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Eastliver
  Hepatobiliary Pancreat Dis Int
 
2010 Vol.  9 No.  1
Published: 2010-02-15

pages 1-112

REVIEW ARTICLES
ORIGINAL ARTICLES/Transplantation
ORIGINAL ARTICLES/Liver
ORIGINAL ARTICLES/Biliary
ORIGINAL ARTICLES/Pancreas
CASE REPORTS
LETTERS TO THE EDITOR
CLINICAL EXPERIENCE
MEETINGS AND COURSES
REVIEW ARTICLES
9 Chan SC, Lo CM, Fan ST
Simplifying living donor liver transplantation Hot!

BACKGROUND: Living donor liver transplantation is a complex surgical operation. Treatment policies and operative techniques evolved in the last two decades.
DATA SOURCES: Our center s experience in living donor liver transplantation was reviewed in conjunction with relevant publications in the literature.
RESULTS: The surgical techniques and perioperative surgical therapeutics could be modified towards simplicity. Examples include regular inclusion of the middle hepatic vein without compromising the venous outflow of the donor s remnant left liver. This provides excellent venous outflow, which is crucial for a small-for-size graft. Immunosuppression and hepatitis B suppression are steroid free and hepatitis B immunoglobulin free respectively.
CONCLUSION: The most practical way to achieve high graft and recipient survival rates with an acceptably low donor risk is through design of a protocol that simplifies the surgery and postoperative management.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 9-14 .
[Abstract] ( 193 ) [HTML KB] [PDF 223KB] ( 2214 )
15 Zhang J, Zhou L, Zheng SS
Clinical management of hepatitis B virus infection correlated with liver transplantation Hot!

BACKGROUND: As a radical cure for post-hepatitis B virus (HBV)-related liver cirrhosis and hepatocellular carcinoma, liver transplantation has been applied in many medical centers. Before the use of effective measures, hepatitis B recurrence and the existence of HBsAg(+) donors, patients with hepatitis B-related diseases are contraindicated for liver transplantation. Application of interferon, hepatitis B immunoglobulin (HBIG), and nucleotide analogues (e.g., lamivudine) has made great progress in the clinical care of HBV. However, there are still many shortcomings such as low viral suppression rate, rising expense, and the induction of HBV tyrosine-methionine-aspartate-aspartate (YMDD) mutation. This article systema-tically reviews the current evidence that immunotherapy, conventional drug combinations, and some special fields of HBV infection correlate with liver transplantation.
DATA SOURCES: Studies were identified by searching MEDLINE and PubMed for articles using the keywords "hepatitis B virus", "hepatitis B vaccination", "lamivudine", "adefovir", "entecavir", "tenofovir", "HBV genotype", and "liver transplantation" up to October 2009. Additional papers were identified by a manual search of the references from the key articles.
RESULTS: Hepatitis B vaccine and human monoclonal antibody have very good clinical prospects. Compared with traditional therapies, the new medical regimens have many benefits such as boosting viral suppression rate and decreasing medical expenses. The triple therapy for YMDD mutation also has an excellent therapeutic effect and a low barrier to resistance. New nucleos(t)ide analogues (entecavir and tenofovir) eliminate virus more effectively with few adverse reactions, and may replace lamivudine or HBIG in future.
CONCLUSIONS: Hepatitis B vaccine needs further large-scale and rigorous randomized controlled trials to confirm its effective dose and injection frequency. Monoclonal antibody is still experimental, and the next step is to carry out the relevant animal and human studies. A consensus standard regimen for the treatment of hepatitis B should be developed.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 15-21 .
[Abstract] ( 251 ) [HTML KB] [PDF 308KB] ( 2353 )
ORIGINAL ARTICLES/Transplantation
22 Lan X, Li B, Wang XF, Wei YG, Yan LN, Zhao JC
Potential etiopathogenesis of seventh day syndrome following living donor liver transplantation: ischemia of the graft?

BACKGROUND: Seventh-day syndrome (7DS) is an early serious complication following liver transplantation with a high mortality because of its unknown etiopathogenesis. This study aimed to analyze the potential etiopathogenesis of 7DS.
METHODS: A retrospective analysis of 98 consecutive living donor liver transplants performed from 2001 to 2007 at our center revealed that 5 patients had suffered from 7DS; their age, MELD score, portal vein inflow and other parameters were compared with those of the other recipients.
RESULTS: The 5 patients showed common features: (a) initial uneventful recovery, and a dramatic rise of serum liver enzyme levels 1 to 2 weeks later; (b) decreased inflow in the portal vein accompanied by augmentation of serum creatinine and urea nitrogen level; and (c) serial liver biopsy findings of apoptosis and ischemic necrosis of hepatocytes. Four of the 5 patients died. Age, waiting time to transplantation, MELD score, operation time, cold ischemic time, portal interceptive time and diameter of the portal vein were not significantly different between the 2 groups, but a difference was found in the flow rate of the portal vein (t=3.234, P<0.001).
CONCLUSIONS: The 5 patients suffered from a decreased portal vein inflow, ischemic liver necrosis, and renal failure. Hence, hypoperfusion of the liver graft was considered to be the etiopathogenesis of 7DS, for which, however sufficient evidence is lacking. More studies of 7DS are needed.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 22-26 .
[Abstract] ( 192 ) [HTML KB] [PDF 441KB] ( 1856 )
ORIGINAL ARTICLES/Liver
27 Sharma P, Sharma BC, Sarin SK
Critical flicker frequency for diagnosis and assessment of recovery from minimal hepatic encephalopathy in patients with cirrhosis

BACKGROUND: Minimal hepatic encephalopathy (MHE) impairs quality of life and predicts overt hepatic encephalopathy (HE) in cirrhotic patients. Diagnosis of MHE requires cumbersome tests. Lactulose is effective in the treatment of MHE. This study aimed to evaluate the use of critical flicker frequency (CFF) for the diagnosis of MHE in cirrhotic patients after treatment.
METHODS: One hundred and ten patients were evaluated by psychometry (number connection tests A, B or figure connection tests A, B), P300 auditory event related potential (P300ERP), venous ammonia, and CFF for MHE. MHE was diagnosed by abnormal psychometry (>2SD age matched controls) and P300ERP. MHE patients were treated with lactulose for one month. Response was defined by normalization (<2SD of matched controls) of both psychometry and P300ERP.
RESULTS: Of the 110 patients [Child Turcott Pugh score A:B:C 39:42:29, (age 41.6±11.6 years, M:F 82:28)], 75 (68%) had abnormal results of psychometric tests, and 74 (67%) had prolonged P300ERP. Fifteen (20%) patients with abnormal results of psychometric tests had normal P300ERP. Thus sixty (54.5%) patients were diagnosed as having MHE. After treatment for one month, 34 (57%) recovered while 26 (43%) continued to have abnormal resents of psychometric or P300ERP tests. CFF was <39 Hz in 72 (65.4%) patients before treatment and in 20 (33.3%) after treatment. CFF sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for the assessment of recovery of MHE were 65%, 91%, 85%, 77% and 80%, respectively.
CONCLUSION: CFF is a simple, relatively reliable, and accurate test without any dependence on age or literacy in the diagnosis and assessment of recovery of patients with MHE.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 27-32 .
[Abstract] ( 292 ) [HTML KB] [PDF 247KB] ( 2876 )
33 Zhou YM, Yang JM, Li B, Yin ZF, Xu F, Wang B, Xu W, Kan T
Risk factors for early recurrence of small hepatocellular carcinoma after curative resection Hot!

BACKGROUND: Poorer prognosis is seen in patients with hepatocellular carcinoma (HCC) after curative hepatic resection with early recurrence (≤1 year) than in those with late recurrence (>1 year). This study aimed to identify risk factors for postoperative early recurrence of small HCC (≤3 cm in diameter).
METHODS: The study population consisted of 158 patients who underwent curative resection for small HCC between January 2002 and July 2004. Risk factors for early recurrence were analyzed.
RESULTS: Thirty-three (20.8%) patients developed early recurrence after surgery. Univariate analysis showed the following significant risk factors for early recurrence in small HCC: serum alpha-fetoprotein (AFP) level >100 ng/ml, lack of tumor capsule formation, microscopic vascular invasion, high Edmonson-Steiner grades, and cytokeratin-19 (CK-19) expression (P<0.05). Multivariate stepwise logistic regression analysis showed that serum AFP level >100 ng/ml (odds ratio 2.561, 95% confidence interval 1.057 to 6.206, P=0.037) and microscopic vascular invasion (odds ratio 4.549, 95% confidence interval 1.865 to 11.097, P=0.001) were independent factors.
CONCLUSIONS: Postoperative early recurrence is related to serum AFP level >100 ng/ml and microscopic vascular invasion in patients with small HCC. Adjuvant therapy and careful follow-up are required for patients with these risk factors.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 33-37 .
[Abstract] ( 217 ) [HTML KB] [PDF 231KB] ( 2727 )
38 Zhang XJ, Jiang Y, Wang X, Tian FZ, Lv LZ
Comparatively lower postoperative hepatolithiasis risk with hepaticocholedochostomy versus hepaticojejunostomy

BACKGROUND: Optimal surgical technique plays a key role in preventing the postoperative recurrence of hepatolithiasis. Tian et al developed the subcutaneous tunnel and hepatocholangioplasty using the gallbladder (STHG) technique and applied it in hepatolithiasis patients who had an approximately normal gallbladder and sphincter of Oddi. However, the technique is controversial. In the present study, a canine model was established for hepatocholangioplasty (HC) and hepaticojejunostomy (HJ) to simulate STHG and Roux-en-Y cholangiojejunostomy in the clinic, respectively. Then, the alterations of bile components in the vicinity of the anastomosis were compared. This may provide an experimental guide for choosing an optimal technique for the treatment of hepatolithiasis in the clinic.
METHODS: The animals were randomly separated into a control group (5 dogs) and a model group (stenosis of the common bile duct; 24 dogs). The 24 dogs in the model group were randomly divided into an HC group and an HJ group (12/group). Bile was collected from the bile duct at 1 and 5 months after the operation, and the bile components were determined.
RESULTS: The levels of total bile acid, cholesterol, total bilirubin, and phospholipid in the HC group were higher than those in the HJ group (P<0.05). However, no statistical difference was seen in unconjugated bilirubin and calcium ions. The mucin level in bile in the HC group was lower than that in the HJ group at 5 months after the operation (P<0.05). The postoperative lipid peroxidation level was remarkably lower than that in the HJ group (P<0.05). However, the superoxide dismutase level was remarkably higher than that in the HJ group (P<0.05). Finally, a significant difference was found in the positive bacterial culture rate in bile between the groups.
CONCLUSION: Changes of bile components near the anas-tomosis after HC might be more preferable for preventing hepatolithiasis formation than HJ.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 38-43 .
[Abstract] ( 210 ) [HTML KB] [PDF 326KB] ( 2044 )
44 Huang YQ, Xu F, Yang JM, Huang B
Primary hepatic neuroendocrine carcinoma: clinical analysis of 11 cases

BACKGROUND: Primary hepatic neuroendocrine carcinoma (PHNEC) is extremely rare, and fewer than 300 cases have been reported in the English/Chinese-language literature, therefore it is difficult to make a proper diagnosis and determine a therapeutic approach.
METHODS: Eleven PHNEC patients were admitted to our hospital between January 1996 and May 2008. Laboratory examination, digestive endoscopy, B-ultrasonography, CT, MRI, or PET-CT were performed on the patients for preoperative diagnosis. All patients received liver resection. Some patients received transcatheter arterial chemoembolization (TACE), percutaneous ethanol injection treatment (PEIT), or octreotide injection when a recurrence was found. The patients clinical data were recorded and all patients were followed up.
RESULTS: The patients were confirmed pathologically as having PHNEC. Their median follow-up time was 33 months (12-107 months). All patients survived, and the longest post-operative survival time was 107 months, the longest disease-free survival time was 98 months, the 1-year survival rate was 100%, and the 1-year recurrence rate was 45.5% (5/11).
CONCLUSIONS: Since PHNEC is easy to confuse with hepatocellular carcinoma, careful screening of symptoms is needed to avoid misdiagnosis. Resection is the first choice of treatment for PHNEC and provides the most favorable outcomes including long-term survival. Other treatment such as TACE and PEIT can be considered as well, especially when a tumor recurs.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 44-48 .
[Abstract] ( 271 ) [HTML KB] [PDF 295KB] ( 2565 )
49 He B, Zhao S, Zhang W, Li Y, Han P
Effect of sodium salicylate on oxidative stress and insulin resistance induced by free fatty acids

BACKGROUND: It has been reported that high-dose salicylates improve free fatty acids (FFAs)-induced insulin resistance and β-cell dysfunction in vitro, but the mechanism remains uncertain. In insulin-resistant rats, we found that the supplementation of sodium salicylate is associated with a reduction of plasma malondialdehyde (MDA), a marker of oxidative stress. Few studies have investigated the effects of salicylates on oxidative stress levels in insulin-resistant animal models. This study aimed to assess the effect of sodium salicylate on insulin sensitivity and to explore the potential mechanism by which it improves hepatic and peripheral insulin resistance.
METHODS: Intralipid+heparin (IH), saline (SAL), or intralipid+heparin+sodium salicylate (IHS) were separately infused for 7 hours in normal Wistar rats. During the last 2 hours of the infusion, hyperinsulinemic-euglycemic clamping was performed with [6-3H] glucose tracer. Plasma glucose was measured using the glucose oxygenase method. Plasma insulin and C-peptide were determined by radioimmunoassay. MDA levels and glutathione peroxidase (GSH-PX) activity in the liver and skeletal muscle were measured with colorimetric kits.
RESULTS: Compared with infusion of SAL, IH infusion increased hepatic glucose production (HGP), and decreased glucose utilization (GU) (P<0.05). The elevation of plasma free fatty acids increased the MDA levels and decreased the GSH-PX activity in the liver and muscle (P<0.01). Sodium salicylate treatment decreased HGP, elevated GU (P<0.05), reduced MDA content by 60% (P<0.01), and increased the GSH-PX activity by 35% (P<0.05).
CONCLUSIONS: Short-term elevation of fatty acids induces insulin resistance by enhancing oxidative stress levels in the liver and muscle. The administration of the anti-inflammatory drug sodium salicylate reduces the degree of oxidative stress, therefore improving hepatic and peripheral insulin resistance. IKK-β and NF-κB provide potential pathogenic links to oxidative stress.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 49-53 .
[Abstract] ( 247 ) [HTML KB] [PDF 340KB] ( 2145 )
ORIGINAL ARTICLES/Biliary
54 Ji F, Zhao JL, Jin X, Jiao CH, Hu YY, Xu QW, Chen WX
Endoscopic nasojejunal feeding tube placement in patients with severe hepatopancreatobiliary diseases: a retrospective study of 184 patients

BACKGROUND: Total parenteral nutrition (TPN) has been recognized as the mainstay of nutritional support in patients with severe hepatopancreatobiliary (HPB) diseases for decades. However, recent studies advocate the utilization of endoscopic nasojejunal feeding tube placement (ENFTP), rather than the conventional approach. This study was designed to compare the clinical value of ENFTP and TPN in patients with severe HPB diseases.
METHODS: Two groups of patients with severe HPB diseases were analyzed retrospectively. One group of 88 patients received ENFTP, and the other 96 received TPN. Routine blood levels, serum glucose and prealbumin, hepatic and renal function, serum lipid, and calcium were measured at baseline and after 1, 2, and 4 weeks of nutritional support. Also, complication rate, mortality, nutritional support time, mechanical ventilation time, mean length of time in intensive care unit, and duration of hospital stay were analyzed.
RESULTS: After 4 weeks of nutritional support, the degree of recovery of red blood cells, prealbumin, and blood glucose was greater in the ENFTP than in the TPN group (P<0.05). Furthermore, the ENFTP group showed a lower incidence of septicemia, multiple organ dysfunction syndrome, peri-pancreatic infection, biliary infection, and nosocomial infection, in addition to shorter nutritional support time and hospital stay (P<0.05).
CONCLUSIONS: ENFTP is much more effective than TPN in assisting patients with severe HPB diseases to recover from anemia, low prealbumin level, and high serum glucose, as well as in decreasing the rates of various infections (pulmonary infection excluded), multiple organ dysfunction syndrome rate, nutrition support time, and length of hospital stay. Therefore, ENFTP is safer and more economical for clinical application.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 54-59 .
[Abstract] ( 242 ) [HTML KB] [PDF 253KB] ( 3239 )
60 Ji W, Ding K, Li LT, Wang D, Li N, Li JS
Outpatient versus inpatient laparoscopic cholecystectomy: a single center clinical analysis

BACKGROUND: Outpatient laparoscopic cholecystectomy (OPLC) developed in the United States and other developed countries as one of the fast-track surgeries performed in ambulatory centers. However, this practice has not been installed as a routine practice in the major general hospitals and medical centers in China. We designed this case-control study to evaluate the feasibility, benefits, and safety of OPLC.
METHODS: Two hundred patients who had received laparoscopic cholecystectomy for various benign gallbladder pathologies from April 2007 to December 2008 at Jinling Hospital of Nanjing University School of Medicine were classified into two groups: OPLC group (100 patients), and control group (100), who were designated for inpatient laparoscopic cholecystectomy (IPLC). Data were collected for age, gender, indications for surgery, American Society of Anesthesiology (ASA) class, operative time, blood loss during surgery, length of hospitalization, and intra- and post-operative complications. The expenses of surgery and in-hospital care were calculated and analyzed. The operative procedures and instrumentation were standardized for laparoscopic cholecystectomy, and the procedures were performed by two attending surgeons specialized in laparoscopic surgery. OPLC was selected according to the standard criteria developed by surgeons in our hospital after review. Reasons for conversion from laparoscopic to open cholecystectomy were recorded and documented.
RESULTS: One hundred patients underwent IPLC following the selection criteria for the procedure, and 99% completed the procedure. The median operative time for IPLC was 24.0 minutes, blood loss was 16.2 ml, and the time for resuming liquid then soft diet was 10.7 hours and 22.0 hours, respectively. Only one patient had postoperative urinary infection. The mean hospital stay for IPLC was 58.2 hours, and the cost for surgery and hospitalization was 8770.5 RMB yuan on average. Follow-up showed that 90% of the patients were satisfied with the procedure. In the OPLC group, 99% of the patients underwent the procedure with a median operative time of 21.6 minutes and bleeding of 14.7 ml. The patients took liquid 11.3 hours then soft diet 20.1 hours after surgery. The mean postoperative hospital stay was 28.5 hours. In this group, 89% of the patients were discharged within the first 24 hours, and the remaining 11% were released within 48 hours after surgery. Two patients developed local complications. The cost for surgery and hospitalization was 7235.7 RMB yuan, which was 17.5% less than that in the IPLC group. At follow-up, 94% of the patients were satisfied with the surgery and short hospital stay.
CONCLUSIONS: OPLC can effectively treat a variety of benign, non-acute gallbladder diseases with shortened waiting time and postoperative hospital stay. OPLC benefits the hospital with a rapid bed turnover rate, and reduces cost for surgery and hospitalization.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 60-64 .
[Abstract] ( 223 ) [HTML KB] [PDF 208KB] ( 2936 )
ORIGINAL ARTICLES/Pancreas
65 Sivaraj SM, Vimalraj V, Saravanaboopathy P, Rajendran S, Jeswanth S, Ravichandran P, Vennilla R, Surendran R
Is bactibilia a predictor of poor outcome of pancreaticoduodenectomy?

BACKGROUND: Although bile infection has been proposed to increase infective complications following pancreaticoduodenectomy, its association with infective complications and non-infective complications like pancreatic fistula is still controversial.
METHODS: Seventy-six patients who had undergone pancreaticoduodenectomy between July 2007 and December 2008 were included in a prospective database and their data analyzed. In all patients intraoperative bile from the bile duct was cultured. Preoperative, intra-operative, and post-operative variables were recorded and analyzed.
RESULTS: Bile culture showed positive growth in 35 patients and negative growth in 41. Twenty patients in the positive group underwent ERCP and stenting. The patients with a positive bile culture had a higher incidence of infective complications including intra-abdominal abscess (n=8), wound infection (n=27), bacteremia (n=10), and renal insufficiency (n=9). There was no increase in the rate of non-infective complications of pancreaticoduodenectomy including pancreatic fistula (n=7), delayed gastric emptying (n=9), and post-operative hemorrhage (n=3). The hospital stay was significantly prolonged in the patients with a positive bile culture (P=0.0002).
CONCLUSIONS: Pre-operative biliary drainage is significantly associated with bile infection, and bile infection increases the overall rates of infective complications and renal insufficiency. Because of the high incidence of complications is associated with infected bile, routine intra-operative bile culture is recommended in patients undergoing pancreaticoduodenectomy. Pre-operative prophylaxis is dependent on sensitivity of cases to perioperative antibiotics and intra-operative bile culture report. Because of its significant association with infected bile, biliary stenting should be used in strictly selected cases.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 65-68 .
[Abstract] ( 274 ) [HTML KB] [PDF 192KB] ( 2683 )
69 Shen YM, Yang XC, Song ML, Qin CH, Yang C, Sun YH
Growth inhibition induced by short hairpin RNA to silence survivin gene in human pancreatic cancer cells

BACKGROUND: Survivin is known to be overexpressed in various human malignancies, including pancreatic cancer, and mediates cancer cell proliferation and tumor growth, so the regulation of this molecule could be a new strategy for treating pancreatic cancer. In this study, short hairpin RNAs (shRNAs) specific to survivin were introduced into human pancreatic cancer Patu8988 cells to investigate the inhibitory effects on survivin expression and cell proliferation in vitro and in vivo.
METHODS: Three kinds of shRNA specific to the survivin gene were designed and cloned into eukaryotic expression plasmid pGenesil-1 vector. Subsequently the recombinant plasmids were transfected into human pancreatic cancer Patu8988 cells with lipfectamineTM 2000 reagent. The mRNA and protein expressions of survivin in the transiently transfected Patu8988 cells were determined by RT-PCR, flow cytometry, and Western blotting analysis. The proliferation inhibition rates of stably transfected Patu8988 cells were determined by MTT assay. The antitumor activities of the three kinds of survivin-shRNA plasmids were evaluated in BALB/c nude mice inoculated with Patu8988 cells and bearing human pancreatic cancer.
RESULTS: The three survivin-shRNA plasmids named pGenesil-1-survivin-1, pGenesil-1-survivin-2 and pGenesil-1-survivin-1+2 (with double interfering RNA sites) were successfully constructed, and were confirmed by restriction enzyme cutting and sequencing. At 48 hours after transfection, the expression of survivin mRNA and protein was inhibited in Patu8988 cells transfected with pGenesil-1-survivin-1, pGenesil-1-survivin-2, and pGenesil-1-survivin-1+2 when compared with that of either pGenesil-1-NC (with scrambled small interfering RNA) transfected cells or control cells (P<0.05). The MTT results showed that the proliferation rates of Patu8988 cells stably transfected with survivin-shRNA plasmids were reduced when compared with that of either pGenesil-1-NC transfected cells or control cells (P<0.01). Furthermore, when Patu8988 cells stably transfected with survivin-shRNA were injected into BALB/c nude mice, tumor growth was dramatically lower and the tumor was smaller than that of either pGenesil-1-NC transfected cells or control cells (P<0.01). The inhibitory effect of pGenesil-1-survivin-1 was the best among the three kinds of survivin-shRNA plasmids, but no combination of inhibitory effects was found in pGenesil-1-survivin-1+2.
CONCLUSIONS: shRNAs specific to survivin have gene silencing effects and inhibit pancreatic cancer cell proliferation. shRNA activity against survivin could be of potential value in gene therapy for pancreatic cancer. However, shRNAs with double combining sites did not significantly enhance the interference compared with single site shRNAs, therefore further studies on this are needed.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 69-77 .
[Abstract] ( 264 ) [HTML KB] [PDF 643KB] ( 2143 )
78 ??l C, Dinler K, Hasdemir O, Büyüka?ik O, Bu?dayci G
Oxidative stress and lipid peroxidation products: effect of pinealectomy or exogenous melatonin injections on biomarkers of tissue damage during acute pancreatitis

BACKGROUND: Melatonin (N-acetyl-5-methoxytripta-mine) is a free radical scavenger and a strong antioxidant, secreted by the pineal gland. In this study, we evaluated the effects of decreasing and increasing serum melatonin levels on malonyldialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) levels in pancreatic tissue from rats with experimental acute pancreatitis.
METHODS: Experimental acute pancreatitis was induced in three groups of Wistar albino rats (10 animals per group) by pancreatic ductal ligation. The first group had only acute pancreatitis and served as the control. Surgical pinealectomy was added to acute pancreatitis in the second group, removing the source of endogenous melatonin (low melatonin levels group). The third group was given 0.1 ml daily intraperitoneal injections of 20 mg/ml melatonin solution for one week (high melatonin levels group). The effects of melatonin levels were evaluated by comparison of the levels of MDA, SOD, and GS in pancreatic tissue.
RESULT: We found that intraperitoneal melatonin injections decreased the levels of MDA and increased the levels of SOD and GSH in pancreatic tissue.
CONCLUSION: Exogenous melatonin has a preventive effect on lipid peroxidation and oxidative damage in acute pancreatitis.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 78-82 .
[Abstract] ( 255 ) [HTML KB] [PDF 260KB] ( 2604 )
83 Zhang XP, Zhang J, Ma ML, Cai Y, Xu RJ, Xie Q, Jiang XG, Ye Q
Pathological changes at early stage of multiple organ injury in a rat model of severe acute pancreatitis

BACKGROUND: Severe acute pancreatitis (SAP) is a commonly seen acute abdominal syndrome characterized by sudden onset, rapid progression and high mortality rate. The damage in peripheral organs may be more severe than that in the pancreas, and can even lead to multiple organ dysfunction. It is critical to recognize early pathological changes in multiple organs. This study aimed to assess the early pathological features of damaged organs in a rat model of SAP.
METHODS: Thirty clean grade healthy male Sprague-Dawley rats weighing 250-300 g were randomly divided into a model control group (n=15) and a sham-operated group (n=15). The SAP rat model was induced by sodium taurocholate. Samples of blood and from multiple organs were collected 3 hours after operation. We assessed the levels of IL-6, TNF-α, PLA2, NO, ET-1, MDA, amylases and endotoxin in blood and observed the early pathological changes in multiple damaged organs.
RESULTS: Levels of IL-6, TNF-α, PLA2, NO, ET-1 and MDA in serum and of amylase and endotoxin in plasma of the model control group rats were significantly higher than those of the sham-operated group (P<0.01). Different degrees of pathological change were observed in multiple damaged organs.
CONCLUSION: Multiple organ injury may occur at the early stage of SAP in rats.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 83-87 .
[Abstract] ( 217 ) [HTML KB] [PDF 325KB] ( 2609 )
CLINICAL EXPERIENCE
88 Singh V, Singh G, Gupta V, Gupta R, Kapoor R
Contrast-free air cholangiography-assisted unilateral plastic stenting in malignant hilar biliary obstruction

BACKGROUND: Endoscopic palliation in malignant hilar biliary obstruction requires endoscopic retrograde cholangiopancreatography (ERCP), whereas contrast injection leads to cholangitis. Contrast-free metal stenting with or without magnetic resonance cholangiopancreatography (MRCP) has shown encouraging results, but MRCP and metal stents are costly. There have been no reports on the use of air cholangiography.
METHODS: We prospectively evaluated the role of air cholangiography-assisted unilateral plastic stenting in 10 patients with type Ⅱ malignant hilar biliary obstruction. A retrospectively analysed group of 10 patients treated with contrast-free unilateral metal stenting served as historical controls.
RESULTS: Ten patients with unresectable type Ⅱ malignant hilar biliary obstruction were studied. Air cholangiography detected type Ⅱ obstruction in all patients, similar to MRCP. The patients underwent unilateral stenting. Successful endoscopic drainage was achieved in all patients. The mean patency of the stent was 95.8±17.5 days in the study group and 143.9±115.1 days in the control group (P=0.20). The mean survival was 121.8±41.6 days in the study group and 154.9±122.5 days in the control group (P=0.42). Kaplan-Meier analysis showed an estimated median survival of 100:95% CI (65.9, 134.1) days in the study group and 98:95% CI (84.1, 111.9) days in the control group (P=0.62). Cholangitis occurred in none of the patients and there were no 30-day deaths nor major complications. Air cholangiographyassisted unilateral plastic stenting was cheaper than contrast-free unilateral metal stenting.
CONCLUSION: Air cholangiography-assisted unilateral plastic stenting is as safe and effective as contrast-free unilateral metal stenting in type Ⅱ malignant hilar biliary obstruction for palliating patients, but it is cheaper.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 88-92 .
[Abstract] ( 235 ) [HTML KB] [PDF 278KB] ( 2173 )
CASE REPORTS
93 Dar FS, Asai K, Haque AR, Cherian T, Rela M, Heaton N
Liver transplantation for acute intermittent porphyria: a viable treatment?

BACKGROUND: Acute intermittent porphyria (AIP) is the most common hepatic porphyria. Its clinical presentation includes severe disabling and life-threatening neurovisceral symptoms and acute psychiatric symptoms. These symptoms result from the overproduction and accumulation of porphyrin precursors, 5-aminoleuvulinic acid (ALA) and porphobilinogen (PBG). The effect of medical treatment is transient and is not effective once irreversible neurological damage has occurred. Liver transplantation (LT) replaces hepatic enzymes and can restore normal excretion of ALA and PBG and prevent acute attacks.
METHOD: Two cases of LT for AIP were identified retrospectively from a prospectively maintained LT database.
RESULT: LT was successful with resolution of AIP in two patients who suffered from repeated acute attacks.
CONCLUSION: LT can correct the underlying metabolic abnormality in AIP and improves quality of life significantly.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 93-96 .
[Abstract] ( 278 ) [HTML KB] [PDF 231KB] ( 2622 )
97 Muroni M, D'Angelo F, Pezzatini M, Sebastiani S, Noto S, Pilozzi E, Ramacciato G
Synchronous gastric adenocarcinoma and pancreatic ductal adenocarcinoma

BACKGROUND: The association between gastric and pancreatic carcinoma is a relatively rare condition. In gastric carcinoma patients, the prevalence of second tumors varies 2.8% to 6.8% according to the reported statistics. Gastric cancer associated with pancreatic cancer is uncommon.
METHODS: We report a case of a 73-year-old patient hospitalized for vomiting and weight loss. Esophagogastroduodenoscopy demonstrated an ulcerative lesion of the gastric antrum. Computed tomography and magnetic resonance showed a gastric thickening in the antral and pyloric portion and a nodular mass (3×1.7 cm) in the uncinate portion of the pancreas.
RESULTS: The patient underwent pancreaticoduodenectomy according to Whipple regional type Ⅰ Fortner. Histological examination of the specimen demonstrated a moderately differentiated adenocarcinoma of the stomach and a poorly differentiated ductal adenocarcinoma of the pancreas.
CONCLUSIONS: Long survival is rare in patients with associated gastric and pancreatic cancer. Surgical resection remains the only potentially curative treatment.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 97-99 .
[Abstract] ( 208 ) [HTML KB] [PDF 265KB] ( 1961 )
100 Ge CL, Luo XG, Liu YF
Thrombosis of gallbladder vein presenting as acute peritonitis

BACKGROUND: Thrombosis of the gallbladder vein occurs rarely, and few clinical features have been reported. We report here with a case of gallbladder vein thrombosis presenting as acute peritonitis in a 75-year-old man.
METHODS: The old man with sudden continuous abdominal pain resorted to the emergency room and treated for peritonitis associated with acute cholecystitis. The treatment failed to slow the progress of the disease, and massive ascites appeared with thickening of the gallbladder wall. Laparotomic investigation was conducted later.
RESULT: Pathologically, thrombosis of the gallbladder vein was diagnosed.
CONCLUSIONS: The thrombosis of the gallbladder vein is characterized by thickening of the gallbladder wall, ascites, and sudden continuous abdominal pain. The causes of deep vein thrombosis at this unusual site vary.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 100-102 .
[Abstract] ( 249 ) [HTML KB] [PDF 204KB] ( 1789 )
103 Kebir FZ, Lahmar A, Arfa N, Manai S, Ouaer MAE, Bouraoui S, Gouttalier C and Mezabi-Regaya S
Acinar cell carcinoma of the pancreas in a young patient with chronic pancreatitis

BACKGROUND: Acinar cell carcinoma (ACC) is a rare malignancy of the pancreas arising from acinar cells. Unlike ductal adenocarcinoma, this tumor rarely presents with pancreatitis.
METHODS: We present a case of ACC associated with chronic calcifying pancreatitis, and a review of the literature focusing on diagnosis and management.
RESULTS: A 43-year-old man was proposed for Wirsungojejunal derivation for chronic pancreatitis. Histopathological examination of the tissue extracted revealed an ACC. Duodenopancreatectomy was performed. Six months post-operatively, the patient developed hepatic metastasis and was treated with gemcitabine as palliative chemotherapy.
CONCLUSIONS: The clinical presentation of ACC of the pancreas is not specific and the tumor can be under-diagnosed when associated with chronic pancreatitis. Data regarding course, treatment, and prognosis of this tumor are generally lacking.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 103-106 .
[Abstract] ( 243 ) [HTML KB] [PDF 250KB] ( 2203 )
LETTERS TO THE EDITOR
107 Gupta N, Gupta SK, Kapoor HS
Gallbladder and cystic duct agenesis diagnosed laparoscopically

To the Editor:
Anatomical variations of the biliary tree are not uncommon but isolated agenesis of the gallbladder is rare,[1] with a reported incidence of 0.013%-0.075%.[2] This variation remains undiagnosed since the patient is often asymptomatic. In spite of available diagnostic modalities, preoperative diagnosis is sometimes difficult.
A 28-year-old woman presented with symptoms of dyspepsia and upper abdominal discomfort. Routine biochemical and hematological investigations demonstrated no abnormalities. With a shrunken gallbladder with an acoustic shadow shown by sonography, the patient was hospitalized for laparoscopic cholecystectomy. Intraoperatively, no gallbladder was observed in its normal position. The whole supraduodenal part of the common bile duct was explored but no evidence of the gallbladder or cystic duct was found. Other abnormal locations, including the retrohepatic on the left side, falciform ligament, and lesser omentum were also excluded. The procedure was terminated at this stage. In the postoperative period, magnetic resonance cholangiopancreatography was carried out to confirm the diagnosis of gallbladder agenesis (Fig.). Associated congenital anomalies like annular pancreas and lumbar hernia were also re-examined intra- and post-operatively, but nothing was found. The patient was put on proton pump inhibitors and responded well.
In the 3rd week of fetal life, ventral thickening of the endoderm at the distal end of the foregut forms the liver. The caudal end of this endoderm proliferates to form the gallbladder and cystic duct. Gallbladder or cystic duct agenesis is a rare condition, about 450 cases have been reported.[1-8] It is difficult to diagnose gallbladder agenesis preoperatively. Annular pancreas and lumbar hernia are other anomalies associated with gallbladder agenesis.[9, 10] In the present case, there was no other associated anomaly.
If the gallbladder is not found at its normal or abnormal locations on laparoscopy, open exploration of the extrahepatic biliary system can be avoided. Newer imaging modalities are relatively non-invasive and can provide good information on biliary tract anatomy preoperatively. All patients with gallbladder agenesis undergoing abdominal exploration pose a challenge to the surgeon to correctly identify the anomaly and avoid injury to the bile duct.[11]

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 107-108 .
[Abstract] ( 238 ) [HTML KB] [PDF 193KB] ( 1733 )
108 Colaneri RP, Nunes BS, Herman P
Melanoma of the gallbladder misdiagnosed as gallbladder cancer

To the Editor:
Metastatic melanoma of the gallbladder is extremely rare, and despite appropriate therapy its prognosis is poor with few patients surviving more than 2 years. We present a case of gallbladder involvement by malignant melanoma in a 63-year-old man initially diagnosed with gallbladder cancer. The man with a history of malignant melanoma resected from his back 18 years ago was admitted to our hospital because of severe right upper abdominal pain two days before admission.
Ultrasonography and magnetic resonance showed an 8 cm mass in the gallbladder lumen (Fig. 1). Chest X-ray, tumoral markers (CEA and CA19-9), and blood analyses showed nothing abnormal. Gallbladder cancer was suspected for immediate surgical treatment. A cholecystectomy with resection of liver segments Ⅳb and Ⅴ and a lymphadenectomy of the hepatic hilus were performed for the gallbladder cancer. The mass inside the gallbladder lumen measured 8 cm and had a single attachment point to the mucosal surface, darkly colored (Fig. 2). Histological evaluation showed a malignant melanoma with no signs of lamina propria or muscularis invasion. None of the 12 dissected lymph nodes showed signs of metastasis. The postoperative course was uneventful and the patient was discharged on postoperative day 5.
Melanoma can metastasize to any organ, and gastrointestinal metastases occur in 2%-4% of the patients.[1] Isolated metastasis to the gallbladder is rare and most patients have widespread disease by the time of diagnosis.[2] Over 50% of metastatic gallbladder lesions are from melanomas and this can be explained by the hematogenous spread of melanoma to the abdomen.[3]
Most patients with melanoma metastatic to the gallbladder are asymptomatic, and the most common symptom is acute cholecystitis due to cystic duct obstruction.[3] Right upper quadrant or epigastric pain, weight loss, nausea, and vomiting may be present.[3] Radiographic examination is useful to determine gall-bladder masses. Ultrasonography is the most useful tool for assessing gallbladder lesions and can reveal an intracholecystic nodule or mass. CT scan has an important role in the detection of metastatic disease.
In the present case, the mass inside the gallbladder was misdiagnosed as a gallbladder cancer, and was treated according to this hypothesis.
Since gallbladder melanoma is a rare entity, there is no optimal therapy for this kind of tumor. Its prognosis is very poor, with a survival period of 8.54 months for metastatic lesions.[4] Apparently, aggressive surgical therapy tends to prolong the survival rate, and to improve the quality of life of patients.[2] The treatment is dependent on the extension of the disease and the status of the patient. In the present case the tumor was limited to the gallbladder, and surgery, misindicated for a gallbladder cancer, aimed to prevent symptoms or tumor complications and to improve the prognosis. The patient remained well without symptoms, and 2 years latter showed a metastasis to the tonsil that was resected. Ten months later, the patient presented 2 pulmonary metastases and was referred to reavaliation by the clinical oncologist.
The role of adjuvant chemotherapy and immuno-therapy is still controversial for metastatic gastrointestinal melanoma.[1] In patients with a gallbladder mass and a history of cutaneous melanoma, isolated metastatic melanoma has to be diagnosed despite its rarity. In spite of its poor prognosis, a surgical approach seems to be the best treatment.

Hepatobiliary Pancreat Dis Int. 2010; 9(1): 108-109 .
[Abstract] ( 284 ) [HTML KB] [PDF 193KB] ( 1768 )
MEETINGS AND COURSES
110
Meetings and courses
Hepatobiliary Pancreat Dis Int. 2010; 9(1): 110-112 .
[Abstract] ( 241 ) [HTML KB] [PDF 165KB] ( 1593 )

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