Chemotherapy of primary and secondary liver tumors

Liver is the most common site of metastatic disease. Although primary liver tumors are relatively rare in the Czech Republic, liver tumors represent a frequently encountered problem because of high incidence of colorectal and pancreatic cancer. Regimens of systemic chemotherapy or biologic therapy are used for secondary liver tumors according the primary site. It was demonstrated in randomized clinical studies that some of these regimens significantly prolong survival. Although only palliative therapy is possible for most of the patients with liver metastases, resection should be considered in patients with isolated liver involvement. Liver resection represents a curative approach and long-term success seems to be enhanced by neoadjuvant (preoperative) chemotherapy or adjuvant (postoperative) hepatic arterial chemotherapy. Hepatic arterial chemotherapy is also effective in the palliative treatment of unresectable liver metastases. Although it is still uncertain whether hepatic arterial chemotherapy increases survival of patients compared to systemic chemotherapy, it may be regarded as the best available treatment in selected patients because of better palliation associated with higher objective response rate and less systemic toxicity. Along with systemic and hepatic arterial chemotherapy, other approaches are being currently investigated in the treatment of primary and secondary liver tumors, including the use of biologic agents, agents with non-cytotoxic mechanism of action, or chronomodulated chemotherapy.     

The distribution of metastases of different primary tumors in the liver

The distribution of the number and volume of liver metastases in both lobes of the liver was investigated. The density of the metastases and their volume were analyzed. The study of 71 human metastatic livers revealed an almost homogeneous pattern of metastatic distribution. There was no difference whether the spread of the tumor cells had occurred via the portal vein or the hepatic artery. Both sides of the liver were affected similarly.     

Differential tension between secondary and primary mitral chordae in an acute in-vivo porcine model

BACKGROUND AND AIM OF THE STUDY: Chordae tendineae may be instrumental for valvular-ventricular interaction, i.e. the reciprocal exchange of force between the left ventricular myocardium and the mitral apparatus. Chordae tendineae are divided into primary leading edge chordae and secondary belly chordae, and differences in thickness and distribution may reflect different functions of the two types. Primary chordae may be fundamental for leading edge control and for correct leaflet coaptation, while secondary chordae may act as the main mediators of valvular-ventricular interaction. It was postulated that tension in secondary chordae of the anterior leaflet is greater than in the primary chordae. The study aim was to investigate the distribution of chordae tendineae tension in the porcine mitral valve in vivo. METHODS: During extracorporeal bypass, miniature chordal force transducers were implanted on four chordae in 23 Danish Landrace pigs. Chordae tendineae tension was recorded online in the open-chest condition with spontaneous circulation in three different hemodynamic conditions: baseline with no intervention; partial aortic occlusion; and during dobutamine infusion. RESULTS: Systolic tension in secondary chordae under baseline conditions was significantly higher than in primary chordae (0.7 N versus 0.2 N, respectively). No significant impact on this distribution by changing the hemodynamic condition could be identified. CONCLUSION: Chordal tension is distributed towards the secondary chordae, with a tension more than three-fold that in the primary counterpart. The magnitude of chordal tension seems to be determined primarily by ventricular pressure. This finding supports the hypothesis that secondary chordae are more important mediators of the valvular-ventricular interaction than are primary chordae.     

Differential effect of interleukin-2 treatment on primary and secondary immunizations in HIV infected individuals

OBJECTIVES: As interleukin (IL)-2 therapy increases CD4 cell counts in HIV infected subjects, it emerged as a candidate for the partial restoration of immune competence in this disease. METHODS: We studied the frequencies of antigen-specific T cells using single cell resolution cytokine ELISPOT assays and titers of specific antibodies before and after immunization of HIV infected subjects who were treated with HAART or HAART plus IL-2. RESULTS: Subjects seronegative to hepatitis A were vaccinated with hepatitis A antigen. In the non-IL-2 treated group, hepatitis A-specific T cells producing IL-2 and IL-4 along with specific antibodies were induced, showing that these subjects are immune competent and capable of mounting a primary immune response. Additional IL-2 treatment had no significant effect on this primary T cell response; however, booster immunizations with tetanus toxoid or the gp120 depleted HIV vaccine Remune induced higher frequencies of specific interferon (IFN)-gamma producing T cells in IL-2 treated subjects. No impact of IL-2 treatment on these secondary B cell responses was seen. CONCLUSION: Overall, our study showed that IL-2 therapy had no immune enhancing effect on the induction of a primary response, but increased the frequency of IFN-gamma producing memory cells after booster immunization.     

Impact of positron emission tomography on strategy in liver resection for primary and secondary liver tumors

Purpose Outcome of patients with metastatic disease mainly depends on accurate preoperative tumor staging. ¹⁸[F]fluorodeoxyglucose positron emission tomography (18F-PET) has been proven to be a valuable diagnostic tool in a number of different tumors but its direct influence on liver surgery has not been thoroughly investigated.Materials and methods Between July 1999 and March 2000, 50 consecutive patients with 174 suspected liver lesions were admitted to the University Hospital Jena. All 50 patients underwent abdominal ultrasound, CT-scan, and 18-FDG positron emission tomography scanning. In 23 patients the diagnostic work-up was completed by MRI scan.Results Altogether there were a total of 174 histologically proven intrahepatic lesions, nine of which were benign. The sensitivity, specificity, and positive predictive value of PET for all hepatic lesions was 82%, 25%, and 96% compared with 63%, 50%, and 96% for abdominal ultrasound, 71%, 50%, and 97% for CT-scan, and 83%, 57%, and 97% for MRI-scan. In 23 of 50 patients 24 extrahepatic lesions were identified. In these patients the sensitivity and specificity of PET—compared to abdominal ultrasound, CT-scan, and MRI-scan for all extrahepatic lesions—was 63% and 60%, 29% and 25%, 47% and 50% and 40% and 50%, respectively. The findings on PET scan had a direct impact on operative management in nine patients (18%).Conclusions Our series demonstrates good sensitivity and specificity for the detection of primary and secondary liver lesions which is superior to ultrasound and CT scan but not to MRI scan. The main value of PET scan consists in the detection of extrahepatic tumor (64%). Due to better detection of extrahepatic tumor, FDG-PET is a very useful addition to the currently used anatomically-based images in all cases of advanced tumor spread with high risk of extrahepatic tumor.     

Mortality in primary and secondary myocarditis

Background

Lymphocytic myocarditis presents as a primary disorder or in association with a systemic disease. Whether primary and secondary myocarditis have the same prognosis is unknown.

Methods

Patients (n = 171) referred to the Johns Hopkins Cardiomyopathy service from 1984 to 1998 with newly diagnosed cardiomyopathy were observed for an average of 5.9 years after an original diagnosis of biopsy-proven myocarditis or until reaching the end point of death. Giant-cell myocarditis was excluded from this study. Myocarditis was classified as secondary when a systemic disease was present at the time of presentation; otherwise, myocarditis was classified as primary. Survival rates among patients with primary and secondary myocarditis were compared with Kaplan-Meier analysis and Cox proportional hazard models incorporating clinical variables, including baseline hemodynamics and treatment with immunosuppressive therapy.

Results

The mortality rate associated with secondary myocarditis varied substantially depending on the underlying systemic disorder. Peripartum myocarditis, when compared with idiopathic myocarditis, had a reduced mortality rate (relative hazard, 0.23 [0.06-0.98]; P <.05), which was attenuated after controlling for confounding variables (relative hazard, 0.62 [0.13-2.98]; P = .55). In contrast, human immunodeficiency virus myocarditis had a particularly poor prognosis (relative hazard, 6.70 [3.51-12.79]; P <.05), even after controlling for confounding variables. Myocarditis associated with systemic inflammatory disorders showed a trend toward increased mortality rate (relative hazard, 2.46 [0.65-9.38]; P = .19). For both primary and secondary myocarditis, advanced age and pulmonary hypertension were important clinical predictors of death.

Conclusions

The prognosis of patients with secondary myocarditis, when compared with patients with idiopathic myocarditis, seems most affected by the primary disease process.     

Pharmacology of antitumor agents from higher plants.

Some pharmacologic properties of nine antitumor agents from higher plants are described. The agents are vincristine, vinblastine the epiodophyllotoxin derivatives VM-26 and VP-16-213, maytansine, bruceantin, thalicarpine, camptothecin, and lapachol. When sufficient information is available, the agents are discussed with regard to their antitumor activity, mechanism of action, pharmacologic disposition, structure-activity relationships, and toxicity.     

Influence of the vascular damaging agents DMXAA and ZD6126 on hypericin distribution and accumulation in RIF-1 tumors

Purpose  

We investigated the influence of two types of vascular damaging agents (VDAs) (DMXAA vs. ZD6126) and sequence of administration (VDA 24 h before HYP vs. HYP 1 h before VDA) to evaluate the effect on hypericin (HYP) accumulation and distribution in necrotic tumors.     

Risk of secondary malignancies in testicular tumors

The work is aimed at the occurrence of secondary malignancies after therapy for primary testicular tumors. The target of the work was determination of the number and type of secondary tumors, their effect on the survival and comparison of relative risk of the origination of secondary tumors depending on particular treatment modalities. Total of 313 patients with testicular tumors were assessed, who experienced orchiectomy in 1968 to 1998 with subsequent irradiation, chemotherapy or combination of the two modalities. Total of 22 secondary tumors, i.e. 7%, were found in the group. The relative risk of the secondary malignancy development was of 1.04. The median time till the secondary tumor occurrence was of 143 months. Total of 213 patients were subjected to radiotherapy, which was associated with enhanced risk of the secondary tumor development (RR = 8.38); the risk in 100 patients treated by chemotherapy was lower (RR = 0.38). The relative risk of the origination of the secondary malignancy located in the region of preceding irradiation is low (RR = 0.52). In the case of the occurrence of secondary malignancies, the median symptomless survival and the total survival decreased from 271 months to 187.3 and 199.8 months, respectively. Most patients with testicular tumors have favourable long-term prognosis and thus, it is desirable to know the risk of secondary malignancies and to include it into plan of long-term subsequent follow-up.