Relationship between pretransplantation liver status and health-related quality of life after grafting: a single-center prospective study.

BACKGROUND: Severity of liver disease evaluated with Model for End-Stage Liver Disease (MELD)/Child-Pugh-Turcotte (CPT) score is of importance in liver transplantation (LTx) assessment. The Medical Outcomes Study Short Form (SF-36) is a widely used generic questionnaire of health-related quality of life (HRQoL). This study was a prospective analysis of the effect of pretransplantation liver status on HRQoL after the procedure. MATERIALS AND METHODS: One hundred and seven (62 male, 45 female, median age 52 years) consecutive patients were included. MELD/CPT score and diabetes status were evaluated during LTx assessment. Patients were divided into 3 groups depending on the period after LTx: 6 to 12 months (group I), 13 to 36 months (group II), and >37 months (group III). They also were divided into 2 groups depending on the age at LTx: group I (<50 years) and group II (>50 years). SF-36 was used in the assessment of HRQoL. RESULTS: Correlation between pretransplantation MELD/CPT score and HRQoL was only seen in the general health domain of the SF-36 in patients from group I (r = 0.64; P = .004 and r = 0.61; P = .02, respectively). Diabetes exerted a significant effect on the physical component summary (P = .02), again in group I. No significant correlation was observed between MELD/CPT score and the presence of diabetes in groups II and III. Regarding age at LTx, no significant correlation between MELD/CPT score and HRQoL was seen. CONCLUSIONS: Liver status assessed with MELD and CPT scores before transplantation has a minor effect on HRQoL after LTx and exerts no significant effect in patients evaluated >12 months after LTx. Patients with diabetes seem to have worse quality of life early after surgery; however, diabetic and nondiabetic patients had comparable HRQoL scores later on after LTx.

Pure laparoscopic full-left living donor hepatectomy for calculated small-for-size LDLT in adults: proof of concept.

Adult-to-adult living donor liver transplantation (A2ALDLT) is an accepted mode of treatment for end-stage liver disease. Right-lobe grafts have usually been preferred in view of the higher graft volume, which lowers the risk of a small-for-size syndrome. However, donor left hepatectomy is associated with less morbidity than when it is compared to right hepatectomy. Laparoscopic donor hepatectomy (LDH) has been considered almost exclusively in pediatric transplantation. The results of laparoscopic left-liver graft procurement for calculated small-for-size A2ALDLT in four donors are presented. The graft-to-recipient body weight ratio was <0.8 in all recipients. The mean portal vein flow and the pressure and hepatic artery flows were measured at 190 ± 56 mL/min/100 g, 13 ± 1.4 mm/Hg and 109 ± 19 mL/min, respectively. No early postoperative donor complications were recorded. One graft was lost due to intrahepatic abscesses. Asymptomatic stenosis of a right posterior duct was treated with a Roux-en-Y loop 4 months later in one donor. We show that LDH of the full-left lobe is feasible. LDH is a very demanding operation, potentially decreasing donor morbidity. Standardization of this procedure, making it accessible to the growing number of experienced laparoscopic liver surgeons, could help renewing the interest for A2ALDLT in the Western world.

Liver transplantation with piggyback anastomosis using a linear stapler: a case report.

The so-called piggyback technique of liver transplantation (PB-LT) preserves the recipient's caval vein, shortening the warm ischemic time. It can be reduced even further by using a linear stapler for the cavocaval anastomosis. Herein, we have presented a case of a patient undergoing a side-to-side, whole-organ PB-LT for cryptogenic cirrhosis. Upper and lower orifices of the donor caval vein were closed at the back table using a running 5-0 polypropylene suture. Three stay sutures were then placed on caudal parts of both the recipient and donor caval with a 5-mm venotomies. The endoscopic linear stapler was placed upward through the orifices and fired. A second stapler was placed more cranially and fired resulting in a 8-9 cm long cavocavostomy. Some loose clips were flushed away from the caval lumen. The caval anastomosis was performed within 4 minutes; the time needed to close the caval vein stapler insertion orifices (4-0 polypropylene running suture) before reperfusion was 1 minute. All other anastomoses were performed as typically sutured. The presented technique enables one to reduce the warm ischemic time, which can be of particular importance with marginal grafts.

Pancreatoduodenectomy with subtotal stomach-preserving and uncut Roux reconstruction.

BACKGROUND/PURPOSE: Pylorus-preserving pancreatoduodenectomy (PD) has become the therapy of choice for resectable tumors located in the head of the pancreas and periampullary region. In addition, a distal gastrectomy may still be required for tumors located in the dorsal part of the pancreatic head or when there is evidence of proximal duodenal invasion. This may lead to postoperative complications, including gastric dumping, marginal ulceration, and bile reflux gastritis. This study reports on the postoperative course following subtotal stomach-preserving PD with the uncut Roux reconstruction diverting biliary and pancreatic secretions from the gastric remnant. METHODS: A technique combining subtotal stomach-preserving PD with the uncut Roux reconstruction was applied in 10 patients. The postoperative clinical follow-up data are reviewed, and clinical criteria of biliary gastric reflux and gastritis were evaluated. RESULTS: The postoperative course was uneventful in 4 patients and complicated in 6 patients. Delayed gastric emptying occurred in 3 patients. No deaths occurred in the postoperative period. One patient suffered from occasional nausea with abdominal discomfort for which endoscopy and cholescintigraphy were performed. Endoscopy confirmed complete occlusion of the afferent jejunal limb and showed marginal ulceration within the gastrojejunal anastomosis. Cholescintigraphy showed signs of enterogastric reflux. The check-up endoscopy following typical antisecretory therapy revealed complete ulcer healing. Four patients died of tumor recurrence 6, 7, 8, and 12 months following surgery. CONCLUSION: This pilot study suggests that the uncut Roux reconstruction may represent a good alternative to gastrointestinal reconstruction following PD. Further studies including the determination of intragastric bile acid concentration and radionuclide isotope scanning in a larger number of patients are warranted.

Upper gastrointestinal endosonography in patients evaluated for liver transplantation.

BACKGROUND: Endosonography (EUS), which merges endoscopic and ultrasound examinations, is a useful modality to display abnormal vessels that develop in the intrinsic circulation, frequently called "deep" varices. If these pathological veins exceed of 5 mm diameter, they significantly increase the risk of bleeding among patients with cirrhosis. In the most recent pilot study EUS proved useful to assess children for orthotopic liver transplantation (OLT). AIM: We performed a cross-sectional study of EUS on 33 (22 males and 11 females) adult cirrhotic subjects being assessed for OLT. MATERIALS/METHODS: We used an echoendoscope at 7.5 MHz/12 MHz/20 MHz to evaluate the esophagus and stomach, including "deep" periesophageal/perigastric varices (adjacent to the muscularis propria) and paraesophageal/paragastric varices (outside the muscularis propria). "Deep" varices were considered to be large if >5 mm. RESULTS: On endoscopy, 26 (79%) patients showed esophageal varices (EV), including 11 (33%) with large (>5 mm) varices. Gastric varices (GV) were observed in 13 (39%) subjects, with 3 patients displaying large (>5 mm) varices. On EUS large "deep" EV (both para and periesophageal) were observed in 12 (36%) subjects, among whom 5 (42%) did not have large varices on endoscopy. Large "deep" GV were found on EUS in 12 (36%) subjects. On endoscopy 4 of them (33%) showed no varices and 3 (25%) had small GV. CONCLUSIONS: EUS offers a precise evaluation of portal hypertension in OLT candidates. "Deep" potentially dangerous varices, which are undetected with routine endoscopy, were noted in a significant proportion of patients. The role of EUS in prioritizing subjects for OLT must be evaluated in a prospective study.

Administration of a recombinant factor Vlla in patients undergoing liver transplantation for fulminant hepatic failure.

BACKGROUND: Fulminant hepatic failure (FHF) is associated with profound clotting disturbances leading to the risk of a major blood loss during orthotopic liver transplantation (OLT). Application of a recombinant factor VIIa (rVIIa) that promptly corrects clotting abnormalities remains controversial in the OLT setting. We conducted a retrospective analysis of the effect of rVIIa on the prothrombin time (PT) and other perioperative parameters in patients transplanted for FHF in our center. MATERIALS AND METHODS: Nineteen consecutive patients (9 males/10 females) of overall mean age of 33 +/- 13 years underwent the procedure due to: Wilson's (n = 8), non-A-non-B hepatitis (n = 6) or Amanita phalloides toxicity (n = 5). All subjects received rVIIa at a mean dose of 54 +/- 16 microg/kg body weight at 10 minutes before the skin incision. The PT was measured at 15 minutes and 12 hours after injection. Data were analyzed with StatView program with P < .05 considered significant. RESULTS: Rapid correction of PT was observed in all patients: the mean PT before injection was 37 +/- 14 versus 14 +/- 3 after 15 minutes (P < .0001). Twelve hours after the injection the PT was 19 +/- 5 (P < .0001 vs before injection and P < .0007 vs 15 minutes after injection). Two patients died at 1 and 4 days after OLT. Mean red blood cell requirement was 5 +/- 4 U and fresh frozen plasma was 11 +/- 5 U. The mean operative time was 527 +/- 126 minutes and intensive care unit stay 8 +/- 9 days. None of the patients developed thromboembolic complications. CONCLUSION: Administration of rVIIa caused a rapid improvement in the PT shortly after injection. It was safe and not associated with any thromboembolic events in our series.

Immunosuppression with low-dose daclizumab in liver transplant recipients with impaired kidney function: a single-center experience.

BACKGROUND: Nephrotoxicity of calcineurin inhibitors (CNI) may exert detrimental effects, particularly in orthotopic liver transplantation (OLT) patients with impaired kidney function. Immunosuppression with daclizumab permits delayed introduction of CNI, and may be preferred for patients with kidney dysfunction. This retrospective analysis of our experience using daclizumab was performed among patients who underwent transplantation with impaired kidney function. METHODS: We analyzed 168 patients. A serum creatinine (Cr) level >1.5 mg/dL was the indication for a protocol with low-dose daclizumab (50 mg intravenous [IV], day 0 and day 4), mycophenolate mofetil (MMF; 500 mg twice daily IV/orally), and tapering doses of prednisolone from day 0 after OLT. CNI were introduced at day 4-15 after OLT. Patients with a Cr level <1.5 mg/dL received immunosuppression with CNI+MMF+steroids or CNI+steroids. RESULTS: Fourteen patients fulfilled the criterion for daclizumab immunosupression. Their Cr and creatinine clearance (CrCl) values at OLT were 2.85 +/- 1.22 mg/dL and 19 +/- 11 mL/min, respectively. In the remaining 154 patients, Cr and CrCl results were 0.88 +/- 0.3 mg/dL and 107 +/- 82 mL/min, respectively. At discharge, the daclizumab group showed Cr and CrCl estimates of 0.97 +/- 0.45 mg/dL and 86 +/- 34 mL/min (P < .0001 for both, when compared with prior to OLT). Both Cr and CrCl levels at discharge were not different from those values of patients who underwent transplantation with normal kidney function. The incidence of acuterejection was 14% in the daclizumab group and 18% in the other recipients (P = not significant [NS]). CONCLUSIONS: Immunosuppression with low-dose daclizumab and delayed introduction of CNI was safe and did not increase the risk of an acute rejection episode, thus offerring an excellent therapeutic option for patients who undergo transplantation with impaired kidney function.

Assessment of a modified Child-Pugh-Turcotte score to predict early mortality after liver transplantation.

OBJECTIVE: The Model for End-Stage Liver Disease (MELD) predicts mortality on the transplant list; however, it has not been of much use to predict posttransplant outcomes. Several prognostic models have been tested among patients with cirrhosis; nevertheless, their predictive value has not been established in the posttransplant setting. We recently modified the Child-Pugh-Turcotte (CPT) score by adding creatinine levels (CPT + Cr), which has proven useful for patients with alcoholic cirrhosis. This retrospective analysis sought to predict early (1 month) mortality using CPT + Cr versus 5 other prognostic models in patients who underwent orthotopic liver transplantation (OLT) at our center. MATERIALS AND METHODS: We included 48 consecutive patients (30 males, 18 females, median age 51 years). The predictive values of CPT + Cr were compared with CPT scores without or with the Huo modification, CPT + Na, MELD, and MESO, which is the MELD to serum Na ratio. Pearson correlations and ROC curves as evidenced by the area under the curve (AUC) were determined for each index. P < .05 was considered to be significant. RESULTS: CPT + Cr showed the highest correlation with the risk of death (r = .368, P = .01); MELD and MESO were the lowest (r = .204, P = NS; and r = .254, P = NS, respectively). ROC analysis showed the best predictive value of CPT and CPT-Crea with AUC of 0.758 (P = .010) and 0.748 (P = .011) respectively, as compared to 0.689 for MESO and 0.659 for MELD (both NS). CONCLUSIONS: A modified CPT score with creatinine levels may be of value to predict early death after OLT. Its usefulness must be validated in a prospective study of a large patient cohort.

Modified Charlson Comorbidity Index in predicting early mortality after liver transplantation.

BACKGROUND: The Charlson Comorbidity Index for orthotopic liver transplantation (CCI-OLT) is a modified clinical score recently proposed to be useful for the assessment of long-term survival after OLT. It includes 9 associated conditions selected upon a multivariate analysis of a large cohort of transplant recipients. Its role in predicting early mortality after OLT has not yet been investigated. We sought to CCI-OLT as a potential predictor of 1-month mortality after OLT. MATERIALS/METHODS: One hundred ninety-seven OLT were performed in our center between March 2002 and February 2009. After exclusion of patients who underwent transplantation for fulminant hepatic failure or those who underwent regrafting, we included a group of 169 patients. Viral (39%) and alcohol-induced (23%) cirrhosis were the most common indications for OLT. The CCI-OLT index was assessed in all patients. RESULTS: In total, 146 (86%) subjects survived and 23 (14%) died within 1 month after LT. Fifty-one (30%) patients suffered at least 1 comorbidity that was included in the CCI-OLT. Direct comparison between survivor versus nonsurvivor groups showed no significant difference in terms of the total frequency of comorbidities (30.1% vs 30.4%; P > .99) or the number or the type of comorbidity. The most commonly associated condition in both groups was diabetes mellitus. CONCLUSION: Unlike the case of long-term survival, CCI-OLT did not seem to predict early (1-month) mortality after OLT.

Reduction of biliary complication rate using continuous suture and no biliary drainage for duct-to-duct anastomosis in whole-organ liver transplantation.

Biliary complications (BC) following orthotopic liver transplantation (OLT) are related to various factors including surgical technique and use of biliary drains for a duct-to-duct (DD) anastomosis. Herein we have reported the influence of changes in surgical technique on BC following OLT in our center. From February 2002 to February 2007, we performed 101 whole-organ OLT with a DD anastomosis in 99 adults, of whom we analyzed 84 subjects. We excluded recipients who died within 30 days of OLT without any evidence of BC and 1 patient with a biliary stricture secondary to a hepatic artery thrombosis. Until late 2004, a DD anastomosis with interrupted sutures over an external biliary drain (DD/BD) was performed in 35 patients (Group I). Subsequently, no biliary drain was used for the DD anastomosis (DD/non-BD), using a continuous suture in 49 patients (Group II). The DD anastomosis with interrupted sutures over a biliary drain was associated with a higher incidence of both total (31% vs 8%; P = .008) and late BC (>30 days; 20% vs 2%; P = .008) with a trend toward more leaks (17% vs 4%; P = .06). All biliary leaks in patients with DD/BD reconstruction occurred at the exit site of the biliary drain following its removal. No significant differences were observed when we compared the incidence of biliary strictures and the necessity for surgical intervention. One patient died due to a BC. Our results indicated that a DD anastomosis performed with a continuous suture technique and no external biliary drainage reduced the incidence of BC after whole-organ OLT.

Vascular complications following adult piggyback liver transplantation with end-to-side cavo-cavostomy: a single-center experience.

BACKGROUND: Vascular complications remain a significant cause of morbidity, graft loss, and mortality following orthotopic liver transplantation (OLT). These problems predominantly include hepatic artery and portal vein thrombosis or stenosis. Venous outflow obstruction may be specifically related to the technique of piggyback OLT. MATERIALS AND METHODS: Between February 2002 and February 2009, we performed 200 piggyback OLT in 190 recipients. A temporary portacaval shunt was created in 44 (22%) cases, whereas end-to-side cavo-cavostomy was routinely performed for graft implantation. Pre-existent partial portal or superior mesenteric vein thrombosis was present in 17 (12%) cirrhotics in whom we successfully performed eversion thrombectomy, which was followed by a typical end-to-end portal anastomosis. The donor hepatic artery was anastomosed to the recipient aorta via an iliac interposition graft in 31 (16%) patients. RESULTS: The 14 (7%) vascular complications included hepatic artery thrombosis (n = 5), hepatic artery stenosis (n = 3), aortic/celiac trunk rupture (n = 2), portal vein stenosis (n = 2), and isolated left and middle hepatic venous outflow obstruction (n = 1). There was also 1 case of arterial steal syndrome via the splenic artery. No patient experienced portal or mesenteric vein thrombosis. Therapeutic modalities included re-OLT, arterial/aortic reconstruction and splenic artery ligation. Vascular complications resulted in death of 5 (36%) patients. CONCLUSION: Our experience indicated that piggyback OLT with an end-to-side cavo-cavostomy showed a low risk of venous outflow obstruction. Partial portal or mesenteric vein thrombosis is no longer an obstacle to OLT; it can be successfully managed with the eversion thrombectomy technique.

Outcome of emergency liver transplantation including mortality on the waiting list: a single-center experience.

Patients with irreversible fulminant hepatic failure (FHF) as well as recipients with primary graft nonfunction (PNF) and early hepatic artery thrombosis (HAT) die unless they undergo emergent liver transplantation (OLT). Therefore, they have the highest priority in organ allocation systems. Herein we describe our initial experience with 18 emergency among 103 OLT procedures performed in 99 adults from February 2002 through February 2007. Their diagnoses were FHF (n = 16), PNF (n = 1), and early HAT (n = 1). Ten subjects (56%) underwent emergency OLT after a mean 1.6 (range, 1 to 4) days after listing, whereas 8 (44%) patients died while awaiting a graft for a mean of 5.9 days (range, 2 to 17). All the transplants were performed according to the piggyback technique with routine preoperative use of intravenous recombinant factor VIIa (rVIIa) to control the coagulopathy, which resulted in significant (P < .0001), prompt correction of prothrombin time from a mean of 61 (range, 22 to 300) to 14 (range, 11 to 22) seconds at 15 minutes after drug administration. A mean of 4 (range, 0 to 14) units of RBC and 9 (range, 3 to 18) units of fresh frozen plasma were transfused during the procedure. Eight (80%) transplanted patients are alive in good condition with normal liver function at a mean of 18 (range, 4 to 36) months follow-up. Two patients died in the early postoperative period after massive aortic bleeding and biliary sepsis. In summary, only 56% of patients requiring emergency OLT received grafts achieving good medium and long-term survivals, which was significantly lower compared with Western European centers where this proportion reaches 90%. This outcome could be improved by international organ-sharing arrangements for emergency transplantation or living donation alternatives.

Liver transplantation for fulminant hepatic failure without venovenous bypass and without portacaval shunting.

Preservation of the caval vein during liver transplantation (OLT) has gained wide acceptance but portosystemic bypass or temporary portocaval shunt is still believed to be indicated in patients with fulminant hepatic failure. Herein we have described our initial experience with piggyback OLT without venovenous bypass and without portocaval shunting in five such patients. Division of the portal vein was always delayed until the native liver was completely dissected off the caval vein. The donor hepatic artery was anastomosed to the recipient aorta via an iliac interposition graft placed in the supraceliac position in two and at an infrarenal site in three patients. The ahepatic phase urinary output was low in the two patients in whom we applied supraceliac cross-clamping of the aorta. The mean ahepatic phase was 53 (45 to 67) minutes in four recipients who remained hemodynamically stable throughout surgery and prolonged to 5 hours in one patient due to a complicated supraceliac aortic anastomosis. Its repair resulted in hemodynamic instability, multiorgan failure, and death at 4 days following OLT. Four (80%) patients are alive in good condition with normal liver function after a mean of 12 (5 to 25) months of follow-up. In summary, liver transplantation for fulminant hepatic failure may be safely performed without venovenous bypass and without temporary portocaval shunting if the ahepatic phase is minimized and portal flow to the liver maintained up to the moment of hepatic excision. Arterial anastomosis with the supraceliac aorta prolongs the ahepatic phase and may impair kidney function: therefore, it should be avoided in these patients.

Rapid correction of prothrombin time after low-dose recombinant factor VIIA in patients undergoing orthotopic liver transplantation.

Orthotopic liver transplantation (OLTx) is associated with a major risk of blood loss resulting from portal hypertension, collateral circulation, and clotting disturbances. Application of a recombinant factor VIIa (rFVIIa) has been reported to promptly correct clotting abnormalities reducing the risk of intraoperative bleeding. This study included 8 patients who underwent OLTx for end-stage liver cirrhosis, with protrombin times (PT) exceeding the upper limit of normal by more than 4 seconds before surgery. All subjects were administered a small single intravenous dose of rFVIIa [mean 68.37 microg/kg body mass (range, 32.88-71.64)] 10 minutes prior to the skin incision. The PT was then measured 15 minutes later, following graft reperfusion, and 12 hours since drug application. All patients showed rapid correction of PT within 15 minutes after injection (median PT before injection 20.25 seconds vs 11.5 seconds after injection, P <.0001). Following the reperfusion PT was found to be prolonged again. These values are not significantly differ from those before surgery and are comparable to PT values after reperfusion in patients who did not receive rFVIIa. None of the patients developed thromboembolic complications. In conclusion, lower than recommended dose of rFVIIa caused rapid improvement in the PT shortly after injection. After reperfusion PT became prolonged again, which may account for the lack of thromboembolic complications observed in this group of patients.

Comparison of MEGX (monoethylglycinexylidide) and antipyrine tests in patients with liver cirrhosis.

The aim of the study was to compare the feasibility of the MEGX (monoethylglycinexylidide) and antipyrine tests in reference to standard biochemical parameters used for liver assessment in cirrhotic patients. The study was carried out in 44 subjects: 14 healthy controls and 30 cirrhotic patients classified according to the Child-Pugh's score to subgroups A (n=11), B (n=12) and C (n=7). All subjects underwent two dynamic liver tests, i.e. MEGX (monoethylglycinexylidide) and antipyrine test in a crossover schedule with at least 5-day interval. For the MEGX, lidocaine was administrated intravenously, at a dose of 1 mg/kg, and blood samples for MEGX assay were collected after 15 minutes. MEGX concentrations were measured by fluorescence polarization immunoassay. The antipyrine concentrations were evaluated following a single oral administration of 1000 mg antipyrine. The blood was sampled for 24 hours after the drug administration, and antipyrine concentrations were measured spectrophotometrically. Standard biochemical parameters used for liver assessment were measured by means of routine laboratory methods. It was concluded that in patients liver with cirrhosis, liver dynamic tests were better predictors of hepatic function. The MEGX test was more feasible in clinical setting, but it was noted that antipyrine test was more sensitive in staging liver cirrhosis.

Pharmacokinetics of intravenously administered digoxin and histopathological picture in rabbits with experimental bile duct obstruction.

This study aimed to examine the effect of obstructive cholestasis on the pharmacokinetics of digoxin. Eighteen male rabbits were randomly ascribed to the two study groups: the sham-operated control group and the examined group - with common and cystic bile duct ligations. Digoxin was administered intravenously as a single dose of 0.02 mg/kg, and blood samples were withdrawn for up to 24 h. Digoxin concentrations were determined by the FPIA method. The pharmacokinetic parameters were calculated using a noncompartmental analysis. During the whole observation period the blood serum concentrations of digoxin were statistically higher in animals with obstructive cholestasis versus the controls. A significant increase in the area under the plasma concentration-time curve, decrease in the total body clearance and in the volume of distribution on the 6th day after the bile ducts ligation as compared to the sham-operated controls, were observed. The obtained results suggest an impaired elimination of digoxin in obstructive cholestasis in rabbits.

Pharmacokinetics of propranolol and atenolol in patients after partial gastric resection: a comparative study.

OBJECTIVE: Partial gastric resection alters the anatomy and secretory activity of the gastrointestinal tract. It might be expected that the consequences of such changes should affect the pharmacokinetics, especially concerning the absorption of orally administered drugs. Propranolol and atenolol, as representatives of lipophilic and hydrophilic beta-adrenoreceptor antagonists, have been studied in order to define their pharmacokinetic characteristics in patients after partial gastrectomy. METHODS: The study was carried out in 29 patients after gastric resection with Billroth I (B1) anastomosis and in 18 healthy volunteers as controls. Pharmacokinetics of propranolol and atenolol was investigated after a single oral dose of 80 mg and 100 mg, respectively, following a cross-over schedule. Blood samples were collected ten times during the 24 h after the drug administration. Pharmacokinetic parameters of propranolol and atenolol were calculated using a one-compartment open model with first-order absorption. RESULTS: The average blood plasma concentrations of propranolol in gastrectomised patients were lower than those in controls, reaching significance between 1.5 h and 6.0 h of the observation period. Pharmacokinetic parameters of propranolol were different in subjects submitted to surgery compared with healthy persons. We observed a significant decrease in the area under the concentration-time curve (32%) and the peak plasma concentration (20%), and an increase in half-life (25%). Mean plasma concentrations and pharmacokinetic parameters of atenolol in patients following partial gastric resection were not significantly different from those in the controls. No relationship between time interval following partial gastrectomy and pharmacokinetic parameters of the investigated drugs was noted. CONCLUSION: Partial gastrectomy with B1 anastomosis affects the pharmacokinetics of propranolol (lipophilic drug) but not atenolol (hydrophilic drug).

Antitumor effect of electrochemical therapy on transplantable mouse cancers.

The aim of our study was to assess the antitumor effect of electrochemical therapy (ECT) in the mice bearing advanced transplantable tumours. Mouse mammary cancer 16/C (group 1) and fibrosarcoma F69-3 (group 2) were transplanted subcutaneously (s.c.) into the C3H or BALB/c mice, respectively. Twenty animals in each group bearing measurable s.c. tumours were randomly divided into two subgroups (experimental and control). Two electrodes were inserted into tumours and low level direct current (6-7 V, 5-21 mA) was passed. The animals were observed and tumors were measured twice a week. The animals were sacrificed and autopsied when the tumor diameter reached 2.0 cm. Two animals of each group (experimental and control) were sacrificed for histopathological tumor examination on the 1st and 6th day after ECT. A significant inhibition of tumor growth in mice subjected to ECT was observed, both in those with s.c. growing mammary cancer and with fibrosarcoma. This inhibition was associated with marked prolongation of survival time of ECT-treated mice. It appeared that the mice with mammary cancers were more susceptible to ECT therapy than those with growing s.c. fibrosarcoma. The histopathological studies of tumor specimens from ECT-treated mice showed extensive foci of necrosis with shrinkage of cell nuclei deprived of chromatin. In conclusion, the treatment which inhibits the growth of experimental mammary and fibrosarcoma tumors was demonstrated. However, in no mice complete regression of tumours was observed.

CYP2D6 and GSTM1 genotypes in a Polish population.

OBJECTIVE: The aim of the present study was to investigate the distribution of the CYP2D6 and GSTM1 genotypes in a Polish population. METHODS: One hundred and forty-five unrelated healthy individuals from the western region of Poland were studied. The CYP2D6 genotype was analysed by means of polymerase chain reaction (PCR) amplification for the CYP2D6*3 and CYP2D6*4 alleles. The GSTM1 genotype was also analysed by means of a PCR assay to determine two genotypes: GSTM1-1 (positive) and GSTM1-0 (negative). RESULTS: Fourteen subjects (9.6%) were classified as poor metabolisers. The frequency of CYP2D6*4 and CYP2D6*3 was 23.1% and 2.1%, respectively. The frequency of GSTM1 nulled genotype in a Polish population came to 49%. CONCLUSION: The frequencies of poor metabolisers for CYP2D6 and GSTM1 nulled genotype among a Polish population were similar to those observed in other Caucasian populations.