Circumferential resection margins of rectal tumours post-radiotherapy: how can MRI aid surgical planning?

BACKGROUND: Magnetic resonance imaging (MRI) is known to have high predictive accuracy for circumferential resection margin (CRM) involvement of pre-treatment rectal tumours. This study aims to assess predictive accuracy of MRI for CRM involvement in rectal cancers post-long-course chemoradiotherapy (CRT) and in particular to understand how this information can influence surgical planning. METHODS: Forty-seven rectal cancers treated with CRT followed by bowel resection in one hospital since 2005 were reviewed for clinical, radiological and pathological characteristics. Using a validated pro forma, a radiologist blinded to final histology and original MRI report predicted CRM status from post-CRT MRI images. Results were compared to histological CRM status of final specimen, and differential analysis by type of surgical operation was performed. RESULTS: Overall accuracy of MRI for CRM involvement post-CRT was 72 % with a negative predictive value of 92 %. Abdominoperineal excision (APE) post-CRT was associated with non-significantly higher rates of histologically involved CRM than anterior resection (AR; 41 vs. 21 %) as were mucinous adenocarcinomas when compared to non-mucinous (56 vs. 21 %). Overall accuracy and positive predictive value were non-significantly higher for cancer treated with a standard APE than AR, and negative predictive value was high for both groups. CONCLUSIONS: MRI post-CRT has high negative predictive value for CRM status. Such information is of particular clinical relevance in low rectal cancers treated with APE as it can indicate when a standard surgical approach is likely to be sufficient.

Transrectal high-intensity focused ultrasonography is feasible as a new therapeutic option for advanced recurrent rectal cancer: report on the first case worldwide.

High-intensity focused ultrasonography is the only completely non-invasive thermal therapy. To date its applications have been limited but clinical indications are expanding with enhanced technological advances that have increased the accuracy of targeting and decreased the duration of treatment times. We report its first use for rectal cancer.

The dedicated emergency surgeon: towards consultant-based acute surgical admissions.

INTRODUCTION: The management of an efficient acute surgical service with conflicting pressures of managing elective and emergency work, compounded by waiting list targets and the maximum 4-h wait for patients in accident and emergency poses a significant challenge. We assess the impact of appointing a dedicated emergency surgeon on the delivery of our emergency surgery service. PATIENTS AND METHODS: A comparative retrospective review was undertaken of all surgical admissions (n = 1622) over a 9-month period (between February and November) in the year before and after (2004 and 2005) the appointment of a dedicated emergency surgeon. The impact on service, training and possible financial consequences of this appointment was assessed. RESULTS: A total of 798 surgical admissions in 2004 were compared with 824 admissions in 2005 for the 9-month periods of this study. In 2004, 258 patients were operated on compared with 286 in 2005 (NS). There was a significant increase in day-time operating from 57% in 2004 to 74% in 2005 (P < 0.001) and a significant increase in consultant-supervised operations from 14% to 52% (P < 0.001), with a consequent fall in out-of-hours operating (43% to 26%; P < 0.001). In addition, there was a significant increase in early (within 48 h) discharges from 41% to 53% (P < 0.001). The salary of the new appointment is more than offset by the quantifiable savings of approximately pound90,000 per annum based on the increased proportion of earlier discharges alone as well as the improved quality of care provided. CONCLUSIONS: The appointment of a dedicated emergency surgery consultant has resulted in an increase in day-time consultant-supervised operating, shorter hospital stay for emergency admissions, improved training for surgical trainees, as well as providing potential financial savings for the trust.

The long-term results of diltiazem treatment for anal fissure.

The effects of diltiazem treatment on symptoms of chronic anal fissures and their long-term outcome were investigated. One hundred and twelve patients were supplied with 6-week course of 2% diltiazem cream for twice-daily topical application. The medical notes and extended follow-up by telephone for 112 patients were recorded and statistically analysed. The success rate and satisfaction of topical diltiazem were each over two thirds. Nearly 80% of patients reported no adverse effects, and it seems that those complaints attributed to diltiazem rarely led to reduced compliance. After diltiazem therapy for fissure, 59% of patients required further treatment (medical and/or surgical) over the average 2-year period of follow-up. The reported adverse effects of topical diltiazem treatment in patients with anal fissures were more common than previously thought, although compliance was rarely affected. During consultation regarding the advantages and disadvantages of surgical vs. chemical sphincterotomy, patients should be aware that the majority of patients receiving diltiazem as the primary treatment for anal fissure subsequently require further treatment.

Histological examination of circular stapled 'doughnuts': questionable routine practice?

BACKGROUND: Left-sided colonic resections are often anastomosed by the use of the circular stapling gun. Most surgeons routinely submit the resulting set of 'doughnuts' for histological examination. AIM: The aim of this study is to question the need for this practice by providing our own experience of the impact of 'doughnut' submission on patient management. PATIENTS AND METHODS: Patients who had undergone a stapled anastomosis for colorectal cancer resection (1998-2004) were identified from the department cancer database and clinical records and histopathological reports were reviewed for all cases. RESULTS: From a consecutive series of 100 sets of doughnuts only two showed histological abnormality (inflammatory change and a metaplastic polyp). Three patients had local recurrence over the follow-up period: 12, 14 and 36 months after surgery. Histological review of the 'doughnuts' in these patients did not show any abnormality. None of the above findings had any influence on subsequent management. CONCLUSION: Histological examination of the 'doughnuts' has a considerable impact in terms of time and resource use. This study has shown no benefit in performing routine histological examination of the 'doughnuts'.

Comparison of CT and MRI in the pre-operative staging of rectal adenocarcinoma and prediction of circumferential resection margin involvement by MRI.

OBJECTIVE: It has been suggested that MRI may be used as the sole modality of choice in pre-operative staging in rectal cancers. Knowledge of tumour stage and a threatened Circumferential Resection Margin (CRM) pre-operatively are essential for planning neo-adjuvant therapy and as predictors of local recurrence. At present most units utilize CT scanning to assess these parameters. The aim of our study was two fold: firstly to examine the accuracy of preop CT and MRI staging of rectal cancers compared with final histology and secondly to assess the accuracy of MRI in predicting penetration of the mesorectal envelope (ME). PATIENTS AND METHODS: All patients with biopsy proven rectal adenocarcinoma underwent thin slice MRI and CT scan pre-operatively. Forty-seven patients have been prospectively entered into the study: 24 male (median age 68 years; range 38-91 years). Eleven patients were unsuitable for surgery leaving 36 patients available for study. RESULTS: CT correctly staged patients with T1/T2 rectal cancers more often than MRI (77% vs. 43%, P = 0.226). Patients with T1/T2 tumours were overstaged more often by MRI compared with CT (54% vs. 23%, P = 0.226). A greater proportion of patients with T3 tumours were correctly staged by MRI than CT (76% vs. 41%, P = 0.08); and more T3 disease was understaged by CT than MRI (54 vs. 18%, P = 0.032). CT and MRI staged T4 disease equally. In the assessment of mesorectal envelope integrity, MRI had a sensitivity of 80% and a specificity of 84%. The positive predictive value was 44% and the negative predictive value 96%. CONCLUSIONS: These results suggest significant differences between accurate pre-operative "T" staging by CT and MRI for rectal cancer. MRI has the potential however, to accurately assess mesorectal envelope invasion. Further analysis is required to assess whether MRI can be used as the sole modality in pre-operative staging of rectal cancers.

Unusual perianal tumours masquerading as abscesses.

Tumours of the perianal region and anal canal are uncommon and can present in a variety of ways. Acute anorectal sepsis is a common condition that usually presents as a painful lump close to the anal margin. Tumours in the perianal region may mimic the symptoms and signs of anorectal sepsis, thereby leading to a delay in diagnosis and management. We report three patients who presented to our department with symptoms and signs suggestive of perianal abscess but which on further investigation were discovered to be due to unusual perianal tumours. Only one of the tumours was found to be malignant--a primary perianal mucinous adenocarcinoma; the other two were benign, a leiomyoma and an aggressive angiomyxoma. A high index of clinical suspicion is required to the diagnosis of perianal tumours when assessing patients with painful perianal lumps, particularly those with a long history and those of ethnic origin. Every effort should be made to establish a preoperative diagnosis so that correct treatment can be delivered.

Major colorectal cancer resection should not be denied to the elderly.

AIMS: Adjuvant therapy after surgery for colorectal cancer is often denied to the elderly for various reasons. This study was to determine morbidity and mortality risk after surgery in the elderly and whether this is affected by adjuvant therapy. METHODS: Data were collected prospectively and entered on a database for all patients undergoing resection of colorectal cancer between January 1994 and July 2000. A total of 304 patients were included, 65 aged 80 years and over. RESULTS: There were 84 deaths, 21 (30%) in the over 80s, and 63 (26%) in the under 80s (P=0.51). The 'in-hospital' mortality was 10.1% in the over 80s and 3.8% in the under 80s (P=0.056). In the over 80s the colon was more affected than the rectum (P=0.002). The over 80s were less likely to be offered adjuvant therapy, 7.2% vs 42.1% (P<0.001). The 5 year survival (all-cause mortality) in the over 80s was 58.5% and 47.6% in the under 80s (P=0.25). Cox's regression analysis of all patients identified the following factors to be independently related to overall survival: age>80 years, post-operative leak, increasing Dukes stage and distant recurrence of disease. CONCLUSION: This study has demonstrated that surgery should not be denied to elderly patients with colorectal cancer as despite a higher post-operative morbidity and mortality rate and with the absence of adjuvant therapy, favourable long-term outcome can be achieved by resectional surgery alone.

Successful treatment of chronic anal fissure with diltiazem gel.

OBJECTIVE: Diltiazem is a calcium channel blocker that has shown potential to heal chronic anal fissures. We have prospectively evaluated the treatment of patients with anal fissure with diltiazem gel (SLA Pharma, UK). PATIENTS AND METHODS: All patients with chronic anal fissure from September 1999 to May 2000 were treated topically with 8 mg 2% diltiazem hydrochloride gel (equivalent to 2 cm of gel supplied by SLA Pharma) three times daily. The 23 patients (12 female), median age 45 (range 22-80) years had a 2-36 month (median 6 months) history of fissure. These were associated with a sentinel tag in 9 (39%) patients. RESULTS: The fissure healed in 11 (48%) of 23 patients, including 6 (75%) of 8 patients who previously failed to heal with GTN ointment. There were no recurrences at 3 months and no adverse effects. Of the 12 patients who did not respond to diltiazem, 4 have undergone sphincterotomy. CONCLUSION: Diltiazem gel has a healing rate similar to that observed with GTN ointment but there were no adverse effects, the recurrence rate was lower, and diltiazem was effective in 75% of patients previously treated unsuccessfully with GTN ointment.

Reasons for failure of glyceryl trinitrate treatment of chronic fissure-in-ano: a multivariate analysis.

PURPOSE: Although glyceryl trinitrate ointment has become the first-line treatment for chronic anal fissure, healing rates are lower than after lateral internal sphincterotomy. The purpose of this study was to identify which factors are associated with treatment failure of glyceryl trinitrate ointment. METHODS: All patients who presented with chronic anal fissure from March 1997 to November 1998 were treated with 0.2 percent glyceryl trinitrate ointment. They were prospectively evaluated until healing or lateral internal sphincterotomy occurred, and long-term follow-up was obtained by standardized telephone questionnaire. A Cox model multivariate analysis was used with seven variables to determine significant factors related to healing. RESULTS: Sixty-four patients (42 men and 22 women; mean age, 37.5 years) with chronic fissure-in-ano were treated with 0.2 percent glyceryl trinitrate ointment. Sentinel piles were observed in 19 patients (29.7 percent). Twenty-six patients (40.6 percent) were healed initially, but 12 (46.2 percent) experienced recurrence. Mean follow-up time was 15.6 (+/-5.5) months. Twenty-nine patients (45.3 percent) had known risk factors for anal fissure, including constipation (n = 21; 32.8 percent), recent childbirth (n = 6; 9.3 percent), colonoscopy (n = 1; 1.6 percent), and anoreceptive intercourse (n = 1; 1.6 percent). Fissures were significantly less likely to heal initially (P < 0.05), more likely to recur (P < 0.05), and more likely to remain unhealed in the long term (P < 0.05) in the presence of a sentinel pile. Fissures with a history of more than six months were less likely to heal initially (P < 0.05). CONCLUSION: The presence of a sentinel pile adversely affects the outcome of treatment of chronic anal fissures with glyceryl trinitrate ointment, and a long history of the fissure reduces the rate of initial healing. Reasons for these findings are discussed.

Oophorectomy in primary colorectal cancer.

Colorectal cancer is a common cancer affecting women which may metastasize to the ovaries. We present five cases of ovarian metastases requiring surgery and review the debate regarding oophorectomy at the primary resection for colorectal cancer. Although prophylactic oophorectomy has not been proven to affect survival, further surgery for symptomatic ovarian metastases may be avoided and the increased risk of developing primary ovarian cancer is abolished.

A double-blind randomized placebo-controlled trial of oral indoramin to treat chronic anal fissure.

BACKGROUND: Indoramin is an alpha1-adrenoceptor antagonist and has been shown to reduce anal resting pressure. Its therapeutic potential has not been explored. The aim of this study was to determine the outcome of treatment with oral indoramin on patients with chronic anal fissure in the setting of a double-blind randomized placebo-controlled trial. METHODS: Twenty-three patients with chronic anal fissure were computer randomized to receive a 6-week course of oral indoramin (20 mg) or placebo in identical capsules, twice daily and with bulk-forming laxatives. Pain was assessed by a visual analogue scale from 0 to 10. Anal resting pressure, heart rate and blood pressure were recorded. Patients were reviewed 1 h after taking the capsule and at 2, 6 and 12 weeks thereafter. RESULTS: Fourteen patients were randomized to indoramin and 9 to placebo. Maximum anal resting pressure was reduced from a mean of 96.4 cm H2O (+/- 32) to 67.6 cm H2O (+/- 26), 1 h after indoramin (P=0.02) and there was no significant change after placebo. There were no significant changes in heart rate or blood pressure. Pain was reduced in the placebo group from a score of 4.9 to 2.0 after 6 weeks (P < 0.01) but not in the indoramin group. After 6 weeks, healing had occurred in one (7%) patient in the indoramin group and in 2 (22%) in the placebo group (P > 0.1). After 3 months, the chronic anal fissure in the indoramin group had recurred. The trial was terminated early because of poor healing rates. CONCLUSION: An oral dose of indoramin (20 mg) administered twice daily reduced anal resting pressure by 30% compared with pretreatment levels but was ineffective in healing chronic anal fissures.

Microvascular disease and anastomotic dehiscence in the colon.

Platelet-derived serotonin released in response to tissue manipulation during surgery may contribute to mesenteric arterial vasospasm leading to postoperative anastomotic leakage after colorectal resection. Organ bath experiments were used to demonstrate the efficacy of naftidrofuryl fumarate (NFT) to oppose serotonin-induced vasoconstriction of human mesenteric arteries. Cumulative dose-response curves were derived with and without NFT at 10(-9) and 10(-6) mol/l concentrations. The difference in maximal contractility between the three sets of curves (n = 8 for each) was significant (P < 0.0001). Sensitivity to serotonin in each of the three curves was measured by calculating the concentration for half-maximal response; differences were again significant (P < 0.0001). NFT reduced serotonin-induced contractility in a dose-dependent fashion in rings of human mesenteric arteries in vitro. This suggests a possible role for NFT in reducing mesenteric vasospasm in colorectal surgery.

Prognostic value of nucleolar organizer regions in colorectal neoplasia.

The aims of the study were, firstly, to determine the frequency of nucleolar organizer regions (NORs) in normal colonic mucosa, adenomas and carcinomas, secondly, to determine the relationship of NOR frequency to adenoma diameter, carcinoma stage, patient survival and tumour recurrence. NOR frequency was determined in invasive carcinoma and adjacent normal mucosa in resection specimens from 46 patients with colorectal carcinoma and in 15 colorectal adenomas obtained at colonoscopy. NOR frequency was correlated with conventional prognostic criteria: adenoma diameter and carcinoma stage, tumour recurrence and patient survival. NOR frequency was significantly (P = 0.02) greater in carcinoma (median = 3.64) and adenoma (median = 2.30) compared to non-neoplastic mucosa (median = 1.96). NOR frequency was not significantly related to adenoma diameter, carcinoma node status, patient survival or tumour recurrence. NOR frequency increases with progression through adenoma to carcinoma. The poor association with conventional prognostic factors suggests that NOR frequency is of no value in prediction of adenoma or carcinoma behaviour and therefore does not closely reflect factors determining malignant cell behaviour.

HER2 (c-erbB-2) oncoprotein expression in colorectal adenocarcinoma: an immunohistological study using three different antibodies.

Paraffin wax sections of 70 surgically resected colorectal adenocarcinomas were examined for the overexpression of HER2/c-erbB-2 oncoprotein using three different specific antibodies and the avidin-biotin immunoperoxidase technique. The patients included 38 men and 32 women aged between 47 and 80 years. The tumours were derived from various parts of the large intestinal tract, and represented all three stages of Dukes' classification and the three histological grades of differentiation. Many tumour sections also included adjacent normal or transitional mucosa. Eight tubular adenomas found in the colectomy specimens in association with some carcinomas were also examined. No positive membrane staining was seen in any of the 70 carcinomas, four adenomas, two hyperplastic polyps, nor in the adjacent normal or transitional mucosa. It is suggested that the overexpression of c-erbB-2 gene product is unlikely to be as common and as pronounced in colorectal adenocarcinoma as it is in ductal carcinoma of the breast.

Factors influencing variability of localisation of antibodies to carcinoembryonic antigen (CEA) in patients with colorectal carcinoma--implications for radioimmunotherapy.

Tumour localisation of anti-tumour antibodies varies greatly between patients. Factors which may be responsible for this have been investigated in 56 patients with colorectal carcinoma with a view to improving radioimmunotherapy. Thirty-seven to seventy-four MBq of 125-I labelled mouse monoclonal antibody to CEA, was given intravenously and tumour resected 70-480 h later. Percentage injected activity kg-1 (% inj.act kg-1) in tumour, was inversely correlated with the time interval between injection and operation (P = 0.004). To assess the influence of other parameters on localisation, patients were divided into two time groups according to time interval between injection and operation, 70-120 h (n = 33) and 144-480 h (n = 23). In neither group was there a significant correlation of % inj.act kg-1 with time. The % inj.act kg-1 in tumour showed a significant correlation with that in the blood for both groups (P = 0.005 and P = 0.01). There was no significant correlation for either time group between % inj.act kg-1 in tumour and serum CEA values, the per cent of tumour cells positive for CEA and vascularity. Tumour to blood ratios varied considerably (range 0.3-28.5:1) suggesting that factors other than time and persistence of activity in the blood contribute to efficient targeting. Tumour to blood ratios were inversely correlated with % inj.act kg-1 in blood for the 70-120 h group (P = 0.007), and were positively correlated with % inj.act kg-1 in tumour (P = 0.012). Autoradiography showed that antibody localised predominantly on tumour cells but was distributed heterogeneously, was not solely related to the expression of antigen and in some cases accumulated in necrotic more than viable areas of tumour. Penetration of antibody into malignant acinar structures was poor and CEA-positive cells closer to the blood supply were targeted to a greater extent than distant cells. Preoperative administration of radiolabelled antibody to CEA may be helpful in selecting patients with favourable localisation for radioimmunotherapy.

The value of radioimmunoguided surgery in first and second look laparotomy for colorectal cancer.

Radioimmunoguided surgery (RIGS) using an anti-CEA (A5B7) monoclonal antibody has been assessed in 52 patients (43 primary excisions and nine second look procedures) undergoing surgery for colorectal carcinoma. The antibody localized in 97.8 percent of primary tumours and in 88.8 percent of the principal tumor in second look procedures. Additional information concerning the extent of primary tumor was obtained in 11 of 43 patients (25.5 percent) undergoing excision of primary carcinoma and five of nine patients (55 percent) in the second look series. Incorrect information was obtained about the extent of the primary tumour in six patients (11.3 percent), whereas no incorrect information was obtained during second look procedures. RIGS correctly predicted the subsequent Dukes' staging in 77 percent of first look cases (sensitivity 65 percent, specificity 90 percent), although accurate identification of individual nodes was impossible. The technique influenced the surgical procedure performed in 2 of 43 cases (4.6 percent) in primary surgery and in three of nine patients undergoing second look laparotomy (33 percent). RIGS in primary colorectal carcinoma may provide additional information concerning extent of locally advanced tumors in particular and the principle that the subsequent surgery may be influenced has been established. The technique appears to have a greater role in second look procedures where it may help determine the extent of recurrent tumour. Larger follow-up series are required to define how the additional information provided by this technique may best be exploited.