Concurrent gemcitabine+S-1 neoadjuvant chemotherapy contributes to the improved survival of patients with small borderline-resectable pancreatic cancer tumors

Masui, Toshihiko; Doi, Ryuichiro; Kawaguchi, Yoshiya; Asahi, Satoru; Nakano, Kenji; Itö, Tatsuo; Anazawa, Takayuki; Takaori, Kyoichi; Üemoto, Shinji

doi:10.1007/s00595-016-1310-z

Cited by 22 publications

(49 citation statements)

References 28 publications

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“…The main reason of this problem is the low response rate for chemotherapy [42–46]. In our study, every patients accepted adjuvant chemotherapy if physical condition permits, and 20 patients (43.5%) in total accept chemotherapy (gemcitabine + S1) after the operation.…”

Section: Discussionmentioning

confidence: 89%

Superior mesenteric artery margin in pancreaticoduodenectomy for pancreatic adenocarcinoma

Liu

Tian

et al. 2016

Oncotarget

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The aim of this study is trying to describe more details of superior mesenteric artery margin in pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, to evaluate biological and prognostic implications of tumor budding in this margin, and to provide more evidence for evaluation of R0 surgery in pancreaticoduodenectomy. 46 patients in 5-years period are included in this study. Immunochemistry and immunofluorescence are used to analyze tumor budding and epithelial–mesenchymal transition. Superior mesenteric artery margin might be described from four aspects including location, gross appearance, microscopic appearance and tumor budding. We find that 1mm rule for R1 surgery is more appropriate to predict prognosis (P = 0.009) than 0mm rule (P = 0.141). Expression of cytokeratin in tumor budding is significantly lower than primary tumor (P = 0.001), and it suggests that tumor budding may participate the procedure of epithelial–mesenchymal transition. High-grade tumor budding and decreasing cytokeratin of tumor budding correlate with distant metastasis and has negative influence on prognosis. So superior mesenteric artery margin might be not only an area that tumor cells may invade, but also a pathway for distant metastasis. It is necessary to evaluate superior mesenteric artery margin in pancreaticoduodenectomy for pancreatic cancer.

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Section: Discussionmentioning

confidence: 89%

Superior mesenteric artery margin in pancreaticoduodenectomy for pancreatic adenocarcinoma

Liu

Tian

et al. 2016

Oncotarget

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“…The most common reported adverse events were gastrointestinal (emesis, nausea and diarrhoea) and haematological (thrombopenia, leucopenia). Toxicity of at least grade III was reported in 21 studies, with a rate of up to 64 per cent, involving mostly leucopenia, thrombocytopenia, nausea and fatigue. Katz and colleagues reported a grade III toxicity rate of 64 per cent, in a study in which FOLFIRINOX (leucovorin, 5‐fluorouracil, irinotecan and oxaliplatin) chemotherapy was combined with radiotherapy at a dose of 50·4 Gy.…”

Section: Resultsmentioning

confidence: 99%

“…Kim et al 34 21 40 65 24⋅9 9 0 8 6 3 9 Ielpo et al 42 11 61⋅8 † 20 73 100 n.r. Masui et al 43 18 63 21⋅7 8 3 8 7 3 3 Takai et al 44 32 61⋅8 1 9 ⋅2 75 n.r. n.r.…”

Section: Neoadjuvant Treatmentunclassified

“…Fujii et al 20 Kato et al 24 Hirono et al .25* Hirono et al 25 † Murakami et al 26 Hirono et al 25 † Small et al 32 Chuong et al 46 Dholakia et al 47 Esnaola et al 33 Kim et al 34 Patel et al 45 Ohigashi et al 38 Boone et al 48 Oh et al 40 Rose et al 49 Tzeng et al 41 Fujii et al 20 Sho et al 51* Sho et al 51 † Moningi et al 50 Rashid et al 52 Murakami et al 26 Ielpo et al 42 Katz et al 39 Masui et al 43 Shaib et al .36 Neoadjuvant treatment 0 1 0 2 0 3 0 4 0 5 0…”

Section: Upfront Surgerymentioning

confidence: 99%

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Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer

Versteijne¹,

Vogel

Besselink

et al. 2018

British Journal of Surgery

418

354

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BackgroundStudies comparing upfront surgery with neoadjuvant treatment in pancreatic cancer may report only patients who underwent resection and so survival will be skewed. The aim of this study was to report survival by intention to treat in a comparison of upfront surgery versus neoadjuvant treatment in resectable or borderline resectable pancreatic cancer.MethodsMEDLINE, Embase and the Cochrane Library were searched for studies reporting median overall survival by intention to treat in patients with resectable or borderline resectable pancreatic cancer treated with or without neoadjuvant treatment. Secondary outcomes included overall and R0 resection rate, pathological lymph node rate, reasons for unresectability and toxicity of neoadjuvant treatment.ResultsIn total, 38 studies were included with 3484 patients, of whom 1738 (49·9 per cent) had neoadjuvant treatment. The weighted median overall survival by intention to treat was 18·8 months for neoadjuvant treatment and 14·8 months for upfront surgery; the difference was larger among patients whose tumours were resected (26·1 versus 15·0 months respectively). The overall resection rate was lower with neoadjuvant treatment than with upfront surgery (66·0 versus 81·3 per cent; P < 0·001), but the R0 rate was higher (86·8 (95 per cent c.i. 84·6 to 88·7) versus 66·9 (64·2 to 69·6) per cent; P < 0·001). Reported by intention to treat, the R0 rates were 58·0 and 54·9 per cent respectively (P = 0·088). The pathological lymph node rate was 43·8 per cent after neoadjuvant therapy and 64·8 per cent in the upfront surgery group (P < 0·001). Toxicity of at least grade III was reported in up to 64 per cent of the patients.ConclusionNeoadjuvant treatment appears to improve overall survival by intention to treat, despite lower overall resection rates for resectable or borderline resectable pancreatic cancer.PROSPERO registration number: CRD42016049374.

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“…Pancreatic ductal adenocarcinoma (PDAC) is a fatal neoplasm with poor prognosis . Despite developments in detection and management, only approximately 8% of PDAC patients survive for 5 years after diagnosis . Surgery is the only curative treatment for PDAC; however, only 20% of cases are considered resectable at the time of detection .…”

Section: Introductionmentioning

confidence: 99%

Role of histone deacetylase 1 in distant metastasis of pancreatic ductal cancer

et al. 2018

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Current therapies for pancreatic ductal cancer (PDAC) do not sufficiently control distant metastasis. Thus, new therapeutic targets are urgently needed. Numerous studies have suggested that the epithelial‐mesenchymal transition (EMT) is pivotal for metastasis of carcinomas. The fact that the EMT is reversible suggests the possibility that it is induced by an epigenetic mechanism. In this study, we aimed to investigate the role of histone deacetylase 1 (HDAC1), which is an epigenetic mechanism on distant metastasis of PDAC. We investigated the HDAC1 expression in 103 resected PDAC specimens obtained from patients who were treated with/without preoperative therapy using immunohistochemistry. To validate the findings in the clinical samples, we evaluated the HDAC1 activity, the EMT‐associated genes and the migration/invasion ability in vitro, and performed an HDAC1 inhibitor assay. The high expression of HDAC1 in clinical samples was significantly associated with poor progression‐free survival, especially distant metastasis‐free survival. In vitro, HDAC1 inhibitors decreased the invasion ability and reversed the EMT change; the only factor to show a concomitant decrease was the expression of SNAIL. We confirmed that the HDAC1 expression was associated with the SNAIL expression in clinical samples. Moreover, the resistant cells and parental cells did not show any significant differences in the expression of HDAC1; this was consistent with the finding that preoperative therapy did not alter the HDAC1 expression in clinical samples. The targeting of HDAC1, which could suppress metastasis by inhibiting the EMT, is a promising treatment option for PDAC.

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Concurrent gemcitabine+S-1 neoadjuvant chemotherapy contributes to the improved survival of patients with small borderline-resectable pancreatic cancer tumors

Abstract: In the neoadjuvant setting, gemcitabine and S-1 improved the negative surgical margin rate in BRPC patients, but it did not improve survival. Thus, neoadjuvant chemotherapy should be given to BRPC patients at an earlier stage.

Cited by 22 publications

References 28 publications

Superior mesenteric artery margin in pancreaticoduodenectomy for pancreatic adenocarcinoma

Superior mesenteric artery margin in pancreaticoduodenectomy for pancreatic adenocarcinoma

Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer

Role of histone deacetylase 1 in distant metastasis of pancreatic ductal cancer

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