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Aim: Approximately 25% of anal cancer patients undergo abdominoperineal excision or more extensive surgery. Following surgery, a high perineal complication rate has been reported. Enhanced recovery after surgery (ERAS) is an evidence-based multimodal interventional programme introduced to mitigate the risk of complications. This study aims to describe perineal healing in relation to ERAS compliance, type of resection and method of perineal reconstruction in patients with anal cancer after salvage surgery., Method: This is a retrospective cohort study including all patients undergoing abdominal surgery for squamous cell anal cancer in Stockholm between January 2005 and December 2015. Data collection was from registers supplemented by chart review. All patients were followed until death or 1 year after surgery. The associations between ERAS compliance, patient and treatment characteristics and perineal wound healing were evaluated using logistic regression., Results: In total, 101 patients (67 women) were included, of whom 72 were ERAS compliant. Of patients alive, healing after surgery occurred in 61/98 and 84/89 at 3 months and 1 year, respectively. Perineal healing at 3 months was statistically significantly associated with younger age and type of perineal reconstruction (in favour of vertical rectus abdominis myocutaneous flap). No associations were observed at 1 year but almost all wounds were healed., Conclusion: Age and type of perineal reconstruction appear to be significantly associated with improved healing at 3 months whereas compliance to an ERAS protocol and type of resection do not. Nearly all patients had a fully healed perineal wound 1 year after surgery for anal cancer., (© 2020 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Background/aim: For patients with locally recurrent rectal cancer (LRRC) extensive surgery is often the only curative option and patient selection is crucial. This study aimed to investigate whether magnetic resonance imaging (MRI) characteristics of the primary tumour can predict oncological outcome after surgery for locally recurrent rectal cancer (LRRC)., Patients and Methods: All patients undergoing surgery for LRRC with a curative intent at the Karolinska University Hospital 2003-2013 were included. MRI examinations of the primary tumour were re-evaluated., Results: In total, 54 patients were included. A tumour volume decrease of <70% after preoperative radiotherapy or chemoradiotherapy (C)RT for the primary tumour was correlated with a lower proportion of R0 resection of the LRRC (OR=0.07, 95% CI=0.01-0.84). No association between MRI characteristics of the primary tumour and prognosis after LRRC surgery was found., Conclusion: Long-term outcomes after surgery for LRRC were not significantly associated with MRI characteristics of the index tumour. However, factors associated with increased risk of R1 resection of LRRC were identified., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: Surgical treatment of colorectal cancer with synchronous colorectal liver metastases (SCRLM) can follow three different strategies with regard to the timing of liver resection. The aim of this study was to describe the selection of surgical strategy, focusing on differences between colon and rectal cancer with SCRLM, postoperative morbidity/mortality and survival., Method: This was a retrospective population-based study of patients with SCRLM registered in the Swedish Colorectal Cancer Registry in the Stockholm/Gotland region during 2010-2017 and treated with surgical resection of the primary tumour and liver metastases (LM). Patients were followed for 5 years or censored at 22 November 2018., Results: A total of 238 patients met the inclusion criteria during the study period. Patients with rectal cancer were treated with the 'liver first' strategy in 70% of cases, whereas the main treatment strategies for colonic tumours were 'simultaneous resection' (44%) and 'primary first' (37%). Rectal cancer had a superior 5-year survival rate compared with colon tumours with SCRLM (62 vs. 47%; p = 0.033). There was no difference in survival between treatment strategies irrespective of primary tumour location. Postoperative complications occurred most commonly among rectal tumours treated with simultaneous resection (p = 0.024)., Conclusion: Patients with rectal cancer and SCRLM were more often treated with the 'liver first' strategy than patients with colon cancer. Patients with rectal cancer and SCRLM where both primary tumour and LM were operated on had significantly better survival than corresponding patients with colon cancer., (© 2020 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Background: Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control., Methods: In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocarcinoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within 5 weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5 × 5 Gy over a maximum of 8 days) followed by six cycles of CAPOX chemotherapy (capecitabine 1000 mg/m 2 orally twice daily on days 1-14, oxaliplatin 130 mg/m 2 intravenously on day 1, and a chemotherapy-free interval between days 15-21) or nine cycles of FOLFOX4 (oxaliplatin 85 mg/m 2 intravenously on day 1, leucovorin [folinic acid] 200 mg/m 2 intravenously on days 1 and 2, followed by bolus fluorouracil 400 mg/m 2 intravenously and fluorouracil 600 mg/m 2 intravenously for 22 h on days 1 and 2, and a chemotherapy-free interval between days 3-14) followed by total mesorectal excision. Choice of CAPOX or FOLFOX4 was per physician discretion or hospital policy. Patients allocated to the standard of care group received 28 daily fractions of 1·8 Gy up to 50·4 Gy or 25 fractions of 2·0 Gy up to 50·0 Gy (per physician discretion or hospital policy), with concomitant twice-daily oral capecitabine 825 mg/m 2 followed by total mesorectal excision and, if stipulated by hospital policy, adjuvant chemotherapy with eight cycles of CAPOX or 12 cycles of FOLFOX4. The primary endpoint was 3-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour, or treatment-related death, assessed in the intention-to-treat population. Safety was assessed by intention to treat. This study is registered with the EudraCT, 2010-023957-12, and ClinicalTrials.gov, NCT01558921, and is now complete., Findings: Between June 21, 2011, and June 2, 2016, 920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4·6 years (IQR 3·5-5·5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23·7% (95% CI 19·8-27·6) in the experimental group versus 30·4% (26·1-34·6) in the standard of care group (hazard ratio 0·75, 95% CI 0·60-0·95; p=0·019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression)., Interpretation: The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer., Funding: Dutch Cancer Foundation, Swedish Cancer Society, Spanish Ministry of Economy and Competitiveness, and Spanish Clinical Research Network., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision is widely accepted as the standard of care for high-risk rectal cancer. Adjuvant chemotherapy is advised in several international guidelines, although the survival benefit remains unclear and compliance is poor. The current multidisciplinary approach has led to major improvements in local control, yet the occurrence of distant metastases has not decreased accordingly. The combination of short-course radiotherapy (SCRT) and chemotherapy in the waiting period before surgery might have several benefits, including higher compliance, downstaging and better effect of systemic therapy., Methods: This is an investigator-initiated, international multicentre randomized phase III trial. High-risk rectal cancer patients were randomized to SCRT followed by chemotherapy (6 cycles CAPOX or alternatively 9 cycles FOLFOX4) and subsequent surgery, or long-course radiotherapy (25-28 × 2-1.8 Gy) with concomitant capecitabine followed by surgery and optional postoperative chemotherapy (8 cycles CAPOX or 12 cycles FOLFOX4) according to local institutions' policy. The primary endpoint is time to disease-related treatment failure. Here, we report the compliance, toxicity and postoperative complications in both study groups., Findings: Between June 2011 and June 2016, 920 patients were enrolled. Of these, 901 were evaluable (460 in the experimental arm and 441 in the standard arm). All patients in the experimental arm received 5 × 5 Gy radiotherapy, and 84% of all patients received at least 75% of the prescribed chemotherapy. In the standard arm, the compliance for CRT was 93% and 58% for postoperative chemotherapy. Toxicity ≥grade 3 occurred in 48% of patients in the experimental arm, compared to 25% of patients in the standard arm during preoperative treatment and 35% of patients during postoperative chemotherapy. No statistically significant differences in surgical procedures or postoperative complications were observed., Interpretation: High compliance (84%) of preoperative systemic treatment could be achieved with the experimental approach. Although considerable toxicity was observed during preoperative therapy, this did not lead to differences in surgical procedures or postoperative complications. Longer follow-up time is needed to assess the primary endpoint and related outcomes., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: This study aimed to describe the short-term perineal healing rates in patients with perineal reconstruction using a biological mesh following extralevator abdominoperineal excision (elAPE)., Methods: In a retrospective, descriptive single-centre cohort study, 88 consecutive patients treated with elAPE and perineal closure using a biological mesh between January 2011 and December 2015 were reviewed. All available data from electronic hospital records was collected. Patients were followed for 1 year following surgery and perineal wound status assessed at 3 months and at 1 year., Results: In total, 63 patients were male and all but 8 patients were treated for primary rectal cancer. All patients but 3 had received radiotherapy prior to surgery. Multivisceral excisions were performed in 19 patients. Omentoplasty was performed in 55 patients and 3 different types of meshes were used during the study period. At 3 months, 58 patients (66%) had a healed perineum. No association was detected between patient, tumour or perioperative characteristics and perineal wound status at 3 months. At 1 year, 4 patients were deceased and among the remaining 84, the perineal wound was healed in 77 patients (92%)., Conclusion: The use of biological meshes in perineal reconstruction following elAPE is feasible and safe, and the perineal wound is healed in the majority of the patients within 3 months., (© 2018 S. Karger AG, Basel.)

Introduction: The optimal method for perineal reconstruction after extralevator abdominoperineal excision (elAPE) for low rectal cancer remains controversial. This study aimed to assess whether simultaneous perineal reconstruction and parastomal reinforcement with Strattice™ Reconstructive Tissue Matrix after elAPE could prevent hernia formation., Methods: In this prospective, multicentre, observational, non-comparative study of consecutive patients undergoing elAPE for low rectal cancer underwent simultaneous perineal reconstruction and colostomy site reinforcement with Strattice™ mesh. All patients underwent long course chemoradiotherapy prior to surgery and had excision of the coccyx. Patients were assessed for perineal wound healing at 7 day, 1, 3, 6 and 12 months, perineal and parastomal hernia defects on clinical and radiological assessment at 1 year following surgery., Results: 19 patients (median age = 67 years, median BMI = 26, M:F = 11:8) were entered the study. 10 (52.6%) patients underwent laparoscopic elAPE. The median length of post-operative stay was 9 days. Complete wound healing was observed for 8(42%) patients at 1 month, 12(63%) at 3 months, and 19(100%) patients at 12 months. Median time for radiological and clinical assessment for hernias was 12 months. No perineal hernia was detected in 17 patients following CT assessment. Dynamic MRI was undertaken in 11 patients at 12 months and all showed no evidence of perineal hernia. 3 (16%) patients had a parastomal hernia detected radiologically. No mesh was removed during the 12 months follow up period., Conclusion: Perineal and parastomal reconstruction with biological mesh is a feasible approach for parastomal and perineal hernia prevention after laparoscopic and open elAPE.

Background: Multi-visceral resection, including parts of the urinary tract, is sometimes warranted to achieve cancer clear resection margins and optimize survival in patients with locally advanced colorectal and anal cancer. The aim of this study was to assess morbidity after urinary tract reconstruction dictated by colorectal and anal malignancy and to identify potential predictors of urological complications., Methods: All patients undergoing surgery for colorectal or anal malignancy, including urinary tract resection and synchronous reconstruction, performed at the Karolinska University Hospital during 2004-2015 were included in this retrospective cohort study. Data was collected from medical records with follow-up until at least one year after the index surgery. Complications were graded according to the Clavien-Dindo classification system of surgical complications., Results: The study included 189 patients; 121 underwent cystectomy and 68 partial ureter resection. The rate of high grade urological complications was 22%. The risk of major urological complications was significantly higher in patients subjected to ureter resection compared to after cystectomy (OR 2.60, 95% CI 1.23-5.49). Also, preoperative radiotherapy and intestinal anastomotic dehiscence significantly increased the risk of high grade urological complications., Conclusion: To achieve potentially curative resections with uninvolved margins in patients with locally advanced colorectal and anal cancer, multi-visceral resection including urinary tract reconstruction can be performed with reasonable morbidity., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Aim: Although the rate of local recurrence (LR) after colorectal cancer surgery has decreased, it still poses major surgical and oncological challenges. The aims of this study, based on an audit from a tertiary referral centre, was to evaluate determinants associated with outcomes after surgery for pelvic LR and how these have changed over time., Method: Retrospective analysis of all resections for pelvic LR of colorectal cancer performed at the Karolinska University Hospital from January 2003 until August 2009 (period 1) and from September 2009 until November 2013 (period 2) ., Results: Ninety-five patients with pelvic LR were operated on with a curative intent. An R0 resection was achieved in 77% and an R1 resection in 23%. Lateral compartments were invaded in 48% and this proportion increased in resections performed in period 2 (37% vs 60%, P = 0.05). R1 resections were associated with a higher risk of local re-recurrence than R0 resections (64% vs 16%; OR = 8.90, 95% CI: 2.71-29.78). Lateral recurrences were associated with a lower R0-resection rate than nonlateral recurrences (63% vs 90%; OR = 0.20, 95% CI: 0.05-0.64) and a higher risk of treatment failure in terms of local re-recurrence or distant metastases, or death, as first event (hazard ratio [HR] = 1.75, 95% CI: 1.06-2.75). However, in a multivariate analysis only R1 resections remained a significant prognostic factor for treatment failure (HR = 2.37, 95% CI: 1.32-4.27)., Conclusion: The proportion of lateral pelvic recurrences has increased over time. In comparison with non-lateral LRs, lateral LRs are more difficult to resect radically and are associated with worse overall and disease-free survival. However, with radical surgery many patients with pelvic locally recurrent colorectal cancer may be offered curative treatment., (Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.)

Aim: Reconstruction with an ileosigmoidal anastomosis (ISA) or ileorectal anastomosis (IRA) is a surgical option after a subtotal colectomy. Anastomotic leakage (AL) is a problematic complication and high rates have been reported, but there is limited understanding of the risk factors involved. The aim of this study was to assess the established and potential predictors of AL following ISA and IRA., Method: This was a retrospective cohort study including all patients who had undergone ISA or IRA at three Swedish referral centres for colorectal surgery between January 2007 and March 2015. Data regarding clinical characteristics, treatment and outcome were collected from medical records. Univariate and multivariate logistic regression models were used to determine the association between patient and treatment related factors and the cumulative incidence of AL., Results: In total, 227 patients were included. Overall, AL was detected amongst 30 patients (13.2%). Amongst patients undergoing colectomy with synchronous ISA or IRA (one-stage procedure), AL occurred in 23 out of 120 (19.2%) compared with seven out of 107 (6.5%) after stoma reversal with ISA or IRA (two-stage procedure) (P = 0.004). In addition, the multivariate analyses revealed a statistically significantly lower odds ratio for AL following a two-stage procedure (OR 0.10, 95% CI 0.03-0.41, P = 0.001)., Conclusions: This study confirms high rates of AL following ISA and IRA. In particular, a synchronous procedure with colectomy and ISA/IRA carries a high risk of AL., (Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.)

Background: Despite the close relationship between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD), the association between colectomy and the prognosis of PSC remains controversial., Aim: To explore whether colectomy prior to PSC-diagnosis is associated with transplant-free survival., Methods: A nationwide cohort study in Sweden including all patients aged 18 to 69 years in whom both PSC and IBD was diagnosed between 1987 and 2014 was undertaken. Each patient was followed from date of both PSC and IBD diagnoses until liver transplantation or death, or 31 December 2014. Patients with colon in situ, and colectomy prior to PSC-diagnosis were compared. Survival analyses were performed using the Kaplan-Meier method and multivariable Cox regression models., Results: Of the 2594 PSC-IBD patients, 205 patients were treated with colectomy before PSC-diagnosis. During follow-up, liver transplantations were performed in 327 patients and 509 died. The risk of liver transplantation or death was lower in patients treated with colectomy prior to PSC-diagnosis (HR 0.71, 95% CI 0.53-0.95) than in patients with colon in situ. Male gender, longer time between IBD and PSC-diagnosis and older age were all associated with an increased risk of liver transplantation or death. Colectomy after PSC-diagnosis was however not associated with an increased risk of liver transplantation or death during long-term follow-up., Conclusions: In PSC-IBD patients, colectomy prior to PSC-diagnosis is associated with a decreased risk of liver transplantation or death., (© 2017 John Wiley & Sons Ltd.)

In recent decades cancer care has seen improvements in the speed and accuracy of diagnostic procedures; the effectiveness of surgery, radiation therapy and medical treatments; the power of information technology; and the development of multidisciplinary, specialist-led approaches to care. Such innovations are essential if we are to continue improving the lives of cancer patients across Europe despite financial pressures on our healthcare systems. Investment in innovation must be balanced with the need to ensure the sustainability of healthcare budgets, and all health professionals have a responsibility to help achieve this balance. It requires scrutiny of the way care is delivered; we must be ready to discontinue practices or interventions that are inefficient, and prioritise innovations that may deliver the best outcomes possible for patients within the limits of available resources. Decisions on innovations should take into account their long-term impact on patient outcomes and costs, not just their immediate costs. Adopting a culture of innovation requires a multidisciplinary team approach, with the patient at the centre and an integral part of the team. It must take a whole-system and whole-patient perspective on cancer care and be guided by high-quality real-world data, including outcomes relevant to the patient and actual costs of care; this accurately reflects the impact of any innovation in clinical practice. The European CanCer Organisation is committed to working with its member societies, patient organisations and the cancer community at large to find sustainable ways to identify and integrate the most meaningful innovations into all aspects of cancer care., (Copyright © 2017. Published by Elsevier Ltd.)

Objectives To compare preoperative staging, multidisciplinary team-assessment, and treatment in patients with screening detected and non-screening detected colorectal cancer. Methods Data on patient and tumour characteristics, staging, multidisciplinary team-assessment and treatment in patients with screening and non-screening detected colorectal cancer from 2008 to 2012 were collected from the Stockholm-Gotland screening register and the Swedish Colorectal Cancer Registry. Results The screening group had a higher proportion of stage I disease (41 vs. 15%; p < 0.001), a more complete staging of primary tumour and metastases and were more frequently multidisciplinary team-assessed than the non-screening group ( p < 0.001). In both groups, patients with endoscopically resected cancers were less completely staged and multidisciplinary team-assessed than patients with surgically resected cancers ( p < 0.001). No statistically significant differences were observed between the screening and non-screening groups in the use of neoadjuvant treatment in rectal cancer (68 vs.76%), surgical treatment with local excision techniques in stage I rectal cancer (6 vs. 9%) or adjuvant chemotherapy in stages II and III disease (46 vs. 52%). Emergency interventions for colorectal cancer occurred in 4% of screening participants vs. 11% of non-compliers. Conclusions Screening detected cancer patients were staged and multidisciplinary team assessed more extensively than patients with non-screening detected cancers. Staging and multidisciplinary team assessment prior to endoscopic resection was less complete compared with surgical resection. Extensive surgical and (neo)adjuvant treatment was given in stage I disease. Participation in screening reduced the risk of emergency surgery for colorectal cancer.

Background: Preoperative radiotherapy (RT) for rectal cancer reduces local recurrence rates and possibly also mortality. Patient-related parameters such as age and comorbidity have a major impact on selection to preoperative RT. The aim of this study was to investigate how this selection influences the outcome in rectal cancer regardless of dose or fractionation of RT., Methods: Data from the Swedish Colorectal Cancer Registry and the Swedish National Patient Register on all patients without distant metastasis who underwent elective trans-abdominal surgery for rectal cancer 2000-2010 in the Stockholm-Gotland region was retrieved. Factors influencing survival and recurrence were identified by Cox regression analyses., Results: There were 2300 patients included. Among these 70.3% received preoperative RT. Three-year overall survival (OS), disease-free survival (DFS) and local recurrence rate were 80.2, 68.6 and 4.7%, respectively. All outcome measures were significantly improved over time. In a multivariable analysis in patients with comorbidity (Charlson comorbidity index score ≥1), OS were significantly better following preoperative RT than after surgery alone (HR 0.65, 95% CI 0.49-0.87). OS among patients with advanced age (≥80 years), was not influenced by preoperative RT., Conclusion: OS among patients with comorbidity was better following preoperative RT than after surgery alone while no differences were seen among the elderly. This indicates that the selection process may be optimised for the patients with advanced age but comorbidity should be used cautiously for exclusion of patients from preoperative RT., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background and Aims: Previous studies describing the cumulative failure rate after reconstructive surgery in patients with inflammatory bowel disease have been restricted to specific hospitals, and the generalizability of these results in a population-based setting is unknown. The aim of this study was to investigate the cumulative failure rate and risk factors for failure after reconstructive surgery in patients with inflammatory bowel disease., Methods: The study cohort includes all patients with inflammatory bowel disease in Sweden who underwent colectomy in 2000 through 2013 who were later treated with reconstructive surgery with ileal pouch-anal anastomosis or ileorectal anastomosis. Each patient was followed from admission for reconstructive surgery until admission for failure (a diverting stoma or permanent stoma), date of death, migration or December 31, 2013. Cumulative failure distributions were obtained with the Kaplan-Meier method, and multivariable Cox regression models were used to calculate the risk of failure., Results: Of the 1809 patients with inflammatory bowel disease treated with colectomy and reconstructive surgery, 83% had ulcerative colitis. During follow-up, 270 patients failed, and the cumulative failure rate was 4.1%, 13.2%, and 15.3% after 1, 3, and 5 years, respectively. The risk of failure was lower after treatment with ileal pouch-anal anastomosis than with ileorectal anastomosis [hazard ratio (95% confidence interval): 0.72 (0.56-0.93)]. Gender, hospital volume, and timing of reconstruction were not significantly associated with the risk of failure., Conclusions: The 5-year cumulative failure rate in a nationwide setting was 15.3%, and hospital volume was not associated with the risk of failure., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To report complications after colonoscopy and surgery in patients with neoplasia detected through a population based colorectal cancer (CRC) screening programme in the capital region of Sweden., Methods: Patients who after a positive FOBT screening result underwent colonoscopy from 1 January 2008 to 30 June 2012 were included. Mortality and complications within 30 days after colonoscopy or subsequent surgery were identified through national registers, and complications were assessed through review of medical charts. Complications were graded using the Clavien-Dindo classification., Results: After 2984 colonoscopies, the complication rate was 1%. The risk of post-polypectomy bleeding was 14/1000. The risk of perforation was 1/1000 after a diagnostic colonoscopy and 2.5/1000 after a colonoscopy with polypectomy. One patient developed a post-polypectomy syndrome. There was one death which was not related to the colonoscopy. After surgery for 37 adenomas and 155 CRCs, the total complication rates were 27% and 50%, respectively. The rate of anastomotic leakage was 13% and 12% after surgery for adenomas and CRC, respectively. There were no deaths after surgery. The overall complication rate after colonoscopy and surgery for adenomas and cancer was 4%., Conclusions: Overall complication rates were acceptable and mortality low; however, the rate of anastomotic leakage after surgery for both adenomas and CRC was higher than expected., (© The Author(s) 2016.)

Aim: Many patients with inflammatory bowel disease (IBD) need colectomy, but the rate of reconstructive surgery with restoration of intestinal continuity is unknown. The aim of this study was to investigate the probability, rate and timing of reconstructive surgery after colectomy in patients with IBD in a population-based setting., Method: The study cohort included all patients with IBD in Sweden who underwent colectomy from 2000 to 2009. Each patient was followed from admission for colectomy to admission for reconstructive surgery, date of death, migration or 31 December 2010. Kaplan-Meier survival curves and multivariable Poisson regression models were used to describe the probability, rate and timing of reconstructive surgery., Results: Out of 2818 IBD patients treated with colectomy, 61.0% were male and 78.9% had ulcerative colitis. No reconstructive surgery had been performed in 1595 (56.6%) patients by the end of follow-up. Of the remaining 1223 patients, 526 underwent primary reconstructive surgery and 697 had a secondary reconstruction following a median interval of 357 days from primary surgery in the form of colectomy. The probability of reconstructive surgery was dependent on age (55.6% and 18.1% at ages 15-29 and ≥ 59 years, respectively), and the chance of reconstructive surgery was higher in hospitals that performed more than 13 colectomies for IBD per year [incidence rate ratio and 95% confidence interval 1.27 (1.09-1.49)]., Conclusion: Fewer than half of the patients having a colectomy for IBD underwent subsequent reconstructive surgery. Older age and low hospital volume were risk factors for no reconstructive surgery., (Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.)

Background: Preoperative radiotherapy and chemoradiotherapy for rectal cancer reduce local recurrence rates but is also associated with side effects. Thus, it is important to identify patients in whom the benefits exceed the risks. This study assessed the pretherapeutic parameters influencing the selection to preoperative treatment., Methods: Data on all patients in the Stockholm-Gotland area, Sweden, who underwent elective trans-abdominal surgery for rectal cancer in 2000-2010, was retrieved from the Regional Cancer Registry and the Swedish National Patient Register. Clinical variables were analysed in relation to selected preoperative therapy. Odds Ratios were derived from univariable and multivariable logistic regression models., Results: In total 2619 patients were included. Of these 1789 (68.3%) received preoperative radiotherapy or chemoradiotherapy. Over time, use of preoperative therapy increased (p < 0.001). In a multivariable model, age (≥ 80 years) and comorbidity (Charlson Comorbidity Index score ≥ 2) were strongly correlated to omittance of preoperative treatment (OR: 0.05; 95% CI: 0.04-0.07 and 0.29; 95% CI: 0.21-0.39) but there was no difference between genders. Pre-treatment tumour stage was a strong predictor for selection to preoperative (chemo-) radiotherapy. However, 8.2% of patients with intermediate or advanced tumours were selected to no preoperative treatment while 55.0% of patients with early tumours were selected to preoperative therapy., Conclusions: The use of preoperative (chemo-) radiotherapy increased over time. Suboptimal adherence to guidelines appears to exist leading to a risk of overtreatment and to a small extent also undertreatment. More robust selection criteria, also including age and comorbidity should be developed., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Squamous cell carcinoma of the anus (SCCA) is a rare cancer but its incidence is increasing throughout the world, and is particularly high in the human immunodeficiency virus positive (HIV+) population. A multidisciplinary approach is mandatory (involving radiation therapists, medical oncologists, surgeons, radiologists and pathologists). SCCA usually spreads in a loco-regional manner within and outside the anal canal. Lymph node involvement at diagnosis is observed in 30%-40% of cases while systemic spread is uncommon with distant extrapelvic metastases recorded in 5%-8% at onset, and rates of metastatic progression after primary treatment between 10 and 20%. SCCA is strongly associated with human papilloma virus (HPV, types 16-18) infection. The primary aim of treatment is to achieve cure with loco-regional control and preservation of anal function, with the best possible quality of life. Treatment dramatically differs from adenocarcinomas of the lower rectum. Combinations of 5FU-based chemoradiation and other cytotoxic agents (mitomycin C) have been established as the standard of care, leading to complete tumour regression in 80%-90% of patients with locoregional failures in the region of 15%. There is an accepted role for surgical salvage. Assessment and treatment should be carried out in specialised centres treating a high number of patients as early as possible in the clinical diagnosis. To date, the limited evidence from only 6 randomised trials [1,2,3,4,5,6,7], the rarity of the cancer, and the different behaviour/natural history depending on the predominant site of origin, (the anal margin, anal canal or above the dentate line) provide scanty direction for any individual oncologist. Here we aim to provide guidelines which can assist medical, radiation and surgical oncologists in the practical management of this unusual cancer., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: A high post-operative mortality has been reported following colectomy in patients with inflammatory bowel disease (IBD), especially in some patient groups., Aims: To investigate the 40-day mortality following colectomy in patients with IBD. The secondary aim was to assess whether colectomised IBD patients have an increased mortality compared to the general population., Methods: This is a population-based register study of all patients with IBD in Sweden who underwent total colectomy in 2000-2010. The cohort was identified using international classification codes for ulcerative colitis (UC) and Crohn's disease (CD). Patients registered with both UC and CD before colectomy (UCCD) were analysed separately. Each patient was followed-up to the date of death, migration or 31st of December 2010, whichever came first. Kaplan-Meier survival curves, Cox proportional hazards models and relative mortality rates were used to describe mortality., Results: In the cohort of 3084 patients, 2424 were diagnosed with UC, 326 with CD and 334 with UCCD. The 40-day, 1-year and 3-year mortality was 1.3%, 3.1% and 6.0%, respectively. The highest 40-day mortality was seen in patients ≥59 years of age (4.4%). Colectomy at the primary hospitalisation for IBD did not significantly increase the risk of post-operative mortality, nor did hospital volume. The relative survival after 3 years was 0.99, 0.98, 0.97 and 0.90 in those <30, 30-43, 44-58 and ≥59 years old, respectively., Conclusion: The 40-day mortality following total colectomy in IBD patients in Sweden is low, except in patients ≥59 years old., (© 2014 John Wiley & Sons Ltd.)

Background: Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer., Methods and Design: Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life., Discussion: Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative chemotherapy. In a multi-centre setting this regimen is compared to current standard with the aim of improving survival for patients with locally advanced rectal cancer., Trial Registration: ClinicalTrials.gov NCT01558921.

Objective: The aim of this study was to assess the outcomes of patients undergoing pelvic exenteration (PE) for recurrent gynecologic malignancy., Methods: A retrospective review using all medical records of 28 consecutive patients who underwent PE between January 2002 and December 2011 at a single institution was conducted. Complications were graded according to Clavien-Dindo. Overall survival (OS) and disease-free survival (DFS) were estimated by the method of Kaplan-Meier., Results: Pelvic exenteration was performed for recurrent cancer in all patients. Distribution of primaries was as follows: cervix (n = 10), vagina (n = 5), ovary (n = 5), uterus (n = 4), tube (n = 2), Bartholin gland (n = 1), and vulva (n = 1). In all but 1 case, PE was performed with curative intent. Pelvic exenteration was total (n = 11), anterior (n = 2), or posterior (n = 15). Reconstructive procedures included urinary tract (n = 13), gastrointestinal tract (n = 26), pelvic floor (n = 6), and vagina (n = 5). There was no postoperative mortality within 30 days. All patients developed 1 or several early complications of various grades, and 22 patients (79%) developed late complications. Twelve patients (43%) underwent reoperation because of complications to PE, and 2 patients died within follow-up as a consequence of their PE. A complete tumor resection (R0) was obtained in 23 patients (82%). With a median follow-up of 27 months (range, 2-110 months), the 5-year OS and DFS rates were 70% and 41%, respectively. R0 resection was associated with increased OS (P < 0.001) and DFS (P = 0.015)., Conclusions: Pelvic exenteration for recurrent gynecologic malignancies can be associated with long-term survival in selected patients. However, postoperative complications are common and can be lethal.

On theoretical grounds, nicotine has been implicated as a modifier of cancer progression. We investigated possible associations of smoking or use of Scandinavian moist snuff (snus) with survival after cancer among Swedish male construction workers. Snus use is associated with substantial exposure to nicotine but not to the combustion products in smoke. Among 336,381 workers with detailed information on tobacco use in 1971-1992, we observed 40,230 incident cancers. Complete follow-up through 2007 was accomplished through linkage to population and health registers. Hazard ratios (HRs) and 95% confidence intervals (CIs) for death from any cause, cancer-specific death and death from other causes were derived from Cox proportional hazards regression models adjusted for age at diagnosis, body mass index at study entry and period of diagnosis. Never users of any tobacco served as reference. Increased risks of cancer-specific death were observed both among exclusive smokers (HR(all cancer) 1.15, 95% CI: 1.10-1.21) and never-smoking snus users (1.15, 95% CI: 1.05-1.26). As regards deaths due to other causes, exclusive smokers had higher relative risks than exclusive snus users (p = 0.03). A history of tobacco use, even exclusive use of the seemingly benign snus, is associated with moderately increased cancer-specific mortality. Although nicotine might play a role, the mechanisms warrant further investigation., (Copyright © 2012 UICC.)

We report a combined laparoscopic and open technique for extralevator abdominal perineal excision of the rectum. The key steps are a laparoscopic rectal dissection limited distally by the coccyx. The open, prone, perineal dissection affords excellent views and allows a cylindrical specimen to be obtained. The resulting perineal defect is closed by a biological mesh. Extralevator abdominal perineal excision of the rectum offers a superior oncological specimen with reduced circumferential resection margin involvement compared to traditional techniques. Combined with a laparoscopic approach, this also has the potential to improve postoperative recovery and reduce morbidity.

Background: Preoperative irradiation with 5 × 5 Gy in randomized trials reduces local recurrence rate and may improve survival in patients with resectable rectal cancer., Objective: The aim of this study was to determine whether the same favorable effects could be observed in a population-based study., Design: This study was conducted via a retrospective analysis of prospectively collected data from the Swedish Rectal Cancer Registry., Settings: This study examined population-based data from Sweden., Patients: All newly diagnosed rectal cancers in Sweden are reported to the Swedish Rectal Cancer Registry., Interventions: Between 1995 and 2001, 6878 patients (stages I-III) were operated on with an anterior resection, an abdominoperineal resection, or a Hartmann's procedure. Short-course irradiation was given to 41% of patients preoperatively. To reduce bias, patients operated on with a Hartmann procedure or older than 75 years were excluded when 5-year survival was analyzed (n = 3466). Tumors were analyzed according to height (0-5 cm, 6-10 cm, 11-15 cm)., Main Outcome Measures: Five-year cumulative local recurrence and survival rates., Results: The 5-year cumulative local recurrence rate was 6.3% (95% CI 5.4-7.4) for patients receiving preoperative irradiation and 12.1% (95% CI 10.8-13.5) for patients not receiving preoperative irradiation. Multivariate analyses indicated the risk of local recurrence was 50% lower for patients receiving preoperative irradiation compared with patients not receiving irradiation (hazard ratio = 0.50; 95% CI 0.40-0.62). Among patients younger than 76 years and operated on with an anterior resection or abdominoperineal resection, the 5-year cumulative survival rate was 0.70 (95% CI 0.69-0.72). Disease-free and overall survivals were higher in irradiated patients, and the difference was statistically significant in low tumors., Conclusions: In this population-based analysis, the favorable effect of preoperative short-course irradiation on local recurrence rates, seen in randomized trials, was confirmed for the entire Swedish population irrespective of tumor height and stage. Data also suggested an effect on 5-year survival, especially in patients with low tumors (0-5 cm).

Aim: Predictive tools for local recurrence (LR) of rectal cancer are needed. This study assessed the predictive value of tumour budding detected by MNF-116 and laminin-5 γ2 chain (Ln-5 γ2)., Method: In a case-control study, the surgical specimens of 48 patients with LR after from primary resection of rectal carcinoma and 82 control patients matched for gender and preoperative radiation from a population of 1180 patients operated with total mesorectal excision were studied. The presence of budding was examined using immunohistochemistry with Ln-5 γ2 and pan-cytokeratin staining with MNF-116., Results: Tumour budding counts ranged from 0 to 106 buds (mean 43, median 38) for all patients. Significantly more tumours with more than 35 buds were seen in the LR than in the control group (67 vs 44%; P = 0.02). The spread of budding was also more extensive in the LR than in the control group (63 vs 49%, P = 0.03). In a multivariate analysis with tumour, node, metastasis stage, MNF-116-stained budding was an independent predictor of local failure (P = 0.02). The budding frequency was higher in irradiated tumours in comparison with tumours that had not received irradiation (mean 53 vs 38, P = 0.03). For Ln-5 γ2, more tumours with ≥ 10 buds were seen in the group with LR than among the control patients, but this difference was not statistically significant (73 vs 57%; P = 0.09). No additive value was found in the multivariate logistic regression model when Ln-5 γ2-stained budding frequency was added to MNF-116 and tumour, node, metastasis stage. The agreement between budding frequency determined by MNF-116 and Ln-5 γ2 was moderate, with a κ-coefficient of 0.34 (0.16-0.51)., Conclusion: Tumour budding determined by MNF-116 staining may serve as a predictive marker for LR in rectal cancer., (© 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.)

Although some authorities consider smoking to be an established risk factor for colorectal cancer, the international literature is not entirely consistent. Further, only 1 study has addressed the association with smokeless tobacco and none with Scandinavian moist snuff (snus). This retrospective cohort study included 336,381 male Swedish construction workers with detailed information on tobacco use at cohort entry in 1971-1992. Complete follow-up through 2007 was accomplished by means of linkage to population and health registers. Hazard ratios (HRs) and 95% confidence intervals (CIs) derived from Cox proportional hazards regression models estimated relative risks, adjusted for age and body mass index. Subjects who were never-users of any tobacco served as reference. After up to 37 years of follow-up, pure smoking was associated with a marginally increased risk of colon cancer (HR 1.08, 95% CI 0.99-1.19), a modestly elevated risk of rectal cancer (HR 1.16, 95% CI 1.04-1.30) and a substantial excess risk of anal cancer (HR 2.41, 95% CI 1.06-5.48). Snus use was not significantly associated with an increased risk of colorectal or anal cancer, although the point estimate for colon cancer was similar to that observed among smokers. Swedish data provide meager support for the association between tobacco use and colorectal cancer. A general tendency among Swedish men to quit smoking in recent decades might have attenuated true associations. A link between smoking and anal cancer was confirmed., (Copyright © 2010 UICC.)

Purpose: This study aimed to identify risk factors for local failure in an effort to optimize treatment for rectal cancer., Methods: A total of 154 patients with local failure after abdominal resection were identified from a population-based consecutive series of 2315 patients who underwent operations for rectal cancer in the Stockholm region between January 1995 and December 2004. Surgeons trained in total mesorectal excision performed the surgery, and preoperative radiotherapy was given according to defined protocols. Data from the 9 hospitals in the region, prospectively registered in a database, were reviewed with regard to tumor location and stage, radiation therapy, surgical treatment, and follow-up., Results: In a multivariable analysis, independent risk factors for local failure were distal tumor location and advanced tumor and nodal stage, omission of preoperative radiation, residual disease, and hospitals with lower caseload. Low anterior resection and total mesorectal excision were deployed more often in centers with low failure rates. Discriminators for radiation therapy were patients with male gender, less advanced age, and tumors situated <6 cm from the anal verge., Conclusion: The variability of patient outcome according to local failure depends on tumor stage, nodal stage, and location. Omission of radiation therapy and surgical performance are important additional risk factors to consider when optimizing treatment for rectal cancer.

Background: Anorectal melanoma is rare and surgery is the recommended primary treatment. There has been some debate whether abdominoperineal resection (APR) or local excision is most appropriate. The aim of this study was to provide a population-based analysis of symptoms, treatment and outcome., Methods: From the Swedish National Cancer Registry, 251 patients with anorectal melanoma were identified from 1960 to 1999. Medical reports were collected and reviewed retrospectively. R0 resection was defined by clear macroscopic margins and a pathology report showing a margin greater than 10 mm. Survival was compared with the log rank test, and Cox multivariable analysis was performed., Results: APR and local excision was performed in 66 and 86 patients respectively. Median survival after surgery was 14 months, with no statistically significant difference between the two groups. Seventy-two patients in whom an R0 resection was achieved, irrespective of approach, had a significantly better overall 5-year survival rate than patients with involved margins (19 versus 6 per cent; P < 0.001). Multivariable analysis showed resection status and tumour stage to be independent prognostic variables., Conclusion: Both APR and LE seem appropriate for anorectal melanoma provided clear margins can be achieved; prognosis is poor regardless of surgical approach., (Copyright 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Purpose: To analyze 251 patients (101 males and 150 females) diagnosed with ano-rectal malignant melanoma (ARMM) reported to the Swedish National Cancer Registry during 1960-1999., Methods: Incidence, gender and age profiles, primary anatomical sites and density of the melanomas along with geographic distribution, and prognosis were investigated., Results: The age-standardized incidence of ARMM was significantly higher for females (1.0 per 10(6) females) than for males (0.7 per 10(6) males) throughout the 40-year-period. The incidence increased with age peaking at 75-84 years in both genders. 54% of the tumours were primary in the anal canal, 24% engaged the whole ano-rectal unit and 10% were located at the anal verge (11% unknown primary site). Although ARMM were rare in absolute numbers, their density (number of tumours/square unit) was higher than that of cutaneous malignant melanomas (CMM) on average. No linkage between the geographic distribution of ARMM and population density was found. The prognosis was very poor albeit with a significant gender difference with a five-year survival rate of 10.6% for males and 15.7% for females. The survival rates for both genders improved during the 40-year-period but significantly more for females than males., Conclusion: The reason(s) for the difference in incidence and prognosis according to gender is unknown. The majority of ARMM emerged primary in the anal canal and a primary location exclusively in the colonic mucosa of the rectum is questionable. The higher density of ARMM as compared to the average density of CMM tallies with the result of our previous studies on vulvar melanoma and might be instrumental in exploring non-UV light associated factors in melanoma genesis. The concentration of patients with anal squamous cell carcinoma to population-dense urban areas, as previously reported, was not found in cases of ARMM.

Purpose: To determine the sites of local recurrence after total mesorectal excision for rectal cancer in an effort to optimize the radiation target., Methods and Materials: A total of 155 patients with recurrence after abdominal resection for rectal cancer were identified from a population-based consecutive cohort of 2,315 patients who had undergone surgery by surgeons trained in the total mesorectal excision procedure. A total of 99 cross-sectional imaging studies were retrieved and re-examined by one radiologist. The clinical records were examined for the remaining patients., Results: Evidence of residual mesorectal fat was identified in 50 of the 99 patients. In 83 patients, local recurrence was identified on the imaging studies. All recurrences were within the irradiated volume if the patients had undergone preoperative radiotherapy or within the same volume if they had not. The site of recurrence was in the lower 75% of the pelvis, anatomically below the S1-S2 interspace for all patients. Only 5 of the 44 recurrences in patients with primary tumors >5 cm from the anal verge were in the lowest 20% of the pelvis. Six recurrences involved the lateral lymph nodes., Conclusion: These data suggest that a lowering of the upper limit of the clinical target volume could be introduced. The anal sphincter complex with surrounding tissue could also be excluded in patients with primary tumors >5 cm from the anal verge.

Background: It has been claimed that patients with squamous cell carcinoma of the anal canal (SCCAC) showing intraepithelial lymphocytes have a poor prognosis., Materials and Methods: The histological sections from 277 consecutive SCCAC were reviewed. Cases having a priori a high number of tumoral-intraepithelial lymphocytes (HTIL) were selected. The remaining cases showed only a few to none tumoral-intraepithelial lymphocytes., Results: Eight patients (all females) representing 3% of the 277 SCCAC had HTIL. All these 8 patients with SCCAC/HTIL had clinical stage II and III while these stages comprised 83% of the remaining SCCAC cases., Conclusion: Despite the 8 SCCAC/HTIL patients having a more advanced clinical stage than the remaining 269 SCCAC patients, these 8 patients had longer survival. Between 5 and 15 years follow-up, all SCCAC/HTIL patients had survived, whereas during the same time interval 28 (10.4%) of the SCCAC patients without HTIL had died of their tumor.

A recent report indicates that patients with squamous cell carcinoma of the anal canal (SCCAC) and intraepithelial lymphocytes have a poor prognosis. Against that background, histological sections from 277 consecutive SCCACs were reviewed searching for cases with massive tumor-infiltrating lymphocytes (TILs; >/= 50 lymphocytes /100 tumor cells). Of the 277 SCCACs, 8 (3%) had massive TILs. These 8 patients (all females) had both more advanced clinical stage than the remaining 269 control SCCAC patients. Follow-up studies revealed that the 8 patients with SCCACs having massive TILs had a much better 15 years survival rate than control SCCAC patients. It is concluded that despite SCCAC patients with massive TILs had a more advanced clinical stage than SCCAC controls, SCCAC with massive TILs patients had a longer survival rate (with no deaths after 5 years) than control cases. The search via proteomic methodology for the lymphocyte-attracting tumor protein might bring forward a novel co-adjuvant therapy, capable to increase prolonged survival time in patients having SCCAC without massive TILs.

Unlabelled: Human papillomavirus (HPV) infections of the genital tract are sexually transmitted and prevalent worldwide. In this study, the role of HPV in 72 patients with anal squamous cell carcinoma was investigated., Patients and Methods: Polymerase chain reaction (PCR) in combination with in situ hybridization was used to identify HPV-DNA in the patients' biopsies. The HPV typing was conducted by pyrosequencing. Cell cycle and DNA content were analysed by cytometry., Results: Ninety percent of the carcinoma biopsies carried high-risk oncogenic HPV in their malignant cells. Eighty-one percent of these demonstrated a single infection with HPV16, 18 or 33 and 19% were double infected with HPV16 and HPV18. Accumulations of viral genes were seen at the necrotic area of the tumours. The HPV genome in the tumour cell influenced significantly the host cell cycle progression, but not DNA aberrations. Within these patients, HPVstatus in the malignant cells was not found to be associated with patient survival time., Conclusion: High-risk oncogenic HPV may play an important role in the initiation of host cell proliferation in anal squamous cell carcinoma. However, infection with HPV may not have any direct influence itself on the clinical outcome of these patients considering the treatments currently available.

Ultimately aiming at a more individualized therapeutic approach in epidermoid anal cancer, this study explored the prognostic and predictive impact of a set of tumour markers. From a population-based cohort of 276 patients with epidermoid anal cancer, treated according to prospective protocols, 215 pre-treatment biopsies were investigated using immunohistochemistry. The expression of p53, p21, Cyclin A and CD31 was measured semi-quantitatively. The expression rate was classified as high when immunostaining was seen in > 5% of the tumour cells for p53 and p21, > 20% in Cyclin A and, above median vessel count for CD31. Marker expression was correlated to survival and treatment response. A high Cyclin A expression correlated significantly with improved overall (77% vs 59%, p = 0.005) and tumour-specific (81% vs 64%, p = 0.009) survival at 5 years. Also, the locoregional failure rate was significantly lower in patients with a high Cyclin A expression (12% vs 24%, p < 0.05). In a multivariate Cox analysis Cyclin A was an independent prognostic factor. A low p21 expression correlated with a reduced rate of locoregional failure (14% vs 27%, p < 0.05) but no impact on survival was found. For p53 and CD31 no significant correlations were obtained. Cyclin A may be an indicator of radiosensitivity and a valuable prognostic marker in epidermoid anal cancer.

Purpose: Abdominoperineal resection is associated with considerable morbidity, in particular, the perineal wound. Omentoplasty has been proposed as a means of reducing the perineal complication rate after abdominoperineal resection. This study was designed to assess the available evidence for omentoplasty in abdominoperineal resection., Methods: A MEDLINE search from January 1970 to July 2005 was performed to locate English language articles relating to omentoplasty in abdominoperineal resection. Manual search via reference lists identified additional articles. Articles reporting results from at least ten patients in whom abdominoperineal resection with an omentoplasty was performed were considered. All included reports were reviewed by using a predetermined protocol., Results: Among the ten reports identified, no randomized trials, four studies with control groups, and six case series were found. Primary healing was the outcome measure that was most consistently reported in the different articles. Most authors reported positive results after omentoplasty, and one study showed significant improvement in perineal healing rate at six months. Significant reduction in sinus formation and wound dehiscence also was reported. Only few complications related to the omentoplasty, none of which was fatal, were reported., Conclusions: Although results from the studies included in this review indicate that there may be benefits from including an omentoplasty when performing an abdominoperineal resection, the lack of randomized studies results in only weak evidence.

Background: Markers for guidance with regard to individual prognosis and treatment planning are sought in epidermoid anal cancer. This study assessed the prognostic and predictive value of tumour budding., Patients and Methods: From a population-based consecutive series of patients who were prospectively recorded, it was possible to investigate 209 (76%) of the pretreatment biopsies. Immunohistochemistry with a monoclonal antibody for the gamma2 chain of laminin-5 was used to detect tumour budding (defined as dissociated single cancer cells or clusters of up to five cells)., Results: Tumour budding was detected in 104 (50%) of the 209 samples. No significant correlation was found between tumour budding and clinicopathological characteristics. Patients with tumour budding had a statistically significantly better 5-year overall survival rate compared with patients lacking tumour budding (74% versus 64%, P <0.05). Albeit not statistically significant, other outcome variables such as tumour-specific survival, recurrence after initial complete response and rate of distant metastases, were all in favour of patients with tumour budding. Multivariate analysis reveals tumour budding as an independent positive prognostic factor., Conclusions: Tumour budding detected by laminin-5 immunohistochemistry may be of prognostic value in the treatment of epidermoid anal cancer. However, further studies are needed to clarify the possible clinical implications.

Purpose: The primary therapy in epidermoid anal cancer is radiotherapy, generally with chemotherapy. The use of neoadjuvant chemotherapy has been infrequently reported in the literature. This study presents results from a large population-based series and provides comparisons between different treatments., Methods and Materials: Between 1985 and 2000, 308 patients with invasive epidermoid anal cancer were diagnosed in the Stockholm Health Care Region. Treatment was given according to defined protocols. External beam radiotherapy alone or with concomitant bleomycin and neoadjuvant chemotherapy followed by radiotherapy alone were the primary treatments. Radical surgery was reserved for poor responders or recurrences. Data were reviewed with regard to treatment, outcome, and prognostic factors., Results: Among the 276 patients (90%) treated with curative intent, 264 (96%) received treatment in accordance with the protocols. The overall 5-year survival rate was 68%. Among the 142 patients with locally advanced tumors (T > or =4 cm or N+), patients treated with neoadjuvant platinum-based chemotherapy (n = 91) had significantly better complete response rates compared with patients treated with radiotherapy with or without bleomycin (n = 51) (92% vs. 76%, p < 0.01). A significantly increased overall 5-year survival rate was also found among patients receiving neoadjuvant therapy (63% vs. 44%, p < 0.05)., Conclusion: Structured treatment protocols result in favorable outcome on a population level. The results further suggest a significant therapeutic gain from including neoadjuvant chemotherapy in the treatment of locally advanced anal cancer.

Background: In the management of isolated locoregional failure after (chemo)radiation therapy for anal epidermoid cancer, salvage abdominoperineal resection (APR) is the treatment of choice. The results of a 15-year consecutive population-based series are reviewed., Methods: Details of all patients with anal epidermoid cancer treated from 1985 to 2000 in the Stockholm Health Care Region were recorded prospectively. Among 308 patients with biopsy-proven anal epidermoid cancer, there have been 39 isolated locoregional failures after sphincter-preserving therapy. Thirty-five patients have undergone salvage APR. The medical records of these 35 patients were reviewed retrospectively with regard to surgical and oncological results., Results: There were no postoperative deaths. There was considerable morbidity related to the perineal wound, with postoperative perineal infections in 13 patients and delayed healing beyond 3 months in 23 patients. Complications unrelated to the perineal wound were found in 13 patients. The crude 5-year survival rate for the 35 patients was 52 per cent (median follow-up 33 months). Patients with persistent disease fared significantly worse than those with locoregional recurrence (crude 5-year survival rate 33 versus 82 per cent; P < 0.05, log rank test)., Conclusion: Salvage APR in anal epidermoid cancer is associated with a high complication rate but may result in long-term survival.