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Biomedical subjects

A W Hemming

Publications and source records attributed to A W Hemming.

At least 37 records · Page 2Linked to original sources
PubMed1998

Domino liver transplantation for familial amyloid polyneuropathy.

Familial amyloid polyneuropathy is an autosomal dominant disorder in which the liver produces a variant prealbumin that is deposited along nerves, leading to a progressive and fatal polyneuropathy that begins in the third decade of life. Liver transplantation has been the only successful treatment to date. Apart from the production of the variant protein, there are no other abnormalities in these amyloid livers. We describe two cases in which, at the time of transplantation, the amyloid livers were subsequently used for transplantation in another patient, and we discuss the implications.

Adult↗
PubMed1998

A pharmacoeconomic analysis of Neoral without intravenous cyclosporine in liver transplantation in Canada.

Neoral, a microemulsion formulation of cyclosporin A (CsA), has improved absorption compared to Sandimmune and has allowed induction of immunosuppression in liver transplantation (LT) without the use of intravenous (i.v.) CsA. The improved bioavailability with less inter- and intra-patient dosing variability coupled with the lack of requirement for i.v. CsA may provide a mechanism for cost savings when Neoral is used for induction immunosuppression. This retrospective case-control study compares the relative costs associated with Neoral induction without i.v. CsA versus induction with i.v. CsA followed by oral CsA in adult liver transplant recipients. Twenty consecutive patients receiving Neoral 12-15 mg/kg per d were compared to a control group of 21 patients receiving i.v. CsA followed by oral CsA for induction. Both groups received the same rapidly tapered dose of methyl-prednisilone. Health care resource utilization was assigned based on days in hospital and acute rejection episodes (ARE). Hospital per diem rates at specified care levels were used to assign costs associated with hospital stay, while a previously developed case-costing model was used to assign costs to episodes of acute rejection. All patients were followed for a 3-month period post-transplant. Although there was a trend towards shorter hospital stay in the Neoral group the majority of cost savings were achieved by reducing costs associated with episodes of acute rejection. There were seven and 19 episodes of ARE in the Neoral and i.v. CsA groups respectively (p < 0.05.) A separate cost effective assessment of the effect of reducing rejection by decision tree analysis demonstrated a cost reduction of $2162 per patient. The savings achieved with Neoral proved robust on sensitivity analysis. The change of practice to an induction immunosuppression regimen of Neoral without i.v. CsA has achieved a cost savings in adult liver transplantation at our center.

Adult↗
PubMed1996

A microemulsion of cyclosporine without intravenous cyclosporine in liver transplantation.

A microemulsion formulation of cyclosporine (CsA) has improved absorption compared with the original form. The purpose of this case control study was to assess the safety and efficacy of the microemulsion without intravenous CsA for induction immunosuppression in adult liver transplantation. Twenty-one consecutive patients receiving induction immunosuppression with the microemulsion 15 mg/kg/day were compared with 20 patients receiving intravenous CsA and the original oral form. Both groups received the same dose of methylprednisilone. Twenty of 21 patients receiving the microemulsion required no intravenous CsA to achieve target CsA levels. All patients receiving the original form received initial intravenous CsA. There was no difference in trough CsA levels between the two groups at 24 and 48 hours. The microemulsion group had 24 hr and 48 hr trough CsA levels of 227+/-15 and 520+/-300 ng/ml by monoclonal RIA while the intravenous CsA group had 24 and 48 hr trough levels of 293+/-18 and 405+/-91 ng/ml. CsA levels analyzed by HPLC were 20% lower than by RIA. The frequency of adverse events resulting in reduction of drug dosage was similar for the microemulsion and the original form: neurotoxicity (23 vs. 40%, P=.30); nephrotoxicity (25 vs. 45%, P=.32), and no patients required dialysis. There was no difference in septic complications. One patient required discontinuation of the microemulsion in an attempt to reverse severe neurotoxicity. A total of 75% of microemulsion patients were rejection free at 3 months while only 35% of CsA patients remained rejection free (P=0.02). These data suggest that the use of the microemulsion without intravenous CsA in liver transplantation is safe and efficacious, and may result in decreased episodes of acute rejection.

Adult↗
PubMed1996

Treatment of Budd-Chiari syndrome with portosystemic shunt or liver transplantation.

BACKGROUND: Budd-Chiari syndrome is an uncommon disorder caused by obstruction to hepatic venous outflow, causing varying degrees of hepatic injury depending on the extent, severity, and acuity of the obstruction. PATIENTS AND METHODS: We reviewed the indications for operative intervention and the results of treating 32 patients with Budd-Chiari syndrome seen at Toronto Hospital between 1968 and 1995. RESULTS: Twenty-one patients underwent portosystemic shunt (PSS) and 7 patients underwent liver transplantation (LT) as their initial operative management. Three patients who initially had PSS subsequently required LT. Patients with cirrhosis found on biopsy and preservation of hepatocellular function were treated with PSS and showed no difference in outcome when compared with patients without cirrhosis (P = 0.35). Patients who were treated by PSS with retrohepatic vena caval compression, as shown by high caval gradients had outcomes similar to those for patients with low gradients (P = 0.31). Using the Kaplan-Meier method, 5-year survival of PSS patients was 57%. Liver transplantation was used to manage patients with hepatic decompensation, as well as patients with vena caval occlusion or failed PSS. The 5-year Kaplan-Meier survival for LT was 67%. CONCLUSIONS: Both PSS and LT are effective options in the management of Budd-Chiari syndrome. Portosystemic shunt is the preferred initial approach even with cirrhosis or retrohepatic caval compression as long as there is preservation of liver function and a patent vena cava. Liver transplantation should be used as primary therapy for patients with irreversible hepatic decompensation or vena caval occlusion, and it can be an effective salvage procedure following failed PSS.

Adolescent↗
PubMed1996

The University of Toronto liver transplant program.

The University of Toronto liver transplant program began in 1985 at a time when the procedure had already evolved from an experimental form of surgery to an accepted treatment for many forms of liver failure. The program was established not only to provide clinical care for patients but also to address academically the barriers which impeded success. The program brought together experts in medicine, surgery, pathology, and the basic sciences of immunology, virology and molecular biology. Our group has had a special interest in transplantation for viral hepatitis. We demonstrated the role of HBV DNA as a prospective factor in both viral recurrence and survival. We further studied a number of agents to prevent re-infection including PGE, HBIG and more recently lamivudine. Although the short-term results of transplantation for HCV appear excellent, reinfection of the graft and development of chronic hepatitis and cirrhosis may make long-term results problematic. Therefore, we have directed attention to studies of pathogenesis and treatment of HCV in liver transplantation. Our studies have demonstrated a unique role for ribavirin as an immunomodulatory agent which can benefit the course of posttransplant HCV. Future studies will examine combination therapy in an attempt to eradicate the virus. Our group also has been interested in PNF and FHF and have demonstrated a positive effect of PGE in this setting. As we look to the future, the greatest challenges facing transplantation are the shortage of organ donors and the toxic effects of long-term immunosuppression. Our group now has established research efforts both in tolerance induction and xenotransplantation which we feel are necessary to make transplantation an effective, universal treatment for end stage organ failure.

Adult↗
PubMed1995

Laparoscopic staging of intraabdominal malignancy.

Laparoscopic visualization techniques have improved dramatically over the last 5 years and have led to reassessment of the laparoscope for use in the staging of intraabdominal malignancy. One hundred sixty-two consecutive cases undergoing preoperative staging laparoscopy from January 1988 to December 1993 were reviewed in order to determine the value of laparoscopy as a staging tool. Indications for staging laparoscopy were predominantly hepatopancreaticobiliary (85%); however, other primaries such as stomach and colon were included. In 36% of cases information found at laparoscopy precluded resection and prevented unnecessary laparotomy. Additional information that was felt to be helpful in planning resection was found in 30% of cases. In 12% of cases unresectability was found only at the time of laparotomy and was missed by staging laparoscopy. We conclude that laparoscopy is a useful preoperative staging tool and can help avoid unnecessary laparotomy for intraabdominal malignancy in one-third of patients.

Abdominal Neoplasms↗
PubMed1994

Surgical management of choledochal cysts.

Choledochal cysts are an unusual cause of biliary obstruction with up to 85% of reported cases being of the type I variety, that is, fusiform dilations of the common bile duct. Recommended management of this type I cyst is complete surgical excision; however, difficulties arise in type IVa cysts when the cystic dilation extends up into the intrahepatic biliary tree. The purpose of this study is to review the management of choledochal cysts with particular reference to the type IVa variety. Statistical analysis of outcome differences was undertaken using Fisher's exact test. A total of 23 consecutive patients with choledochal cysts seen at our institution in a 5-year period were reviewed: 8 patients had type I cysts, 1 patient had a type III cyst, and 14 patients had type IVa cysts. All type I cysts underwent complete cyst excision with hepaticojejunostomy and modified Houston loop formation. Of 14 patients with type IVa cysts, 13 underwent complete excision of the extrahepatic portion of the cyst with hepatico- and cystojejunostomy and modified Hutson loop formation. One patient required hepatic lobectomy. With a mean follow-up of 33 months, 4 patients with type IVa choledochal cyst have had episodes of recurrent cholangitis, with access to the library tree being achieved via the Hutson loop in 3 of the 4 patients. Three of these cases represented anastomotic strictures that were treated nonoperatively. We concluded that recurrent cholangitis and anastomotic stricture after resection of type IVa choledochal cysts is frequent and recommend Hutson loop formation at the time of primary resection.

Adolescent↗
PubMed1993

Photodynamic therapy of squamous cell carcinoma. An evaluation of a new photosensitizing agent, benzoporphyrin derivative and new photoimmunoconjugate.

Photodynamic therapy for cancer depends on the relatively selective distribution of photosensitizing agents to malignant as compared with normal tissues, rendering the malignant cells more susceptible to light-mediated damage. Photodynamic therapy has been used with only moderate success to date. The purpose of this study was to compare a new photosensitizing agent, benzoporphyrin derivative (BPD), to the standard agent presently in use, photofrin II, in a hamster cheek pouch model of squamous cell carcinoma. As well we have investigated the potential of using a tumour-specific monoclonal antibody-BPD conjugate to improve the tumour localizing properties of BPD. Treatment consisted of photodynamic therapy with either photofrin II, BPD, or a tumour-specific anti-epidermal growth factor receptor-BPD conjugate. Control groups of light alone, anti-EGFr, tumour non-specific MoAb, and tumour non-specific MoAb-BPD conjugate were included with the contralateral cheek pouch of each animal acting as a dark control. An assessment of differential delivery of BPD to tumour and to normal mucosa was undertaken using a spectrophotometric assay. Parametric statistical analysis included Student's t-tests and linear regression while non-parametric analysis was undertaken using Fisher's exact test. Animals receiving BPD alone demonstrated tumour-to-tissue levels of approximately 2:1 while animals receiving the tumour-specific anti-EGFr-BPD conjugate had significantly better tumour:tissue ratios of 26:1 (P < 0.005). Animals treated with photofrin II had a 1 month cancer-free survival of 27% while animals treated with BPD had an improved survival of 67% (P = 0.03). The group treated with the tumour-specific anti-EGFr-BPD conjugate at a twentieth the total dose of BPD had an 80% 1 month cancer-free survival which was not statistically different from the group treated with BPD alone. Benzoporphyrin appears to be a more effective photosensitizing agent than Photofrin II and its tumour selectivity can be improved using a tumour specific monoclonal antibody conjugate.

Animals↗
PubMed1993

Evaluation of 50 consecutive segmental hepatic resections.

The development of increasingly sensitive imaging techniques along with improved follow-up and screening of high-risk patients has led to hepatic tumors, both primary and secondary, being detected while still at an early stage. Improved understanding of hepatic anatomy along with advances in surgical technique has led to the ability to undertake hepatic resections based on the segmental hepatic anatomy as described by Couinaud. The purpose of this paper is to assess the safety, technique, and oncologic efficacy of segmental hepatic resection. Fifty consecutive patients undergoing segmental hepatic resection during a 3-year time period ending in January 1992 were reviewed. Parametric statistical analysis was undertaken using Student's t-tests. Overall mortality was 2% with a morbidity rate of 8%. Transfusion requirements were 1 +/- 1.5 U; however, cirrhotic patients showed a significantly increased transfusion requirement of 2.0 +/- 1.3 U versus 0.7 +/- 1.3 U (p = 0.03). Sixty percent of patients required no transfusion at all. The mean duration of inflow occlusion was 42 +/- 17 minutes. Resection margins were clear of tumor by greater than 1 cm in 48 of 50 patients. Segmental hepatic resection is a safe and effective technique that occasionally may offer advantages over formal resection. Some aspects of the technique are reviewed.

Adolescent↗
PubMed1993

Blunt traumatic liver injury associated with clostridial infection of early onset.

Hepatic clostridial infections associated with blunt abdominal trauma are rare. Generally they occur from 2 weeks to 3 months after injury and are thought to result from the growth of normal enteric organisms, which are carried to the liver by the portal venous system and infect devitalized tissue. The authors describe two patients in whom the hepatic infection became established in less than 24 hours after injury and was due to Clostridium spp. The patients were successfully treated by hepatic resection and combination antimicrobial therapy. Hyperbaric oxygen was used as an adjunct in one case.

Abdominal Injuries↗
PubMed1992

Prognostic markers of colorectal cancer: an evaluation of DNA content, epidermal growth factor receptor, and Ki-67.

Between January 1989 and August 1991, 62 patients undergoing resection for colorectal adenocarcinoma were assessed in a prospective fashion on the basis of various tumor characteristics that are thought to indicate prognosis. Parameters measured included epidermal growth factor receptor (EGFr) expression, a cell membrane receptor known to be overexpressed in a variety of tumors, Ki-67, a monoclonal antibody marker of cell proliferation, as well as flow cytometry and standard histologic examination. Statistical analysis included chi square with Yates correction when appropriate, Wilcoxon W, and multivariate logistic regression. EGFr positive tumors were associated with worse Dukes' stage (27% of EGFr negative tumors were Dukes' C or D vs. 58% of EGFr positive tumors, P = 0.03), as well as more aneuploid characteristics by flow cytometry (48% EGFr negative = aneuploid vs. 82% EGFr positive = aneuploid, P = 0.01). Lymphatic invasion was more frequent in EGFr positive tumors (P = 0.03). These factors proved to be independent of each other by multivariate analysis. Ki-67 did not correlate with any of the measured parameters and was of extremely limited use in the evaluation of the study population. Multivariate analysis indicated that aneuploid tumors were associated with worse Dukes' stage than diploid tumors. Histologic parameters such as lymphatic and vascular invasion as well as histologic grade are compared to the other parameters involved with prognosis.

Adenocarcinoma↗
PubMed1992

Indocyanine green clearance as a predictor of successful hepatic resection in cirrhotic patients.

Twenty-two cirrhotic patients who underwent hepatic resection from July 1989 to March 1991 at Vancouver General Hospital were analyzed prospectively in order to determine whether there was any preoperative evaluation of liver function that would help identify those patients who would not survive hepatic resection. Patients were analyzed on the basis of age, type of resection, and a variety of so-called standard liver function tests. In addition, all patients were evaluated preoperatively with an indocyanine green (ICG) clearance test, a relatively new test that we attempted to evaluate in terms of its role in hepatic resection in cirrhotic patients. Parametric statistical evaluation used included Student's t-test and multivariate regression, as well as discriminate analysis. The nonparametric evaluation used was the Wilcoxon rank sum test. Overall, the 30-day mortality rate was 18%, with those patients who did not survive resection having a significantly lower ICG clearance than those who underwent successful resection (p less than 0.0001). No other liver function test was useful in determining the outcome of resection. Similarly, neither age nor type of resection appeared to influence outcome. Use of discriminate analysis (p = 0.0029) allowed the identification of a cutoff point for ICG clearance below which hepatic resection should not be attempted.

Hepatectomy↗