Israel Medical Association Journal

Surgical resection offers the best opportunity for cure in patients with colorectal cancer metastasis to the liver, with 5 year survival rates of up to 58% following resection. However, only a small percentage of patients are eligible for resection at the time of diagnosis and the average recurrence rate is still high. Consequently, research endeavors have focused on methods aimed to increase the number of patients eligible for surgical resection, refine the selection criteria for surgery, and improve the disease-free and overall survival time in these patients. Improvements in imaging techniques and the increasing use of FDG-PET allow more accurate preoperative staging and superior identification of patients likely to benefit from surgical resection. Advances in the use of neoadjuvant chemotherapy allows up to 38% of patients previously considered unresectable to be significantly downstaged and eligible for hepatic resection. Many reports have critically evaluated the surgical techniques applied to liver resection, the concurrent or alternative use of local ablative therapies, such as radiofrequency ablation, and the subsequent utilization of adjuvant chemotherapy in patients undergoing surgical resection for hepatic metastases.

Background: The Fibrotest-Actitest™ is a six-parameter scoring system that allows quantification of liver fibrosis and inflammation. This test has been validated by several studies in hepatitis B and C viruses and alcoholic liver disease, with a high correlation between the liver biopsy and the results of the FT-AT[1] (AUROC between 0.78 and 0.95).The FT-AT was introduced in Israel (Rambam Laboratory) in March 2005.

Objectives: To assess the results of HCV[2] patients who underwent the test during the period March 2005 to February 2006.

Methods: Serum was taken and brought to the central laboratory performing the tests within 4 hours. Six parameters were evaluated using commercial kits approved by the designer of the test (Biopredictive): total bilirubin, gamma-glutamyltransferase, alpha-2 macroglobulin, haptoglobin, alanine aminotransferase, and apolipoprotein-A1. The results were sent to the website of Biopredictive (France), which provided the FT-AT score online using a patented formula.

Results: Of the 325 patients tested, only 4 were not interpretable because of hemolysis. Patients' age ranged from 7 to 72 years (median 42); 54% were female. Liver biopsy was performed in 81 patients and was compared with the results of the Fibrotest. Findings were as follows: 27% of the patients were F0, 19% F1, 20% F2, 17% F3 and 17% F4; 18% were A0, 32% A1, 28% A2 and 22% A3. The AUROC curve comparing the Fibrotest with liver biopsy with a cutoff point at F2 and A2 for significant fibrosis and inflammation was 0.85 and 0.79 respectively.

Conclusion: Fibrotest is a simple and effective method to assess liver fibrosis and inflammation and can be considered an alternative to liver biopsy in most patients with HCV.

Background: The model for end-stage liver disease is the best available predictor of waiting list mortality among liver transplant candidates.

Objectives: To validate the applicability of MELD[1] in Israel.

Methods: All candidates awaiting liver transplantation in our institution were followed prospectively since 2002. We measured the concordance (c-statistic) equivalent to the area under the receiver operating characteristic curve in order to assess the predictive power of MELD. Other independent mortality risk factors were identified by a separate multivariate analysis. Mortality rates within different MELD and Child‑Pugh‑Turcotte scores were compared to the original (United States) MELD data.

Results: Of 86 patients listed for transplantation, 40 were transplanted (36 in Israel and 4 abroad). Of the other 46 patients, 24 are alive and still listed, and 22 died (25%, ~7%/year). The area under the ROC[2] curve for MELD score was 0.79 (0.83 USA) compared to a CPT[3] score of 0.71 (O.76 USA). High MELD scores, occurrence of spontaneous bacterial peritonitis, and diagnosis of hepatocellular carcinoma were independent risk factors of mortality. Death rates per mid MELD score (20–29) were significantly higher than the USA results.

Conclusions: MELD is valid in Israel and superior to CPT in predicting waiting list mortality. Although longer waiting time due to organ scarcity is a key factor, death rates in the mid-range (10–29) MELD groups indicate further audit of the care of patients with end‑stage liver disease.

Objectives: To report 3 years national experience with orthotopic liver transplantation, and to evaluate patient and perioperative risk factors that could affect 1 year graft survival.

Methods: The study related to all 124 isolated adult liver transplantations performed in Israel between October 1997 and October 2000. Data were abstracted from the medical records. One-year graft survival was described using the Kaplan-Meier survival curve and three multivariate logistic regression models were performed: one with preoperative case-mix factors alone, and the other two with the addition of donor and operative factors respectively.

Results: Of the 124 liver transplantations performed, 32 failed (25.8%). The 1 year survival was lower than rates reported from both the United States and Europe, but the difference was not significant. Of the preoperative risk factors, recipient age ≥ 60 years, critical condition prior to surgery, high serum bilirubin and serum hemoglobin ≤ 10 g/dl were independently associated with graft failure, adjusting for all the other factors that entered the logistic regression equation. Extending the model to include donor and operative factors raised the C-statistic from 0.79 to 0.87. Donor age ≥ 40, cold ischemic time > 10 hours and a prolonged operation (> 10 hours) were the additional predictors for graft survival. A MELD score of over 18 was associated with a sixfold increased risk for graft failure (odds ratio = 6.5, P = 0.001).

Conclusions: Graft survival in Israel is slightly lower than that reported from the U.S. and Europe. Adding donor and operative factors to recipient characteristics significantly increased our understanding of 1 year survival of liver grafts.

Objectives: To determine the overall prevalence of PBC[1] in southern Israel and the specific rates for different immigrant groups between January 1993 and October 2004.

Methods: Multiple case-finding methods were used to identify all cases of PBC in the study region. Age-adjusted prevalence rates were compared among the different immigrant groups.

Results: A total of 47 cases of PBC were identified with an overall prevalence of 55 cases per million. All patients were women, and all except for a Bedouin Arab were Jewish. Foreign-born patients comprised 70% of our PBC cohort even though they represent only 45.4% of the regional population. This predominance of immigrants did not change when the rates were adjusted for age (P < 0.001). The prevalence rates were 40, 177, and 58 cases per million for those born in Israel, North Africa or Asia, and Eastern Europe, respectively. The age-specific prevalence rate for women older than 40 years varied from 135 cases per million among those born in Israel to 450 among immigrants from Eastern Europe and the former USSR to 700 cases per million among immigrants from North Africa and Asia.

Conclusions: The prevalence of PBC in southern Israel is similar to that reported from some European countries. The rate is much higher among Jews than Arabs and among immigrants to Israel compared to native Israelis.

Objectives: To assess the effect of a vaginal ring delivering estradiol and progesterone in postmenopausal women and to determine whether continuous administration can relieve climacteric symptoms, produce an acceptable pattern of vaginal bleeding and control endometrial proliferation.

Methods: Twenty-nine postmenopausal women with an intact uterus were studied. All had climacteric symptoms. The vaginal rings contained 0.36 g estradiol and either 3.6 g progesterone (high dose progesterone) or 1.8 g (low dose progesterone), and were kept in place for 4–6 months. Serum progesterone, estradiol and estrone were measured and endometrial thickness determined. All women kept a daily diary of bleeding/spotting and completed a questionnaire on climacteric symptoms at monthly intervals. The low dose progesterone group comprised 14 women and the high dose progesterone group 15 women.

Results: A total of 18 patients (9 in each group) completed the study. Mean levels of estradiol, estrone and progesterone were at their peak after 2 to 4 weeks. All rings were effective in alleviating vasomotor symptoms, although there was evidence of the "escape from effect" in month 6. Endometrial thickness increased in 6 of the 29 women but biopsy in each case showed no evidence of hyperplasia. Of the 18 women who completed the study, 5 had amenorrhea throughout, 7 had amenorrhea after 3 months, and the remainder had one or two bleeding episodes after 3 months. Therapy was discontinued in 11 women.

Conclusions: A vaginal ring delivering estradiol and progesterone controlled climacteric symptoms, prevented endometrial proliferation, and provided an acceptable bleeding pattern. It should be viewed as a promising alternative for short-term estrogen-progesterone therapy.