s-1-(combination) and Carcinoma--Pancreatic-Ductal

To evaluate the therapeutic efficacy and safety of S1 monotherapy or combination with nab-paclitaxel for the treatment of elderly patients with metastatic or locally advanced pancreatic adenocarcinoma.. PubMed, Embase, Cochrane Central Library, China Biology Medicine, and China National Knowledge Infrastructure databases were searched without time limits according to the inclusion criteria. RevMan (Version 5.3) software was used for data extraction and meta-analysis. Objective response rate (ORR) and disease control rate (DCR) were used to evaluate therapeutic effects while side effects including leukopenia, thrombocytopenia, neurotoxicity, vomit, and alopecia were extracted for evaluation. There was no need for ethical review in this study because no ethical experiments were conducted and all data used were public data. All relevant data are within the paper and its Supporting Information files.. Four retrospective studies comprising 308 elderly patients with metastatic or locally advanced pancreatic adenocarcinoma were included in the analysis. One hundred fifty-one patients underwent S1 monotherapy and 157 received S1 combined nab-paclitaxel. Meta-analysis indicated that compared with S1 monotherapy, S1 combined with nab-paclitaxel had higher ORR (OR 2.25, 95% CI: 1.42-3.55; P = .0005) and DCR (OR 2.94, 95% CI: 1.55-5.58; P = .0009). The adverse reaction of leukopenia was higher in the combined therapy group (OR 1.85, 95% CI: 1.09-3.13, P = .02), but no significant difference was found in thrombocytopenia, neurotoxicity, vomiting, and alopecia between the 2 groups (P > .05).. Nab-paclitaxel plus S1 was more efficient in terms of ORR and DCR than S1 monotherapy in elderly pancreatic ductal adenocarcinoma patients while the side effect was controllable with a higher probability of leukopenia. Thus, combined nab-paclitaxel and S1 could be safely used in elderly patients.

Topics: Age Factors; Aged; Aged, 80 and over; Albumins; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Drug Combinations; Humans; Leukopenia; Neoplasm Staging; Oxonic Acid; Paclitaxel; Pancreatic Neoplasms; Progression-Free Survival; Tegafur

To investigate the efficacy and safety of nab-paclitaxel plus S-1 (nab-P/S) versus nab-paclitaxel plus gemcitabine (nab-P/G) as first-line chemotherapy in patients with advanced pancreatic ductal adenocarcinoma (PDAC).. Treatment-naïve patients with advanced PDAC were equally randomized to receive nab-P/S or nab-P/G. The primary endpoint was the objective response rate (ORR). The secondary endpoints were ORR of the primary lesion, disease control rate, progression-free survival (PFS), overall survival (OS) and safety. The trial was registered at https://clinicaltrials.gov as NCT03636308.. A total of 110 patients were planned for enrollment, but the trial was prematurely closed because no better ORR was observed with nab-P/S among the first 40 patients assigned between 08/2018 and 06/2019. The ORR was numerically higher with nab-P/S versus nab-P/G (35.0% vs 25.0%, P = 0.49). The ORRs of the primary lesion for both arms were similar (30.0% and 25.0%, P = 0.72). Disease control rate was 70.0% in each arm. There was no significant difference in PFS and OS between the two arms (median PFS, 6.3 vs 5.7 months, P = 0.34; median OS, 10.2 vs 10.2 months, P = 0.92). Risks of hematological toxicity, liver injury and rash were significantly decreased in the nab-P/S arm.. A biweekly combination of nab-P/S yielded comparable efficacy with nab-P/G but improved safety profile. It may be a promising and convenient alternative as first-line and neoadjuvant settings for advanced PDAC.

Topics: Adenocarcinoma; Adult; Aged; Albumins; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Paclitaxel; Pancreatic Neoplasms; Progression-Free Survival; Tegafur

Neoadjuvant therapy reportedly shows only marginal clinical benefit in pancreatic ductal adenocarcinoma (PDAC), especially in resectable cases. However, with more effective regimens, neoadjuvant therapy may become a standard of care for resectable cases. A prospective, open-label, multicenter phases 1 and 2 trial of neoadjuvant therapy was conducted using full-dose gemcitabine and S-1 concurrently with 50.4 Gy of radiation therapy (GSRT) for resectable PDAC. This report describes the phase 2 results.. The phase 2 part of this study enrolled 57 patients with cytologically or histologically proven PDAC deemed resectable based on imaging before neoadjuvant therapy. These patients received GSRT. After reevaluation by computed tomography scan, surgical exploration was performed, followed by adjuvant therapy. According to the prescribed protocol of the clinical trial, statistical analyses included 57 phase 2 patients and 6 phase 1 patients who received the same dosage as in phase 2.. This trial enrolled 63 patients (42 men and 21 women) with a median age of 70 years. Leukopenia or neutropenia of grade 3 or higher occurred for 79% of the patients, but no other severe adverse events were observed. Among the 63 patients, 54 underwent surgical resection. Intention-to-treat analysis of the 63 patients showed an excellent median survival time lasting as long as 55.3 months. The patients who completed neoadjuvant therapy, surgery, and adjuvant therapy had a 5-year survival rate of 56.6%.. This regimen showed outstanding clinical efficacy with acceptable tolerability for patients with resectable PDAC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Intention to Treat Analysis; Male; Neoadjuvant Therapy; Oxonic Acid; Pancreatic Neoplasms; Prospective Studies; Tegafur

Pancreatic cancer is a refractory malignancy, and the development of a new effective treatment strategy is needed. We generated a dendritic cell vaccine by culturing monocytes obtained by apheresis of blood from each patient, inducing their differentiation into dendritic cells, and pulsing with tumor antigen peptides. However, the clinical efficacy of the vaccine has not been established. We therefore decided to conduct an exploratory clinical trial of dendritic cell vaccine loaded with Wilms' tumor gene 1 peptides (TLP0-001) as a potential new treatment for patients with advanced pancreatic cancer refractory to standard chemotherapy.. This is an investigator-initiated, double-blind, comparative trial. The patients were allocated to two groups in a 1:1 ratio through a central registration by dynamic allocation. A total of 185 patients with inoperable or metastatic pancreatic cancer who were refractory or intolerant to standard primary chemotherapy with gemcitabine plus nab-paclitaxel will be allocated to secondary treatment either with placebo in combination with S-1 (the control group) or TLP0-001 in combination with S-1 (the investigational product group). The primary objective of this trial is to evaluate the safety and efficacy (as measured by overall survival) of the investigational product by comparing the two groups. This clinical trial will be performed in accordance with Japanese Good Clinical Practice guidelines.. Clinical trials of the standard regimen, including gemcitabine, for advanced pancreatic cancer are ongoing worldwide. However, a strategy for after the primary treatment has not been established. We therefore decided to conduct this study to evaluate the safety and efficacy of TLP0-001 as a secondary treatment for pancreatic cancer in anticipation of the approval of this new drug in Japan. This trial is conducted with full consideration of safety, as it is the first-in-human clinical trial of TLP0-001; thus, the trial will be conducted only at the Second Department of Surgery at Wakayama Medical University until the safety is confirmed by interim analysis. We plan to conduct a multicenter trial at 18 institutions in Japan after confirmation of the safety.. University Hospital Medical Information Network Clinical Trials Registry, UMIN000027179 . Registered on 9 April 2017.

Topics: Adult; Aged; Cancer Vaccines; Carcinoma, Pancreatic Ductal; Dendritic Cells; Double-Blind Method; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Japan; Male; Middle Aged; Multicenter Studies as Topic; Oxonic Acid; Pancreatic Neoplasms; Peptide Fragments; Randomized Controlled Trials as Topic; Tegafur; Time Factors; Treatment Outcome; WT1 Proteins; Young Adult

The ideal neoadjuvant treatment protocol for patients with pancreatic cancer (PDAC) remains unclear. We evaluated the efficacy and safety of neoadjuvant hypofractionated chemoradiotherapy with S-1 for patients with resectable (R) and borderline resectable (BR) PDAC.. Fifty-seven patients were enrolled in this study, including 33 R and 24 BR [19 BR tumors with portal vein contact (BR-PV) and 5 BR tumors with arterial contact (BR-A)]. The total rates of protocol treatment completion and resection were 91% (50/57) and 96% (55/57), respectively. Seven patients failed to complete S-1 due to cholangitis (n = 5) or neutropenia (n = 2). The most common grade 3 toxicities [Common Terminology Criteria for Adverse Events (CTCAE) version 4.0] were anorexia (7%), nausea (5%), neutropenia (4%), and leukopenia (4%). No patient experienced grade 4 toxicity. Pathologically negative margins (R0) were achieved in 54 of 55 patients (98%) who underwent pancreatectomy. Pathological response was classified as Evans grade I in 8 patients (15%), IIa in 31 patients (56%), IIb in 14 patients (25%), III in 1 patient (2%), and IV in 1 patient (2%), and operative morbidity (Clavien-Dindo grade IIIb or less) was observed in 4 patients (8%). The 1- and 2-year overall survival (OS) rates were 91 and 83% in R patients, respectively, and 77 and 58% in BR patients, respectively (p = 0.03).. Neoadjuvant S-1 with concurrent hypofractionated radiotherapy is tolerable and appears promising for patients with R and BR PDAC.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Pancreatic Ductal; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Margins of Excision; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Pancreaticoduodenectomy; Prospective Studies; Radiation Dose Hypofractionation; Survival Rate; Tegafur

To evaluate the clinical efficacy and tolerability of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel combined with S-1, "an oral fluoropyrimidine derivative containing tegafur, gimestat, and otastat potassium" in chemotherapy-naive pancreatic ductal adenocarcinoma (PDAC) patients with peritoneal metastasis.. PDAC patients with peritoneal metastasis (peritoneal deposits and/or positive peritoneal cytology) have an extremely poor prognosis. An effective treatment strategy remains elusive.. Paclitaxel was administered i.v. at 50 mg/m and i.p. at 20 mg/m on days 1 and 8. S-1 was administered at 80 mg/m/d for 14 consecutive days, followed by 7 days of rest. The primary endpoint was 1-year overall survival (OS) rate. The secondary endpoints were antitumor effect and safety (UMIN000009446).. Thirty-three patients who were pathologically diagnosed with the presence of peritoneal dissemination (n = 22) and/or positive peritoneal cytology (n = 11) without other organ metastasis were enrolled. The tumor was located at the pancreatic head in 7 patients and the body/tail in 26 patients. The median survival time was 16.3 (11.47-22.57) months, and the 1-year survival rate was 62%. The response rate and disease control rate in assessable patients were 36% and 82%, respectively. OS in 8 patients who underwent conversion surgery was significantly higher than that of nonsurgical patients (n = 25, P = 0.0062). Grade 3/4 hematologic toxicities occurred in 42% of the patients and nonhematologic adverse events in 18%. One patient died of thrombosis in the superior mesenteric artery.. This regimen has shown promising clinical efficacy with acceptable tolerability in chemotherapy-naive PDAC patients with peritoneal metastasis.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Drug Administration Schedule; Drug Combinations; Female; Humans; Infusions, Intravenous; Injections, Intraperitoneal; Male; Middle Aged; Oxonic Acid; Paclitaxel; Pancreatic Neoplasms; Peritoneal Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

The objective of this study was to determine the recommended dose (RD) of a biweekly S-1, oxaliplatin, and irinotecan (SOXIRI) regimen in patients with unresectable pancreatic ductal adenocarcinoma.. This phase I study used a traditional "3+3" dose-escalation design, with four dose levels. A dose-escalation schedule consisted of two doses of S-1 (60 and 80 mg/m(2) twice daily) for 2 weeks in alternate-day administration, three doses of irinotecan (125, 150, and 180 mg/m(2)) on day 1, and a single dose of oxaliplatin (85 mg/m(2)) on day 1 of a 2-week cycle. Dose-limiting toxicities (DLTs) were assessed in the first four cycles to determine the maximum tolerated dose. This clinical study was registered at UMIN000014339.. Fifteen patients received this regimen (median, eight cycles; range 4-12). At dose level 3 (S-1, 80 mg/m(2); irinotecan, 150 mg/m(2)), 2/6 patients experienced DLTs of grade 3 fatigue and grade 4 neutropenia. At dose level 4, all three patients experienced DLTs: grade 3 fatigue (n = 1) and grade 4 neutropenia (n = 2). The RD was 80, 85, and 150 mg/m(2) of S-1, oxaliplatin, and irinotecan, respectively. We found the following: response rate, 47 %; disease control rate, 80%; median progression-free survival, 6.7 months; overall survival, 13.4 months.. The SOXIRI regimen's RD is 80, 85, and 150 mg/m(2) of S-1, oxaliplatin, and irinotecan, respectively.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Pancreatic Ductal; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Combinations; Feasibility Studies; Female; Humans; Irinotecan; Male; Maximum Tolerated Dose; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pancreatic Neoplasms; Survival Rate; Tegafur; Treatment Outcome

To determine the recommended dose (RD) for full-dose S-1 and low-dose gemcitabine combined with radiotherapy in patients with non-metastatic advanced pancreatic cancer.. Adult patients with non-metastatic advanced pancreatic cancer (Union for International Cancer Control T stage 3 or 4) were eligible. The weekly intravenous gemcitabine (level 0-1: 200 mg/ml,level 2: 300 mg/m on Days 1, 8, 15, 22, 29, 36) dose was escalated starting from level 1 in a 3+3 design along with full dose twice-daily oral S-1 (level 0: 60 mg/m2/day, level 1-2: 80 mg/ml/day), and was administered on the same days as radiotherapy (1.8 Gy x 28 days).. Eight patients were included in this study. A dose-limiting toxicity (DLT) (grade 4 neutropenia) was observed in one of the first three patients in level 1, and three additional patients received the level 1 dose without any severe adverse events. DLTs (grade 3/4 neutropenia) were then observed in the first two patients given level 2 dose. Therefore, level 1 was designated as the RD. Common grade 3/4 toxicities included neutropenia (62.5%), anorexia (37.5%), and pneumonitis (12.5%).. The combination of S-1 and gemcitabine with concurrent radiotherapy is a feasible regimen at the level 1 dose.

Topics: Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Chemoradiotherapy; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Radiation Pneumonitis; Tegafur; Treatment Outcome

Use of the fourth-generation oral fluoropyrimidine S-1 together with gemcitabine has shown striking anticancer effects. In this single-arm phase I trial of preoperative combination therapy using gemcitabine and S-1 concurrently with radiotherapy, we verified the safety and feasibility and determined the maximum-tolerated dose of each drug in patients with resectable pancreatic cancer.. A standard 3+3 dose escalation scheme was used. Patients with cytologically or histologically proven resectable pancreatic ductal adenocarcinoma were administered 30-min intravenous gemcitabine infusions on days 1, 8, 22, and 29 and S-1 orally on days 1-5, 8-12, 22-26, and 29-33. A total radiation dose of 50.4 Gy (1.8 Gy/day, 5 times per week, 28 fractions) was concurrently delivered. Surgical exploration was scheduled 4-7 weeks after the final radiation fraction.. Twenty-one patients were enrolled. No treatment-related deaths occurred during this study. Recommended doses were determined to be 80 mg/m(2) of S-1 daily and 1,000 mg/m(2) of gemcitabine. CA19-9 was reduced to <50 % of baseline values in 12 (75 %) of 16 measurable patients. Nineteen of 21 enrolled patients successfully underwent surgical resection.. Preoperative chemoradiotherapy consisting of gemcitabine and S-1 concurrent with full-dose radiation is feasible and well tolerated.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Chemoradiotherapy; Deoxycytidine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Gemcitabine; Humans; Infusions, Intravenous; Male; Middle Aged; Oxonic Acid; Tegafur; Treatment Outcome

Surgical resection is the only curative strategy for pancreatic ductal adenocarcinoma (PDAC), but recurrence rates are high even after purported curative resection. First-line treatment with gemcitabine and S-1 (GS) is associated with promising antitumor activity with a high response rate. The aim of this study was to assess the feasibility and efficacy of GS in the neoadjuvant setting.. In a multi-institutional single-arm phase 2 study, neoadjuvant chemotherapy (NAC) with gemcitabine and S-1, repeated every 21 days, was administered for two cycles (NAC-GS) to patients with resectable and borderline PDAC. The primary end point was the 2-year survival rate. Secondary end points were feasibility, resection rate, pathological effect, recurrence-free survival, and tumor marker status.. Of 36 patients enrolled, 35 were eligible for this clinical trial conducted between 2008 and 2010. The most common toxicity was neutropenia in response to 90% of the relative dose intensity. Responses to NAC included radiological tumor shrinkage (69%) and decreases in CA19-9 levels (89%). R0 resection was performed for 87% in resection, and the morbidity rate (40%) was acceptable. The 2-year survival rate of the total cohort was 45.7%. Patients who underwent resection without metastases after NAC-GS (n = 27) had an increased median overall survival (34.7 months) compared with those who did not undergo resection (P = 0.0017).. 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.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Female; Follow-Up Studies; Gemcitabine; Humans; Laparoscopy; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Pancreatic Neoplasms; Prognosis; Prospective Studies; Radiotherapy Dosage; Remission Induction; Survival Rate; Tegafur

Pancreatic cancer has a poor prognosis, and it is traditionally treated with chemotherapy. Fortunately, immunotherapy has rapidly changed the landscape of solid tumor treatment, and improving the survival of cancer patients. However, pancreatic cancer is non-immunogenic, and single agent immunotherapies are unfavorable to its prognosis.. Here, we report a case of stage IV pancreatic cancer in a patient with TSC2 and SMAD4 mutations treated with immunotherapy when the disease progressed after multi-line chemotherapy. Next generation sequencing (NGS) confirmed the presence of TSC2 and SMAD4 mutations and microsatellite stability (MSS). When the disease progressed after chemotherapy, a combination strategy was devised consisting of chemotherapy (S-1) and sintilimab. The patient had a partial response to therapy with this regimen, the lesions were significantly reduced and nearly disappeared. In metastatic pancreatic cancer, responses of this magnitude are rarely seen.. This outcome reveals that this combination can be effective in treating metastatic pancreatic cancer, especially in pancreatic cancer patients with SMAD4 and TSC2 mutations. This may help increase the use of this therapy in large-scale clinical research.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; DNA Mutational Analysis; Drug Combinations; Drug Resistance, Neoplasm; Fluorouracil; High-Throughput Nucleotide Sequencing; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Mutation; Neoplasm Staging; Oxaliplatin; Oxonic Acid; Pancreatic Neoplasms; Prognosis; Programmed Cell Death 1 Receptor; Response Evaluation Criteria in Solid Tumors; Smad4 Protein; Tegafur; Tuberous Sclerosis Complex 2 Protein

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Male; Microwaves; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Propensity Score; Radiofrequency Ablation; Retrospective Studies; Survival Rate; Tegafur; Tumor Burden

Although adjuvant chemotherapy is considered a standard treatment for resected pancreatic ductal adenocarcinoma (PDAC), its utility in stage ⅠA patients is unclear. We aimed to investigate the recurrence rate, surgical outcome, prognostic factors, effectiveness of adjuvant chemotherapy, and determination of groups in whom adjuvant chemotherapy is effective in patients with stage ⅠA PDAC.. We retrospectively analyzed 73 patients who underwent pancreatectomy and were pathologically diagnosed with stage ⅠA PDAC between 2000 and 2018. We evaluated the relation between clinicopathological factors, recurrence rates, and outcomes such as the recurrence-free and disease-specific survival rates (RFS and DSS, respectively).. The 5-year RFS and DSS rates were 52% and 58%, respectively. In multivariate analysis, a platelet-to-lymphocyte ratio (PLR) ≥ 170, prognostic nutrition index (PNI) < 47.5, and pathological grade 2 or 3 constituted risk factors for a shorter DSS (hazard ratios: 4.7, 4.6, and 4.1, respectively). Patients with 0-1 of these risk factors (low-risk group; n = 47) had significantly higher 5-year DSS rates than those with 2-3 risk factors (high-risk group; n = 26) (80% vs. 23%; P < 0.001). Patients in the low-risk group showed similar 5-year RFS rates regardless of whether they received or not adjuvant chemotherapy (75% vs 70%, respectively; P = 0.49). Contrarily, high-risk patients who underwent adjuvant chemotherapy had higher 5-year RFS rates than those who did not receive adjuvant chemotherapy (32% vs 0%; P = 0.045).. In stage IA PDAC, adjuvant chemotherapy seems to be effective only in a subgroup of high-risk patients.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Chemotherapy, Adjuvant; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Follow-Up Studies; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Pancreaticoduodenectomy; Retrospective Studies; Tegafur; Treatment Outcome

Multiple guidelines for pancreatic ductal adenocarcinoma (PDAC) suggest that all stages of patients need to receive postoperative adjuvant chemotherapy. S-1 is a recently emerged oral antitumour agent recommended by the guidelines. However, which population would benefit from S-1 needs to be determined, and predictors of chemotherapy response are needed for personalized precision medicine. This pilot study aimed to initially identify whether whole-tumour evaluation with MRI and radiomics features could be used for predicting the efficacy of S-1 and to find potential predictors of the efficacy of S-1 as evidence to assist personalized precision treatment.. Forty-six patients with PDAC (31 in the primary cohort and 15 in the validation cohort) who underwent curative resection and subsequently adjuvant chemotherapy with S-1 were included. Pre-operative abdominal contrast-enhanced MRI was performed, and radiomics features of the whole PDAC were extracted from the primary cohort. After univariable analysis and radiomics features selection, a multivariable Cox regression model for survival analysis was subsequently used to select statistically significant factors associated with postoperative disease-free survival (DFS). Predictive capacities of the factors were tested on the validation cohort by using Kaplan-Meier method.. Multivariable Cox regression analysis identified the probability of T. Whole-tumour radiomics feature of T

Topics: Analysis of Variance; Antimetabolites, Antineoplastic; Carcinoma, Pancreatic Ductal; Chemotherapy, Adjuvant; Contrast Media; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Pilot Projects; Postoperative Care; Precision Medicine; Retrospective Studies; Survival Analysis; Tegafur; Treatment Outcome

The study aimed to investigate the potential benefit of more than 4 courses of S1 adjuvant chemotherapy for patients with pancreatic ductal adenocarcinoma (PDAC) after surgery.. Data were retrospectively collected from consecutive patients who underwent S-1 adjuvant chemotherapy following curative pancreatectomy between January 2016 and December 2018. Four-courses and > 4 courses cohorts were compared for overall survival (OS) as a primary outcome, and relapse-free survival (RFS) and adverse event incidence as secondary outcomes.. Four-courses and > 4 courses cohorts comprised 99 patients and 64 ones, respectively. TNM stage (stage II vs. I: HR, 2.125; 95% CI, 1.164-4.213; P = 0.015), duration of S-1 administration (4 vs. > 4 courses: HR, 3.113; 95% CI, 1.531-6.327; P = 0.002) and tumor grade (G3 vs. G1/2: HR, 3.887; 95% CI, 1.922-7.861; P < 0.001) were independent prognostic factors. Under the condition of patients' survival time beyond 8 months, the OS of patients in > 4 courses cohort was significantly prolonged compared with that of 4 courses cohort (4 vs. > 4 courses: HR, 2.284; 95% CI, 1.197-4.358; P = 0.012), especially for patients in TNM stageII (4 vs. > 4 courses: HR, 2.906; 95% CI, 1.275-6.623; P = 0.011).RFS and adverse events incidence did not signifcantly difer between both cohorts.. Prolonged duration of S-1 intake is beneficial to prognosis of patients with PDAC resection.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Pancreatic Ductal; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Prognosis; Retrospective Studies; Tegafur; Time Factors; Young Adult

Active hexose-correlated compound (AHCC) is a standardized extract from cultured Lentinula edodes mycelia, used as a potent biological response modifier in cancer treatment. We evaluated the nutritional effect of AHCC, given during neoadjuvant therapy, to patients with pancreatic ductal adenocarcinoma (PDAC). Thirty patients with resectable or borderline-resectable PDAC received neoadjuvant therapy with gemcitabine plus S-1. We compared, retrospectively, the outcomes of 15 patients who received AHCC combined with neoadjuvant therapy with those of 15 patients who did not receive AHCC combined with neoadjuvant therapy. The median changes of the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutrition index (PNI) were significantly better in the AHCC group. The relative dose intensity of neoadjuvant therapy was also significantly higher in the AHCC group. Thus, AHCC may improve the nutritional status during neoadjuvant therapy of patients with pancreatic ductal adenocarcinoma. To validate these results and examine the long-term impact of AHCC, a prospective phase II study for PDAC is ongoing.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoadjuvant Therapy; Nutrition Assessment; Nutrition Therapy; Nutritional Status; Oxonic Acid; Pancreatic Neoplasms; Phytotherapy; Polysaccharides; Shiitake Mushrooms; Tegafur; Treatment Outcome

Evaluation of recurrence pattern and risk factors for recurrence are essential for good rates of survival after upfront pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC).. This retrospective study included 167 consecutive patients who underwent upfront PD for resectable PDAC between 2000 and 2018. Postoperative recurrences were classified into three patterns according to initial recurrence site: isolated locoregional, isolated distant, and simultaneous locoregional and distant recurrences.. This study found 114 patients who developed postoperative recurrence (68.3%), including 37 patients with isolated locoregional recurrence (32.5%), 67 patients with isolated distant recurrence (58.8%), and 10 patients with simultaneous locoregional and distant recurrences (6.0%). When locoregional recurrence was classified based on the location of recurrent lesions, locoregional recurrence most commonly occurred around the superior mesenteric artery (SMA) (70.2%), followed by around the hepatic artery (25.5%) and in the paraaortic region (14.9%). Multivariate analyses showed that complete circumferential lymphadenectomy around the SMA, including not only the right side, but also the left side, was an independent factor for reduction of locoregional recurrence (P = 0.019, odds ratio [OR]: 2.217). Lymph node metastasis was an independent risk factor for both locoregional (P < 0.001, OR: 3.686) and distant recurrences (P < 0.001, OR: 4.315). Non-completion of postoperative adjuvant therapy was a risk factor for distant recurrence (P < 0.001, OR: 3.748).. Based on our data, complete circumferential lymphadenectomy around the SMA might contribute to local control, and multidisciplinary treatment including neoadjuvant therapy might be needed for resectable PDAC with high risk for recurrence.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Chemotherapy, Adjuvant; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Mesenteric Artery, Superior; Middle Aged; Neoplasm Recurrence, Local; Organ Sparing Treatments; Oxonic Acid; Pancreatic Neoplasms; Pancreaticoduodenectomy; Peripheral Nerves; Retrospective Studies; Survival Rate; Tegafur

Neoadjuvant therapy is increasingly used to control local tumor spread and micrometastasis of pancreatic ductal adenocarcinoma (PDAC). Pathology assessments of treatment effects might predict patient outcomes after surgery. However, there are conflicting reports regarding the reproducibility and prognostic performance of commonly used tumor regression grading systems, namely College of American Pathologists (CAP) and Evans' grading system. Further, the M.D. Anderson Cancer Center group (MDA) and the Japan Pancreas Society (JPS) have introduced other grading systems, while we recently proposed a new, simple grading system based on the area of residual tumor (ART). Herein, we aimed to assess and compare the reproducibility and prognostic performance of the modified ART grading system with those of the four grading systems using a multicenter cohort. The study cohort consisted of 97 patients with PDAC who had undergone post-neoadjuvant pancreatectomy at four hospitals. All patients were treated with gemcitabine and S-1 (GS)-based chemotherapies with/without radiation. Two pathologists individually evaluated tumor regression in accordance with the CAP, Evans', JPS, MDA and ART grading systems, and interobserver concordance was compared between the five systems. The ART grading system was a 5-tiered system based on a number of 40× microscopic fields equivalent to the surface area of the largest ART. Furthermore, the final grades, which were either the concordant grades of the two observers or the majority grades, including those given by the third observer, were correlated with patient outcomes in each system. The interobserver concordance (kappa value) for Evans', CAP, MDA, JPS and ART grading systems were 0.34, 0.50, 0.65, 0.33, and 0.60, respectively. Univariate analysis showed that higher ART grades were significantly associated with shorter overall survival (p = 0.001) and recurrence-free survival (p = 0.005), while the other grading systems did not show significant association with patient outcomes. The present study revealed that the ART grading system that was designed to be simple and more objective has achieved high concordance and showed a prognostic value; thus it may be most practical for assessing tumor regression in post-neoadjuvant resections for PDAC.

Topics: Aged; Carcinoma, Pancreatic Ductal; Chemoradiotherapy, Adjuvant; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Japan; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Prognosis; Reproducibility of Results; Survival Analysis; Tegafur; Treatment Outcome

Although postoperative adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC) improves survival, its efficacy varies among individuals. Identification of biomarkers that can predict the efficacy of adjuvant chemotherapy for PDAC is essential.. To investigate the predictive value of secreted protein acidic and rich in cysteine (SPARC) expression in patients with PDAC treated with adjuvant gemcitabine in combination with S-1 (adjuvant GS) or adjuvant gemcitabine alone (adjuvant G alone).. Stromal SPARC and cytoplasmic SPARC were examined immunohistochemically in 211 PDAC patients treated with adjuvant GS or G alone after resection. The association of SPARC expression with clinicopathological factors, disease-free survival (DFS) and overall survival (OS) were analyzed.. In multivariate analysis, borderline resectable with arterial contact (BR-A) (P = .002), higher preoperative CA 19-9 level (≥91 U/ml) (P = .005), moderately or poorly (P = .003), presence of lymph node metastasis (P = .012) and high stromal SPARC expression (P = .013) were independent predictors of poor DFS. Moreover, BR-A (P = .003), higher preoperative CA 19-9 level (≥91 U/ml) (P = .007) and high stromal SPARC expression (P < .001) were identified as independent predictors of poor OS. In contrast, cytoplasmic SPARC expression did not affect DFS and OS.. High stromal SPARC expression was an independent predictor of poor DFS and OS in patients treated with adjuvant GS or G alone. Stromal SPARC expression could be a relevant biomarker for prediction of prognosis in PDAC patients after resection treated with adjuvant GS or G alone.

Topics: Aged; Antineoplastic Agents; Carcinoma, Pancreatic Ductal; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Gene Expression Regulation, Neoplastic; Humans; Male; Osteonectin; Oxonic Acid; Retrospective Studies; Survival Analysis; Tegafur

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease; however, the frequency of recurrence can be reduced if curative surgery following adjuvant chemotherapy is applied. At present, adjuvant chemotherapy is uniformly performed in all patients, as it is unclear which tumor types are controlled best or worst. We investigated patients with recurrence to establish the optimum treatment strategy.. Of 138 patients who underwent curative surgery for PDAC, 85 developed recurrence. Comprehensive clinicopathological factors were investigated for their association with the survival time after recurrence (SAR).. The median SAR was 12.6 months. Treatments for recurrence included best supportive care, GEM-based therapy and S-1. The performance status [hazard ratio (HR) 0.12, P < 0.001], histological invasion of lymph vessels (HR 0.27, P < 0.001), kind of treatment for recurrence (HR 5.0, P < 0.001) and initial recurrence site (HR 2.9, P < 0.001) were independent significant risk factors for the SAR. The initial recurrence sites were the liver (n = 21, median SAR 8.8 months), lung (n = 10, 14.9 months), peritoneum (n = 6, 1.7 months), lymph nodes (n = 6, 14.7 months), local site (n = 17, 13.9 months) and multiple sites (n = 25, 10.1 months). A shorter recurrence-free survival (< 1 year) and higher postoperative CA19-9 level were significantly associated with critical recurrence (peritoneal/liver).. Several risk factors for SAR were detected in this study. Further investigations are needed to individualize the adjuvant chemotherapy for each patient with PDAC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoma, Pancreatic Ductal; Chemotherapy, Adjuvant; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Precision Medicine; Retrospective Studies; Risk Factors; Survival Rate; Tegafur

We compared the clinical outcomes of pancreatic ductal adenocarcinoma (PDAC) resection after neoadjuvant chemoradiation therapy (NACRT) vs. chemotherapy (NAC).. The study population comprised 81 patients with UICC stage T3/4 PDAC, treated initially by NACRT with S-1 in 40 and by NAC with gemcitabine + S-1 in 41. This was followed by pancreatectomy with routine nerve plexus resection in 35 of the patients who had received NACRT and 32 of those who had received NAC. We compared the survival curves and clinical outcomes of these two groups.. The rates of clinical response, surgical resectability, and margin-negative resection were similar. The NACRT group patients had significantly higher rates of Evans stage ≥IIB tumors (29 vs. 0 %, respectively, p = 0.010) and negative lymph nodes (49 vs. 16 %, respectively, p = 0.021) than the NAC group patients. There was no difference in disease-free survival between the groups, but the disease-specific survival of the NAC group patients was better than that of the NACRT group patients (p = 0.034). Patients undergoing pancreatectomy with nerve plexus resection following NACRT had significantly higher rates of intractable diarrhea and ascites but consequently received significantly less adjuvant chemotherapy and therapeutic chemotherapy for relapse.. NACRT followed by pancreatectomy with nerve plexus resection is superior for achieving local control, but postoperative diarrhea and ascites may prohibit continuation of adjuvant chemotherapy or chemotherapy for relapse (UMIN4148).

Topics: Adult; Aged; Ascites; Carcinoma, Pancreatic Ductal; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Combined Modality Therapy; Deoxycytidine; Diarrhea; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Postoperative Complications; Tegafur; Treatment Outcome

Preoperative chemoradiotherapy (CRT) is a novel, emerging treatment strategy for pancreatic ductal adenocarcinoma (PDAC), but it remains unclear whether post-surgery adjuvant chemotherapy is feasible following preoperative CRT. This retrospective study evaluates the feasibility of adjuvant therapy after preoperative CRT.. The subjects of this study were 99 consecutive patients who underwent pancreatectomy for PDAC between January, 2007 and February, 2013 in our hospital. Sixty patients received preoperative CRT: as gemcitabine (GEM) and 40 Gy radiation in 28 (G-CRT group), and as GEM, S-1, and 50.4 Gy radiation in 32 (GS-CRT group). We also evaluated 39 patients who underwent surgery alone (SA group). We investigated adjuvant chemotherapy induction and completion rates and the frequency of adverse events rated ≥grade 3, based on Common Terminology Criteria for Adverse Events (version 4.0) in all three groups.. In the G-CRT, GS-CRT, and SA groups, the induction rates were 78 % (22/28), 78 % (25/32), and 72 % (28/39), respectively; completion rates were 86 % (19/22), 88 % (22/25), and 82 % (23/28), respectively; and adverse event frequencies were 36 % (8/22), 28 % (7/25), and 43 % (12/28), respectively. No significant difference was found among the three groups.. Preoperative CRT was demonstrated to be safe and did not compromise the feasibility of adjuvant chemotherapy.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Feasibility Studies; Female; Gemcitabine; Humans; Male; Middle Aged; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Preoperative Period; Radiotherapy Dosage; Retrospective Studies; Tegafur

For the establishment of personalized therapy, we investigated biomarkers that can contribute to the selection of adjuvant therapy for pancreatic ductal adenocarcinoma (PDAC).. Between 2005 and 2014, of 141 consecutive patients with PDAC who underwent R0 or R1 resection, 61 patients given gemcitabine and 31 patients given S-1 as adjuvant therapy were enrolled. We evaluated the correlation between treatment outcomes and the expressions of intratumoral human antigen R (HuR), human equilibrative nucleoside transporter 1 (hENT1), thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD).. There were no significant differences in clinicopathological features between the gemcitabine and S-1 groups. Among those with high HuR expression and high hENT1 expression, the disease-free survival (DFS) was significantly higher with gemcitabine than with S-1 (MST: 26.2 vs. 11.8 months, P = 0.024; 20.2 vs. 10.2 months, P = 0.029, respectively). Moreover, high HuR/hENT1 (high HuR or high hENT1) was significantly associated with better outcome for gemcitabine (HR for DFS: 0.43, P = 0.027) and low HuR/hENT1 was significantly associated with worse outcome for gemcitabine (HR for DFS: 2.24, P = 0.021). TS and DPD expression levels were not informative in this examination.. HuR and hENT1 were good candidates as selective biomarkers and this study's concept could contribute to personalized therapy for PDAC patients.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy, Needle; Carcinoma, Pancreatic Ductal; Chemotherapy, Adjuvant; Cohort Studies; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Gemcitabine; Hospitals, University; Humans; Immunohistochemistry; Japan; Kaplan-Meier Estimate; Lymph Nodes; Male; Middle Aged; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Patient Selection; Precision Medicine; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Statistics, Nonparametric; Survival Rate; Tegafur

Pancreatic adenosquamous carcinoma coexisting with intraductal papillary mucinous neoplasm(IPMN)is extremely rare. We report a rare case of pancreatic adenosquamous carcinoma that developed after resection of intraductal papillary mucinous adenoma(IPMA). A 67-year-old man was suspected of having a pancreatic cystic lesion. MRCP demonstrated a cystic lesion measuring 25mm in the pancreatic tail, which had an enhanced nodule. We therefore diagnosed branch duct type IPMN of the pancreas. Although pancreatic juice cytology did not indicate malignancy, we performed laparoscope-assisted distal pancreatectomy. The reason why the IPMN lesion had an enhanced nodule. The histopathological diagnosis was IPMA without malignancy. One year and 5 months after surgery, blood analysis showed an elevated tumor marker level, and abdominal CT demonstrated a pancreatic head tumor with lymphadenopathy. EUS-FNA was performed and the patient was diagnosed with pancreatic adenosquamous carcinoma based on immunohistochemical staining. We administered chemotherapy with gemcitabine and S-1. After 3 courses of this chemotherapy, the size of the pancreatic tumor and the tumor marker level decreased. The patient achieved a partial response. He is still receiving chemotherapy after 7 courses.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Adenosquamous; Carcinoma, Pancreatic Ductal; Deoxycytidine; Drug Combinations; Gemcitabine; Humans; Male; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Tegafur

Pancreatic cancer (PC) with arterial invasion is currently a contraindication to resection and has a miserable prognosis.. Seventeen patients with locally advanced PC involving the celiac axis and/or common hepatic artery (CHA) who received chemoradiotherapy (CRT) composed of gemcitabine, S-1, and external beam irradiation over the last 2 years were investigated. Thirteen patients underwent pancreatectomy with major arterial resection: 6 distal pancreatectomies with resection of the celiac axis, 4 total pancreatectomies with resection of both the celiac axis and the CHA, and 3 pancreatoduodenectomies with resection of the CHA. Preoperative arterial embolization and/or arterial reconstruction to prevent ischemic gastropathy and hepatopathy was performed in 7 of the 13 patients.. Distant metastases were found in 3 patients after CRT. One patient did not consent to operation after CRT. The morbidity rate of the 13 patients who underwent surgery was 62% (8/13), but no deaths occurred. Although there were no responders on CT, >90% of tumor cells were necrotic on histopathology in 5 of 13 tumors after CRT. Invasion of the celiac axis remained in 5 tumors, and extrapancreatic plexus invasion remained in 8 tumors, but an R0 resection was achieved in 12 of 13 tumors. Lymph node metastases were found in 3 of 13 cases. The overall 1-year survival rate from commencement of CRT and resection was 12 of 13 patients.. Neoadjuvant CRT containing gemcitabine and S-1 and subsequent pancreatectomy with major arterial resection for patients with locally advanced PC with arterial invasion were carried out safely with an acceptable R0 resection acceptable morbidity and mortality, and encouraging survival (12 of 13) at 1 year postoperatively.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Celiac Artery; Chemoradiotherapy, Adjuvant; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Hepatic Artery; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Prognosis; Tegafur; Vascular Neoplasms

We report 2 cases of curative resection of pancreatic cancer after neoadjuvant chemotherapy. A 60-year-old woman was diagnosed as having borderline resectable pancreatic ductal adenocarcinoma with invasion of the nerve plexus covering the superior mesenteric artery. The preoperative chemotherapy, 4 courses of gemcitabine and S-1, reduced the volume of tumor; pancreaticoduodenectomy with portal vein resection after chemotherapy resulted in R0 resection. Pathological examination of the resected specimen showed fibroid tissue with myxoid degeneration and mucinous lake surrounded by differentiated adenocarcinoma. A 40-year-old woman was diagnosed as having borderline resectable pancreatic ductal adenocarcinoma with invasion of the common hepatic artery and splenic artery. The preoperative chemotherapy, 4 courses of gemcitabine and S-1, reduced the tumor volume; distal pancreatectomy with portal vein resection after chemotherapy obtained R0 resection. Pathological examination of the resected specimen revealed that the majority of the tumor was fibrotic and necrotic tissue, and few cancer cells remained viable. Neoadjuvant chemotherapy has a potential to increase the rate of R0 resection. Furthermore, preoperative chemotherapy can help avoid unnecessary surgery by allowing time for potential metastasis to become obvious.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Portal Vein; Tegafur; Treatment Outcome

A 69-year-old woman was admitted to a nearby clinic complaining of abdominal pain. Abdominal CT showed a 10 cm diameter huge cystic lesion in the body and tail of the pancreas. The patient was referred to our institution for treatment. Endoscopic ultrasonography (EUS) revealed a cystic mass with a solid lesion. Endoscopic retrograde pancreatography(ERP) demonstrated mucous at the opening of the papilla of Vater and dilatation of the pancreatic duct with a solid nodule. Contrast radiography revealed a fistula from the tumor to the jejunum. A biopsy specimen from the lesion showed adenocarcinoma. Intraoperative findings showed a tumor occupying the pancreas body and tail with suspected invasion to the stomach, jejunum, and transverse colon. We performed distal pancreatectomy with partial resection of stomach, jejunum, and colon. Pathological findings showed an invasive type of IPMC, with invasion to the subserosal layer of the stomach and colon and the mucous layer of the jejunum. While IPMC is recognized as a slow growing malignancy, some cases of invasive carcinoma with fistulation into adjacent organs have been reported. To our knowledge, a case of IPMC penetrating to 3 adjacent organs is rare.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Chemotherapy, Adjuvant; Colon; Deoxycytidine; Drug Combinations; Duodenum; Fatal Outcome; Female; Gemcitabine; Humans; Neoplasm Invasiveness; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Stomach; Tegafur

Little is known about the immunological effect of neoadjuvant chemoradiotherapy (NACRT) in the tumor microenvironment of pancreatic ductal adenocarcinoma. The objective of this study was to examine the immunological modifications induced by NACRT in patients with pancreatic cancer.. Fifty-two patients with pancreatic cancer who underwent surgical resection were enrolled in this study. NACRT was administered to 22 patients, whereas the other 30 patients underwent surgical resection without NACRT. The resected tumor specimens were analyzed for the presence of tumor-infiltrating lymphocytes by using immunohistochemical staining for CD4, CD8, CD68, CD163, Foxp3, and major histocompatibility complex class I (MHC class I) antigen.. The number of CD4+ and CD8+ lymphocytes was significantly higher in patients who received NACRT than in those who did not receive NACRT. No significant difference in MHC class I expression was observed between the groups. In the NACRT group, patients with a high accumulation of CD8+ cells experienced longer overall survival than those with a low number of CD8+ cells.. NACRT may induce the accumulation of CD4+ and CD8+ cells in the tumor microenvironment and a high accumulation of CD8+ cells might be a good prognostic marker for pancreatic cancer treated with NACRT.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; CD8-Positive T-Lymphocytes; Chemoradiotherapy; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Female; Follow-Up Studies; Gemcitabine; Humans; Lymphocytes, Tumor-Infiltrating; Male; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Prognosis; Survival Rate; Tegafur; Tumor Microenvironment

Several previous studies reported that the neutrophil-to-lymphocyte ratio (NLR) could be a promising prognostic factor for patients with cancer. We aimed to determine the prognostic value of NLR in patients with advanced pancreatic cancer (APC) following palliative chemotherapy. We retrospectively reviewed 252 consecutive APC patients receiving palliative chemotherapy between January 2006 and December 2012. We classified the patients according to the pretreatment NLR values (≤ 5 or >5) into two groups and investigated the difference in treatment outcomes, including time to treatment failure (TTF) and overall survival (OS). A total of 212 patients had pretreatment NLR values of ≤ 5 (group A), while 40 patients had an NLR of >5 (group B). TTF and OS were significantly shorter in group B than in group A (3.1 vs. 8.7 months and 6.0 vs. 12.8 months, respectively; both P < 0.01). After adjustment for putative prognostic factors, including distant metastasis, status of recurrent/unresectable disease, pretreatment carbohydrate antigen 19-9 levels, and carcinoembryonic antigen levels using the Cox regression model, elevated pretreatment NLR remained an independent poor prognostic factor for OS (hazard ratio, 1.92; 95% confidence interval, 1.27-2.90; P < 0.01). In addition, patients in group B whose NLR dropped to ≤ 5 before the second cycle of chemotherapy showed longer TTF and OS compared with those whose NLR remained at >5. Our results support the idea that NLR can be a promising prognostic and predictive marker for APC patients receiving palliative chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Cohort Studies; Deoxycytidine; Drug Combinations; Erlotinib Hydrochloride; Female; Gemcitabine; Humans; Lymphocytes; Male; Neutrophils; Oxonic Acid; Palliative Care; Pancreatic Neoplasms; Prognosis; Prospective Studies; Quinazolines; Survival Analysis; Tegafur; Treatment Outcome

A 63-year-old woman was admitted to our Hospital for treatment of pancreatic head ductal carcinoma, and underwent pancreaticoduodedectomy (PD) in October 2007. At one month after surgery, she received systemic adjuvant chemotherapy using S-1 for three months. Because the serum carbohydrate antigen 19-9 (CA19-9) value was elevated at 23 months after surgery, the patient underwent systemic chemotherapy using gemcitabine. The serum CA19-9 decreased, but abdominal Computed Tomography (CT) revealed a hepatic metastasis in the ventrolateral segment of left hepatic lobe at 28 months after surgery. The chemotherapy was changed to oral S-1. At 35 months after surgery, abdominal CT revealed reduction of liver metastasis and that the serum CA19-9 was normalized, but chemotherapy had to be withdrawn because of severe myelosuppression. Because of her good general condition, the patient underwent partial hepatectomy for the liver metastasis. Histopathological examination demonstrated a complete response. Thirty six months after hepatectomy and 6 years after PD, the patient remains well without recurrence. We herein report a case of successful treatment for metachronous liver metastasis from pancreatic ductal carcinoma after PD by chemotherapy and hepatectomy and review the current literature.

Topics: Antineoplastic Agents; Carcinoma, Pancreatic Ductal; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Hepatectomy; Humans; Liver Neoplasms; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Pancreaticoduodenectomy; Tegafur

Pancreatectomy with regional lymphadenectomy remains the only curative treatment option for pancreatic cancer. There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer.. Our objective was to retrospectively evaluate whether postoperative adjuvant chemotherapy using S-1 is clinically beneficial in managing resectable pancreatic cancer.. Patients were divided into three groups: those undergoing surgery alone, those receiving gemcitabine infusion, and those receiving S-1 orally.. Of 189 studied patients, the median overall survival was 15.0 months after surgery alone, 33.0 months in the gemcitabine group, and 45.0 months in patients receiving S-1. A multivariate analysis identified regional lymph node metastasis, positive surgical margins, and absence of adjuvant chemotherapy as independent negative prognostic factors. S-1 was not inferior to gemcitabine in terms of survival outcomes and showed a favorable hazard ratio compared with gemcitabine in the subsets of patients with positive vascular invasion.. There was no difference between adjuvant chemotherapy with S-1 and gemcitabine in overall survival for patients with curative pancreatic cancer. Our results suggested that S-1 can be used as a second agent to gemcitabine after surgical resection for ordinary adenocarcinoma of the pancreas.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Pancreatic Ductal; Chemotherapy, Adjuvant; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm, Residual; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Prognosis; Retrospective Studies; Survival Rate; Tegafur

The patient was a 62-year-old man who underwent distal pancreatectomy and partial resection of transverse colon with diagnosis of cystic tumor of pancreas tail in July 2006. In histology, the tumor was an invasive carcinoma derived from intraductal tumor. So, Chemotherapy using gemcitabine (GEM) was administered. Eleven months after the operation, abdominal contrast-enhanced CT showed a cystic tumor in the subdiaphragm and CEA increased to 15 .2 ng/mL. Combination chemotherapy using GEM and S-1 was administered under the diagnosis of peritoneal recurrence. CEA decreased to a normal level, but 19 months after the operation, CA19-9 increased to 187 .7 U/mL. Then, radiotherapy (a total of 40 Gy) was performed. Twenty two months after the radiotherapy, though chemotherapy using S-1 was continued, CA19-9 re- increased to 134 .2 U/mL. Abdominal contrast-enhanced CT and PET detected no other recurrent lesion. A tumor resection was performed in January 2010. In immunostaining MUC1(+), MUC2(-), MUC5AC(+), MUC6(+) and mucus expression forms as well as with previous specimen, and was diagnosed as recurrence of the invasive carcinoma derived from intraductal tumor.

Topics: Antineoplastic Agents; Carcinoma, Pancreatic Ductal; Chemoradiotherapy; Deoxycytidine; Drug Combinations; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Invasiveness; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Peritoneal Neoplasms; Recurrence; Tegafur; Tomography, X-Ray Computed