the low molecular weight heparin (dalteparin), administered for 28 days after major abdominal surgery compared to 7 days' treatment. PATIENTS/METHODS: A multicenter, prospective, assessor-blinded, open-label, randomized trial was performed in order to evaluate prolonged thromboprophylaxis after major abdominal surgery. In total, 590 patients were recruited, of whom 427 were randomized and received at least 1 day of study medication, and 343 reached an evaluable endpoint. The primary efficacy endpoint was objectively verified VTE occurring between 7 and 28 days after surgery. All patients underwent bilateral venography at day 28. RESULTS: The cumulative incidence of VTE was reduced from 16.3% with short-term thromboprophylaxis (29/178 patients) to 7.3% after prolonged thromboprophylaxis (12/165) (relative risk reduction 55%; 95% confidence interval 15-76; P=0.012). The number that needed to be treated to prevent one case of VTE was 12 (95% confidence interval 7-44). Bleeding events were not increased with prolonged compared with short-term thromboprophylaxis. CONCLUSIONS: Four-week administration of dalteparin, 5000 IU once daily, after major abdominal surgery significantly reduces the rate of VTE, without increasing the risk of bleeding, compared with 1 week of thromboprophylaxis.

Quality of life after rectal resection for cancer, with or without permanent colostomy.

BACKGROUND: For almost one hundred years abdominoperineal excision has been the standard treatment of choice for rectal cancer. With advances in the techniques for rectal resection and anastomosis, anterior resection with preservation of the sphincter function has become the preferred treatment for rectal cancers, except for those cancers very close to the anal sphincter. The main reason for this has been the conviction that the quality of life for patients with a colostomy after abdominoperineal excision was poorer than for patients undergoing a sphincter-preserving technique. However, patients having sphincter-preserving operations may experience symptoms affecting their quality of life that are different from those with stoma-patients. OBJECTIVES: To compare the quality of life in rectal cancer patients with or without permanent colostomy. SEARCH STRATEGY: We searched PUBMED, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Colorectal Cancer Group's specialised register. Abstract books from major gastroenterological and colorectal congresses were searched. Reference lists of the selected articles were scrutinized. SELECTION CRITERIA: All controlled clinical trials and observational studies in which quality of life was measured in patients with rectal cancer having either abdominoperineal excision or low anterior resection, using a validated quality of life instrument, were considered. DATA COLLECTION AND ANALYSIS: One reviewer (JP) checked the titles and abstracts identified from the databases and hand search. Full text copies of all studies of possible relevance were obtained. The reviewer decided which studies met the inclusion criteria. Both reviewers independently extracted data. If information was insufficient the original author was contacted to obtain missing data. Extracted data were crosschecked and discrepancies resolved by consensus. MAIN RESULTS: Thirty potential studies were identified. Eleven of these, all non-randomised and representing 1412 participants met the inclusion criteria. Six trials found that people undergoing abdominoperineal excision did not have poorer quality of life measures than patients undergoing anterior resection. One study found that a stoma only slightly affected the person's quality of life. Four studies found that patients receiving abdominoperineal excision had significantly poorer quality of life than after anterior resection. Due to heterogeneity, meta-analysis of the included studies was not possible. AUTHORS' CONCLUSIONS: The studies included in this review do not allow firm conclusions as to the question of whether the quality of life of people after anterior resection is superior to that of people after abdominoperineal excision. The included studies challenged the assumption that anterior resection patients fare better.Larger, better designed and executed prospective studies are needed to answer this question.

Mechanical bowel preparation for elective colorectal surgery.

BACKGROUND: For over a century the presence of bowel content during surgery has been linked to anastomotic leakage. Mechanical bowel preparation has been considered an efficient agent against leakage and infectious complications. This dogma is not based on solid evidence, but on observational data and expert's opinions. OBJECTIVES: To determine the effectiveness and safety of prophylactic mechanical bowel preparation for morbidity and mortality rates in elective colorectal surgery. SEARCH STRATEGY: We searched MEDLINE, EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials. We also searched relevant medical journals, and conference proceedings from major gastroenterological congresses and contacted experts in the field. We used the search strategy described by the Colorectal Cancer Review Group, without limitations for date of publication and language. I SELECTION CRITERIA: Randomised, clinical trials that compared any strategy in mechanical bowel preparation with no mechanical bowel preparation. DATA COLLECTION AND ANALYSIS: Data were independently extracted by the reviewers and cross-checked. The same reviewers assessed the methodological quality of each trial. Details of the randomisation (generation and concealment), blinding, whether an intention-to-treat analysis was done, and the number of patients lost to follow-up was recorded. For analysis the Peto odds ratio (OR) was used as defaults. MAIN RESULTS: Of the 1592 patients (9 trials), 789 were allocated to mechanical bowel preparation (Group A) and 803 to no preparation (Group B) before elective colorectal surgery. For anastomotic leakage (main outcome) the results were: - Low anterior resection: 9.8% (11 of 112 patients in Group A) compared with 7.5% (9 of 119 patients in Group B); Peto OR 1.45, 95% confidence interval (CI): 0.57 to 3.67 (non-significant); - Colonic surgery: 2.9% (Group A) compared with 1.6% (Group B) ; Peto OR 1.80, 95% CI: 0.68 to 4.75 (non-significant); Overall anastomotic leakage: 6.2% (Group A) compared with 3.2% (Group B); Peto OR 2.03, 95% CI: 1.276 to 3.26 (p=0.003). For the secondary outcome of wound infection the result was: 7.4% (Group A) compared with 5.4% (Group B); Peto OR 1.46, 95% CI: 0.97 - to 2.18 (p=0.07); Sensitivity analyses excluding studies with dubious randomisation, studies published as abstracts only, and studies involving children did not change the overall conclusions AUTHORS' CONCLUSIONS: There is no convincing evidence that mechanical bowel preparation is associated with reduced rates of anastomotic leakage after elective colorectal surgery. On the contrary, there is evidence that this intervention may be associated with an increased rate of anastomotic leakage and wound complications. It is not possible to be conclusion on the latter issue because of the clinical heterogeneity of trial inclusion criteria, methodological inadequacies in trial (in particular, poor reporting of concealment and allocation), potential performance biases, and failure of intention-to-treat analyses. Nevertheless, the dogma that mechanical bowel preparation is necessary before elective colorectal surgery should be reconsidered.

The potential role of new therapies in deep-vein thrombosis prophylaxis.

The value of prophylaxis against venous thromboembolism (VTE) is increasingly accepted in most surgical specialties, although the potential reduction in fatal pulmonary embolism has recently been questioned. The burden of VTE in hospital patients nevertheless remains high, partly attributable to underuse of thromboprophylaxis and partly attributable to occurrence of VTE in high-risk patients because recommended antithrombotic therapies fail to provide full protection. Improved physician education has been shown to increase the application of antithrombotic measures, and research efforts are focused on developing novel antithrombotic agents with greater efficacy and safety in clinical use. Several novel indirect and direct thrombin inhibitors have been investigated. The heparinoid danaparoid has shown superiority over unfractionated heparin in several indications, but only the recombinant hirudin, desirudin, has exhibited greater efficacy than low-molecular-weight heparin (LMWH) in thromboprophylaxis for patients undergoing elective hip-replacement surgery, without increasing the risk of bleeding. Three large-scale clinical trials have shown desirudin to be the most effective thromboprophylactic agent currently available in elective hip-replacement surgery; this agent has now been licensed for use in orthopedic surgery. Research is ongoing into the feasibility of still more effective and convenient therapies, such as oral antithrombins.

Dihydroergotamine in postoperative ileus.

The effects of dihydroergotamine (DHE) on postoperative ileus after major abdominal surgery were studied. Forty-one patients received 0.5 mg DHE subcutaneously twice a day from the day of surgery to the seventh postoperative day. Thirty-three patients served as controls. There were no significant differences in the time to the first postoperative passage of flatus or delivery of stools nor in the quantity of laxatives given. It is concluded that DHE does not reduce the duration of postoperative ileus.