Transarterial embolization is an acceptable bridging therapy to hepatocellular carcinoma prior to liver transplantation

BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive malignant neoplasm that requires liver transplantation(LT).Despite patients with HCC being prioritized by most organ allocation systems worldwide,they still have to wait for long periods.Locoregional therapies(LRTs)are employed as bridging therapies in patients with HCC awaiting LT.Although largely used in the past,transarterial embolization(TAE)has been replaced by transarterial chemoembolization(TACE).However,the superiority of TACE over TAE has not been consistently shown in the literature.AIM To compare the outcomes of TACE and TAE in patients with HCC awaiting LT.METHODS All consecutive patients with HCC awaiting LT between 2011 and 2020 at a single center were included.All patients underwent LRT with either TACE or TAE.Some patients also underwent percutaneous ethanol injection(PEI),concom-itantly or in different treatment sessions.The choice of LRT for each HCC nodule was determined by a multidisciplinary consensus.The primary outcome was waitlist dropout due to tumor progression,and the secondary outcome was the occurrence of adverse events.In the subset of patients who underwent LT,complete pathological response and post-transplant recurrence-free survival were also assessed.RESULTS Twelve(18.5%)patients in the TACE group(only TACE and TACE+PEI;n=65)and 3(7.9%)patients in the TAE group(only TAE and TAE+PEI;n=38)dropped out of the waitlist due to tumor progression(P log-rank test=0.29).Adverse events occurred in 8(12.3%)and 2(5.3%)patients in the TACE and TAE groups,respectively(P=0.316).Forty-eight(73.8%)of the 65 patients in the TACE group and 29(76.3%)of the 38 patients in the TAE group underwent LT(P=0.818).Among these patients,complete pathological response was detected in 7(14.6%)and 9(31%)patients in the TACE and TAE groups,respectively(P=0.145).Post-LT,HCC recurred in 9(18.8%)and 4(13.8%)patients in the TACE and TAE groups,respectively(P=0.756).Posttransplant recurrence-free survival was similar between the groups(P log-rank test=0.71).CONCLUSION Dropout rates and posttransplant recurrence-free survival of TAE were similar to those of TACE in patients with HCC.Our study reinforces the hypothesis that TACE is not superior to TAE as a bridging therapy to LT in patients with HCC.

Molecular mechanisms of liver ischemia reperfusion injury:Insights from transgenic knockout models

Ischemia reperfusion injury is a major obstacle in liver resection and liver transplantation surgery.Understanding the mechanisms of liver ischemia reperfusion injury(IRI) and developing strategies to counteract this injury will therefore reduce acute complications in hepatic resection and transplantation,as well as expanding the potential pool of usable donor grafts.The initial liver injury is initiated by reactive oxygen species which cause direct cellular injury and also activate a cascade of molecular mediators leading to microvascular changes,increased apoptosis and acute inflammatory changes with increased hepatocyte necrosis.Some adaptive pathways are activated during reperfusion that reduce the reperfusion injury.IRI involves a complex interplay between neutrophils,natural killer T-cells cells,CD4+ T cell subtypes,cytokines,nitric oxide synthases,haem oxygenase-1,survival kinases such as the signal transducer and activator of transcription,Phosphatidylinositol 3-kinases/Akt and nuclear factor κβ pathways.Transgenic animals,particularly genetic knockout models,have become a powerful tool at elucidating mechanisms of liver ischaemia reperfusion injury and are complementary to pharmacological studies.Targeted disruption of the protein at the genetic level is more specific and maintained than pharmacological inhibitors or stimulants of the same protein.This article reviews the evidence from knockout models of liver IRI about the cellular and molecular mechanisms underlying liver IRI.

Veno occlusive disease: Update on clinical management

Hepatic veno-occlusive disease is a clinical syndrome characterized by hepatomegaly, ascites, weight gain and jaundice, due to sinusoidal congestion which can be caused by alkaloid ingestion, but the most frequent cause is haematopoietic stem cell transplantation (STC) and is also seen after solid organ transplantation. The incidence of veno occlusive disease (VOD) after STC ranges from 0 to 70%, but is decreasing. Survival is good when VOD is a mild form, but when it is severe and associated with an increase of hepatic venous pressure gradient > 20 mmHg, and mortality is about 90%. Prevention remains the best therapeutic strategy, by using non-myeloablative conditioning regimens before STC. Prophylactic administration of ursodeoxycholic acid, being an antioxidant and antiapoptotic agent, can have some benefit in reducing overall mortality. Defibrotide, which has pro-fibrinolytic and antithrombotic properties, is the most effective therapy; decompression of the sinusoids by a transjugular intrahepatic portosystemic shunt (TIPS) can be tried, especially to treat VOD after liver transplantation and when multiorgan failure (MOF) is not present. Liver transplantation can be the last option, but can not be considered a standard rescue therapy, because usually the concomitant presence of multiorgan failure contraindicates this procedure.

New insights into the coagulopathy of liver disease and liver transplantation

The liver is an essential player in the pathway of coagulation in both primary and secondary haemostasis. Only von Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrombotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore, these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrombopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haemostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery.

Decreased apoptosis in advanced-stage/high-grade hepatocellular carcinoma complicating chronic hepatitis C is mediated through the downregulation of p21 ras

Objective and background： Although p21 ras has been reported to be upregulated in hepatocellular carcinoma complicating chronic hepatitis C type I, p21 ras has a different role in advanced stages, as it has been found to be downregulated. The goal of this study was to investigate the status of p21 ras in early-stage/low-grade and late-stage/high-grade hepatocellular carcinoma and its possible link to apoptosis. Material and methods： Thirty-five cases each of chronic HCV hepatitis type 4 （group I） and cirrhosis with hepatocellular carcinoma （HCC） complicating chronic HCV hepatitis （groups Ⅱ and Ⅲ） were immunohistochemically evaluated using a p21 ras polyclonal antibody. The apoptotic index was determined in histologic sections using the terminal deoxynncleotidyl transferase-mediated d-UTP biotin nick end labeling （TUNEL） assay. Results： Significant differences （P=0.001） were detected in p21 ras protein expression between the three groups. A near 2-fold increase in p21 ras staining was observed in the cirrhotic cases compared to the hepatitis cases, and p21 ras expression was decreased in the HCC group, p21 ras expression correlated with stage （r=0.64, P--0.001） and grade （r=-0.65, P=0.001） in the HCC group and grade in the HCV group （r=0.44, P=0.008）. Both p21 ras expression and TUNEL-LI were significantly lower in large HCCs compared to small HCCs （P=0.01 each）. The TUNEL values were negatively correlated with stage in the HCC group （r=-0.85, P=0.001）. The TUNEL values were also negatively correlated with grade in both the HCV and HCC groups （r=0.89, P=0.001 and r=0.53, P=0.001, respectively）. The p21 ras scores were significantly correlated with the TUNEL-LI values in the HCC group （r=0.63, P=0.001） and HCV group （r=0.88, P=0.001）. Conclusions： p21 ras acts as an initiator in HCC complicating type 4 chronic HCV and is downregulated with HCC progression, which most likely promotes tumor cell survival because it facilitates the downregulation of apoptosis with tumor progression.

Liver preservation prior to transplantation: Past, present, and future

Since Dr. Thomas Starzl performed the first series of successful liver transplants(LTs), important advances have been made in immunosuppression, operative techniques, and postoperative care. In 1988, Belzer's group reported the first successful LT using the University of Wisconsin preservation solution(UW).Since then, UW has replaced EuroCollins solution and allowed prolonged and safer preservation of liver, kidney, and pancreas allografts, thus contributing to the improvement of transplant outcomes. Although UW is still considered the standard of care in the United States and in several countries worldwide, a recent meta-analysis revealed similar LT outcomes among UW, Celsior solution, and the Institut Georges Lopez-1 preservation solution, which were slightly superior to those obtained with histidine-tryptophan-ketoglutarate preservation solution.Dynamic preservation has been recently developed, and liver allografts are preserved mainly through the following methods: hypothermic machine perfusion, normothermic machine perfusion, and subnormothermic machine perfusion. Their use has the potential advantage of improving clinical results in LT involving extended criteria donor allografts. Although associated with increased costs, techniques employing machine perfusion of liver allografts have been considered clinically feasible. This editorial focuses on recent advances and future perspectives in liver allograft preservation.

Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine

AIM: To evaluate whether pyrrolidine dithiocarbamate (PDTC), an enhancer of HO production, attenuates intestinal IR injury.METHODS: Eighteen male rats were randomly allocated into three groups: (a) sham; (b) IR, consisting of 30 min of intestinal ischemia, followed by 2-h period of reperfusion; and (c) PDTC treatment before IR. Intestinal microvascular perfusion (IMP) was monitored continuously by laser Doppler fiowmetry. At the end of the reperfusion, serum samples for lactate dehydrogenase (LDH) levels and biopsies of ileum were obtained. HO activity in the ileum was assessed at the end of the reperfusion period.RESULTS: At the end of the reperfusion in the IR group,IMP recovered partially to 42.5% of baseline (P<0.05vs sham), whereas PDTC improved IMP to 67.3% of baseline (P<0.01 vs IR). There was a twofold increase in HO activity in PDTC group (2 062.66±106.11) as compared to IR (842.3±85.12) (P<0.001). LDH was significantly reduced (P<0.001) in PDTC group (585.6±102.4)as compared to IR group (1 973.8±306.5). Histological examination showed that the ileal mucosa was significantly less injured in PDTC group as compared with IR group.CONCLUSION: Our study demonstrates that PDTC improves the IMP and attenuates IR injury of the intestine possibly via HO production. Additional studies are warranted to evaluate the clinical efficacy of PDTC in the prevention of IR injury of the small intestine.

Emergency resection surgery for colorectal cancer: Patterns of recurrent disease and survival

AIM To evaluate prognostic pathological factors associated with early metachronous disease and adverse longterm survival in these patients.METHODS Clinical and histological features were analysed retrospectively over an eight-year period for prognostic impact on recurrent disease and overall survival in patients undergoing curative resection of a primary colorectal cancer. RESULTS A total of 266 patients underwent curative surgery during the study period. The median age of the study cohort was 68 year(range 26 to 91) with a followup of 7.9 years(range 4.6 to 12.6). Resection was undertaken electively in 225(84.6%) patients and emergency resection in 35(13.2%). Data on timing of surgery was missing in 6 patients. Recurrence was noted in 67(25.2%) during the study period and was predominantly early within 3 years(82.1%) and involved hepatic metastasis in 73.1%. Emergency resection(OR = 3.60, P = 0.001), T4 stage(OR = 4.33, P < 0.001) and lymphovascular invasion(LVI) (OR = 2.37, P = 0.032) were associated with higher risk of recurrent disease. Emergency resection, T4 disease and a high lymph node ratio(LNR) were strong independent predictors of adverse long-term survival. CONCLUSION Emergency surgery is associated with adverse disease free and long-term survival. T4 disease, LVI and LNR provide strong independent predictive value of longterm outcome and can inform surveillance strategies to improve outcomes.

Early radiological assessment of locally advanced pancreatic cancer treated with electrochemotherapy

AIM To report early imaging assessment of ablated area post electrochemotherapy(ECT) in patients with locally advanced pancreatic cancer(LAPC). METHODS ECT was performed in 19 LAPC patients enrolled in an approved ongoing clinical phase Ⅰ/Ⅱ study. Before and after ECT, 18 patients underwent computed tomography(CT) scan, 11 patients underwent morphological and functional magnetic resonance(MR) scan(dynamic contrast enhanced-MRI) calculating wash-in slope(WIS) and wash-out slope(WOS); diffusion weighted imaging calculating pseudo-diffusivity(Dp), perfusion fraction(fp) and tissue diffusivity(Dt); 10 patients underwentpositron emission tomography(PET). Response evaluation criteria in solid tumour(RECIST) on MR and CT were used to assess tumour therapy response. Choi on CT, PET response criteria in solid tumors(PERCIST) on PET and functional parameters on MR were used to evaluate treatment response.RESULTS For each patient no significant reduction was measurable by CT and MR using RECIST. According Choi criteria a partial response was obtained in 18/18(100.0%) patients. According PERCIST criteria 6/10(60.0%) patients showed a partial response, 3/10(30.0%) stable disease and 1/10(10.0%) progression disease. Moreover, using functional MR parameters, a significant reduction of viable tumour after ECT can be observed. According ΔWIS and ΔWOS 9/11(81.8%) patients exhibited a partial response and 2/11(18.2%) stable disease; 8/11(72.7%) patients were considered in partial response by ΔDp evaluation and 3/11(27.3%) in stable disease; according ΔDt 7/11(63.6%) patients showed a partial response, 1/11(9.1%) showed progression of disease and 3/11(27.3%) were stable. Perfusion fraction fp showed a significant reduction after ECT only in four patients. No significant difference was observed after ECT in signal intensity of T1-weighted images and T2-weighted images, and in equilibrium-phase of contrast study, according to χ2 test was observed. A good correlation was reported between ΔHounsfield unit and Δmaximum standardized uptake value and between Δfp and ΔWOS, with a significant statistically difference(P < 0.05) using Spearman correlation coefficient.CONCLUSION Perfusion and diffusion MR derived parameters, Choi, PERCIST criteria are more performant than morphological MR and CT criteria to assess ECT treatment response.

Quality of life assessment in patients with chronic pancreatitis receiving antioxidant therapy

AIM:To undertake a baseline study comparing quality of life(QoL) in patients with chronic pancreatitis(CP) on Antox to those with CP,matched for disease duration,who were not on this medication.METHODS:CP was defined according to the Zurich classification.Sixty eight consecutive patients with CP who were taking Antox(antioxidants) were compared with 69 consecutive control CP patients not on Antox.European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core questions 30 and Pancreatic Modification(28 questions) were used to assess QoL.Out of a total of 137 patients 28 in each group were matched for disease duration(within 12 mo).Median disease duration was 8(1-22) years in the Antox group and 7(1-23) years in the Non-Antox cohort(P = NS,Mann-Whitney U-test).Other parameters(age,gender,etiology,endocrine and exocrine insufficiency) were similar between groups.RESULTS:Median visual analogue pain score in the Antox group was 3(0-8) compared with 6(0-8) in the Non-Antox group(P < 0.01).Perceptions of cognitive,emotional,social,physical and role function were impaired in the Non-Antox group compared to Antox patients(P < 0.0001,P = 0.0007,P = 0.0032 and P < 0.005 and P < 0.001,respectively).Analgesics and opiate usage was significantly lower in the Antox group(P < 0.01).Overall physical health and global QoL was better in the Antox group(P < 0.0001,95% CI:1.5-3).CONCLUSION:Contemporary quality of life assessments show that after correction for disease duration and cigarette smoking,patients with CP taking antox had better scores than non-antox controls.

Reappraisal of xenobiotic-induced,oxidative stress-mediated cellular injury in chronic pancreatitis:A systematic review

AIM:To reappraise the hypothesis of xenobiotic induced,cytochrome P450-mediated,micronutrient-deficient oxidative injury in chronic pancreatitis.METHODS:Individual searches of the Medline and Embase databases were conducted for each component of the theory of oxidative-stress mediated cellular injury for the period from 1st January 1990 to 31st December2012 using appropriate medical subject headings.Boolean operators were used.The individual components were drawn from a recent update on theory of oxidative stress-mediated cellular injury in chronic pancreatitis.RESULTS:In relation to the association between exposure to volatile hydrocarbons and chronic pancreatitis the studies fail to adequately control for alcohol intake.Cytochrome P450(CYP)induction occurs as a diffuse hepatic and extra-hepatic response to xenobiotic exposure rather than an acinar cell-specific process.GSH depletion is not consistently confirmed.There is good evidence of superoxide dismutase depletion in acute phases of injury but less to support a chronic intraacinar depletion.Although the liver is the principal siteof CYP induction there is no evidence to suggest that oxidative by-products are carried in bile and reflux into the pancreatic duct to cause injury.CONCLUSION:Pancreatic acinar cell injury due to short-lived oxygen free radicals(generated by injury mediated by prematurely activated intra-acinar trypsin)is an important mechanism of cell damage in chronic pancreatitis.However,in contemporary paradigms of chronic pancreatitis this should be seen as one of a series of cell-injury mechanisms rather than a sole mediator.

Immune-mediated bile duct injury:The case of primary biliary cirrhosis

Autoimmune cholangitis would be the appropriate name to define the immune-mediated bile duct injury following the breakdown of tolerance to mitochondrial proteins and the appearance of serum autoantibodies and autoreactive T cells.Nevertheless,the conditionis universally named primary biliary cirrhosis(PBC).The disease etiology and pathogenesis remain largely unknown despite the proposed lines of evidence.One twin study and numerous epidemiology reportssuggest that both a susceptible genetic background and environmental factors determine disease onsetwhile a recent genome-wide association study proposed highly significant associations with several commongenetic polymorphisms in subgroups of patients.Specific infectious agents and chemicals may contribute to the disease onset and perpetuation in a geneticallysusceptible host,possibly through molecular mimicry.Importantly,several murine models have been proposed and include strains in which PBC is genetically determined or induced by immunization with chemicals and bacteria.From a pathogenetic standpoint,new exciting data have demonstrated the unique apoptotic features of bile duct cells that allow the mitochondrial autoantigens to be taken up in their intact form within apoptotic blebs.We are convinced that the application of the most recent molecular techniques will soon pro-vide developments in PBC etiology and pathogenesis with likely implications in diagnostics and therapeutics.

Retransplantation for graft failure in chronic hepatitis C infection: A good use of a scarce resource?

AIM: To investigate the outcome of patients with hepatitis C virus (HCV) infection undergoing liver retransplantation. METHODS: Using the UK National Registry, patients undergoing liver transplantation for HCV-related liver disease were identified. Data on patient and graft characteristics, as well as transplant and graft survival were collected to determine the outcome of HCV patients undergoing retransplantation and in order to identify factors associated with transplant survival. RESULTS: Between March 1994 and December 2007, 944 adult patients were transplanted for HCV-related liver disease. At the end of follow-up, 617 of these patients were alive. In total, 194 (21%) patients had first graft failure and of these, 80 underwent liver retransplantation, including 34 patients where the first graft failed due to recurrent disease. For those transplanted for HCV-related disease, the 5-year graft survival in those retransplanted for recurrent HCV was 45% [95% confidence interval (CI): 24%-64%] compared with 80% (95% CI: 62%-90%) for those retransplanted for other indications (P = 0.01, log-rank test); the 5-year transplant survival after retransplantation was 43% (95% CI: 23%-62%) and 46% (95% CI: 31%-60%), respectively (P = 0.8, log-rank test). In univariate analysis of all patients retransplanted, no factor analyzed was significantly associated with transplant survival. CONCLUSION: Outcomes for retransplantation in patients with HCV infection approach agreed criteria for minimum transplant benefit. These data support selective liver retransplantation in patients with HCV infection.

Management of hepatitis C infection before and after liver transplantation

Chronic hepatitis C(CHC) is the most common indication for liver transplantation(LT). Aggressive treatment of hepatitis C virus(HCV) infection before cirrhosis development or decompensation may reduce LT need and risk of HCV recurrence post-LT. Factors associated with increased HCV risk or severity of recurrence include older age, immunosuppression, HCV genotype 1 and high viral load at LT. HCV recurrence post-LT leads to accelerated liver disease and cirrhosis development with reduced graft and patient survival. Currently, interferon(IFN)-based regimens can be used in dualagent regimens with ribavirin, in triple-agent antiviral strategies with direct-acting antivirals(e.g., protease inhibitors telaprevir or boceprevir), or before transplant in compensated patients to reduce HCV viral load to prevent or reduce the risk of post-LT recurrence and complications; they cannot be used in patients with decompensated cirrhosis. IFN-based regimens are used in less than half of HCV-infected patients waiting for LT due to extremely low efficacy and poor tolerability. However, antiviral therapy is indicated after LT in patients with histologically confirmed CHC despite tolerability issues. Improvements in side effect management have increased survival in patients achieving therapeutic targets. HCV treatment pre- and post-LT results in significant health care costs especially when lack of efficacy leads to disease worsening, although studies have shown sofosbuvir treatment before LT vs conventional post-LT dual antiviral is cost effective. The suboptimal efficacy and tolerability of IFN-based therapies, plus the significant economic burden, means the need for effective and well tolerated IFN-free antiHCV therapy for pre- and post-LT remains high.

Staged liver resection for colorectal metastases:a valuable strategy or a waste of time?

BACKGROUND:The use of staged liver resections for colorectal metastases has been increasing in recent times.The aim of this study was to determine the practices and outcomes of those surgeons attending the Australia and New Zealand Hepatic, Pancreatic and Biliary Association(ANZHPBA)meeting in 2008 who perform staged resections. METHODS:A questionnaire was sent to all members of the ANZHPBA and the international faculty who were invited to attend the annual meeting held in Coolum,Queensland, Australia in October 2008. RESULTS:There were 30 responses from 7 centres across the UK,Germany and Australia.Twenty-eight patients completed treatment.The study population was predominantly male (n=20,67%),with an average age of 59.4 years.All patients had bilobar disease.A right-sided first resection was planned in 39%of cases.Seventeen percent of patients underwent portal vein embolization prior to first resection.A second operation was performed at an average of 2.8 months from the first resection.Overall,50%(n=14)of patients eventually achieved a complete(R0)staged procedure.Twelve complications after the first resection were seen in 32%patients(n=9).Twenty- three patients underwent a second liver resection.Twenty-five complications after the second resection were present in 57% (n=13). CONCLUSIONS:Two-stage liver resections are beneficial if both stages are completed and an R0 resection is achieved. While there is increased morbidity and mortality,we believe that staged liver resection for colorectal metastases is a valuable strategy in selected cases.

Improving definition of the term “synchronous liver metastases” from colorectal cancer

The liver is the most frequent site of metastasis in colorectal cancer with up to a quarter of patients having liver metastases at the time of initial diagnosis and a further third subsequently developing liver lesions.Patients who present with metastatic liver disease after treatment of the primary(termed metachronous disease)receive care focused on this new metastatic disease.In contrast,the management of patients who present with colorectal cancer and concurrent liver

Contemporary techniques and outcomes of surgery for locally advanced renal cell carcinoma with focus on inferior vena cava thrombectomy:The value of a multidisciplinary team

Objective:To report the outcomes of surgery for a contemporary series of patients with locally advanced non-metastatic renal cell carcinoma(RCC)treated at a referral academic centre,focusing on technical nuances and on the value of a multidisciplinary team.Methods:We queried our prospective institutional database to identify patients undergoing surgical treatment for locally advanced(cT3-T4 N0-1 M0)renal masses suspected of RCC at our centre between January 2017 and December 2020.Results:Overall,32 patients were included in the analytic cohort.Of these,12(37.5%)tumours were staged as cT3a,8(25.0%)as cT3b,5(15.6%)as cT3c,and 7(21.9%)as cT4;6(18.8%)patients had preoperative evidence of lymph node involvement.Nine(28.1%)patients underwent nephron-sparing surgery while 23(71.9%)received radical nephrectomy.A template-based lymphadenectomy was performed in 12 cases,with evidence of disease in 3(25.0%)at definitive histopathological analysis.Four cases of RCC with level IV inferior vena cava thrombosis were successfully treated using liver transplant techniques without the need for extracorporeal circulation.While intraoperative complications were recorded in 3(9.4%)patients,no postoperative major complications(Clavien-Dindo3)were observed.At histopathological analysis,2(6.2%)patients who underwent partial nephrectomy harboured oncocytoma,while the most common malignant histotype was clear cell RCC(62.5%),with a median Leibovich score of 6(interquartile range 5e7).Conclusion:Locally advanced RCC is a complex and heterogenous disease posing several challenges to surgical teams.Our experience confirms that provided careful patient selection,surgery in experienced hands can achieve favourable perioperative,oncological,and functional outcomes.

Long-term outcome of patients with chronic pancreatitis treated with micronutrient antioxidant therapy

BACKGROUND： Micronutrient antioxidant therapy did not relieve pain in a European randomized trial of patients with chronic pancreatitis without malnutrition. However, intervention was undertaken only for 6 months leaving unanswered the question of whether long-term antioxidant therapy may modulate chronic pancreatitis. The aim of this study is to assess the outcome of long-term use of micronutrient antioxidant therapy in patients with chronic pancreatitis.METHODS： This is a single center clinical cohort report of patients with chronic pancreatitis prescribed micronutrient antioxidant therapy and followed for up to 10 years. Data were collected on demographic detail, clinic pain assessment, insulin requirements, interventions and outcome.RESULTS： A group of 30 patients with a diagnosis of chronic pancreatitis constitute the study population. Median age at time of diagnosis was 40 years（range 14-66）; 19（63%） were male and the median duration of symptoms was 2 years（range 0-18）. Alcohol was the dominant cause in 22（73%） patients and 16（53%） patients were Cambridge stage 1. Twenty-four（80%） patients had pain at presentation. During antioxidant treatment of 4 years（range 1-10）, pain decreased but the proportion with abdominal pain compared to those who were pain-free remained constant（P=0.16; two-way ANOVA with Bonferroni correction）. There was a significant increase in requirement for insulin（P=0.028） with time together with use of both endoscopic and surgical interventions.CONCLUSIONS： This is the first study to report long-term disease-specific outcome in patients with chronic pancreatitis prescribed micronutrient antioxidant therapy. There appears to be no effect of intervention on outcome.

Liver biopsy in a district general hospital:Changes over two decades

瞄准：在英国在一所区域综合医院在二十年学习肝活体检视实践。方法：我们识别了从辐射学和肠胃病学部门的数据库有在 1986 和 2006 之间的至少一肝活体检视的所有病人。有不完全的临床的数据的题目从学习被排除。结果：103 肝活体检视的一个总数被执行。临床的数据为 88 个病人是可得到的，与 95 活体检视。在 1986 和 1996 之间，(95%) 18 从活体检视执行了的 19 肝是盲目的，(33%) 6 为主要胆汁性肝硬变。在 1996 和 2006 之间，(18%) 14 从 76 活体检视是盲目的；并且指示是反常的肝测试(33%) ，丙肝(12%) 和目标活体检视(11%) 。肝活体检视在 5 是不起帮助作用的(5%) 题目。疼痛是肝活体检视(5%) 的最普通的复杂并发症。没有活体检视相关的死亡被报导。与盲目活体检视技术向更技术的失败和复杂并发症有一个趋势。结论：在小区域医院里执行的肝活体检视为安全、有用诊断并且阶段目的。反常的肝测试，非酒精的脂肝疾病和指向的活体检视是逐渐地普通的指示。指导超声的肝活体检视现在是比较喜欢的方法并且与更少复杂并发症被联系。