Laparoscopic management of benign solid and cystic lesions of the liver

OBJECTIVE: The authors present their experience in the laparoscopic management of benign liver disease. The aim of the study is to analyze technical feasibility and evaluate immediate and long-term outcome. SUMMARY BACKGROUND DATA: Indications for the laparoscopic management of varied abdominal conditions have evolved. Although the minimally invasive treatment of liver cysts has been reported, the laparoscopic approach to other liver lesions remains undefined. METHODS: Between September 1990 and October 1997, 43 patients underwent laparoscopic liver surgery. There were two groups of benign lesions: cysts (n = 31) and solid tumors (n = 12). Indications were solitary giant liver cysts (n = 16), polycystic liver disease (n = 9), hydatid cyst (n = 6), focal nodular hyperplasia (n = 3), and adenoma (n = 9). Only solid tumors, hydatid cysts, and patients with polycystic disease and large dominant cysts located in anterior liver segments were included. All giant solitary liver cysts were considered for laparoscopy. Patients with cholangitis, cirrhosis, and significant cardiac disease were excluded. Data were collected prospectively. RESULTS: The procedures were completed laparoscopically in 40 patients. Median size was 4 cm for solid nodules and 14 cm for solitary liver cysts. Conversion occurred in three patients (7%), for bleeding (n = 2) and impingement of a solid tumor on the inferior vena cava (n = 1). The median operative time was 179 minutes. All solitary liver cysts were fenestrated in less than 1 hour. There were no deaths. Complications occurred in 6 cases (14.1%). Two hemorrhagic and two infectious complications were noted after management of hydatid cysts. There were no complications after resection of solid tumors. Three patients received transfusions (7%). The median length of stay was 4.7 days. Median follow-up was 30 months. There was no recurrence of solitary liver or hydatid cysts. One patient with polycystic disease had symptomatic recurrent cysts at 6 months requiring laparotomy. CONCLUSION: Laparoscopic liver surgery can be accomplished safely in selected patients with small benign solid tumors located in the anterior liver segments and giant solitary cysts. The laparoscopic management of polycystic liver disease should be reserved for patients with a limited number of large, anteriorly located cysts. Hydatid disease is best treated through an open approach.     

Selective toxicity of the tricyclic thiophene NSC 652287 in renal carcinoma cell lines: differential accumulation and metabolism

The tricyclic compound 2,5-bis(5-hydroxymethyl-2-thienyl)furan (NSC 652287) has shown a highly selective pattern of differential cytotoxic activity in the tumor cell lines comprising the National Cancer Institute (NCI) Anticancer Drug Screen. The mechanism underlying the selective cytotoxicity is unknown. We hypothesized that differential sensitivity to the compound observed in several renal tumor cell lines could be the result of selective accumulation or differential metabolism of this agent. We demonstrated here that the capacity of certain renal cell lines to accumulate and retain the compound, determined by accumulation of [14C]NSC 652287-derived radioactivity and by flow cytometric determination of unlabeled compound, paralleled the sensitivity of the renal cell lines to growth inhibition by NSC 652287: A-498 > TK-10 > ACHN approximately/= to UO-31. The ability of the cell lines to metabolize [14C]NSC 652287 to a reactive species capable of binding covalently to cellular macromolecules also directly correlated with sensitivity to the compound. Different patterns of metabolites were generated by relatively more drug-sensitive cell lines in comparison with drug-resistant cell lines. The metabolizing capacity for NSC 652287 was localized primarily to the cytosolic (S100) fraction. The rate of metabolism in the cytosolic fraction from the most sensitive renal cell line, A-498, was faster than that observed in the cytosolic fractions from the other, less sensitive cell lines. The data support the hypothesis that both selective cellular accumulation and the capacity to metabolize NSC 652287 to a reactive species by certain renal carcinoma cell types are the basis for the differential cytotoxicity of this compound class.     

Validation of a quality of life questionnaire for critically ill patients

Objective Development and validation of quality of life questionnaire for critical care patients.Design Prospective study.Setting Intensive care unit (ICU) of a general hospital and ICUs of 83 Spanish hospitals.Sample Patients admitted to the ICU>18 years of age; close family members.Method A committee of experts designed a questionnaire with characteristics judged essential for intensive care use: easy, quick administration (5–10 min); capable of completion by patient or close family member, by direct or telephone interview. Fifteen items relevant to critical care patients were grouped in three subscales: basic physiological activities, normal daily activities, and emotional state. Reproducibility of interobserver, intraobserver, patient/family member and telephone/direct interviews was analysed and also internal consistency, responsiveness, and main components.Results Internal consistency (578 patients): Cronbach's alpha coefficient=0.85. Reproducibility: intraobserver reproducibility (n=150): Spearman correlation coefficient=0.92. Interobserver (n=85); correlation=0.92. Patient/family member (n=81): correlation=0.92. Telephone/direct interview (n=54): correlation=0.96. Validity: factorial analysis confirmed that the three subscales were fundamental questionnaire components. There was good concordance between questionnaire/subscale and Glasgow Outcome Scale (GOS) results. Responsiveness: quality of life score changes between preadmission and 6 months' postdischarge correlated with GOS findings (weighted kappa index=0.56).Conclusions Questionnaire meets objectives recommended for critical care use, and fulfills essential requirements of validity and reproducibility when applied to critically ill patients.This study forms part of the PAEEC (Project for the Epidemiological Analysis of Critical Care Patients), and was supported by a grant from the Fondo de Investigaciones Sanitarias (F.I.S.-91/0703), and by the Granada University Research Group (Number 3244)     

Situational management

In this paper, the organizational theory of situational planning is used to establish a decentralized management model for complex health units. Because of cultural limitations imposed on a perspective of change and rationalization, considerations are made in relation to a given form of dealing with culture, keeping in mind the feasibility of the management model. A particular type of communicative management emerges as a general need revealed by the analysis of the object at issue: the management of professional organizations.     

Radiosensitive populations and recovery in X-ray-induced apoptosis in the developing cerebellum

Sprague-Dawley rats received a single dose of 2 Gy X-rays at the age of 1 or 3 days and were killed at different intervals. Dying cells with the morphological characteristics of apoptosis appeared in the external and internal granular layers (EGL and IGL) and white matter (WM) of the cerebellum, mainly 3–6 h after irradiation, and decreased thereafter to reach normal values between 48 h and 5 days later. This process was curbed by the injection of cycloheximide at a dose of 1 g/g body weight. In addition, the number of mitoses in EGL rapidly decreased after irradiation and did not reach normal values until a few days later. Proliferating cell nuclear antigen (PCNA)-immunoreactive cells, which were chiefly found in EGL but also in IGL and WM, dramatically decreased in number from 3 to 48 h after irradiation. PCNA-immunoreactive cells reappeared and reached age-matched values in the following days. Hu (considered as an early neuronal marker) and vimentin immunocytochemistry disclosed that Hu-nonreactive cells in the upper level of EGL, Hu-immunoreactive cells in the inner level of EGL, Bergmann glia and many astrocytes in WM, as well as many non-typified cells in WM, were radiosensitive populations, whereas Purkinje cells were not. The present results indicate that irradiation at P1 or P3 blocks mitosis in EGL and kills sensitive cells mainly in the late G1 and S phases of the cell cycle, probably by apoptosis through a protein synthesis-mediated process. Radiosensitive cells are germinal cells and neuroblasts in EGL, Bergmann glia, astrocytes in WM, and non-typified cells, probably glial cell precursors, in WM. Surviving cells in EGL and PCNA-immunoreactive cells in other cortical layers and white matter reconstitute the cerebellum following a single dose of X-rays.This work was supported in part by CEC project FI3P-CT92-0015 and FIS grant 93-131. M. Olivé is the recipient of a grant from the Pi i Sunyer Foundation. R. Rivera has a grant from the CIRIT     

Safety effectiveness of closed-transfer,mixing-loading,and application equipment in preventing exposure to pesticides

Blood cholinesterase (CHE) activities and urinary dialkyl phosphate levels of five mixer-loaders and four mixer-loader applicators, using a closed-transfer system in conjunction with mixing-loading and application equipment, were monitored over a period of 18 weeks. Airborne pesticide residues in the breathing zone during mixing-loading and the transfer of concentrated liquid pesticide from their original container to mix and spray tanks were determined along with airborne residues during ground application. Blood ChE activities of the majority of the workers increased slightly during the study with increased use of toxic organophosphates and carbamates. Urinary dialkyl phosphate levels varied between 0.02 and 2.4 ppm. During the study, the blood ChE activities of two mixer-loaders decreased and dialkyl phosphate levels of 2.4 ppm were found in the urine of one worker. An investigation indicated that the workers had failed to use the provided closed-transfer system. Airborne residues from liquid pesticides during closed transfer and mixing-loading averaged 5.8g/m³, while residues from dusty powders averaged 152g/m³. Airborne residues during ground application averaged 3.7/m³ during the workday. Mevinphos residues on cloth patches averaged 0.2g/cm².     

Temporal relationship between the decrease in arterial pressure and sodium retention in conscious spontaneously hypertensive rats with carbon tetrachloride-induced cirrhosis

It has been proposed that the initial event of sodium retention in cirrhosis is a peripheral arteriolar vasodilation causing underfilling of the arterial vascular compartment and stimulation of the renin-aldosterone and sympathetic nervous systems. To test this hypothesis, systolic blood pressure, sodium balance and urinary excretion of sodium and aldosterone were sequentially measured in 13 conscious spontaneously hypertensive rats submitted to a cirrhosis induction program with carbon tetrachloride and phenobarbital and in 14 control hypertensive animals. No significant differences were found between control and cirrhotic rats in any of the measured parameters during the first 7 wk of the study. The eighth week sodium retention developed in cirrhotic rats as indicated by a positive sodium balance and a marked decrease of sodium excretion. At the same time a significant reduction in systolic blood pressure and a great increase in urinary excretion of aldosterone were detected. These changes were more marked the ninth week of the study. In cirrhotic rats there was a highly significant direct correlation between systolic blood pressure and urinary sodium excretion. Postmortem examination showed a histological picture of cirrhosis in all animals given carbon tetrachloride and ascites in six of them. These results indicate that the onset of hyperaldosteronism and sodium retention in conscious spontaneously hypertensive rats with carbon tetrachloride-induced cirrhosis is chronologically related to a significant decrease in arterial pressure, thus supporting the "peripheral arterial vasodilation hypothesis" of ascites.     

Pilot study evaluating the pharmacokinetics, pharmacodynamics, and safety of the combination of exemestane and tamoxifen.

PURPOSE: We conducted a pilot study assessing the effects of the selective estrogen receptor modulator, tamoxifen, on the pharmacokinetics, pharmacodynamics, and safety of the steroidal, irreversible aromatase inhibitor (AI), exemestane, when the two were coadministered in postmenopausal women with metastatic breast cancer. EXPERIMENTAL DESIGN: Patients with documented or unknown hormone receptor sensitivity were eligible. Patients received oral exemestane at 25-mg once daily. Starting day 15, oral tamoxifen at 20-mg once daily, was added. We measured plasma concentrations of exemestane, estrone, estrone sulfate, and estradiol after 14 days of exemestane monotherapy and after approximately 4 weeks of combination therapy. The incidence and severity of adverse events were assessed by physical examination and patient reporting. RESULTS: We treated 18 patients. All had received prior chemotherapy and/or hormonal therapy, eight and six, respectively, with single-agent selective estrogen receptor modulators or irreversible aromatase inhibitors; no hormonal therapy was given within 30 days of study entry. Plasma exemestane concentrations and estrone, estrone sulfate, and estradiol suppression were unchanged after approximately 4 weeks of tamoxifen coadministration. All drug-related adverse events were grades 1 or 2; none was unexpected. Although not a formal study end point, antitumor activity was noted, with two partial responses and four cases of stable disease among 17 evaluable patients after a 9-month median follow-up (range, 2.5-19 months). CONCLUSIONS: This pilot study provides evidence that coadministration of tamoxifen does not affect exemestane pharmacokinetics or pharmacodynamics and that the combination is well-tolerated and active. Further clinical investigation is warranted.     

Cytoprotective influence of ZVAD-fmk and glycine on gel-entrapped rat hepatocytes in a bioartificial liver

BACKGROUND: This study was designed to determine if an anti-necrotic compound, glycine, and/or an anti-apoptotic agent, ZVAD-fmk, improved the viability and function of hepatocytes in a bioartificial liver. METHODS: Isolated rat hepatocytes were entrapped in collagen gel (1.0-10.0 x 10(6) cells/mL) and cultured in serum-free medium (1:10 ratio of gel:media) supplemented with glycine alone, ZVAD-fmk alone, or glycine and ZVAD-fmk. The cytoprotective effects of glycine and ZVAD-fmk on gel-entrapped rat hepatocytes (GERH) were determined after anoxic exposure (0-20 hours). Cell functionality (measured by urea production), cell viability (quantitated by vital staining with fluorescein diacetate:ethidium bromide [FDA:EB]), and the mechanism of cell death (verified by electron microscopy and DNA fragmentation studies) were determined for each condition. RESULTS: The viability of GERH declined gradually and then stabilized 12 hours after hepatocyte isolation. The rate of urea production by GERH was directly proportional to the number of viable hepatocytes. Apoptotic death predominated at low cell density, and necrotic cell death became significant at high cell density. Hepatocyte necrosis became more significant after exposure to longer periods of anoxia (4, 8, 12, and 20 hours). ZVAD-fmk provided dose-dependent cytoprotection to GERH with an optimum benefit at a concentration of 60 mumol/L. After anoxic exposure or under high cell density culture, glycine demonstrated a maximum benefit of inhibiting necrosis at a concentration of 3 mmol/L. The beneficial effects of glycine and ZVAD-fmk were additive. CONCLUSIONS: The metabolic activity of a hepatocyte bioartificial liver may benefit from the use of cytoprotective agents such as ZVAD-fmk and glycine.