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.

Clinical relevance of surgical site infection as defined by the criteria of the Centers for Disease Control and Prevention.

Surgical site infection (SSI) is a common complication after abdominal surgery and the Centers for Disease Control and Prevention (CDC) criteria are commonly used for diagnosis and surveillance. The aim of this study was to evaluate whether SSI diagnosed according to CDC is clinically relevant (CRSSI) and whether there is agreement between evaluations according to the CDC criteria, the ASEPSIS score (Additional treatment, presence of Serous discharge, Erythema, Purulent exudate, Separation of the deep tissues, Isolation of bacteria and duration of Stay) and CRSSI. We included 54 patients diagnosed with SSI and a matched control group (N=46) without SSI according to the CDC criteria after laparotomy. Two blinded experienced surgeons evaluated the hospital records and determined whether patients had CRSSI, based on the following criteria: antibiotic treatment, surgical intervention, prolonged hospital stay or referral to an intensive care unit for SSI. The rate of CRSSI was 38 of 54 (70%) in patients with CDC-diagnosed SSI and none in patients without a CDC-diagnosed SSI. Sixty-one percent of the CDC-diagnosed SSIs were superficial, of which 48% were considered clinically relevant. There was substantial agreement between the CDC criteria and CRSSI [kappa=0.69; 95% confidence interval (CI): 0.55-0.83] and fair agreement between the ASEPSIS score and the CDC criteria (kappa=0.23; 95% CI: 0-0.49) and between the ASEPSIS score and CRSSI (kappa=0.39; 95% CI: 0.17-0.61). The CDC criteria represent a suitable standard definition for monitoring and identifying SSI, even if some cases of less clinically significant superficial SSI are included.

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.

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,

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.

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.

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.

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.

Rectal adenocarcinoma and transanal endoscopic microsurgery. Diagnostic challenges, indications and short term results in 142 consecutive patients.

PURPOSE: The objective of this study was to present short-term results of transanal endoscopic microsurgery (TEM) of rectal adenocarcinomas registered in a national database. METHODS: A Danish TEM group was established in 1995. The group organized a database for prospective and consecutive registration of all TEM procedures. The perioperative course of all rectal cancers treated with TEM and registered in this database is analysed. RESULTS: One hundred forty-two patients had TEM for rectal cancer. In 43%of the patients, the cancer diagnosis was not recognized before TEM. Eighty-five percent of all tumors were classified as benign based on macroscopic appearance; on digital rectal examination, 35% were benign, rectal ultrasound classified 15% as benign, and the preoperative biopsy was benign in 36%. Forty-three cancers (29%) were classified as low risk cancers. High ages were an indication for TEM in 22% and concurrent disease in 21%. Minor complications were encountered in 39 cases, major complications in 4 cases, and 1 patient died within 30 days. CONCLUSION: All larger rectal tumors should be evaluated for malignancy before treatment, even if TEM is the only surgical option, due to high age and comorbidiy. Rectal ultrasound appears to produce the fewest false negative results, but it should be combined with biopsies and clinical evaluation. Multiple biopsies may be beneficial in the case of larger adenomas. When resecting large sessile tumors, there is a considerable risk of incomplete radicality. The short term mortality and morbidity of TEM is low even in old patients with comorbidiy.

Long-term outcome in 445 patients after diagnosis of diverticular disease.

OBJECTIVE: To describe the long-term outcome after primary diagnosis of diverticular disease (DD) with respect to demographics, lifestyle, severity of disease and primary treatment. METHOD: Retrospective cohort study of all 445 consecutive patients admitted to the department during 1989-1995 with the diagnosis DD with prospective follow up. Follow up was performed on all patients during May 2002 by searching the Danish Patient Register and National Register. Logistic regression analyses were applied for defining risk factors for readmission or death. For defined risk factors Kaplan-Meier survival statistics was performed. RESULTS: The male/female ratio was 30/70. Median age was 75 years (men being younger than women, P < 0.01). About 73% received conservative treatment primarily. At follow up 35.3% had suffered clinical recurrence of DD, of these 15.9% were subsequently operated. However, 3.6% of the patients died of causes related to diverticulitis. Possible high-risk groups for recurrence were males and their age above 70 years. CONCLUSION: Age and sex are possible predictors for recurrence of DD. Elective surgery seems not to be justified after just one attack of DD.

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.