BACKGROUND: Autoimmune hepatitis is a chronic, generally progressive inflammatory disorder of the liver, of which the cause is unclear. It was demonstrated that genetic factors are involved in its pathogenesis. Previous studies showed that human leukocyte antigen in the major histocompatibility complex (MHC) is associated with susceptibility to autoimmune hepatitis. Current genome scanning studies suggest that genes outside the MHC also play a critical role in autoimmune disorders. This article focuses on our current understanding of the polymorphisms of these genes and their roles in the pathogenesis of autoimmune hepatitis.
DATA SOURCES: Studies were identified by searching MEDLINE and PubMed for articles using the keywords autoimmune hepatitis, polymorphism, CTLA-4, Fas, TNF-α, TGF-β1, TBX21 and VDR up to May 2011. Additional papers were identified by a manual search of the references from key articles.
RESULTS: According to the case-control studies on genetic polymorphisms, at least six genes (CTLA-4, Fas, TNF-α, TGF-β1, TBX21 and VDR) are involved in autoimmune hepatitis besides HLA. So far, there has been no agreement about gene susceptibility and the actual clinical significance of these genes is still controversial.
CONCLUSION: Studies on gene polymorphisms outside the MHC and knowledge of genetic predispositions for autoimmune hepatitis may not only elucidate pathogenic mechanisms, but also provide new targets for therapy in the future.

BACKGROUND: Neurological injury is a common complication in the early period after liver transplantation, posing an enormous obstacle to treatment efficiency and patient survival. Nicorandil is a mitochondrial ATP-sensitive potassium channel (mitoKATP) opener. It has been reported to be effective in reducing brain injury in recent studies. However, it is still unclear whether nicorandil has cerebral protective effect in patients undergoing liver transplantation.
METHODS: Fifty patients scheduled for liver transplantation were randomly divided into a nicorandil group (group N) (n=25), in which patients received 10 mg nicorandil through a nasogastric tube 30 minutes before induction of anesthesia, and a control group (group C) (n=25) who received 10 mL normal saline. The Mini-Mental State Examination (MMSE) was performed before anesthesia (day 0), and on days 3 and 7 after surgery. Blood samples were obtained before induction of anesthesia (T1), and at 12 (T2) and 36 hours (T3) after surgery for determination of serum neuron-specific enolase (NSE) and S100β protein (S100β) concentrations.
RESULTS: During surgery, 5 patients in each group were eliminated due to severe reperfusion or renal insufficiency. Therefore, 20 patients remained in each group. The MMSE scores after operation were significantly lower than those before operation in group C. However, there was no difference at days 3 and 7 compared with day 0 in group N. Serum NSE concentrations after surgery were significantly higher than baseline (at T1) in both groups, except at T3 in group N. Serum S100β concentration after surgery was significantly higher than baseline (at T1) in both groups. The MMSE scores at days 3 and 7 in group N were significantly higher than those in group C. The concentrations of serum NSE and S100β at T2 and T3 in group N were significantly lower than those in group C.
CONCLUSIONS: Oral nicorandil, as a premedication before liver transplantation, improves postoperative MMSE scores. It also attenuates the increase of NSE and S100β in blood, indicating its cerebral protective effect.

BACKGROUND: Steroids have been the mainstay of immunosuppressive regimen in liver transplantation. However, the use of steroids is associated with various post-transplant complications. This study evaluated the efficacy and safety of reduced immunosuppressive regimen with steroids (steroid elimination within 24 hours post-transplant) in a cohort of Chinese liver transplant recipients.
METHODS: Seventy-six patients in line with the selection criteria were enrolled in this prospective study. All patients received anti-IL-2 receptor antibody induction and tacrolimus-based maintenance therapy. The recipients were divided into two groups according to the duration of steroid use: 40 transplant in a 3-month withdrawal group and the remaining 36 in a 24-hour elimination group. Recipient survival, post-operative infections, biopsy-proven acute rejection and steroid-resistant acute rejection, non-healing wound, recurrence of hepatitis B virus (HBV) and hepatocellular carcinoma (HCC), de novo diabetes, hyperlipidemia and hypertension were assessed in the two groups.
RESULTS: There was no significant difference in patient survival, incidence of acute rejection episodes and hyperlipidemia, and recurrence of HBV and HCC between the two groups. However, the incidence rates of post-transplant infection, non-healing wound, de novo diabetes and hypertension were significantly lower in the 24-hour elimination group than in the 3-month withdrawal group (all P values <0.05).
CONCLUSION: Under anti-IL-2 receptor antibody induction and tacrolimus-based maintainance, steroid elimination within 24 hours post-transplant is associated with reduced steroid-related complications without increasing the risk of rejection.

BACKGROUND: The use of livers from nonviable fetuses is particularly attractive for its potential to solve the current limitations of organ availability for the pediatric recipient. Therefore, it is essential to study the feasibility of orthotopic fetal liver transplantation.
METHOD: We measured the hepatic and extra-hepatic anatomical structures of fetal and neonatal lambs and established an orthotopic liver transplantation model of the fetal lamb.
RESULTS: Mean weight of the liver of fetal lambs at 142 to 145 days gestation was 34.75 g and the mean diameter of the portal vein was 3.03 mm, the supra-hepatic vena cava was 5.88 mm, and the infra-hepatic vena cava was 4.00 mm, which matched the corresponding sizes in neonatal lambs aged up to 2 weeks. Using standard surgical procedures we completed the vascular inosculation of fetal liver. However, all the newborn lamb recipients survived less than 24 hours.
CONCLUSIONS: Orthotopic transplantation of the fetal liver is anatomically and technically feasible. However, perioperative issues need to be resolved prior to clinical application.

BACKGROUND: Systemic administration of CTLA4Ig has been applied in inducing immunological tolerance of hepatocyte implants, but has potential for systemic immune inhibition. This study was designed to induce hepatocyte immunological tolerance by locally expressing CTLA4Ig in an attempt to improve the effectiveness of cell transplantation.
METHODS: A normal human liver cell line (L02) was transfected with adenovirus vector containing the CTLA4Ig gene (Ad-CTLA4Ig-EGFP) in vitro, and the expression of CTLA4Ig by transfected cells was assessed by fluorescent imaging and immunocytochemical staining. Transfected cells then were injected into the spleen of Sprague-Dawley rats, the survival of cells was determined by immunohistochemistry, and the immune status was examined through CD4+ and CD69+ T cell-counts and ELISA detection of IL-2 in peripheral blood.
RESULTS: L02 cells expressed CTLA4Ig in the cytoplasm for >4 weeks. Surviving L02 cells were observed in the experimental group at 3 and 4 weeks post-transplantation, while none was detected in the control group. Furthermore, the percentages of CD4+ and CD4+CD69+ T cells in the CTLA4-transfected group were 24.5% and 45.1%, markedly lower than those in the control group at 4 weeks post-transplantation (P<0.01). Furthermore, the IL-2 level was also lower in the CTLA4-transfected group than in the control group.
CONCLUSION: Adenovirus-mediated CTLA4Ig gene transfer into human hepatocytes has the potential to become an effective method of inducing immunological tolerance in hepatocyte transplantation.

BACKGROUND: Pig islet xenotransplantation has the potential to overcome the shortage of donated human islets for islet cell transplantation in type 1 diabetes. Testing in non-human primate models is necessary before clinical application in humans. Intraportal islet transplantation in monkeys is usually performed by surgical infusion during laparotomy or laparoscopy. In this paper, we describe a new method of percutaneous transhepatic portal catheterization (PTPC) as an alternative to current methods of islet transplantation in rhesus monkeys.
METHODS: We performed ultrasound-guided PTPC in five adult rhesus monkeys weighing 7-8 kg, with portal vein catheterization confirmed by digital subtraction angiography. We monitored for complications in the thoracic and abdominal cavity. To evaluate the safety of ultrasound-guided PTPC, we recorded the changes in portal pressure throughout the microbead transplantation procedure.
RESULTS: Ultrasound-guided PTPC and infusion of 16 000 microbeads/kg body weight into the portal vein was successful in all five monkeys. Differences in the hepatobiliary anatomy of rhesus monkeys compared to humans led to a higher initial complication rate. The first monkey died of abdominal hemorrhage 10 hours post-transplantation. The second suffered from a mild pneumothorax but recovered fully after taking only conservative measures. After gaining experience with the first two monkeys, we decreased both the hepatic puncture time and the number of puncture attempts required, with the remaining three monkeys experiencing no complications. Portal pressures initially increased proportional to the number of transplanted microbeads but returned to pre-infusion levels at 30 minutes post-transplantation. The changes in portal pressures occurring during the procedure were not significantly different.
CONCLUSIONS: Ultrasound-guided PTPC is an effective, convenient, and minimally invasive method suitable for use in non-human primate models of islet cell transplantation provided that care is taken with hepatic puncture. Its advantages must be weighed against the risks of procedure-related complications.

BACKGROUND: Family history of hepatocellular carcinoma (HCC) has been identified as a risk factor for the development of the disease. The aim of this study is to evaluate the impact of such a history on HCC patients survival.
METHODS: Data of all HCC patients (n=4532) managed at our center from 1989 to 2008 were prospectively collected. The patients were quizzed on their various characteristics including family HCC history.
RESULTS: Totally 475 (10.48%) patients had a family history of HCC. They presented the disease at a significantly earlier age (median 53 vs 59 years, P<0.0001) and at an earlier stage (the United Network for Organ Sharing staging system). They had significantly better liver function in terms of Child-Pugh classification and serum albumin and bilirubin levels. Significantly more of them presented the disease without symptoms (44.0% vs 29.4%, P<0.0001). They also had significantly better overall survival under these specifications: patients in the whole study cohort, patients who had minor hepatectomy, patients with stage I disease, patients with stage II disease, and patients with stage III disease.
CONCLUSIONS: Contrary to what is generally believed, we found in this study cohort that patients with a family history of HCC had better overall survival than those without such a history. We believe this was in part due to earlier diagnosis of the disease and better liver function in this group of patients. However, the effects of genetic factors on the risk of HCC cannot be overlooked and are yet to be identified.

BACKGROUND: Hypersplenism is commonly seen in patients with non-cirrhotic portal hypertension (NCPH). While a splenectomy alone can effectively relieve the hypersplenism, it does not address the underlying portal hypertension. The present study was undertaken to analyze the impact of shunt and non-shunt operations on the resolution of hypersplenism in patients with NCPH. The relationship of symptomatic hypersplenism, severe hypersplenism and number of peripheral cell line defects to the severity of portal hypertension and outcome was also assessed.
METHODS: A retrospective analysis of NCPH patients with hypersplenism managed surgically between 1999 and 2009 at our center was done. Of 252 patients with NCPH, 64 (45 with extrahepatic portal vein obstruction and 19 with non-cirrhotic portal fibrosis) had hypersplenism and constituted the study group. Statistical analysis was done using GraphPad InStat. Categorical and continuous variables were compared using the chi-square test, ANOVA, and Student s t test. The Mann-Whitney U test and Kruskal-Wallis test were used to compare non-parametric variables.
RESULTS: The mean age of patients in the study group was 21.81±6.1 years. Hypersplenism was symptomatic in 70.3% with an incidence of spontaneous bleeding at 26.5%, recurrent anemia at 34.4%, and recurrent infection at 29.7%. The mean duration of surgery was 4.16±1.9 hours, intraoperative blood loss was 457±126 (50-2000) mL, and postoperative hospital stay 5.5±1.9 days. Following surgery, normalization of hypersplenism occurred in all patients. On long-term follow-up, none of the patients developed hepatic encephalopathy and 4 had a variceal re-bleeding (2 after a splenectomy alone, 1 each after an esophago-gastric devascularization and proximal splenorenal shunt). Patients with severe hypersplenism and those with defects in all three peripheral blood cell lineages were older, had a longer duration of symptoms, and a higher incidence of variceal bleeding and postoperative morbidity. In addition, patients with triple cell line defects had elevated portal pressure (P=0.001), portal biliopathy (P=0.02), portal gastropathy (P=0.005) and intraoperative blood loss (P=0.001).
CONCLUSIONS: Hypersplenism is effectively relieved by both shunt and non-shunt operations. A proximal splenorenal shunt not only relieves hypersplenism but also effectively addresses the potential complications of underlying portal hypertension and can be safely performed with good long-term outcome. Patients with hypersplenism who have defects in all three blood cell lineages have significantly elevated portal pressures and are at increased risk of complications of variceal bleeding, portal biliopathy and gastropathy.

BACKGROUND: Continuous lamivudine therapy is associated with high rates of YMDD mutations, which are the main causes of drug resistance. The current study explores the association of the emergence of YMDD mutations with pretherapy HBV genotype, HBV-DNA levels, HBeAg status, and serum alanine aminotransferase (ALT) levels in Chinese patients receiving lamivudine therapy for chronic hepatitis B.
METHODS: A total of 319 chronic hepatitis B patients who received lamivudine therapy for more than a year were enrolled in this study. YMDD mutations, HBV genotype, HBV-DNA levels, HBeAg status, and ALT levels were determined prior to their lamivudine treatment and every three months for a year of this therapy.
RESULTS: Among the 319 patients, 137 (42.95%) were infected with genotype B and 182 (57.05%) with genotype C. Up to 94 patients (29.47%) developed YMDD mutations within one year of lamivudine therapy. Furthermore, 50 patients with HBV genotype B and 44 patients with genotype C developed YMDD mutations (36.50% vs 24.18%, P<0.05). Logistic regression analysis showed that pretherapy HBV genotype, HBV-DNA levels, and HBeAg status are independent factors for the emergence of YMDD mutations (HBV genotype: OR=2.159, 95% CI 1.291-3.609, P=0.003; HBV-DNA: OR=1.653, 95% CI 1.231-2.218, P=0.001; HBeAg: OR=2.021, 95% CI 1.201-3.399, P=0.008).
CONCLUSIONS: HBV genotype, HBV-DNA levels, and HBeAg status at baseline are the independent factors associated with the emergence of YMDD mutations among Chinese patients receiving lamivudine therapy for chronic hepatitis B. These findings are helpful to the development of therapeutic strategies for these patients.

BACKGROUND: In vitro experiments and mice models have confirmed the importance of Sprouty 2 (Spry2) in inhibiting tumorigenesis and the progression of human cancer. However, the prognostic value of Spry2 in cancer patients remains unknown. This study is aimed to investigate the clinical relevance and prognostic significance of Spry2 expression in patients with hepatocellular carcinoma (HCC).
METHODS: With samples from 240 randomly-selected HCC patients who underwent surgery, immunohistochemistry was used to investigate Spry2 expression on tissue microarrays. The correlation of Spry2 expression with survival was estimated by the Kaplan-Meier method and univariate/multivariate Cox proportional hazard regression analysis. Spry2, ERK and phospho-ERK expression in HCC cell lines was detected by Western blotting.
RESULTS: Among the patients, 86.3% (207 of 240) exhibited down-regulation of Spry2 expression. Patients negative for Spry2 showed poorer survival (P=0.002) and increased recurrence (P=0.003). Multivariate analysis further established Spry2 as an independent predictor of postoperative recurrence in HCC patients (HR=1.47; 95% CI, 1.02-2.08; P=0.037). Down-regulation of Spry2 was associated with highly malignant phenotypes like vascular invasion and advanced tumor stages, and was positively correlated with the metastatic potential of HCC cell lines.
CONCLUSION: In the era of molecular targeted therapy, the expression of Spry2 in HCC may have relevant clinical significance and turn out to be a key factor in prognostic assessment and in treatment planning.

BACKGROUND: In China, hepatitis C virus (HCV) infection is characterized by an increasing prevalence during aging. This study was undertaken to evaluate the efficacy of treatment with peginterferon alpha-2a and ribavirin in elderly chronic hepatitis C (CHC) patients and study the factors related to the sustained virologic response (SVR). METHODS: The medical records of 417 patients treated with peginterferon and ribavirin were retrospectively analyzed. These patients were divided into two groups according to age: patients aged ≥65 years (n=140) and patients aged <65 years (n=277). The rate of ribavirin reduction or discontinuation and virologic response rates of the two groups were compared. The factors influencing SVR were studied by multivariate analysis. RESULTS: Ribavirin reduction or discontinuation was more frequent in patients aged ≥65 years than patients aged <65 years (37.1%, 52/140 vs 20.2%, 56/277; χ2=13.883, P<0.001). For genotype 1, patients aged ≥65 years had a higher relapse rate (50.0%, 42/84 vs 29.2%, 52/178; χ2=10.718, P=0.001) and a lower SVR rate (40.0%, 42/105 vs 60.0%, 126/210; χ2=11.250, P=0.001) than patients aged <65 years. There were no significant differences in virologic response rates between the two groups for patients with genotype 2. For genotype 1, in patients aged ≥65 years, the SVR rate of females was lower than that of males (28.6%, 12/42 vs 47.6%, 30/63; χ2=8.150, P=0.004); in the high viral load group, patients aged ≥65 years had a lower SVR rate than patients aged <65 years (30.0%, 18/60 vs 54.8%, 69/126; χ2=10.010, P=0.002). In multivariate logistic regression analysis, the independent factors associated with SVR in patients aged ≥65 years were sex (P=0.020), genotype (P=0.005), ribavirin reduction or discontinuation (P=0.009) and presence of rapid virologic response (RVR) (P=0.001). CONCLUSIONS: The rate of ribavirin reduction or discontinua-tion and relapse rate of patients aged ≥65 years with genotype 1 are high, and the SVR rate is low. Age has no impact on virologic responses rates for genotype 2. Among patients ≥65 years old, genotype 2 patients and genotype 1 patients with a low baseline viral load or achieving RVR or male may benefit from combination therapy.

BACKGROUND: 12-lipoxygenase (12-LOX) has been reported to be an important gene in cancer cell proliferation and survival, and tumor metastasis. However, its role in hepatocellular carcinoma (HCC) cells remains unknown.
METHODS: Expression of 12-LOX was assessed in a diethyl-nitrosamine-induced rat HCC model, and in SMMC-7721, HepG2 and L-02 cells using immunohistochemical staining and reverse transcriptase-polymerase chain reaction (RT-PCR). GST-π and Ki-67 were determined in vivo by immunohistochemical staining. Apoptosis was evaluated by TUNEL assay. Cell viability and apoptosis were determined by MTT assay and flow cytometry, respectively. Apoptosis-related proteins in SMMC-7721 and HepG2 cells were detected by Western blotting.
RESULTS: Immunohistochemical staining and RT-PCR showed that 12-LOX was over-expressed in rat HCC and two HCC cell lines, while the expression was inhibited by baicalein, a specific inhibitor of 12-LOX. Baicalein inhibited cell proliferation and induced apoptosis in rat HCC and both cell lines in a dose- and time-dependent manner. Our in vivo study demonstrated that baicalein also reduced neoplastic nodules. Mechanistically, baicalein reduced Bcl-2 protein expression coupled with a slight increase of the expression of Bax and activation of caspase-3. Furthermore, baicalein inhibited the activation of ERK-1/2 (phosphorylated). Interestingly, the effects of baicalein were reversed by 12(S)-HETE, a metabolite of 12-LOX.
CONCLUSIONS: Inhibition of 12-LOX leads to reduced numbers of HCC cells, partially caused by increased apoptosis. 12-LOX may be a potential molecular target for HCC prevention and treatment.

BACKGROUND: Dendritic cells (DCs) can initiate the expansion of regulatory T cells (Tregs), which play an indispensable role in inducing transplantation tolerance. Some studies have investigated the effect of the immunosuppressant rapamycin (Rapa) on Tregs in vitro. However, the in vivo effect of Rapa combined with immature DCs (iDCs) on Tregs is unknown. This study was undertaken to determine whether allogenic iDCs combined with a short course of Rapa have the ability to selectively expand the CD4+CD25+Foxp3+ Tregs in a rat model.
METHODS: Brown Norway rats were injected intravenously with 2×106 Lewis iDCs followed by 1 mg/kg per day Rapa intraperitoneally for 7 consecutive days. On day 8, the levels of CD4+CD25+Foxp3+ Treg cells in peripheral blood and spleen cells were analyzed by flow cytometry. IL-2, IL-4, TGF-β1, and IFN-γ levels in serum were assessed by ELISA. The experimental animals were divided into four groups: control, Rapa-treated, iDC-treated, and combination-treated.
RESULTS: CD4+CD25+Foxp3+ Tregs comprised 7%-8% of CD4+ T cells in control rats. Rapa combined with iDCs enhanced this percentage in the peripheral blood and spleen. However, the levels of Tregs did not significantly change after treatment with Rapa or iDCs alone. The levels of CD4+CD25-Foxp3+ T cells and CD4+CD25+Foxp3- T cells in CD4+ T cells did not significantly change in the combined group. The TGF-β1 level in serum from the combined group increased significantly compared with the other groups.
CONCLUSIONS: A significantly higher percentage of CD4+ CD25+ Foxp3+ Tregs was found in rats treated with allogenic iDCs and a short course of Rapa, along with an increase in the TGF-β1 level in serum. This improved protocol may be a promising therapeutic strategy to increase Tregs, which are beneficial to the induction of peritransplant tolerance.

BACKGROUND: Stenting of malignant hilar strictures remains a standard endoscopic treatment in patients with unresectable tumors. The aim of this two-center prospective study was to compare unilateral versus bilateral drainage in hilar malignant stenosis Bismuth-Corlette type II.
METHODS: During a 3-year period, a total of 49 patients with hilar tumors (Bismuth-Corlette type II) were referred for endoscopic treatment, following the criteria of unresectability. Ultrasound, computed tomography scan and magnetic resonance cholangiopancreatography (MRCP) were previously performed in all patients in order to facilitate endoscopic retrograde cholangiopancreatography (ERCP). The stricture was first passed by the hydrophilic guide-wire and then contrast medium was injected. Mechanical bile duct dilation was performed, followed by plastic stent placement only in the liver lobe which was previously opacified. The procedures were performed under conscious sedation. The patients were followed up for the next 12 months with a stent exchange every 3 months. Primary outcome was assessed by patient survival in the first 12 months after the procedure.
RESULTS: All 49 patients were treated with ERCP while 39 (79.59%) had successful stent placement. Among these, 32 had hilar cholangiocarcinoma (82%) and 7 (18%) had gallbladder cancer. Two groups of patients had Bismuth II strictures: A, 21 patients (54%) with unilateral contrast injection and drainage, and B, 18 (46%) with bilateral contrast injection and drainage. A total of 57 plastic stents were used (10 Fr, 89%; 11.5 Fr, 11%). Group B showed a lower bilirubin level 7 days after the procedure (P=0.008). Early complications were cholangitis (3 patients, 2 in group A and 1 in group B) and acute pancreatitis (2 patients, 1 each in A and B) with no statistical difference between the groups. Late complications were stent migration (5 patients, 1 in A and 4 in B) and stent clogging (6 patients, 2 in A and 4 in B) showing a significant difference between the groups (P<0.01). The first stent replacement after 3 months was successful in 87% of patients (four died due to disease progression and one due to cardiopulmonary insufficiency) showing no statistical difference between the groups. At 6 months follow-up, 72% patients survived, with no statistical difference between the groups. A final follow-up (12 months) showed the survival rate of 18% (4 patients from group A and 3 from group B) (P>0.05).
CONCLUSIONS: A minimally invasive approach, based on the criterion that every bile duct being opacified needs to be drained, is associated with a lower incidence of early complications. Considering that the clinical outcome measured by bilirubin level was lower in patients with bilateral drainage 7 days after the procedure, we assumed that drainage of 50% or more of the liver volume leads to sufficient drainage effectiveness.

BACKGROUND: Pancreaticopleural fistula (PPF) are uncommon. Complex multidisciplinary treatment is required due to nutritional compromise and sepsis. This is the first description of long-term follow-up of patients with PPF.
METHODS: Eleven patients with PPF treated at a specialist unit were identified. Causation, investigation, treatment and outcomes were recorded.
RESULTS: Pancreatitis was the etiology of the PPF in 9 patients, and in the remaining 2 the PPF developed following distal pancreatectomy. Cross-sectional imaging demonstrated the site of duct disruption in 10 cases, with endoscopic retrograde cholangiopancreatography identifying the final case. Suppression of pancreatic exocrine secretion and percutaneous drainage formed the mainstay of treatment.Five cases resolved following pancreatic duct stent insertion and three patients required surgical treatment for established empyema. There were no complications. In all cases that resolved there has been no recurrence of PPF over a median follow-up of 50 months (range 15-62).
CONCLUSIONS: PPF is an uncommon event complicating pancreatitis or pancreatectomy; pancreatic duct disruption is the common link. A step-up approach consisting of minimally invasive techniques treats the majority with surgery needed for refractory sepsis.

Duplication of the inferior vena cava (IVC) involves large veins on both sides of the aorta that join anteriorly at the level of the renal arteries to become the suprarenal IVC. We report CT scan and intraoperative images of a patient with duplication of the IVC who underwent pancreaticoduodenectomy with para-aortic lymphadenectomy for carcinoma of the pancreatic head: nodal dissection along the left caval vein was not carried out. The anatomical background of the lymphatic flow to the para-aortic lymph nodes and the theoretic basis for lymph node dissection of the para-aortic area in cases of double IVC are highlighted. Lymphadenectomy along the left caval vein is not necessary in patients with double IVC who undergo pancreaticoduodenectomy with extended lymphadenectomy for carcinoma of the pancreatic head in the absence of preoperative appearance of para-aortic disease.