Search

Bioimaging in the near-infrared window is of great importance to study the dynamic processes

Bioimaging in the near-infrared window is of great importance to study the dynamic processes in vivo with deep penetration, high spatiotemporal resolution, and minimal tissue absorption, scattering...

Background & Aims Many patients with pancreatic ductal adenocarcinoma (PDAC) develop recurrent or metastatic diseases after surgery, so it is important to identify those most likely to benefit from aggressive therapy. Disruption of tissue microarchitecture is an early step in pancreatic tumorigenesis and a parameter used in pathology grading of glandular tumors. We investigated whether changes in gene expression during pancreatic epithelial morphogenesis were associated with outcomes of patients with PDAC after surgery. Methods We generated architectures of human pancreatic duct epithelial cells in a 3-dimensional basement membrane matrix. We identified gene expression profiles of the cells during different stages of tubular morphogenesis (tubulogenesis) and of PANC-1 cells during spheroid formation. Differential expression of genes was confirmed by immunoblot analysis. We compared the gene expression profile associated with pancreatic epithelial tubulogenesis with that of PDAC samples from 27 patients, as well as with their outcomes after surgery. Results We identified a gene expression profile associated with tubulogenesis that resembled the profile of human pancreatic tissue with differentiated morphology and exocrine function. Patients with PDACs with this profile fared well after surgery. Based on this profile, we established a 6−28 gene tubulogenesis-specific signature that accurately determined the prognosis of independent cohorts of patients with PDAC (total n = 128; accuracy = 81.2%−95.0%). One gene, ASPM , was down-regulated during tubulogenesis but up-regulated in human PDAC cell lines and tumor samples; up-regulation correlated with patient outcomes (Cox regression P = .0028). Bioinformatic, genetic, biochemical, functional, and clinical correlative studies showed that ASPM promotes aggressiveness of PDAC by maintaining Wnt-β-catenin signaling and stem cell features of PDAC cells. Conclusions We identified a gene expression profile associated with pancreatic epithelial tubulogenesis and a tissue architecture−specific signature of PDAC cells that is associated with patient outcomes after surgery.

Summary Background Deregulation of mammalian target of rapamycin (mTOR) signalling is common in human hepatocellular carcinoma (HCC). Aim To determine the maximum tolerated dose (MTD) of the oral mTOR inhibitor everolimus in advanced HCC patients. Methods Patients with locally advanced or metastatic HCC (Child-Pugh class A or B) were enrolled in an open-label phase 1 study and randomly assigned to daily (2.5–10 mg) or weekly (20–70 mg) everolimus in a standard 3 + 3 dose-escalation design. MTD was based on the rate of dose-limiting toxicities (DLTs). Secondary endpoints included safety, pharmacokinetics and tumour response. In a post hoc analysis, serum hepatitis B virus (HBV) DNA levels were quantified. Results Thirty-nine patients were enrolled. DLTs occurred in five of 21 patients in the daily and two of 19 patients in the weekly cohort. Daily and weekly MTDs were 7.5 mg and 70 mg respectively. Grade 3/4 adverse events with a ≥10% incidence were thrombocytopenia, hypophosphataemia and alanine transaminase (ALT) elevation. In four hepatitis B surface antigen (HBsAg)-seropositive patients, grade 3/4 ALT elevations were accompanied by significant (>1 log) increases in serum HBV levels. The incidence of hepatitis flare (defined as ALT increase >100 IU/mL from baseline) in HBsAg-seropositive patients with and without detectable serum HBV DNA before treatment was 46.2% and 7.1% respectively (P

Background. Pancreatic fistula is still the major postoperative morbidity after distal pancreatectomy (DP). An inductive heat technology via needle arrays in a system of alternating magnetic fields (AMFs) was designed to seal off the pancreatic end. Methods. Twenty Lanyu pigs were divided into 2 groups for DP: the conventional group had hand-sewn closure of the pancreatic end (n = 10), and the AMF group received thermal DP by AMF (n = 10). Pathological examinations of the resected and remnant pancreas were studied immediately after resection and on the 14th postoperative day (POD), respectively. The severity and the incidence of pancreatic abscess were compared. Results. The incidence and severity of pancreatic abscess were significantly decreased in the AMF group than those in the conventional group ( P = .009). In the immediate postoperative period, microscopic examination of the pancreatic resected end showed prominent coagulative necrosis, loss of NADPH-diaphorase activity, and significant apoptosis at the resected pancreas in the AMF group compared with the control group. Fourteen days after AMF ablation, the pancreatic stump end was covered with thick fibrosis, and histological study of the remnant pancreas showed that the parenchyma had well recovered with positive NADPH-diaphorase activity, and the pancreatic duct was sealed off successfully by prominent periductal fibrosis and intraductal plug. The body weight gain on the 14th POD was significantly increased in the AMF group (from 23.8 ± 1.8 kg to 25.4 ± 5.5 kg) compared with the conventional group (from 25.3 ± 2.1 to 25.4 ± 6.0 kg; P = .003). Conclusions. Inductive heats by the AMF system via needle array can be performed easily and can seal the pancreatic cut surface well during DP.

Purpose To evaluate the therapeutic efficacy of 3-month triplet induction chemotherapy (ICT) followed by concomitant chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer (LAPC). Patients and Methods Chemonaive patients with measurable, histologically confirmed LAPC were eligible. The ICT consisted of biweekly gemcitabine (800 mg/m 2 ) infusion at a fixed dose rate (10 mg/m 2 /min), followed by 85 mg/m 2 oxaliplatin and 48-h infusion of 5-fluorouracil/leucovorin (3000/150 mg/m 2 ) for 6 cycles. Patients without disease progression 4 weeks after ICT would receive weekly 400 mg/m 2 gemcitabine and 5040 cGy radiation in 28 fractions. After CCRT, patients were subjected for surgical intervention and/or maintenance chemotherapy until progression or intolerable toxicity. Results Between December 2004 and August 2008, 50 patients were enrolled. The best responses after ICT were partial response (PR) in 9, stable disease in 26, and progressive disease or not evaluable in 15. Among the former 35 patients, 2 had disease progression before CCRT, and 3 declined to have CCRT. Of the 30 patients receiving CCRT, an additional 4 and 1 patient(s) achieved PR at the end of CCRT and during maintenance chemotherapy, respectively. On intent-to-treat analysis, the overall best response was PR in 14 patients and stable disease in 21. The overall response rate and disease control rate were 28% (95% confidence interval [CI], 16.2–42.5%) and 70% (95% CI, 44.4–99.2%), respectively. The median time to progression and overall survival of the intent-to-treat population was 9.3 (95% CI, 5.8–12.8) months and 14.5 (95% CI, 11.9–17.1) months, respectively. One- and two-year survival rates were 68% (95% CI, 55.1–80.9%) and 20.6% (95% CI, 8.7–32.5%), respectively. Neutropenia was the most common Grade 3–4 toxicity of both ICT and CCRT, with a frequency of 28% and 26.7%, respectively. Significant sensory neuropathy occurred in 9 patients (18%). Conclusion Three months of triplet ICT followed by gemcitabine-based CCRT is feasible, moderately active, and associated with encouraging survival in patients with LAPC.

The present study was done to investigate the prevalence of zinc deficiency after pancreatoduodenectomy (PD) and its correlation with pancreatic exocrine insufficiency.Patients were included in this study if they had undergone PD for periampullary tumors without recurrence and had received follow-up for more than 6 months between February 2006 and June 2007. Serum levels of zinc, fasting glucose, albumin, and iron were obtained. The pancreatic exocrine function was evaluated by a fecal elastase-1 assay, stool fat assessment, and a pancreatic duct-parenchymal ratio (DPR) at the L1 level using abdominal computed tomography (CT). The quality of life was estimated with a questionnaire of EORTC QLQ-C30 and PAN26. All of these patients were then supplemented with oral pancreatic enzymes for 4 weeks to evaluate the effect of these enzymes on zinc deficiency.Forty-eight eligible patients, 27 men and 21 women, were included. The mean age was 61.3 ± 1.7 years. Thirty-three (68%) patients had a zinc deficiency with a mean zinc level of 72.3 ± 2.9 mcg/dl (normal range: 80-120 mcg/dl). Patients with lower serum zinc levels tended to have typical presentations of zinc deficiency (P = 0.039, χ(2)). The serum zinc level was significantly negatively correlated with pancreatic duct diameter, DPR, and positive stool fat during the late follow-up period. The most common presentations of patients with lower serum zinc levels were skin rash, photophobia, and glossitis. These gastrointestinal disorders, as well as symptoms of zinc deficiency, improved after pancreatic enzyme supplementation.Zinc deficiency after PD was a common phenomenon and correlated with pancreatic exocrine insufficiency.

Tumor cell growth is influenced by the cellular microenvironment including the presence of immune cells and blood vessels. Currently, no transplantable gastric cancer syngeneic animal models exist; therefore, we set out to establish a mouse gastric carcinoma cell line, which was named mouse gastric carcinoma cell line 3I (MGCC3I), from forestomach carcinoma developed in benzo[a]pyrene-treated ICR mice. MGCC3I cells showed epithelial-like morphology, multinuclear giant cell formation, and retained an intestinal phenotype, which are similar to human gastric cancer carcinoma cells. The expression of gastric cancer markers MUC1, MUC2, and MUC5AC, and oncogenes c-myc, c-met, cyclin E1, and cancer stem cell marker CD44 was determined in MGCC3I cells. MGCC3I cells formed poorly differentiated stomach tumors following orthotopic implantation into the stomachs of syngeneic ICR mice. Histone deacetylase inhibitors are recognized as a new class of anticancer drugs. The immunological therapeutic effects of the histone deacetylase inhibitors sodium butyrate and valproic acid were evaluated in this new animal tumor model. Sodium butyrate inhibited MGCC3I stomach tumor formation in animal models. Increased tumor infiltration by CD8 T cells and neutrophils was observed in mice treated with sodium butyrate or valproic acid. Depletion of CD8 T cells significantly attenuated tumor regression mediated by histone deacetylase inhibitors, which is correlated with enhancement of the MHC class I pathway in MGCC3I cells. Taken together, we have successfully established an orthotopic transplantable gastric tumor animal model and demonstrated its usefulness in revealing the role of CD8 T cells in the therapeutic effects of sodium butyrate.

Tumor-associated macrophages (TAMs) promote cancer cell proliferation and distant metastases. Osteopontin (OPN) is overexpressed in several human cancer cells and in TAMs. Therefore, we set out to determine the role of OPN-expressing macrophages in cancer.In 100 ampullary cancers, diffuse cytoplasmic positivity for OPN was found in infiltrating TAMs in 36 patients and marginal TAMs in 32 patients; OPN(+) macrophages were absent in 32 patients. Expression patterns of OPN in TAMs were associated with pancreatic invasion, tumor stage, TNM stage, lymphovascular invasion and recurrence with peritoneal carcinomatosis. Patients were stratified according to a median tumor size of 2 cm. Patients with tumor sizes ≥2 cm and OPN(+) infiltrating TAMs had a poorer disease-specific survival rate than those with OPN(+) marginal TAMs. Macrophage-associated cytokine expression in ampullary cancer cells was also assessed; levels of macrophage migration inhibitory factor (MIF) in cancer cells were higher than in normal duodenal mucosa.Specimens from ampullary cancer patients at National Cheng Kung University Hospital were collected for immunohistochemistry. Plasma OPN was measured by enzyme-linked immunosorbent assay. Tumor and normal epithelial cells from fresh tissues were separated by laser-assisted microdissection for reverse-transcription polymerase chain reaction and quantitative real-time PCR analyses.Expression of OPN and location of TAMs in bulky ampullary cancer predict recurrence. In addition, cytoplasmic staining of MIF is enhanced in ampullary cancer cells. Patients with bulky tumor, OPN(+) infiltrating TAMs and MIF expression had a worst disease-specific survival.

CD44 and osteopontin (OPN) are functionally related molecules that, alone or in combination, play miscellaneous biological and pathophysiologic roles. CD44 cleavage, one unique feature of CD44, occurs in human cancers, but its function remains unclear. This study aimed to assess the clinicopathologic significance and mechanism of CD44 cleavage in gastrointestinal stromal tumor (GIST) with respect to OPN and OPN/CD44 interaction.CD44 cleavage was evaluated by immunoblotting in 31 primary GIST tumor specimens with paired normal tissues. OPN/CD44 interaction was examined by in situ proximity ligation assay. The associations of CD44 cleavage activity with clinicopathologic parameters, cyclin D1 expression, beta-catenin expression, OPN expression, and OPN/CD44 interaction were analyzed.CD44 cleavage activity was demonstrated in 87.1% of GIST, in contrast to its absence in normal tissues. Increased CD44 cleavage activity was significantly associated with enhanced mitosis by multivariate analysis, in addition to being related to tumor size, recurrence, high-risk status, and poor survival by univariate analysis. Mitosis was significantly higher in GIST with increased CD44 cleavage activity, which also positively correlated with tumor-specific beta-catenin and cyclin D1 overexpression, indicating a mitotic effect through aberrant cell cycle. Both OPN and OPN/CD44 interactions were significantly associated with CD44 cleavage.Our study demonstrates the clinicopathological significance of CD44 cleavage in GIST. There is a significantly increased mitosis associated with CD44 cleavage in relation to OPN/CD44 interaction and dysregulated cell cycle in GIST.

Background and Objectives Distant metastasis resulting from carcinoma cell detachment from the primary tumor involves modification of adhesion molecules. This study was conducted to examine the correlation of E-cadherin/β-catenin expression with survival and recurrence in ampullary neoplasms. Methods Patients with diagnoses of ampullary neoplasms were enrolled in the study. Demographics, operative findings, and histopathological data were collected by retrospective chart review. Expression of E-cadherin and β-catenin were detected by immunohistochemistry. Results A total of 110 patients were enrolled in the study. Preservation of membranous staining of E-cadherin was noted in 41 (37%) patients, aberrant cytoplasmic staining in 48 (44%) patients, and complete loss in 21 (19%) patients. Loss of E-cadherin was associated with pancreatic invasion, recurrence, and poor prognosis. Membranous staining of β-catenin was noted in 65 (59%) patients, cytoplasmic or nuclear accumulation in 16 (15%) patients, and complete loss in 29 (26%) patients. Loss of β-catenin expression was associated with tumor markers, ulcerative type, liver metastases, and poor prognosis. Pancreatic invasion, lymph node involvement, and loss of β-catenin expression were predictors of disease recurrence. Conclusions Loss of the E-cadherin/β-catenin complex is related to poor prognosis in ampullary cancer. Loss of β-catenin is predictor of recurrence in multivariate analysis. J. Surg. Oncol. 2010; 101:356–362. © 2010 Wiley-Liss, Inc.

Summary Background & aims A structured fat emulsion containing 50% medium-chain triglycerides (MCTs) is used for total parenteral nutrition for surgical patients. Due to stability and safety considerations, it is commonly infused separately from dextrose solution, increasing cost and risk of contamination. We evaluated the physiochemical stability and clinical safety of an all-in-one admixture. Methods The physiochemical stability of an all-in-one admixture containing 20% medium- and long-chain triglycerides (Venolipid MCT/LCT 20%), dextrose, amino acids, electrolytes, trace elements and vitamins was compared to a two-in-one system. Solutions were stored at 4 °C for 1 week; appearance, pH, osmolality and particle size and distribution were analyzed at room temperature on days 1, 4 and 7. Clinical safety of the all-in-one admixture versus use of separate systems was determined in patients after major upper abdominal surgery in a prospective, randomized, controlled study (total n = 30). Results During storage, the all-in-one admixture maintained its colour. No precipitation, flocculation or creaming was observed. The pH and average particle size did not change significantly. There were no adverse clinical events related to the all-in-one admixture after continuous infusion for 5 days. Conclusion The all-in-one admixture containing Venolipid MCT/LCT 20% can be stored at 4 °C for 1 week and safely used in patients after major upper abdominal surgery.

Background Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the gastrointestinal tract. Surgery remains the mainstay of curative treatment. Recurrence after surgery was frequent and was associated with poor prognosis. In this study, we tried to identify predictors of recurrence in resectable GISTs. Methods Between January 1995 and December 2005, 100 patients undergoing surgical resection for GISTs in 2 hospitals were studied. Results There were 67 gastric and 33 intestinal GISTs. Recurrence was noted in 11 patients (median follow-up of 43 months). Overall 5-year survival was 84%. Multivariate analysis demonstrated that tumor size ≥10 cm was associated with higher recurrence rates ( P = .032) and was the only independent poor prognostic factor for survival ( P = .020). Conclusions We concluded that tumor size ≥10 cm carried both a higher risk of recurrence and worse survival in resectable GISTs and could be considered an indicator for adjuvant therapy.

CD44 is a transmembrane glycoprotein belonging to the cell-adhesion molecule family. It has been identified as being involved in tumor progression and metastasis, and its expression has been found to be of prognostic significance in several human malignancies. The aim of this study was to assess CD44 expression in gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumor of the gastrointestinal tract. Between January 1995 and March 2006, 92 patients undergoing surgical resection for GIST in National Cheng Kung University Hospital were evaluated. To study the significance of CD44 expression, immunohistochemical staining of CD44 in tumor specimens was performed, and the clinicopathological information of patients was reviewed. Fifty-nine of 81 patients (73%) showed positive CD44 expression. Loss of CD44 expression was associated with disease progression (p = 0.019). Kaplan-Meier analysis revealed better progression-free survival among patients with strong CD44 expression (++ and +++) (p = 0.034), absence of disease progression (p

Results after curative liver resection in hepatocellular carcinoma are unsatisfactory with regard to high postoperative intrahepatic recurrence and liver failure. This study evaluates telomerase activity in liver with and without tumor as a predictor of recurrence and survival.Liver tissue with and without tumor from 53 hepatocellular carcinoma patients receiving curative resection during the period of 1998-2000 was used for detecting telomerase activity by PCR-ELISA. Clinicopathological data were compared to identify predictors of recurrence and survival.Telomerase activity was detected in 98% of liver tissue with tumor and 70% liver tissue without. Telomerase activity in cancerous liver correlated significantly with HCV infection (P = 0.012) and cirrhotic change in liver parenchyma (P = 0.006). Telomerase activity in non-cancerous liver correlated with high serum AFP level (P = 0.002). The telomerase activity of liver tissue with and without tumor is significant higher in patients with recurrence than in those without recurrence, 413.7 +/- 100.5 versus 110.8 +/- 32.7, P = 0.006, and 34.7 +/- 14.2 versus 4.2 +/- 1.4, P = 0.039. Recurrence could be predicted by abnormally high tumor telomerase activity (P = 0.026) or by advanced TNM stage (P = 0.001). TNM stage or high serum ALT level could predict multinodular intrahepatic recurrence (P = 0.028 and P = 0.030). High serum AFP combined with high telomerase activity in liver without tumor had a significant ability to predict poor survival (OR: 11.19, CI: 1.95-64.12, P = 0.007).Tumor telomerase is an independent predictor of recurrence. Simultaneous high remnant liver telomerase and high serum AFP is a strong negative predictor of survival.

Acute intestinal ischemic disorder (AIID) is an uncommon vascular disease with high mortality. According to etiology, it can be categorized into three groups: arterial occlusive mesenteric ischemia (AOMI), mesenteric venous thrombosis (MVT), and nonocclusive mesenteric ischemia (NOMI). This study analyzes the effect of classification on surgical outcome.All AIID patients who underwent operative treatment at National Cheng Kung University Hospital between January 1989 and August 2003 were enrolled in this study. Preoperative information on these patients was compared to find predictors of outcome.Data from 77 patients (49 men and 28 women, median age 70 years) were analyzed. The etiology was AOMI in 30 patients, MVT in 19 patients, and NOMI in 28 patients. Median age was younger in MVT (54 years) than in AOMI (70 years) or NOMI (72 years). In addition, MVT usually involved the jejunum (74%, versus 31% in AOMI and 46% in NOMI), whereas both AOMI and NOMI involved ileum and colon. The patients with AOMI had shorter duration of symptoms and higher ratio of underlying hypertension than those with MVT. The overall mortality rate was 53.2% (41/77). The day 1 and day 30 mortality were 0% and 10.5% in MVT, 16.7% and 30% in AOMI, and 42.9% and 67.9% in NOMI, respectively (P0.05). Both the etiology and the APACHE II scores were significant risk factors for day 30 and long-term mortality. The patients with NOMI had higher POSSUM physiologic scores than patients with MVT. The P-POSSUM regression equation can accurately predict mortality.Patients with MVT had a more favorable prognosis, whereas those with NOMI had the worst outlook. The APACHE II and POSSUM scoring systems are useful in predicting the clinical outcome. Early diagnosis and classification of AIID patients are useful for aggressive treatment to improve the clinical outcome.

The cellular function of electroneutral K-Cl cotransport (KCC) is to regulate epithelial ion transport and osmotic homeostasis. Here we investigate the mechanisms by which insulin-like growth factor 1 (IGF-1) cooperates with KCC to modulate breast cancer biology. IGF-1 stimulates KCC activity of MCF-7 breast cancer cells in a dose- and time-dependent manner. Increased KCC3 and KCC4 abundances contribute to IGF-1-enhanced KCC activity. Endogenous cellular invasiveness was modestly attenuated by KCC4-specific siRNA and the residual invasiveness was much less sensitive to IGF-1 stimulation. KCC3 knockdown significantly reduced basal growth rate and almost abolished IGF-1-stimulated cell proliferation. Consistently, MCF-7 cells obtained advantage in cell proliferation and invasiveness by overexpression of KCC3 and KCC4, respectively. Blockade of gene transcription by actinomycin D abolished IGF-1-mediated increase in KCC3 and KCC4 mRNA, indicating that IGF-1 increases KCC abundance through the regulation of KCC genes. IGF-1 treatment triggered phosphatidylinositol 3-kinase and mitogen-activated protein kinase (MAPK) cascades which were differentially required for IGF-1-stimulated biosynthesis of KCC3 and KCC4. Loss-of-function mutations in KCC significantly inhibited the development and progression of xenograft tumor in SCID mice. The expression level of IGF-1 and KCC polypeptides in the surgical specimens showed a good linear correlation, suggesting autocrine or paracrine IGF-1 stimulation of KCC production in vivo. Among patients with early-stage node-negative breast cancer, disease-free survival (DFS) and overall survival (OS) curves were significantly different based on IGF-1 and KCC expression. Thus, we conclude that KCC activation by IGF-1 plays an important role in IGF-1 receptor signaling to promote growth and spread of breast cancer cells. J. Cell. Physiol. 210: 626–636, 2007. © 2006 Wiley-Liss, Inc.

Literature reports indicate that the incidence of delayed gastric emptying (DGE) is higher after pylorus-preserving pancreaticoduodenectomy (PPPD) than after conventional pancreaticoduodenectomy (CPD), but DGE is traditionally diagnosed from patient-reported subjective sensations. Our clinical radiological experience suggests higher rates for physiological DGE post-CPD. We therefore sought to quantify rates of subjective DGE (sDGE, based on patient complaint) verses objective DGE (oDGE, based on scintography) post-CPD and post-PPPD. Contractile motility of post-PPPD residual stomach was also studied. For 21 PPPD and 33 CPD patients between October 1997 and June 2000, sDGE and oDGE data were collected preoperatively, on postoperative day 14, and 6 months postoperatively, with cholescintography for pylorus ring competency on postoperative day 14. The incidence of sDGE was higher for PPPD (42%) than for CPD (15%) at 14 days, with zero sDGE for both at 6 months. The incidence oDGE was higher for CPD (91%) than for PPPD (76%) at 14 days, with a 6-month incidence of 4.7% in PPPD but approximately 33% for CPD. Solid-phase emptying in PPPD showed that residual stomach retained partial gastric emptying function at 14 days but not at 6 months. Cholescintography showed abnormal pylorus closure function in 2 of 21 PPPD patients but was not related to DGE. Literature reports of higher DGE incidence post-PPPD are true only for subjective symptoms. Radiological measurement of oDGE shows that both CPD and PPPD manifest approximately 80% incidence of DGE in the early postoperative period. At 6 months, approximately 33% of CPD show persistent oDGE. We concluded that (1) the concept of DGE should distinguish between subjective and objective symptoms; (2) loss of distal stomach mechanoreceptors in CPD reduces patients sensation of oDGE, producing "silent" DGE; (3) both CPD and PPPD have high and approximately equal rates oDGE; (4) the previously unnoticed silent oDGE in CPD may contribute to the higher rates of ulceration and related morbidity in association with CPD.

Background/Purpose: The relationship between liver regeneration and spleen size after major hepatectomy in normal and cirrhotic liver was studied by single photon emission computed tomography (SPECT). Materials and methods: Twenty-six patients, 18 patients with normal liver and eight patients with cirrhotic liver, receiving major hepatectomy were included. Liver and spleen volumes were measured by SPECT before major hepatectomy, 6 months, 1 year and 2 years after operation. The correlation of liver and spleen volume during liver regeneration was analyzed. Results: In both groups, the residual liver volume increased within the first year and decreased in the second year. No difference in regeneration ability was found. The spleen volume in cirrhotic liver was increased, with a trend similar to normal liver during the first year. In contrast, the increased spleen volume persisted up to the second year in cirrhotic patients. Age per year, the female sex, and body surface index had a positive correlation with increased percentage of liver volume. The spleen volume per 100 ml with time played a significantly negative role in increasing percentage of liver volume, confidence interval: −2.16 to −27.92, P=0.011. Conclusion: In early cirrhotic liver within normal functional limits, the liver still could regenerate as a normal liver after major hepatectomy in 1 year. Age, the female sex, and body surface index had positive correlation but the size of spleen volume played a negative role to regenerative liver volume.

Introduction Receptor-mediated estrogen activation participates in the development and progression of breast cancer. Estrogen receptor (ER)-α polymorphism has been found to be associated with breast cancer and clinical features of the disease in Caucasians. Epidemiologic studies have revealed that age–incidence patterns of breast cancer in Asians differ from those in Caucasians. Genomic data for ER-α in either population is therefore of value in the clinical setting for that ethnic group. Methods A case–control study was conducted to establish a database of ER-α polymorphisms in a Taiwanese population in order to compare Western and Taiwanese (Asian) distributions and to evaluate ER-α polymorphism as an indicator of clinical outcome. The ER-α gene was scanned in a Taiwanese clinical breast cancer group (189 patients) and in healthy individuals (177 healthy control individuals). PCR single-strand conformation polymorphism technology was employed and real-time PCR melting curve analysis was performed. Results Three sites of silent single nucleotide polymorphism (SNPs) were found, as reported previously in Western studies, but at significantly different frequencies. Among the three SNPs, the frequency of allele 1 (TCT → TCC) in codon 10 was significantly lower in breast cancer patients (32.0%) than in control individuals (40.4%; P = 0.018). We found that allele 1 (ACG → ACA) in codon 594 was less common in breast cancer patients with a family history of breast cancer (5.9%) than in those without such a history (19.6%; P = 0.049). Individually, both allele 1 in codon 325 (CCC → CCG) and allele 1 in codon 594 exhibited a reverse association with the occurrence of lymph node metastasis. Furthermore, incorporation of both SNP markers further increased predictive accuracy. Conclusions Our data suggest that ER-α polymorphisms are correlated with various aspects of breast cancer in Taiwan. ER-α genotype, as determined during presurgical evaluation, might represent a surrogate marker for predicting breast cancer lymph node metastasis.

Background: To formulate individually tailored therapy for patients with early-stage breast cancer, it is necessary to identify biomarkers for predicting metastasis and survival. Methods: A homogeneous cohort of 92 T1-2N0M0 breast carcinoma patients with a long-term follow-up were divided into two groups: the metastasis group (n = 41) and the disease-free group (n = 51). We evaluated the ability of risk discrimination of six biomarkers, including S100A4, Met, bcl-2, p53, survivin, and HER-2/neu, in early-stage breast cancer. Results: In multiple logistic regression analysis, only S100A4 expression (odds ratio = 5.37, p = 0.008) and Met expression (odds ratio = 6.91, p = 0.002) were independent predictors of distant relapse. Multivariate Cox models showed S100A4 and Met expressions were associated with 10-year disease-free survival (DFS) (risk ratio 3.2 and 4.0, respectively); however, tumor size and histological grade were not significant predictors. The 10-year DFS of T1-2N0M0 patients was 55.4%. T1-2N0M0 patients with S100A4-positive tumors had a significantly worse 10-year DFS than those with S100A4-negative tumors (29.0 vs. 68.9 %, p = 0.001). The 10-year DFS in T1-2N0M0 patients with Met-negative tumors was 82.4 vs. 39.7% if Met expression was positive (p = 0.0002). S100A4, but not Met, was still a significant predictor of 10-year DFS in T1N0M0 breast carcinoma patients (p = 0.02). For the T2N0M0 subgroup, both S100A4 and Met were significantly correlated with survival. The 10-year DFS of T2N0M0 patients with S100A4-negative and Met-negative tumors was 92.3%; in those with S100A4-positive and Met-positive tumors, however, it was only 11.8%. Conclusions: S100A4 expression is an indicator of a poor prognosis for T1N0M0 breast cancer. In addition, the combination of S100A4 and Met expression gives the best risk group discrimination in the T2N0M0 subgroup. S100A4 expression appears to be an earlier step in the metastatic progression compared to Met expression in early-stage breast carcinoma.

Hepatitis C virus (HCV) infection is etiologically associated with the development of hepatocellular carcinoma (HCC) worldwide. HCV has been reported to exist and replicate in both HCC and adjacent non-cancerous liver tissue, but limited information was available on HCV viral load and quasispecies composition in HCC relative to adjacent non-cancerous hepatocytes. Previous study has also suggested CD81, a surface hepatocyte protein, as a receptor for HCV. To clarify the above, HCV-RNA and CD81-RNA titers in 20 paired hepatectomized liver and serum were quantitatively measured by chemiluminescent RT-cPCR. Hypervariable region 1 (HVR-1) variations of parallel specimens were analyzed after subcloning in 6 patients. HCV-RNA levels in serum and non-cancerous liver were markedly higher for HCV genotype 1 than genotype non-1. HCV levels were markedly higher in non-cancerous liver than in HCC (P = 0.001) in a genotype-independent manner, with a mean ratio of 56:1 for non-cancerous tissue to HCC. Both non-cancerous and HCC tissues had the same level of CD81-RNA expression, which was not linked to HCV load. HCV-RNA quantity in both HCC and non-cancerous liver correlated with the number of HVR-1 quasispecies in the tissue, and distinct HVR-1 subclones existed. J. Med. Virol. 68:188–196, 2002. © 2002 Wiley-Liss, Inc.

Background. Even after partial gastrectomy, Helicobacter pylori may persist in the residual stomach but be less abundant in the bacterial load. H. pylori stool antigen is a reliable noninvasive tool to detect H. pylori infection in patients without gastrectomy. We thus test whether [1] the course of H. pylori eradication therapy could be diminished [2]; stool antigen can effectively detect H. pylori infection for the patients with gastrectomy. Methods. One hundred and eight patients who had undergone partial gastrectomy were enrolled to receive panendoscopy and provided stool samples for H. pylori stool antigen within 3 days after endoscopy. The H. pylori-infected patients were then randomized to receive either a 3- or 7-day triple therapy for H. pylori eradication. Six weeks later, to evaluate the success of H. pylori eradication, patients received a follow-up endoscopy and again provided stool samples for H. pylori stool antigen. Results. Seventy out of 108 patients, proven to have H. pylori infection, were evenly randomized into 3-day and 7-day therapy groups. The H. pylori eradication rates were similar between the 3-day and 7-day triple therapy (90.9 vs. 93.8%, p > .05). Before therapy, the H. pylori stool antigen was 93% sensitive and 100% specific to detect H. pylori. After therapy, H. pylori stool antigen remain 100% sensitive and 88.3% specific to detect the failure of eradication therapy. Conclusion.H. pylori stool antigen is a highly reliable tool to screen H. pylori infection before therapy and to assess the success of eradication therapy in partial gastrectomy patients. To eradicate H. pylori infection for patients with partial gastrectomy, the duration of triple therapy can be shortened.

Objective: Recently, tissue polypeptide specific antigen (TPS) has been introduced as a cell proliferation marker. Little is known about its clinical significance in hepatocellular carcinoma (HCC). This study aimed to clarify serum TPS levels and tumor invasiveness of HCC. Methods: Serum TPS levels were determined with a monoclonal TPS IRMA assay in 69 patients with HCC. A correlation between serum TPS levels and clinical, biochemical, and pathological features was sought and compared with that of α-fetoprotein (AFP). In 57 healthy subjects, 56 patients with biopsy-proven chronic hepatitis and in 49 patients with liver cirrhosis, serum TPS levels were assayed and compared. Results: Serum TPS levels were significantly correlated with glutamic oxalacetic transaminase (p < 0.0001), glutamic pyruvic transaminase (p < 0.001), and lactate dehydrogenase (p = 0.027). There tended to be a positive relationship between serum TPS levels and tumor size, histological differentiation, capsular invasion, portal invasion, and clinical staging, although it did not reach statistical significance. A significant correlation, however, was observed between AFP and tumor size (p = 0.01), number (p = 0.042), histological grading (p = 0.028), portal invasion (p = 0.009), and clinical staging (p = 0.03). Patients with HCC had significantly higher TPS than healthy subjects (p < 0.001). However, there was substantial overlap between patients with HCC, chronic hepatitis, and liver cirrhosis. Conclusions: Our data suggest that serum TPS is not significantly related to tumor invasiveness in patients with HCC. Serum TPS levels are affected by the proliferative activity of the underlying chronic liver disease, which is frequently associated with HCC in Chinese patients. As a cell proliferation marker, serum TPS should be interpreted cautiously in the presence of chronic liver disease.

Background: This study was conducted to determine (1) whether Helicobacter pylori infection decreases in conjunction with time elapsed after gastrectomy and (2) the diagnostic efficacy of 13 C urea breath test (UBT) for H pylori in patients after gastrectomy. Methods: From January 1997 to June 1998, 86 patients who had undergone gastrectomy and 180 patients with dyspepsia without gastrectomy were enrolled. A UBT for the analysis of excess 13 CO 2 / 12 CO 2 ratio (ECR) was obtained for each patient. Each patient also underwent endoscopy to obtain gastric biopsies for histology and H pylori culture. The presence of H pylori by either histology or culture served as the standard to test the efficacy of UBT. The 86 patients with a prior gastrectomy were categorized into 3 subgroups (I, less than 1 year; II, 1 to 3 years; III, greater than 3 years), according to the interval between surgery and UBT. The initial H pylori status of these 86 patients was determined by histologic evaluation of the resected stomach. Results: At trial initiation, the postgastrectomy group had a lower H pylori infection rate (52.3%) as compared with the dyspeptic control group (80%). The initial H pylori status among subgroups I, II, and III was similar. There was a trend for the presence of H pylori in the stomach to decrease with increasing time elapsed after surgery (I to III: 68.8%, 48.3%, 36%, respectively; p Conclusion: The prevalence of H pylori diminishes with time elapsed after gastrectomy. UBT for detection of H pylori is more effective in patients without prior gastrectomy than in patients who have undergone gastrectomy and is less effective than endoscopy for patients who have had a gastrectomy. (Gastrointest Endosc 2000;51:670-5.)

Background and Aims: The expression of hepatitis B viral (HBV) antigens in liver tissue reflects the replicative status of chronic HBV infection. We have previously recognized a novel marginal pattern of hepatitis B surface antigen (HBsAg) in hepatocytes, which usually clusters in groups and emerges at the late non-replicative phase. This study was designed to investigate whether the marginal-type HBsAg represented the gene product of a specific HBV-surface mutant. Methods: Microdissection of cirrhotic nodules homogeneously expressing marginal HBsAg was performed on two of 12 resected livers from HBsAg-seropositive patients with hepatocellular carcinoma. The gene presumably encoding marginal HBsAg was polymerase chain reaction (PCR)-cloned, sequenced and analysed. In vitro transfection and expression of the cloned surface mutant plasmids were performed on the Huh7 cell line to illustrate intrahepatic HBsAg expression. Results: Immunohistochemical staining revealed that the marginal HBsAg was positive for pre-S1 and thus contained large surface proteins.The PCR cloning and sequencing of the genes presumably encoding marginal-type HBsAg in both cases revealed the same deletion at the 5¢ terminus (nt 2‐55) of preS2. A point mutation on the small-surface (S) antigen was also found in one case. The pre-S2 deletion sequence and the mutation sites of the S gene coincide with human lymphocyte antigen-restricted Tand/or B-cell epitopes. In vitro transfection of the mutant plasmid revealed a blot-like retention or accumulation of HBsAg in the cytoplasm or at the periphery of hepatocytes, accompanied by a decreased secretion of HBsAg in the culture supernatant, mimicking intrahepatic expression. Conclusion: A natural pre-S2 deletion mutant was identified in hepatocytes expressing a novel marginal pattern of HBsAg, which probably contains mutant, large, surface proteins. The biological significance of the pre-S2 deletion mutant should be interesting in view of the clustering proliferation of hepatocytes expressing marginal HBsAg. © 2000 Blackwell Science Asia Pty Ltd

Aim BRCA1, a nuclear phosphoprotein, normally functions as a negative regulator of the cell cycle and may be an active inhibitor of neoplastic progression. Mutation of the BRCA1 gene has been demonstrated in 80% of familial breast cancer. Decreased mRNA levels or aberrant subcellular locations of BRCA1 have been identified in breast cancer lines and in sporadic cases of breast cancer tissues. The expression of BRCA1 in large series of variously differentiated breast carcinomas with correlation with other biological parameters has not been clarified. Methods and results The BRCA1 expression in normal breast tissue (n = 15) and in sporadic cases of invasive ductal carcinoma (n = 108) was determined using immunohistochemistry. BRCA1 expression was correlated with other prognostic parameters including p53, c-erbB-2, bcl-2, oestrogen receptor (ER), histological grade, tumour size, axillary lymph node status and age. BRCA1 was exclusively (100%) localized in the nuclei of normal ductal and lobular epithelia. However, this nuclear expression pattern was variable in breast carcinoma (76.8%). Loss of nuclear BRCA1 expression (22 of 108 cases, 20.4%) correlated well with high histological grade (P

This study was performed to examine the immunohistochemical expression of fibroblast growth factor-1 and fibroblast growth factor-2 in normal liver and a total of 31 cases of hepatocellular carcinoma (HCC). Reactivity for both types of angiogenic factor did not exist in any cellular component of normal liver. For HCC, variable amounts of fibroblast growth factor-1 were detected in 6 of 31 cases (19.4%). There was no apparent relationship between the expression pattern and clinicopathologic factors (P > 0.1, respectively), except a positive correlation with histologic grading (P = 0.04). No tumor showed reactivity for fibroblast growth factor-2 in their cancer cells. However, both types of peptide could be demonstrated in the pericellular stroma of HCC. With a mean follow-up at 60 months, fibroblast growth factor-1 expression did not correlate with patients' outcome (P > 0.1). Our study suggested that fibroblast growth factor-1 appears to play a certain role in hepatocarcinogenesis.

Although the operative mortality of pancreaticoduodenal resection has decreased recently, the operative morbidity resulting from a leaking pancreatic anastomosis remains high. We described our experience in 50 consecutive cases with a simple, secure end to side pancreaticojejunostomy. We used a paediatric nasogastric tube in the pancreatic remnant duct as a temporary external pancreatic drain. There were 29 men and 21 women ranging from 12 to 84 years with a median age of 61 years. Forty-two patients underwent a standard Whipple procedure and eight a pylorus preserving pancreaticoduodenectomy. Average operating time was 270 minutes with a range of 170 to 480 minutes. The pancreaticojejunostomy could be constructed in a mean of 8 minutes. Intraoperative blood loss ranged from 150 to 3500 mL with a mean of 910mL. Twenty-five patients (50 %) received no blood transfusion. The consistency of the pancreatic remnant was hard in 12 patients (24 %) and normal in 38 patients (76 %). The pancreatic duct was dilated (>4mm) in 15 patients (30 %). There was no operative mortality and only three (6.0 %) minor leaks from the pancreatic anastomosis which healed spontaneously. It was difficult to determine if the leaks were related to the consistency of the pancreatic remnant, the size of the pancreatic duct, the amount of intraoperative blood loss, operating time, sex of the patient or experience of the surgeon, as there were only three leaks. We concluded that our technique for pancreaticojejunal anastomosis following pancreaticoduodenectomy was safe and applicable to, standard Whipple or pylorus preserving pancreaticoduodenectomy, small or dilated pancreatic ducts, normal or fibrotic pancreas.

Definitive surgical management of major acute injuries to the second and third portions of the duodenum has been enigmatic. Sometimes, the defect is so large that it is unwise to do primary repair, and resection at this critical portion of the intestinal tract is technically hazardous or impossible. A serosal or mucosal patch technique has been used to repair this kind of duodenal defect with encouraging results. Since the use of this technique has proved effective, such a defect was not necessarily treated with the more complicated pancreaticoduodenectomy and was managed with less morbidity and mortality. But these techniques are still controversial. So, we tried a pedicle flap, called the transverse abdominis musculo-peritoneal (TRAMP) flap, for repair of large duodenal defect. We have used this flap in 25 rabbits, and the specimens were followed up to a period of 3 months. The flap showed satisfactory results and is presented as another option for repair of large duodenal defects.

A retrospective review of 130 patients with peripheral-type cholangiocarcinomas (PTCC), hilar-type cholangiocarcinomas (HTCC), extrahepatic cholangiocarcinomas (EHCC), gallbladder cancers (GBCA), and periampullary cancers (PACA), seen at National Cheng Kung University Hospital and Tainan Municipal Hospital from June 1987 to July 1993 was performed. There were 47 (36%) HTCC, 32 (25%) PACA, 24 (19%) PTCC, 17 (13%) GBCA, and 10 (8%) EHCC patients. The distribution is completely different from that reported in western countries. These cancers mainly occur in elderly patients. HTCC and GBCA were predominantly noted in female patients. Biliary cancers in Taiwan were not related to liver fluke infestation, inflammatory bowel disease or hepatitis B virus infection. However, a close association with biliary lithiasis was found. The incidence of gallstones was 67, 39, 20, 29 and 19% for PTCC, HTCC, EHCC, GBCA and PACA, respectively. The most common presentation for PTCC and GBCA was abdominal pain, or jaundice for HTCC, EHCC and PACA. These symptoms correlate well with the location of the tumors. Among serum tumor markers, the elevation of CA19-9 was most frequent, occurring in 86% of the patients while CA125 and CEA occurred in 47% and 30% of the patients, respectively. During the course of disease, infection developed in 61% of the patients and was the main cause of death in 25%. Biliary tract infection and sepsis were the two leading manifestations and occurred in 49% and 32% of the patients, respectively. Overall survival was poor except in patients whose tumor could be completely resected.

The suprahepatic region is a rare ectopic location of the gallbladder. It usually combines with right lobe anomaly of the liver. Here we report two unusual cases of suprahepatic gallbladder with agenesis or hypogenesis of the right lobe of the liver and biliary cancer. A patient with a gallbladder tumor was admitted to our emergency room with acute cholecystitis and liver abscess. Imagining examinations and operation confirmed the suprahepatic position of gallbladder, agenesis of the right lobe, and dissemination of gallbladder cancer. In the patient with cholangiocarcinoma, CT scans and percutaneous transhepatic cholangiography documented the presence of a hilar tumor and hypogenesis of the right lobe. Both of these patients died from biliary tract cancer soon after operation.

e20514 Background: The mainstay treatment of primary GIST is surgery, but GIST often recurs even after complete resection. This study assessed the safety and efficacy of adjuvant IM in patients (pts) with resected GIST at intermediate/high risk of tumor recurrence. Methods: This open-label, single arm, prospective Ph II study (NCT01172548) was conducted in Asia Pacific/Africa/Russia/Middle East/Europe in eligible pts: aged ≥18 years (yrs), having had complete gross resection of primary GIST within 70 days of enrollment, with CD117 +ve, WHO PS ≤1, and no other adjuvant therapy. The planned sample size was 150 pts. Pts were to receive IM (400 mg/day, po) for 2 yrs post surgery. Dose modifications were allowed for toxicity. The primary endpoint was recurrence-free survival (RFS) rate at 2 yrs (based on CT/MRI and survival) in ITT pts (all pts who received ≥1 dose of study drug); null hypothesis based on historic data controls treated with surgery alone: RFS rate at 2 yrs of 0.7 (1 yr rate 0.98) (NCT00041197). A protocol-planned analysis at 1 yr in all enrolled pts (mITT) included safety, RFS, and overall survival. The study was approved by IRB/IEC/REB; all pts provided written informed consent. Results: Pt accrual was complete with 127 pts in the mITT population. Most pts (n=94, 74%) were

Hepatocellular carcinoma (HCC), a major cause of cancer-related death in Southeast Asia, is frequently associated with hepatitis B virus (HBV) infection. HBV X protein (HBx), encoded by a viral non-structural gene, is a multifunctional regulator in HBV-associated tumor development. We investigated novel signaling pathways underlying HBx-induced liver tumorigenesis and found that the signaling pathway involving IκB kinase β (IKKβ), tuberous sclerosis complex 1 (TSC1), and mammalian target of rapamycin (mTOR) downstream effector S6 kinase (S6K1), was upregulated when HBx was overexpressed in hepatoma cells. HBx-induced S6K1 activation was reversed by IKKβ inhibitor Bay 11-7082 or silencing IKKβ expression using siRNA. HBx upregulated cell proliferation and vascular endothelial growth factor (VEGF) production, and these HBx-upregulated phenotypes were abolished by treatment with IKKβ inhibitor Bay 11-7082 or mTOR inhibitor rapamycin. The association of HBx-modulated IKKβ/mTOR/S6K1 signaling with liver tumorigenesis was verified in a HBx transgenic mouse model in which pIKKβ, pS6K1, and VEGF expression was found to be higher in cancerous than non-cancerous liver tissues. Furthermore, we also found that pIKKβ levels were strongly correlated with pTSC1 and pS6K1 levels in HBV-associated hepatoma tissue specimens taken from 95 patients, and that higher pIKKβ, pTSC1, and pS6K1 levels were correlated with a poor prognosis in these patients. Taken together, our findings demonstrate that HBx deregulates TSC1/mTOR signaling through IKKβ, which is crucially linked to HBV-associated HCC development.

A 46-YEAR-OLD WOMAN was referred to National Cheng-Kung University Hospital in January, 1997 with a diagnosis of renal hyperparathyroidism. She was uremic and had received hemodialysis for 10 years. She had bone pain and muscular weakness for 2 years and experienced 2 episodes of fractures during this period. There were no palpable neck masses, and the remainder of the physical examination showed no significant findings. Laboratory assessments revealed a serum calcium concentration of 11.1 mg/dL (normal range, 8.1-10.1 mg/dL), a serum phosphorus concentration of 6.3 mg/dL (normal range, 2.5-5.0 mg/dL), an alkaline phosphatase level of 813 U/L (normal range, 30110 U/L), and an intact parathyroid hormone level of 1242 pg/mL (normal range, 10-65 pg/mL). Roentgenograms of the skull showed a pepper-andsalt appearance of the cranial bone and roentgenograms of the hands showed subperiosteal resorption of phalangeal bones. Sonographic examination of the neck revealed 5 hypoechoic nodules, 2 on the right and 3 on the left side. During an operation, 4 hyperplastic parathyroid glands adjacent to the thyroid gland were identified. Subtotal parathyroidectomy and cervical thymectomy were performed, leaving a wellvascularized remnant of the left superior parathyroid gland of about 60 mg. Special attention was paid to the left lateral neck because 3 hypoechoic nodules were shown by preoperative sonography. Within the left carotid sheath, a fusiform swelling of the vagus nerve that initially was thought to be a neurogenic tumor was seen opposite the upper pole of the thyroid (Figure). The perineurium was split longitudinally and a 1.0 × 0.5–cm brownish mass was carefully enucleated from between the vagus fibers. Unexpectedly, on examination of frozen and permanent sections, the intravagal tissue was proved to be hyperplastic parathyroid. Postoperatively, the serum calcium level dropped immediately to below the normal range and was maintained in the normal range with supplements of oral calcium carbonate and 1,25dihydroxyvitamin D3.

To assess the effectiveness of preoperative biliary drainage (PBD) by preoperative serum bilirubin level in patients with periampullary lesions receiving pancreaticoduodenectomy.Between Jan. 1995 to May 2005, 240 consecutive cases received pancreaticoduodenectomy at the National Cheng Kung University Hospital, Taiwan and were included retrospectively. Factors possibly affecting postoperative morbidity and mortality were analyzed.One hundred and forty-three patients (59.6%) underwent preoperative biliary drainage (the PBD group) and 97 patients without drainage (the non-PBD group). The total postoperative morbidity rate was 49.6% and postoperative mortality was 2.9%. There was no difference in total postoperative morbidity and mortality between groups, but higher incidence of sepsis/bacteremia in the PBD patients (p = 0.03), and more cardiovascular events (p = 0.05) in the non-PBD patients. More bile leakage developed in the non-PBD patients, but only with marginal significance (p = 0.09). In the PBD group, patients with preoperative serum bilirubin levelor = 5 mg/dL had higher likelihood to acquire an infectious complication, (OR: 2.70; CI: 1.21-6.04), and surgical site infectious (OR: 2.70; CI: 1.21-6.04), intraabdominal abscess (OR: 2.74; CI: 0.94-8.03), and wound infection (OR: 2.44; CI: 0.97-6.16).Preoperative biliary drainage increased postoperative infectious complications but it also decreased cardiovascular events. However, adequate preoperative biliary drainage is the key to decrease infectious complications.

BACKGROUND: The recurrence of hepatocellular carcinoma (HCC) after hepatectomy is a serious event. It has been demonstrated that different ground-glass hepatocyte (GGH) patterns harbor specific hepatitis B virus (HBV) pre-S deletion mutants and represent preneoplastic lesions in chronic HBV infection. In the current study, the authors investigated whether a specific GGH pattern in nontumorous liver tissues was associated with the recurrence of HBV-related HCC after surgery. METHODS: Clinicopathologic data from 82 patients with HBV-related HCC were reviewed. GGH patterns were assessed on hematoxylin and eosin-stained sections. Tissue hepatitis B surface antigen (HBsAg) expression was evaluated by immunohistochemical staining. Serum profiles of pre-S status, viral load, and HBV genotype were determined and correlated with clinical recurrence and survival after surgery. RESULTS: The results indicated that the clustered pattern of GGHs or HBsAg expression was associated significantly with decreased local recurrence-free survival (LRFS) during a mean follow-up of 46.4 months (P

Background/Aim: Hemostasis is a major difficulty associated with hepatectomies. The authors designed a new thermal surgery system to reduce blood loss. Methods: The newly designed system consists of an alternating magnetic field generator and stainless steel needle arrays with thermosensitive bands. Lanyu pigs were used: 4 for the Kelly crushing method and 4 for the newly designed method. The procedures used were S4-S5 segmentectomies or left lateral segmentectomies, after which the amount of blood loss and operation times were compared. The pigs were observed for 4 weeks, after which liver pathologies were studied. Results: The blood loss in the method proposed by the authors was almost 0 mL, whereas with the Kelly crushing method it was 116 ± 35 mL. The method proposed in this study can save 15 to 25 minutes of operation time. The resected liver margins exhibited prominent apoptosis and fibrotic change in the remnant livers. Conclusions: The method proposed is a novel new way of performing thermal surgery.

The progression of hepatic steatosis after pancreaticoduodenectomy (PD) is controversial. This study was designed to determine whether PD would influence the course of hepatic steatosis.Patients admitted for PD and distal pancreatectomy (DP) from January 2004 to January 2008 were enrolled. Exclusion criteria included liver metastasis, severe obesity (body mass index30), diabetic mellitus, excessive alcohol consumption, and unavailable preoperative and 6-month postoperative unenhanced CT images. The pre-PD and post-PD liver attenuation, ratio, and difference of liver-to-spleen attenuation between liver and spleen attenuation were compared.Fifty patients who underwent PD and 20 patients who underwent DP were eligible. The mean follow-up period was 18.2 +/- 1.6 months for the PD group and 19.7 +/- 1.7 months for the DP group. Liver attenuation after PD was significantly decreased from 52.3 +/- 1.1 H. to 47.6 +/- 2 H. (p = 0.044), but no difference was observed in spleen attenuation. The liver-to-spleen attenuation ratio after PD also was significantly decreased: 1.12 +/- 0.02 versus 1.01 +/- 0.04 (p = 0.033). No difference in liver attenuation was found in the DP group. The female gender was a significant risk factor.The liver attenuation of CT images decreases in patients who receive PD, which implicates that hepatic steatosis can develop after PD; however, the mechanism needs to be elucidated.

Osteopontin (OPN) is a multifunctional secreted glycophosphoprotein involved in miscellaneous physiologic and pathologic processes and is functionally related to the transmembrane receptor CD44. Although OPN expression has been identified to be associated with poor prognosis in several gastrointestinal malignancies, its expression in gastrointestinal stromal tumor (GIST) has not been thoroughly investigated. This study was designed to evaluate the clinicopathologic significance of OPN expression in patients with resectable GIST.OPN expression was analyzed for its clinicopathologic significance in surgical specimens from 99 patients with resectable GIST by immunohistochemistry. In situ Proximity Ligation Assay was used for examining OPN and CD44 interaction in tumor tissues and GIST cell lines. The in vitro effects of OPN and its interaction with CD44 also were assessed.Increased OPN expression was a significant poor prognostic factor that independently predicted recurrence and poor disease-free survival in patients with resectable GIST. The interaction of OPN and CD44 was confirmed by their significant correlation in both GIST tumor tissues and cell lines by in situ Proximity Ligation Assay analysis. OPN and its interaction with CD44 were related to increased mitosis and significantly enhanced GIST tumor cell proliferation in vitro.Our study identified the clinicopathologic significance and biologic effects of OPN expression in resectable GIST. Increased OPN expression was an independent poor prognostic factor and its interaction with CD44 significantly correlated with increased mitosis as well as in vitro proliferation-promoting effects.

Distant metastasis resulting from carcinoma cell detachment from the primary tumor involves modification of adhesion molecules. This study was conducted to examine the correlation of E-cadherin/beta-catenin expression with survival and recurrence in ampullary neoplasms.Patients with diagnoses of ampullary neoplasms were enrolled in the study. Demographics, operative findings, and histopathological data were collected by retrospective chart review. Expression of E-cadherin and beta-catenin were detected by immunohistochemistry.A total of 110 patients were enrolled in the study. Preservation of membranous staining of E-cadherin was noted in 41 (37%) patients, aberrant cytoplasmic staining in 48 (44%) patients, and complete loss in 21 (19%) patients. Loss of E-cadherin was associated with pancreatic invasion, recurrence, and poor prognosis. Membranous staining of beta-catenin was noted in 65 (59%) patients, cytoplasmic or nuclear accumulation in 16 (15%) patients, and complete loss in 29 (26%) patients. Loss of beta-catenin expression was associated with tumor markers, ulcerative type, liver metastases, and poor prognosis. Pancreatic invasion, lymph node involvement, and loss of beta-catenin expression were predictors of disease recurrence.Loss of the E-cadherin/beta-catenin complex is related to poor prognosis in ampullary cancer. Loss of beta-catenin is predictor of recurrence in multivariate analysis.

Follicular dendritic cells (FDC) are a subset of the immune system and present in the germinal centers of lymphoid follicles in the spleen and lymph nodes. They are functionally as antigen-presenting cells and thus improving the quality of the humoral immune response. Follicular dendritic cell tumor is rare but considered low-grade sarcoma. Including our case, there were totally 17 cases with FDC tumor involved the liver from Medline. In these cases, the mean age was 47 years old, ranged from 19 to 82. It was much more common in females than in males (13:4). The clinical manifestations of these patients included abdominal discomfort, palpable mass, weight loss and malaise. The average size of the tumor was 11 cm. Most of the FDC tumors were associated with Epstein-Barr virus expression, 13/17 (76.5%). Surgical resection remains the mainstay of the treatment.