Systematic review on the treatment of ischaemic colitis.

AIM: Ischaemic colitis is uncommon. Aetiological factors include abdominal aortic surgery, drugs (especially inotropics) or rheumatoid diseases, such as Takayasu's or Buerger's diseases. However, there is often no triggering factor, and it may be part of multifactorial cardiac, respiratory, renal or metabolic failure. METHOD: A systematic review of the current literature on the management of ischaemic colitis was carried out. RESULTS: Ten retrospective trials (841 patients) were included. No randomized controlled or prospective trial of the management of ischaemic colitis was found. CONCLUSION: There is very little evidence base for the management of this condition.

Radioimmunoguided surgery in colorectal cancer using a genetically engineered anti-CEA single-chain Fv antibody.

In radioimmunoguided surgery (RIGS), a radiolabeled antibody is given i.v. before surgery and a hand-held gamma-detecting probe is used to locate tumor in the operative field. The rapid blood clearance and good tumor penetration of single-chain Fv antibodies (scFv) offer potential advantages over larger antibody molecules used previously for RIGS. A Phase I clinical trial is reported on RIGS with scFv (MFE-23-his) to carcinoembryonic antigen (CEA). Thirty-four patients undergoing surgery for colorectal carcinoma (17 primary tumors, 16 liver metastases, and 1 anastomotic recurrence) and 1 patient with liver metastases of pancreatic carcinoma received 125I-labeled MFE-23-his scFv (125I-MFE-23-his) 24, 48, 72, or 96 h before operation. 125I-MFE-23-his showed biexponential blood clearance with alpha and beta half-lives of 0.32 and 10.95 h, respectively. The abdomen was scanned during surgery with a hand-held gamma detecting probe (Neoprobe Corp.). 125I-MFE-23-his showed good tumor localization; comparison with histology showed overall accuracy of 84%. Highest median ratios for tumor:normal tissue and tumor:blood were recorded 72 or 96 h after scFv injection for patients undergoing resection of liver metastases. High levels of radioactivity were found in the kidneys. Five patients had grade 1 fever, and three had a grade 1 rise in blood pressure according to the Common Toxicity Criteria. There was a significant correlation between these ratios and those measured in excised tissues using a laboratory gamma counter (P < 0.001). MFE-23-his scFv antibody localizes in CEA-producing carcinomas. The short interval between injection and operation, the lack of significant toxicity, and the relatively simple production in bacteria make MFE-23-his scFv suitable for RIGS.

Radioimmunodetection: technical problems and methods of improvement.

Radioimmunodetection (RAID) is a technique which uses radiolabelled antibodies to visualize tumours, taking advantage of antigens preferentially expressed by malignant tissue. Gamma radiation emitted by radioisotopes can be detected using an external gamma camera (RAID), or intraoperatively with a hand-held Geiger counter (radioimmunoguided surgery, RIGS). RAID has significant inherent problems. Many have been overcome as a result of nearly 50 years of research, and others still remain as obstacles precluding the routine use of the technique. This article summarizes the technical limitations of RAID and outlines the relative successes of the methods evolved to overcome them.

The influence of age on the surgical management of carcinoma of the stomach.

The medical records of 31,808 patients with gastric cancer registered with the West-Midlands Cancer Registry between 1957-1981 were reviewed to determine the influence of age on presentation, stage assessment, management, survival and mortality rates. When analysed by stage, and excluding post-operative deaths, survival was similar in all age groups. This study confirms stage of disease to be the single most important prognostic factor. The inverse relationship between laparotomy and age implies inadequate assessment of stage in the elderly. The poor prognosis in unresected cases suggests that increased precise staging by laparotomy or laparoscopy will have minimal adverse effects. On the other hand this may result in increased resections and survival.

Proliferation and p53 expression in anal cancer precursor lesions.

BACKGROUND: Anal squamous cell carcinoma (SCC) develops from dysplastic anal warts. This study quantifies the expression of p53 and Ki67 in pre-invasive and invasive anal lesions. MATERIALS AND METHODS: Samples of 70 patients with anal warts (n = 20), low grade anal intraepithelial neoplasia (LG AIN) (n = 12), high grade anal intraepithelial neoplasia (HG AIN) (n = 27) and anal SCC (n = 11) were stained using immunohistochemical techniques. Eight patients with normal anal skin were used as controls. RESULTS: Both the expression of p53 and Ki67 increased significantly (p < 0.001) and gradually as the lesions became dysplastic and invasive. The main increase in p53 expression was as the lesions progressed from anal warts (7.38 +/- 11.93-mean +/- SD) to low grade AIN (20.778 +/- 13.14). CONCLUSION: p53 is involved in the progression of anal cancer and its expression increases from early in the development of pre-invasive anal lesions. p53 and Ki67 may be useful markers of early dysplasia and should be considered in the screening of high risk patients.

Biliary acute pancreatitis.

Severe biliary acute pancreatitis is frequently associated with persisting bile duct stones, which has important implications with regard to management. In mild cases, cholecystectomy with operative cholangiography during the same admission is the treatment of choice. In patients with a severe attack, however, management remains controversial. There is increasing evidence to suggest that early biliary decompression with endoscopic sphincterotomy is associated with a lower morbidity and mortality than a conservative regime. In certain situations endoscopic sphincterotomy may also obviate the need to explore the common bile duct, and in high-risk patients may allow surgery to be avoided altogether.

On-table pneumoperitoneum in the management of complicated incisional hernias.

'On-table' pneumoperitoneum before repair of 'complicated' incisional hernias has been used in eight patients considered to be at high risk of recurrence. In four patients the procedure revealed the presence of occult defects. The procedure was uncomplicated and a primary repair without the need for a prosthetic implant was possible in all cases. Six patients remain well with no sign of recurrence at a median follow-up of 96 months (range 22-120 months). Two patients died from conditions unrelated to the method of repair; acute necrotising pancreatitis on the 10th postoperative day and lobar pneumonia 2 months postoperatively. Peroperative pneumoperitoneum is a simple procedure which obviates the need for a prosthetic implant in selected patients. It is therefore particularly useful in the management of incisional hernias associated with sepsis, stomas or in patients requiring synchronous bowel resection.

The molecular biology of colorectal cancer development and the associated genetic events.

Colorectal carcinoma remains the second most common malignancy in the western world. Mortality has remained stable despite advances in surgical and adjuvant radio- and chemotherapy regimens. This has renewed interest in the understanding of the basic principles of the molecular biology of colorectal carcinogenesis. The condition is characterised by multiple mutations in common oncogenes and tumour suppressor genes encompassing the inherited conditions familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer. The latter is characterised by genomic instability due to mismatch repair gene defects. These conditions and the role of the tumour protease systems, e.g. the plasminogen activation system and the matrix metalloproteinases, involved in the degradation of the extracellular matrix, provide an ideal role model for the study of carcinogenesis. The understanding and future application of these basic mechanisms, combined with the recent innovative work on the potential prophylactic role of COX2 inhibition, may provide further insight in the ultimate quest for a 'cure'. In the long-term, this concept may have to be achieved at the molecular level.

Gastro-oesophageal reflux: the disease of the millennium.

Gastro-oesophageal reflux disease (GORD) is attributable primarily to acid and bile reflux through the lower oesophageal sphincter. Bile reflux has been implicated in severe oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma. Developments in evaluating and managing GORD and Barrett's are discussed, with their aetiological role in junctional gastro-oesophageal malignancies.

Clinical advances in the evaluation of oesophageal disease.

The rising incidence of gastro-oesophageal reflux disease and its sequelae means the evaluation of oesophageal disease is set to expand beyond routine endoscopic assessment. The techniques used in the evaluation of both benign and malignant oesophageal disease are outlined in this article.

The influence of symptom type and duration on the fate of the metaplastic columnar-lined Barrett's oesophagus.

BACKGROUND: Prolonged gastro-oesophageal reflux resulting in columnar metaplasia of the oesophagus is the main risk factor for oesophageal adenocarcinoma. AIM: To examine the duration of symptoms and associations of different symptoms with the development of columnar-lined oesophagus, dysplasia and adenocarcinoma. METHODS: UK multicentre cohort study of patients with columnar-lined oesophagus whose date of symptom onset (1082 patients) and/or types of symptoms reported (1681 patients) were documented. Follow-up was examined by analysis of histological reports from the registering centers. RESULTS: Symptoms of dysphagia/odynophagia and nausea/vomiting were associated with development of dysplasia. High-grade dysplasia and adenocarcinoma were associated with dysphagia/odynophagia and weight loss. Median duration from symptom onset to detection of columnar-lined oesophagus without intestinal metaplasia: 2.6 years, columnar-lined oesophagus with intestinal metaplasia: 5.0 years, indefinite changes for dysplasia: 19.3 years and low-grade dysplasia: 30.0 years. One tenth of patients had developed high-grade dysplasia at 9.6 years and one tenth had developed adenocarcinoma at 13.8 years from symptom onset. CONCLUSIONS: In patients with columnar-lined oesophagus, symptoms of dysphagia/odynophagia and nausea/vomiting were associated with a higher risk of development of dysplasia and adenocarcinoma. There is a trend for longer duration of symptoms to the detection of dysplasia.

Impact of HIV and AIDS on surgical practice.

INTRODUCTION: Surgical intervention has become a common component in the management of patients infected with the human immunodeficiency virus (HIV) or suffering from the clinical consequences of acquired immunodeficiency syndrome (AIDS). We investigated the evolution of this involvement at a tertiary referral centre for this condition over a 16-year period. PATIENTS AND METHODS: Detailed retrospective examination of the medical records of HIV-positive patients treated at the Royal Free Hospital between 1986 and 2002 was undertaken. Clinical, pathological and operative details of those patients who underwent surgical intervention were recorded. RESULTS: Of the 2100 cases reviewed, 477 patients underwent a combined total of 772 surgical procedures. Of the 772 operations, 95 (12.3%) were performed as emergencies. Anorectal surgery represented the highest group with a total of 195 procedures (25.26%) being undertaken. The majority of patients (59%) had AIDS at the time of surgery, and 27.04% had a significant co-existing medical problem. Overall postoperative complication rate was 10.1%, with the risk being significantly greater in those undergoing intra-abdominal surgery and emergency procedures. CONCLUSIONS: This is the largest study to audit the impact of HIV/AIDS in general surgical practice in the UK retrospectively. Surgery for HIV patients can be safely conducted with a low complication rate for the diagnostic and anorectal procedures that comprise the vast majority of surgery in HIV/AIDS patients. Medical treatment for patients with HIV/AIDS has developed dramatically over the last two decades. In parallel, this has resulted in a heavy, new and varied workload for general surgeons, who have also had to adapt in order to deal with the challenging spectrum of this disease.

EpCAM an immunotherapeutic target for gastrointestinal malignancy: current experience and future challenges.

Despite advances in surgery and adjuvant regimes, gastrointestinal malignancy remains a major cause of neoplastic mortality. Immunotherapy is an emerging and now successful treatment modality for numerous cancers that relies on the manipulation of the immune system and its effector functions to eradicate tumour cells. The discovery that the pan-epithelial homotypic cell adhesion molecule EpCAM is differentially expressed on gastrointestinal tumours has made this a viable target for immunotherapy. Clinical trials using naked anti EpCAM antibody, immunoconjugates, anti-idiotypic and dendritic cell vaccines have met variable success. The murine IgG2a Edrecolomab was shown to reduce mortality and morbidity at a level slightly lower than treatment with 5FU and Levamisole when administered to patients with advanced colorectal carcinoma in a large randomised controlled trial. Fully human and trifunctional antibodies that specifically recruit CD3-positive lymphocytes are now being tested clinically in the treatment of minimal residual disease and ascites. Although clinical trials are in their infancy, the future may bring forth an EpCAM mediated approach for the effective activation and harnessing of the immune system to destroy a pathological aberrance that has otherwise largely escaped its attention.

Increased apoptosis and decreased proliferation of colorectal cancer cells using insulin-like growth factor binding protein-4 gene delivered locally by gene transfer.

OBJECTIVE: Insulin-like growth factor (IGF)-I induces proliferation of transformed cells. Its binding proteins (IGFBP) are involved in local regulation of IGF. This study assessed the effects of overexpression of IGFBP-4 on the development of cancer in vivo. METHOD: Nude mice were subcutaneously inoculated with HT-29 colorectal cancer cells (3 x 10(6)). When the tumour became visible (1 week after inoculation), animals received either 150 microg of mammalian expression vector containing IGFBP-4 cDNA or vector alone (n = 6 each) by peritumoural injection. Tumour size was measured during the growth. After 3 weeks of IGFBP-4 induction, animals were killed and tumour tissue samples were collected for examining the level of IGFBP-4 expression. Tumour mitotic activities were determined by counting numbers of mitotic cells on the tissue section. Apoptosis was investigated by terminal deoxynucleotidyl transferase-mediated dUDP nick end labelling assay. RESULTS: Following IGFBP-4 treatment, tumour showed large necrotic areas, significantly increased numbers of apoptotic cells (36.67 +/- 7.36 vs 7.07 +/- 1.91, P < 0.01 vs control), decreased cells undergoing mitosis (2.31 +/- 0.32 vs 3.61 +/- 0.27, P < 0.01 vs control) and higher expression of IGFBP-4 (P < 0.05 vs control). CONCLUSION: IGFBP-4 gene transfer increased apoptosis and decreased mitosis, but tumour volume was not significantly altered possibly due to cellular debris filling the centre of tumours.

Diet and colorectal cancer: implications for the obese and devotees of the Atkins diet.

Colorectal cancer (CRC) is the second most common cause of cancer-related death in the Western world and its prevalence is increasing. Potential causes of this increase are changes in diet and the increases in obesity seen. This paper looks at the literature surrounding diet and obesity and the links to this increase in CRC. Heralded as a weight loss miracle we investigate whether the literature suggests the Atkins diet may actually do more harm than good by acting to increase an individual's risk of CRC. Obesity has been demonstrated to be a major factor in the increase in CRC although links to changes in diet are more tenuous. Published studies on diet suggest the Atkins diet may help reduce rather than increase the risk of CRC.

Ischaemic preconditioning improves microvascular perfusion and oxygenation following reperfusion injury of the intestine.

BACKGROUND: Ischaemia-reperfusion (IR) injury of the intestine occurs commonly during abdominal surgery. Ischaemic preconditioning (IPC) provides a way of protecting the organ from damage inflicted by IR. This study was designed to evaluate the beneficial effect of IPC, focusing on the intestinal microcirculation and oxygenation in intestinal IR injury. METHODS: Rats were allocated to three groups. Animals in the IR and IPC groups underwent 30 min of intestinal ischaemia followed by 2 h of reperfusion. In the IPC group this was preceded by 10 min of ischaemia and 10 min of reperfusion. Animals in the third group underwent laparotomy but no vascular occlusion. Intestinal microvascular perfusion, oxygenation and portal venous blood flow (PVF) were monitored continuously. At the end of the reperfusion period, blood samples were obtained for measurement of lactate dehydrogenase (LDH) and biopsies of ileum for histological evaluation. RESULTS: : IPC improved intestinal microvascular perfusion and tissue oxygenation significantly at the end of the reperfusion period (P < 0.001). PVF improved significantly in the IPC compared with the IR group (P = 0.005). The serum LDH concentration was significantly lower in the IPC than the IR group (mean(s.e.m.) 667.1(86.8) versus 1973.8(306.5) U/l; P < 0.001) Histological examination showed that ileal mucosa was significantly less injured in the IPC group. CONCLUSIONS: This study demonstrated that IPC improves intestinal microvascular perfusion and oxygenation.

A national audit of antimicrobial prophylaxis in vascular surgery.

A standard questionnaire on antimicrobial prophylaxis for elective and emergency vascular surgery was sent to 262 practising members of the Association of Vascular Surgeons (U.K.). The response rate was 68.3%. A cephalosporin based regime was used in 61.1% of cases while penicillin was used in 39.3% and an aminoglycoside in 6.5%. More than one antibiotic was routinely used in 15.6% of cases, with specific anti-anaerobic cover in 19%. Prophylaxis was used in all cases using a prosthetic graft, but in only 76% of cases using autogenous vein (p < 0.05). A single dose regime was most commonly used for autogenous vein graft (14% vs. 4.5%, p < 0.05), whilst overall a three dose regime was most popular. Some 2.8% of respondents specified a differing regime for supra- and infrainguinal surgery whilst 4.5% modified their regime in emergency cases. Despite its theoretical limitations, a three dose cephalosporin regime is the most commonly prescribed "prophylactic" regime for all forms of vascular surgery in the U.K.

Ileosigmoid knotting.

Intestinal obstruction is a common cause of emergency surgical admission. The most frequent causes are well known and may often be safely treated conservatively in the first instance. The rarer causes of intestinal obstruction require prompt diagnosis and surgery if they are not to progress rapidly to strangulation and gangrene. One such cause is the ileosigmoid knotting, which is associated with a high morbidity and mortality. With increasing travel activity and population migration this condition is now being seen outside its original geographical sites of origin. This article focuses on the aetiology, pathophysiology, clinical features, investigations and the various surgical options for the management of the ileosigmoid knotting. Studies and case reports in English literature were identified by PubMed, ISIS, Embase and CAS searches between the years 1966-2004 using the following free text keywords: ileo- sigmoid knotting, ileosigmoid knot(ting), intestinal knot(ting), compound volvulus and double volvulus. All the reference lists were reviewed to retrieve additional articles. Aggressive resuscitation, prompt surgical relief of obstruction, appropriate antibiotics, accurate intra-operative assessment of the viability of the involved loops of intestine and the use of modern postoperative intensive care will help reduce the mortality and morbidity associated with this life threatening condition.

Submammary approach for the excision of mammographically localised lesions of the breast.

OBJECTIVE: To describe the results of a submammary incision for the removal of impalpable, mammographically diagnosed lesions. DESIGN: Open study. SETTING: District hospital. SUBJECTS: 8 patients with deep, impalpable, mammographically suspicious lesions. INTERVENTIONS: Excision biopsy by the submammary approach. MAIN OUTCOME MEASURES: Complete excision judged radiologically and histologically, and cosmetic result. RESULTS: All lesions were completely excised both radiologically and histologically. Three patients had ductal carcinoma in situ and five had benign microcalcification. Cosmetic results were excellent in all cases. CONCLUSION: The incision gives excellent results after excision biopsy of deep or peripheral lesions of the breast, but is contraindicated if invasive carcinoma is suspected.