Bilateral versus unilateral botulinum toxin injections for chronic anal fissure: a randomised trial.

BACKGROUND: Botulinum toxin injected into the internal anal sphincter is used in the treatment of chronic anal fissure but there is no standardised technique for its administration. This randomised single centre trial compares bilateral (either side of fissure) to unilateral injection. METHODS: Participants were randomised to receive bilateral (50 + 50 units) or unilateral (100 units) Dysport® injections into the internal anal sphincter in an outpatient setting. Injection-related pain assessed by visual analogue scale was the primary outcome measure. Secondary outcomes were healing rate, fissure pain, incontinence, and global health scores. RESULTS: Between October 2008 and April 2012, 100 patients with chronic anal fissure were randomised to receive bilateral or unilateral injections. Injection-related pain was comparable in both groups. There was no difference in healing rate. Initially, there was greater improvement in fissure pain in the bilateral group but at 1 year the unilateral group showed greater improvement. Cleveland Clinic Incontinence score was lower in the unilateral group in the early post-treatment period and global health assessment (EuroQol EQ-VAS) was higher in the unilateral group at 1 year. CONCLUSIONS: Injection-related pain was similar in bilateral and unilateral injection groups. Unilateral injection was as effective as bilateral injections in healing and improving fissure pain without any deterioration in continence.

A prospective case-control study of extralevator abdominoperineal excision (ELAPE) of the rectum versus conventional laparoscopic and open abdominoperineal excision: comparative analysis of short-term outcomes and quality of life.

BACKGROUND: Conventional abdominoperineal excision (APE) of the rectum is associated with higher circumferential resection margin (CRM) involvement, increased local recurrence, and reduced survival compared to anterior resection. A more radical extralevator APE (ELAPE) technique may improve oncological outcome. However, this technique may confer additional morbidity, and little comparative data on short-term outcomes have been reported. This study compares short-term outcomes and quality of life (QOL) after open and laparoscopic ELAPE, laparoscopic APE (LAPE), and open APE (OAPE). METHODS: Data on all ELAPE and 10 consecutive LAPE and OAPE were extracted from a prospective database. Perioperative care and follow-up were standardized. QOL was assessed using EORTC questionnaires. RESULTS: Sixteen ELAPE (14 laparoscopic), 10 LAPE, and 10 OAPE were included. Demographics, tumour stage, and neoadjuvant therapy use were comparable. Operative time was higher with ELAPE than LAPE and OAPE (295, 207.5, and 157.5 min, respectively, p = 0.01). A porcine collagen perineal mesh was used in 9 patients undergoing ELAPE but in no LAPE or OAPE patients. No difference in 30-day complications, re-admission, or length of stay was noted. ELAPE and LAPE were associated with earlier removal of urinary catheter (p = 0.02), yet other enhanced recovery after surgery (ERAS) parameters were equivalent. All ELAPE resections were R0 with no positive CRM identified. One LAPE and 2 OAPE were R1 resections. Analysis revealed no deterioration in QOL with ELAPE, with equivalent global health status. CONCLUSIONS: The results of this study suggest that ELAPE is not associated with deterioration in short-term outcomes or QOL when compared with LAPE or OAPE.

Early experience with laparoscopic extralevator abdominoperineal excision within an enhanced recovery setting: analysis of short-term outcomes and quality of life.

INTRODUCTION: Conventional abdominoperineal excision for low rectal cancer has a higher local recurrence and reduced survival compared to anterior resection. An extralevator abdominoperineal excision (ELAPE) may improve outcome through removal of increased tissue in the distal rectum. Experience with ELAPE is limited and no studies have reported on quality of life (QOL) following this procedure. We describe a minimally invasive approach to ELAPE within an enhanced recovery programme, and present short-term results and QOL analyses. METHODS: All laparoscopic ELAPEs were included in a prospective database. Demographics, intra-operative and post-operative outcomes were evaluated. Postoperative QOL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) questionnaires QLQ-C30 and QLQ-CR29. RESULTS: Thirteen laparoscopic ELAPEs were performed over a two-year period. All were enrolled in an enhanced recovery programme. The median age was 76. The median tumour height was 20 mm (range: 0-50 mm) from the dentate line and all patients received neoadjuvant treatment. The median duration of surgery was 300 minutes (range: 120-488 minutes), the mean blood loss was 150 ml and one procedure was converted to open surgery. There was no circumferential resection margin involvement or tumour perforation. The median duration of use of intravenous fluid, patient controlled analgesia and urinary catheterisation was 2, 2 and 2.5 days respectively and the median length of hospital stay was 7.5 days. Two patients developed perineal wound dehiscence. QOL analysis revealed high global health status (90.8), physical (91.3), emotional (98.3) and social functioning (100) scores, which compared favourably with EORTC reference values and published QOL scores following conventional abdominoperineal excision. CONCLUSIONS: Laparoscopic ELAPE within an enhanced recovery setting is a feasible and safe approach with acceptable short-term outcomes and post-operative quality of life.

Correlation of pS2 expression of involved lymph nodes in relation to primary breast carcinoma.

Expression of the pS2 protein in breast carcinoma is a useful guide to prognosis and response to tamoxifen. We have investigated pS2 protein expression in both the primary tumour and lymph node metastases (LNM) using a computer-assisted image analysis system. In a consecutive series of 208 patients undergoing surgical excision of primary breast cancer with axillary clearance, 89 patients were found to have involved lymph nodes. We found a highly significant correlation between pS2 expression in primary tumours and their LNM when 5% was taken as the cut-off for positive staining (Fischer Exact, P < 0.0001). There was also a highly significant correlation between the proportion of positive staining between the local metastases and primary tumours (Spearman's rank order correlation = 0.87; P < 0.0001). We conclude that the pS2 status of LNM can be accurately predicted from the pS2 status of the primary tumour. As such, appropriate adjuvant therapy for primary breast cancer, or second line therapy for disseminated disease can be selected on the pS2 status of the primary tumour alone.

The effect of 5-fluorouracil and alpha interferon and 5-fluorouracil and leucovorin on cellular anti-tumour immune responses in patients with advanced colorectal cancer.

Interferon alpha (IFN-alpha) enhances the activity of 5-fluorouracil (5-FU) in the treatment of advanced colorectal cancer although the mechanism is not understood. We have investigated the effect of this combination on cellular immunity and compared this with standard therapy of 5-FU/L-leucovorin, in 24 patients with advanced colorectal cancer. This study has demonstrated an enhancement of the cellular immune response in patients given 5-FU/IFN-alpha with augmentation of natural killer (NK) cell function and abrogation of 5-FU-induced suppression of lymphokine-activated killer (LAK) cell activity.

Interleukin-8 expression in Helicobacter pylori infected, normal, and neoplastic gastroduodenal mucosa.

AIMS: To investigate the expression of interleukin-8 (IL-8) in Helicobacter pylori infected normal and neoplastic gastroduodenal mucosa, and in established gastric cancer cell lines. METHODS: Immunofluorescence techniques were used to localise IL-8 in cryosections of gastric (n = 25) and duodenal (n = 17) endoscopic biopsy specimens an in resected gastric tumour tissue samples from 16 patients. Two gastric cancer cell lines (Kato 3 and MKN 45) were examined for IL-8 protein expression by immunofluorescence and for the presence of IL-8 mRNA by reverse transcription followed by the polymerase chain reaction (RT-PCR). RESULTS: IL-8 was localised to the epithelium in histologically normal gastric mucosa, with particularly strong expression in the surface cells. IL-8 expression was also a feature of surface epithelium in the duodenal bulb, but was much reduced in the second part of the duodenum. In chronic H pylori-associated gastritis gastritis gastric epithelial IL-8 expression was increased and expression of IL-8 within the lamina propria was evident. By contrast, large areas of IL-8 negative epithelium were observed in the body mucosa of a subject with Ménétrier's disease. In gastric carcinoma the tumour cells were positive for IL-8. IL-8 was also detected by immunofluorescence in unstimulated Kato 3 and MKN 45 cells, and constitutive IL-8 gene expression in these cell lines was confirmed by detection of IL-8 mRNA by RT-PCR. CONCLUSIONS: Immunoreactive IL-8, a potent neutrophil chemotactic and activating factor, is present in the epithelium of both normal and inflamed gastric mucosa with increased expression in the latter. There is site dependent variation in epithelial IL-8 expression within the gastroduodenal mucosa. The expression of the pro-inflammatory cytokine IL-8 in gastric carcinoma cells may influence peritumoural cellular infiltrates.

Peri-operative modulation of cellular immunity in patients with colorectal cancer.

The peri-operative cellular immune response is depressed in patients with gastrointestinal cancer, a factor which may facilitate malignant dissemination. We have investigated the effects of peri-operative rIL-2 and a combination of rIL-2 and interferon-alpha (IFN-alpha) on both peripheral blood lymphocyte function and number in patients undergoing surgical resection for colorectal cancer. Fifty-two patients were randomly allocated to either control, rIL-2 or rIL-2 with IFN-alpha treatment arms. In vitro studies were performed pre-operatively and on post-operative days 1, 4, 7 and 10. Natural killer (NK) and lymphokine-activated killer (LAK) cell function were profoundly depressed in control patients (P < 0.001; P < 0.01), an effect abrogated in both treatment groups; indeed NK function was augmented in the rIL-2 and IFN-alpha group on the first post-operative day in association with an increase in the percentage of cells expressing CD16 and CD56 (P < 0.01). Flow cytometric analysis of lymphocyte subsets in the control group was unremarkable, except for an early post-operative fall in numbers of lymphocytes. Treatment with either rIL-2 or rIL-2 and IFN-alpha produced an initial profound reduction in T lymphocyte numbers, followed by a 'rebound' lymphocytosis of activated CD3+ T cells, as demonstrated by a significant increase in co-expression of CD25, CD38 and CD45RO. No significant differences were observed between either of the treatment groups. Adjuvant immunotherapy affects peri-operative anti-tumour immune responses, and this may influence long term outcome in patients undergoing surgery for gastrointestinal cancer.

Perioperative immunotherapy with recombinant interleukin 2 in patients undergoing surgery for colorectal cancer.

Major surgery impairs the cellular immune response. We have therefore studied the immunological effects of low-dose recombinant interleukin 2 given to patients undergoing surgery for colorectal cancer to determine whether this agent has potential in perioperative adjuvant immunotherapy. Patients were randomly allocated to control (n = 13) or treatment groups (n = 12). Immunological studies of both lymphocyte function and subset number were performed preoperatively and on Days 1, 4, 7, and 10. Treatment with recombinant interleukin 2 prevented the postoperative fall in both natural killer and lymphokine-activated killer cell cytotoxicity, clearly demonstrated in the control group. The treatment group also showed in vivo T-cell activation with an initial lymphopenia followed by a rebound lymphocytosis and upregulation of the subset markers CD25 (interleukin 2 receptor) and CD45RO (T-memory cells). These combined effects may have important consequences in controlling metastatic dissemination of tumor during the vulnerable perioperative period.