AK2 is an AMP-sensing negative regulator of BRAF in tumorigenesis.

The RAS-BRAF signaling is a major pathway of cell proliferation and their mutations are frequently found in human cancers. Adenylate kinase 2 (AK2), which modulates balance of adenine nucleotide pool, has been implicated in cell death and cell proliferation independently of its enzyme activity. Recently, the role of AK2 in tumorigenesis was in part elucidated in some cancer types including lung adenocarcinoma and breast cancer, but the underlying mechanism is not clear. Here, we show that AK2 is a BRAF-suppressor. In in vitro assays and cell model, AK2 interacted with BRAF and inhibited BRAF activity and downstream ERK phosphorylation. Energy-deprived conditions in cell model and the addition of AMP to cell lysates strengthened the AK2-BRAF interaction, suggesting that AK2 is involved in the regulation of BRAF activity in response to cell metabolic state. AMP facilitated the AK2-BRAF complex formation through binding to AK2. In a panel of HCC cell lines, AK2 expression was inversely correlated with ERK/MAPK activation, and AK2-knockdown or -knockout increased BRAF activity and promoted cell proliferation. Tumors from HCC patients showed low-AK2 protein expression and increased ERK activation compared to non-tumor tissues and the downregulation of AK2 was also verified by two microarray datasets (TCGA-LIHC and GSE14520). Moreover, AK2/BRAF interaction was abrogated by RAS activation in in vitro assay and cell model and in a mouse model of HRASG12V-driven HCC, and AK2 ablation promoted tumor growth and BRAF activity. AK2 also bound to BRAF inhibitor-insensitive BRAF mutants and attenuated their activities. These findings indicate that AK2 monitoring cellular AMP levels is indeed a negative regulator of BRAF, linking the metabolic status to tumor growth.

Surgical Strategy for T2 Gallbladder Cancer: Nationwide Multicenter Survey in Korea.

BACKGROUND: Although all guidelines suggest that T2 gallbladder (GB) cancer should be treated by extended cholecystectomy (ECx), high-level scientific evidence is lacking because there has been no randomized controlled trial on GB cancer. METHODS: A nationwide multicenter study between 2000 and 2009 from 14 university hospitals enrolled a total of 410 patients with T2 GB cancer. The clinicopathologic findings and long-term follow-up results were analyzed after consensus meeting of Korean Pancreas Surgery Club. RESULTS: The 5-year cumulative survival rate (5YSR) for the patients who underwent curative resection was 61.2%. ECx group showed significantly better 5YSR than simple cholecystectomy (SCx) group (65.4% vs. 54.0%, P = 0.016). For N0 patients, there was no significant difference in 5YSR between SCx and ECx groups (68.7% vs. 73.6%, P = 0.173). Systemic recurrence was more common than locoregional recurrence (78.5% vs. 21.5%). Elevation of cancer antigen 19-9 level preoperatively and lymph node (LN) metastasis were significantly poor prognostic factors in a multivariate analysis. CONCLUSION: ECx including wedge resection of GB bed should be recommended for T2 GB cancer. Because systemic recurrence was more common and recurrence occurred more frequently in patients with LN metastasis, postoperative adjuvant therapy should be considered especially for the patients with LN metastasis.

Alterations in the p53-SOCS2 axis contribute to tumor growth in colon cancer.

Altered expression of suppressor of cytokine signaling (SOCS) is found in various tumors. However, regulation of SOCS2 by upstream molecules has yet to be clearly elucidated, particularly in tumor cells. SCOCS2 expression was examined in tumor cells transfected with an inducible p53 expression system. The impact of SOCS2 on cell proliferation was measured with in vitro assays. Inhibition of tumorigenicity by SOCS2 knockdown was assessed via a mouse model. Expression profiles were compared and genes differentially expressed were identified using four types of p53-null cells (Saos, HLK3, PC3, and H1299) and the same cells stably expressing p53. Twelve kinds of target genes were simultaneously upregulated or downregulated by p53 in three or more sets of p53-null cells. SOCS2 expression was reciprocally inhibited by inducible p53 expression in p53-null cells, even colon cancer cells. SOCS2 promoter activity was inhibited by wild type but not mutant p53. SOCS2 knockdown inhibited tumor growth in vitro and in an animal xenograph model. SOCS2 overexpression was detected in a murine model of azoxymethane/dextran sulfate sodium-induced colitis-associated colon cancer compared to mock-treated controls. SOCS2 expression was heterogeneously upregulated in some human colon cancers. Thus, SOCS2 was upregulated by p53 dysfunction and seemed to be associated with the tumorigenic potential of colon cancer.

Low-dose mycophenolate mofetil in tablet form or capsule form combined with tacrolimus in the early period after kidney transplantation: a prospective randomized trial
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AIMS: The tablet form (500 mg) of mycophenolate mofetil (MMF) provides more convenience of taking drugs and cost-effectiveness than the capsule form (250 mg). We examined the efficacy and safety of MMF in its different forms combined with tacrolimus in kidney transplant recipients. METHODS: This multicenter, 26-week, randomized trial was performed to compare the efficacy and safety of the tablet form of MMF versus the capsule form of MMF in 156 kidney transplant recipients. Allograft function, the incidence of efficacy failure (biopsy-proven acute rejection (BPAR), death, graft loss, or loss to follow-up), and adverse events were compared. RESULTS: The mean dose (mg/day) of MMF at 26 weeks was comparable: 1,052.6 ± 194.2 in the tablet group vs. 1,155.6 ± 298.1 in the capsule group (p = 0.063). Trough levels of tacrolimus at 26 weeks were comparable. The mean estimated glomerular filtration rate of the tablet group at 26 weeks post-transplant was not inferior to that of the capsule group. The incidence of efficacy failure was similar in the two groups: tablet group, 5.2% and capsule group, 7.7% (difference -2.5%; 95% confidence interval -5.22 - 10.21%). The incidence of BPAR until 26 weeks post-transplant in the tablet group was 3.9%, compared to 7.7% in the capsule group (p = 0.346). There was no significant difference in the incidence of discontinuations and serious adverse events between the groups. CONCLUSION: Low-dose MMF in tablet form combined with tacrolimus can be considered as an efficacious and safe immunosuppressive regimen in the early period after kidney transplantation.
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Sectional Localization of a Small Hepatocellular Carcinoma in the Right Hepatic Lobe by Computed Tomography: Comparison between the Conventional and Portal Vein Tracing Methods.

PURPOSE: To compare the accuracy of the conventional and portal vein tracing methods in the right hepatic lobe in multidetector computed tomography (MDCT). MATERIALS AND METHODS: This retrospective study included patients with hepatocellular carcinoma (HCC) lesions in the right hepatic lobe who underwent multiphasic MDCT and C-arm CT hepatic arteriography (C-arm CTHA) for chemoembolization. The accuracies of the conventional and portal vein tracing methods were evaluated using C-arm CTHA as the gold standard. RESULTS: A total of 147 patients with 205 HCC nodules were included. The C-arm CTHA could identify all the tumour-feeding arteries and consequently demonstrated that 120 lesions were located in the anterior section, 78 in the posterior section, and 7 in the border zone. The accuracy rates of conventional vs. portal vein tracing methods were 71.7 % vs. 98.3 % for the anterior section lesions, 67.9 % vs. 96.2 % for the posterior section, and 28.6 % vs. 57.1 % for the border zone. The portal vein tracing method was more accurate than the conventional method (P<0.001). CONCLUSIONS: The portal vein tracing method should be used for sectional localization of HCCs in the right lobe, because it predicts the location more accurately than the conventional method. KEY POINTS: • Portal tracing method is more accurate than conventional method for tumour localization. • The conventional method is especially inaccurate in right anteroinferior or posterosuperior quadrants. • Scissurae between right anterior and posterior section may not be vertical but tilted.

C-KIT-positive undifferentiated tumor of the liver: A case report.

With recent advances in cancer stem cell analysis, it has been postulated that the transformation of hepatic stem and progenitor cells underlies the development of certain liver cancers. Human C-KIT is a transmembrane type III receptor protein with intrinsic tyrosine kinase activity that has been proposed as a marker for human embryonic stem cells. In addition, human C-KIT functions in maintaining the undifferentiated state of stem cells, and has been identified as a marker for human hematopoietic and hepatic stem/progenitor cells. The present study identified an unusual case of a C-KIT-positive hepatic tumor with an undifferentiated stem cell phenotype distinct from existing descriptions of liver tumors. A 69-year-old male with Ampulla of Vater (AoV) cancer was admitted to the hospital for the treatment of a hepatic mass that was incidentally detected during evaluation of AoV cancer. Microscopically, the hepatic tumor was composed of solidly packed small, round and uniform undifferentiated cells, which resembled that of a small-blue-round-cell tumor. The immunophenotype of neoplastic cells (C-KIT+/EpCAM+/E-cadherin+/keratin 7-/keratin 19-/α-fetoprotein-/albumin-) supported primitive stem cell features with no hepatic or biliary phenotypes. Polymerase chain reaction and direct DNA sequencing revealed no C-KIT mutations. It is suggested that this tumor may have originated from transformed C-KIT+/EpCAM+/E-cadherin+ cells, which are more primitive and undifferentiated than bipotential hepatic progenitor cells.

Region-specific differences in the human myenteric plexus: an immunohistochemical study using donated elderly cadavers.

PURPOSE AND METHODS: To identify site-dependent and individual differences in neuronal nitric oxide synthase (nNOS)-positive nerves of the myenteric plexus, we examined full-thickness walls of the stomach, pylorus, duodenum, ileum, colon, and rectum in 7 male and 8 female cadavers (mean ages, 80 and 87 years, respectively). RESULTS: The areas occupied by nNOS-positive nerve fibers in the myenteric plexus were fragmentary and overlapped with areas occupied by vasoactive intestinal polypeptide-positive fibers. The nNOS-positive fiber-containing areas per 1-mm length of intermuscular space tended to be larger at more anal sites, with positive areas four times greater in the rectum than in the stomach. Interindividual differences in rectal areas were extremely large, ranging from 0.017 mm(2) in one 80-year-old man to 0.067 mm(2) in another 80-year-old man. Similarly, the numbers of nNOS-positive ganglion cell bodies per 1-mm length in the rectum ranged from 4 to 28. These areas and numbers were weakly correlated (r = 0.62; p = 0.02). Interindividual differences in the rectum appeared not to depend on either age or gender. CONCLUSIONS: Anatomic studies using donated cadavers carried the advantage of obtaining any parts of intestine within an individual, in contrast to surgically removed specimens. We speculated excess control of evacuation with laxatives as one of causes of atrophy of the rectal myenteric plexus.

Surgical strategy for T1 gallbladder cancer: a nationwide multicenter survey in South Korea.

BACKGROUND: The aim of this study was to investigate the clinical features and clinical outcomes of T1 gallbladder (GB) cancer and to determine an appropriate surgical strategy for T1 GB cancer. METHODS: A nationwide multicenter study, in which 16 University Hospitals in Korea participated, was performed from 1995 to 2004. A total of 258 patients, 117 patients with T1a and 141 patients with T1b disease were enrolled. Clinicopathologic findings and long-term follow-up results were analyzed after a consensus meeting of the Korean Pancreas Surgery Club was held. RESULTS: Simple cholecystectomy was performed in 95 patients (81.2 %) with T1a tumor and in 89 patients (63.1 %) with T1b tumor (p < 0.01). Lymph node metastasis was observed in 2.9 % of T1a patients and in 9.9 % of T1b patients (p = 0.391). A significant difference in 5-year disease-specific survival (DSS) rates was observed between T1a and T1b patients (96.4 vs 84.8 %, respectively, p = 0.03). However, no significant 5-year DSS rate difference was observed between those who underwent simple cholecystectomy or extended cholecystectomy, regardless of whether lymph node dissection was performed or whether lymph node metastasis was present. There was no significant difference in recurrence-free survival between simple cholecystectomy and extended cholecystectomy. CONCLUSIONS: There was no superiority of extended cholecystectomy over simple cholecystectomy in the aspect of survival and recurrence especially in T1b gallbladder cancer. Furthermore, the effectiveness of regional lymphadenectomy for treatment purpose remains questionable. Therefore, simple cholecystectomy could be recommended as a surgical strategy of T1 gallbladder cancer.

Endoscopic stenting in bile duct cancer increases liver volume.

BACKGROUND: Objective evaluation tools for assessing the effectiveness of stenting in palliative treatment of malignant biliary obstruction are not satisfactory. Effects of biliary stenting on liver volume change have never been studied. OBJECTIVE: We aimed to use volumetry to analyze liver volume changes after endoscopic stenting in bile duct cancer according to the location and number of stents. DESIGN: Retrospective review. SETTING: University hospital. PATIENTS: Patients with a diagnosis of hilar or distal bile duct cancer and who underwent biliary metal stenting. INTERVENTIONS: ERCP with self-expandable metal stent placement. MAIN OUTCOME MEASUREMENTS: Liver volume change after biliary stenting and its comparison according to the location (hilar vs distal common bile duct) and number (hilar bilateral vs hilar unilateral). RESULTS: There were 60 patients; 31 were treated for hilar bile duct cancer (13 for bilateral stent and 18 for unilateral stent) and 29 for distal bile duct cancer. Overall mean follow-up duration was 11.7 ± 4.9 weeks. Liver volume increased 17.4 ± 24.1%. The rate of liver growth was rapid during the early period from 4 to 8 weeks. Stenting in hilar bile duct cancer tended to increase liver volume more than distal biliary stents (22.5% vs 11.9%, P = .091). In hilar bile duct cancer, unilateral and bilateral stents showed similar liver volume increases (20.1% and 25.8%, respectively; P = .512). LIMITATIONS: Single center, retrospective. CONCLUSIONS: Biliary stenting markedly increased liver volume in both hilar and distal bile duct cancer. Our data suggest that liver volume assessment could be a useful tool for evaluating stent efficacy.

A hybrid semi-automatic method for liver segmentation based on level-set methods using multiple seed points.

The present study developed a hybrid semi-automatic method to extract the liver from abdominal computerized tomography (CT) images. The proposed hybrid method consists of a customized fast-marching level-set method for detection of an optimal initial liver region from multiple seed points selected by the user and a threshold-based level-set method for extraction of the actual liver region based on the initial liver region. The performance of the hybrid method was compared with those of the 2D region growing method implemented in OsiriX using abdominal CT datasets of 15 patients. The hybrid method showed a significantly higher accuracy in liver extraction (similarity index, SI=97.6 ± 0.5%; false positive error, FPE = 2.2 ± 0.7%; false negative error, FNE=2.5 ± 0.8%; average symmetric surface distance, ASD=1.4 ± 0.5mm) than the 2D (SI=94.0 ± 1.9%; FPE = 5.3 ± 1.1%; FNE=6.5 ± 3.7%; ASD=6.7 ± 3.8mm) region growing method. The total liver extraction time per CT dataset of the hybrid method (77 ± 10 s) is significantly less than the 2D region growing method (575 ± 136 s). The interaction time per CT dataset between the user and a computer of the hybrid method (28 ± 4 s) is significantly shorter than the 2D region growing method (484 ± 126 s). The proposed hybrid method was found preferred for liver segmentation in preoperative virtual liver surgery planning.

Clinical feasibility and nutritional effects of early oral feeding after pancreaticoduodenectomy.

BACKGROUNDS/AIMS: Pancreaticoduodenctomy (PD) is associated with high rates of postoperative morbidity and mortality. Although many studies have shown that early postoperative enteral nutrition improves postoperative outcomes, limited clinical information is available on postoperative early oral feeding (EOF) after PD. The aim of this study was to evaluate the clinical feasibility, safety, and nutritional effects of EOF after PD. METHODS: Clinical outcomes were investigated in 131 patients who underwent PD between 2003 and 2013, including 81 whose oral feeding was commenced within 48 hours (EOF group) and 50 whose oral feeding was commenced after resumption of bowel movements (traditional oral feeding [TOF] group). Postoperative complications, energy intake, and length of stay (LOS) were reviewed. RESULTS: Demographic factors were similar in the two groups. The EOF group had a significantly shorter LOS (25.9±8.5 days vs. 32.3±16.3 days; p=0.01) than the TOF group. The rates of anastomotic leak (1.2% vs. 16%, p=0.00) and reoperation (3.7% vs. 20%, p=0.01) were significantly lower in the EOF group. In the clinically acute phase from postoperative day 1 to day 5, the mean daily calorie intake (847.0 kcal vs. 745.6 kcal; p=0.04) and mean daily protein intake (42.2 g vs. 31.9 g; p=0.00) in the EOF group were significantly higher than that in the TOF group. CONCLUSIONS: Postoperative EOF is a clinically safe, feasible, and effective method of nutritional support after PD.

Multicystic biliary hamartoma of the liver.

Multicystic biliary hamartoma (MCBH) is a very rare hamartomatous cystic nodule of the liver, which has recently been described as a new entity of a hepatic nodular lesion. We report a unique case of MCBH with a review of the literatures. A hepatic multicystic mass of segment 3 was detected in a 52-year-old male by abdominal computed tomography, and resection of this lesion was performed. Macroscopic examination revealed a 2.7×2.0 cm nodular mass with a multicystic honeycomb cut surface. Histologically, this lesion consisted of multiple dilated cystic ducts lined by biliary type epithelial cells, periductal glands and connective tissue, which included small amounts of hepatic parenchyma and blood vessels. Recognition of this unusual lesion is essential to avoid confusion with other cystic tumors of the liver, and to learn more about its natural history and response to treatment.

Clinicopathological characteristics and prognostic factors in combined hepatocellular carcinoma and cholangiocarcinoma.

BACKGROUNDS/AIMS: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an uncommon subtype of primary liver cancer that has rarely been reported in detail. This study was performed in order to evaluate the clinicopathological characteristics and prognostic factors of cHCC-CC in single center. METHODS: The clinicopathological features of patients diagnosed and operated with cHCC-CC at Chonbuk National Hospital between July 1998 and July 2007 were retrospectively studied by comparing them with patients with only hepatocellular carcinoma (HCC) who had undergone a hepatic resection during the same period. RESULTS: Ten out of 152 patients who had undergone a hepatic resection were diagnosed with cHCC-CC and thus included in this study (M : F=8 : 2, median age: 52±11.1 years). According to the parameters of the 7th American Joint Committee on Cancer T staging, there were 76 (50.0%), 44 (28.9%), 9 (5.9%), 18 (11.8%) and 5 (3.3%) patients with T stages 1, 2, 3a, 3b and 4, respectively. The overall survival period was longer in the HCC only group (68±40.4 months) than in the combined cHCC-CC group (23±40.1 months) (p<0.0001). The 5-year survival rate was 10% in the cHCC-CC group and 60% in the HCC group (p<0.0001). The disease free survival for patients with cHCC-HCC and HCC were 16±37.4 and 51±44.3 months, respectively (p<0.0001). Univariate analysis revealed that age, gender, transarterial chemoembolization (TACE), and T stage were statistically significant in terms of patient's overall survival. However, there were no significant clinicopathological factors identified by the multivariate analysis. CONCLUSIONS: Even after the hepatic resection in the HCC, the prognosis is poorer if the patient has cholangiocellular components compared to the usual HCC.

Retropancreatic fascia is absent along the pancreas facing the superior mesenteric artery: a histological study using elderly donated cadavers.

To determine the fascial configuration between the superior mesenteric artery and vein and the posterior aspect of the pancreas, we examined histological sections of 10 elderly donated cadavers without pathology in the abdomen. The retropancreatic fascia was absent along the pancreatic parenchyma facing the artery and vein. Abundant nerves along the artery were separated from the pancreas by loose tissue almost 10 mm in thickness. In addition, anterior renal fasciae facing the pancreatic body were not evident in these specimens, possibly due to the degeneration of the left adrenal gland with age. Thus, a definite renal fascia was restricted on the lateral and posterior sides of the left kidney. These findings suggest that interactions between a pancreatic tumor and nerves would require migration of cancer cells over a long distance. Conversely, attachment of the enlarged tumor mass to the nerves may be necessary for the invasion. The anterior renal fascia may fuse with the retropancreatic fascia.

Hispidin analogue davallialactone attenuates carbon tetrachloride-induced hepatotoxicity in mice.

In this study the protective effects of davallialactone (1), isolated from Inonotus xeranticus, have been examined against carbon tetrachloride (CCl4-induced acute liver injury. Mice received subcutaneous injection of 1 (2.5, 5, and 10 mg/kg) for three days before CCl4 injection (1 mg/kg). Protection from liver injury by 1 was confirmed by the observation of decreased serum transaminases and diminished necrosis of liver tissue. Reduced hepatic injury was very similar to that observed with silymarin, a known hepatoprotective drug used in this work for comparison. The groups treated with 1 had reduced reactive oxygen species (ROS), reduced serum malonyldialdehyde levels, and increased levels of liver Cu/Zn superoxide dismutase, as compared to the CCl4 control group. The expression of heme oxygenase-1 in the liver tissue was increased and the activity of liver cytochrome P4502E1 was restored in the mice treated with 1. In addition, levels of serum tumor necrosis factor-alpha (TNF-α), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2), numbers of macrophage, and cleaved caspase-3-positive hepatocytes were reduced in the groups treated with 1. These findings suggest that davallialactone has protective effects against CCl4-induced acute liver injury, and this protection is likely due to the suppression of ROS-induced lipid peroxidation and inflammatory response.

Right gastric venous drainage: angiographic analysis in 100 patients.

OBJECTIVE: To evaluate the pattern of right gastric venous drainage by use of digital subtraction angiography. MATERIALS AND METHODS: A series of 100 consecutive patients who underwent right gastric arteriography during transcatheter arterial chemoembolization for hepatocellular carcinoma were included in this study. Angiographic findings were retrospectively analyzed with respect to the presence or absence of the right and aberrant gastric veins, multiplicity of draining veins, aberrant right gastric venous drainage sites, and the termination pattern of aberrant right gastric veins (ARGVs). We also compared the relative size of the right and left gastric veins. RESULTS: A total of 49 patients collectively had 66 ARGVs. The common drainage sites for the ARGVs included the hepatic segment IV (n = 35) and segment I (n = 15). The termination pattern of ARGV could be classified into 4 different types. The most common type was termination as a superficial parenchymal blush formation in small areas without demonstrable portal branches. A statistically significant difference was found for the dominancy of the right gastric vein in gastric venous drainage between the two groups with or without ARGV (p < 0.05, Fisher's exact test). In the group of patients without ARGV (n = 51), the right gastric vein was equal to (n = 9) or larger than (n = 17) the left gastric vein in 26 patients (26 of 51, 51%). CONCLUSION: The incidence of ARGV is higher than expected with four distinct types in its termination pattern. The right gastric vein may play a dominant role in gastric venous drainage.

Surgical outcomes and prognostic factors influencing long-term survival in patients with gallbladder cancer.

BACKGROUNDS/AIMS: The aim of this study is to analyze surgical outcomes and prognostic factors affecting survival after surgical resection in patients with gallbladder cancer. METHODS: We retrospectively reviewed 86 patients treated surgically for gallbladder cancer from January 2000 to December 2009 at Chonbuk National University Hospital. Clinicopathologic factors, surgical treatment and outcome data were analyzed. RESULTS: Among the 86 patients (44 male, 42 female) with gallbladder cancer, the mean age was 62.9 years (range: 32-80) and the median survival was 42.4±3.5 month. The overall cumulative survival rates of 86 patients were for 1 year, 83.7%; 3 year, 67.4%; 5 year survival, 61.7%. Univariate analysis revealed that preoperative serum alanine aminotransferase, alkaline phosphatase, total bilirubin, carcinoembryonic antigen (CEA), T staging, N staging were statistically significantly associated with survival. CEA (p=0.004) and T staging (p=0.005) were associated with survival in multivariate analysis. Two-year survival rates were analyzed according to the methods of surgical resection, with simple cholecystectomy showing 100%, whereas extended cholecystectomy showed about 83% in T1b. We could not find out any adverse effect of the simple cholecystectomy for survival. CONCLUSIONS: CEA and T stage are independent significant prognostic factor associated with patient survival in our study. Simple cholecystectomy can be regarded as curative resection in stage T1b. Longer observation periods and more cases will be needed to confirm these conclusions.

Computer-assisted three-dimensional reconstruction of the fetal pancreas including the supplying arteries according to immunohistochemistry of pancreatic polypeptide.

PURPOSE: Computer-assisted three-dimensional reconstruction of the fetal human pancreas was prepared to reconsider topographical relation between the dorsal/ventral anlagen and the vascular supply. METHODS: Tissue sections from the upper abdominal viscera of three fetuses were examined. Sections were immunohistochemically stained to determine pancreatic polypeptide expression, a marker of the ventral pancreas. RESULTS: The immunohistochemical findings were used to create three-dimensional computer-assisted reconstructions to identify pancreatic arteries. The narrowest part of the pancreas, or the neck, corresponding to a part of the dorsal pancreas, was located on the left side of the common bile duct, portal vein and gastroduodenal artery (GDA). The posterior arterial arcade accompanied the ventral pancreas, whereas the anterior arcade did not. In contrast to the GDA, the splenic artery was clearly separated from the neck in fetuses. The GDA appears to be the primary and stable arterial supply for the neck of the pancreas. CONCLUSIONS: This observation may have implications for the preservation of the neck with the GDA during pancreaticoduodenectomy for benign and low-grade malignant diseases.

Fetal intrahepatic gallbladder and topographical anatomy of the liver hilar region and hepatocystic triangle.

The fetal gallbladder (GB) is embedded in a deep fossa surrounded by the liver parenchyma. Using 15 specimens with intrahepatic GB (crown-rump length 45-92 mm; approximately 9-13 weeks of gestation), we assessed the fetal topographical anatomy of the hepatocystic triangle and the porta hepatis. The cystic duct displayed a long upward course (0.9-4.5 mm along the supero-inferior axis) from the GB, along the duodenum, to the common bile duct in the hepatoduodenal ligament, via an independent mesentery separated from liver parenchyma by a recess of the peritoneal cavity. Notably, the course varied in length among specimens, not among stages. At the porta hepatis, we were able to distinguish the supraportal course of the posterior right hepatic duct overriding a portal vein branch to segment 8 (6/15) from the other, infraportal course (9/15). In the latter type, the portal vein bifurcation was superior to the cystic duct course. Two margins of the hepatocyctic triangle were very long in fetuses because of the inferiorly located intrahepatic GB. Thus, the triangle seems to be difficult to identify in prenatal ultrasound. During changes in location after 9 weeks, the GB fundus remains attached to the liver because the cystic artery was often embedded in the liver parenchyma. A failure in the embedding and re-exposure process of the GB may result in anomalous peritoneal folds around the GB.

Overexpression of peptidyl-prolyl isomerase Pin1 attenuates hepatocytes apoptosis and secondary necrosis following carbon tetrachloride-induced acute liver injury in mice.

Pin1, a member of the parvulin family of PPIase enzymes, plays a crucial role in the post phosphorylation regulation that governs important roles in the cell signaling mechanism and regulates a variety of cellular events. In this study, we investigated the role of Pin1 in carbon tetrachloride (CCl(4))-induced apoptosis and necrosis of hepatocytes during acute liver injury of mice. An in vivo study was done with the overexpression of Pin1 in the mouse liver; using Pin1-adenoviruse (ad-Pin1) followed by CCl(4) injection to induce acute liver injury. Pin1 overexpression in the liver of the experimental mice attenuated acute liver injury induced by CCl(4) . Serum aminotransferases and the number of apoptotic cells were decreased compared to those of control virus injected mice. In addition, Pin1 overexpression increased NF-kB activity, as evidenced by increased DNA binding. In conclusion, Pin1 reduces acute liver injury of mice due to CCl(4) by modulating apoptotic signals and by increasing NF-kB activity.