Systematic review of the use of topical diltiazem compared with glyceryltrinitrate for the nonoperative management of chronic anal fissure.

AIM: The study analyzed clinical trials investigating the effectiveness of diltiazem (DTZ) and glyceryltrinitrate (GTN) for the nonsurgical management of chronic anal fissure (CAF). METHOD: Randomized trials on the effectiveness of DTZ and GTN were analyzed systematically using RevMan(®) where combined outcome was expressed as risk ratio (RR). RESULTS: Seven randomized controlled trials that included 481 patients were analyzed. Two-hundred and thirty-eight patients were treated with DTZ and 243 patients were treated with GTN. There was significant heterogeneity [Tau(2) = 0.24, χ2 = 13.16, d.f. = 6 (P < 0.05); I(2) = 54%] among the included trials. In the random-effects model, DTZ was associated with a lower incidence of side effects (RR = 0.48; 95% CI = 0.27, 0.86; z = 2.46; P < 0.01), headache (RR = 0.39; 95% CI = 0.24, 0.66; z = 3.54; P < 0.004) and recurrence (RR = 0.68; 95% CI = 0.52, 0.89; z = 2.77; P < 0.006) of CAF. Both GTN and DTZ were equally effective (RR = 1.10; 95% CI = 0.90, 1.34; z = 0.92; P = 0.36) in the nonsurgical management of CAF. CONCLUSION: This systematic review of seven trials validates and strengthens the finding of a previously published meta-analysis of two randomized trials. Both DTZ and GTN are equally effective in the management of CAF. However, DTZ is associated with a lower incidence of headache and recurrent fissure. Therefore DTZ should be the preferred first line of treatment for CAF.

Unexpected findings at diagnostic laparoscopy: caecal incarceration with concurrent appendicitis in a patient with bilateral broad ligament defects.

Internal herniations through broad ligament defects are very rare. We present the first report of the triad of broad ligament defect, internal herniation of the caecum and appendicitis. A 36-year-old woman with phocomelia presented with right iliac fossa pain and vomiting. The patient had no previous history of trauma or surgery. Abdominal ultrasound showed a small amount of free fluid. At laparoscopy, bilateral broad ligament defects were found, with herniation of the caecum and an inflamed appendix through the right-sided defect. A laparoscopic salpingo-oophorectomy was required for reduction of the herniated bowel, and an appendicectomy was performed. Broad ligament defects may be congenital or acquired. In this case, in light of the limb abnormality and absence of previous surgery, a congenital aetiology is more likely. Ultrasound scan is not reliable and, although computed tomography may be of help, a diagnostic laparoscopy is the best investigation.

Transanal endoscopic microsurgery: local recurrence rate following resection of rectal cancer.

OBJECTIVE: Transanal endoscopic microsurgery (TEM) is a safe and effective treatment for the excision of benign rectal adenomas. In recent years it has been used for the excision of malignant lesions, although its use in this context remains controversial. The aim of this study was to investigate the local recurrence of rectal cancers following local excision by TEM. METHOD: Forty-two patients with rectal cancer were treated by TEM between 1998 and 2005. However, six patients went on to have immediate radical surgery and are excluded from the study. Of the remaining 36 the treatment intention was for cure in 16 (38.1%), compromise in 17 patients unfit for radical surgery (40.5%), and palliation in three (7.1%). RESULTS: The mean age of patients was 75 years (range 41-90). The mean lesion area was 15 cm(2) (range 0.8-42) and mean distance from the dentate line was 6.6 cm (range 0-11). The mean follow up was 34 months (range 4-94). During the follow-up period there have been eight local recurrences (22%). The recurrence rates were 26% (6/23) for pT1, 22% (2/9) for pT2 and 0% (0/4) for pT3 lesions. The mean time to recurrence was 18.3 months (range 5-42). CONCLUSION: Transanal endoscopic microsurgery is a safe procedure with obvious advantages over radical procedures. However, in this study the local recurrence rate is high. The recurrence rate may be an acceptable compromise in elderly or medically unfit patients but is hard to justify for curative intent.

Transanal endoscopic microsurgery: risk factors for local recurrence of benign rectal adenomas.

OBJECTIVE: Transanal endoscopic microsurgery (TEM) is a minimally invasive technique for excision of selected benign and malignant rectal neoplasms. It is considered a safe and effective treatment but recurrence rates of 1-13% are reported for benign lesions. The aim of this study was to assess risk factors for local recurrence of benign rectal lesions and to evaluate mortality and morbidity following TEM. METHOD: Data were prospectively collected from all patients undergoing TEM for benign adenomas from January 1998 to March 2005. The procedure was performed by a single surgeon and patients were regularly followed up. RESULTS: One hundred and forty-six procedures were included, with a median patient age of 74 years (range 22-92 years). The mean lesion area was 16 cm(2) (range 0.3-150 cm(2)) and the median distance from the dentate line was 9 cm (range 0-17 cm). Immediate complications included bleeding (six) and acute urinary retention (six). There has been one (0.68%) procedure-related death. After a median follow up of 39 months (range 4-89 months) there have been seven recurrences (4.8%), recurring at a mean time of 23.3 months (range 5-48 months). Only microscopic involvement of the circumferential resection margin was found to be significantly associated with recurrence (P = 0.0059). Recurrence was not associated with age, size of lesion, previous treatment, severity of dysplasia or use of the harmonic scalpel. CONCLUSION: TEM is a safe and effective treatment for benign rectal adenomas. Circumferential resection margin involvement is associated with recurrence, which tends to occur late. Therefore extended follow up is recommended.

Combination chemotherapy in advanced gastrointestinal cancers: ex vivo sensitivity to gemcitabine and mitomycin C.

Advanced or metastatic disease is common in both oesophagogastric and colorectal cancers, with poor 5-year survival despite palliative chemotherapy. We have investigated the sensitivity of gastrointestinal tumours to gemcitabine in combination with mitomycin C (GeM), using a modified ex vivo ATP-based tumour chemosensitivity assay (ATP-TCA). Tumour material from 41 colorectal and 22 oesophagogastric cancers were assessed. The GeM combination showed variable but definite activity in most of the samples tested. The results show that GeM achieves >95% inhibition at concentrations within the range achievable clinically in 60% of colorectal tumours (21 out of 35) and 38% of oesophagogastric tumours (five out of 13) tested. We did not identify any significant difference in sensitivity using concurrent or sequential exposure of tumour-derived cells to these two drugs. The results from this study suggest that GeM may be a useful combination in the treatment of advanced gastrointestinal malignancy.

Synergistic activity of gamma-linolenic acid and cytotoxic drugs against pancreatic adenocarcinoma cell lines.

BACKGROUND: Gamma-linolenic acid (GLA) is growth inhibitory both in vitro and in vivo, at doses non-toxic to non-cancer cells. Chemotherapeutic agents have limited activity in pancreatic cancer. Interactions between GLA and cytotoxic drugs have not previously been investigated; any synergy might improve the therapeutic effect of these agents. AIM: To investigate possible interactions between GLA and 5-fluorouracil (5-FU) or gemcitabine against pancreatic cancer cell lines in vitro. METHODS: Two pancreatic cancer cell lines were exposed to GLA alone and in combination with 5-FU or gemcitabine. Residual viable biomass was measured using the MTT assay and the results analysed by the median effect method of Chou and Talalay [Adv Enzyme Regul 1984;22:27-55]. RESULTS: GLA concentrations of 3.9- 125 microg/ml had a synergistic or additive growth inhibitory effect on all tested concentrations of gemcitabine. Synergism was demonstrated between GLA and 5-FU only at concentrations of 62.5-125 microg/ml of 5-FU. CONCLUSION: GLA has a synergistic effect with gemcitabine at concentrations that correspond to in vivo therapeutic doses. GLA with 5-FU is synergistic only at a tight range of high concentrations of 5-FU. GLA lacks toxic side effects and may be useful in combination with gemcitabine.

The use of ultrasound by breast surgeons in outpatients: an accurate extension of clinical diagnosis.

AIMS: To assess the accuracy of breast ultrasound scan (USS) performed by a surgeon in outpatients and to evaluate the additional contribution of USS to clinical diagnosis. METHODS: A prospective study of 302 patients with symptomatic breast disease (322 lumps) was performed. Group 1 consisted of 213 clinic USS of lumps surgically removed for appropriate clinical indications. In Group 2, a USS was performed on 231 lumps by both the surgeon and radiologists as part of triple assessment. Each clinic USS was compared to the surgical pathology (Group 1) or USS performed by the radiologist (Group 2). RESULTS: In Group 1 (n=213), 89 lumps were proven benign and 124 malignant on histology. Ultrasound scans performed by the surgeon compared to histology had a sensitivity of 98.3% and specificity of 91.7%. An abnormal clinic USS heightened the index of suspicion in 22/213 (10.3%) of cases felt clinically to be benign but subsequently confirmed malignant on histology. Fifty-seven lumps felt to be indeterminate clinically were correctly identified on USS by surgeon as benign (n=56) or malignant (n=1). In Group 2 (n=231), there was complete concordance of USS scans by surgeon and radiologists in 197 (96%) and complete discordance in eight (3.9%) patients. Of the discordant scans, the surgeon correctly identified 7/8 diagnoses on histology. A USS examination by the radiologists provided a correct diagnosis of 6/14 scans scored by the clinician as indeterminate. CONCLUSION: USS performed in outpatients by a breast surgeon is accurate and a useful adjunct to clinical assessment. This enables rapid diagnosis in one-stop breast clinics, selecting difficult diagnostic procedures for USS by radiologists at the same visit.