Publications by authors named "Chang-Mu Sung"

14 Publications

  • Page 1 of 1

The optimal timing of interval laparoscopic cholecystectomy following percutaneous cholecystostomy based on pathological findings and the incidence of biliary events.

J Hepatobiliary Pancreat Sci 2021 Jun 15. Epub 2021 Jun 15.

Division of General Surgery, Chang Gung Memorial Hospital, Taoyuan City, Taiwan.

Background: The incidence of biliary events (BE) following percutaneous cholecystostomy (PC) in acute cholecystitis (AC) patients is high. Therefore, definitive laparoscopic cholecystectomy (LC) is recommended. We aimed to investigate the optimal timing of LC following PC with regard to the clinical course and pathological findings.

Methods: All 744 AC patients with PC were included. The incidence and median number of BE were investigated with the concept of competing risks. The 344 patients with interval LC were divided into two groups based on the pathological findings of resected gallbladders: the acute/acute-and-chronic group (AANC group) (n = 221) and the chronic group (n = 123). A comparative analysis of the demographic data and perioperative outcomes was performed.

Results: Among the 744 AC patients with PC, 142 patients experienced recurrent BE. The cumulative incidence of BE was 26.6%, and the median time to recurrence was 67.5 days. The PC-to-LC days of the chronic group were longer than those of the AANC group (73.51 vs 63.00, P < .001). The multivariate analysis indicated that the operation time was longer in the AANC group than in the chronic group (P = .040).

Conclusion: In terms of the clinical course and sequential pathological changes in the gallbladder, a 9- to 10-week interval after PC is the optimal timing for LC.
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http://dx.doi.org/10.1002/jhbp.1012DOI Listing
June 2021

Management of Patients With Acute Cholecystitis After Percutaneous Cholecystostomy: From the Acute Stage to Definitive Surgical Treatment.

Front Surg 2021 15;8:616320. Epub 2021 Apr 15.

Division of General Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

Percutaneous cholecystostomy (PC) has become an important procedure for the treatment of acute cholecystitis (AC). PC is currently applied for patients who cannot undergo immediate laparoscopic cholecystectomy. However, the management following PC has not been well-reviewed. The efficacy of PC tubes has already been indicated, and compared to complications of other invasive biliary procedures, complications related to PC are rare. Following the resolution of AC, patients who can tolerate anesthesia and the surgical risk should undergo interval cholecystectomy to reduce the recurrence of biliary events. For patients unfit for surgery, whether owing to comorbidities, anesthesia risks, or surgical risks, expectant management may be applied; however, a high incidence of recurrence has been noted. In addition, several interesting issues, such as the indications for cholangiography via the PC tube, removal or maintenance of the PC catheter before definitive treatment, and timing of elective surgery, are all discussed in this review, and a relevant decision-making flowchart is proposed. PC is an effective and safe intervention, whether as expectant treatment or bridge therapy to definitive surgery. High-level evidence of post-PC care is still necessary to modify current practices.
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http://dx.doi.org/10.3389/fsurg.2021.616320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083985PMC
April 2021

The rectal mucosal but not fecal microbiota detects subclinical ulcerative colitis.

Gut Microbes 2021 Jan-Dec;13(1):1-10

Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital , Taoyuan, Taiwan.

Ulcerative colitis (UC), a subtype of inflammatory bowel disease, is characterized by repetitive remission and relapse. Gut microbiome is critically involved in pathogenesis of UC. The shifts in microbiome profile during disease remission remain under-investigated. Recent studies revealed that UC pathogenesis is likely to originate in the mucosal barrier. Therefore, we investigated the effectiveness of mucosal tissue microbiomes to differentiate patients with subclinical UC from healthy individuals. The microbiomes of cecal and rectal biopsies and feces were characterized from 13 healthy individuals and 45 patients with subclinical UC. Total genomic DNA was extracted from the samples, and their microbial communities determined using next-generation sequencing. We found that changes in relative abundance of subclinical UC were marked by a decrease in Proteobacteria and an increase in Bacteroidetes phyla in microbiome derived from rectal tissues but not cecal tissue nor feces. Only in the microbiome of rectal tissue had significantly higher community richness and evenness in subclinical UC patients than controls. Twenty-seven operational taxonomic units were enriched in subclinical UC cohort with majority of the taxa from the Firmicutes phylum. Inference of putative microbial functional pathways from rectal biopsy microbiome suggested a differential increase in interleukin-17 signaling and T-helper cell differentiation pathways. Rectal biopsy tissue was suggested to be more suitable than fecal samples for microbiome assays to distinguish patients with subclinical UC from healthy adults. Assessment of the rectal biopsy microbiome may offer clinical insight into UC disease progression and predict relapse of the diseases.
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http://dx.doi.org/10.1080/19490976.2020.1832856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872041PMC
February 2021

Serum metabolites may be useful markers to assess vascular invasion and identify normal alpha-fetoprotein in hepatocellular carcinoma undergoing liver resection: a pilot study.

World J Surg Oncol 2020 Jun 3;18(1):121. Epub 2020 Jun 3.

Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan.

Purpose: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with a dismal prognosis. Vascular invasion, among others, is the most robust indicator of postoperative recurrence and overall survival after liver resection for HCC. Few studies to date have attempted to search for effective markers to predict vascular invasion before the operation. The current study would examine the plasma metabolic profiling via H-NMR of HCC patients undergoing liver resection and aim to search for potential biomarkers in the early detection of HCC with normal alpha-fetoprotein (AFP) and the diagnosis of vascular invasion preoperatively.

Materials And Methods: HCC patients scheduled to receive liver resections for their HCC were recruited and divided into two separate groups, investigation cohort and validation cohort. Their preoperative blood samples were collected and subjected to a comprehensive metabolomic profiling using H-nuclear magnetic resonance spectroscopy (NMR).

Results: There were 35 HCC patients in the investigation group and 22 patients in the validation group. Chronic hepatitis B remained the most common etiology of HCC, followed by chronic HCV infection. The two study cohorts were essentially comparable in terms of major clinicopathological variables. After H-nuclear NMR analysis, we found in the investigation cohort that HCC with normal alpha-fetoprotein (AFP < 15 ng/mL) had significantly higher serum level of O-acetylcarnitine than those with higher AFP (AFP ≥ 15 ng/mL, P = 0.025). In addition, HCC with microscopic vascular invasion (VI) had significantly higher preoperative serum level of formate than HCC without microscopic VI (P = 0.023). These findings were similar in the validation cohort.

Conclusion: A comprehensive metabolomic profiling of HCC demonstrated that serum metabolites may be utilized to assist the early diagnosis of AFP-negative HCC patients and recognition of microvascular invasion in order to facilitate preoperative surgical planning and postoperative follow-up. Further, larger scale prospective studies are warranted to consolidate our findings.
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http://dx.doi.org/10.1186/s12957-020-01885-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271504PMC
June 2020

Predicting Clinical Outcomes of Cirrhosis Patients With Hepatic Encephalopathy From the Fecal Microbiome.

Cell Mol Gastroenterol Hepatol 2019 18;8(2):301-318.e2. Epub 2019 Apr 18.

Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address:

Background & Aims: Gut dysbiosis plays a role in hepatic encephalopathy (HE), while its relationship at the acute episode of overt HE (AHE), the disease progression and clinical outcomes remains unclear. We aimed to identify AHE-specific microbiome and its association to patients' outcomes.

Methods: We profiled fecal microbiome changes for a cohort of 62 patients with cirrhosis and AHE i) before treatment, ii) 2-3 days after medication and iii) 2-3 months after recovery, and three control cohorts i) healthy individuals, patients with ii) compensated or iii) decompensated cirrhosis.

Results: Comparison of the microbiome shift from compensated, decompensated cirrhosis, AHE to recovery revealed the AHE-specific gut-dysbiosis. The gut microbiome diversity was decreased during AHE, further reduced after medication, and only partially reversed during the recovery. The relative abundance of Bacteroidetes phylum in the microbiome decreased, whereas that of Firmicute, Proteobacteria and Actinobacteria increased in patients during AHE compared with those with compensated cirrhosis. A total of 70 operational taxonomic units (OTUs) were significantly different between AHE and decompensated cirrhosis abundances. Of them, the abundance of Veillonella parvula increased the most during AHE via a metagenomics recovery of the genomes. Moreover, the relative abundances of three (Alistipes, Bacteroides, Phascolarctobacterium) and five OTUs (Clostridium-XI, Bacteroides, Bacteroides, Lactobacillus, Clostridium-sedis) at AHE were respectively associated with HE recurrence and overall survival during the subsequent one-year follow-up.

Conclusions: AHE-specific gut OTUs were identified that may be involved in HE development and able to predict clinical outcomes, providing new strategies for the prevention and treatment of HE recurrence in patients with cirrhosis.
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http://dx.doi.org/10.1016/j.jcmgh.2019.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718362PMC
July 2020

Cadherin 17 is related to recurrence and poor prognosis of cytokeratin 19-positive hepatocellular carcinoma.

Oncol Lett 2018 Jan 1;15(1):559-567. Epub 2017 Nov 1.

Department of Surgery, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, R.O.C.

A previous study demonstrated that cytokeratin 19 (CK19) expression in hepatocellular carcinoma (HCC) is an indicator of HCC invasiveness, including lymph node metastasis (LNM), tumor infiltration/non-encapsulation and poor prognosis. The exact mechanism by which CK19 expression results in poor prognosis remains unclear. Through the use of an Affymetrix U133A oligonucleotide microarray [20 patients with hepatitis B virus (HBV)-HCC], it was demonstrated that cadherin 17 (CDH17) significantly correlated with CK19 expression (R, 0.867; P<0.001) in HBV-HCC. Immunohistochemical analysis (114 patients with HBV-HCC) also demonstrated a significant correlation between CK19 and CDH17 expressions in primary tumor tissue (R, 0.414; P<0.001). In addition, CK19 and CDH17 expressions levels revealed a significant association with LNM (P<0.001). Cox regression multivariate analysis demonstrated that indocyanine green retention at 15 min >10% and CDH17 expression were independent prognostic factors for disease free survival (P=0.010 and 0.002, respectively). studies showed that epidermal growth factor can induce the expression of both CK19 and CDH17, and CDH17 in turn can enhance the expression of CK19 in HCC. In summary, this study demonstrated that the early recurrence and poor prognosis of CK19(+) HCC may be due to the expression of CDH17, a gene known to be associated with vascular invasion, tumor metastasis, and advanced tumor stage of HCC. Thus, novel therapeutics by targeting CDH17 may be beneficial for CK19(+) HCC.
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http://dx.doi.org/10.3892/ol.2017.7320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768062PMC
January 2018

RAM score is an effective predictor for early mortality and recurrence after hepatectomy for hepatocellular carcinoma.

BMC Cancer 2017 Nov 9;17(1):742. Epub 2017 Nov 9.

Department of Surgery, Chang Gung Memorial Hospital, No. 5, Fuxing St., Guishan Dist., Taoyuan, 333, Taiwan, Republic of China.

Background: Liver resection had been regarded as a standard treatment for primary hepatocellular carcinoma (HCC). However, early mortality and recurrence after surgery were still of major concern. RAM (Risk Assessment for early Mortality) scoring system is a newly developed tool for assessing early mortality after hepatectomy for HCC. In this study, we compared RAM scoring system with ALBI and MELD scores for their capability of predicting short-term outcome.

Methods: We retrospectively reviewed patients with hepatocellular carcinoma who were treated with hepatectomy at Chang Gung Memorial Hospital between 1986 and 2015. Their clinical characteristics and perioperative variables were collected. We applied RAM, albumin-bilirubin (ALBI), and model for end-stage liver disease (MELD) scoring systems to predict early mortality and early recurrence in HCC patients after surgery. We investigated the discriminative power of each scoring system by receiver operating characteristic (ROC) curve and area under the ROC curve (AUC).

Results: A total of 1935 patients (78% male) who underwent liver resection for HCC were included in this study. The median follow-up period was 41.9 months. One hundred and forty-nine patients (7.7%) died within 6 months after hepatectomy (early mortality). All the three scoring systems were effective predictor for early mortality, with higher score indicating higher risk of early mortality (AUC of RAM = 0.723, p < 0.001; AUC of ALBI = 0.682, p < 0.001; AUC of MELD = 0.590, p = 0.002). Cox regression multivariate analysis demonstrated that the RAM class was the most significant independent predictor of early mortality after surgery, while MELD grade failed to discriminatively predict early mortality. In addition to early mortality, the RAM score was also predictive of early recurrence in HCC after surgery.

Conclusions: This study demonstrated that RAM score is an effective and user-friendly bedside scoring system to predict early mortality and early recurrence after hepatectomy for HCC. In addition, the predictive capability of RAM score is superior to ALBI and MELD scores. Further study is warranted to validate our findings.
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http://dx.doi.org/10.1186/s12885-017-3748-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680811PMC
November 2017

Risk factors for early mortality after hepatectomy for hepatocellular carcinoma.

Medicine (Baltimore) 2016 Sep;95(39):e5028

aDepartment of Surgery, Chang Gung Memorial Hospital, Linkou bCollege of Medicine, Chang Gung University, Guishan, Taoyuan cGraduate Institute of Clinical Medical Sciences, Chang Gung University, Guishan, Taoyuan dDepartment of Anesthesiology,Chang Gung Memorial Hospital, Linkou eDepartment of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taiwan (R.O.C.).

Despite advances in surgical technique and medical care, liver resection for hepatocellular carcinoma (HCC) remains a high-risk major operation. The present study evaluated the risk factors for early mortality after hepatectomy.We retrospectively reviewed records of patients undergoing liver resection for HCC between 1983 and 2015. A point score (Risk Assessment for early Mortality (RAM) score) for hepatectomy was developed based on multivariate analyses.Three hundred eighty-three patients (11.3%) expired within 6 months after the operation. Logistic regression analyses identified that operative duration >270 minutes and blood loss >800 cc were significant predictors of major surgical complications (P = 0.013 and 0.002, respectively). On the other hand, diabetes mellitus, albumin ≤3.5 g/dL, α-fetoprotein (AFP) >200 ng/mL, major surgical procedure, blood loss >800 cc, and major surgical complications were independent risk factors for early mortality after hepatectomy (P = 0.019, <0.001, <0.001, 0.006, 0.018, and <0.001, respectively). Risk Assessment for early Mortality score (RAM score) identified 3 subgroups of patients with distinct 6-month mortality rate, with Class III (score 10) having highest risk of early mortality.Our study demonstrated that meticulous surgical techniques to minimize blood loss and avoid prolonged operative time may help decrease the occurrence of major surgical complications. In addition to major surgical complications, diabetes mellitus, hypoalbuminemia, high AFP, massive blood loss, and major surgical procedure are also associated with early mortality after liver resection. Further study is warranted to validate the utility of RAM score as a bedside scoring system to predict postoperative outcome.
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http://dx.doi.org/10.1097/MD.0000000000005028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5265968PMC
September 2016

Optimizing Human Bile Preparation for Two-Dimensional Gel Electrophoresis.

Biomed Res Int 2016 4;2016:5185317. Epub 2016 Feb 4.

Department of Physical Medicine & Rehabilitation, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan.

Aims: Bile is an important body fluid which assists in the digestion of fat and excretion of endogenous and exogenous compounds. In the present study, an improved sample preparation for human bile was established.

Methods And Material: The method involved acetone precipitation followed by protein extraction using commercially available 2D Clean-Up kit. The effectiveness was evaluated by 2-dimensional electrophoresis (2DE) profiling quality, including number of protein spots and spot distribution.

Results: The total protein of bile fluid in benign biliary disorders was 0.797 ± 0.465 μg/μL. The sample preparation method using acetone precipitation first followed by 2D Clean-Up kit protein extraction resulted in better quality of 2DE gel images in terms of resolution as compared with other sample preparation methods. Using this protocol, we obtained approximately 558 protein spots on the gel images and with better protein spots presentation of haptoglobin, serum albumin, serotransferrin, and transthyretin.

Conclusions: Protein samples of bile prepared using acetone precipitation followed by 2D Clean-Up kit exhibited high protein resolution and significant protein profile. This optimized protein preparation protocol can effectively concentrate bile proteins, remove abundant proteins and debris, and yield clear presentation of nonabundant proteins and its isoforms on 2-dimensional electrophoresis gel images.
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http://dx.doi.org/10.1155/2016/5185317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757711PMC
December 2016

Distinct patterns of the lipid alterations between genotype 1 and 2 chronic hepatitis C patients after viral clearance.

PLoS One 2014 14;9(8):e104783. Epub 2014 Aug 14.

Department of Laboratory Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan.

Background: The hepatitis C virus (HCV) genotype-specific impacts on the host metabolic alterations remained inconclusive.

Methods: A prospective study including 229 (118 genotype 1 (G1) and 111 G2) consecutive chronic HCV patients who had completed a course of anti-HCV treatment and underwent pre- and 24 weeks post-treatment surveys of metabolic profiles was conducted. Patients were stratified according to the therapeutic response, viral genotype and baseline insulin resistance (IR: homeostasis model assessments of IR (HOMA-IR) ≥ 2.5). Paired t-tests were used to compare the pre- and post-treatment variables.

Results: Significant post-therapeutic increases in cholesterol, triglyceride, HDL, LDL, apolipoprotein A1 and apolipoprotein B were observed in patients with sustained virological response (SVR) but not in those without. Among those with SVR, post-therapeutic increases in HDL (p<0.001) and apolipoprotein A1 (p = 0.012) were only found in G2, whereas increased triglyceride/HDL (p = 0.01) ratios were only found in G1 patients. When stratified by baseline IR among those with SVR, a significant increase in post-treatment HDL (p = 0.019) and apolipoprotein A1 (p = 0.012) but a decrease in HOMA-IR (p = 0.04), C-peptide (p = 0.019) and hemoglobin A1c (p = 0.047) were found in patients with baseline IR; a significant increase in HOMA-IR (p = 0.002) was found in patients without baseline IR. The latter change was observed only in G1 (p = 0.01) but not G2 patients. Although the pre-treatment metabolic profiles of G1 and G2 patients were indifferent, G1 had higher post-treatment triglyceride/HDL ratios (p = 0.041) and triglyceride (p = 0.044) levels than G2 patients.

Conclusions: G2 benefit more than G1 patients from viral clearance in metabolic alterations, particularly in those without baseline IR.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104783PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133245PMC
March 2016

HCV core-induced nonobese hepatic steatosis is associated with hypoadiponectinemia and is ameliorated by adiponectin administration.

Obesity (Silver Spring) 2012 Jul 23;20(7):1474-80. Epub 2012 Feb 23.

Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linko, Taiwan.

Obesity-related hepatic steatosis is commonly associated with central fat accumulation and alterations in adipocytokine secretion; however, the connection between nonobese hepatic steatosis and adipocytokines remains unclear. We aim to investigate this connection using an animal model of conditional hepatitis C virus (HCV) core-transgenic mice. Double transgenic mice (DTM) with doxycycline (dox)-regulated hepatic overexpression of the HCV core protein were fed standard rodent chow ad libitum following 1 month of a dox-rich diet. The mice exhibited nonobese hepatic steatosis at 2 months of age. The levels of leptin and adiponectin were assessed in 2-month-old DTM (i.e., HCV core-tetracycline transactivator (tTA)) and single transgenic mice (STM; i.e., tTA). The total fat mass and the body fat distribution of the mice were evaluated using dual-energy X-ray absorptiometry (DEXA) and magnetic resonance imaging (MRI). Microarray analyses and quantitative real-time PCR were conducted using RNA obtained from the visceral fat of paired DTM and STM. Adiponectin was administered intraperitoneally to the 2-month-old DTM. No significant differences of the various fat components were noted between the DTM and STM. Leptin mRNA was downregulated in the visceral fat of DTM (P = 0.011), and serum adiponectin protein levels were reduced in the DTM compared with those in the STM (P = 0.035). Adiponectin treatment also significantly ameliorated hepatic steatosis in the DTM compared to the controls (P = 0.024). In conclusion, HCV core-induced nonobese hepatic steatosis is associated with downregulation of the leptin gene in visceral fat and concurrent hypoadiponectinemia; however, these effects may be ameliorated by adiponectin treatment.
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http://dx.doi.org/10.1038/oby.2012.45DOI Listing
July 2012

Retrospective comparison between a regular and a split-dose protocol of 5-fluorouracil, cisplatin, and mitoxantrone for the treatment of far advanced hepatocellular carcinoma.

BMC Cancer 2011 Mar 31;11:117. Epub 2011 Mar 31.

Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.

Background: In patients with advanced hepatocellular carcinoma (HCC), combination chemotherapy using 5- fluorouracil, cisplatin, and mitoxantrone (FMP) could achieve a response rate > 20%, but the beneficial effect was compromised by formidable adverse events. Chemotherapy given in a split-dose manner was associated with reduced toxicities. In this retrospective study, we compared the efficacies and side effects between a regular and a split-dose FMP protocol approved in our medical center.

Methods: From 2005 to 2008, the clinical data of 84 patients with far advanced HCC, who had either main portal vein thrombosis and/or extrahepatic metastasis, were reviewed. Of them, 65 were treated by either regular (n = 27) or split-dose (n = 38) FMP and had completed at least one therapeutic course. The remaining 19 patients were untreated. Clinical parameters, therapeutic responses, survivals and adverse events were compared.

Results: The median overall survival was 6.0, 5.2, and 1.5 months, respectively, in patients receiving regular FMP, split-dose FMP, and no treatment (regular versus split-dose group, P = 0.447; regular or split-dose versus untreated group; P < 0.0001). Patients receiving split-dose treatment had a significantly lower risk of grade 3/4 neutropenia (51.9 versus 10.5%, P = 0.0005). When the two treated groups were combined, the median overall survival was 10.6 and 3.8 months respectively for patients achieving disease control and progressive disease (P < 0.001). Cox proportion hazard model identified Child-Pugh stage B (hazard ratio [HR], 2.216; P = 0.006), presence of extrahepatic metastasis (HR, 0.574; P = 0.048), and achievement of disease control (HR, 0.228; P < 0.001) as independent factors associated with overall survival. Logistic regression analysis revealed that anti-hepatitis C virus antibody (odds ratio [OR], 9.219; P = 0.002) tumor size (OR, 0.816; P = 0.036), and previous anti-cancer therapy (OR, 0.195; P = 0.017) were significantly associated with successful disease control.

Conclusions: Comparable overall survival was observed between patients receiving regular and split-dose FMP therapies. Patients receiving split-dose therapy had a significantly lower risk of grade 3/4 neutropenia. Positive anti-hepatitis C virus antibody, smaller tumor size, and absence of previous anti-cancer therapy were independent predictors for successful disease control.
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http://dx.doi.org/10.1186/1471-2407-11-117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079691PMC
March 2011

Hydrodynamics-based transfection of the combination of betacellulin and neurogenic differentiation 1 DNA ameliorates hyperglycemia in mice with streptozotocin-induced diabetes.

Diabetes Technol Ther 2011 May 15;13(5):519-25. Epub 2011 Mar 15.

Liver Research Center and Department of Hepatogastroenterology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Background: The biohazards caused by the viral delivery of pancreatic transcription factors, including neurogenic differentiation 1 (Neurod1) and Betacellulin (Btc), to the murine liver limit application of this procedure in reversing diabetes. We aimed to evaluate the feasibility of hydrodynamics-based transfection (HBT) with Neurod1 and Btc in improving hyperglycemia.

Methods: Murine hepatocellular carcinoma (Hepa1-6) cells were transfected with the combination of Neurod1-expressing plasmid, pcDNA3.1/V5-His A (pcDNA)-Neurod1, and Btc-expressing plasmid, pcDNA3.1/V5-His A (pcDNA)-Btc. Hepatic delivery of a combination of pcDNA-Neurod1 and pcDNA-Btc (experimental group) or pcDNA (control group) to mice with streptozocin-induced diabetes was achieved by HBT. The sequential serum glucose and alanine aminotransferase (ALT) levels were assessed.

Results: On day 3 after transfection, the transfection efficiencies of pcDNA-Btc and pcDNA-Neurod1 in the Hepa1-6 cells were 20% and 8%, respectively; respective values in the mouse livers were 30% and 10%. At 1 week after HBT, aside from hepatic expression of insulin, the experimental mice had a significantly lower sugar level (8-14 days after HBT, P values ranged from 0.034 to <0.001) than the control mice; the difference remained for 1 week but diminished afterward. The ALT levels and the body weight change were not different between the two groups. No mortality was noted in both groups.

Conclusions: The hypoglycemic effect of Neurod1 and Btc delivered by HBT was transient and associated with negligible complications. In studies on the short-term hypoglycemic effects of Neurod1 and Btc in vivo, HBT is a potential alternative to viral delivery of Neurod1 and Btc to the murine liver.
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http://dx.doi.org/10.1089/dia.2010.0140DOI Listing
May 2011

Predictive factors for lymph node metastasis in early gastric cancer.

World J Gastroenterol 2010 Nov;16(41):5252-6

Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, China.

Aim: To analyze the predictive factors for lymph node metastasis (LNM) in early gastric cancer (EGC).

Methods: Data from patients surgically treated for gastric cancers between January 1994 and December 2007 were retrospectively collected. Clinicopathological factors were analyzed to identify predictive factors for LNM.

Results: Of the 2936 patients who underwent gastrectomy and lymph node dissection, 556 were diagnosed with EGC and included in this study. Among these, 4.1% of patients had mucosal tumors (T1a) with LNM while 24.3% of patients had submucosal tumors with LNM. Univariate analysis found that female gender, tumors ≥ 2 cm, tumor invasion to the submucosa, vascular and lymphatic involvement were significantly associated with a higher rate of LNM. On multivariate analysis, tumor size, lymphatic involvement, and tumor with submucosal invasion were associated with LNM.

Conclusion: Tumor with submucosal invasion, size ≥ 2 cm, and presence of lymphatic involvement are predictive factors for LNM in EGC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2975097PMC
http://dx.doi.org/10.3748/wjg.v16.i41.5252DOI Listing
November 2010
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