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T J Hugh

Publications and source records attributed to T J Hugh.

10 recordsLinked to original sources
PubMed1999

beta-catenin expression in primary and metastatic colorectal carcinoma.

beta-catenin plays a fundamental role in the regulation of the E-cadherin-catenin cell adhesion complex. It also functions in growth signalling events, independently of the cadherin-catenin complex, and these signalling pathways are disturbed in colorectal cancer. Mutations in either the APC or beta-catenin genes in colorectal cancer cells result in up-regulation of protein expression and subsequent cytoplasmic and nuclear distribution of beta-catenin. In this study, we examined beta-catenin expression in 47 primary colorectal tumors and the corresponding liver metastases. Immunohistochemical studies demonstrated loss of membranous beta-catenin expression in 26% of primary tumors and 60% of liver metastases and a concomitant increase in cytoplasmic and nuclear staining. Widespread nuclear expression of beta-catenin was found in 64% of primary tumors and 21% of liver metastases. No associations were found between any form of beta-catenin expression and either tumor stage or tumor grade. Cellular distribution of beta-catenin was also examined by detergent extraction and Western blot analysis in 16 primary tumors and 23 liver metastases. This analysis showed that most tumors demonstrated reduced beta-catenin in the cytoskeletal fraction and increased beta-catenin in the cytosolic fraction. Furthermore, 3 liver metastases were found to contain a truncated beta-catenin protein of approximately M(r) 80,000. Immunoprecipitation studies showed that the truncated beta-catenin proteins only bound weakly to E-cadherin and beta-catenin compared with non-truncated beta-catenin. These results demonstrate gross alterations in the cellular distribution of beta-catenin in primary colorectal cancers with metastatic potential, as well as in the metastatic tumors. These changes may be the consequence of APC or beta-catenin gene mutations, or possibly result from a post-translational modification of the E-cadherin-catenin complex.

Adult↗
PubMed1999

Cadherin-catenin expression in primary colorectal cancer: a survival analysis.

Both cell adhesion and cell signalling events are mediated by components of the cadherin-catenin complex. Loss of expression of the components of this complex have been shown to correlate with invasive behaviour in many tumour types although their exact role in colorectal cancer remains unclear. Immunohistochemical analysis of the expression of components of the cadherin-catenin complex in colorectal cancers from 60 patients was undertaken. Loss of memberanous expression of E-cadherin, alpha-catenin and beta-catenin was demonstrated in 52%, 85% and 40% of tumours respectively. Focal nuclear expression of beta-catenin (< 75% of cells per section), usually associated with cytoplasmic expression, was clearly demonstrated in 19 (32%) tumours while widespread nuclear expression (> 75% of tumour cells per section) was seen in 11 (18%) tumours. Loss of membranous alpha-catenin expression significantly correlated with tumour de-differentiation (P = 0.009). There was a trend towards an association between advanced tumour stage and loss of membranous expression of alpha-catenin or beta-catenin, although these associations were not statistically significant. Univariate analysis revealed that advanced Dukes' stage, tumour de-differentiation, loss of membranous beta-catenin expression, cytoplasmic beta-catenin expression and widespread nuclear expression of beta-catenin all correlated with short survival following apparently curative resection of the primary tumour. However, only Dukes' stage (P = 0.002), tumour grade (P = 0.02) and widespread nuclear expression of beta-catenin (P = 0.002) were independent predictors of short survival. Disturbed growth signalling events in colorectal tumours are thought to result in nuclear accumulation of beta-catenin. Consequently, tumours with widespread nuclear expression of beta-catenin are likely to have severely abnormal growth characteristics, and which therefore might be predictive of short survival in these patients.

Cadherins↗
PubMed1997

Management strategies for colorectal liver metastases--Part I.

Colorectal cancer is a common malignancy and the incidence of this disease is increasing. Approximately 50% of patients with colorectal cancer die from recurrent disease following an apparently curative resection of the primary tumour and the liver is the most frequent site of relapse. Although only a small proportion of patients will benefit from resection of liver metastases, this form of treatment offers the only possibility of cure. In selected patients, 5-year survival rates of 25-35% may be achieved following liver resection. A poor prognosis after resection of hepatic metastases is likely when there are more than three metastatic deposits, involved resection margins often as a result of ¿wedge' resections, when there is extrahepatic disease, or when there is nodal involvement at the primary tumour site. Regional hepatic artery infusion chemotherapy may provide palliation and possibly even prolongation of survival for some patients with unresectable metastases. Cytoreductive techniques may also provide palliation in selected patients with hepatic metastases unsuitable for resection; cryotherapy is the most promising of these methods.

Clinical Trials as Topic↗
PubMed1997

Management strategies for colorectal liver metastases--Part II.

Liver metastases are relatively common in colorectal cancer and a small proportion of patients may benefit from resection of these liver metastases. In a selected subgroup of patients, 5-year survival rates of 25-35% may be achieved following liver resection. These survival figures compare favourably with those of patients with untreated liver secondaries. In the second part of this review the surgical and non-surgical treatment options for treating colorectal liver metastases are examined in detail.

Adult↗
PubMed1997

The aetiology and management of hepatic metastases.

Hepatic metastases are a common event in the metastatic spread of primary tumours and indicate advanced disease. However, the presence of hepatic metastases does not necessarily imply incurability; in selected patients resection of hepatic metastases may result in 5-year survival rates of 25-35%, usually in patients with colorectal liver metastases in whom solitary metastases are more frequent than with other primary tumours. However, hepatic metastases from Wilm's tumours, adrenal tumours, renal cell carcinoma, and neuroendocrine tumours may also be resected with similar success rates. A poor prognosis after resection of hepatic metastases is likely when there are more than three metastatic deposits, involved resection margins (often as a result of 'wedge' resections), when there is extrahepatic disease, or nodal involvement at the primary tumour site. Cyto-reductive procedures may provide excellent palliation and possibly long-term survival in selected patients with hepatic metastases unsuitable for resection. However, further study is required to establish the appropriate role for these treatments.

Hepatectomy↗
PubMed1994

Childhood intussusception in a regional hospital.

This study reviews all childhood intussusceptions treated over a 6 year period in a regional centre with six visiting general surgeons and two paediatricians. Clinical presentation, management, complications and outcomes were noted and an attempt was made to follow up all cases. There were 20 patients, with a median age of 6 months (range 10 weeks to 17 months). Only one patient had all four classical features of intussusception (pain, vomiting, 'red currant jelly' stools and abdominal mass). Seven patients were managed successfully by barium enema reduction, but 14 required operation, four following failed radiological reduction. There was one intestinal perforation due to attempted barium enema reduction and one patient required a reoperation for ileal gangrene following operative reduction. There were no deaths and there have been no subsequent recurrent intussusceptions although three cases were lost to follow up. There was a delay in diagnosis in some cases (average duration from onset to diagnosis was 34 h). Although delay was incurred by parents in some cases and in peripheral hospitals in others, there is a need for greater awareness by surgeons of the significance of subtle features such as pallor and lethargy in a child with persistent vomiting. Delay in diagnosis is likely to lead to an increased need for primary surgical intervention. Adverse features (age > 3 months or < 2 years; symptoms > 24 h; small bowel obstruction; dehydration > 5%) were predictive of an increased likelihood of surgical resection, and may help avoid inappropriate attempts at radiological reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Barium Sulfate↗
PubMed1992

Laparoscopic cholecystectomy. A prospective study of outcome in 100 unselected patients.

OBJECTIVE: To describe the outcome of laparoscopic (percutaneous) cholecystectomy in the management of gallbladder stones. PATIENTS AND METHODS: One hundred unselected consecutive patients referred for cholecystectomy, or admitted as emergencies with complicated gallbladder disease. Ten patients had acute cholecystitis, three had empyema, three had gallstone pancreatitis, and 11 had a history of recent jaundice. Common bile duct stones were dealt with by endoscopic sphincterotomy. OUTCOME MEASURES: Intraoperative and postoperative complications, 30-day mortality rate, duration of hospital stay, and length of postoperative disability. RESULTS: Three patients were excluded and underwent open cholecystectomy. Laparoscopic cholecystectomy was attempted in the remaining 97, and successfully completed in 87; 10 were converted to open cholecystectomy. There were no significant intraoperative complications. Two patients had a postoperative haemorrhage and one had a transient bile leak; none required reoperation. There was one death from myocardial infarction 12 days after operation. Minor complications occurred in 12 patients. Mean operating time was 88 minutes. The average length of hospital stay was 72 hours, and most patients returned to normal activities after seven days. CONCLUSIONS: Laparoscopic cholecystectomy offers an outcome comparable to standard cholecystectomy and is applicable to 90% of patients requiring removal of the gallbladder. Laparoscopic cholecystectomy has significant advantages over open cholecystectomy in terms of reduced postoperative pain and disability.

Adolescent↗