HER2 (ErbB2) receptors, a potential therapeutic target in squamous cell carcinoma of oesophagus.
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Biomarkers, Tumor↗
Biomedical subjects
M C Winslet
Publications and source records attributed to M C Winslet.
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.
Animals↗
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.
Colorectal Neoplasms↗
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.
Humans↗
Carcinoid tumour of the appendix.
BACKGROUND: Appendiceal carcinoid tumours are found in 0.3-0.9 per cent of patients undergoing appendicectomy. Controversy exists over the management following appendicectomy, especially with regard to the role of right hemicolectomy in patients with tumours smaller than 2 cm in diameter. METHODS AND RESULTS: The literature pertaining to the behaviour of appendiceal carcinoids was reviewed in order to formulate indications for right hemicolectomy. Metastatic disease from appendiceal carcinoids is a rare occurrence, but is more common when lesions are larger than 2 cm in diameter. The risk-benefit balance of right hemicolectomy needs to be better defined, and an improved understanding of tumour cell biology may aid prognostic accuracy and decision-making. CONCLUSION: There is limited evidence on which to base clear indications for right hemicolectomy in patients with a diagnosis of appendiceal carcinoid. Acceptable indications are carcinoids larger than 2 cm in size, any high-grade malignant carcinoid (including those with a high mitotic index), mesoappendiceal invasion, lesions at the base of the appendix with tumour-positive margins, and goblet cell adenocarcinoid tumours.
Appendiceal Neoplasms↗
Surgery for carcinoid tumours of the lower gastrointestinal tract.
INTRODUCTION: Carcinoid tumours are rare neoplasms that originate from neuroendocrine cells of the primitive gastrointestinal tract. Mid- and hind-gut tumours comprise the majority of these rare tumours. With many recent advances in medical treatment the role and importance of surgery and the surgeon needs to be assessed. METHOD: A Medline, Pubmed and Embase databases search was undertaken. All relevant articles were cross-referenced. RESULTS AND CONCLUSIONS: Incidental findings of carcinoid tumours should be treated at initial surgery whilst elective surgery and further management should be undertaken in specialist centres by a multidisciplinary team. Asymptomatic patients have a better prognosis than those with symptoms. In advanced cases surgery combined with chemotherapy and liver resection is appropriate. The outlook for the majority of cases is good.
Carcinoid Tumor↗
Angiogenesis in anal warts, anal intraepithelial neoplasia and anal squamous cell carcinoma.
INTRODUCTION: Most cases of anal carcinoma seem to develop from high grade anal intraepithelial neoplasia (AIN) caused by persistent anal warts. Similar pre-invasive epithelial genital lesions (e.g. those of the cervix and vulva) have been shown to be associated with increased angiogenesis. In this study we examined biopsies of anal lesions ranging from warts to invasive anal carcinoma, with the aim of assessing the degree of angiogenesis in pre-invasive anal lesions. METHOD: Samples from 70 patients (51 male) who had undergone excision biopsy or resection of anal wart lesions (20), low grade AIN (12), high grade AIN (27) and anal squamous cell carcinoma (SCC) (11) were studied. Samples (6) from normal HIV-anal skin were used as controls. The samples were stained for von Willebrand factor, a specific marker of endothelial cells. Angiogenesis was measured by microvessel density (MVD) analysis, quantifying the microvessels in the stroma adjacent to the epithelial lesion. RESULTS: There was a statistically significant (P < 0.001) progressive increase in MVD between low grade AIN, high grade AIN and anal SCC. The difference in MVD between normal skin, warts and low grade AIN was not statistically significant. CONCLUSION: There are progressive abnormal patterns of angiogenesis in highly dysplastic lesions, similar to those found in cervical and vulvar pathology. These findings may have biological, prognostic and therapeutic implications.
Anal Canal↗
Unusual causes of small-bowel obstruction.
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Foreign Bodies↗
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.
Adenocarcinoma↗
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.
Adult↗
Energy metabolism following prolonged hepatic cold preservation: benefits of interrupted hypoxia on the adenine nucleotide pool in rat liver.
The ability of brief hypothermic reperfusion (HtR) to restore hepatic energy metabolism following periods of cold hypoxic preservation was studied in isolated rat livers after storage times of 5, 10, and 24 h. In addition, investigations were performed on the effects of HtR used to restore liver oxidative metabolism in the middle of a prolonged (24 h) hypoxic preservation period. A histidine-lactobionate-raffinose solution was used for the initial cold portal flush in all groups. Results showed that cold hypoxia for either 5 or 10 h yielded livers capable of similar recoveries of ATP, energy charge, and total adenine nucleotides, but that HtR after 24 h cold preservation resulted in reduced regeneration of ATP, a lower energy charge, and a fall in tissue adenine nucleotides. When livers were stored for 24 h but subjected to brief HtR after either 5 or 10 h before return to hypoxic storage, improved recoveries of the energy metabolites were seen over those recorded after 24 h hypoxia alone. The fact that these improvements were not due to an improved supply of adenine nucleotide precursors was demonstrated by studying groups which were given HtR with perfusate containing precursors of adenine nucleotides (adenosine, adenine, and inosine) after 24 h cold hypoxia. These data are consistent with the hypothesis that poor metabolic recovery after long-term hepatic cold preservation results more from decreased mitochondrial oxidative phosphorylation than from a lack of precursors for adenine nucleotide resynthesis. In addition, restoring oxidative metabolism at hypothermia for brief periods can to some extent protect final metabolic status after prolonged storage.
Adenine Nucleotides↗
In vitro assessment of Lipiodol-targeted radiotherapy for liver and colorectal cancer cell lines.
Intra-arterial Lipiodol has been used to deliver targeted therapies to primary, and some metastatic, liver cancers. Targeted radiotherapy has been used by substituting the iodine in Lipiodol with 131Iodine (131I). Early clinical results are encouraging, but the variable response may partly depend on local pharmacokinetics. This study evaluated the in vitro cytotoxic effects of 131I-Lipiodol on human hepatocellular carcinoma (Hep-G2), human colorectal metastatic cancer (SW620), human colorectal hepatic cancer (LoVo) and human umbilical vein endothelial cells (HUVEC) cell lines. The cell cultures were exposed to 131I-Lipiodol for 48 h, following which cell counts and viability were assessed by haemocytometer, S-Rhodamine uptake and radioactivity assay. The effect of exposure to control Lipiodol, 131I-Lipiodol and 131I alone was evaluated. 131I-Lipiodol was cytotoxic against all the cancer cell lines but not against the non-malignant (HUVEC) cell line. The cytotoxicity effects were very similar in all the cancer cell lines. There were no cytotoxic effects following exposure to plain 131I in any of the cell lines (malignant and non-malignant). A similar trend was seen with radioactivity counts using a gamma counter. The cytotoxic effect of 131I-Lipiodol had a graded effect with an increase in cytotoxicity following the increase in the radioactive dose. This study showed that there was a marked cytotoxic effect by 131I-Lipiodol on all the cancer cell lines. There was no difference between the controls and the 131Iodine. This suggests that effective 131I-Lipiodol targeted therapy is dependent on the uptake and retention of Lipiodol by malignant cells.
Cell Division↗
Fungal ball of the oesophagus.
Candidal colonization of the gastrointestinal tract is common, but localized complications are rare. A case of an oesophageal fungal ball is described.
Candidiasis↗
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.
Antibodies, Monoclonal↗
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.
Adenoma↗
Barrett's oesophagus.
Barrett's oesophagus represents the replacement of stratified squamous epithelium by metaplastic columnar epithelium for 3 cm of the distal oesophagus. Gastro-oesophageal reflux, which affects 40% of the adult population, is the principal aetiological factor. This results in predominantly acid but also bile reflux (due to duodenogastrooesophageal reflux) through the lower oesophageal sphincter, transient relaxation of which accounts for the main mechanism of reflux. Conventional Barrett's oesophagus is reported in 11-13% of patients with symptomatic reflux and short segment Barrett's oesophagus (< 3.0 cm) in 18%. Approximately 50% of these patients have recognised complications on presentation, eg, carcinoma (15%). The disparity between clinical symptoms and endoscopic severity is due to reduced oesophageal mucosal sensitivity as a consequence of prolonged mucosal acid exposure. These rather alarming figures combined with the knowledge that Barrett's oesophagus is a pre-malignant condition (the diagnosis is associated with a 25-130-fold increase of malignancy) may account for the substantial increase in junctional gastrooesophageal malignancies. Symptomatic Barrett's oesophagus should be managed with full-dose proton pump inhibitors, eg, lansoprazole. Anti-reflux surgery should be reserved for the medically fit patient with recurrent symptomatic relapse in the histological absence of premalignant change. There is no evidence suggesting that surgery can be used as a prophylactic measure against malignancy. Encouraging short-term results have been obtained with photodynamic therapy in the management of high-grade dysplasia. However, columnar epithelium has been found underlying the regenerated squamous epithelium, suggesting that life-long surveillance is warranted.
Barrett Esophagus↗
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.
Barrett Esophagus↗
Pneumococcal lipopolysaccharide stimulation of B-lymphocytes in non-immunised BALB/c mice.
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Animals↗