Nonparasitic cysts of the liver: results and options of surgical treatment

Nonparasitic cysts of the liver (NPHC) are highly variable in respect to appearance and therapeutic approach. The treatment of these cysts varies according to the nature and appearance of the disease. Based on the variable nature of disease and the various therapeutic options, all of which were attempted in our patients, the most suitable mode of treatment for different forms of NPHC are discussed. Ninety-one patients with NPHC who had been treated surgically from 1977 through 1995 were examined retrospectively. Asymptomatic peripheral cysts measuring up to 10 cm do not require further treatment. Computed tomography (CT)-guided aspiration (n = 9) should be regarded as a palliative measure. Within a short period, CT-guided aspiration led to recurrence of symptoms in seven of our patients. Standard treatment of NPHC is fenestration with widest possible excision of the cystic wall, which can be performed laparoscopically (n = 10) or by the conventional surgical mode (n = 54). One patient was initially operated by the laparoscopic technique but developed bleeding, which necessitated conversion to the open mode. Three patients underwent synchronous laparoscopic cholecystectomy. Recurrence rates were similar: 11% in the laparoscopically treated group and 13% in the group that underwent conventional open surgery. Conventional surgical treatment was always successful in cases of solitary cysts. However, in cases of multiple cysts measuring more than 5 cm, conventional surgery was followed by recurrence of symptoms in 26% of patients (7/27), who then had to undergo a second operation. Partial resection of the liver (n = 9) was successfully performed in cases of polycystic disease (n = 5) with concomitant enlargement of the organ as well as in cases of large solitary cysts of the left lobe of the liver (n = 4). In patients in whom we found that the cysts communicated with the ductal system (n = 3), we performed a cystojejunostomy to drain the bile. The complication rate was low. In addition to frequent postoperative ascites, which necessitated no further intervention, we observed infectious complications in four patients. Twenty patients (22%) expired during a mean follow-up period of 6.2 years. Interestingly, deaths were frequently associated with malignancy (11/20). After fenestration of multiple cysts measuring > 5 cm, the patients are at high risk for recurrence. Hence partial resection of the liver is an excellent therapeutic alternative in selected patients with polycystic disease and massive enlargement of the organ in whom the disease could not be controlled by simple fenestration. The results of this study show that laparoscopic fenestration should replace the conventional surgical technique as the gold standard in cases of NPHC because the laparoscopic technique is less stressful for the patient and is associated with a rate of success similar to that of the conventional technique.     

Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia

PURPOSE: Expression of the multidrug resistance gene (MDR1) p170 protein is frequent in leukemic blasts from patients with relapsed acute myelogenous leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was performed. PATIENTS AND METHODS: Starting doses (LVL0) of MITO (3.25 mg/m2/d on days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6. Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1 and 3, and samples for MDR1 expression were taken on day 0. RESULTS: Severe mucositis developed in all patients at LVL0; therefore, MITO and VP doses were reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic toxicities observed. The peripheral blood was cleared of leukemia in three LVL0 and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate was observed in eight of 10. No patient achieved complete remission (CR), and all died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was detected by fluorescent-activated cell sorter (FACS) analysis in five of seven cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from the marrow occurred in four of six MDR1-positive and one of three MDR1-negative patients. Despite the fact that LVL0 doses had to be reduced due to toxicity, coadministration of PSC did not produce a consistent effect on MITO PK; however, it did repeatedly lead to increased levels of VP in the serum. CONCLUSION: We conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity. Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior study without PSC.     

Characterization of the epidermal growth factor receptor in pig oviduct and endometrium

Two different plaque variants of Japanese encephalitis virus were selected from a wild-type Taiwanese isolate using Vero cells. One variant was found to exhibit small plaque morphology with retarded virus replication kinetics in Vero cells, and was demonstrated to be resistant to monoclonal antibody (mAb) E3.3 neutralization. The other variant showed large plaque morphology, was sensitive to mAb E3.3 neutralization, and manifested reduced virulence in mice on both intracranial and intraperitoneal inoculations. These two variants propagated in Vero cells retained high levels of infectivity but had relatively low HA titers as compared with the parent strain. The envelope sequences of these two variants showed four amino acid differences at residues E-85 (Glu/Arg), E-306 (Glu/Gly), E-331 (Ser/Arg), and E-387 (Met/Arg). Our results indicated the neutralizing epitope of Japanese encephalitis virus did not overlap with virus virulence determinant.     

Subcutaneous soft tissue tumours at the site of implanted microchips in mice

An experiment using 4279 CBA/J mice of two generations was carried out to investigate the influence of parental preconceptual exposure to X-ray radiation or to chemical carcinogens. Microchips were implanted subcutaneously in the dorsolateral back for unique identification of each animal. The animals were kept for lifespan under standard laboratory conditions. In 36 mice a circumscribed neoplasm occurred in the area of the implanted microchip. Females were significantly more frequently affected than male mice. An influence of age or different treatment on the s.c. tumour incidence in two mice generations could not be observed. Macroscopically, firm, pale white nodules up to 25 mm in diameter with the microchip in its center were found. Microscopically, soft tissue tumours such as fibrosarcoma and malignant fibrous histiocytoma were detected.     

Antibodies of the anti-Yo and anti-Ri type in the absence of paraneoplastic neurological syndromes: a long-term survey of ovarian cancer patients

PURPOSE: To determine the association between lipids, microalbuminuria and systemic blood pressure. Urinary albumin excretion rate (AER) was determined in timed overnight urine samples by radioimmunoassay. Microalbuminuria was defined when two out of three urine samples had AER ranging 20-200 micrograms/min. Lipids were determined by colorimetric methods (total cholesterol, HDL cholesterol and triglycerides). METHODS: Fifty patients with insulin dependent diabetes mellitus (28 females, 22 males) aged 21.9 +/- 7 years and with diabetes duration of 6.8 +/- 5.8 years attending the outpatients diabetes clinic were studied cross-sectionally. RESULTS: Microalbuminuria was present in 12% of our patients. A high systolic blood pressure (SBP) was found in microalbuminuric patients (p = 0.003). No difference concerning serum lipids were found in comparison between normo and microalbuminuric patients, although 20% of all patients had increased cholesterol and LDL cholesterol and 4% had high HDL cholesterol and triglycerides levels. Stepwise multiple regression analysis showed that SBP was the only significant independent variable to influence AER (r = 0.42 r2 = 0.18 p = 0.002). CONCLUSION: Although in our study, microalbuminuria was associated only with SBP, the independent alteration of lipids in young IDDM patients must be considered as a possible additional risk factor for cardiovascular disease.     

Apoptosis and resistance to daunorubicin in human leukemic cells

We compared test methods based on specific mechanisms of daunorubicin (DNR) resistance to more global procedures. Assessment of P-glycoprotein (P-gp) expression and function by means of immunocytochemistry, DNR accumulation, and modulation of resistance and accumulation by the P-gp inhibitor cyclosporin A (CsA) were selected as parameters for multidrug resistance (MDR). On the other hand, we used the MTT assay and measured apoptosis and proliferative activity (S- and G2M-phases of the cell cycle) by flow cytometry. Validation of test methods was achieved for four leukemic cell lines (HL-60, KG-1a, K562/WT, K562/ADM). This battery of tests was then applied to mononuclear cells (MNC) from 18 leukemic patients. Low proficiency of MNC to undergo apoptosis and low proliferative activity rather than P-gp-mediated MDR correlated with DNR resistance as measured by the MTT assay. Bell-shaped dose-response curves for apoptosis, however, which reflect a switch from the apoptotic to the necrotic death mode with increasing cellular damage tend to limit practicability in clinical testing, because appropriate dose range and time points need to be explored. Thus, measurement of apoptosis by flow cytometry may be less convenient than the MTT assay for determination of chemosensitivity, if clinical samples with unknown patterns of responsiveness are to be tested. Spontaneous apoptosis in untreated MNC following 24 h incubation in vitro correlated significantly with DNR sensitivity in the MTT assay. A lack of essential viability factors (eg growth factors or cytokines) in vitro which are known to prevent apoptosis may contribute to DNR sensitivity.     

Source separation using a criterion based on second-orderstatistics

It is often assumed that blind separation of dynamically mixed sources cannot be done with second-order statistics. It is shown that separation of dynamically mixed sources indeed can be performed using second-order statistics only. A criterion based on second-order statistics for the purpose of separating crosswise mixtures is stated. The criterion is used in order to derive a gradient-based separation algorithm, as well as a Newton-type separation algorithm. The uniqueness of the solution representing the separation is also investigated. This reveals that (1) the channel system is parameter identifiable under weak conditions, and (2) if the sources have the same color, there exists at most two solutions. The local convergence behavior of the proposed algorithm is studied and reveals a sufficient condition for local convergence. Furthermore, the estimates of the channel system are shown to be consistent or to locally minimize the criterion