A Mixture Method for Robust Detection HCV Early Diagnosis Biomarker with ML Approach and Molecular Docking.

Given the substantial correlation between early diagnosis and prolonged patient survival in HCV patients, it is vital to identify a reliable and accessible biomarker. The purpose of this research was to identify accurate miRNA biomarkers to aid in the early diagnosis of HCV and to identify key target genes for anti-hepatic fibrosis therapeutics. The expression of 188 miRNAs in 42 HCV liver patients with different functional states and 23 normal livers were determined using RT-qPCR. After screening out differentially expressed miRNA (DEmiRNAs), the target genes were predicted. To validate target genes, an HCV microarray dataset was subjected to five machine learning algorithms (Random Forest, Adaboost, Bagging, Boosting, XGBoost) and then, based on the best model, importance features were selected. After identification of hub target genes, to evaluate the potency of compounds that might hit key hub target genes, molecular docking was performed. According to our data, eight DEmiRNAs are associated with early stage and eight DEmiRNAs are linked to a deterioration in liver function and an increase in HCV severity. In the validation phase of target genes, model evaluation revealed that XGBoost (AUC = 0.978) outperformed the other machine learning algorithms. The results of the maximal clique centrality algorithm determined that CDK1 is a hub target gene, which can be hinted at by hsa-miR-335, hsa-miR-140, hsa-miR-152, and hsa-miR-195. Because viral proteins boost CDK1 activation for cell mitosis, pharmacological inhibition may have anti-HCV therapeutic promise. The strong affinity binding of paeoniflorin (-6.32 kcal/mol) and diosmin (-6.01 kcal/mol) with CDK1 was demonstrated by molecular docking, which may result in attractive anti-HCV compounds. The findings of this study may provide significant evidence, in the context of the miRNA biomarkers, for early-stage HCV diagnosis. In addition, recognized hub target genes and small molecules with high binding affinity may constitute a novel set of therapeutic targets for HCV.

Protein Abundance of Drug Metabolizing Enzymes in Human Hepatitis C Livers.

Hepatic drug metabolizing enzymes (DMEs), whose activity may be affected by liver diseases, are major determinants of drug pharmacokinetics. Hepatitis C liver samples in different functional states, i.e., the Child-Pugh class A (n = 30), B (n = 21) and C (n = 7) were analyzed for protein abundances (LC-MS/MS) and mRNA levels (qRT-PCR) of 9 CYPs and 4 UGTs enzymes. The protein levels of CYP1A1, CYP2B6, CYP2C8, CYP2C9, and CYP2D6 were not affected by the disease. In the Child-Pugh class A livers, a significant up-regulation of UGT1A1 (to 163% of the controls) was observed. The Child-Pugh class B was associated with down-regulation of the protein abundance of CYP2C19 (to 38% of the controls), CYP2E1 (to 54%), CYP3A4 (to 33%), UGT1A3 (to 69%), and UGT2B7 (to 56%). In the Child-Pugh class C livers, CYP1A2 was found to be reduced (to 52%). A significant trend in down-regulation of the protein abundance was documented for CYP1A2, CYP2C9, CYP3A4, CYP2E1, UGT2B7, and UGT2B15. The results of the study demonstrate that DMEs protein abundances in the liver are affected by hepatitis C virus infection and depend on the severity of the disease.

Protein Abundance of Drug Transporters in Human Hepatitis C Livers.

Transmembrane drug transport in hepatocytes is one of the major determinants of drug pharmacokinetics. In the present study, ABC transporters (P-gp, MRP1, MRP2, MRP3, MRP4, BCRP, and BSEP) and SLC transporters (MCT1, NTCP, OAT2, OATP1B1, OATP1B3, OATP2B1, OCT1, and OCT3) were quantified for protein abundance (LC-MS/MS) and mRNA levels (qRT-PCR) in hepatitis C virus (HCV)-infected liver samples from the Child-Pugh class A (n = 30), B (n = 21), and C (n = 7) patients. Protein levels of BSEP, MRP3, MCT1, OAT2, OATP1B3, and OCT3 were not significantly affected by HCV infection. P-gp, MRP1, BCRP, and OATP1B3 protein abundances were upregulated, whereas those of MRP2, MRP4, NTCP, OATP2B1, and OCT1 were downregulated in all HCV samples. The observed changes started to be seen in the Child-Pugh class A livers, i.e., upregulation of P-gp and MRP1 and downregulation of MRP2, MRP4, BCRP, and OATP1B3. In the case of NTCP, OATP2B1, and OCT1, a decrease in the protein levels was observed in the class B livers. In the class C livers, no other changes were noted than those in the class A and B patients. The results of the study demonstrate that drug transporter protein abundances are affected by the functional state of the liver in hepatitis C patients.

Gene Expression and Protein Abundance of Hepatic Drug Metabolizing Enzymes in Liver Pathology.

Hepatic drug metabolizing enzymes (DMEs) markedly affect drug pharmacokinetics. Because liver diseases may alter enzymatic function and in turn drug handling and clinical efficacy, we investigated DMEs expression in dependence on liver pathology and liver failure state. In 5 liver pathologies (hepatitis C, alcoholic liver disease, autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis) and for the first time stratified according to the Child-Pugh score, 10 CYPs (CYP1A1, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5) and 4 UGTs (UGT1A1, UGT1A3, UGT2B7 and UGT2B) enzymes were quantified for protein abundance (LC-MS/MS) and gene expression (qRT-PCR). CYP2E1 was the most vulnerable enzyme, and its protein levels were significantly reduced just in Child-Pugh class A livers. The protein abundance of CYP1A1, CYP2B6, CYP2C19, CYP2D6 as well as UGT1A1, UGT1A3 and UGT2B15 was relatively stable in the course of progression of liver function deterioration. Alcoholic liver disease and primary biliary cholangitis were involved in the most prominent changes in the protein abundances, with downregulation of 6 (CYP1A2, CYP2C8, CYP2D6, CYP2E1, CYP3A4, UGT2B7) and 5 (CYP1A1, CYP2B6, CYP2C8, CYP2E1, CYP3A4) significantly downregulated enzymes, respectively. The results of the study demonstrate that DMEs protein abundance is affected both by the type of liver pathology as well as functional state of the organ.

Hepatic drug-metabolizing enzymes and drug transporters in Wilson's disease patients with liver failure.

BACKGROUND: Wilson's disease is a genetic disorder inherited in a recessive manner, caused by mutations in the copper-transporter ATP7B. Although it is a well-known disease, currently available treatments are far from satisfactory and their efficacy varies in individual patients. Due to the lack of information about drug-metabolizing enzymes and drug transporters profile in Wilson's disease livers, we aimed to evaluate the mRNA expression and protein abundance of selected enzymes and drug transporters in this liver disorder. METHODS: We analyzed gene expression (qPCR) and protein abundance (LC-MS/MS) of 14 drug-metabolizing enzymes and 16 drug transporters in hepatic tissue from Wilson's disease patients with liver failure (n = 7, Child-Pugh class B and C) and metastatic control livers (n = 20). RESULTS: In presented work, we demonstrated a downregulation of majority of CYP450 and UGT enzymes. Gene expression of analyzed enzymes ranged between 18 and 65% compared to control group and significantly lower protein content of CYP1A1, CYP1A2, CYP2C8, CYP2C9, CYP3A4 and CYP3A5 enzymes was observed in Wilson's disease. Moreover, a general decrease in hepatocellular uptake carriers from SLC superfamily (significant at protein level for NTCP and OATP2B1) was observed. As for ABC transporters, the protein abundance of BSEP and MRP2 was significantly lower, while levels of P-gp and MRP4 transporters were significantly higher in Wilson's disease. CONCLUSIONS: Altered hepatic expression of drug-metabolizing enzymes and drug transporters in Wilson's disease patients with liver failure may result in changes of drug pharmacokinetics in that group of patients.

Identifying Differentially Expressed MicroRNAs, Target Genes, and Key Pathways Deregulated in Patients with Liver Diseases.

Liver diseases are important causes of morbidity and mortality worldwide. The aim of this study was to identify differentially expressed microRNAs (miRNAs), target genes, and key pathways as innovative diagnostic biomarkers in liver patients with different pathology and functional state. We determined, using RT-qPCR, the expression of 472 miRNAs in 125 explanted livers from subjects with six different liver pathologies and from control livers. ANOVA was employed to obtain differentially expressed miRNAs (DEMs), and miRDB (MicroRNA target prediction database) was used to predict target genes. A miRNA-gene differential regulatory (MGDR) network was constructed for each condition. Key miRNAs were detected using topological analysis. Enrichment analysis for DEMs was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). We identified important DEMs common and specific to the different patient groups and disease progression stages. hsa-miR-1275 was universally downregulated regardless the disease etiology and stage, while hsa-let-7a*, hsa-miR-195, hsa-miR-374, and hsa-miR-378 were deregulated. The most significantly enriched pathways of target genes controlled by these miRNAs comprise p53 tumor suppressor protein (TP53)-regulated metabolic genes, and those involved in regulation of methyl-CpG-binding protein 2 (MECP2) expression, phosphatase and tensin homolog (PTEN) messenger RNA (mRNA) translation and copper homeostasis. Our findings show a novel panel of deregulated miRNAs in the liver tissue from patients with different liver pathologies. These miRNAs hold potential as biomarkers for diagnosis and staging of liver diseases.

Monocarboxylate Transporter 1 (MCT1) in Liver Pathology.

Membrane monocarboxylate transporter 1 (SLC16A1/MCT1) plays an important role in hepatocyte homeostasis, as well as drug handling. However, there is no available information about the impact of liver pathology on the transporter levels and function. The study was aimed to quantify SLC16A1 mRNA (qRT-PCR) and MCT1 protein abundance (liquid chromatography-tandem mass spectrometry (LC---MS/MS)) in the livers of patients diagnosed, according to the standard clinical criteria, with hepatitis C, primary biliary cirrhosis, primary sclerosing hepatitis, alcoholic liver disease (ALD), and autoimmune hepatitis. The stage of liver dysfunction was classified according to Child-Pugh score. Downregulation of SLC16A1/MCT1 levels was observed in all liver pathology states, significantly for ALD. The progression of liver dysfunction, from Child-Pugh class A to C, involved the gradual decline in SLC16A1 mRNA and MCT1 protein abundance, reaching a clinically significant decrease in class C livers. Reduced levels of MCT1 were associated with significant intracellular lactate accumulation. The MCT1 transcript and protein did not demonstrate significant correlations regardless of the liver pathology analyzed, as well as the disease stage, suggesting posttranscriptional regulation, and several microRNAs were found as potential regulators of MCT1 abundance. MCT1 membrane immunolocalization without cytoplasmic retention was observed in all studied liver pathologies. Overall, the study demonstrates that SLC16A1/MCT1 is involved in liver pathology, especially in ALD.

Protein Abundance of Hepatic Drug Transporters in Patients With Different Forms of Liver Damage.

Hepatocellular transporter levels were quantified using quantitative reverse transcription polymerase chain reaction and liquid chromatography-tandem mass spectrometry methods. Liver function deterioration (Child-Pugh class C) produced significant protein abundance (mean values) increase (to healthy livers) in P-gp (to 260% (CV (coefficient of variation) 82%)) and MRP4 (CV 230%) (not detected in healthy livers), decrease in MRP2 (to 30% (CV 126%)), NTCP (to 34% (CV 112%)), OCT1 (to 35% (CV 153%)), OATP1B1 (to 46% (CV 73%)), and OATP2B1 (to 27% (CV 230%)), whereas BSEP (CV 99%), MRP3 (CV 106%), OAT2 (CV 97%), OCT3 (CV 113%), and OATP1B3 (CV 144%) remained unchanged. Alcoholic liver disease produced significant protein downregulation of MRP2 (to 30% (CV 134%)), NTCP (to 76% (CV 78%)), OAT2 (to 26% (CV 117%)), OATP1B1 (to 61% (CV 76%)), OATP1B3 (to 79% (CV 160%)), and OATP2B1 (to 73% (CV 90%)) of healthy tissue values. Hepatitis C produced BSEP (to 47% (CV 99%)) and OATP2B1 (to 74% (CV 91%)) protein reduction. Primary biliary cholangitis and primary sclerosing cholangitis demonstrated P-gp and MRP4 protein upregulation (to 350% (CV 47%) and 287% (CV 38%), respectively). Autoimmune hepatitis revealed P-gp (to 410% (CV 49%)) and MRP4 (CV 96%) increase, and MRP2 (to 18% (CV 259%)) protein decrease. Drug transporters' protein abundance depends on liver pathology type and its functional state.

Expression of genes involved in xenobiotic metabolism and transport in end-stage liver disease: up-regulation of ABCC4 and CYP1B1.

BACKGROUND: Expression of drug-metabolizing enzymes and drug transporters in liver is mainly regulated by a system of nuclear receptors. The aim of the current study was to investigate the expression of nuclear receptors, as well as these enzymes and transporters, in liver samples from patients suffering from end-stage liver disease of various etiologies (HCV infection, alcohol liver disease, and primary sclerosis cholangitis). METHODS: Gene expression was measured using quantitative real-time PCR with surgical specimens from livers of patients with end-stage liver disease, and non-tumoral liver tissue that served as control. RESULTS: Our study confirmed that the expression of most phase I enzymes is suppressed in end-stage liver disease, and is correlated with a decrease in NR1I2 and NR1I3, the main regulators of xenobiotic metabolism. While mRNA levels of phase II enzymes were generally unchanged, some ABC transporters were up-regulated. The most spectacular increases in expression were observed with ABCC4 (MRP4) - at the mRNA level, and CYP1B1 - at both the mRNA and protein levels. We also demonstrated that IL-6 can induce CYP1B1 expression independently of CYP1A1, in a human hepatocellular liver carcinoma cell line. CONCLUSIONS: As CYP1B1 is an enzyme which converts various substrates into carcinogenous metabolites, its overexpression in liver may be one of the factors increasing the risk of hepatic cancers in patients with liver disease. CYP1A1 and CYP1B1 are often referred to as model AHR target genes, but CYP1A1 was down-regulated in diseased liver samples. This points to the existence of differences in regulation of these two genes.

Aggressive surgical management of recurrent lymph node and pancreatic head metastases of resected fibrolamellar hepatocellular carcinoma: a case report.

CONTEXT: Fibrolamellar hepatocellular carcinoma is a rare liver tumor with the propensity to metastasize to the lymph nodes months or years after initial surgery. However, its metastatic spread to the pancreas was previously reported only in a child. CASE REPORT: We present an unusual case of a young female patient who was repeatedly treated by surgical excision of abdominal and mediastinal lymph node recurrences between 2 and 6 years after left hepatic lobectomy for fibrolamellar hepatocellular carcinoma. At 8 years following her initial surgery, the patient was diagnosed with pancreatic head metastasis and a pancreaticoduodenectomy was performed. Postoperative course was uneventful and the patient did not experience recurrence within the last 18 months. CONCLUSION: The metastasis of fibrolamellar hepatocellular carcinoma to the pancreas is highly exceptional but possible and its excision appears warranted as well.

Liver transplantation as an ultimate step in the management of iatrogenic bile duct injury complicated by secondary biliary cirrhosis.

BACKGROUND: This report summarizes a single center's experience with liver transplantation (LT) performed for secondary biliary cirrhosis resulting from iatrogenic bile duct injury (BDI) sustained during cholecystectomy. MATERIAL/METHODS: Secondary biliary cirrhosis was the indication for LT in 5 (1.7%) out of 300 LTs performed in our center between Feb 2002 and April 2011. We analyzed the medical history of the patients, perioperative course and outcome following LT. RESULTS: The BDI was classified as Strasberg A in 1 case, B in two cases, and E in 2 cases. There was no hepatic arterial or portal vein injury in any patient. All of the surgical repairs prior to the development of cirrhosis were performed in general surgical units. The median time between BDI and listing the patient for LT was 11 years. The cadaveric whole-organ LT was done in all patients using the Piggy-Back technique. All patients are alive with a median follow-up of 53 months. CONCLUSIONS: Liver transplantation in patients with secondary biliary cirrhosis appears to result from a series of inadequate multiple surgical repairs following BDI. The immediate referral of such patients to centers with bile duct surgery experience is crucial.

Nuclear factor erythroid 2-like 2 (Nrf2) expression in end-stage liver disease.

The transcription factor Nrf2, encoded by NFE2L2 gene is a key regulator of cellular defense against oxidative and electrophilic stress, also governing the expression of many phase II detoxification enzymes. Nrf2 is negatively regulated by KEAP1 protein. Recent studies have shown that Nrf2 might also constitute an important mediator of inflammatory processes. In the current study the expression of Nrf2 in livers from patients with end-stage liver disease has been investigated. Surgical specimens were obtained from explanted livers of 24 patients with end-stage liver disease of different etiology. Control samples were obtained from nontumoral liver tissue from 6 patients with metastatic liver tumors. Nrf2 expression was evaluated by means of qRT-PCR, Western-blot and immunohistochemical staining. KEAP1 gene expression was investigated at mRNA level. The expression of the NFE2L2 gene was decreased in all groups of end-stage liver disease samples as compared with the controls (mean 0.470±1.20 of the value observed in the control samples, p=0.003). Decreased values of NFE2L2/KEAP1 mRNA ratio were also observed in end-stage liver disease groups (0.60±0.24 of the value observed in the control samples, p=0.019). The results were generally confirmed in Western-blot and immunohistochemical analysis of Nrf2 protein. Different expression pattern of Nrf2 regulated genes in end-stage liver disease samples were observed: glutamate-cysteine ligase (GCLC) and glutathione-S-transferase A1 (GSTA1) were significantly down-regulated in most liver disease groups, whereas heme oxidase 1 (HMOX1) and NAD(P)H dehydrogenase [quinone] 1 (NQO1) were not significantly suppressed. Treatment of HepG2 cells with pro-inflammatory cytokines resulted in significant decrease of GSTA1, NFE2L2 and GCLC expression, while the exposure had no significant influence on KEAP1, HMOX1, and NQO1 mRNA levels. Nrf2 deficiency may be one of the factors underlying impaired liver function in detoxification processes. It remains to be established in further studies if the observed decrease of Nrf2 expression is just a result of liver cirrhosis or is primary, playing a role in disease pathogenesis.

Direct pressure measurement in the hepatic artery during liver transplantation: can it prevent the "steal" syndrome?

Splenic artery "steal" syndrome after orthotopic liver transplantation (OLT) is an important cause of graft dysfunction. Direct pressure measurement in the hepatic (HA) and radial artery (RA) may identify patients at risk allowing its prevention. This observational study compared radial and hepatic mean arterial pressures (MAP) measured during 100 OLTs performed in 99 recipients, in whom the HA was considered suitable for the anastomosis. A difference of ≥5 mmHg between the radial and hepatic MAP was arbitrarily chosen as the criterion for inflow modulation. Seven patients fulfilled this criterion showing a MAP gradient that was significantly different compared to the others (-10.8±3.3 vs. 2.6±5.0; p<0.0001). They underwent splenic artery ligation (n=5), arcuate ligament division (n=1) and aortohepatic bypass grafting (n=1) that all resulted in immediate normalization of the arterial inflow pressure to the graft. The splenic artery "steal" syndrome occurred in one patient (day 2 after OLT) in whom the mean HA pressure normalized during OLT following arcuate ligament division, suggesting pathology within the graft as the most likely etiology. Our results indicate that radial MAP can reflect the hepatic MAP during OLT. If a substantial pressure gradient is found, it can be corrected by intraoperative splenic artery ligation or arcuate ligament division.

Pancreatoduodenectomy with a modified duct-to-mucosa pancreaticojejunostomy: an analysis of 101 consecutive patients.

BACKGROUND/AIMS: The aim of the study was to analyze in-hospital morbidity and mortality after pancreatoduodenectomy (PD) with a modified duct-to-mucosa pancreaticojejunostomy. METHODOLOGY: We retrospectively analyzed 101 consecutive patients who underwent PD at our center between January 2002 and December 2010. Two-layered duct-to-mucosa pancreaticojejunostomy was performed over an internal transanastomotic stent in all patients. RESULTS: The overall in-hospital morbidity and mortality rate was 48% and 6%, respectively. Three patients died as a consequence of local complications including mesenteric ischemia in two and acute necrotizing pancreatitis in one case. Pancreatic fistula occurred in one (1%) patient and was treated conservatively with good outcome. The wound infection was the most common surgical complication (20/101; 20%) and occurred more often in patients who had a biliary stent inserted endoscopically prior to surgery (15/38; 39%), as compared to those without the stent (5/63; 8%; p=0.0003). CONCLUSIONS: The results of the present study suggest that a two-layered duct-to-mucosa pancreaticojejunostomy with internal transanastomotic stent is a safe anastomosis, associated with a very low risk of pancreatic fistula. The presence of a biliary stent at the time of surgery represents a risk factor for the development of postoperative wound infection.

Laparoscopic adrenalectomy for functioning and non-functioning adrenal tumours.

BACKGROUND: The purpose of this study was a retrospective analysis of outcomes following laparoscopic adrenalectomy (LA) performed for benign adrenal tumours responsible for various endocrinological disorders. The patients were diagnosed with non-functioning (NFT) and functioning adrenal tumours (FT) including pheochromocytoma (PH), Conn's syndrome (CO) and Cushing's (CS) syndrome. MATERIAL AND METHODS: A total of 165 LAs were carried out between August 1995 and September 2009 via either the transperitoneal (n = 38) or retroperitoneal (n = 127) approach. The analysed factors included demographic data of patients, the American Association of Anaesthesiology score (ASA), indication for surgery, tumour size and side, intraoperative and postoperative outcome of LA including duration of surgery, blood loss, time until ambulation, length of hospital stay, time until return to normal activity, the complication rate, as well as the conversion rate to open adrenalectomy. RESULTS: There were 111 patients with NFT and 54 with FT. Patients with NFT were significantly older than those with CO (p < 0.05). The mean size of the lesion differed between CO and other adrenal tumours (p < 0.05) as well as between NFT and PH (p < 0.05). All the lesions except aldosteronomas were detected predominantly in the right adrenal gland (p < 0.05). However, despite the different characteristic and clinical disorders related to laparoscopically removed adrenal tumours, the intraoperative and postoperative outcomes did not significantly differ in most cases between the analysed groups of patients. CONCLUSION: This study shows that LA is a safe, effective, and well-tolerated procedure despite the hormonal activity of the removed lesions. Minimal invasive surgery may be recommended as the 'gold standard' in the treatment of both functioning and non-functioning benign tumours of the adrenal gland.

Surgical management and outcome of bile duct injuries following cholecystectomy: a single-center experience.

PURPOSE: Biliary injury is a severe complication of cholecystectomy. The Hepp-Couinaud reconstruction with the hepatic duct confluence and the left duct may offer best long-term outcome as long as the confluence remains intact (Bismuth I-III). Complex liver surgery is usually indicated in most proximal (Bismuth IV) injuries in non-cirrhotic patients. The aim of this study was to evaluate the surgical treatment and outcome of bile duct injuries managed in a referral hepatobiliary unit. METHODS: We retrospectively analyzed surgical management and outcome of biliary injuries following cholecystectomy in 35 patients (27 laparoscopic) referred to our center between June 2001 and December 2009. There was no liver cirrhosis diagnosed in any patient. High injuries (Bismuth III-IV) were found in 14 patients. Management after referral included the Hepp-Couinaud hepaticojejunostomy in 32 patients with Bismuth I-III injuries, which in four cases with biliary peritonitis was preceded by abdominal lavage and prolonged external biliary drainage. Liver transplantation was performed in two patients with Bismuth IV injuries. RESULTS: After median follow-up of 59 months (range, 6-102), 34 (97%) patients are alive and 32 (92%) remain in good general condition with normal liver function. One patient who had combined biliary and colonic injury died of sepsis before repair. Recurrent strictures following the Hepp-Couinaud repair developed in two (6%) patients with high injuries combined with right hepatic arterial injury. CONCLUSION: The Hepp-Couinaud hepaticojejunostomy offers durable results, even after previous interventions have failed. In case of diffuse biliary peritonitis, delayed biliary reconstruction following external biliary drainage may be the best option.

From open to laparoscopic adrenalectomy: thirty years' experience of one medical centre.

INTRODUCTION: Laparoscopic adrenalectomy (LA) has become the standardized treatment of benign adrenal lesions over the last two decades, making the indications to open adrenalectomy (OA) limited. The purpose of this study was to show the thirty years of experience in open (OA) and laparoscopic adrenalectomy (LA) gained in one medical centre as well as to compare the results of OA and LA performed for benign adrenal lesions. MATERIAL AND METHODS: Three hundred patients underwent 127 open and 173 laparoscopic adrenalectomies between 1979 and 2009 at M. Curie Hospital in Szczecin, Poland. Analyzed factors included patients demographic data, ASA score, indication for surgery, tumour size and side, characteristics of the removed tumours, intraoperative and postoperative outcome of LA and OA, postoperative pain sensation, intraoperative and postoperative complications, and conversion rate from LA to OA. Tumours with diameter exceeding 8 cm were excluded. RESULTS: There were no significant differences regarding the analyzed preoperative data in both groups of patients. The mean operative time was longer in the LA group (137 v. 82 min., p < 0.0001) and the blood loss was lower in LA group (110 v. 254 mL, p < 0.0001). The mean time until resumption of normal diet was shorter after LA (22 v. 44 h), as was the mean time until ambulation (17 v. 36 h), mean length of the hospital stay (4.6 v. 6.8 days), and mean time until return to normal activities (14 v. 23 days, p < 0.0001 for each difference). The analgesic requirement on the first and the second day postoperatively was lower in the LA group (p < 0.0001). The incidence of intraoperative and postoperative complications did not differ significantly between both analyzed groups. The rate of the conversion from LA to OA was 16%. The histopathological diagnosis was adenoma of the adrenal gland in the majority of cases. CONCLUSIONS: This study shows that LA is a safe, effective, and well-tolerated procedure. It may be recommended as a "gold standard" surgery in a case of benign functioning or non-functioning adrenal tumours with diameter less than 8 cm. (Pol J Endocrinol 2010; 61 (1): 94-101).

The arterial anastomosis in liver transplantation: complications, treatment and outcome.

BACKGROUND/AIMS: Arterial complications continue to be a major source of morbidity, graft loss and mortality after liver transplantation (OLT). In this study we analyzed the incidence, treatment and outcome of arterial complications in patients who underwent OLT in our center. METHODOLOGY: Between February 2002 and May 2009, 210 whole-organ OLTs were performed in 199 adults. Analyzed patients were divided into group I (the first 100 OLTs) and group II (subsequent 110 OLTs). Factors that could contribute to the development of arterial complications were analyzed. RESULTS: Fourteen (6.5%) arterial complications occurred in 13 patients resulting in graft loss in 4 (31%) and mortality in 5 (38%) cases. There were two (1%) serious intraoperative bleedings requiring major arterial reconstruction. The most frequent arterial complication was hepatic artery thrombosis (3.3%; 7/210), requiring re-OLT in 5 cases and resulting in death in 4 patients. Hepatic artery kinking was found in 3 (1.4%) patients while the splenic artery steal syndrome and hepatic artery stenosis coexistent with portal vein stenosis occurred in one patient each. The incidence of arterial complications (9% vs. 4.6%; p=NS), related graft loss (3% vs. 0.9%; p=NS) and mortality (4% vs. 0.9%; p=NS) were comparable in both groups. CONCLUSIONS: Arterial complications remain a major source of graft loss and mortality after OLT. Their occurrence and related graft loss and mortality were not associated with a significant learning curve in our series. Hepatic artery thrombosis although rare, is a devastating complication requiring re-OLT in majority of cases. Early diagnosis and prompt therapy are crucial to improve outcome.

Partington-rochelle pancreaticojejunostomy for chronic pancreatitis: analysis of outcome including quality of life.

BACKGROUND/AIMS: Obstruction of the main pancreatic duct in chronic pancreatitis (CP) leads to an increased intraductal and intraparenchymal pressure causing pain. In this study we evaluated the outcome of surgical treatment of CP including the quality of life following Partington-Rochellepancreaticojejunostomy (PRP) performed for intractable pain. METHODOLOGY: Between July 2002 and May 2008, PRP was performed in 17 patients in whom the diameter of the main pancreatic duct exceeded 7mm and there was no inflammatory tumor in the pancreatic head. Perioperative morbidity and mortality were analyzed in all patients. The long term outcome including the quality of life (Karnofsky index) was evaluated in 9 patients who were followed with a mean 28 (range 13-60) months since surgery. RESULTS: Complications in the postoperative period were found in 3 (18%) patients including 1 death due to a myocardial infarction shortly after surgery. All patients submitted to the long-term evaluation reported a significant (p < 0.0001) pain reduction by an average of 6.2 (5-8) points in a 10-points visual analogue scale. The Karnofsky index increased significantly from a mean 52% (40-70%) before surgery up to 82% (70-90%) following surgery and long-term. CONCLUSIONS: PRP leads to a substantial quality of life improvement in patients with CP.