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Biomedical subjects

J P Lodge

Publications and source records attributed to J P Lodge.

At least 19 recordsLinked to original sources

Cyclooxygenase-2 expression in colorectal cancer liver metastases.

Cyclooxygenase-2 (COX-2) is up-regulated in 85-90% of primary human colorectal cancers and is a putative target for the chemopreventative activity of non-steroidal anti-inflammatory drugs. However, COX-2 expression by human colorectal cancer liver metastases has been poorly characterized. We studied a consecutive series of 38 patients who underwent liver resection for metastatic disease, for whom long-term (up to 57 months), prospective follow-up data were available. Semi-quantitative immunohistochemistry for COX-2 was performed on 54 metastases from 35 patients, for whom adequate histological material was available. Diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100% of metastases (COX-2 score 1, n = 25; score 2, n = 29). There was no relationship between metastasis size or differentiation grade and the level of COX-2 protein expression. There was no difference in colorectal cancer-free or overall survival between patients with high (score 2) and low (score 1) COX-2 scores (Kaplan-Meier survival analysis and log rank test, both P = 0.97). Multivariate Cox regression analysis identified age, incomplete resection and presence of extra-hepatic disease as independent predictors of disease-free and overall survival following surgery. COX-2 protein was also localized to a subset of stromal fibroblasts and mononuclear cells within metastases as well as hepatocytes from resection specimens. COX-2 protein was expressed by cancer cells in all human colorectal cancer liver metastases which were studied. Investigation of the effect of selective COX-2 inhibition on metastasis growth and metastasis cancer cell proliferation/apoptosis in vivo are warranted.

Colorectal Neoplasms↗

Ex vivo and in situ resection of inferior vena cava with hepatectomy for colorectal metastases.

OBJECTIVE: To describe the surgical techniques and early results of inferior vena cava (IVC) resection in patients with advanced liver tumors. SUMMARY BACKGROUND DATA: Involvement of the IVC by hepatic tumors, although rare, is considered inoperable by standard resection techniques. Concomitant hepatic and IVC resection is required to achieve adequate tumor clearance. METHODS: Between February 1995 and February 1999, 158 patients underwent hepatic resection for colorectal metastases in the authors' unit. Eight patients, aged 42 to 80 years (mean 62 years), with hepatic metastases from colorectal cancer underwent concomitant resection of the IVC and four to six hepatic segments. Resections were carried out under total hepatic vascular exclusion in four patients and ex vivo in four patients. Between 30 degrees and 360 degrees of the retrohepatic IVC was resected and replaced with an autogenous vein patch (n = 1), a ringed Gore-Tex tube graft (n = 2), a Dacron tube graft (n = 1), or a patch (n = 3) or was repaired by primary suturing (n = 1). RESULTS: There were two early deaths from multiple organ failure. One patient survived 30 months after ex vivo resection but died of renal cell carcinoma, and another died with recurrent disease at 9 months. The remaining four patients remained alive 5 to 12 months after surgery, with no hepatic failure or venous obstruction; tumor recurrence was present in two. Nonthrombotic occlusion of the neocava occurred in one patient and was stented successfully. CONCLUSIONS: Although concomitant hepatic and IVC resection is associated with a considerable surgical risk, this aggressive surgical approach offers hope for patients with hepatic tumors involving the IVC, who would otherwise have a dismal prognosis. This procedure can be performed under total hepatic vascular exclusion, with or without venovenous bypass, and by ex vivo bench resection.

Adenocarcinoma↗

Laser Doppler flowmetry is useful in the clinical management of small bowel transplantation. The Liver Transplant Group.

OBJECTIVE: Laser Doppler flowmetry (LDF) has been used as a research tool to measure splanchnic perfusion. In this report, we aim to demonstrate the clinical value of this technique in perioperative monitoring of transplanted small bowel. METHODS: A 24 year old man underwent small bowel transplantation using a previously described technique. Microvascular blood flow in the transplanted bowel was measured using an LDF splanchnic probe. Postoperatively this was applied to the stoma facilitating direct measurements of graft mucosal flow. Measurements (perfusion units (PU)) were documented prior to implantation, post-reperfusion, postoperatively, during graft ischaemia, and in response to therapeutic interventions (dopexamine and phenylephrine infusions). RESULTS: Prior to transplantation, biological zero was established. Flow at five, 15, and 60 minutes after reperfusion was 74 (1.9) PU, 87.5 (3.3) PU, and 141.5 (2.5) PU, respectively. Postoperative mucosal flow was 141.6 (2.9) PU. Subsequent LDF measurement detected absence of flow even though clinical signs suggested only moderate reduction. This was confirmed on surgical re-exploration and facilitated prompt resection of a non-viable segment. Fluid and dopexamine administration resulted in a dose dependent improvement in flow, independent of blood pressure. Addition of phenylephrine increased total mucosal flow and unmasked a cyclical component. CONCLUSION: This case demonstrates the clinical value of LDF as an "alarm" to indicate graft perfusion failure and as a monitor for therapeutic interventions. Phenylephrine and dopexamine may both be of value in improving mucosal flow in the transplanted small bowel.

Adrenergic alpha-Agonists↗

Hepatic lesion detection after superparamagnetic iron oxide enhancement: comparison of five T2-weighted sequences at 1.0 T by using alternative-free response receiver operating characteristic analysis.

PURPOSE: To compare the accuracy of five T2-weighted sequences in the detection of liver lesion at magnetic resonance (MR) imaging after superparamagnetic iron oxide (SPIO) enhancement. MATERIALS AND METHODS: Forty-nine candidates for hepatic resection with known coloretal metastases were examined. Before SPIO enhancement, fast spin-echo (SE) images were obtained. After enhancement, the same fast SE sequence and long; TR/short TE, short TE, long TR/TE, and T2-weighted fast low-angle shot (FLASH) sequences were used. All images were viewed independently by four observers who were blinded to the results of the other imaging sequences, the results of the other observers, and the findings at surgery and histopathologic examination. Four weeks after the initial reading, the combined long TR/short TE and long TR/TE dual-echo images were also viewed as an additional set. The alternative free response receiver operating characteristic (ROC) method was used to analyze the results, which were correlated with findings at surgery, intraoperative ultrasonography, and histopathologic examination. RESULTS: Irrespective of lesion size, the accuracy of all sequences after enhancement was significantly greater than that of the nonenhanced fast SE sequence (P < .01). Dual-echo and FLASH sequences were significantly more accurate than the enhanced fast SE sequence (P < .03 or P < .02, respectively). For all lesions, lesions smaller than 1 cm, and lesions 1 cm or larger, mean accuracies were as follows: dual-echo, 0.75, 0.54, and 0.93; FLASH, 0.75, 0.54, and 0.95; and enhanced fast SE, 0.72, 0.49, and 0.92. CONCLUSION: At 1.0 T, dual-echo and FLASH sequences are the most accurate pulse sequences after SPIO enhancement.

Aged↗

Biliary strictures complicating pancreaticoduodenectomy.

BACKGROUND: Biliary-enteric anastomotic strictures may complicate pancreaticoduodenectomy. Anastomotic ischaemia and reflux of gastric and enteric contents with secondary bacterobilia and cholangitis may contribute. METHODS: Four patients (3 females, 1 male) with a mean age of 50 yr (range 26-73 yr) presented 1-12 yr following pancreaticoduodenectomy with features suggestive of biliary-enteric anastomotic stricture formation. These included recurrent cholangitis, obstructive jaundice, and liver abscess. Diagnosis was confirmed by percutaneous or endoscopic cholangiography. Endoscopic and radiological management were unsuccessful, and revision surgery in the form of a Roux-en-Y hepaticojejunostomy was required. RESULTS: Three patients remain asymptomatic 10-30 mo postoperatively. Jaundice recurred at 15 mo in one patient owing to re-stricture formation and the development of secondary biliary cirrhosis; a liver transplantation is being considered. CONCLUSION: Early diagnosis and prompt management of biliary-enteric stricture is essential if secondary biliary cirrhosis is to be avoided. Definitive therapy is best accomplished with a Roux-en-Y hepaticojejunostomy that places the gastric and biliary anastomoses onto separate jejunal limbs.

Adult↗

Liver transplantation for metastatic hemangiopericytoma associated with hypoglycemia.

We report a case of successful liver transplantation in a young man with metastatic hemangiopericytoma confined to the liver. He had a primary retroperitoneal hemangiopericytoma removed in 1982 and was diagnosed as having liver metastases 8 years later. Subsequently, he developed hypoglycemia, which did not respond to chemotherapy. Hepatectomy and transplantation resolved his hypoglycemic attacks. He remained well and symptom free for 4 years. Liver transplantation can provide effective palliation and should be considered in carefully selected patients with localized metastatic cancer.

Adult↗

p53 but not bcl-2 is expressed by most cholangiocarcinomas: a study of 28 cases.

AIMS: To examine the frequency and pattern of expression of p53 and bcl-2 in archival material from patients with cholangiocarcinomas and to evaluate their respective roles in its pathogenesis, diagnosis and prognosis. METHODS AND RESULTS: Twenty-eight surgical cases of cholangiocarcinomas diagnosed at St James's University Hospital and 16 control cases were immunostained with monoclonal antibodies to p53 and bcl-2 using streptavidin-biotin complex method. Pressure cooker was used for antigen retrieval. Of the cholangiocarcinomas, 85.7% (24/28) overexpressed p53. The intensity of staining in these cases varied from 1+ in 2, 2+ in 10 and 3+ in 12 cases. None of the 28 tumours expressed bcl-2. The well differentiated nature of the tumour made assessment of dysplasia difficult, however, where present it did not express p53 or bcl-2. The bile duct epithelium adjacent to the tumour and in the control cases did not show any significant nuclear staining for either antigen. CONCLUSIONS: Overexpression of p53 appears to play an important role as a late event in the pathogenesis of cholangiocarcinomas, while we found no evidence of bcl-2 overexpression. The expression of p53 in 86% of the invasive tumours, as compared to its lack in the adjacent normal bile duct epithelium, makes it potentially useful in the diagnostic histopathology of these cases.

Bile Duct Neoplasms↗