Publications by authors named "Yi-Yin Jan"

146 Publications

Surgical outcome of mirizzi syndrome: Value of endoscopic retrograde cholangiopancreatography and laparoscopic procedures.

J Hepatobiliary Pancreat Sci 2021 Jun 26. Epub 2021 Jun 26.

Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taiwan.

Background: Laparoscopic cholecystectomy (LC) with associated procedures and endoscopic retrograde cholangiopancreatography (ERCP) have been the standard treatments for both common and rare biliary diseases. Mirizzi syndrome (MS) is a rare and complex biliary condition. We report our experience with MS treatment and investigate the value of laparoscopic procedures and ERCP in patient management.

Methods: From 2004 to 2017, 100 consecutive patients with MS were diagnosed by ERCP and underwent surgery in a referral center. Sixty patients were treated with intended LC, and 40 patients were treated with open cholecystectomy (OC). The clinical manifestations, ERCP and associated procedures, surgical procedures, and postoperative outcomes were investigated.

Results: The surgical mortality rate was 1%, while the surgical morbidity rate was 15%. The patients treated with intended LC suffered from less morbidity (5%). The percentage of postoperative residual biliary stones was 32% (n=32), and only 3 patients underwent re-operation (laparotomy) for stone removal. The laparotomy conversion rate in the intended LC group was 16.7% (10/60). The length of hospitalization in the patients with successful LC was significantly shorter than that in the patients with conversion and intended OC. Csendes classification was a risk factor for conversion from LC to OC (type I versus types II to V, p < 0.0001).

Conclusions: A combination of a laparoscopic procedure and ERCP may provide therapeutic benefits for patients with MS.
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http://dx.doi.org/10.1002/jhbp.1016DOI Listing
June 2021

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<0.001). The multivariate analysis indicated that the operation time was longer in the AANC group than in the chronic group (p=0.040).

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

Alternative application of percutaneous cholecystostomy in patients with biliary obstruction.

Abdom Radiol (NY) 2021 06 2;46(6):2891-2899. Epub 2021 Jan 2.

Division of General Surgery, Chang Gung Memorial Hospital, No. 5, Fuxing St., Guishan Dist., Taoyuan, 333, Taiwan.

Purpose: Percutaneous cholecystostomy (PC) is an important modality for acute cholecystitis and has been applied for other clinical scenarios as well. In the present study, we aimed to investigate an alternative use of PC for obstructive jaundice.

Methods: From January 2012 to December 2018, eligible subjects were selected from patients undergoing PC in our institute. The characteristics, spectrum of underlying disease, indication for PC performance, details of the procedure, and treatment effect were all investigated.

Results: During the study period, 1364 patients underwent PC. Seventy patients fulfilled the defined inclusion criteria. While 47 patients were diagnosed with malignant biliary obstruction with or without cholangitis, 23 patients were diagnosed with nonmalignant biliary obstruction and acute cholangitis. There were 63 patients (90%) diagnosed with acute cholangitis. Pancreatic cancer (n = 24, 51%) and advanced malignancy (n = 28, 59%) were noted mostly in the group with malignant biliary obstruction. Treatment effects were proven by laboratory data, including the white blood cell count, C-reactive protein level, and hepatic function.

Conclusion: PC can temporize definitive therapies and serve as an alternative treatment for patients with nonmalignant conditions. For patients with advanced malignancy, PC can serve as a palliative procedure that has a high success rate and low complication rate and effectively relieves biliary obstruction.
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http://dx.doi.org/10.1007/s00261-020-02898-5DOI Listing
June 2021

Predicting cholecystocholedochal fistulas in patients with Mirizzi syndrome undergoing endoscopic retrograde cholangiopancreatography.

World J Gastroenterol 2020 Oct;26(40):6241-6249

Department of General Surgery, Linkou Medical Center, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan 333, Taiwan.

Background: Mirizzi syndrome (MS) is defined as an extrinsic compression of the extrahepatic biliary system by an impacted stone in the gallbladder or the cystic duct leading to obstructive jaundice. Endoscopic retrograde cholangiopancreatography (ERCP) could serve diagnostic and therapeutic purposes in patients with MS in addition to revealing the relationships between the cystic duct, the gallbladder, and the common bile duct (CBD). Cholecystectomy is a challenging procedure for a laparoscopic surgeon in patients with MS, and the presence of a cholecystocholedochal fistula renders preoperative diagnosis important during ERCP.

Aim: To evaluate cholecystocholedochal fistulas in patients with MS during ERCP before cholecystectomy.

Methods: From 2004 to 2018, all patients diagnosed with MS during ERCP were enrolled in this study. Patients with associated malignancy or those who had already undergone cholecystectomy before ERCP were excluded. In total, 117 patients with MS diagnosed by ERCP were enrolled in this study. Among them, 21 patients with MS had cholecystocholedochal fistulas. MS was further confirmed during cholecystectomy to check if cholecystocholedochal fistulas were present. The clinical data, cholangiography, and endoscopic findings during ERCP were recorded and analyzed.

Results: Gallbladder opacification on cholangiography is more frequent in patients with MS complicated by cholecystocholedochal fistulas ( < 0.001). Pus in the CBD and stricture length of the CBD longer than 2 cm were two additional independent factors associated with MS, as demonstrated by multivariate analysis (odds ratio 5.82, = 0.002; 0.12, = 0.008, respectively).

Conclusion: Gall bladder opacification is commonly seen in patients with MS with cholecystocholedochal fistulas during pre-operative ERCP. Additional findings such as pus in the CBD and stricture length of the CBD longer than 2 cm may aid the diagnosis of MS with cholecystocholedochal fistulas.
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http://dx.doi.org/10.3748/wjg.v26.i40.6241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596637PMC
October 2020

Management of Gallstones and Acute Cholecystitis in Patients with Liver Cirrhosis: What Should We Consider When Performing Surgery?

Gut Liver 2021 Jul;15(4):517-527

Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.

Acute cholecystitis and several gallbladder stone-related conditions, such as impacted common bile duct stones, cholangitis, and biliary pancreatitis, are common medical conditions in daily practice. An early cholecystectomy or drainage procedure with delayed cholecystectomy is the current standard of treatment based on published clinical guidelines. Cirrhosis is not only a condition of chronically impaired hepatic function but also has systemic effects in patients. In cirrhotic individuals, several predisposing factors, including changes in the bile acid composition, increased nucleation of bile, and decreased motility of the gallbladder, contribute to the formation of biliary stones and the possibility of symptomatic cholelithiasis, which is an indication for surgical treatment. In addition to these predisposing factors for cholelithiasis, systemic effects and local anatomic consequences related to cirrhosis lead to anesthesiologic risks and perioperative complications in cirrhotic patients. Therefore, the treatment of the aforementioned biliary conditions in cirrhotic patients has become a challenging issue. In this review, we focus on cholecystectomy for cirrhotic patients and summarize the surgical indications, risk stratification, surgical procedures, and surgical outcomes specific to cirrhotic patients with symptomatic cholelithiasis.
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http://dx.doi.org/10.5009/gnl20052DOI Listing
July 2021

Surgical outcomes of patients with maintained or removed percutaneous cholecystostomy before intended laparoscopic cholecystectomy.

J Hepatobiliary Pancreat Sci 2020 Aug 1;27(8):461-469. Epub 2020 May 1.

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

Background: Percutaneous cholecystostomy (PC) followed by definitive cholecystectomy is an alternative treatment for acute cholecystitis (AC). We retrospectively investigated the impact of PC tube removal before definitive cholecystectomy on surgical outcomes.

Methods: From 2012 to 2017, 942 AC patients underwent PC at a single institute. Eligible patients were selected according to inclusion criteria. Demographic data, clinical and laboratory parameters, and treatment outcomes were extracted from medical records. Categorization of patients and subsequent subgroup analysis were based on cholangiography.

Results: The rate of emergent cholecystectomy in the PC tube removal group was higher than that in the PC tube preserved group (OR = 2.969, 95% CI 1.334-6.612, P = 0.008). In subgroup analysis of patients with patent bile flow under cholangiography, the rate of emergent cholecystectomy was higher in the PC tube removal group (OR = 3.173, 95% CI 1.182-8.523, P = 0.022), though the incidence of complications was higher in the PC tube preserved group (P = 0.012). In addition, routine preoperative cholangiography had no clinical impact on surgical outcome.

Conclusion: Percutaneous cholecystostomy tube can be removed before subsequent LC to avoid postoperative complications, though removal of the PC tube is associated with an increased likelihood of emergent cholecystectomy.
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http://dx.doi.org/10.1002/jhbp.740DOI Listing
August 2020

Natural Course of Acute Cholecystitis in Patients Treated With Percutaneous Transhepatic Gallbladder Drainage Without Elective Cholecystectomy.

J Gastrointest Surg 2020 04 3;24(4):772-779. Epub 2019 Apr 3.

Division of Trauma and Emergency Surgery, General Surgery, Chang Gung Memorial Hospital, No. 5, Fuxing St., Guishan Dist., Taoyuan, 333, Republic of China.

Background: Percutaneous transhepatic gallbladder drainage (PTGBD) is an alternative treatment for acute cholecystitis (AC). We aimed to understand the natural course of AC in patients treated with PTGBD but without later definitive treatments, such as laparoscopic cholecystectomy.

Methods: This was a retrospective study of the period from June 2010 to December 2016, during which time 2371 patients were diagnosed with AC and 625 received PTGBD treatment. Among the 625 patients, 237 received no definitive treatment. A biliary event after the initial AC episode was the outcome of interest. In addition, the competing risk of death unrelated to biliary causes was present in the cohort. Therefore, a competing risk model was applied for analysis.

Results: The cumulative incidence of biliary events was 29.8% with a median of 4.27 months, while the competing event, i.e., death unrelated to a biliary event, was noted in 14.9% of patients with a median 23.54 months. The risk factors of biliary events were prolonged PTGBD indwelling and an abnormal PTGBD cholangiogram. The risk factors of death unrelated to a biliary event included a high Charlson comorbidity index and the initial AC severity.

Conclusions: Definitive cholecystectomy is still recommended for patients undergoing PTGBD treatment due to the high incidence of later biliary events. A thorough preoperative evaluation is necessary for those patients before elective cholecystectomy because of the inferior life expectancy and physical status.
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http://dx.doi.org/10.1007/s11605-019-04213-0DOI Listing
April 2020

Characterization of intrahepatic cholangiocarcinoma after curative resection: outcome, prognostic factor, and recurrence.

BMC Gastroenterol 2018 Dec 4;18(1):180. Epub 2018 Dec 4.

Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, 5 Fu-Hsing Street, Kwei-Shan District, Taoyuan City, 33305, Taiwan.

Background: Intrahepatic cholangiocarcinoma (ICC) is a relatively rare subtype of cholangiocarcinoma. The study herein gathered experience of surgical treatment for ICC, and aimed to analyze the prognosis of patients who had received curative-intent liver resection.

Methods: A total of 216 patients who had undergone curative-intent liver resection for ICC between January 1977 and December 2014 was retrospectively reviewed.

Results: Overall, the rates of 5-years recurrence-free survival (RFS) and overall survival (OS) were 26.1 and 33.9% respectively. Based on multivariate analysis, four independent adverse prognostic factors including morphology patterns, maximum tumor size > 5 cm, pathological lymph node involvement, and vascular invasion were identified as affecting RFS after curative-intent liver resection for ICC. Among patients with cholangiocarcinoma recurrence, only 27 (16.9%) were able to receive surgical resection for recurrent cholangiocarcinoma that had a significantly better outcome than the remaining patients.

Conclusion: Despite curative resection, the general outcome of patients with ICC is still unsatisfactory because of a high incidence of cholangiocarcinoma recurrence after operation. Tumor factors associated with cholangiocarcinoma remain crucial for the prognosis of patients with ICC after curative liver resection. Moreover, aggressive attitude toward repeat resection for the postoperative recurrent cholangiocarcinoma could provide a favorable outcome for patients.
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http://dx.doi.org/10.1186/s12876-018-0912-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278092PMC
December 2018

Survival impact of the number of lymph node retrieved on patients with node-negative gastric cancer: more is better?

Transl Gastroenterol Hepatol 2017 7;2:103. Epub 2017 Dec 7.

Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.

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http://dx.doi.org/10.21037/tgh.2017.12.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763007PMC
December 2017

Imatinib dose escalation versus sunitinib as a second-line treatment against advanced gastrointestinal stromal tumors: A nationwide population-based cohort study.

Oncotarget 2017 Sep 3;8(41):71128-71137. Epub 2017 Apr 3.

Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.

Background: Although treatment with imatinib in advanced gastrointestinal stromal tumor (GIST) patients has led to significant clinical benefits, the disease will eventually progress due to imatinib resistance. Treatment options after failure of first-line imatinib include imatinib dose escalation or shifting to sunitinib. However, there is no large-scale study to compare the efficacy difference between these two treatment strategies or the role of surgery.

Results: This study recruited 521 advanced GIST patients including 246, 125, and 150 placed in groups 1, 2, and 3, respectively. Groups 1 and 2 had significantly longer overall survival (OS) as compared with the group 3 (median 37.5 months versus 16.0 months; < 0.0001). After adjusting for confounding variables, groups 1 and 2 had longer OS than group 3. A favorable survival trend was seen with surgery, although this benefit disappeared after adjusting for confounding factors.

Materials And Methods: We conducted a nationwide population-based cohort study using data from the Taiwan National Health Insurance Research Database from July 2004 to December 2010. Advanced GIST patients who no longer responded to first-line imatinib were stratified into three groups: imatinib dose escalation (group 1); imatinib dose escalation and a shift to sunitinib (group 2); a direct shift to sunitinib (group 3). The therapeutic success of the three treatment regimens and the effect of surgery were evaluated by overall survival.

Conclusions: For advanced GIST patients who failed first-line imatinib treatment, imatinib dose escalation confers significantly longer OS compared to a direct switch to sunitinib. Surgery does not provide survival benefits.
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http://dx.doi.org/10.18632/oncotarget.16795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642623PMC
September 2017

The impact of preoperative etiology on emergent pancreaticoduodenectomy for non-traumatic patients.

World J Emerg Surg 2017 2;12:21. Epub 2017 May 2.

Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University, Linkou branch, No.5, Fu-Xing Street, Kueishan District, Taoyuan City, 333 Taiwan.

Background: Emergent pancreaticoduodenectomy is a life-saving procedure in certain clinical scenarios when all the conservative treatment fails. The indications can be limited into perforation and bleeding. To clarify the impact of etiology on surgical outcomes of emergent pancreaticoduodenectomy for non-trauma, we analyzed our patients and performed a literature review.

Methods: We reviewed 931 consecutive pancreaticoduodenectomies performed at our institute between January 2001 and July 2015. Patients with emergent pancreaticoduodenectomy for non-trauma etiologies were enrolled, whereas those who suffered from caustic injuries were excluded. The keywords "emergent/emergency" and "pancreaticoduodenectomy/pancreatoduodenectomy" were applied in a literature search. The universally available data for all the enrolled patients including etiology, surgical complications, outcomes, and hospital stays were analyzed. Univariate and multivariate logistic analysis for the contributing factors to surgical mortality were performed.

Results: Six out of 931 (0.6%) registered pancreaticoduodenectomies matched our criteria of inclusion. The literature review obtained 4 series and 7 case reports, which when combined with our patients yielded a cohort of 31 emergent pancreaticoduodenectomies with 13 cases of perforation and 18 of bleeding. The rate of emergent pancreaticoduodenectomy for non-traumatic etiologies is similar between the present study and the other 3 series, ranging from 0.3 to 3%. The overall surgical complication rate was 83.9%. The rate of surgical mortality is significantly higher than in elective pancreaticoduodenectomy by propensity score matching with age and gender (19.4 versus 3.2%,  = 0.015). Univariate and multivariate logistic regression disclosed that etiology is the only preoperative risk factor for surgical mortality (perforation versus bleeding; odds ratio = 39.494,  = 0.031).

Conclusions: Emergent pancreaticoduodenectomy remains a rare operation. Surgical morbidity and mortality are higher than with elective pancreaticoduodenectomy among different reported series. By sorting the preoperative etiologies into two groups, perforation carries a higher risk of surgical mortality than bleeding.
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http://dx.doi.org/10.1186/s13017-017-0133-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414322PMC
September 2018

Validation of TG13 severity grading in acute cholecystitis: Japan-Taiwan collaborative study for acute cholecystitis.

J Hepatobiliary Pancreat Sci 2017 Jun 23;24(6):338-345. Epub 2017 May 23.

Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.

Background: The collaborative multicenter retrospective study of acute cholecystitis (AC) was performed in Japan and Taiwan. The aim for this study was evaluation of the clinical value of TG13 severity grading for AC.

Method: The study was designed as an international multicenter retrospective study of AC from 2011 to 2013. Based on the data, we investigated the TG13 severity grading by analyzing the correlations between grade and prognosis, surgical procedures, histopathology, and organ dysfunction and prognosis.

Results: An investigation revealed that 30-day overall mortality rate was 1.1% for Grade I, 0.8% for Grade II, 5.4% for Grade III. The mortality rate for Grade III was significantly higher than lower grades (P < 0.001). The greater the number of organ dysfunction, the higher the mortality rate (P < 0.001). However, the mortality rate varied depending on the number of organ dysfunction (3.1-25%). With respect to the surgical procedures, laparoscopic cholecystectomy was performed for Grade I patients (P < 0.001), and the higher the grade, the more likely open surgery would be selected (P < 0.001).

Conclusion: TG13 severity grading criteria for AC are providing great benefits in actual clinical settings. From this study, the position of each severity grade was obviously confirmed.
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http://dx.doi.org/10.1002/jhbp.457DOI Listing
June 2017

Clinical application and verification of the TG13 diagnostic and severity grading criteria for acute cholangitis: an international multicenter observational study.

J Hepatobiliary Pancreat Sci 2017 Jun 29;24(6):329-337. Epub 2017 May 29.

Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.

Background: The Tokyo Guidelines 2007 (TG07) first presented the diagnostic and severity grading criteria for acute cholangitis. Subsequently updated in 2013, the Tokyo Guidelines (TG13) have been widely adopted throughout the world as global standard guidelines. We set out to verify the efficacy of these TG13 criteria in an international multicenter study.

Methods: We reviewed 6,063 patients who were clinically diagnosed with acute cholangitis in Japan and Taiwan over a 2-year period. The TG13 diagnostic and severity grading criteria were retrospectively applied, and 30-day mortality was investigated.

Results: A diagnosis of acute cholangitis was made in 5,454 (90.0%) patients on the basis of the TG13 criteria, and in 4,815 (79.4%) patients on the basis of the TG07 criteria. The 30-day mortality rates of patients with Grade III, Grade II, and Grade I were 5.1%, 2.6%, and 1.2%, respectively, and increased significantly along with disease severity. The mortality rate in the 1,272 Grade II cases where urgent or early biliary drainage was performed was 2.0% (n = 25), which was significantly lower than that of 3.7% (n = 28) in the other 748 cases.

Conclusion: By using the TG13 diagnostic and severity grading criteria, more patients with possible acute cholangitis can be diagnosed, and patients whose prognosis can potentially be improved by early biliary drainage can be identified. The TG13 criteria are appropriate and useful for clinical practice.
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http://dx.doi.org/10.1002/jhbp.458DOI Listing
June 2017

Optimal treatment strategy for acute cholecystitis based on predictive factors: Japan-Taiwan multicenter cohort study.

J Hepatobiliary Pancreat Sci 2017 Jun 31;24(6):346-361. Epub 2017 May 31.

Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.

Background: Although early laparoscopic cholecystectomy is widely performed for acute cholecystitis, the optimal timing of a cholecystectomy in clinically ill patients remains controversial. This study aims to determine the best practice for the patients presenting with acute cholecystitis focused on disease severity and comorbidities.

Methods: An international multicentric retrospective observational study was conducted over a 2-year period. Patients were divided into four groups: Group A: primary cholecystectomy; Group B: cholecystectomy after gallbladder drainage; Group C: gallbladder drainage alone; and Group D: medical treatment alone.

Results: The subjects of analyses were 5,329 patients. There were statistically significant differences in mortality rates between patients with Charlson comorbidity index (CCI) scores below and above 6 (P < 0.001). The shortest operative time was observed in Group A patients who underwent surgery 0-3 days after admission (P < 0.01). Multiple regression analysis revealed CCI and low body mass index <20 as predictive factors of 30-day mortality in Grade I+II patients. Also, jaundice, neurological dysfunction, and respiratory dysfunction were predictive factors of 30-day mortality in Grade III patients. In Grade III patients without predictive factors, there were no difference in mortality between Group A and Group B (0% vs. 0%), whereas Group A patients had higher mortality rates than that of Group B patients (9.3% vs. 0.0%) in cases with at least one predictive factor.

Conclusion: Even patients with Grade III severity, primary cholecystectomy can be performed safely if they have no predictive factors of mortality. Gallbladder drainage may have a therapeutic role in subgroups with higher CCI or higher disease severity.
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http://dx.doi.org/10.1002/jhbp.456DOI Listing
June 2017

Percutaneous and endoscopic gallbladder drainage for acute cholecystitis: international multicenter comparative study using propensity score-matched analysis.

J Hepatobiliary Pancreat Sci 2017 Jun 17;24(6):362-368. Epub 2017 May 17.

Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.

Background: Tokyo Guideline 2013 (TG13) proposed three drainage techniques for the treatment of acute cholecystitis. We evaluated the clinical efficacy and adverse events between percutaneous transhepatic intervention (PTGBI) including percutaneous transhepatic gallbladder drainage (PTGBD) and percutaneous transhepatic gallbladder aspiration (PTGBA) and endoscopic transpapillary gallbladder drainage (EGBD).

Methods: A cohort study was performed using propensity score matching to reduce treatment selection bias. This involved the analysis of collected data for 1,764 patients who underwent PTGBI and EGBD.

Results: Propensity score matching extracted 330 pairs of patients. The difference in the clinical success rate within 3 days between PTGBI and EGBD were 62.5% and 69.8%, respectively (P = 0.085). The differences in the suboptimal clinical success rates within 7 days between PTGBI and EGBD were 87.6% and 89.2% (P = 0.579). The differences in the complication rate between PTGBI and EGBD were 4.8% and 8.2% (P = 0.083). The differences in the complication rate among PTGBD, PTGBA and EGBD were 5.6%, 1.6% and 8.2% (P = 0.11). Median required days of PTGBD (3.0 days) was significantly longer than those of PTGBA and EGBD (1.5 and 2.0 days, respectively) (P = 0.001).

Conclusion: The current study showed the PTGBI showed similar clinical efficacy compared with EGBD without significant discrepancy of complication rate for the treatment of acute cholecystitis.
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http://dx.doi.org/10.1002/jhbp.454DOI Listing
June 2017

Updated comprehensive epidemiology, microbiology, and outcomes among patients with acute cholangitis.

J Hepatobiliary Pancreat Sci 2017 Jun 26;24(6):310-318. Epub 2017 May 26.

Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.

Background: The international practice guidelines for patients with acute cholangitis and cholecystitis were released in 2007 (TG07) and revised in 2013 (TG13). This study investigated updated epidemiology and outcomes among patients with acute cholangitis on a larger scale for the first time.

Methods: This is an international multi-center retrospective observational study in Japan and Taiwan. All consecutive patients older than 18 years of age and given a clinical diagnosis of acute cholangitis by clinicians between 1 January 2011 and 31 December 2012 were enrolled. Those who met the diagnostic criteria of acute cholangitis by TG13 were statistically analyzed.

Results: A total of 7,294 patients were enrolled and 6,433 patients met the TG13 diagnostic criteria. The severity distribution was Grade I (37.5%), Grade II (36.2%), and Grade III (26.2%). The 30-day all-cause mortality was 2.4%, 4.7%, and 8.4% in Grade I, II, III severity, respectively (P < 0.001). The incidence of liver abscess and endocarditis as complications of acute cholangitis was 2.0% and 0.26%, respectively.

Conclusions: This is the first large scale study to investigate patients with acute cholangitis. This study provides the basis to define the best practices to manage patients with acute cholangitis in future studies.
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http://dx.doi.org/10.1002/jhbp.452DOI Listing
June 2017

Descriptive review of acute cholecystitis: Japan-Taiwan collaborative epidemiological study.

J Hepatobiliary Pancreat Sci 2017 Jun 14;24(6):319-328. Epub 2017 May 14.

Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.

Background: Since the publication of the Tokyo Guidelines (TG13) for the management of acute cholecystitis (AC), multidirectional studies have been published. However, epidemiological research about AC with big data was not projected. The aim of this study was to reveal the actual clinical conditions of AC.

Method: The study was designed as an international multicenter retrospective study of AC in Japan and Taiwan from 2011 to 2013. The factors investigated comprised data related to demographic, history, physical examinations, laboratory and imaging findings. Based on these data, we investigated the various values of AC, and real situation with respect to severity and treatment.

Results: A total of 5,459 patients with AC were reviewed. Thirty-day mortality rate was 1.1%. Based on the diagnostic criteria, 4,088 patients had a definite diagnosis and 291 had a suspected diagnosis. According to the severity grading, 939 patients were classified as Grade III, 2,308 as Grade II, and 2,130 as Grade I. Cholecystectomy was performed in total of 4,266 patients and 2,765 patients had laparoscopic cholecystectomy. The main etiologies were gallbladder stones in 4,623 cases.

Conclusion: This epidemiological study with large population will undoubtedly contribute to establish the best practice for managing AC worldwide.
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http://dx.doi.org/10.1002/jhbp.450DOI Listing
June 2017

Palliative gastrectomy is beneficial in selected cases of metastatic gastric cancer.

BMC Palliat Care 2017 Mar 14;16(1):19. Epub 2017 Mar 14.

Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, #5, Fushing Street, Kweishan District, Taoyuan City, 333, Taiwan.

Background: Salvage chemotherapy is the mainstay of treatment for metastatic gastric cancer (mGC). This study aimed to clarify the effects of palliative gastrectomy (PG) and identify prognostic factors in mGC patients undergoing PG.

Methods: This was a retrospective review of 333 mGC patients receiving PG or a non-resection procedure (NR) between 2000 and 2010. Clinicopathological factors affecting the prognosis of these patients were collected prospectively and analyzed.

Results: One hundred and ninety-three patients underwent PG and 140 NR. The clinicopathological characteristics were comparable between the two groups except for metastatic pattern. There were no significant differences in postoperative morbidity and mortality between the two groups. The PG group had a significantly longer median overall survival compared with the NR group (7.7 months vs. 4.9 months). In the PG group, age ≤58 years, preoperative albumin level >3 g/dL, ratio of metastatic to examined lymph nodes ≤0.58, and administration of chemotherapy were independent prognostic factors in multivariate analysis.

Conclusions: Patients undergoing PG had better outcomes than those undergoing NR. Among the patients undergoing resection, age ≤58 years, a better preoperative nutritional status, less nodal involvement and postoperative chemotherapy independently affected patient survival.
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http://dx.doi.org/10.1186/s12904-017-0192-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348866PMC
March 2017

An opportunity in difficulty: Japan-Korea-Taiwan expert Delphi consensus on surgical difficulty during laparoscopic cholecystectomy.

J Hepatobiliary Pancreat Sci 2017 Apr 19;24(4):191-198. Epub 2017 Mar 19.

Division of General Surgery, Lin-Kou Chang Gung Memorial Hospital, Tauyuan, Taiwan.

Background: We previously identified 25 intraoperative findings during laparoscopic cholecystectomy (LC) as potential indicators of surgical difficulty per nominal group technique. This study aimed to build a consensus among expert LC surgeons on the impact of each item on surgical difficulty.

Methods: Surgeons from Japan, Korea, and Taiwan (n = 554) participated in a Delphi process and graded the 25 items on a seven-stage scale (range, 0-6). Consensus was defined as (1) the interquartile range (IQR) of overall responses ≤2 and (2) ≥66% of the responses concentrated within a median ± 1 after stratification by workplace and LC experience level.

Results: Response rates for the first and the second-round Delphi were 92.6% and 90.3%, respectively. Final consensus was reached for all the 25 items. 'Diffuse scarring in the Calot's triangle area' in the 'Factors related to inflammation of the gallbladder' category had the strongest impact on surgical difficulty (median, 5; IQR, 1). Surgeons agreed that the surgical difficulty increases as more fibrotic change and scarring develop. The median point for each item was set as the difficulty score.

Conclusions: A Delphi consensus was reached among expert LC surgeons on the impact of intraoperative findings on surgical difficulty.
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http://dx.doi.org/10.1002/jhbp.440DOI Listing
April 2017

Role of splenectomy in proximal gastric cancer patients undergoing total gastrectomy.

Transl Gastroenterol Hepatol 2016 23;1:84. Epub 2016 Nov 23.

Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.

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http://dx.doi.org/10.21037/tgh.2016.11.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244735PMC
November 2016

Survival impact of the number of lymph node dissection on stage I-III node-negative gastric cancer.

Transl Gastroenterol Hepatol 2016 16;1. Epub 2016 Mar 16.

Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.

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http://dx.doi.org/10.21037/tgh.2016.03.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244715PMC
March 2016

The "right" way is not always popular: comparison of surgeons' perceptions during laparoscopic cholecystectomy for acute cholecystitis among experts from Japan, Korea and Taiwan.

J Hepatobiliary Pancreat Sci 2017 Jan 22;24(1):24-32. Epub 2017 Jan 22.

Division of General Surgery, Lin-Kou Chang Gung Memorial Hospital, Tauyuan, Taiwan.

Background: Generally, surgeons' perceptions of surgical safety are based on experience and institutional policy. Our recent pilot survey demonstrated that the acceptable duration of surgery and criteria for open conversion during laparoscopic cholecystectomy (LC) vary among workplaces.

Methods: A web-based survey was distributed to 554 expert LC surgeons in Japan, Korea, and Taiwan. The questionnaire covered LC experience, safety measures and recognition of landmarks, decision-making regarding conversion to open/partial cholecystectomy and the implications of this decision. Overall responses were compared among nations, and then stratified by LC experience level (lifetime cases 200-499, 500-999, and ≥1,000).

Results: The response rate was 92.6% (513/554); 67 surgeons with ≤199 LCs were excluded, and responses from 446 surgeons were analyzed. We observed significant differences among nations on almost all questions. Differences that remained after stratification by LC experience were on questions related to acceptable duration of surgery, adoption rates of intraoperative cholangiography, the "critical view of safety" technique, identification of Rouvière's sulcus, recognition of the SS-Inner layer theory, and intraoperative judgment to abandon conventional LC.

Conclusions: Even among experts, surgeons' perceptions during LC are workplace-dependent. A novel grading system of surgical difficulty and standardized LC procedures are paramount to generate high-level evidence.
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http://dx.doi.org/10.1002/jhbp.417DOI Listing
January 2017

What are the appropriate indicators of surgical difficulty during laparoscopic cholecystectomy? Results from a Japan-Korea-Taiwan multinational survey.

J Hepatobiliary Pancreat Sci 2016 Sep 5;23(9):533-47. Epub 2016 Sep 5.

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

Background: Serious complications continue to occur in laparoscopic cholecystectomy (LC). The commonly used indicators of surgical difficulty such as the duration of surgery are insufficient because they are surgeon and institution dependent. We aimed to identify appropriate indicators of surgical difficulty during LC.

Methods: A total of 26 Japanese expert LC surgeons discussed using the nominal group technique (NGT) to generate a list of intraoperative findings that contribute to surgical difficulty. Thereafter, a survey was circulated to 61 experts in Japan, Korea, and Taiwan. The questionnaire addressed LC experience, surgical strategy, and perceptions of 30 intraoperative findings listed by the NGT.

Results: The response rate of the survey was 100%. There was a statistically significant difference among nations regarding the duration of surgery and adoption rate of safety measures and recognition of landmarks. The criteria for conversion to an open or subtotal cholecystectomy were at the discretion of each surgeon. In contrast, perceptions of the impact of 30 intraoperative findings on surgical difficulty (categorized by factors related to inflammation and additional findings of the gallbladder and other intra-abdominal factors) were consistent among surgeons.

Conclusions: Intraoperative findings are objective and considered to be appropriate indicators of surgical difficulty during LC.
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http://dx.doi.org/10.1002/jhbp.375DOI Listing
September 2016

Prognostic Value of the Metastatic Lymph Node Ratio in Patients With Resectable Carcinoma of Ampulla of Vater.

Medicine (Baltimore) 2015 Oct;94(42):e1859

From the Department of General Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan (C-HH, C-YT, J-TH, C-NY, Y-YJ, T-SY, K-HL), Department of Anatomical Pathology, Chang Gung Memorial Hospital, Linkou, Taiwan (T-DC), Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taiwan (T-SY, W-CC); and Department of Hematology and Oncology, Chang Gung Memorial Hospital, Linkou, Taiwan (W-CC).

Patients with carcinoma of the ampulla of Vater (CAV) have better outcomes among periampullary malignancies. However, little is known about the metastatic lymph node ratio (LNR) as a prognostic factor for resectable CAV. We retrospectively reviewed our CAV patients undergoing curative surgery and analyzed their prognostic factors.A total of 212 CAV patients who received radical surgery at Chang Gung Memorial Hospital, Linkou, between 2000 and 2010 were admitted in this study. The lymph node ratio was defined as the number of metastatic lymph nodes (LNs) divided by the total number of LNs removed. The patients' demographic data, comorbidities, operation type, and tumor features were analyzed retrospectively for survival prediction of patients.The median age of the patients was 62 years, and 57% of the patients were men. The surgical procedure was standard pancreaticoduodenectomy and pylorus-preserving pancreaticoduodenectomy in 53% and 47% of the patients, respectively. The median follow-up duration was 32.6 months, and 50% of the patients had died by the end of the study. The median overall survival time (OS) and disease-free survival time (DFS) were 65.8 and 33.7 months, respectively. In multivariate analysis, patients with a metastatic LNR >0.056 had a significantly poor prognosis in both OS and DFS.A metastatic LNR >0.056 predicted a poor DFS and OS in CAV patients after radical surgery. Greater awareness on the impact of metastatic LNR may help clinicians provide appropriate adjuvant treatment for high-risk CAV patients.
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http://dx.doi.org/10.1097/MD.0000000000001859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620839PMC
October 2015

Gastric cancer patients with end-stage renal disease who underwent radical gastrectomy.

Anticancer Res 2015 Apr;35(4):2263-8

Gastric Cancer Team, Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan, R.O.C.

Background: Radical gastrectomy (RG) with lymph node (LN) dissection is a standard procedure for gastric cancer (GC). Patients with end-stage renal disease (ESRD) usually have high risk for any operative procedure. However, information for ESRD on RG for GC is limited.

Patients And Methods: A total of 2,021 GC patients who underwent RG with LN dissection were retrospectively reviewed. Among them, 26 patients had ESRD. The clinicopathological features and surgical outcomes were compared between GC with ESRD (ESRD-GC group) and GC without ESRD (GC group).

Results: ESRD-GC patients could be independently differentiated from GC patients by lower hemoglobin, negative lymph node (LN) involvement and higher postoperative complications. The overall survival rate of ESRD-GC group seemed better than that of GC group patients. Lesser depth of tumor invasion, LN metastasis and lymphatic invasion and early-staged tumor contributed to favorable prognosis of ESRD-GC group of patients.

Conclusion: RG might be beneficial for GC-ESRD patients especially for early-stage disease; however, RG for GC patients with ESRD should be more cautiously performed, otherwise the benefit might be compromised by higher postoperative complications and even mortality.
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April 2015

WNT-1 inducible signaling pathway protein-1 enhances growth and tumorigenesis in human breast cancer.

Sci Rep 2015 Mar 3;5:8686. Epub 2015 Mar 3.

Department of Anatomy, School of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan Tao-Yuan, Taiwan, 333, R.O.C.

WNT1 inducible signaling pathway protein 1 (WISP1) plays a key role in many cellular functions in a highly tissue-specific manner; however the role of WISP1 in breast cancer is still poorly understood. Here, we demonstrate that WISP1 acts as an oncogene in human breast cancer. We demonstrated that human breast cancer tissues had higher WISP1 mRNA expression than normal breast tissues and that treatment of recombinant WISP1 enhanced breast cancer cell proliferation. Further, ectopic expression of WISP1 increased the growth of breast cancer cells in vitro and in vivo. WISP1 transfection also induced epithelial-mesenchymal-transition (EMT) in MCF-7 cells, leading to higher migration and invasion. During this EMT-inducing process, E-cadherin was repressed and N-cadherin, snail, and β-catenin were upregulated. Filamentous actin (F-actin) remodeling and polarization were also observed after WISP1 transfection into MCF-7 cells. Moreover, forced overexpression of WISP1 blocked the expression of NDRG1, a breast cancer tumor suppressor gene. Our study provides novel evidence that WISP1-modulated NDRG1 gene expression is dependent on a DNA fragment (-128 to +46) located within the human NDRG1 promoter. Thus, we concluded that WISP1 is a human breast cancer oncogene and is a potential therapeutic target.
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http://dx.doi.org/10.1038/srep08686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346832PMC
March 2015

Clinical effect of a positive surgical margin after hepatectomy on survival of patients with intrahepatic cholangiocarcinoma.

Drug Des Devel Ther 2015 17;9:163-74. Epub 2014 Dec 17.

Department of General Surgery, Chang Gung University, Taoyuan, Taiwan.

Background: Several unfavorable prognostic factors have been proposed for peripheral cholangiocarcinoma (PCC) in patients undergoing hepatectomy, including gross type of tumor, vascular invasion, lymph node metastasis, a high carbohydrate antigen 19-9 level, and a positive resection margin. However, the clinical effect of a positive surgical margin on the survival of patients with PCC after hepatectomy still needs to be clarified due to conflicting results.

Methods: A total of 224 PCC patients who underwent hepatic resection with curative intent between 1977 and 2007 were retrospectively reviewed. Eighty-nine patients had a positive resection margin, with 62 having a microscopically positive margin and 27 a grossly positive margin (R2). The clinicopathological features, outcomes, and recurrence pattern were compared with patients with curative hepatectomy.

Results: PCC patients with hepatolithiasis, periductal infiltrative or periductal infiltrative mixed with mass-forming growth, higher T stage, and more advanced stage tended to have higher positive resection margin rates after hepatectomy. PCC patients who underwent curative hepatectomy had a significantly higher survival rate than did those with a positive surgical margin. When PCC patients underwent hepatectomy with a positive resection margin, the histological grade of the tumor, nodal positivity, and chemotherapy significantly affected overall survival. Locoregional recurrence was the most common pattern of recurrence.

Conclusion: A positive resection margin had an unfavorable effect on overall survival in PCC patients undergoing hepatectomy. In these patients, the prognosis was determined by the biology of the tumor, including differentiation and nodal positivity, and chemotherapy increased overall survival.
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http://dx.doi.org/10.2147/DDDT.S74940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277120PMC
March 2016

Imatinib escalation or sunitinib treatment after first-line imatinib in metastatic gastrointestinal stromal tumor patients.

Anticancer Res 2014 Sep;34(9):5029-36

Gastrointestinal Stromal Tumor Team, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan, R.O.C.

Aim: Imatinib mesylate (IM) is effective in metastatic gastrointestinal stromal tumor (GIST) patients; however, disease progression eventually occurs due to IM resistance or intolerance. Treatment options include IM escalation or a direct shift to sunitinib, but comparison of these strategies is required.

Patients And Methods: This study included 91 out of 214 metastatic GIST patients treated with IM, who experienced progression or intolerance between August 2001 and December 2012 at the Chang Gung Memorial Hospital. Treatment efficacy and safety profiles were retrospectively compared between groups of patients who either received escalated IM or were directly switched to sunitinib.

Results: There were no significant differences in age, gender, second-line treatment causes or gene mutations in the IM escalation group (N=63) versus the sunitinib group (N=28). The 2 groups had similar progression-free survival (PFS, p=0.316) and overall survival (OS, p=0.599). Patients without primary KIT exon 9 mutations and who treated with sunitinib had significantly better PFS (14.3 vs. 6.2 months, p=0.037) and a trend toward better OS (not reached vs. 16.4 months, p=0.161) compared to the IM-escalation group. Patients in both groups with responses and stable disease (SD), and IM escalation patients who underwent surgery and who had KIT exon 9 mutations, had favorable PFS. The most common non-hematological adverse events were edema in the IM escalation group and hand-foot syndrome and hypertension in the sunitinib group.

Conclusion: Comparable results were achieved by IM escalation and sunitinib treatment. Physicians should consider kinase mutations and specific adverse effects when choosing between these treatments.
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September 2014

The vitamin D analog, MART-10, represses metastasis potential via downregulation of epithelial-mesenchymal transition in pancreatic cancer cells.

Cancer Lett 2014 Nov 19;354(2):235-44. Epub 2014 Aug 19.

Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan Taoyuan, 333, Taiwan. Electronic address:

Pancreatic cancer (PDA) is a devastating disease and there is no effective treatment available at present. To develop new regiments against PDA is urgently needed. Previously we have shown that vitamin D analog, MART-10 (19-nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3), exerted potent antiproliferative effect on PDA in vitro and in vivo without causing hypercalcemia. Since metastasis is the major cause of PDA-related death, we therefore investigate the anti-metastasis effect of MART-10 on PDA. Our results showed that both 1α,25(OH)2D3 and MART-10 repressed migration and invasion of BxPC-3 and PANC cells with MART-10 much more potent than 1α,25(OH)2D3. 1α,25(OH)2D3 and MART-10 inhibited epithelial-mesenchymal transition (EMT) in pancreatic cancer cells through downregulation of Snail, Slug, and Vimentin expression in BxPC-3 and PANC cells. MART-10 further blocked cadherin switch (from E-cadherin to N-cadherin) in BxPC-3 cells. The F-actin synthesis in the cytoplasm of BxPC-3 cells was also repressed by 1α,25(OH)2D3 and MART-10 as determined by immunofluorescence stain. Both 1α,25(OH)2D3 and MART-10 decreased MMP-2 and -9 secretion in BxPC-3 cells as determined by western blot and zymography. Collectively, MART-10 should be deemed as a promising regimen against PDA.
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http://dx.doi.org/10.1016/j.canlet.2014.08.019DOI Listing
November 2014