Neoadjuvant Chemotherapy with Gemcitabine and S-1 for Resectable and Borderline Pancreatic Ductal Adenocarcinoma: Results from a Prospective Multi-institutional Phase 2 Trial

Motoi, Fuyuhiko; Ishida, Kazuyuki; Fujishima, Fumiyoshi; Ottomo, Shigeru; Oikawa, Masaya; Okada, Takeru; Shimamura, Hiromune; Takemura, Shinichi; Ono, Fuminori; Akada, Masanori; Nakagawa, Kazuhiko; Katayose, Yu; Egawa, Shinichi; Unno, Michiaki

doi:10.1245/s10434-013-3129-9

Cited by 138 publications

(95 citation statements)

References 37 publications

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“…27,28 Increasing numbers of patients will probably receive preoperative chemotherapy in the future. Therefore, methods that effectively prevent obstruction in the long term are needed.…”

Section: Discussionmentioning

confidence: 99%

Influence of cholangitis after preoperative endoscopic biliary drainage on postoperative pancreatic fistula in patients with middle and lower malignant biliary strictures

Kaneko

Inoue

Kida

et al. 2017

Digestive Endoscopy

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Background and Aim: Preoperative cholangitis after preoperative drainage has been reported to increase postoperative complications, particularly pancreatic fistula. We therefore examined the effects of cholangitis after preoperative endoscopic biliary drainage (EBD) on postoperative pancreatic fistula in patients with middle and lower malignant biliary strictures. Methods:The study group comprised 102 patients who underwent EBD among patients who underwent surgery. Results:Of the 102 patients, 33 (32%) had postoperative pancreatic fistulas, and 56 (55%) had preoperative cholangitis after preoperative drainage. Analysis of risk factors for preoperative cholangitis showed that a total bilirubin level of 2.9 mg/dL or higher (hazard ratio [HR], 2.95; 95% confidence interval [CI], 1.223-7.130; P = 0.016) and a surgical waiting time of 29 days or longer (HR, 4.23; 95% CI, 1.681-10.637; P = 0.02) were independent risk factors for cholangitis. Patients with preoperative cholangitis had a significantly higher incidence of pancreatic fistula than did patients without preoperative cholangitis (78.8 vs 21.2%; P = 0.001). Patients with biliary cancer had a significantly higher incidence of pancreatic fistula than did those with pancreatic cancer (72.7 vs 27.2%; P = 0.005). Multivariate analysis showed that preoperative cholangitis (HR, 4.8; 95% CI,; P = 0.001) and biliary cancer (HR, 3.5; 95% CI, 1.335-8.942; P = 0.006) were significant independent risk factors for postoperative pancreatic fistula.Conclusion: Prevention of preoperative cholangitis, a risk factor for postoperative pancreatic fistula, is likely to decrease the incidence of postoperative pancreatic fistula.

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“…27,28 Increasing numbers of patients will probably receive preoperative chemotherapy in the future. Therefore, methods that effectively prevent obstruction in the long term are needed.…”

Section: Discussionmentioning

confidence: 99%

Influence of cholangitis after preoperative endoscopic biliary drainage on postoperative pancreatic fistula in patients with middle and lower malignant biliary strictures

Kaneko

Inoue

Kida

et al. 2017

Digestive Endoscopy

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“…More recently, regimens such as FOLFIRINOX [7] and albumin-bound paclitaxel plus gemcitabine [8] represent a 'new era' of treatment for PDA patients. These new options improve survival, and serve as neoadjuvant chemotherapy for locally advanced and borderline resectable disease [9,10,11]. The identification of rational therapeutic strategies based on the diversity of the molecular signature is therefore warranted.…”

Section: Introductionmentioning

confidence: 99%

Gli2 protein expression level is a feasible marker of ligand-dependent hedgehog activation in pancreatic neoplasms

Sugiyama¹,

Sasajima

Mizukami³

et al. 2016

pjp

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The hedgehog pathway is known to promote proliferation of pancreatic ductal adenocarcinoma (PDA) and has been shown to restrain tumor progression. To understand how hedgehog causes these effects, we sought to carefully examine protein expression of hedgehog signaling components during different tumor stages. Genetically engineered mice, Pdx1-Cre;LSL-Kras G12D and Pdx1-Cre;LSLKras G12D;p53 lox/+ , were utilized to model distinct phases of tumorigenesis, pancreatic intraepithelial neoplasm (PanIN) and PDA. Human pancreatic specimens of intraductal papillary mucinous neoplasm (IPMN) and PDA were also employed. PanIN and IPMN lesions highly express Sonic Hedgehog, at a level that is slightly higher than that observed in PDA. GLI2 protein is also expressed in both PanIN/ IPMN and PDA. Although there was no difference in the nuclear staining, the cytoplasmic GLI2 level in PDA was modest in comparison to that in PanIN/IPMN. Hedgehog interacting protein was strongly expressed in the precursors, whereas the level in PDA was significantly attenuated. There were no differences in expression of Patched1 at early and late stages. Finally, a strong correlation between Sonic Hedgehog and GLI2 staining was found in both human and murine pancreatic tumors. The results indicate that the GLI2 protein level could serve as a feasible marker of ligand-dependent hedgehog activation in pancreatic neoplasms.

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“…Although BRPC may technically be resectable, it has a particularly high risk of margin-positive resection and postoperative recurrence. Furthermore, the prognosis is much worse than that of resectable pancreatic cancer [16,17]. Therefore, recognition of BRPC is important for optimal patient care and evaluation of various new treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Optimal indication of neoadjuvant chemoradiotherapy for pancreatic cancer

Sho

Akahori

Tanaka

et al. 2015

Langenbecks Arch Surg

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Neoadjuvant Chemotherapy with Gemcitabine and S-1 for Resectable and Borderline Pancreatic Ductal Adenocarcinoma: Results from a Prospective Multi-institutional Phase 2 Trial

Abstract: NAC-GS was well tolerated and safe when used in a multi-institutional setting. The R0 resection rate and the 2-year survival rate analysis are encouraging for patients with resectable and borderline PDAC.

Cited by 138 publications

References 37 publications

Influence of cholangitis after preoperative endoscopic biliary drainage on postoperative pancreatic fistula in patients with middle and lower malignant biliary strictures

Influence of cholangitis after preoperative endoscopic biliary drainage on postoperative pancreatic fistula in patients with middle and lower malignant biliary strictures

Gli2 protein expression level is a feasible marker of ligand-dependent hedgehog activation in pancreatic neoplasms

Optimal indication of neoadjuvant chemoradiotherapy for pancreatic cancer

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