David J. Koorey

P53, deleted in colorectal cancer gene, and thymidylate synthase as predictors of histopathologic response and survival in low, locally advanced rectal cancer treated with preoperative adjuvant therapy

AbstractPURPOSE: Adjuvant therapy, either preoperatively or postoperatively, and modifications of surgery have been used to try to improve outcome of surgery for rectal cancer in regard to both local recurrence and survival. Assessment of prognosis in patients after resection is currently primarily based on clinicopathologic factors. These predict the subsequent behavior of the tumor only imperfectly. The aim of this study was to evaluate three potential molecular genetic markers of prognosis (p53, deleted in colorectal cancer gene, and thymidylate synthase) in Dukes Stage B and C low rectal tumors treated with adjuvant therapy and to determine whether they correlate with survival, local recurrence, or the pathologic response to adjuvant therapy (assessed by extent of tumor regression and tumor down-staging). METHODS: Sixty locally advanced low rectal tumors resected after preoperative chemoradiotherapy or radiotherapy alone were studied by immunohistochemical staining for p53, deleted in colorectal cancer gene, and thymidylate synthase. In addition, p53 gene mutations were sought by polymerase chain reaction–single-strand conformation polymorphism analysis. These results were correlated with survival, local recurrence, and pathologic response to adjuvant therapy. RESULTS: Lack of thymidylate synthase staining by immunohistochemistry was associated with tumor down-staging after preoperative chemoradiotherapy but not after radiotherapy or for these two combined groups. There was no correlation between p53, deleted in colorectal cancer gene, or thymidylate synthase immunohistochemical staining or between p53 polymerase chain reaction–single-strand conformation polymorphism and local recurrence or survival in locally advanced low rectal cancers treated with preoperative adjuvant therapies. CONCLUSION: Prediction of prognosis in patients with locally advanced low rectal cancers treated with preoperative adjuvant therapies continues to be problematic. Thymidylate synthase immunohistochemistry appears to be the most promising factor of those assessed in predicting tumor down-staging after preoperative chemoradiotherapy for locally advanced low rectal cancers.

Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis b surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors

Abstract:  Background:  Liver transplantation from hepatitis B core‐antibody (HBcAb)‐positive donors to hepatitis B surface‐antigen (HBsAg)‐negative recipients has been associated with a risk of hepatitis B virus (HBV) infection in the absence of antiviral prophylaxis. The aim of this study is to assess the efficacy of long‐term lamivudine monotherapy to prevent development of HBV infection in HBsAg‐negative recipients of liver allografts from HBcAb‐positive donors.

Early high peak hepatitis C viral load levels independently predict hepatitis C–related liver failure post–liver transplantation

The aim of this study was to examine the importance of the serum hepatitis C viral load within the first year post–liver transplant in determining posttransplant survival. A retrospective analysis of 118 consecutive hepatitis C virus–positive liver transplant recipients who received an allograft from January 1997 to September 2005 was undertaken with a median duration of follow‐up of 32.4 months. Univariate and multivariate analyses were used to examine the effects of recipient, donor, surgical, and viral factors on posttransplant outcomes. A total of 620 viral load estimations were undertaken in the first 12 months following transplantation. Patient and graft survival rates at 1, 3, and 5 years were 87.8%, 79.9%, and 70.1% and 87.0%, 79.2%, and 68.2%, respectively. According to multivariate analysis, a peak viral load ≥ 107 IU/mL (P = 0.004; hazard ratio, 8.68; 95% confidence interval, 2.04–37.02) and exposure to antirejection therapy (P = 0.05; hazard ratio, 2.26; 95% confidence interval, 1.01–5.38) were both independent predictors of diminished patient and graft survival and hepatitis C–related allograft failure. The only other independent predictor of hepatitis C virus–related outcome after transplant was azathioprine use, which was associated with improved outcomes (P = 0.04; hazard ratio, 0.25; 95% confidence interval, 0.07–0.91). A peak viral load in the first year after transplant of >108, 107 to 108, and <107 IU/mL was associated with a mean survival of 11.8, 70.6, and 89.1 months respectively (P ≤ 0.03). The results emphasize the importance of high viral loads in the early posttransplant period as an independent predictor of recipient outcomes. Liver Transpl 15:709–718, 2009.

Histological tumour response to pre-operative combined modality therapy in locally advanced rectal cancer

Pre‐operative combined modality therapy (CMT) is used in locally advanced rectal cancer. Its use affects the clinicopathological staging based on the resected specimen. Assessment of the tumour response in the resected specimen may provide prognostic information. This study was undertaken to determine the histological response to pre‐operative chemoradiation and to assess the interobserver reliability of a newly developed tumour response grading system for rectal cancer.

Severe autoimmune hepatitis first presenting in the early post partum period

BACKGROUND & AIMS Autoimmune hepatitis (AIH) may run an aggressive clinical course if untreated. The influence of pregnancy on AIH is variable. Both flares in disease activity and remissions, often followed by a post partum flare, are well recognized. In contrast, definite AIH first presenting in the early post partum period has not been reported. METHODS We discuss a case series of 5 patients who developed severe AIH within 4 months post partum. RESULTS The diagnosis of AIH was definite based on internationally accepted criteria. Liver injury responded to conventional immunosuppressive therapy in all patients. Immune reactivation in the early post partum period may contribute to this entity. CONCLUSIONS AIH should be considered in the differential diagnosis of liver dysfunction first presenting in the early post partum period.

Outcome of patients with hepatocellular carcinoma referred to a tertiary centre with availability of multiple treatment options including cadaveric liver transplantation.

Hepatocellular carcinoma (HCC) is a primary cancer of the liver with an established causal link to viral hepatitis and other forms of chronic liver disease.

Inferior liver allograft survival from cadaveric donors >50 years of age?

The growing imbalance between the number of cadaveric organ donors and recipients has led to an increasing use of high‐risk donors as an option to expand the donor pool. The aim of this study was to evaluate our experience with the use of older liver (donor>50 yr of age) allografts. 
The medical records, postreperfusion biopsies and laboratory results were reviewed of the 393 patients who underwent orthotopic liver transplantation between 1986 and 1997. The outcome of the 61 patients who received older livers (OL) was compared to that of the other 332 recipients. 
Increasing use of OL was evident from 1992 onwards. Recipients of OL were older than recipients of younger livers (YL, p<0.001) and more commonly had underlying chronic viral hepatitis (CVH) or fulminant hepatic failure (p<0.05). Patient and allograft survival were only slightly less in recipients of OL versus YL (p=NS). Although postperfusion biopsies showed more damage in OL than YL allografts (p<0.05), this was not associated with increased primary graft failure. 
OL allografts can be transplanted with acceptable results into recipients without the concern of early allograft loss. 
Summary of Article: This report of one centres experience with 61 recipients of older donor liver allografts identifies recipient factors that may also have a negative impact on allograft outcome. These factors include a diagnosis of either CVH or fulminant hepatic failure at the time of transplantation. Postreperfusion biopsies of older donor allografts tend to show more damage, but this is not associated with primary non‐function.

Hepatocellular carcinoma: current approaches to diagnosis and management

Abstract

Hereditary lysozyme amyloidosis: Spontaneous hepatic rupture (15 years apart) in mother and daughter. role of emergency liver transplantation

Hepatic rupture is a rare condition, and treatment options are very limited. We report a case of hepatic rupture secondary to hereditary lysozyme amyloidosis that was successfully treated by liver transplantation. The mother of this patient had presented in an identical fashion 15 years earlier in the pretransplant era and died very rapidly. Liver Transpl 12:1152–1155, 2006.

An active liver transplant programme for hepatocellular carcinoma in cirrhotic patients : is it justified?

Even at an early stage, hepatocellular carcinoma (HCC) in patients with cirrhosis is often deemed unresectable because of limited liver reserve. In these circumstances, liver transplantation (LTx) offers some hope for palliation or cure. The results of LTx for selected cirrhotic patients with HCC were analysed. The outcomes were compared with those of patients who underwent LTx for other forms of hepatic malignancy and those who underwent LTx for non‐malignant conditions. Four hundred and eighty LTx were performed in 441 patients between January 1986 and December 1998. Twenty‐eight LTx recipients (25 males, 3 females) of mean age 51 (14–63) yr had cirrhosis and HCC. Twenty‐seven patients had underlying predisposing conditions (11 had hepatitis B, 10 had hepatitis C, 2 had hepatitis B and C, 1 had haemochromatosis, 1 had autoimmune hepatitis, 1 had alcoholic cirrhosis and 1 had α‐1 antitrypsin deficiency). In 22 patients, HCC was diagnosed pre‐LTx, and in 6 patients, the cancers were discovered incidentally. The average tumour size and number were 2.8 (0.4–11.5) cm and 1.3 (1–4), respectively. Two patients with known HCC died during and shortly after the LTx operation. Of the other patients, 3 died; 1 died of HCC recurrence 18 months post‐LTx, 1 died of graft failure from recurrent hepatitis C and 1 died of fungal sepsis. Twenty‐three (82%) patients survived to 22.5 (0.5–96) months post‐LTx without HCC recurrence and with 1‐ and 3‐yr actuarial patient survival rates of 87 and 76%, respectively. Equivalent survival rates of patients who underwent LTx for other malignancies (n=11) were 82 and 46% (p=NS), and for those who underwent LTx for benign causes (n=402), they were 77 and 73% (p=NS). All 15 patients with known HCC, who met the selection criteria now in use, survived. LTx can result in prolonged, cancer‐free survival in a good proportion of patients with cirrhosis and HCC, particularly when the cancers are incidental, or when diagnosed pre‐LTx, conforming to established selection criteria. An active LTx programme for this group of patients is justified.