Prospective Series of Transarterial Chemoembolization of Metastatic Colorectal Cancer to the Liver with 30-60 µm Microspheres Loaded with Irinotecan.

PURPOSE: To describe safety and clinical outcomes among patients with metastatic colorectal cancer (mCRC) to the liver treated with transarterial chemoembolization with HepaSphere™ Microspheres 30-60 µm loaded with irinotecan (ΙRI-HEP-TACE). MATERIAL AND METHODS: In this prospective study (NCT04866290), 100 adults with confirmed mCRC to the liver who were ineligible for resection were enrolled and followed up to 24 months or death. Study outcomes among Salvage (patients not tolerating more cycles of chemotherapy) and Non-salvage patients included overall survival (OS), progression-free survival (PFS), objective response (OR), objective response rate (ORR), best tumor response (BTR), adverse events (AEs), and pharmacokinetics of irinotecan and its active metabolite, 7-ethyl-10-hydroxy-camptothecin (SN38). RESULTS: The median age was 66 years (range: 31-89). Median OS was 15.08 months (95% confidence interval [CI]: 12.33-17.25). PFS was 8.52 months (95% CI: 6.0-9.0; p < 0.001). ORR was 42.2% (95% CI: 31.57-53.50) and 35.9% (95% CI: 25.57-47.62) based on modified RECIST (Response Evaluation Criteria in Solid Tumors) and RECIST 1.1 criteria. BTR was not significantly different between mRECIST and RECIST (p = 0.745). The Non-salvage group had a statistically significant difference in median OS relative to the Salvage group (15.3 vs. 3 months; p < 0.001). Pharmacokinetic analyses demonstrated no correlation of OS with plasma concentration of irinotecan and SN38 (all p > 0.05). Most AEs were Grade 2 (257/279), the most common AE was right upper abdominal pain (180/279). One major AE (tumor rupture) was reported. CONCLUSION: IRI-HEP-TACE is an alternative treatment for patients with Non-salvage mCRC to the liver.

Safety, Efficacy and Distribution of Doxorubicin Loaded Radiopaque Beads in Chemoembolization in Intermediate Stage Hepatocellular Carcinoma (HCC) with Correlation with Local Response.

PURPOSE: The primary objectives of this study were to evaluate safety, and efficacy of Transarterial Chemoembolization (TACE) using doxorubicin-loaded radiopaque microspheres (DC Bead LUMI™) for the treatment of early and intermediate stage Hepatocellular Carcinoma (HCC) not amenable for curative treatments. Distribution of the microspheres was correlated with results post embolization. MATERIALS AND METHODS: This was a prospective, single arm, open label study. The primary outcome measures were distribution of the radiopaque microspheres as showed by computerized tomography (CT) and local response measured by modified Response Evaluation Criteria (mRECIST) after Magnetic Resonance Imaging (MRI). Secondary measures were Time to Progression (TTP) and Overall Survival (OS). RESULTS: Fifty patients were enrolled over 36 months. Median age was 69.0 years; mean sum of target lesions diameters was 78.6 ± 36.8 mm. There were no Grade 4 or 5 adverse events (AEs). At 6 months Complete Response (CR) (18%), Partial Response (PR) (62%), Objective Response OR (80%) and Stable Disease (SD) (20%) were recorded. Before embolization, Diffusion Weighted Imaging (DWI) showed high signal (restricted diffusion). Post procedure, patients with dense deposition (< 5 mm distance of microsphere aggregations) showed 100% absence of enhancement and no restriction in 30.6%. Median TTP was 8.3 months. TTP for patients with CR was 13.3 months and 7.2 and 5.6 for PR and SD, respectively. At 6 and 36 months, survival was 94% and 34%, respectively. CONCLUSION: DC Bead LUMI™ is well tolerated and effective in early and intermediate stage HCC with maximal necrosis obtained in dense deposition in the target.

Five-Years Outcome Analysis of 142 Consecutive Hepatocellular Carcinoma Patients Treated with Doxorubicin Eluting Microspheres 30-60 µm: Results from a Single-Centre Prospective Phase II Trial.

PURPOSE: To assess prospectively long-term results of doxorubicin-loaded HepaSphere 30-60 µm in consecutive patients with hepatocellular carcinoma (HCC) not amenable to curative treatments. PATIENTS AND METHODS: Single-center study from June 2011 to December 2015 in 151 patients treated with 75 mg of doxorubicin per HepaSphere vial. Baseline: Barcelona Clinic Liver Cancer BCLC A/B was 49.3%/50.7%, and median diameter 6.1 cm (mean 6.7 ± 2.0). Liver function, local response (mRECIST), liver time to progression (LTTP), progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were recorded. RESULTS: Final analysis included 142 patients with median follow-up of 46.8 months (range 4-72) without grade 4/5 AEs, and 30-day mortality was 0%. Mean number of scheduled treatments was 2.6 (range 1-3) and on demand 3 (range 1-8). Complete response for single tumor ≤ 5 cm was 75.0% and 66.7% for Child A and Child B, while for > 5 cm was 28.6% and 11.8%, respectively. OS was 31.0 months (mean 33.3 ± 15.2; range 8-69), notably for BCLC A 41 months (mean 41.1 ± 15.3; range 13-69) and for BCLC B 26.0 (mean 26.0 ± 10.5; range 8-51). OS at 1, 3 and 5 years: 95.8%, 75.7% and 21.4% for BCLC A, and 94.4%, 36.1% and 2.7% for BCLC B. Median LTTP for BCLC A was 11 months (mean 11.9 ± 4.7; range 3-24) and 7.5 for BCLC B (mean 7.9 ± 2.9). Local response was significant for OS and LTTP (p < 0.0001), while size and lesion number affected LPFS and OS (p < 0.001). CONCLUSIONS: HepaSphere 30-60 µm loaded with doxorubicin provides a safe and effective treatment option for patients with HCC.

The role of liver resection in the management of intermediate and advanced stage hepatocellular carcinoma. A systematic review.

BACKGROUND: The ideal management for patients with intermediate and advanced stage hepatocellular carcinoma (HCC) is controversial. The main purpose of this systematic review is to examine the role of liver resection in patients with intermediate stage HCC (multinodular HCCs) and in advanced stage HCC [mainly patients with portal vein tumor thrombosis (PVTT)]. METHODS: A systematic search of the literature was performed in Pud Med and the Cochrane Library from 01.01.2000 to 30.06.2016. RESULTS: Twenty-three articles with 2412 patients with multinodular HCCs were selected. Also, 29 studies with 3659 patients with HCCs with macrovascular invasion were selected. In patients with multinodular HCCs the median post-operative morbidity was 25% and the 90-day mortality was 2.7%. The median survival was 37 months and the 5-year survival 35%. The 5-year survival was much better for patients with a number of HCCs ≤3 vs. HCCs >3 (49% vs. 23%). In patients with macrovascular invasion, who underwent hepatic resection, the median post-operative morbidity was 33% and the in-hospital mortality 2.7%. The median survival was 15 months. The 3 and 5year survival was 33% and 20% respectively. Moreover a significant difference in survival was noted according to PVTT stage: 5- year survival for distal PVTT, PVTT of the main intrahepatic PV branch and PVTT extending to the main PV was 45%, 19% and 14.5% respectively. CONCLUSIONS: Liver resection in patients with multinodular HCCs and HCCs with PVTT offers satisfactory long-term survival and should be considered in selected patients.

The role of portal vein embolization in the surgical management of primary hepatobiliary cancers. A systematic review.

BACKGROUND: Primary liver and biliary cancers are very aggressive tumors. Surgical treatment is the main option for cure or long term survival. The main purpose of this systematic review is to underline the indications for portal vein embolization (PVE), in patients with inadequate future liver remnant (FLR) and to analyze other parameters such as resection rate, morbidity, mortality, survival after PVE and hepatectomy for primary hepatobiliary tumors. Also the role of trans-arterial chemoembolization (TACE) before PVE, is investigated. METHODS: A systematic search of the literature was performed in Pub Med and the Cochrane Library from 01.01.1990 to 30.09.2015. RESULTS: Forty articles were selected, including 2144 patients with a median age of 61 years. The median excision rate was 90% for hepatocellular carcinomas (HCCs) and 86% for hilar cholangiocarcinomas (HCs). The main indications for PVE in patients with HCC and presence of liver fibrosis or cirrhosis was FLR <40% when liver function was good (ICGR15 < 10%) and FLR < 50% when liver function was affected (ICGR15:10-20%). The combination of TACE and PVE increased hypertrophy rate and was associated with better overall survival and disease free survival and should be considered in advanced HCC tumors with inadequate FLR. In patients with HCs PVE was performed, after preoperative biliary drainage, when FLR was <40%, in the majority of studies, with very good post-operative outcome. However indications should be refined. CONCLUSION: PVE before major hepatectomy allows resection in a patient group with advanced primary hepato-biliary tumors and inadequate FLR, with good long term survival.

Assessment of nonimmunologic factors in kidney transplant recipients according to Kidney Disease Improving Global Outcomes.

INTRODUCTION: Cardiovascular disease is the primary cause of death among kidney transplant recipients (KTRs), whereas chronic allograft nephropathy (CAN) is the main reason leading to end-stage chronic kidney disease. The etiologies of both entities include immunologic and nonimmunologic factors. The management of modifiable nonimmunologic parameters has recently been identified by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. The aim of our study was to assess the implementation of these guidelines in the outpatient kidney transplantation clinic of our hospital. PATIENT AND METHODS: We retrospectively monitored the records of 48 transplanted KTRs including 32 males of overall mean age 45.1 ± 10.7 years regarding control of anemia, dyslipidemia, mineral bone disorder (MBD), and blood pressure (BP) levels. Data were recorded every 6 months for 2 years, starting 1 year after renal transplantation. RESULTS: The estimated glomerular filtration rate of patients at baseline was 60.3 ± 18.8 mL/min/1.73 m(2) with no significant change during 2 years of follow-up. The control of anemia was satisfactory in 42 patients (88%) with hemoglobin values ≥ 11 g/dL during the follow-up. Regarding dyslipidemia management, the aggregate of patients showed fasting triglycerides ≤500 mg/dL in all measurements. The percentage of KTRs with LDL ≤100 mg/dL tended to improve from baseline versus the end of the study period (20.8% vs 41.7%). Serum calcium was satisfactorily controlled in 77% of patients, serum phosphorus in all patients, whereas parathyroid hormone (PTH) was abnormal in 60% of KTRs with chronic kidney disease stages 3-5. Finally, the BP goal of <130/80 mm Hg was achieved in approximately half of the patients. CONCLUSION: Control of nonimmunologic factors was satisfactory in terms of renal anemia and MBD, whereas dyslipidemia and BP levels were inadequately controlled. There is a clear need for better integration into clinical practice of KDIGO guidelines with regard to modifiable nonimmunologic factors.

Prospective evaluation of two-stage hepatectomy combined with selective portal vein embolisation and systemic chemotherapy for patients with unresectable bilobar colorectal liver metastases.

BACKGROUND: Liver resection is contraindicated in patients with multiple bilobar colorectal liver metastases because of the small liver remnant. An alternative strategy which may be curative is a two-stage hepatectomy in which the cancer is resected from one lobe and regeneration allowed prior to contralateral lobe resection. OBJECTIVE: To assess the feasibility, risks, and outcomes in a prospectively applied strategy for two-stage hepatectomy. METHODS: Over a 6-year period, 14 of 280 patients undergoing liver resection for colorectal liver metastases (5%) were considered for two-stage hepatectomy. Surgery was combined with chemotherapy in all (n = 14) and portal vein embolisation (PVE) selectively (n = 5). Median follow-up was 43 months. RESULTS: Both stages were completed in 11 of 14 patients (78%). There were no deaths. Post-operative complication rates were 0% (1st hepatectomy) and 27% (2nd hepatectomy). The 5-year survival after the second hepatectomy was 50%. The mean disease-free survival was 25 +/- 7.5 months. CONCLUSION: Two-stage hepatectomy combined with systemic chemotherapy and PVE can produce long-term survival in patients with multiple bilobar colorectal liver metastases.

Uric acid and oxidative stress.

Uric acid is the final product of purine metabolism in humans. The final two reactions of its production catalyzing the conversion of hypoxanthine to xanthine and the latter to uric acid are catalysed by the enzyme xanthine oxidoreductase, which may attain two inter-convertible forms, namely xanthine dehydrogenase or xanthine oxidase. The latter uses molecular oxygen as electron acceptor and generates superoxide anion and other reactive oxygen products. The role of uric acid in conditions associated with oxidative stress is not entirely clear. Evidence mainly based on epidemiological studies suggests that increased serum levels of uric acid are a risk factor for cardiovascular disease where oxidative stress plays an important pathophysiological role. Also, allopurinol, a xanthine oxidoreductase inhibitor that lowers serum levels of uric acid exerts protective effects in situations associated with oxidative stress (e.g. ischaemia-reperfusion injury, cardiovascular disease). However, there is increasing experimental and clinical evidence showing that uric acid has an important role in vivo as an antioxidant. This review presents the current evidence regarding the antioxidant role of uric acid and suggests that it has an important role as an oxidative stress marker and a potential therapeutic role as an antioxidant. Further well designed clinical studies are needed to clarify the potential use of uric acid (or uric acid precursors) in diseases associated with oxidative stress.

Alterations in plasma oxidative stress markers after laparoscopic operations of the upper and lower abdomen.

The patient's position during laparoscopic surgery can have a clinically relevant effect on lower limb and splanchnic circulation; this factor has not yet been investigated with respect to oxidative stress markers. In order to assess this effect, a prospective clinical trial was designed wherein 2 groups of patients were studied. In group A, 15 patients underwent upper abdominal nonhepatobiliary operations (13 modified Nissen fundoplications and 2 Taylor vagotomies) in the head-up position. In group B, 15 patients underwent lower abdominal operations (10 laparoscopic colectomies and 5 inguinal hernia repairs) in the head-down position. The pneumoperitoneum was maintained at 14 mm Hg in all cases. Plasma concentrations of thiobarbituric-acid reactive substances (TBARS), a marker of lipid peroxidation, plasma total antioxidant status (TAS), and serum uric acid concentrations were measured preoperatively, 5 minutes after deflation of the pneumoperitoneum, and 24 hours postoperatively. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum activities were measured preoperatively and 24 hours postoperatively. In group A, there was a significant increase in TBARS levels (p<0.005) immediately after deflation of the pneumoperitoneum and a significant decrease in TAS and uric acid levels (p<0.005) in the first postoperative day. There was also a significant postoperative elevation in both ALT and AST activities (p<0.001). In group B, no significant increase was found in postoperative TBARS or transaminase levels. TAS and uric acid levels decreased significantly in the first postoperative day (p<0.05) and (p<0.005, respectively). In conclusion, these results show that a combination of pneumoperitoneum and the head-up position causes significant increase in lipid peroxidation, decrease in plasma TAS, and increase in transaminases. The mechanism responsible for these events could be the low-flow ischemia-reperfusion syndrome induced by the pneumoperitoneum and aggravated by the head-up position.

A model to study total hepatic ischemia-reperfusion injury.

BACKGROUND: Most experimental animal models for studying hepatic ischemia-reperfusion injury (IRI) involve partial or segmental ischemia of the liver or a portocaval shunt procedure to avoid mesenteric congestion. However, these do not reflect the global ischemia that occurs during liver transplantation. A rabbit model of total hepatic ischemia without a portocaval shunt is described. METHODS: Twenty male New Zealand white rabbits (3.5 +/- 0.3 kg) were allocated to four groups: group 1 (n = 5), sham-operated; group 2 (n = 5), 20-minute total hepatic ischemia; group 3 (n = 5), 25-minute total hepatic ischemia; and group 4 (n = 5), 30-minute total hepatic ischemia. Total hepatic ischemia was induced by occluding the portal inflow vessels (portal vein and artery) with an atraumatic vascular loop and were measurements taken for 2 hours during reperfusion. RESULTS: A total hepatic ischemia of 30 minutes caused severe liver injury resulting in cardiac arrest at 2 hours of reperfusion in all five animals due to metabolic acidosis. Twenty minutes of total ischemia was tolerated and did not produce significant liver injury. Twenty-five minutes of total ischemia was tolerated but at 2 hours of reperfusion, resulted in significant liver injury (68 +/- 41, 283.0 +/- 20.5, and 835.2 +/- 52.7 U/L) compared with the sham-operated group (serum ALT, 25.4 +/- 2.7; serum AST, 47.4 +/- 3.0; serum LDH, 307.6 +/- 44.4 U/L; P < .003). CONCLUSIONS: Rabbits can tolerate 25 minutes of total hepatic ischemia without a portosystemic shunt. This 25-minute ischemia model simulates operative conditions during liver transplantation and will be valuable in studies modulating IRI.

Continuous infusion of N-acetylcysteine reduces liver warm ischaemia-reperfusion injury.

BACKGROUND: N-acetylcysteine (NAC) may modulate the initial phase (less than 2 h) of liver warm ischaemia-reperfusion (IR) injury but its effect on the late phase remains unclear. The present study investigated the role of NAC during the early and late phases in a rabbit lobar IR model. METHODS: Liver ischaemia was induced by inflow occlusion to the median and left liver lobes for 60 min, followed by 7 h of reperfusion. In the NAC group (n = 6), NAC was administered intravenously at 150 mg per kg over the 15 min before reperfusion and maintained at 10 mg per kg per h during reperfusion. In the IR group (n = 6), 20 ml 5 per cent dextrose was infused over the 15 min before reperfusion and continued at a rate of 10 ml/h. Animals in a sham operation group (n = 6) underwent laparotomy but no liver ischaemia. All animals were killed at the end of the experiment. RESULTS: Intracellular tissue oxygenation was improved after the second hour of reperfusion in animals treated with NAC compared with that in the IR group (P = 0.023). Hepatic microcirculation improved after 5 h of reperfusion (P = 0.036) and liver injury was reduced after 5 h, as indicated by alanine aminotransferase activity (P = 0.007) and indocyanine green clearance (uptake, P = 0.001; excretion, P = 0.032). CONCLUSION: The main protective effect of NAC becomes apparent 5 h after hepatic ischaemic injury.

Arterialization of the portal vein improves hepatic microcirculation and tissue oxygenation in experimental cirrhosis.

BACKGROUND: Arterialization of the portal vein (APV) has shown beneficial effects on liver regeneration and function in selected patients undergoing liver resection and transplantation. Whether APV improves liver perfusion and function in cirrhosis is unclear. This study investigated the effect of APV on hepatic haemodynamics and liver function in a rat model of cirrhosis. METHODS: Male Sprague-Dawley rats (250-300 g) were divided into three groups: normal controls (n = 7), cirrhosis with sham laparotomy (sham; n = 7) and cirrhosis with APV (APV; n = 9). Portal venous blood flow, portal vein pressure and hepatic parenchymal microcirculation (HPM) were measured before and after APV. Hepatic parenchymal oxygenation was assessed by near-infrared spectroscopy and hepatocellular injury by standard liver function tests. Measurements were taken at baseline, after APV and 7 days after surgery. RESULTS: APV increased portal blood flow and pressure in cirrhotic rats without altering intrahepatic portal resistance. APV increased the HPM in cirrhotic rats by a mean(s.e.m.) of 28.5(0.1) per cent on day 0 and 54.6(0.1) per cent by day 7 (P = 0.001). Liver tissue oxygenation was increased by APV and the plasma gamma-glutamyltranspeptidase level was reduced (mean(s.e.m.) 6.0(0.5) versus 3.8(0.3) units/l before and after APV respectively; P = 0.006) at day 7. CONCLUSION: APV increases portal blood flow, tissue perfusion and oxygenation in cirrhosis.

Value of CT after laparoscopic repair of postsurgical ventral hernia.

BACKGROUND: We examined computed tomographic (CT) findings after laparoscopic repair of postsurgical ventral hernias in patients with and without symptoms. METHODS: Meshes were placed laparoscopically in 18 patients for incisional ventral hernia repair. CT of the abdominal wall was performed 1, 15, and 30 days after repair and when clinical findings indicated the procedure. RESULTS: Scans of four patients showed small fluid collections within the abdominal wall between the hernia sac and the mesh. These collections resolved within the first 30 days without aspiration. Scans of three patients with symptoms 4-8 months later showed fluid collections that required multiple aspirations in one patient and a recurrent hernia that was repaired laparoscopically in another patient. CONCLUSION: Preliminary results suggest that CT is a useful imaging tool in patients with laparoscopic repair of incisional vetral hernia. It showed the correct site of the mesh, subclinical fluid collections in the abdominal wall, and recurrent hernia.

Laparoscopic surgery-induced changes in oxidative stress markers in human plasma.

BACKGROUND: The induction of the pneumoperitoneum increases intraabdominal pressure (IAP), causing splanchnic ischemia, whereas its deflation normalizes IAP and splanchnic blood flow. This procedure appears to represent an ischemia-reperfusion model in humans. METHODS: Thirty laparoscopic cholecystectomies (LC) were performed in 30 patients with a mean age of 54.6 +/- 15.6 years. A group of 20 patients mean age, 57.3 +/- 9.65 who underwent open cholecystectomy (OC) was also studied. Vein plasma levels of thiobarbituric acid-reactive substances (TBARS), a marker of free radical production; plasma total antioxidant status (TAS); and uric acid (UA) levels were measured preoperatively, 5 min after deflation of the pneumoperitoneum or at the end of operation, and 24 h postoperatively. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBL) levels were measured preoperatively and 24 h after the operation. RESULTS: In the LC group, significant elevations in the concentration of TBARS were observed in the early postoperative measurements in comparison with the preoperative measurements. TAS and UA levels were decreased significantly 24 h postoperatively compared to preoperative levels. The postoperative levels of AST, ALT, and TBL increased significantly in comparison with the preoperative levels. In the OC group, no alterations in the concentration of TBARS were observed in the postoperative period. The other parameters had changes similar to those recorded for the LC group. CONCLUSIONS: Free radical-induced lipid peroxidation associated with a decrease in plasma antioxidant capacity and UA levels as well as altered hepatic function is observed after deflation of the pneumoperitoneum. These results suggest that free radicals are generated at the end of a laparoscopic procedure, possibly as a result of an ischemia-reperfusion phenomenon induced by the inflation and deflation of the pneumoperitoneum.

Seroma in laparoscopic ventral hernioplasty.

SUMMARY: Seroma is a frequent complication of laparoscopic or open repair of ventral hernias using expanded polytetrafluoroethylene mesh. Aspiration of this seroma has the risk of introducing bacteria, resulting in infection and the recurrence of the hernia. Between May 1996 and December 2000, 51 patents who underwent 53 laparoscopic ventral hernioplasties (44 incisional, 5 large epigastric, and 4 large umbilical) were randomized to participate in a trial comparing the intraperitoneal onlay mesh repair with or without cauterization of the hernia sac. Group A (26 patients; 28 hernias) patients were operated on by using an expanded polytetrafluoroethylene Dual Mesh patch (Gore and Associates, Flagstaff, AZ, U.S.A.) inserted intraperitoneally and secured by full-thickness stitches and endoscopic clips to cover the hernia defect, while the sac was left intact. Group B (25 patients, 25 hernias) patients were operated on according to the same technique as those in group A, but the hernia sac was cauterized by monopolar cautery (5 cases) or harmonic scalpel (20 cases). After surgery, clinical examination and computed tomography scans were used to confirm or test the existence of seroma and recurrence. In group A, four clinically evident seromas were found. Two of them were resolved with no intervention. In the remaining two cases, multiple aspirations were needed for 4 and 7 months, respectively, but 2 and 3 months, respectively, after resolution of the seroma, a recurrence of the hernia was observed. There was one more recurrence without seroma and three with subclinical seromas (only observed on computed tomography scans). In group B, subclinical seroma (only observed in computed tomography scan) resolved in a few days, and one recurrence without seroma was observed. Although only a small number of patients were studied, our findings suggest that the cauterization of the hernia sac prevents seromas and reduces recurrences in laparoscopic repair of ventral hernias.

Lipid peroxidation and the use of emulsified propofol in laparoscopic surgery.

BACKGROUND: Free radical-induced lipid peroxidation associated with a decrease of antioxidant capacity in plasma is observed after the deflation of the pneumoperitoneum in laparoscopic surgery. In this study, we evaluated the effect of the continuous administration of lipid peroxidation derivatives on emulsified propofol. METHODS: Two groups of 20 patients each who underwent laparoscopic surgery were studied prospectively. Maintenance of anesthesia was achieved with 66% nitrous oxide and either isoflurane or continuous propofol administration. The level of thiobarbituric acid-reactive substances (TBARS) in the plasma was determined as a measure of free radicals before and after surgery. RESULTS: Ten patients in the propofol group had reduced TBARS, as compared to only one in the isoflurane group (p = 0.003). There was a statistically significant difference in age between the patients with reduced TBARS and those without reduced TBARS (p = 0.009) in the propofol group. CONCLUSIONS: Anesthesia with continuous propofol infusion in laparoscopic surgery has a significant scavenging action on the formation of free radicals and exerts its greatest antioxidant effect in patients >/=48 years of age.

Trimetazidine protects low-density lipoproteins from oxidation and cultured cells exposed to H(2)O(2) from DNA damage.

Trimetazidine is a well-established anti-ischemic drug, which has been used for long time in the treatment of pathological conditions related with the generation of reactive oxygen species. However, although extensively studied, its molecular mode of action remains largely unknown. In the present study, the ability of trimetazidine to protect low-density lipoproteins (LDL) from oxidation and cultured cells from H(2)O(2)-induced DNA damage was investigated. Trimetazidine, tested at concentrations 0.02 to 2.20 mM, was shown to offer significant protection to LDL exposed to three different oxidizing systems, namely copper, Fe/ascorbate, and met-myoglobin/H(2)O(2). The oxidizability of LDL was estimated by measuring, (i) the lag period, (ii) the maximal rate of conjugated diene formation, (iii) the total amount of conjugated dienes formed, (iv) the electrophoretic migration of LDL protein in agarose gels (REM), and (v) the inactivation of the enzyme PAF-acetylhydrolase present in LDL. In addition, the presence of trimetazidine decreased considerably the DNA damage in H(2)O(2)-exposed Jurkat cells in culture. H(2)O(2) was continuously generated by the action of glucose oxidase at a rate of 11.8 +/- 1.5 microM per min (60 ng enzyme per 100 microl), and DNA damage was assessed by the single cell gel electrophoresis assay (also called comet assay). The protection offered by trimetazidine in this system (about 30% at best) was transient, indicating modification of this agent during its action. These results indicate that trimetazidine can modulate the action of oxidizing agents in different systems. Although its mode of action is not clarified, the possibility that it acts as a lipid barrier permeable transition metal chelator is considered.

Laparoscopic placement of the Tenckhoff catheter for peritoneal dialysis.

Continuous ambulatory peritoneal dialysis catheters can be inserted by open laparotomy as well as by laparoscopy. A prospective randomized study was scheduled to investigate the results of the laparoscopic versus open laparotomy technique for placement of continuous ambulatory peritoneal dialysis catheters. Fifty patients were enrolled and randomly allocated into two groups of 25 patients each. Group A underwent continuous ambulatory peritoneal dialysis catheter placement via the open laparotomy technique. In 22 patients, catheters were inserted via midline incision, and in 3 patients with histories of previous catheterization, a paramedian incision was used. Continuous ambulatory peritoneal dialysis was started 24 to 48 hours later. Group B underwent laparoscopic placement of the catheter with fixation into the pelvis and suture closure of the port wounds. In 21 patients, this catheter placement was the first such placement, and in 4 patients, a previous catheter had been inserted by the open technique and removed for dysfunction. Continuous ambulatory peritoneal dialysis was started at the end of the procedure. The mean operative time was 22 minutes in group A and 29 minutes in group B (P < 0.001). Fluid leakage was observed in eight patients in group A, but in no patients in group B (P < 0.005). Peritonitis occurred in five patients in group A and in three patients in group B (P > 0.1). Tip migration occurred in five patients in group A and no patients in group B (P < 0.005). In group B, two patients underwent a simultaneous cholecystectomy and one underwent incisional hernia repair. Laparoscopic placement of a Tenckhoff catheter leads to better function than does the open procedure; it allows immediate start of dialysis without fluid leakage and permits simultaneous performance of other laparoscopic procedures.

Intracystic pressure and viability in hydatid disease of the liver.

BACKGROUND: Knowledge on the viability of hydatid cysts of the liver during operation is important to the surgeon may dictate the peri-operative therapeutic manoeuvre undertaken. PATIENTS AND METHODS: A prospective study was performed on 23 patients with 28 hydatid cysts of the liver to assess whether intracystic pressure (ICP) could predict viability of protoscoleces. All patients received albendazole (10 mg/kg body weight/day) for 5 days pre-operatively. The ICP was measured from the apex of the cyst, after laparotomy, using a 16-G needle connected to a water manometer. After manometry, the cyst contents were aspirated and the viability of protoscoleces assessed by their flame cell activity, motility and ability to exclude 5% aqueous eosin. RESULTS: The median ICP was 54 +/- 21 cmH2O for 17 viable cysts and zero for 8 non-viable cysts, while 1 additional non-viable cyst and 2 sterilized cysts had high ICP (sensitivity, 100%; specificity, 72%; accuracy, 89%). The median diameter of the viable cysts was 9.3 +/- 3.5 cm and the non-viable cysts 10.7 +/- 2.6 cm. In the right lobe were located 12 viable and 8 non-viable cysts and in the left lobe, 5 viable and 3 non-viable cysts. No significant difference in diameter or ICP were noted between the hepatic lobes. CONCLUSIONS: These findings suggest that the measurement of ICP is a simple, cheap and reliable method for assessment of the viability of hydatid cysts of the liver.