PURPOSE: The aim of the present study was to determine proper treatment strategies to improve the outcome of patients with gallbladder cancer by an analysis of multiple factors affecting tumor recurrence and patient survival. METHODS: Between January 1991 and April 2006, surgery with curative intent was performed on 120 patients with gallbladder cancer. Of 120 cases, 35 patients had findings that precluded any further intervention, and the remaining 85 patients underwent curative resections that included a simple cholecystectomy in 43 cases, a radical cholecystectomy in 32 cases and an extended cholecystectomy in 10 cases. Clinicopathogical data was analyzed. RESULTS: The presence of jaundice at presentation, gross morphology of the tumor, tumor cell differentiation, presence of a lymph node metastasis, lymphatic invasion and direct invasion to other contagious organ(s) and achievement of a tumor-free resection margin were associated with survival. For stage I gallbladder cancer, in only T2 lesions, patients that undergone a simple cholecystectomy had double the rate of recurrence as compared to patients that undergone a radical cholecystectomy (12.5% versus 26.1%; p = .119). For stage II gallbladder cancer, survival and disease-free survival for patients that undergone a radical cholecystectomy were improved as compared to patients that undergone a simple cholecystectomy; survival and disease-free survival was poor for patients that had undergone an extended cholecystectomy, especially in patients that had bile duct invasion (4/5; 80%). For stage III/IV gallbladder cancer, all patients (n = 6) underwent an extended cholecystectomy and half of the patients survived longer than one year. CONCLUSION: Radical cholecystectomy could be a standard procedure for gallbladder cancer in addition to just stage II cancer. An aggressive approach including resecting contagious organ(s) in locally advanced gallbladder cancer could provide a survival benefit without an increase in complications.
Achievement ; Bile Ducts ; Cell Differentiation ; Cholecystectomy ; Disease-Free Survival ; Gallbladder ; Gallbladder Neoplasms ; Humans ; Jaundice ; Lymph Nodes ; Lymphatic Metastasis ; Recurrence

Diagnosis of gastric and/or hepatic tuberculosis is often delayed or missed because of its non-specific symptomatology and rare occurrence. We present here a rare case of concomitant gastric and hepatic tuberculosis which was preoperatively mistaken for a malignant gastrointestinal stromal tumor (GIST) with hepatic metastasis in a 49- year-old male. The patient, with no past history of pulmonary tuberculosis, was admitted with indigestion and epigastric discomfort for 2 weeks. There were no abnormal findings on physical examination and chest radiology. Gastrofiberscopic examination revealed a large, submucosal tumor with central ulceration on the middle third of the stomach and biopsy targeted on the ulceration site showed only chronic inflammation. Abdominal CT showed an exophytic, ovoid gastric mass having calcified components on the side of lesser curvature with huge, inhomogenous hepatic masses in the left lobe, requiring differentiation from possible hematogenous metastasis of gastric lesion, most likely malignant GIST. The patient underwent distal gastrectomy and left lobectomy of the liver. The case was confirmed pathologically as tuberculosis showing confluent epithelioid cell granulomas and multinucleated giant cells with caseous necrosis.
Biopsy ; Diagnosis ; Dyspepsia ; Epithelioid Cells ; Gastrectomy ; Gastrointestinal Stromal Tumors* ; Giant Cells ; Granuloma ; Humans ; Inflammation ; Liver ; Male ; Necrosis ; Neoplasm Metastasis* ; Physical Examination ; Stomach ; Thorax ; Tomography, X-Ray Computed ; Tuberculosis ; Tuberculosis, Hepatic* ; Tuberculosis, Pulmonary ; Ulcer

Hepatolithiasis is characterized by its frequent recurrence, and its requirement for multiple interventions which can be performed radiologically, endoscopically or surgically. Although hepatic resection - concomitant removal of hepatic stones and its provocative pathology as well - has remained the definitive treatment of hepatolithiasis, the burden of the surgery limits its widespread application. In a certain proportion of patients, those for whom hepatic resection and endoscopic/percutaneous approaches are not indicated, surgical removal of intrahepatic stones can be attempted. In those circumstances, hepatic stones located outside the direct visual field can make the stone-extracting procedure cumbersome. We experienced an operation of a 66-year-old patient who had already received left lateral sectionectomy, cholecystectomy and choledochojejunostomy. His condition was due to impacted, recurrent stones packed between the hepatic hilum and the second confluence of the hepatic duct. Instead of revising the prior choledochojejunostomy site, after entering the jejunum 4 cm below the choledochojejunostomy site, we inserted a rigid nephroscope into the hepatic duct. Under the magnified view presented by a telescope inside the nephroscope, stone extracting was easily done using forceps inserted into the nephroscope. We think a nephroscope is useful in extracting intrahepatic stones, especially for large impacted stones located below the second confluence of the hepatic duct.
Aged ; Bile Ducts, Intrahepatic ; Cholecystectomy ; Choledochostomy ; Endoscopes ; Hepatic Duct, Common ; Humans ; Jejunum ; Recurrence ; Surgical Instruments ; Telescopes ; Visual Fields

PURPOSE: The aim of the present study was to find the proper treatment for improving the survival of patients with hilar cholangiocarcinoma by analyzing many factors affecting the patients' survival. METHODS: Between January 1991 and April 2006, 152 patients with hilar cholangiocarcinoma and who underwent surgery were reviewed. One hundred fifteen patients underwent attempted curative resections, and 37 patients had findings that precluded any further intervention. Of the 115 patients who underwent curative resection, 38 patients underwent resection of the extrahepatic bile duct only and 77 patients underwent concomitant hepatectomy. The clinicopathogical data of these patients was analyzed. RESULTS: The 3 year overall survival and disease-free survival rates were 41.2% and 52.5%, respectively. The overall recurrence rate was 40.9% (47/115) and of patients with recurrence, those who had been treated aggressively survived longer than those who had been treated conservatively (P=.039). Of the patients' factors that affected survival, only preoperative weight loss was meaningful (P=.024). Of the histologic factors, tumor cell differentiation (P=.048) and the presence of lymph node metastasis (P=.028) were associated with survival. Of the perioperative factors, only achievement of complete tumor resection affected survival. On comparing between resection of the extrahepatic bile duct only and concomitant partial hepatectomy, the latter achieved more definitely negative histologic margins (63.6% vs 39.5%, respectively, P=.037) at the expense of a more prolonged operation time and hospital stay and greater complications. CONCLUSION: Preoperative weight loss, poor differentiation, lymph node metastasis and a positive histologic margin could be included in the poor prognostic factors affecting survival. Concomitant liver resection could be rationalized in that it could attain a more negative histologic margin for treating resectable hilar cholangiocarcinoma, but it could increase mortality and morbidity rates.
Bile Ducts, Extrahepatic ; Cell Differentiation ; Cholangiocarcinoma* ; Disease-Free Survival ; Hepatectomy ; Humans ; Length of Stay ; Liver ; Lymph Nodes ; Mortality ; Neoplasm Metastasis ; Recurrence ; Weight Loss

Biliary papillomatosis is a rare disease entity characterized by multiple papillary adenomas along the bile duct mucosa. It is widely accepted that the adenoma-carcinoma sequence represents the process by which most, if not all, cholangiocarcinomas of an intraductal-growing type arise. Interestingly, friable papillary projections easily detached from the primary site can be implanted into the other sites in the bile duct in suitable animal models, resulting in multiple tumors. A 76-year-old male was referred to our hospital due to intermittent abdominal discomfort. Imaging workups revealed two lesions: wall thickening in the proximal portion of the left interhepatic duct and abrupt narrowing of the distal common bile duct. A hepatopancreaticoduodenectomy was carried out and pathological analysis demonstrated a well-differentiated adenocarcinoma of the left hepatic duct and carcinoma in situ of the distal common bile duct on a background of biliary papillomatosis. Six days after the operation, the patient received a re-exploration due to ruptured mesenteric vessels. Unfortunately, 3 months after the initial operation, the patient died of aspiration pneumonia. Biliary papillomatosis can present with a broad spectrum of disease characteristics ranging from adenoma to, usually, low-grade adenocarcinoma. If there is a complete excision, and a favorable postoperative course is secured, excellent survival can be expected after surgery.
Adenocarcinoma ; Adenoma ; Aged ; Bile Ducts ; Carcinoma in Situ ; Cholangiocarcinoma ; Common Bile Duct ; Hepatic Duct, Common ; Humans ; Male ; Models, Animal ; Mucous Membrane ; Papilloma ; Pneumonia, Aspiration ; Rare Diseases

PURPOSE: Even though adipose tissue-derived stem cells (ADSCs) have been spotlighted as a possible alternative for liver transplantation in an experimental setting, the mechanism by which ADSCs improve liver dysfunction remains poorly characterized. The objective of this study was to evaluate the therapeutic ability of undifferentiated ADSCs, and find a few clues on how ADSCs alleviate liver damage by comparing the transplantation routes. METHODS: In vitro generated human ADSCs were checked for surface markers and stage-specific genes for characterization. Afterwards, they were transplanted into C57BL/6 mice with CCl4-induced liver injury. The transplantations were made via tail vein, portal vein, and direct liver parenchymal injection. At 1 and 3 post-transplantation days, serum biochemical parameters and/or liver specimens were evaluated. RESULTS: We have shown here that ADSCs have the characteristics of mesenchymal stem cells, and belong to endodermal and/or early hepatic differentiation stage. After transplantation into the mice with acute liver failure, markers of liver injury, such as alanineaminotransferase, aspartateaminotransferase, as well as ammonia, decreased. Of these transplantation routes, transplantation via tail vein rendered the most prominent reduction in the biochemical parameters. CONCLUSION: Undifferentiated ADSCs have the ability to improve hepatic function in mice with acute liver injury. Moreover, our transplantation route study supports the theory that ADSCs in systemic circulation can exert endocrine or paracrine effects to ameliorate the injured liver.
Ammonia ; Animals ; Endoderm ; Humans ; Liver ; Liver Diseases ; Liver Failure ; Liver Failure, Acute ; Liver Transplantation ; Mesenchymal Stromal Cells ; Mice ; Portal Vein ; Stem Cell Transplantation ; Stem Cells ; Transplants ; Veins

PURPOSE: The design of this study was to determine the most influential factor(s) on post-transplant immunological consequences, particularly with regard to the role of killer cell immunoglobulin-like receptors (KIRs) and their ligands (type I human leukocyte antigen (HLA)) in unstable liver function. METHODS: Retrospectively collected data from 319 recipients undergoing adult living donor liver transplantation (LDLT) using a right lobe graft between January 2002 and August 2008 were analyzed. Patients were categorized according to the serum alanine transaminase (ALT) pattern; stable ALT pattern was defined as ALT pattern during 3 months post-transplantation, except for initial 2 weeks post-transplantation, in which 2 times or less additional elevation(s) of serum alanine transaminase (ALT) (> or =80 IU/L) were observed. When a serum ALT pattern showed fluctuating and/or unpredictable nature, it was defined as an unstable pattern. In addition, genetic information of KIRs and HLA-C allotypes received from 68 recipients and 59 donors was analyzed by way of polymerase chain reaction using sequence-specific primers (PCR-SSP) to determine the factor(s) influencing a serum ALT pattern. RESULTS: Among 319 LDLT recipients included in this study, the actual incidences of AR and unstable ALT pattern were 13.4% (43/319) and 42.3% (135/319), respectively. Unstable ALT pattern correlated with poorer survival following LDLT than stable pattern (P<0.000). Genetically, unstable ALT pattern was related to recipients carrying KIR2DL2(+)/KIR2DS2(+) combined with the heterogeneous HLA-C allotype (HLA-C1/C2), (relative risks 45.0, 95% confidence interval 2.160~937.321; P=0.013). CONCLUSION: This study indicates that, when performing LDLT, pretransplant determination of recipient's KIRs and HLA-C allotypes may be beneficial in coping with post-transplant immunological circumstances.
Adult ; Alanine Transaminase ; Genotype ; HLA-C Antigens ; Humans ; Incidence ; Leukocytes ; Lifting ; Ligands ; Liver ; Liver Transplantation ; Living Donors ; Polymerase Chain Reaction ; Receptors, KIR ; Retrospective Studies ; Tissue Donors ; Transplants

Purpose: Survivin is a typical antiapoptotic protein. It is copiously expressed during human fetal development but is infrequently present in adult tissues. In this experiment, we researched the treatment effect of the secretome that adiposederived stem cells (ASCs) transfected with survivin. Methods: First of all, we generated survivin-overexpressing ASCs transfected with a plasmid comprising a gene encoding survivin. The secreted substances released from survivin-overexpressing ASCs (survivin-secretome) were collected, and were determined their in vitro and in vivo therapeutic potential, especially in the model of liver impairment. Results: In vitro, the survivin-secretome significantly increased cell viability and promoted the expression of proliferationrelated markers (proliferating cell nuclear antigen [PCNA], phospho-signal transducer and activator of transcription 3 (p-STAT3), hepatocyte growth factor [HGF], vascular endothelial growth factor [VEGF]) and anti-apoptosis-related markers (myeloid cell leukemia-1 [Mcl-1] and survivin) (P < 0.05). In vivo using 70% hepatectomy mice, the survivin-secretome group exhibited the lowest serum levels of interleukin-6, tumor necrosis factor-α (P < 0.05). The serum levels of liver transaminases (alanine aminotransferase and aspartate aminotransferase) were also the lowest in the survivin-secretome group (P < 0.05). The survivin-secretome group also exhibited the highest liver regeneration on the 7th day after 70% partial hepatectomy (P < 0.05). In the subsequent liver specimen analysis, the specimens of survivin-secretome exhibited the highest expression of p-STAT3, HGF, VEGF, PCNA, and Mcl-1 and the lowest expression of bcl-2-like protein 4 (P < 0.05). Conclusion Taken together, secretome secreted by survivin-overexpressing ASCs could be an effective way to improve liver regeneration and repair for liver injury treatment.

PURPOSE: The aims of this study were to find the risk factor and outcomes of patients with an early recurrence (ER) of a hepatocellular carcinoma (HCC) after liver transplantation (LT) and the actual impact of transarterial chemoembolization (TACE) before LT for a HCC on patient survival and HCC recurrence. METHODS: Ninety-eight cases of adult LT, performed between September 1995 and January 2006, were evaluated. The risk factors and prognosis of patient with a HCC after transplantation for an ER, defined as a recurrence within 6 months of transplantation, and the effects of Pre-LT TACE on the disease-free and overall survival rates, as well as the patterns of recurrence after LT, were studied. RESULTS: A total of 18 patients (18.4%) experienced a HCC recurrence after LT; 10 and 8 patients had early and late recurrences, respectively. From a univariate analysis, the serum alpha-fetoprotein (P=0.003), tumor size (P=0.003), serosa invasion (P=0.000), tumor grade (P=0.011) and vascular invasion (P=0.014) were statistically significant risk factors for an ER. From a multivariate analysis, the presence of serosa invasion of a HCC was the only independent risk factor for an ER (P=0.009; OR=9.407: 95% CI, 1.764~50.164). There was no difference in the disease free sur-vival and overall survival rates between the TACE and without TACE groups, but the extrahepatic recurrence rate was higher in the TACE than without TACE group. CONCLUSION: Serosa invasion by a HCC is independently associated with an ER of HCC after LT. Pre-LT TACE does not influence the disease-free and overall survivals after LT for a HCC.
Adult ; alpha-Fetoproteins ; Carcinoma, Hepatocellular* ; Humans ; Liver Transplantation* ; Liver* ; Multivariate Analysis ; Prognosis ; Recurrence* ; Risk Factors* ; Serous Membrane ; Survival Rate

Purpose: The aim of the present study was to identify whether the percentages of T cell subset, the serum interferon-gamma (IFN gamma ) as a Th1 cytokine, soluble CD30 (sCD30) as a marker for activation of Th2 cytokine producing T cells, and intracellular cytokines (IL-2, IL-4) can predict the acute cellular rejection episodes of liver transplant patients. Methods: Pretransplant and posttransplant sera on days 1, 3 and 7 after surgery of 88 adult living donor liver transplant recipients were tested for the percentage of T cell subset (CD3+, CD4+ and CD8+ T cells), IL-2, IL-4 production by peripheral mononucleated cells with fluorescence activated cell sorter analysis and for the serum IFN gamma , sCD30 concentrations with commercial ELISA kits. Recipients were subdivided into three groups as control (n=51), ELE (the group which showed elevated liver enzyme but RAI score <2. n=25), and AR (the group with acute rejection which showed RAI score > or =3. n=13). The differences in the level of cytokines among each group were analyzed. Results: The percentages of CD3+ T cell subset at preoperatively and day 1, 7 after surgery in AR were higher than those of control (P <0.05). The IL-2 production in AR was the highest and the IL-4 production was the lowest on posttransplant 7th day among three groups without significance. AR had a significantly higher pretranspant IFN gamma concentration than control (P <0.05). The pretransplant serum level of sCD30 was not different between the control and AR. However, in comparison with control, which showed a steadily decreasing serum sCD30 level after transplantation, 12 of the 14 patients in the AR showed an increase in their sCD30 levels from day 1 to day 3 after transplantation (P <.05). Conclusion: The measurement of serum IFN gamma and sCD30 during pre- and early post-LDLT period might be helpful to evaluate the risk of the occurrence of liver allograft rejection.
Adult ; Allografts* ; Cytokines* ; Enzyme-Linked Immunosorbent Assay ; Fluorescence ; Humans ; Interferon-gamma ; Interleukin-2 ; Interleukin-4 ; Liver* ; Living Donors ; T-Lymphocytes ; Transplantation