Predictive model of failure of outpatient laparoscopic cholecystectomy.

INTRODUCTION: The aim of our study was to review our experience and to determine a predictive model of factors for unanticipated admissions after ambulatory laparoscopic cholecystectomy (LC). MATERIALS AND METHODS: Between January 1999 and June 2003, 410 consecutive LCs were performed as outpatient procedures. We performed univariate analysis and logistic regression models of preoperative and intraoperative variables. The scoring system developed allowed calculating the ambulatorization probability of LC in each patient. Validation and calibration of the model were realized by means of Hosmer-Lemeshow test. RESULTS: Three hundred sixty-three patients were strictly ambulatory (86.8%). Forty-two patients required overnight admission (10.2%), most of them because of social factors, and 5 patients were admitted. Predictive factors related to overnight stay or admission were: age of patient over 65 years [P=0.021; odds ratio (OR)=2.225; 95% confidence interval (CI), 1.130-4.381], operation duration superior to 60 minutes (P=0.046; OR=2.403; 95% CI, 1.106-5.685), and "dissection difficulty" intraoperative score superior to 6 (P=0.034; OR=3.063; 95% CI, 1.086-8.649). The right classification index of the predictive system was 91.7%, reaching a sensibility of 99.7% and specificity of 31.9%. CONCLUSIONS: Outpatient LC is safe and feasible. Age of the patient, operation duration, and complexity of surgical dissection during LC are independent factors influencing ambulatorization rate.

Effect of intracerebroventricular continuous infusion of valproic acid versus single i.p. and i.c.v. injections in the amygdala kindling epilepsy model.

Two protocols were tested to assess anticonvulsant efficacy and drug concentrations after intracerebroventricular (i.c.v.) continuous valproic acid (VPA) infusion, as compared with acute injections in the kindling epilepsy model. Protocol 1: amygdala-kindled rats were injected via intraperitoneal (i.p.) and i.c.v. routes with varying doses of VPA and tested for seizure intensity, afterdischarge and seizure duration, ataxia and sedation. Concentrations of VPA were determined by immunofluorescence in the brain, plasma, cerebrospinal fluid (CSF) and liver in matching rats. Protocol 2: amygdala-kindled rats were implanted with osmotic minipumps containing a VPA solution in saline and connected to intraventricular catheters for 7 days. Seizure threshold, latency and duration, afterdischarge duration, ataxia and sedation were recorded daily before, during, and until 5 days after VPA infusion. In matching animals, CSF, brain, plasma and liver VPA concentration was determined. Acute i.c.v. VPA injection suppressed seizures with a remarkable ataxia and sedation. However, continuous i.c.v. infusion controlled generalised and even focal seizures without producing important side effects, high plasma levels or hepatic drug concentrations. In conclusion, continuous i.c.v. VPA infusion may protect against kindled seizures by minimising ataxia and sedation, and achieving suitable intracerebral, yet low plasma or hepatic drug concentrations, thus avoiding potential systemic toxicity.

Influence of preservation solution on the isolation and culture of human hepatocytes from liver grafts.

A major problem for the isolation and transplantation of hepatocytes is the lack of resources for obtaining viable hepatocytes. Improving this situation would enhance hepatic cell transplantation programs. Our objective was to evaluate the influence of the preservation solutions used during organ retrieval on the quality of hepatocytes isolated from liver tissue. We compared the results of the collagenase perfusion technique for isolation of hepatocytes in human livers flushed with University of Wisconsin (UW) and Celsior preservation solutions. Yield (number of viable cells per gram of tissue), cellular viability, efficiency of cells to attach to culture plates and form a monolayer, and drug metabolizing competence of the hepatocytes were measured. Successful isolation was achieved in 63% of the procedures using the UW solution and 100% of the procedures using the Celsior solution. In the UW group, significantly lower cell viability (38 +/- 41% vs. 79 +/- 14%, p < 0.05), yield of cells (4.0 +/- 5.2 x 10(6) vs. 8.2 +/- 5.6 x 10(6) cells/g, p < 0.05), and protein content at 24 h of culture (0.6 +/- 0.6 vs. 1.2 +/- 0.3 mg protein per plate, p < 0.05) than in Celsior solution were found. However, similar values of P450 activities were found in both groups. The more successful isolation, better yield, and higher cell viability obtained from human liver grafts preserved in Celsior solution, in comparison to UW solution, suggest Celsior solution as the most appropriate for preserving cadaveric hepatic tissue to be used for hepatocyte harvesting.

Combined liver transplantation plus imatinib for unresectable metastases of gastrointestinal stromal tumours.

Therapeutic options for treating unresectable hepatic metastases of leiomyosarcomas were scarce until a few years ago. Recent advances in the study of the biology of intestinal tumours have radically changed our knowledge of their pathogenesis. Many of the tumours previously considered as leiomyosarcomas are now identified as gastrointestinal stromal tumours (GISTs). The introduction of imatinib (an antineoplasic drug that specifically acts on the pathogenesis of these tumours) has shown promising results in patients with advanced GISTs. We present three patients with the initial diagnosis of unresectable hepatic metastases of leiomyosarcomas. They received liver transplants. All three had tumour recurrences after transplantation. Histological re-evaluation identified a stromal origin of the tumours, and the patients were treated with imatinib therapy (400 mg/day). Recurrence occurred in all patients after a mean of 38.3 months, but imatinib treatment achieved control of the tumours. The current survival times with the combination of transplantation and imatinib are 92, 48 and 46 months for the three patients. This series is small and inconclusive, but imatinib treatment showed promising results. The treatment options for patients with unresectable metastases of GISTs must be defined, as in these three patients liver transplantation achieved a disease-free status but all had tumour recurrences before starting the imatinib treatment.

Inguinodynia after two inguinal herniorrhaphy methods.

The aim of this study was to compare the rate and characteristics of postoperative neuralgia after 2 methods of inguinal hernia repairs. Between July 1997 and December 2000, 400 inguinal hernia repairs were performed and followed up in a prospective trial about postoperative nerve irritations: 200 patients with laparoscopic transabdominal hernioplasty (TAPP group), and 200 patients with tension-free hernia repair using Lichtenstein's technique (LICH group). We applied a clinic protocol of data about pain location, neuralgia characteristics, and period of time until the patient was completely pain free. The global rate of nerve irritation in the study was 7.6% (30 cases); in the TAPP group, it was 5.5% (n = 11) and in the LICH group, it was 9.5% (n = 19) (P = .03). The genitofemoral nerve was affected with particularly high frequency (4.3% in the global series); although in laparoscopic repair, the lateral cutaneous nerve of the thigh (LFC) was most damaged (3.3% in TAPP group). We observed more persistent symptoms in LICH group, while in TAPP group the most of cases was transitory (P = .08). There were no significant differences in pain characteristics according to clinical type of hernia. The TAPP method causes less rate of postoperative inguinal neuralgia than Lichtenstein repair, emphasizing more persistent discomfort in anterior approach than laparoscopic repair.

Prospective evaluation of emergency versus delayed laparoscopic cholecystectomy for early cholecystitis.

Treatment of acute cholecystitis is still under debate. The aim of this study was to evaluate the efficacy of early laparoscopic cholecystectomy (ELC) in comparison with conservative treatment followed by delayed laparoscopic cholecystectomy (DLC) in the management of acute cholecystitis. This prospective comparative study involved two groups of patients presenting with acute cholecystitis within 72 hours of the onset of symptoms. ELC was performed in 82 consecutive patients, whereas DLC was performed in 87 patients who previously underwent medical treatment. Surgical variables, hospital stay, and postoperative morbidity were evaluated in both groups. Time of surgery and conversion rate were lower in the ELC group. Postoperative morbidity was similar in both groups. Overall hospital stay was shorter in the ELC group. ELC within 72 hours of the onset of acute cholecystitis is a safe procedure with better results than DLC in terms of surgical timing, conversion rate, and hospital stay.

Potential impact of steatosis on cytochrome P450 enzymes of human hepatocytes isolated from fatty liver grafts.

Liver grafts discarded for transplantation because of macrosteatosis can constitute a valuable source of human hepatocytes for in vitro metabolic and pharmacotoxicological studies or for therapeutic applications. A condition for using hepatocyte suspensions for these purposes is the preservation of their metabolic competence and, particularly, drug-metabolizing enzymes. A reduction in microsomal cytochrome P450 (P450) activities was observed in fatty livers (>40% steatosis) with respect to normal tissue. Similarly, decreased levels of 7-ethoxycoumarin O-deethylation and testosterone metabolism were observed in human hepatocyte cultures prepared from steatotic liver tissue. To clarify the potential impact of lipid accumulation on human hepatic P450 enzymes, we have used an in vitro model of "cellular steatosis" by incubation of cultured hepatocytes with increasing concentrations (0.25-3 mM) of long-chain free fatty acids (FFA). A dose-dependent accumulation of lipids in the cytosol is induced by FFA mixture. Hepatocytes exposed to 1 mM FFA for 14 h showed lower activity values of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4 enzymes than nontreated hepatocytes (about 45-65% reduction). This treatment also produced significant decreases in CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4 mRNA to about 55 to 75% of mRNA levels in control cells. Our results suggest that although human hepatocytes isolated from steatotic liver show reduced P450 activities, they are metabolically competent and can be used for drug metabolism studies.

Liver grafts preserved in Celsior solution as source of hepatocytes for drug metabolism studies: comparison with surgical liver biopsies.

Suitability of human liver grafts preserved in Celsior solution (CS) for preparing metabolically competent hepatocyte cultures has been examined. To this end, basal and induced activity and mRNA levels of major hepatic cytochrome P450 (P450) enzymes have been measured. By 24 h in culture, measurable levels of the 10 P450 mRNAs studied were found in all hepatocyte preparations examined, with CYP2E1, CYP2C9, and CYP3A4 mRNAs being the most abundant. Compared with hepatocytes obtained from surgical liver resections (SLRs), lower content of each P450 mRNA was found in hepatocytes from the CS group; however, the relative distribution of individual P450 mRNAs was similar. Similar results were observed after measuring P450 activities. CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2E1, and CYP3A4 activities in hepatocytes from CS-flushed grafts were lower than but comparable with those of cultures prepared from SLRs. No differences in the metabolite profile of testosterone were found. Treatment of hepatocytes from CS-preserved grafts with model P450 inducers shows that 2 microM methylcholanthrene only increased CYP1A1 and CYP1A2 mRNAs (>100-fold over control), 1 mM phenobarbital markedly increased CYP2A6, CYP2B6, and CYP3A4 mRNA content (>7-fold), and 50 microM rifampicin highly increased CYP3A4 mRNA levels (>10-fold), whereas minor effects (<3-fold) were observed in CYP2A6, CYP2B6, and CYP2C9 mRNAs. This induction pattern of P450s was similar, in terms of magnitude, reproducibility, and specificity, to that shown in primary hepatocytes from surgical biopsies. Overall, our results indicate that, cold-preserved in CS, liver grafts constitute a valuable source of human hepatocytes for drug metabolism studies.

If the donor had an early-stage genitourinary carcinoma and the liver has already been implanted, should we perform the transplantectomy?

Information regarding the outcome of liver grafts from cadaveric donors with genitourinary cancer is scarce. In some cases, the liver has already been implanted when the tumor is detected. What must we do then? Our goal is to evaluate the outcome of recipients of liver allografts from donors with unsuspected early-stage genitourinary carcinoma. We performed 684 liver procurements from cadaveric donors and 582 liver transplants. A malignant genitourinary tumor was detected in the donor after implantation of the donor liver in six cases (1.03%): four renal carcinomas and two prostate cancers. All donors were elderly (mean age, 64.6 years) and died of a cerebrovascular accident. Four patients are still alive and presently free of malignancy, whereas the two other transplant recipients died of hepatitis C virus recurrence at 14 and 55 months after transplantation without evidence of tumor transmission. We did not observe evidence of tumor transmission in any patient after an average follow-up of 51 +/- 20 months. Our results suggest it is not always necessary to perform transplantectomy or use special treatment modalities in recipients of a liver allograft from donors with early-stage (T1 to T2) renal cell carcinoma or early (T1) prostate carcinoma.