Associating liver partition and portal vein ligation for staged hepatectomy as bridging therapy for liver transplantation in an infant with an advanced hepatic rhabdoid tumor.

BACKGROUND: Malignant rhabdoid tumors (MRTs) are rare, aggressive tumors that mainly affect children and currently lack effective chemotherapeutic regimens. Liver MRTs are particularly challenging to manage due to the difficulty of performing one-stage liver resection, and preemptive liver transplantation is associated with high recurrence rates. However, the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique offers a promising surgical approach for advanced-stage liver tumors where conventional liver resection is not feasible. CASE REPORT: A patient with a large liver rhabdoid tumor that had invaded the three main hepatic veins underwent four courses of cisplatin-pirarubicin chemotherapy. ALPPS was performed due to insufficient residual liver capacity, with hepatic parenchymal dissection between the anterior and posterior liver zones in the first stage of surgery. After confirming adequate remaining liver volume, the liver was resected except for S1 and S6 on postoperative day 14. LDLT was performed 7 months after ALPPS due to the gradual deterioration of liver function caused by chemotherapy. The patient was recurrence-free 22 and 15 months after ALPPS and LDLT, respectively. CONCLUSIONS: The ALPPS technique is a curative option for advanced-stage liver tumors that cannot be managed with conventional liver resection. In this case, ALPPS was used successfully to manage a large liver rhabdoid tumor. Then, liver transplantation was performed after chemotherapy. The ALPPS technique should be considered a potential treatment strategy for patients with advanced-stage liver tumors, particularly those who can undergo liver transplantation.

Helicobacter bilis infection induces oxidative stress in and enhances the proliferation of human cholangiocytes.

BACKGROUND: Helicobacter bilis, an enterohepatic Helicobacter species, represents a carcinogenic risk factor for cholangiocytes owing to the prevalence of infections in patients with biliary tract cancer, cholecystitis, and pancreaticobiliary maljunction. However, the effect of H. bilis infection on cholangiocytes and the process and mechanism of carcinogenesis are not known. We aimed to determine the effects of H. bilis on cholangiocytes, focusing on inflammation and oxidative stress. MATERIALS AND METHODS: Helicobacter bilis and MMNK-1 cells were cocultured for 24 h and inflammatory cytokine secretion was evaluated. Furthermore, MMNK-1 cell proliferation, intracellular reactive oxidant species (ROS) production, and DNA damage caused by ROS were investigated. All factors were compared with and without H. bilis infection. RESULTS: Interleukin (IL)-6 and IL-8 secretion were significantly increased in MMNK-1 cocultures with H. bilis (IL-6, 24.3 ± 12.2 vs. 271.1 ± 286.4 pg/ml; IL-8, 167.6 ± 78.7 vs. 1085.1 ± 1047.1 pg/ml, p < .05). MMNK-1 proliferation was also significantly higher in H. bilis cocultures (1.05 ± 0.02 vs. 1.00-fold, respectively; p < .05). Coculturing enhanced the production of ROS in MMNK-1 cells depending on the cell concentration of H. bilis (1.0 vs. 1.17 ± 0.06, p < .05); however, DNA injury was not observed in cocultures with H. bilis (5.35 ± 0.87 vs. 6.08 ± 0.55 pg/µl, p = .06). CONCLUSIONS: Helicobacter bilis infection induced ROS production in and enhanced the proliferation of cholangiocytes.

Effect of pre-transplant sarcopenia on the estimation of standard liver volume in living-donor liver transplant candidates: risk factor for post-transplant small-for-size syndrome? A retrospective study.

The aim of the present study was to investigate whether LT candidates with sarcopenia are at an increased risk of receiving an inappropriate standard liver volume (SLV) estimation by standard body weight (BW)-derived SLV formula. Non-BW-SLV estimation formulas were tested in 262 LDLT donors and compared to a standard BW-SLV formula. The anthropometric parameters used were the thoracic width (TW-SLV) and thoracoabdominal circumference (TAC-SLV). Subsequently, sarcopenic and non-sarcopenic LDLT candidates (total, 217 patients) were compared in terms of estimated BW-SLV (routine method) and non-BW-SLV. In donors, TW-SLV showed comparable concordance with CT scan measured total liver volume as BW-SLV. The performance of TAC-SLV was low. In recipients, the prevalence of pre-LT sarcopenia was 30.4%. Sarcopenic patients were attributed a significantly lower BW-SLV than non-sarcopenic (sarcopenia vs no-sarcopenia, 1063.8 ml [1004.1-1118.4] vs. 1220.7 ml [1115.0-1306.6], P < 0.001), despite comparable TW-SLV, age, body height, and gender prevalence. As a result, sarcopenic patients received a graft with a statistically lower weight at organ procurement and developed more frequently a small-for-size syndrome (SFSS) according to the Dahm et al. (27.7% vs. 6.8%, P < 0.01) and Kyushu (28.7% vs. 9.2%, P < 0.01) definition. Therefore, In sarcopenic patients, BW-SLV formulas are affected by an high risk of SLV underestimation, thus exposing them to an increased risk of post-LT SFSS.

Wisteria floribunda agglutinin-positive human Mac-2-binding protein as a predictive marker of liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfected patients.

AIM: In human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfected patients, the progression of liver failure is reported to be more aggressive than that in HCV mono-infected patients. Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA+ -M2BP) is well recognized as a liver fibrosis glycobiomarker with a unique fibrosis-related glycoalteration. We analyzed HIV/HCV coinfected patients' M2BP levels as a possible marker for predicting liver fibrosis. METHODS: M2BP was measured in 31 HIV/HCV coinfected patients, and we analyzed the correlation between WFA+ -M2BP and several markers of fibrosis, liver function, and tumor markers. We compared the WFA+ -M2BP levels in HIV/HCV coinfected patients with those of HCV mono-infected patients by performing a propensity score matching analysis. RESULTS: In the HIV/HCV coinfected patients, the serum level of WFA+ -M2BP was well correlated with the markers type IV collagen, hyaluronic acid, and alpha-fetoprotein, but not protein induced by vitamin K absence-II. In the propensity score matching with HCV mono-infected patients, the WFA+ -M2BP levels were significantly higher in the HIV/HCV coinfected patients compared with the levels in the HCV mono-infected patients. CONCLUSION: In conclusion, WFA+ -M2BP might be a feasible predictive marker of fibrosis in HIV/HCV coinfected patients.

Elevated Plasma Levels of Mitochondria-Derived Damage-Associated Molecular Patterns during Liver Transplantation: Predictors for Postoperative Multi-Organ Dysfunction Syndrome.

The systemic cytokine response during surgery has been reported to be stimulated by the molecules released from damaged cells, called damage-associated molecular patterns (DAMPs). The relationship between DAMPs and liver transplantation has not been reported. We aimed to clarify the relationship between the plasma levels of DAMPs and the short-term post-transplant outcomes, including mortality and postoperative multi-organ dysfunction syndrome (MODS). This retrospective cohort study enrolled 61 patients who underwent liver transplantation. Mitochondrial DNA fragments, as mitochondria-derived DAMPs (mtDAMPs), were isolated from frozen plasma obtained at the start and the end of transplantation and were quantified by polymerase chain reaction. The short-term post-transplant outcomes were compared among the groups categorized based on the median value of the intraoperative fluctuation of mtDAMPs levels. The mtDAMPs levels were increased from the start to the end of transplantation in 52 recipients (85.2%, n = 61). Regarding mortality, no significant differences were noted between the high group (n = 30) and the low group (n = 31). The higher plasma levels of mtDAMPs were correlated with the longer duration of postoperative vasopressor support (P < 0.05). Importantly, the rate of MODS on post-operative day 1 was significantly higher in the high group (high vs. low group: 21 patients [70%] vs. 11 patients [35.1%], P < 0.01). In conclusion, mtDAMPs were increased in plasma during liver transplantation in most recipients. This elevation was not associated with mortality, but associated with the post-transplant recovery. Measuring plasma mtDAMPs may be helpful for predicting posttransplant recovery among liver-transplant recipients.

Packing procedure effective for liver transplantation in hemophilic patients with HIV/HCV coinfection.

We herein report an effective procedure for liver transplantation (LT) for severe cirrhotic patients with hemophilia. Three hemophilic patients suffering from liver cirrhosis due to human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection underwent deceased donor LT in our institute. Basic clotting parameters were measured and evaluated during LT to determine the optimal packing procedure. All patients were treated with a gauze packing procedure to ensure stable hemostasis in relation to hemophilia during the peri-transplant period. The graft function of all patients recovered well upon gauze removal (depacking) procedure and the patients were finally discharged to home. The administration of clotting factor was discontinued on day 3 after deceased donor LT. No infectious complications occurred in any of the 3 patients. This technique could be an option for achieving successful LT in these patients. Cooperation between transplant surgeons and anesthesiologists can make this challenging operation possible.

Efficacy of Triple-Drug Therapy to Prevent Pancreatic Fistulas in Patients With High Drain Amylase Levels After Pancreaticoduodenectomy.

BACKGROUNDS: Prior studies have suggested that drain amylase level is a predictive marker for developing pancreatic fistulas (PFs) after pancreaticoduodenectomy (PD). However, means of preventing PF after discovering high drain amylase levels have not been previously established. The purpose of this study was to evaluate the efficacy of a combination drug therapy (using three drugs; gabexate mesilate, octreotide, and carbapenem antibiotics, named as triple-drug therapy [TDT]) regimen in preventing PF for patients with high drain amylase levels on postoperative day (POD) 1 after PD. MATERIALS AND METHODS: We divided the 183 patients who underwent PD into two groups in accordance with their enrollment in the study: for those enrolled early in the study (early period), TDT was not administered to patients with high drain amylase level; however, for those enrolled later in the study (late period), TDT was administered if drain amylase levels were over 10,000 IU/L on POD 1. We retrospectively compared the incidence of PF between the two groups. RESULTS: Incidences of PFs were statistically, significantly prevented in the late group (early 17% versus late 6%; P = 0.01). For patients with low levels of drain amylase (<10,000 IU/L), the PF ratio was equivalent between two groups (early 8% versus late 5%; P = 0.56); however, PFs in patients with high drain amylase levels in the late period group were dramatically prevented by TDT administration (early 89% versus late 11%; P < 0.001). CONCLUSIONS: TDT may be a promising therapy to prevent PFs in patients with high drain amylase levels after PD.

Chronological changes in skeletal muscle mass following living-donor liver transplantation: An analysis of the predictive factors for long-term post-transplant low muscularity.

AIM: Sarcopenia is associated with high morbidity and mortality before and after liver transplantation (LT). The aim of the study was to evaluate the chronological changes in skeletal muscle mass (SMM) at different time points post-LT and to identify the risk factors for long-term low SMM. METHODS: The skeletal muscle index at L3 level (L3-SMI) was used for muscle mass measurement, and the recommended cutoff values of the Japanese Society of Hepatology guidelines were used as criteria for defining low muscularity. RESULTS: Preoperative low SMM was recognized in 35.1% of cases. At 1 year after LDLT, 28.9% of patients showed low SMM, without any significant prevalence change in comparison with the preoperative phase (35.1%) or 1 month post-LT (30.7%). Post-LT intensive care unit (ICU) length of stay (OR 1.14, P = 0.03), biliary complications (OR 5.88, P = 0.02), pre-LT low SMM (OR 3.36, P = 0.05), and 1 month post-LT low SMM (OR 10.16, P < 0.01) were found to be independent risk factors for low SMM at 1 year post-LT in multivariate analysis. The development of de novo low SMM at 1 year post-LT was a negative prognostic factor for OS (HR 9.08, P = 0.001). CONCLUSIONS: Intensive care unit length of stay, biliary complications and preoperative and 1 month post-LT low SMM were predictive factors for long-term low SMM. Newly developed low SMM at 1 year post-LT was a prognostic factor for a poor patient survival.

Relationship between various hepatic function scores and the formation of esophageal varices in patients with HIV/hepatitis C virus co-infection due to contaminated blood products for hemophilia.

AIM: It is reportedly difficult to accurately assess the liver reserve capacity of patients with HIV/hepatitis C virus (HCV) co-infection through contaminated blood products by the Child-Pugh (CP) classification. Therefore, we investigated a clinically applicable scoring system in determining the risk of esophageal varices in HIV/HCV co-infected patients, known as latent portal hypertension leading to esophageal varices. METHODS: Forty-three patients with HIV/HCV co-infection underwent clinical examinations, including endoscopy and assessment of hepatic reserve, in our department between 2009 and 2017. Child-Pugh score, the recently developed albumin-bilirubin (ALBI) grade, and the albumin-indocyanine green evaluation (ALICE) were compared to evaluate their diagnostic accuracy for the detection of esophageal varices using the area under the receiver operating characteristic curve (AUROC). RESULTS: The patients were all male hemophiliacs and were positive for both HIV and HCV antibodies, with a median age of 45 years (range, 29-66 years). Thirty-seven patients (84.1%) were classified as CP A at the examination. The comparison of AUROCs showed a superior diagnostic accuracy for ALICE (AUROC = 0.814) to detect esophageal varices. The positive prediction rate was the highest with ALICE if -2.325 was set, and the negative prediction rate was the highest with ALBI if -2.575 was set. The ALICE showed the highest accuracy compared to other two scores. CONCLUSION: The ALICE score was found to be the most valuable system for portal hypertension in HIV/HCV co-infected hemophilia patients. Because of its high specificity, ALICE for secondary surveillance could be used after other markers such as the aspartate aminotransferase to platelet ratio index and Fibrosis-4 index.

Efficacy of an artificial pancreas device for achieving tight perioperative glycemic control in living donor liver transplantation.

Intraoperative hyperglycemia during liver transplantation can induce infectious bacterial complications after surgery. The aim of this study was to evaluate the efficacy of the artificial endocrine pancreas in achieving perioperative blood glucose control and preventing infection in patients undergoing living donor liver transplantation (LDLT). We compared 14 patients with an artificial endocrine pancreas device to 14 patients who underwent glycemic control using the sliding scale method with respect to perioperative blood glucose level and postoperative infection. In this study, we aimed to control the perioperative glucose levels consecutively for 24 hours from the induction of anesthesia. The average blood glucose level in the artificial pancreas group was significantly lower than that in the sliding scale group (118 vs. 141 mg/dL, P < 0.05). The postoperative bacterial infection rate of the artificial pancreas group was significantly lower than that of the sliding scale group within one month after LDLT (35.7% vs. 78.6%, P < 0.05). Multiple regression analysis showed non-application of artificial endocrine pancreas as a significant risk factor of posttransplant infection. The artificial endocrine pancreas enabled the perioperative glucose level to be stably controlled without hypoglycemia. Artificial pancreas may reduce the incidence of postoperative infection after LDLT.

Standardized hybrid living donor hemihepatectomy in adult-to-adult living donor liver transplantation.

The aim of this study was to analyze the outcomes of the most updated version and largest group of our standardized hybrid (laparoscopic mobilization and hepatectomy through midline incision) living donor (LD) hemihepatectomy compared with those from a conventional laparotomy in adult-to-adult living donor liver transplantation (LDLT). Of 237 adult-to-adult LDLTs from August 1997 to March 2017, 110 LDs underwent the hybrid procedure. Preoperative and operative factors were analyzed and compared with conventional laparotomy (n = 126). The median duration of laparoscopic usage was 26 minutes in the hybrid group. Although there was improvement in applying this procedure over time from the beginning of the series of cases studied, blood loss and operative duration were still smaller and shorter in the hybrid group. There was no significant difference between the groups in the incidence of postoperative complications greater than or equal to Clavien-Dindo class III. There was no difference in recipient outcome between the groups. Our standardized procedure of hybrid LD hepatectomy is applicable and safe for all types of LD hepatectomies, and it enables the benefit of both the laparoscopic and the open approach in a transplant center without a laparoscopic expert. Liver Transplantation 24 363-368 2018 AASLD.

Pretransplant serum procalcitonin level for prediction of early post-transplant sepsis in living donor liver transplantation.

AIM: Infection is a frequent cause of in-hospital mortality after liver transplantation (LT). Elimination of possible risks in the pretransplant period, early diagnosis of post-transplant sepsis, and prompt treatment with antimicrobial agents are important. The objectives of this study were to analyze the impact of early post-transplant sepsis on outcomes and to clarify the value of predictive factors for early post-transplant sepsis. METHODS: The study included 136 patients who underwent initial living donor LT (LDLT) at our institute between April 2009 and December 2016. Sepsis was defined using the third international consensus criteria. The results of biochemical tests at the introduction of anesthesia before LDLT were collected for pretransplant evaluation. RESULTS: Post-transplant sepsis was found in 37 patients (27.2%). More patients had a pre-transplant serum procalcitonin (PCT) level >0.5 ng/mL in the sepsis group than in the non-sepsis group (11 [29.7%] vs 10 [10.1%]; P = 0.007). The 1-year survival rate in the sepsis group was significantly lower than in the non-sepsis group (53.8% vs 87.2%; P < 0.001). Multivariate analysis identified pretransplant serum PCT >0.5 ng/mL (odds ratio, 3.8; 95% confidence interval, 1.3-10.9; P = 0.01) as the only independent risk factor for post-transplant sepsis. CONCLUSIONS: Survival of patients with early post-transplant sepsis was poor and the incidence of sepsis was associated with the pretransplant serum PCT level. Re-evaluation of the general condition and rescheduling of LT should be considered in a patient with pretransplant serum PCT >0.5 ng/mL.

Aspartate transaminase-platelet ratio and Fibrosis-4 indices as effective markers for monitoring esophageal varices in HIV/hepatitis C virus co-infected patients due to contaminated blood products for hemophilia.

AIM: We examined the feasibility of the aspartate transaminase (AST)-platelet ratio index (APRI) and Fibrosis-4 (FIB4) score, which are well-established markers for liver fibrosis, as indicators for monitoring esophageal varices in patients who were co-infected with HIV and hepatitis C virus (HCV) due to contaminated blood products for hemophilia in Japan. METHODS: Forty-three HIV/HCV co-infected patients were enrolled. All were hemophilic men (median age 41 years; range, 29-66 years). We analyzed the correlations between fibrosis indices (APRI, FIB4) and various liver function tests, fibrosis markers, liver stiffness measured by acoustic radiation force impulse elastography, and the findings of gastrointestinal endoscopy. RESULTS: Both APRI and FIB4 were well correlated with several of the factors related to liver fibrosis and the existence of esophageal varices in the patients. The cut-off values for detecting esophageal varices estimated as the area under the receiver operating characteristic curve were 0.85 for APRI and 1.85 for FIB4. CONCLUSION: In patients co-infected with HIV/HCV due to contaminated blood products for hemophilia, APRI and FIB4 are effective for monitoring esophageal varices, even among patients who are apparently doing well with good liver function as Child-Pugh grade A.

The donor advocacy team: a risk management program for living organ, tissue, and cell transplant donors.

BACKGROUND AND PURPOSE: Although the incidence of living donor death is low in Japan, statistics show one living liver donor death in more than 7000 living liver transplants. Thus, medical transplant personnel must recognize that the death of a living organ or tissue transplant donor can occur and develop an appropriate risk management program. METHODS AND RESULTS: We describe how Nagasaki University Hospital established and implemented a Donor Advocacy Team (DAT) program: a risk management program for initiation in the event of serious, persistent, or fatal impairment of an organ, tissue, or cell transplantation from a living donor. DISCUSSION: The purposes of the DAT program are as follows: 1. To disclose official information without delay. 2. To provide physical and psychological care to the patient experiencing impairment and their family. 3. To provide psychological care to the medical staff in charge of the transplant. 4. To standardize the responses of the diagnosis and treatment department staff and other hospital staff. 5. To minimize the damage that the whole medical transplantation system may suffer and leverage the occurrence for improvement. To address (1) and (5), actions, such as reporting and responses to the government, mass media, transplant-related societies, and organ transplant networks, have been established to ensure implementation.

Analysis of early relaparotomy following living donor liver transplantation.

We retrospectively analyzed the causes, risk factors, and impact of early relaparotomy after adult-to-adult living donor liver transplantation (LDLT) on the posttransplant outcome. Adult recipients who underwent initial LDLT at our institution between August 1997 and August 2015 (n = 196) were included. Any patients who required early retransplantation were excluded. Early relaparotomy was defined as surgical treatment within 30 days after LDLT. Relaparotomy was performed 66 times in 52 recipients (a maximum of 4 times in 1 patient). The reasons for relaparotomy comprised postoperative bleeding (39.4%), vascular complications (27.3%), suspicion of abdominal sepsis or bile leakage (25.8%), and others (7.6%). A multivariate analysis revealed that previous upper abdominal surgery and prolonged operative time were independent risk factors for early relaparotomy. The overall survival rate in the relaparotomy group was worse than that in the nonrelaparotomy group (6 months, 67.3% versus 90.1%, P < 0.001; 1 year, 67.3% versus 88.6%, P < 0.001; and 5 years, 62.6% versus 70.6%, P = 0.06). The outcome of patients who underwent 2 or more relaparotomies was worse compared with patients who underwent only 1 relaparotomy. In a subgroup analysis according to the cause of initial relaparotomy, the survival rate of the postoperative bleeding group was comparable with the nonrelaparotomy group (P = 0.96). On the other hand, the survival rate of the vascular complication group was significantly worse than that of the nonrelaparotomy group (P = 0.001). Previous upper abdominal surgery is a risk factor for early relaparotomy after LDLT. A favorable longterm outcome is expected in patients who undergo early relaparotomy due to postoperative bleeding. Liver Transplantation 22 1519-1525 2016 AASLD.

Triple-drug therapy to prevent pancreatic fistula after pancreatectomy in a rat model.

BACKGROUND: Pancreatic fistula (PF) is one of post-operative complications in pancreatic surgery, but there is no consensus about the optimal treatment for PF. Our group has established a rat model of PF, and we conducted the present investigation to determine the efficacy of the triple-drug therapy (somatostatin analogue, gabexate mesilate, and imipenem/cilastatin) against PF using our rat model. METHODS: In the PF rat model, the triple-drug therapy was administered to the treated (T) group (n = 4), and we compared the results with those of a control (C) group (n = 4). The rats were sacrificed on postoperative day 3 (POD 3) and the levels of amylase and lipase in serum and ascites were measured. The intra-abdominal adhesion was scored. Each pancreas was evaluated pathologically, and inflammation was scored. RESULTS: The ascitic amylase levels on POD 3 were 1982 (1738-2249) IU/L in the C group and significantly lower at 136 (101-198) IU/L in the T group (p = 0.02). The ascitic lipase levels on POD 3 were 406 (265-478) U/L in the C group and significantly lower at 13 (7-17) U/L in the T group (p = 0.02). The intra-abdominal adhesion score on POD 3 was 2 (1-2) in the C group and significantly lower at 0 (0-1) in the T group (p = 0.02). The histological evaluation showed that the average of pancreatic inflammatory score was 8.5 (8-9) in the C group and significantly milder at 5 (5-7) in the T group (p = 0.01). CONCLUSION: Our findings suggest that the triple-drug therapy could be useful as a treatment for PF in clinical settings.

A selective cyclooxygenase-2 inhibitor (Etodolac) prevents spontaneous biliary tumorigenesis in a hamster bilioenterostomy model.

BACKGROUND: Secondary biliary carcinomas are associated with persistent reflux cholangitis after bilioenterostomy. Cyclooxygenase-2 (COX-2) has been a target for cancer prevention. The aim of this study was to evaluate the chemopreventive efficacy of long-term treatment with a selective COX-2 inhibitor medication during the natural course after bilioenterostomy without chemical induction. METHODS: Syrian golden hamsters which underwent choledochojejunostomy were randomly divided into two groups: the control group (n = 31), which was fed a normal diet, and the etodolac group (n = 33), which was fed 0.01% etodolac (a selective COX-2 inhibitor) mixed in the meal. The hamsters were killed at the postoperative weeks 20-39, 40-59, 60-79, or 80-100. Biliary neoplasms, cholangitis, proliferating cell nuclear antigen labeling index (PCNA-LI) of the biliary epithelium, and prostaglandin E2 (PGE2) production were evaluated. RESULTS: The occurrence rates of biliary neoplasm were 43.8 and 15.2% in the control and etodolac groups, respectively (p < 0.05). The incidence of biliary neoplasm increased as time progressed in the control group, whereas it remained at a low level throughout the experimental period in the etodolac group. PGE2 products tended to be lower in the etodolac group, and PCNA-LI was significantly lower in the etodolac group (p < 0.01). These results suggest that the medication etodolac suppresses cell proliferation of the biliary epithelium, thereby preventing biliary carcinogenesis. CONCLUSIONS: Etodolac is expected to prevent secondary biliary carcinogenesis caused by persistent reflux cholangitis after bilioenterostomy.

Endoscopic transpapillary pancreatic stenting for internal pancreatic fistula with the disruption of the pancreatic ductal system.

BACKGROUND: Internal pancreatic fistula (IPF) is a well-recognized complication of pancreatic diseases. Although there have been many reports concerning IPF, the therapy for IPF still remains controversial. We herein report our experiences with endoscopic transpapillary pancreatic stent therapy for IPF and evaluate its validity. METHOD: Six patients with IPF who presented at our department and received endoscopic transpapillary pancreatic stent therapy were investigated, focusing on the clinical and imaging features as well as treatment strategies, the response to therapy and the outcome. RESULTS: All patients were complicated with stenosis or obstruction of the main pancreatic duct, and in these cases the pancreatic ductal disruption developed distal to the areas of pancreatic stricture. The sites of pancreatic ductal disruption were the pancreatic body in five patients and the pancreatic tail in one patient. All patients received endoscopic stent placement over the stenosis site of the pancreatic duct. Three patients improved completely and one patient improved temporarily. Finally, three patients underwent surgical treatment for IPF. All patients have maintained a good course without a recurrence of IPF. CONCLUSION: Endoscopic transpapillary pancreatic stent therapy may be an appropriate first-line treatment to be considered before surgical treatment. The point of stenting for IPF is to place a stent over the stenosis site of the pancreatic duct to reduce the pancreatic ductal pressure and the pseudocyst's pressure.

Decreased expression of SOX9 in intraductal papillary mucinous neoplasms of the bile duct.

BACKGROUND/AIMS: SOX9 is an important transcription factor required for development and has been implicated in several types of malignant tumor. Our recent study showed that SOX9 played an important role in multi-step carcinogenesis in cases of intraductal papillary mucinous tumor of the pancreas (IPMN-P). This study aimed to investigate the expression of SOX9 in cases of intraductal papillary mucinous tumor of the bile duct (IPMN-B). METHODOLOGY: SOX9 expression was immunohistochemically evaluated in the tumor and corresponding normal bile-duct epithelium of seven IPMN-B patients. RESULTS: In all cases, SOX9 expression in the IPMN-B was low compared with the normal biliary epithelium. CONCLUSIONS: This study demonstrated that SOX9 expression may indicate a link between IPMN-B and IPMN-P. SOX9 may also have potential as a therapeutic target and/or prognostic marker in IPMN-B.