To investigate whether chemotherapy could prolong the postoperative survival time in patients with early stages pancreatic ductal adenocarcinoma (PDAC). A total of 5280 stage ⅠA -ⅡB PDAC patients diagnosed from 2010 to 2015 were selected from surveillance，epidemiology，and end results (SEER) database. Propensity score matching (PSM) analysis was adopted to reduce the baseline differences between the groups. Univariate survival analysis was conducted with the Kaplan-Meier method. Multivariate survival analysis was performed with the Cox proportional hazards model. Univariate and multivariate survival analyses showed that age, differentiation, stage, chemotherapy were independent risk factors for the survival of PDAC patients. After PSM, it is found that adjuvant chemotherapy could prolong the median overall survival time (mOS) for stage ⅠB, ⅡA and ⅡB patients. However, for stage ⅠA patients, there were no significant differences in 3-year survival rate and mOS between patients with chemotherapy (=283) and without chemotherapy (=229) (57.4% vs 55.6%, vs all >0.05). Further analyses show that among 101 patients with well differentiated PDAC and 294 patients with moderately differentiated PDAC, there were no significant differences in survival rate and mOS between patients with and without chemotherapy (all >0.05). Among 117 patients with low-differentiated + undifferentiated PDAC, 3-year survival rate and mOS in patients with chemotherapy were significantly better than those without chemotherapy (48.5% vs 34.1%, vs all <0.05). Chemotherapy regimen used currently is not beneficial for patients with moderately and well differentiated stage ⅠA PDAC, but it is an independent prognostic factor for low-differentiated + undifferentiated PDAC patients.
Adenocarcinoma/pathology* ; Carcinoma, Pancreatic Ductal/surgery* ; Chemotherapy, Adjuvant ; Humans ; Neoplasm Staging ; Pancreatic Neoplasms/drug therapy* ; Prognosis ; Propensity Score

OBJECTIVETo assess the efficacy of Chinese medicine (CM) on patients with pancreatic cancer (PC) in a retrospective population-based study.

METHODSBetween January 1, 2013, and August 30, 2016, according to whether received Western medicine treatment, the patients were included into either integrative medicine (IM) group or CM group. All enrolled patients were orally administrated with Gexia Zhuyu Decoction () or Liujun Ermu Decoction () by syndrome differentiation, twice a day, last for at least 2 months. The primary end point was overall survival (OS).

RESULTSA total of 174 patients with PC were enrolled in this study. In stage I/II, the median OS was 20.5 months in the IM group [95% confidence interval (CI), 12.499 to 28.501] and 11.17 months in the CM group (95% CI, 5.160 to 17.180, P=0.015). The 1- and 2-year survival rates for the two groups were 47.0%, 40.0% and 21.0%, 21.0%, respectively. In stage III/IV, median OS was 13.53 months (95% CI, 8.665 to 18.395) in the IM group versus 6.4 months (95% CI, 0.00 to 15.682) in the CM group, respectively (P=0.32). The 1- and 2-year survival rate for the IM and CM groups were 27.0%, 7.0% and 20.0%, 2.0%, respectively.

CONCLUSIONSIntervention of CM contributes to the different survival benefits for PC in different stages. Multimodality treatment might be a promising strategy for PC patients in early stage. While, in advanced stage, CM might be an alternative candidate for PC patients.

Adult ; Aged ; Aged, 80 and over ; Clinical Trials, Phase III as Topic ; Female ; Humans ; Integrative Medicine ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Pancreatic Neoplasms ; drug therapy ; pathology ; Survival Analysis

PURPOSE: This study was aimed to investigate the effect of pseudolaric acid B (PAB) on proliferation, invasion and epithelial-to-mesenchymal transition (EMT) in pancreatic cancer cells and to explore the possible mechanism. MATERIALS AND METHODS: The pancreatic cancer cell line SW1990 was cultured and treated with PAB dose- and time-dependent manners. Cell proliferation and invasion ability were measured by MTT assay and Matrigel/Transwell test, respectively. Semi-quantitative real-time polymerase chain reaction and Western blotting were conducted to detect the expression of EMT markers and the key molecules. Finally, nude mice subcutaneous transplantation tumor model was used to confirm the therapy efficacy of PAB. RESULTS: PAB could inhibit SW1990 cell proliferation and invasion in time- and dose-dependent manners. Vimentin, fibronectin, N-cadherin, Snail, Slug, YAP, TEAD1, and Survivin were down-regulated (p < 0.01), while E-cadherin, caspase-9, MST1, and pYAP were up-regulated (p < 0.05). Combined PAB and gemcitabine treatment markedly restricted the tumor growth compared with gencitabin or PAB alone groups. CONCLUSION: PAB could inhibit the proliferation and invasion ability of pancreatic cancer cells through activating Hippo-YAP pathway and inhibiting the process of EMT.
Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/metabolism ; Cadherins ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation/drug effects ; Cytokines ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/pharmacology ; Deoxycytidine/therapeutic use ; Diterpenes/pharmacology ; Diterpenes/therapeutic use ; Epithelial-Mesenchymal Transition/drug effects ; Female ; Humans ; Mice, Nude ; Neoplasm Invasiveness ; Pancreatic Neoplasms/diet therapy ; Pancreatic Neoplasms/pathology ; Real-Time Polymerase Chain Reaction ; Signal Transduction/drug effects ; Vimentin/metabolism

Antineoplastic Agents, Immunological ; immunology ; pharmacology ; Cell Line, Tumor ; GPI-Linked Proteins ; antagonists & inhibitors ; immunology ; Humans ; Neoplasm Proteins ; analysis ; immunology ; Pancreatic Neoplasms ; drug therapy ; immunology ; pathology

PURPOSE: Erlotinib-gemcitabine combined chemotherapy is considered as the standard treatment for unresectable pancreatic cancer. This study aimed to determine the clinical factors associated with response to this treatment. MATERIALS AND METHODS: This retrospective study included 180 patients with unresectable pancreatic cancer who received ≥2 cycles of gemcitabine-erlotinib combination therapy as first-line palliative chemotherapy between 2006 and 2014. "Long-term response" was defined as tumor stabilization after >6 chemotherapy cycles. RESULTS: The median progression-free survival (PFS) and overall survival (OS) were 3.9 and 8.1 months, respectively. On univariate analysis, liver metastasis (p=0.023) was negatively correlated with long-term response. Locally advanced stage (p=0.017), a history of statin treatment (p=0.01), and carcinoembryonic antigen levels <4.5 (p=0.029) had a favorable effect on long-term response. On multivariate analysis, a history of statin treatment was the only independent favorable factor for long-term response (p=0.017). Prognostic factors for OS and PFS were significantly correlated with liver metastasis (p=0.031 and 0.013, respectively). A history of statin treatment was also significantly associated with OS after adjusting for all potential confounders (hazard ratio, 0.48; 95% confidence interval, 0.26-0.92; p=0.026). CONCLUSION: These results suggest that statins have a favorable effect on "long-term response" to gemcitabine-erlotinib chemotherapy in unresectable pancreatic cancer patients. Statins may have a chemoadjuvant role in stabilizing long-term tumor growth.
Adenocarcinoma/*drug therapy/secondary ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Deoxycytidine/administration & dosage/analogs & derivatives ; Disease-Free Survival ; Erlotinib Hydrochloride/administration & dosage ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Male ; Middle Aged ; Neoplasm Staging ; Pancreatic Neoplasms/*drug therapy/pathology ; Retrospective Studies ; Survival Rate ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of Chinese herbal medicine combined with systemic chemotherapy and/or regional arterial perfusion for pancreatic cancer with liver metastases (PCLM).

METHODSWe retrospectively selected 292 patients with PCLM who were treated by Chinese herbal medicine combined with systemic chemotherapy and/or regional arterial perfusion at Tianjin Medical University Cancer Hospital from January 2001 to December 2010. All patients were assigned to the Western medicine treatment group (157 cases) and the integrative medicine treatment group (135 cases). Patients in the Western medicine treatment group were treated with gemcitabine (GEM)-based chemotherapy, and partial of them received regional arterial perfusion. Those in the integrative medicine treatment group additionally took Chinese herbs of clearing heat and eliminating mass for at least 4 weeks. The median survival time (MST) , adverse reactions and the incidence of complications were observed.

RESULTSThere was no statistical significance in general data between the two groups (P > 0.05). There was statistical difference in MST between the two groups (4.8 months vs 5.5 months, P < 0.05). No death occurred during chemotherapy or regional arterial perfusion. All toxic or adverse reactions were tolerable.

CONCLUSIONChinese herbal medicine combined with systemic chemotherapy and/or regional arterial perfusion was effective and safe, and it could be optimally selected as palliative therapy for PCLM.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Complementary Therapies ; methods ; Deoxycytidine ; analogs & derivatives ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Pancreatic Neoplasms ; drug therapy ; pathology ; Retrospective Studies

OBJECTIVETo evaluate the safety and efficacy of gemcitabine combined with S-1 in the treatment of advanced pancreatic cancer.

METHODSA retrospective analysis of the clinical data of 49 patients with advanced pancreatic cancer, who did not receive radiotherapy and chemotherapy, were divided into two groups: the study group (25 cases), and control group (24 cases). Patients in the study group received gemcitabine 1 000 mg/m² via intravenous drip at the first and 8th days, and received S-1 80 mg/m², morning and evening (twice a day) for the first 14 days, and 21 days as a treatment cycle of chemotherapy.The control group was given GEMOX regimen: Gemcitabine 1 000 mg/m² via intravenous drip at the first and 8 days, and oxaliplatin 130 mg/m² via intravenous drip at the first day, and 21 d for a treatment cycle of chemotherapy. The efficacy and adverse reactions in patients of the study and control groups were observed and compared.

RESULTSThe efficiency of the study group was 32.0% and disease control rate was 72.0%. The efficiency of the control group was 25.0% and disease control rate was 58.3%. The differences between the two groups were statistically not significant (P > 0.05 for all). The clinical benefit rate in the study group and control group were 80.0% and 50.0%, respectively, showing a significant difference (P < 0.05). The median survival time was 9.7 months in patients of the study group and 9.0 months in the control group, with a significant difference (P < 0.05). The drug toxicity was well tolerated in both groups, and no chemotherapy-related death occurred. The major adverse reactions were myelosuppression and digestive tract reactions, and the adverse reactions in the study group were lower than those in the control group.

CONCLUSIONSGemcitabine combined with S-1 is effective and safe in the treatment of advanced pancreatic cancer, with less side effects, and can be tolerated by the patients.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; therapeutic use ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Drug Administration Schedule ; Drug Combinations ; Humans ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Oxonic Acid ; administration & dosage ; adverse effects ; Pancreatic Neoplasms ; drug therapy ; pathology ; Retrospective Studies ; Tegafur ; administration & dosage ; adverse effects

Pancreatic adenocarcinoma is one of the fatalist malignancies. A large proportion of patients are diagnosed with unresectable stage pancreatic cancer at the time of presentation. Gemcitabine is a standard chemotherapeutic agent since 1997, but survival benefit is not satisfactory. Recent clinical study proved that several new combination chemotherapy regimens are superior to gemcitabine single chemotherapy and extended overall survival. However, its prognosis still remains grim. Current research is taking a multidirectional approach in the hope of developing more effective treatments. This article reviews the major clinical trial data that is the basis for the current chemotherapy regimens used as first- and second-line treatments for advanced pancreatic adenocarcinoma. This article also reviews the current ongoing clinical trials, which include the use of molecular targeting agents and immune therapies.
Adenocarcinoma/*drug therapy/pathology ; Antimetabolites, Antineoplastic/therapeutic use ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Deoxycytidine/analogs & derivatives/therapeutic use ; Humans ; Immunotherapy ; Pancreatic Neoplasms/*drug therapy/pathology ; Protein Kinase Inhibitors/therapeutic use

OBJECTIVETo study the expression and prognostic significance of ERG and SPINK1 expression in endocrine-treated prostatic cancer.

METHODSProstatic needle biopsies from 118 prostatic cancer patients primarily treated with endocrine therapy were reviewed. Immunohistochemical study for ERG and SPINK1 protein was carried out.

RESULTSCo-expression of ERG and SPINK1 was not observed. The frequency of ERG protein expression in the 118 biopsies studied was 9.3% (11/118). The positive expression correlated with T stage (P=0.04) but not with patient age at diagnosis, prostatic specific antigen level, Gleason's score, M stage, tumor area and progression-free survival. Positive expression of SPINK1 was demonstrated in 11.0% (13/118) of the biopsies. SPINK1-positive cases carried a significantly shorter progression-free survival, as compared with SPINK1-negative cases (P=0.022). The expression was not associated with any other clinicopathologic variables. The following expression pattern showed statistically significant correlation with the clinical progress (P=0.029): ERG+/SPINK1- (11/118, 9.3%), ERG-/SPINK1+ (13/118, 11.0%) and ERG-/SPINK1- (94/118, 79.7%).

CONCLUSIONSERG and SPINK1 proteins are mutually exclusive.SPINK1 expression is associated with more aggressive clinical behavior and can serve as a prognostic biomarker in prostatic cancer.

Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal ; therapeutic use ; Carrier Proteins ; metabolism ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Prostatic Neoplasms ; drug therapy ; metabolism ; pathology ; Trans-Activators ; metabolism ; Transcriptional Regulator ERG ; Trypsin Inhibitor, Kazal Pancreatic

BACKGROUND/AIMS: Gemcitabine-based chemotherapy has been used as a standard treatment in patients with unresectable pancreatic cancer. However, the clinical outcomes of this regimen are still unsatisfactory in prolonging survival. We retrospectively analyzed clinical characteristics of patients with advanced pancreatic cancers who received gemcitabine-based chemotherapy and showed long-term survival. METHODS: We enrolled 49 patients who underwent treatment with more than three cycles of gemcitabine-based chemotherapy. Long-term survivor was defined as patient who has survived more than 12 months after diagnosis. The clinical characteristics were analyzed to compare the differences between long-term and short-term survivors. Univariate or multivariate analyses were performed to identify prognostic factors associated with chemo-responses. RESULTS: Twenty patients (41%) survived more than 12 months. Long-term survivors had smaller tumor size (OR 2.190, p=0.049, 95% CI 1.005-4.773) and higher serum BUN level (OR 0.833, p=0.039, 95% CI 0.701-0.990) compared to short-term survivors. Overall median and progression-free survivals were 11 and 4 months, respectively. Presence of distant metastasis (hazard ratio 1.441, p=0.035, 95% CI 1.002-2.908) was a significant independent predictor of progression-free survival. Tumor size (hazard ratio 1.534, p=0.004, 95% CI 1.150-2.045) was associated with overall survival. CONCLUSIONS: Gemcitabine chemotherapy may be more effective and allow longer survivals in patients with clinical characters of smaller tumor size and normal serum BUN level at diagnosis. We suggest a well-designed large controlled study to evaluate the prognostic factors such as clinical characteristics and molecular biological features in patients with advanced pancreatic cancers who receive gemcitabine-based chemotherapy.
Age Factors ; Aged ; Antimetabolites, Antineoplastic/*therapeutic use ; Blood Urea Nitrogen ; CA-19-9 Antigen/blood ; Deoxycytidine/*analogs & derivatives/therapeutic use ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Neoplasm Staging ; Odds Ratio ; Pancreatic Neoplasms/*drug therapy/mortality/pathology ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Sex Factors ; Survival Rate