Life after PROSPER. What do people do for external rectal prolapse?

AIM: A questionnaire completed by members of the ACPGBI in 1997 was a precursor to the PROSPER trial. It showed a significant variation in favoured practice for the surgical treatment of external rectal prolapse. We repeated the same questionnaire to assess how practice has changed since the completion of the trial and its publication. METHOD: An online survey was circulated to all members of the ACPGBI with identical questions to those used in the original in 1997. RESULTS: Similar numbers of recipients responded (122/791 [15.4%] in 2014;153/600 [25.5%] in 1997). The median number of operations per surgeon per year was unchanged (6 [0-30] vs 6 [0-25]). The percentage of surgeons who favoured an abdominal approach in fit patients in 1997 rose significantly from 63.5% to 81.7% in 2014 (P < 0.01). Delorme's remains the most popular perineal procedure (78.5% vs 93.3%), but the Altemeier procedure increased from 14.9% to 39.3%. Ventral rectopexy was the preferred abdominal approach in 2014 (48.6% vs 5.9% [P < 0.01]), with 96.3% of these being performed laparoscopically. The number of surgeons carrying out posterior rectopexy decreased from 92.6% to 45.9% (P < 0.01). Only 9.9% of surgeons still undertook resection rectopexy compared with 39.7% in 1997 (P < 0.01). The numbers of surgeons favouring a perineal approach decreased (18.3% vs 36.5%) although the use of a perineal procedure in elderly or unfit patients was unchanged (38.5% vs 37.9%). CONCLUSION: The surgical management of external rectal prolapse had changed. More surgeons favoured a laparoscopic abdominal approach in 2014 than in 1997 and the use of perineal approaches had decreased. Of these Delorme's operation remained the most popular but the incidence of the use of Altmeier's procedure had increased.

Extended lateral pelvic sidewall excision (ELSiE): an approach to optimize complete resection rates in locally advanced or recurrent anorectal cancer involving the pelvic sidewall.

BACKGROUND: Complete pathological resection of locally advanced or recurrent rectal and anal cancer is regarded as one of the most important determinants of oncological outcome. Disease in the lateral pelvic sidewall has been considered a contraindication for pelvic exenteration surgery owing to the significant likelihood of incomplete resection. METHODS: We describe a novel technique (ELSiE) to resect disease involving the lateral pelvic sidewall. Patient demographics, post-operative histology, length of hospital stay and complications were collected from prospectively maintained electronic patient database. RESULTS: During 2011-2013, six patients underwent pelvic exenteration surgery with the ELSiE approach. All patients had R0 resection. Three patients required sciatic nerve excision. Four patients developed post-operative complications although no major complications occurred. CONCLUSIONS: Patients with locally advanced and recurrent cancer involving the lateral pelvic sidewall may be rendered suitable for potentially curative radical resection with a modification in the approach to the lateral pelvic sidewall. Our pilot series seems to indicate that our novel technique (ELSiE) is feasible, safe and yields high rates of complete pathological resection.

Use of a modified Delphi approach to develop research priorities for the association of coloproctology of Great Britain and Ireland.

AIM: The modified Delphi approach is an established method for reaching a consensus opinion among a group of experts in a particular field. We have used this technique to survey the entire membership of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) to reach a consensus on prioritizing clinical research questions in colorectal disease. METHOD: Three rounds of surveys were conducted using a web-based tool. In the first, the ACPGBI membership was invited to submit research questions. In Rounds 2 and 3 they were asked to score questions on priority. A steering group analysed the results of each round to identify those questions ranked as being of highest priority. RESULTS: Five hundred and two questions were submitted in Round 1. Following two rounds of voting and analysis, a list of 25 priority questions was produced, including 15 cancer-related and 10 noncancer-related questions. CONCLUSION: It is anticipated that these results will: (i) set the research agenda over the next few years for the study of colorectal disease in the United Kingdom, (ii) promote development and (iii) define funding of new research and prioritize areas of unmet clinical need where the potential clinical impact is greatest.

Survival analysis of elderly patients with a fracture of the odontoid peg.

Fractures of the odontoid peg are common spinal injuries in the elderly. This study compares the survivorship of a cohort of elderly patients with an isolated fracture of the odontoid peg versus that of patients who have sustained a fracture of the hip or wrist. A six-year retrospective analysis was performed on all patients aged > 65 years who were admitted to our spinal unit with an isolated fracture of the odontoid peg. A Kaplan-Meier table was used to analyse survivorship from the date of fracture, which was compared with the survivorship of similar age-matched cohorts of 702 consecutive patients with a fracture of the hip and 221 consecutive patients with a fracture of the wrist. A total of 32 patients with an isolated odontoid fracture were identified. The rate of mortality was 37.5% (n = 12) at one year. The period of greatest mortality was within the first 12 weeks. Time made a lesser contribution from then to one year, and there was no impact of time on the rate of mortality thereafter. The rate of mortality at one year was 41.2% for male patients (7 of 17) compared with 33.3% for females (5 of 15). The rate of mortality at one year was 32% (225 of 702) for patients with a fracture of the hip and 4% (9 of 221) for those with a fracture of the wrist. There was no statistically significant difference in the rate of mortality following a hip fracture and an odontoid peg fracture (p = 0.95). However, the survivorship of the wrist fracture group was much better than that of the odontoid peg fracture group (p < 0.001). Thus, a fracture of the odontoid peg in the elderly is not a benign injury and is associated with a high rate of mortality, especially in the first three months after the injury.

Prognostic significance of extramural vascular invasion in T4 rectal cancer.

AIM: Extramural vascular invasion (EMVI) has been proposed as an adverse prognostic indicator in colorectal cancer, although its use remains both variable and controversial. This study aimed to determine the survival effect of EMVI in T4 rectal cancer. METHOD: Patients undergoing surgery with curative intent for primary T4 rectal cancer between 1971 and 2011 were included from two prospectively collected rectal cancer databases. The main end-point was 3-year survival. RESULTS: From 1142 patients undergoing resection of rectal cancer during the study period, 126 (11.0%) had T4 rectal cancer and were included in the study group. Sphincter preservation was performed in 61 (48%) and a pathologically negative resection margin (R0) was achieved in 104 patients (82.5%). EMVI was present in 51 patients (40.5%) and was an independent predictor of positive lymph node status (adjusted odds ratio 2.66, P = 0.013). Considering all patients, EMVI was associated with reduced overall survival (P = 0.007) and disease-free survival (P = 0.002), but not local recurrence-free survival (P = 0.198). In only those undergoing R0 resection, EMVI predicted reduced disease-free survival with positive nodal status (P = 0.021); it did not predict survival with negative nodal status. CONCLUSION: Overall, EMVI was a strong prognostic marker of survival. However, after complete surgical resection in patients with node-negative disease, EMVI did not predict local recurrence.

PROSPER: a randomised comparison of surgical treatments for rectal prolapse.

AIM: Rectal prolapse is a profoundly disabling condition, occurring mainly in elderly and parous women. There is no accepted standard surgical treatment, with previous studies limited in methodological quality and size. PROSPER aimed to address these deficiencies by comparing the relative merits of different procedures. METHOD: In a pragmatic, factorial (2 × 2) design trial, patients could be randomised between abdominal and perineal surgery (i), and suture vs resection rectopexy for those receiving an abdominal procedure (ii) or Altemeier's vs Delorme's for those receiving a perineal procedure (iii). Primary outcome measures were recurrence of the prolapse, incontinence, bowel function and quality of life scores (Vaizey, bowel thermometer and EQ-5D) measured up to 3 years. RESULTS: Two hundred and ninety-three patients were recruited: 49 were randomised between surgical approaches (i); 78 between abdominal procedures (ii); and 213 between perineal procedures (iii). Recurrence rates were higher than anticipated, but not significantly different in any comparison: Altemeier's vs Delorme's 24/102 (24%) and 31/99 (31%) [hazard ratio (HR) 0.81; 95% CI 0.47, 1.38; P = 0.4]; resection vs suture rectopexy 4/32 (13%) and 9/35 (26%) (HR 0.45; 95% CI 0.14, 1.46; P = 0.2); perineal vs abdominal 5/25 (20%) and 5/19 (26%) (HR 0.83; 95% CI 0.24, 2.86; P = 0.8). Vaizey, bowel thermometer and EQ-5D scores were not significantly different in any of the comparisons. CONCLUSION: No significant differences were seen in any of the randomised comparisons, although substantial improvements from baseline in quality of life were noted following all procedures.

The epidemiology of cervical spondylotic myelopathy.

OBJECTIVES: This is an observational study looking at the epidemiology of cervical spondylotic myelopathy of patients presenting to our hospital. MATERIALS AND METHODS: The notes and MRI scans of 41 patients presenting to the Leicester General Hospital with a clinical diagnosis of cervical myelopathy between January 2004 and December 2008 were reviewed retrospectively. RESULTS: Cervical myelopathy was found to be more common in male patients to the ratio of approximately 2.7:1, with an average age at diagnosis of 63.8 years. Multi-level disease was seen in the majority of patients, with C5/6 being the most commonly affected level. CONCLUSIONS: Cervical myelopathy predominantly affects men in their 7th decade of life. It is often a multi-level disease with C5/6 being the most commonly affected. It has little in common with cervical radiculopathy and is more analogous to lumber spinal stenosis.

Human papillomavirus infection and anal dysplasia in renal transplant recipients.

BACKGROUND: Immunosuppression is a known risk factor for anal human papillomavirus (HPV) disease, including anal squamous cell carcinoma. Additional risk factors for HPV-related disease have not been studied in the renal transplant population. The demographics of anal HPV and associated risk factors were investigated in this population. METHODS: Anal cytology and polymerase chain reaction were used to assess anal HPV disease in a cohort of transplant recipients at the Royal London Hospital. Risk factors associated with increased immunosuppression and HPV exposure were collated to determine any association with anal disease. RESULTS: Anal dysplasia was associated with anal oncogenic HPV infection (P < 0.001), duration of immunosuppression (P = 0.050), previous genital warts (P = 0.018) and receptive anal intercourse (P = 0.013). CONCLUSION: Anal dysplasia was related to immunosuppression and patient factors in this cohort.

Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR Anal Cancer Trial (ACT I).

BACKGROUND: The first UKCCCR Anal Cancer Trial (1996) demonstrated the benefit of chemoradiation over radiotherapy (RT) alone for treating epidermoid anal cancer, and it became the standard treatment. Patients in this trial have now been followed up for a median of 13 years. METHODS: A total of 577 patients were randomised to receive RT alone or combined modality therapy using 5-fluorouracil and mitomycin C. All patients were scheduled to receive 45 Gy by external beam irradiation. Patients who responded to treatment were recommended to have boost RT, with either an iridium implant or external beam irradiation. Data on relapse and deaths were obtained until October 2007. RESULTS: Twelve years after treatment, for every 100 patients treated with chemoradiation, there are an expected 25.3 fewer patients with locoregional relapse (95% confidence interval (CI): 17.5-32.0 fewer) and 12.5 fewer anal cancer deaths (95% CI: 4.3-19.7 fewer), compared with 100 patients given RT alone. There was a 9.1% increase in non-anal cancer deaths in the first 5 years of chemoradiation (95% CI +3.6 to +14.6), which disappeared by 10 years. CONCLUSIONS: The clear benefit of chemoradiation outweighs an early excess risk of non-anal cancer deaths, and can still be seen 12 years after treatment. Only 11 patients suffered a locoregional relapse as a first event after 5 years, which may influence the choice of end points in future studies.

Outcomes following repair of traumatic cloacal deformities.

BACKGROUND: Severe obstetric injury can result in a defect similar to a congenital cloacal deformity, with associated faecal incontinence and sexual dysfunction. The aim of this study was to assess the efficacy of surgical repair of such injuries. METHODS: Patients were identified retrospectively from hospital records. Long-term follow-up data were collected by telephone interview. RESULTS: Outcomes in 31 consecutive patients seen over a 14-year period were reviewed. An overlapping external sphincter repair, with repair of the anorectum and vagina, was performed in 29 patients. Detailed long-term follow-up data were available for 20 patients at a median of 5 years after surgery. Three patients had a stoma at presentation. Surgical repair reduced incontinence to solid stool from seven of 17 to none of 20 patients, to liquid stool from 14 of 17 to ten of 20, and to flatus from 17 of 17 to 12 of 20. Nine patients reported improvement in sexual function. CONCLUSION: Surgical repair of a cloacal injury is associated with significant improvements in faecal incontinence and sexual function. Outcomes are similar to those seen with repair of less severe injuries, and may be maintained in the long term.

Hypoxia-inducible factor-1alpha and -2alpha are expressed in most rectal cancers but only hypoxia-inducible factor-1alpha is associated with prognosis.

The hypoxia-mediated response of tumours is a major determining factor in growth and metastasis. Understanding tumour biology under hypoxic conditions is crucial for the development of antiangiogenic therapy. Using one of the largest cohorts of rectal adenocarcinomas to date, this study investigated hypoxia-inducible factor-1alpha (HIF-1alpha) and HIF-2alpha protein expression in relation to rectal cancer recurrence and cancer-specific survival. Patients (n=90) who had undergone surgery for rectal adenocarcinoma, with no prior neoadjuvant therapy or metastatic disease, and for whom adequate follow-up data were available were selected. Microvessel density (MVD), HIF-1alpha and HIF-2alpha expressions were assessed immunohistologically with the CD34 antibody for vessel identification and the NB100-131B and NB100-132D3 antibodies for HIF-1alpha and HIF-2alpha, respectively. In a multifactorial analysis, results were correlated with tumour stage, recurrence rate and long-term survival. Microvessel density was higher across T and N stages (P<0.001) and associated with poor survival (hazard ratio (HR)=8.7, P<0.005) and decreased disease-free survival (HR=4.7, P<0.005). hypoxia-inducible factor-1alpha and -2alpha were expressed in >50% of rectal cancers (HIF-1alpha, 54%, 48/90; HIF-2alpha, 64%, 58/90). HIF-1alpha positivity was associated with both TNM stage (P<0.05) and vascular invasion (P<0.005). In contrast, no associations were demonstrated [corrected] between HIF-2alpha [corrected] and any pathological features or [corrected] outcome. The study showed an independent association between HIF-1alpha expression and advanced TNM stage with poor outcome. Our results indicate that HIF-1alpha, but not HIF-2alpha, might be used as a marker of prognosis, in addition to methods currently used, to enhance patient management.

Assessment of microvessel density and carbonic anhydrase-9 (CA-9) expression in rectal cancer.

AIM: The mechanism by which neoplasias respond to hypoxia determines their biological behavior and prognosis. Understanding the biology of tumors under hypoxic conditions is crucial for the development of anti-angiogenic therapy. Using the largest cohort of rectal adenocarcinomas to date, this study aimed to assess microvessel density (MVD) and carbonic anhydrase-9 (CA-9) expression and to correlate the results with recurrence and cancer-specific survival. MATERIALS AND METHODS: Patients (n=101) who underwent surgery for rectal adenocarcinoma without previous neoadjuvant therapy or metastatic disease were selected. MVD and CA-9 expression were assessed immunohistologically by using the CD34 antibody and the MN/CA9 M75 antibody, respectively. In a multifactorial analysis, the results were correlated with tumor stage, recurrence rate, and long-term survival. RESULTS: MVD was higher with increased T- and N-stages (p<0.01) and associated positively with poor survival (hazard ratio (HR) 1.3 per 10 vessel increase, p<0.01). CA-9 was expressed in 73% of cancers. Negative lymph node status correlated with CA-9 positivity (p<0.05), reflected in a higher rate of CA-9 positivity in earlier Dukes' stages (p<0.05). CA-9 positivity across tumor node metastasis (TNM) stages approached significance (Stage I/II: 80% CA-9 positive vs. 20% CA-9 negative; Stage III: 63% CA-9 positive vs. 37% negative, p=0.051). A trend was seen towards better cancer-specific survival in patients with CA-9 positive carcinomas (HR 0.51, p=0.07) on univariate analysis. DISCUSSION: MVD was higher in more advanced T- and N-stages and may be used as a determinant of survival in patients with rectal adenocarcinomas. CA-9 expression was seen more often in earlier Dukes' stages, possibly representing an early tumor hypoxic response. CA-9 expression by adenocarcinoma cells may confer long-term survival advantage in surgically treated rectal cancer.

No socioeconomic inequalities in colorectal cancer survival within a randomised clinical trial.

There is strong evidence that colorectal cancer survival differs between socioeconomic groups. We analysed data on 2481 patients diagnosed during 1989-1997 and recruited to a randomised controlled clinical trial (AXIS, ISRCTN32414363) of chemotherapy and radiotherapy for colorectal cancer. Crude and relative survival at 1 and 5 years was estimated in five categories of socioeconomic deprivation. Multiple imputation was used to account for missing data on tumour stage. A multivariable fractional polynomial model was fitted to estimate the excess hazard of death in each deprivation category, adjusting for the confounding effects of age, stage, cancer site (colon, rectum) and sex, using generalised linear models. Relative survival in the trial patients was higher than in the general population of England and Wales. The socioeconomic gradient in survival was much smaller than that seen for colorectal cancer patients in the general population, both at 1 year -3.2% (95% CI -7.3 to 1.0%, P=0.14) and at 5 years -1.7% (95% CI -8.3 to 4.9%, P=0.61). Given equal treatment, colorectal cancer survival in England and Wales does not appear to depend on socioeconomic status, suggesting that the socioeconomic gradient in survival in the general population could well be due to health-care system factors.

Can depth of tumour invasion predict lymph node positivity in patients undergoing resection for early rectal cancer? A comparative study between T1 and T2 cancers.

OBJECTIVE: The present study investigated the risk of lymph node metastasis according to the depth of tumour invasion in patients undergoing resection for rectal cancer. METHOD: The histology of patients undergoing oncological resection with regional lymphadenectomy for rectal cancer at St Marks Hospital from 1971 to 1996 was reviewed. Of the total number of 1549 patients, 303 patients with T(1) or T(2) rectal cancers were selected. The tumour type, grade, evidence of vascular invasion, depth of submucosal invasion (classed into 'sm1-3') were evaluated as potential predictors of lymph node positivity using univariate and multi-level logistic regression analysis. RESULTS: Tumour stage was classified as T(1) in 55 (18.2%) and T(2) in 248 (81.2%) patients. The incidence of lymph node metastasis in the T(1) group was 12.7% (7/55), compared to 19% (47/247) in the T(2) group. The node positive and negative groups were similar with regard to patient demographics, although the former contained a significantly higher number of poorly differentiated (P = 0.001) and extramural vascular invasion tumours (P = 0.002). There was no significant difference in the number of patients with sm1-3, or T(2) tumour depths within the lymph node positive and negative groups. On multivariate analysis the presence of extramural vascular invasion (odds ratio = 10.0) and tumour grade (odds ratio for poorly vs well-differentiated = 11.7) were independent predictors of lymph node metastasis. CONCLUSION: Whilst the degree of vascular invasion and poor differentiation of rectal tumours were significant risk factors for lymph node metastasis, depth of submucosal invasion was not. This has important implications for patients with superficial early rectal cancers in whom local excision is being considered.

The impact of surgically induced ischaemia on protein levels in patients undergoing rectal cancer surgery.

The goal of targeted therapy has driven a search for markers of prognosis and response to adjuvant therapy. The surgical resection of a solid tumour induces tissue ischaemia and acidosis, both potent mediators of gene expression. This study investigated the impact of colorectal cancer (CRC) surgery on prognostic and predictive marker levels. Tumour expression of thymidylate synthase, thymidine phosphorylase, cyclin A, vascular endothelial growth factor (VEGF), carbonic anhydrase-9, hypoxia inducible factor-1alpha, and glucose transporter-1 (GLUT-1) proteins was determined before and after rectal cancer surgery. Spectral imaging of tissue sections stained by immunohistochemistry provided quantitative data. Surgery altered thymidylate synthase protein expression (P=0.02), and this correlated with the change in the proliferation marker cyclin A. The expression of hypoxia inducible factor-1alpha, VEGF, and GLUT-1 proteins was also different following surgery. Colorectal cancer surgery significantly impacts on intratumoral gene expression, suggesting archival specimens may not accurately reflect in situ marker levels. Although rectal cancer was the studied model, the results may be applicable to any solid tumour undergoing extirpation in which molecular markers have been proposed to guide patient therapy.