Re-evaluation of HER2 status in metastatic breast cancer and tumor-marker guided therapy with vinorelbine and trastuzumab

Background: HER2 is overexpressed in 20 - 30% of breast cancers. Compared to chemotherapy alone, chemotherapy with trastuzumab improves clinical outcome in patients with HER2- positive metastatic breast cancer ( MBC). In general, HER2 status in a primary lesion predicts the status of metastases, so that biopsy of metastatic lesions appears unnecessary. Case Report: A 39- year old woman was diagnosed with primary breast cancer in November 2000. Using the method and scoring system of the DAKO Hercep Test, the tumor has shown low HER2 expression ( DAKO score 1+). After failure of several chemotherapy regimens for metastatic disease ( liver, skeletal), the patient underwent CT- guided needle biopsy of the liver which showed HER2 positive adenocarcinoma ( DAKO score 3+). In consequence, the patient was treated with vinorelbine ( 30 mg/ m(2) d1,8,15 q4w) and trastuzumab ( 4 mg/ kg loading dose, 2 mg/ kg weekly). During a treatment period of 4 months imaging results as well as tumor marker kinetics indicated an excellent response with sustained decrease of tumor markers. A retrospective analysis of the HER2 shed antigen in metastatic stage revealed excessively increased serum levels and supports HER2 overexpression observed in liver metastasis. The kinetics of the HER2 shed antigen during therapy for metastatic disease were found to be in phase with the kinetics of CEA and CA15- 3. Conclusion: This case report demonstrates that re- evaluation of the HER2 status may be helpful in single patients not sufficiently responding to treatment of metastatic disease. Determination of HER2 overexpression may be facilitated by a determination of the HER2 shed antigen level in peripheral blood

Surgical technique of orthotopic liver transplantation

Athough significant strides have been made in the surgical technique of orthotopic liver transplantation, numerous problems and nuisances are still encountered. Further surgical refinements will certainly evolve. The development of better preservation techniques, the use of intraoperative flowmeters, and the availability of new technologies, such as an artificial liver, should impact and advance the techniques of liver transplantation significantly and improve the overall results even further

Orthotopic liver transplantation for alcoholic cirrhosis.

Fifteen patients with Laennec's cirrhosis underwent orthotopic liver transplantation between 1963 and the end of 1979. The first eight patients died perioperatively or within two months, but four of the next seven patients had long survival; three are still alive after 11 to 14 years. After the introduction of cyclosporine therapy, 41 more patients with alcoholic cirrhosis were treated with liver transplantation from 1980 to June 1987. The one-year survival is 73.2%, and, after one to three years, 28 (68%) of the recipients are living. Of the 35 patients in the combined old and new series who lived for six months or longer, only two returned to alcohol abuse. Social and vocational rehabilitation has been the rule in these recipients who were selected primarily because of urgency of need, because they or their families insisted on treatment, and because they and their families thereby committed themselves to long-standing programs of alcoholism care

Sinnvoller Einsatz von Tumormarkern

Tumor markers refer to all detectable and measurable analytes which are able to indicate a solid tumor or contribute to its characterization or judgment concerning tumor spread and therapy efficacy. Among the markers, humoral circulating tumor substances, such as precursors of normal antigens, ectopically produced hormones or enzymes, ontogenetic old reactivated antigens, hybridoma-defined mucins and cytokeratins are of special interest. Up to now, no tumor specific biomarker has been detected, all markers known so far are physiological components of blood; thus, their diagnostic capacity is more related to quantity than to quality. The tumor marker concentration depends on the tumor blood supply and reflects tumor mass and tumor spread as a sum of marker expression, synthesis, release, the catabolism of the organism, as well as the marker excretion. Changes in biomarker levels without correlation to tumor load can be due to impairment of the liver and kidney function or due to invasive diagnostic methods (endoscopy, biopsy, ureteral catheter) or due to acute reactions on treatment (surgery, radio-chemotherapy). Due to problems with standardization between assays from different producers measuring the same antigen, interpretation of biomarkers of single measurements, such as PSA (prostate specific antigen), must be performed using assay specific reference ranges and interpretation of serial measurements must be performed using the identical assay. The test result has to be indicated together with the assay used (kit and producer). Among the potential indications for tumor marker determinations, the early detection or screening of a tumor is unrealistic - except PSA in prostate cancer detection. In rare cases, biomarkers can be helpful in tumor localization (HTG (human thyreoglobuline), PSA) and support of primary diagnosis, the knowledge about their prognostic relevance is increasing, the most widely used indication is therapy control and follow-up care in context with medical imaging. Provided that markers are critically selected following the localization of the tumor, that serial determinations are performed using the identical assay and that the clinical question is relevant, tumor markers contribute to a significant degree to diagnosis, prognosis, therapy control and early detection of metastatic or recurrent disease. Especially in the field of diagnostic oncology, the quality of the investigator is significantly linked to the quality of the test result

A prospective randomized trial comparing sequential ganciclovir-high dose acyclovir to high dose acyclovir for prevention of cytomegalovirus disease in adult liver transplant recipients

Cytomegalovirus disease is an important cause of morbidity following liver transplantation. To date there has not been an effective prophylaxis for CMV disease after liver transplantation. One hundred forty-three patients were randomized to receive either high dose oral acyclovir (800 mg 4 times a day) alone for 3 months after transplantation (acyclovir group) or intravenous ganciclovir (5 mg/kg twice a day) for 14 days followed by high dose oral acyclovir to complete a 3-month regimen (ganciclovir group). Of 139 patients available for evaluation, 43 of 71 (61%) patients from the acyclovir group developed CMV infection compared with 16 of 68 (24%) from the ganciclovir group (relative risk, 3.69; 95% confidence interval, 2.07-6.56; PcO.OOOOl). Of those randomized, CMV disease was seen in 20 (28%) of the acyclovir group compared with 6 (9%) of the ganciclovir group (relative risk, 5.11; 95% confidence interval, 2.05-12.75; P=0.0001). The median time to onset of CMV infection was 45 days in the acyclovir group compared with 78 days in the ganciclovir group (P=0.004). The median time to onset of CMV disease was 40 days in the acyclovir group compared with 78 days in the ganciclovir patients (P=0.02). With respect to primary CMV infection, there was no difference in the rates in the 2 groups, but tissue invasive disease and recurrent CMV disease were less frequent in the ganciclovir group. It is concluded that a course of 2 weeks of ganciclovir immediately after transplantation followed by high dose oral acyclovir for 10 weeks is superior to a 12-week course of high dose oral acyclovir alone for prevention of both CMV infection and CMV disease after liver transplantation. However, the lack of significant effect in seronegative recipients who received grafts from seropositive donors suggests that other strategies are needed to prevent CMV infection in this high risk population. © 1994 by Williams & Wilkins

Non-Newtonian Mixed Thermo-Elastohydrodynamics of Hypoid Gear Pairs

Transmission efficiency is the main objective in the development of vehicular differential systems, comprising hypoid gear pairs. The overall aim is to contribute to improved vehicle fuel efficiency and thus levels of harmful emissions for modern desired eco-drive axles. Detailed predictive analysis plays an important role in this quest, particularly under realistic operating conditions, comprising high contact loads and shear rates. Under these conditions, the hypoid gear pairs are subject to mixed non-Newtonian thermo-elastohydrodynamic conditions, which is the approach undertaken in this paper. Such an approach for hypoid gear pair has not hitherto been reported in the literature

Liver transplantation for tyrosinemia. A review of 10 cases from the University of Pittsburgh.

Results of liver transplantation in 10 patients with tyrosinemia are reviewed. The indications for transplantation were: hepatoma in three, acute liver failure in two, and progressive chronic liver disease in five. One patient died during surgery. Of the remaining nine who survived the operation, one died at six months as a result of bronchial aspiration and aspiration pneumonia, and a second transplanted for hepatoma died five months later with metastases. Seven patients are alive 6 months to 6 1/2 years following transplantation. Of these seven patients, six have normal liver function and a good performance status. One is awaiting retransplantation for chronic rejection. Hepatocellular carcinoma (HCC) was found either preoperatively or incidentally in five patients, all older than 2 years at the time of their transplant. Four of these are alive and well without evidence of tumor with follow-ups between 3 1/2 and 6 1/2. Four of the five patients less than 2 years of age had hepatocellular dysplasia without evidence of carcinoma on histologic examination of the resected liver. This experience suggests that liver transplantation should be considered seriously for children with hereditary tyrosinemia who are more than 2 years of age because beyond that age the incidence of hepatocellular carcinoma (HCC) increases substantially