Role of tumour location and surgical extent on prognosis in T2 gallbladder cancer: an international multicentre study.

BACKGROUND: In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection. METHODS: Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted. RESULTS: Data from 937 patients were available for evaluation. The overall 5-year disease-free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5-year disease-free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5-year disease-free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five-year disease-free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic. CONCLUSION: Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection.

ANTECEDENTES: En el cáncer de vesícula biliar, la ubicación del tumor subdivide el estadio T2 en tumores con invasión del lado peritoneal y del lado del hígado (T2a y T2b). Para los tumores que invaden el lado peritoneal (T2a) se sugiere que se puede obviar la resección hepática sin que ello comprometa el pronóstico. Sin embargo, este argumento no ha sido validado. El estudio tuvo como objetivo investigar el valor pronóstico de la localización del tumor en el cáncer de vesícula biliar T2 y establecer la extensión adecuada de la resección quirúrgica. MÉTODOS: Se recogieron los datos clínicos de pacientes que se sometieron a cirugía por cáncer de vesícula biliar en 14 hospitales de Corea, Japón, Chile y Estados Unidos. Se realizaron análisis de la supervivencia y de los factores de riesgo. RESULTADOS: Se dispuso de datos de 937 pacientes para ser evaluados. La tasa de supervivencia global libre de enfermedad a los 5 años fue del 70,6%, y las de T2a y T2b del 74,5% y 65,5% (P = 0,028). Con respecto a la resección hepática, la colecistectomía extendida presentó una tasa mejor de supervivencia libre de enfermedad a los 5 años que la colecistectomía simple (73,0% versus 61,5%, P = 0,012). La tasa de supervivencia libre de enfermedad a los 5 años fue marginalmente mejor para la colecistectomía extendida que para la colecistectomía simple tanto en T2a (76,5% versus 66,1%, P = 0,094) como en T2b (68,2% versus 56,2%, P = 0,084). Las tasas de supervivencia libre de enfermedad a los 5 años no fueron diferentes entre la resección hepática en cuña y la segmentectomía S4b+S5 (74,1% versus 71,5%, P = 0,720). En el análisis multivariable, los factores de riesgo independientes para la recidiva fueron la presencia de síntomas (cociente de riesgos instantáneos, hazard ratio, HR 1,52, P = 0,002), la resección R1 (HR 1,96, P = 0,004) y el estadio N1/N2 (N1 HR 3,40, P < 0,001; N2 HR 9,56, P < 0,001). El 70,8% de las recidivas eran metastásicas. CONCLUSIÓN: La localización del tumor no fue un factor pronóstico independiente en el cáncer de vesícula biliar T2. La colecistectomía extendida fue marginalmente superior que la colecistectomía simple. La cirugía radical debe incluir una resección hepática y una linfadenectomía adecuada.

Randomized multicentre trial comparing external and internal pancreatic stenting during pancreaticoduodenectomy.

BACKGROUND: There is no consensus on the best method of preventing postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). This multicentre, parallel group, randomized equivalence trial investigated the effect of two ways of pancreatic stenting after PD on the rate of POPF. METHODS: Patients undergoing elective PD or pylorus-preserving PD with duct-to-mucosa pancreaticojejunostomy were enrolled from four tertiary referral hospitals. Randomization was stratified according to surgeon with a 1 : 1 allocation ratio to avoid any related technical factors. The primary endpoint was clinically relevant POPF rate. Secondary endpoints were nutritional index, remnant pancreatic volume, long-term complications and quality of life 2 years after PD. RESULTS: A total of 328 patients were randomized to the external (164 patients) or internal (164) stent group between August 2010 and January 2014. The rates of clinically relevant POPF were 24·4 per cent in the external and 18·9 per cent in the internal stent group (risk difference 5·5 per cent). As the 90 per cent confidence interval (-2·0 to 13·0 per cent) did not fall within the predefined equivalence limits (-10 to 10 per cent), the clinically relevant POPF rates in the two groups were not equivalent. Similar results were observed for patients with soft pancreatic texture and high fistula risk score. Other postoperative outcomes were comparable between the two groups. Five stent-related complications occurred in the external stent group. Multivariable analysis revealed that soft pancreatic texture, non-pancreatic disease and high body mass index (23·3 kg/m2 or above) predicted clinically relevant POPF. CONCLUSION: External stenting after PD was associated with a higher rate of clinically relevant POPF than internal stenting. Registration number: NCT01023594 (https://www.clinicaltrials.gov).

Evaluation of phosphorus adsorption capacity of sesame straw biochar on aqueous solution: influence of activation methods and pyrolysis temperatures.

The phosphorus (P) adsorption characteristic of sesame straw biochar prepared with different activation agents and pyrolysis temperatures was evaluated. Between 0.109 and 0.300 mg L(-1) in the form of inorganic phosphate was released from raw sesame straw biochar in the first 1 h. The release of phosphate was significantly enhanced from 62.6 to 168.2 mg g(-1) as the pyrolysis temperature increased. Therefore, sesame straw biochar cannot be used as an adsorbent for P removal without change in the physicochemical characteristics. To increase the P adsorption of biochar in aqueous solution, various activation agents and pyrolysis temperatures were applied. The amount of P adsorbed from aqueous solution by biochar activated using different activation agents appeared in the order ZnCl2 (9.675 mg g(-1)) > MgO (8.669 mg g(-1)) ⋙ 0.1N-HCl > 0.1N-H2SO4 > K2SO4 ≥ KOH ≥ 0.1N-H3PO4, showing ZnCl2 to be the optimum activation agent. Higher P was adsorbed by the biochar activated using ZnCl2 under different pyrolysis temperatures in the order 600 °C > 500 °C > 400 °C > 300 °C. Finally, the amount of adsorbed P by activated biochar at different ratios of biochar to ZnCl2 appeared in the order 1:3 ≒ 1:1 > 3:1. As a result, the optimum ratio of biochar to ZnCl2 and pyrolysis temperature were found to be 1:1 and 600 °C for P adsorption, respectively. The maximum P adsorption capacity by activated biochar using ZnCl2 (15,460 mg kg(-1)) was higher than that of typical biochar, as determined by the Langmuir adsorption isotherm. Therefore, the ZnCl2 activation of sesame straw biochar was suitable for the preparation of activated biochar for P adsorption.

Surgical treatment of solid pseudopapillary neoplasms of the pancreas and risk factors for malignancy.

BACKGROUND: The aim of this study was to identify clinical predictors of malignancy and surgical strategies for pancreatic solid pseudopapillary neoplasm (SPN) by analysis of surgical outcomes at a single institution. METHODS: All patients who underwent surgery for SPN between 1995 and 2010 were identified. Histopathology slides of all patients were reviewed by a specialized pathologist and the neoplasms were classified according to the criteria of the World Health Organization 2010. RESULTS: Of the 106 patients identified, 85 (80·2 per cent) were female, and the median age was 36 (range 10-65) years. Median tumour size was 4·5 (range 1·0-15·0) cm. Some 17 patients (16·0 per cent) were classified as having a high-grade malignant SPN. Tumour size of at least 5 cm was associated with high-grade malignant potential (P = 0·022). Although lymph nodes were removed from 40 patients (37·7 per cent), there were no nodal metastases. A total of five patients underwent en bloc resection of adjacent structures, including two with portal vein involvement. After a median follow-up of 56·9 months, two patients with high-grade malignant SPN had evidence of tumour recurrence in the lymph nodes and liver. CONCLUSION: SPN with a diameter of 5 cm or more is associated with a high-grade malignant phenotype. Complete surgical removal is associated with low recurrence rates.

Neural transdifferentiation of human bone marrow mesenchymal stem cells on hydrophobic polymer-modified surface and therapeutic effects in an animal model of ischemic stroke.

Human bone marrow-derived mesenchymal stem cells (MSCs) have multi-lineage differentiation potential and can become cells of mesodermal and neural lineages. These stem cells thus hold considerable clinical promise for the treatment of neurodegenerative diseases. For successful regeneration of damaged neural tissues, directed differentiation of neural or neuronal precursor cells from MSCs and integration of transplanted cells are pivotal factors. We induced MSCs into neurogenesis using a modified protocol. The therapeutic potency of the resulting neural progenitor cells in a rat model of ischemic stroke was analyzed. Using a highly hydrophobic diphenylamino-s-triazine-bridged p-phenylene (DTOPV)-coated surface and adopting a procedure for propagation of neural stem cells, we efficiently converted MSCs into neurosphere-like cellular aggregates (NS-MSCs). The spherical cells were subsequently induced to differentiate into neural cells expressing neuroectodermal markers. To determine whether these cells had neuronal fates and induced neuro-protective effects in vivo, NS-MSCs were intra-cerebrally administered to rats 48h after permanent middle cerebral artery occlusion (pMCAo). The results showed a remarkable attenuation of ischemic damage with significant functional recovery, although the cells were not fully incorporated into the damaged tissues on post-operative day 26. Improvement in the NS-MSC-transplanted rats was faster than in the MSC group and suppression of inflammation was likely the key factor. Thus, our culture system using the hydrophobic surface of a biocompatible DTOPV coating efficiently supported neural cell differentiation from MSCs. Neural-primed MSCs exhibited stronger therapeutic effects than MSCs in rat brains with pMCAo.

Surgical strategies for non-functioning pancreatic neuroendocrine tumours.

BACKGROUND: The purpose of this study was to identify management strategies for non-functioning pancreatic neuroendocrine tumours (NF-PNETs) by analysis of surgical outcomes at a single institution. METHODS: Archived records of patients with NF-PNETs who underwent surgery between 1994 and 2010 were reviewed. RESULTS: Among 125 patients, the median tumour size was 2·5 (range 0·15-20·5) cm. Of the 51 NF-PNETs with a diameter of no more than 2 cm, 12 (24 per cent) were diagnosed as carcinoma. Overall 20 patients (16·0 per cent) had metastases to the lymph nodes. The minimum size of the tumour with lymph node metastasis was 1·2 cm. Having a NF-PNET of 2 cm or larger significantly increased the probability of a poorly differentiated carcinoma (P = 0·006), and having a NF-PNET of at least 2·5 cm significantly increased the probability of lymph node metastasis (P = 0·048). The 5-year cumulative survival rate after curative resection was 89·7 per cent. During a median follow-up of 31·5 months, there were 27 recurrences (23·1 per cent) and 13 disease-specific deaths (11·1 per cent) among the 117 patients who had an R0 resection. All patients who underwent repeat operations were alive without additional recurrence after a mean(s.d.) follow-up of 27·1(18·0) months. CONCLUSION: Curative surgery should be performed for control of primary NF-PNETs. Lymph node dissection for NF-PNETs of 2·5 cm or larger and at least node sampling for tumours with a diameter of 1 cm or more are recommended. Debulking surgery should be considered for advanced tumours.

Farnesoid X receptor, overexpressed in pancreatic cancer with lymph node metastasis promotes cell migration and invasion.

BACKGROUND: Lymph node metastasis is one of the most important adverse prognostic factors for pancreatic cancer. The aim of this study was to identify novel lymphatic metastasis-associated markers and therapeutic targets for pancreatic cancer. METHODS: DNA microarray study was carried out to identify genes differentially expressed between 17 pancreatic cancer tissues with lymph node metastasis and 17 pancreatic cancer tissues without lymph node metastasis. The microarray results were validated by real-time PCR. Immunohistochemistry and western blotting were used to examine the expression of farnesoid X receptor (FXR). The function of FXR was studied by small interfering RNA and treatment with FXR antagonist guggulsterone and FXR agonist GW4064. RESULTS: Farnesoid X receptor overexpression in pancreatic cancer tissues with lymph node metastasis is associated with poor patient survival. Small interfering RNA-mediated downregulation of FXR and guggulsterone-mediated FXR inhibition resulted in a marked reduction in cell migration and invasion. In addition, downregulation of FXR reduced NF-κB activation and conditioned medium from FXR siRNA-transfected cells showed reduced VEGF levels. Moreover, GW4064-mediated FXR activation increased cell migration and invasion. CONCLUSIONS: These findings indicated that FXR overexpression plays an important role in lymphatic metastasis of pancreatic cancer and that downregulation of FXR is an effective approach for inhibition of pancreatic tumour progression.

The outcomes after surgical resection in pancreatic endocrine tumors: an institutional experience.

AIM: Sporadic pancreatic endocrine tumors (PET) can be managed surgically with excellent outcomes. The aim of this study was to analyze surgical outcomes and factors influencing survival. METHODS: Between 1995 and 2007, 96 patients with sporadic PET who underwent surgery at our institution were retrospectively reviewed for clinicopathologic variables and outcomes according to the World Health Organization (WHO) classifications. RESULTS: Thirty-nine patients had well-differentiated tumors (WDT) with benign behavior, 23 had uncertain behavior, 27 had low-grade carcinoma, and 7 were diagnosed with high-grade carcinoma. R0 resection was performed in 84 patients. No recurrence was observed in WDT regardless of its behavior or curability but 16 of 34 patients with carcinoma had recurrence. Five-year overall survival (OS) for R0-resected patients with carcinoma was 57%, and OS at 3 years for R1/R2-resected patients was 23% (P = 0.012). The WHO classification and R0 resection were independent prognostic factors in multivariate analysis. CONCLUSIONS: This single institutional experience demonstrated that surgical resection is curative for WDT and recurrences are frequent in spite of curative resection for malignant PET. The WHO classification and R0 resection remained independent prognostic factor.

Mechanical force augments the anti-osteoclastogenic potential of human gingival fibroblasts in vitro.

BACKGROUND AND OBJECTIVE: The cellular response of human gingival fibroblasts to a mechanical force is considered to be primarily anti-osteoclastic because they produce relatively high levels of osteoprotegerin. However, there is little information available on the effects of compression force on the production of osteoprotegerin and osteoclastic differentiation by these cells. In this study, we examined how mechanical force affects the nature of human gingival fibroblasts to produce osteoprotegerin and inhibit osteoclastogenesis. MATERIAL AND METHODS: Human gingival fibroblasts were exposed to mechanical force by centrifugation for 90 min at a magnitude of approximately 50 g/cm(2). The levels of osteoprotegerin, receptor activator of nuclear factor-kappaB ligand (RANKL), interleukin-1beta and tumor necrosis factor-alpha were measured at various time-points after applying the force. The effect of the centrifugal force on the formation of osteoclast-like cells was also determined using a co-culture system of human gingival fibroblasts and bone marrow cells. RESULTS: Centrifugal force stimulated the expression of osteoprotegerin, RANKL, interleukin-1beta and tumor necrosis factor-alpha by the cells, and produced a relatively high osteoprotegerin to RANKL ratio at the protein level. Both interleukin-1beta and tumor necrosis factor-alpha accelerated the force-induced production of osteoprotegerin, which was inhibited significantly by the addition of anti-(interleukin-1beta) immunoglobulin Ig isotype; IgG (rabbit polyclonal). However, the addition of anti-(tumor necrosis factor-alpha) immunoglobulin Ig isotype; IgG1 (mouse monoclonal) had no effect. Centrifugal force also had an inhibitory effect on osteoclast formation. CONCLUSION: Application of centrifugal force to human gingival fibroblasts accelerates osteoprotegerin production by these cells, which stimulates the potential of human gingival fibroblasts to suppress osteoclastogenesis. Overall, human gingival fibroblasts might have natural defensive mechanisms to inhibit bone resorption induced by a mechanical stress.

A potential role of connexin 43 in epidermal growth factor-induced proliferation of mouse embryonic stem cells: involvement of Ca2+/PKC, p44/42 and p38 MAPKs pathways.

OBJECTIVES: The gap junction protein, connexin (Cx), plays an important role in maintaining cellular homeostasis and cell proliferation by allowing communication between adjacent cells. Therefore, this study has examined the effect of epidermal growth factor (EGF) on Cx43 and its relationship to proliferation of mouse embryonic stem cells. MATERIALS AND METHODS: Expressions of Cx43, mitogen-activated protein kinases (MAPKs) and cell cycle regulatory proteins were assessed by Western blot analysis. Cell proliferation was assayed with [(3)H]thymidine incorporation. Intercellular communication level was measured by a scrape loading/dye transfer method. RESULTS: The results showed that EGF increased the level of Cx43 phosphorylation in a time- (> or =5 min) and dose- (> or =10 ng/mL) dependent manner. Indeed, EGF-induced increase in phospho-Cx43 level was significantly blocked by either AG 1478 or herbimycin A (tyrosine kinase inhibitors). EGF increased Ca(2+) influx and protein kinase C (PKC) translocation from the cytosolic compartment to the membrane compartment. Moreover, pre-treatment with BAPTA-AM (an intracellular Ca(2+) chelator), EGTA (an extracellular Ca(2+) chelator), bisindolylmaleimide I or staurosporine (PKC inhibitors) inhibited the EGF-induced phosphorylation of Cx43. EGF induced phosphorylation of p38 and p44/42 MAPKs, and this was blocked by SB 203580 (a p38 MAPK inhibitor) and PD 98059 (a p44/42 MAPK inhibitor), respectively. EGF or 18alpha-glycyrrhetinic acid (GA; a gap junction inhibitor) increased expression levels of the protooncogenes (c-fos, c-jun and c-myc), cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2), CDK4 and p-Rb], [(3)H]thymidine incorporation and cell number, but decreased expression levels of the p21(WAF1/Cip1) and p27(Kip1), CDK inhibitory proteins. Transfection of Cx43 siRNA also increased the level of [(3)H]thymidine incorporation and cell number. EGF, 18alpha-GA or transfection of Cx43 siRNA increased 2-DG uptake and GLUT-1 protein expression. CONCLUSIONS: EGF-induced phosphorylation of Cx43, which was mediated by the Ca(2+)/PKC, p44/42 and p38 MAPKs pathways, partially contributed to regulation of mouse embryonic stem cell proliferation.

Prognostic model to predict survival following first-line chemotherapy in patients with metastatic gastric adenocarcinoma.

BACKGROUND: This study was to devise a prognostic model for metastatic gastric cancer patients undergoing first-line chemotherapy. PATIENTS AND METHODS: A retrospective analysis was carried out on 1455 gastric cancer patients, who received first-line chemotherapy from September 1994 to February 2005. RESULTS: At multivariate level, poor prognostic factors were no previous gastrectomy [P = 0.003; relative risk (RR), 1.191; 95% confidence interval (CI) 1.061-1.338], albumin < 3.6 g/dl (P = or <0.001; RR, 1.245; 95% CI 1.106-1.402), alkaline phosphatase > 85 U/l (P = or <0.001; RR, 1.224; 95% CI 1.092-1.371), Eastern Cooperative Oncology Group performance status of two or more (P = or <0.001; RR, 1.690; 95% CI 1.458-1.959), the presence of bone metastases (P = 0.001; RR, 1.460; 95% CI 1.616-1.836), and the presence of ascites (P = or < 0.001; RR, 1.452; 95% CI 1.295-1.628). Of 1434 patients, 489 patients (34.1%) were categorized as low-risk group (zero to one factors), 889 patients (62.0%) as intermediate-risk group (two to four factors), and 56 patients (3.9%) as high-risk group (five to six factors). Median survival durations for low, intermediate, and high-risk groups were 12.5 months, 7.0 months, and 2.7 months, respectively. CONCLUSIONS: This model should facilitate the individual patient risk stratification and thus, more appropriate therapies for each metastatic gastric cancer patient.

Characterisation of heavy metal tolerance and biosorption capacity of bacterium strain CPB4 (Bacillus spp.).

A heavy metal resistant bacterium Bacillus spp. strain CPB4 was isolated from heavy metal contaminated soil in Korea and further characterised. The CPB4 strain showed a high capacity for uptake of heavy metal Pb (Pb > Cd > Cu > Ni > Co > Mn > Cr > Zn) both in single and in mixed heavy metal solution. Optimal conditions for heavy metal uptakes of CPB4 strain were 20-40 degrees C culture temperature, 5-7 pH and 24 h pre-culture times. TEM showed that large amounts of the electron-dense granules (heavy metal complexes) were found mainly on the cell wall and cell membrane. Furthermore, more than 90% of adsorbed heavy metals were distributed both in cell wall and in cell membrane fractions. The amount of heavy metal uptake was remarkably decreased by reducing the crude protein contents when cells were treated by alkali solutions. Therefore, this study showed one of the possible examples for useful bioremediation.

Treatment of non-biodegradable cutting oil wastewater by ultrasonication-Fenton oxidation process.

To treat cutting oil wastewater produced in metal surface treatment industry, Ultrasonication (US)-Fenton process, which is one of the advanced oxidation processes, was used. The optimum conditions to treat non-biodegradable pollutants using the US-Fenton process were that the application rates of H2O2 and FeSO4 were 10% and 3 g/L, respectively, the value of pH was 3, and the ultrasonication time was 30 min. It identified non-degradable pollutants such as ethylene diamine tetraacetic acid (EDTA) and Triethanolamine (TEA) in the cutting oil wastewater. TLC analysis of two compounds of treated water by the coagulation process was similar to that of raw water. However, TLC analysis of two compounds of US-Fenton process was different from that of raw water, meaning that US-Fenton process decomposed the EDTA and TEA. To study the possibility of application with the US-Fenton process to pilot plant, the pollutants treatment efficiency of three different methods, such as US-Fenton process, activated sludge process and coagulation process, in continuous experiments were compared. The removal rate of pollutants by the US-Fenton process according to the effluent time was higher than any other processes. The removal rates of COD, SS, T-N and T-P by US-Fenton process were 98, 93, 75 and 95%, respectively.

Toluene-induced accumulation of trehalose by Pseudomonas sp. BCNU 106 through the expression of otsA and otsB homologues.

AIM: The objective of this study was to investigate toluene-induced accumulation mechanism of trehalose in a toluene-tolerant bacterium Pseudomonas sp. BCNU 106. METHODS AND RESULTS: The accumulation of trehalose by a toluene-tolerant bacterium Pseudomonas sp. BCNU 106 was examined at various cultivation time by measuring the total intracellular trehalose content, trehalase activity and mRNA levels of the trehalose-biosynthetic genes. The pattern of trehalose accumulation corresponded to the mRNA expression pattern of the trehalose-biosynthetic genes with the maximum level at 12 h or 4 h of cultivation with 10% (v/v) toluene, respectively. The trehalose-biosynthetic genes were also cloned and sequenced. Furthermore, the effects of toluene addition on the intracellular osmotic pressure and pH were investigated. It was shown that homeostasis was maintained in the bacterial cells. CONCLUSIONS: In a toluene-tolerant bacterium Pseudomonas sp. BCNU 106, a significant amount of trehalose was accumulated through the toluene-induced expression of the trehalose-biosynthetic genes after the exposure to toluene. SIGNIFICANCE AND IMPACT OF THE STUDY: The accumulation of the high level of intracellular trehalose was preceded by the expression of otsA/B genes in toluene-tolerant bacteria, contributing to the elucidation of the tolerance mechanism.

Primary malignant retroperitoneal tumors: analysis of a single institutional experience.

AIMS: In order to achieve complete resection in the surgical management of retroperitoneal tumors, it is crucial to know the tumor's anatomical location relative to neighboring organs. METHODS: Forty-nine patients with primary malignant retroperitoneal tumors were divided by tumor location into two groups [upper abdomen (group 1) or lower abdomen (group 2)], and clinicopathological features, tumor recurrence, and patient survival were assessed. RESULTS: No significant differences in preoperative clinical characteristics existed between two groups, and liposarcoma was the most frequently observed tumor type. The difference in the rates of complete resection between the two groups was not statistically significant (75.9% for group 1 and 85% for group 2). En-bloc combined resection was performed in 52% and 30% of patients in groups 1 and 2, respectively. The local recurrence rate in group 2 (31.3%) was higher than that in group 1 (9.5%), despite the fact that the differences in rates of complete resection and distant recurrence rates (14.3% in group 1 and 12.5% in group 2) between the two groups were not statistically significant. The overall 5-year survival rates were 67.9% for group 1 and 43.2% for group 2 (p=0.038). The 5-year survival rate of patients with tumors smaller than 10 cm was 78.4%, while that of patients with tumors larger than 10 cm was 38.1% (p=0.017). The 5-year survival rate after complete excision was 61%, whereas that after incomplete resection or biopsy only was 40.0% (p<0.0001). CONCLUSIONS: An upper abdominal tumor location is a positive prognostic factor even if small tumor size (<10 cm) and complete resection of the tumor are still more important factors to improve outcome in patients with malignant primary retroperitoneal tumors. Because complete resection was shown to be the most important prognostic factor, an aggressive and careful surgical approach is recommended for the treatment of such tumors.

Liver transplantation for hepatocellular carcinoma with bile duct thrombi.

In a few cases of hepatocellular carcinoma (HCC), jaundice results from obstructive causes, including tumor invasion or thrombi in the bile duct. We have reported herein our experience with liver transplantation (OLT) for HCC cares showing bile duct thrombi (BDT). From September 1996 to August 2004, 140 adult patients underwent OLT for HCC at our center. Four patients (2.9%) who had OLT performed for HCC had BDT and were included in this study. The patients were all men of mean age 57.0 years. The initial total bilirubin levels were in the range of 2.0 to 30.5 mg/dL. The sizes of the tumors ranged from 2.0 cm to 3.0 cm in diameter, all were single lesions. The median follow-up period was 20.6 months (range: 17.6 to 28.1 months). The only case in which the BDT was identified intraoperatively died 20 months after OLT due to multiple intrahepatic recurrences. The other three patients were alive, showing no evidence of recurrence at the end of follow-up. Although a series of four is too small to reach any conclusion, we suggest that OLT may be a treatment option for HCC with BDT in selected cases.

Outcome of patients with recurrent hepatocellular carcinoma in liver transplantation.

Liver transplantation (OLT) is the treatment of choice for patients with hepatic cirrhosis related hepatocellular carcinoma (HCC). Among 156 liver transplant patients for HCC from June 1996 to February 2005, 23 had recurrent HCC. To evaluate risk factors that affect early recurrence of HCC after OLT, we divided the 23 patients into two groups: early (< or =12 months) and late (>12 months) recurrences. Among them, 15 patients were dead and eight alive patients had been followed to 31 July 2005. The most common recurrence site was the grafted liver (n = 15), next was bone (n = 11), lung (n = 8), lymph node (n = 6), brain (n = 4), skin (n = 2), adrenal gland (n = 1). There were no significant differences between the two groups in age or tumor size, number of tumors, cell differentiation, alpha-feto protein levels, tumor staging, number of patients within Milan criteria, steroid pulse therapy, infectious diseases, and immunostaining of tumor. In our study, there were no risk factors that predict early tumor recurrence. We noticed that more patients in the early recurrence group were excluded by Milan criteria due to a more progressed tumor staging with higher mean levels of serum alpha-feto protein.

Microvascular tumor embolism: independent prognostic factor after liver transplantation in hepatocellular carcinoma.

Microscopic tumor cell dissemination may be a more important factor in the recurrence of hepatocellular carcinoma (HCC) after liver transplantation, probably because of posttransplant immunosuppression. The presence of microvascular tumor embolism was undetermined as a factor for HCC recurrence after orthotopic liver transplantation (OLT). This study evaluated whether microvascular tumor embolism affects recurrence-free survival and correlates with other clinicopathologic factors after OLT among patients with HCC. From September 1996 to June 2003, 72 OLTs for HCC were enrolled in this study. Median follow-up was 22.8 months. Among 41 patients without microvascular tumor embolism, 1-year, 2-year, and 5-year recurrence-free survival rates were all 97.6%, while these rates were 77.3%, 68.2%, and 59.7%, respectively, for 31 patients (43.1%) with microvascular tumor embolism (P = .0006). The 5-year recurrence-free survival rate showed significant differences for a pT2 tumor (P = .0073), for maximal tumor size <3 cm (P = .0328), for > or =5 cm solitary tumor (P = .0095), and for the presence of a tumor capsule (P = .0012), within the Milan criteria (P = .0376). At multivariate analysis, significant independent predictors for HCC recurrence were microvascular tumor embolism and histopathologic grade. In conclusion, microvascular tumor embolism is an independent predictor of HCC recurrence after liver transplantation. Although OLT is a safe and effective treatment for HCC within the Milan criteria, the presence of microvascular tumor embolism at pathologic examination can predict its recurrence. In these cases, the feasibility of immunosuppressive therapy or adjuvant chemotherapy must be considered to prevent tumor recurrence.

Auxiliary partial orthotopic liver transplantation in the treatment of acute liver failure: a case report.

A successful experience with auxiliary partial orthotopic liver transplantation (APOLT) for acute liver failure is reported in a 29-year-old woman who experienced jaundice, generalized erythema for 7 days, and decreased mentation for 3 days. Two months prior, she suffered pulmonary tuberculosis, being currently treated with antituberculous medications, which caused the fulminant hepatic failure. We decided to perform APOLT based on two facts. The first was the possibility that the diseased native liver may recover sufficiently to withdraw the immunosuppressants. Second, the pulmonary tuberculosis may have been worsened by immunosuppression. We removed the extended lateral section of the recipient for the graft. The left hepatic vein of the extended left lateral graft was anastomosed to the left hepatic vein of the recipient. The left portal vein of the graft was anastomosed to the left portal vein of the recipient. The right portal vein of the recipient was left without any manipulation. A duct-to-duct anastomosis was performed. On postoperative day 3, antituberculous medications were started. On the postoperative day 37, she was discharged without any problems. On the postoperative day 120, she showed no event of rejection, and her pulmonary symptoms improved. We performed the operation without transection of the portal branch to the native liver, but no functional competition has been discovered.

Factors affecting graft survival after living donor liver transplantation.

Living donor liver transplantation (LDLT) has been considered as an alternative option to resolve the shortage of cadaveric donor organs, despite the ethical aspects of the donor procedure. The objective of this study was to analyze the risk factors affecting graft survival in LDLT. From June 1996 to December 2002, 141 patients who underwent LDLT were retrospectively analyzed. Graft survival rates were 82.5%, 80%, 77.3%, and 77.3% at 6 months, 1 year, 3 years, and 5 years, respectively. The factors influencing graft survival in univariate analysis were graft-to-recipient body weight ratio (GRWR) less than 0.8% (P = .0009), intraoperative transfusion of more than six packed RBC units in addition to the use of cell saver amounts (P = .0001), left lobe grafts in adults causing small-for-size situations (P = .0135), and donor age (P = .0472). The multivariate analysis demonstrated that GRWR less than 0.8% (P = .002) and intraoperative transfusion of more than six packed RBC units (P = .014) were independent factors that decreased graft survival rates. The graft selection of greater than 0.8% of GRWR and reduction of intraoperative RBC transfusion improve graft survival.