Objective:To investigate the clinical significance of the primary tumor size in patients with endometrial carcinoma (EC).Methods:A total of 385 patients with EC admitted to Peking University People's Hospital from January 2006 to December 2016 with complete follow up data were selected, whose tumor size data before biopsy were retrospectively studied.Results:(1) The mean diameter of the primary tumor was (3.6±1.8) cm (range: 1-15 cm). And 48 cases were 0-<2 cm, 78 cases were 2-<3 cm, 92 cases were 3-<4 cm, 73 cases were 4-<5 cm, 94 cases were ≥5 cm. The diameter of the tumor was associated with age <60 years old, premenopause, CA 125≥35 kU/L, non-parturition, poor differentiation, stage Ⅲ-Ⅳ, depth of myometrial infiltration ≥1/2, cervical interstitial involvement, adnexal metastasis and lymph node metastasis (all P<0.05), but not associated with body mass index, hypertension, diabetes mellitus, pathology, lymph-vascular space invasion (all P>0.05). (2) Among the 334 patients underwent lymphadenectomy, 45 (13.5%, 45/334) cases with lymph node metastasis were observed. Stratified analysis showed that lymph node metastasis and recurrence rate of patients with EC gradually increased with the increase of tumor size ( P<0.05). Adopting 2, 3, 4 and 5 cm as cut-off values of tumor size, there were significant differences in the rate of lymph node metastasis and recurrence among them observed ( P<0.05), except for lymph node metastasis rate and recurrence rate when the cut-off value was 2 cm ( P>0.05). (3) An receiver operating characteristic (ROC) curve analysis showed that a tumor diameter of 4.25 cm was the cut-off prognostic value to predict lymph node metastasis and recurrence of EC. Conclusions:Tumor diameter is significantly correlated with lymph node metastasis and recurrence in patients with EC. Tumor size should be considered in determining the scope of surgery and adjuvant therapy.

Objective To evaluate the efficacy of stereotactic body radiation therapy (SBRT) on the survival of patients with early stage pancreatic cancer.Methods The clinical data of 103 T1-2N0M0 pancreatic cancer patients treated by CyberKnife SBRT at the Department of Radiation Oncology of Changhai Hospital from January 2012 to December 2016 was retrospectively analyzed.Kaplan-Meier method was used for survival analysis and Cox proportional hazards model was utilized to identify survival related factors.Results The median overall survival(OS) of T1-2N0M0 pancreatic cancer patients who had unresectable pancreatic cancer or refused surgery was 17.7 (16.1-19.3) months.1-year and 2-year OS rate were 86.3％ and 24.6％,respectively.The median progression free survival(PFS) was 13.0(10.7-15.3) months.1-year and 2-year PFS rate were 54.5％ and 6.3％,respectively.Patients with chemoradiation,BED10 ≥60 Gy and CA19-9 decrease ＞ 50％ after treatment had longer OS and PFS.Conclusions SBRT is a safe and effective treatment for patients with T1-2N0M0 pancreatic cancer.

Objective To identify the effect of stereotactic body radiation therapy (SBRT) on the survival of patients with recurrent pancreatic cancer after surgery.Methods The data of 104 patients with recurrent pancreatic cancer after surgery who underwent SBRT in the Department of Radiation Oncology of Changhai Hospital,Navy Medical University from February 2012 to December 2016 were retrospectively analyzed.The prescription doses ranged from 35-40 Gy/4-8 f.Survival analysis was performed using the Kaplan-Meier method,and relevant factors affecting patients' survival were screened by the Cox proportional hazards model.Results The median overall survival (OS) and progression free survival (PFS) was 12.5 (11.0-14.0) months and 7.3 (6.0-8.7) months,respectively,while the 1-year rate of OS and PFS was 55.8％ and 22.1％,respectively.Multivariate analysis indicated that tumor stage,biological effect dose (α/β =10,BED10),the decrease of CA19-9 level after treatment,and follow-up chemotherapy were all related factors affecting overall survival;tumor stage,BED10,the degree of pain relief and the decrease of CA19-9 level after treatment were related factors affecting PFS.Conclusions Patients suffering recurrent pancreatic cancer with early tumor stage,normal CA19-9 level and mild pain before treatment could be better treated by SBRT,BED10 ≥60 Gy and follow-up chemotherapy after radiotherapy can prolong the survival of patients.

Objective To investigated the influence of different combined treatment sequence of stereotactic body radiation therapy (SBRT) and chemotherapy (CT) on the survival of very elderly patients with locally advanced pancreatic cancer ( LAPC) .Methods The data of LAPC patients ≥60 years old treated by CyberKnife SBRT at Shanghai Changhai Hospital from January 2012 to December 2016 was retrospectively analyzed.According to treatment sequences , patients were divided into three groups:CT+SBRT group ( first chemotherapy and then SBRT ) , SBRT+CT group ( first SBRT and then chemotherapy ) and CT+SBRT+CT group ( first chemotherapy , then SBRT and finally chemotherapy ) .Patients were recommended to receive a 6-month chemotherapy .Intravenous administration of 1000 mg/m2 gemcitabine was initiated on day 1, 8, and 15 every 4 weeks or S-1 was orally given at a dose of 80 mg/m2 for 28 days followed by a 14-day rest , which repeated for 6 cycles.Radiotherapy parameters: the median total prescription dose was 36(30-45)Gy; the median per fraction dose was 7(5-9)Gy;the median number of fractions was 5(5-8) fractions;the median biological equivalent dose (BED10) were 61.92(48-85.5) Gy, respectively.The interval between SBRT and chemotherapy ranged from 2 to 3 weeks.Patients were followed every 3 months.The main outcome measures were overall survival ( OS) and median progression free survival ( PFS) .Second outcome measure was adverse events.Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0) was employed to evaluate adverse events , and RTOG/EORTC was used to assess the adverse events of radiotherapy .Overall survival (OS) and PFS were calculated by Kaplan-Meier method.Univariate and multivariate logistic regression model were used to analyze the independent risk factors .Results A total of 260 patients were enrolled in the study , including 28 patients treated with CT+SBRT, 163 patients undergoing SBRT +CT and 69 patients treated with CT+SBRT+CT.The median OS and PFS were 13.2(95％CI 12.8-13.6)months and 8.2(95％CI 7.7-8.7)months, respectively.OS in CT +SBRT, SBRT +CT and CT +SBRT +CT group was 12.2 (10.9-13.9),13.4 ( 12.9-13.9 ) and 13.1 ( 12.7-13.5 ) months, and the differences were not statistically significant(P=0.425).PFS in CT+SBRT, SBRT+CT and CT+SBRT+CT group was 6.4(5.9-6.9), 8.3(7.8-8.8) and 8.2(7.2-9.2)months, and the differences were statistically significant (P=0.008).In univariate analysis , ECOG, SIRI, the extent of decreased CA 19-9 after treatment and BED 10 were important factors of OS.In multivariate analysis, the CA19-9 response and BED10 were independent factors for OS . Multivariate analysis showed that the extent of decreased CA 19-9 after treatment and BED 10 were important factors of OS.In CT+SBRT group, patients had lower ECOG score (χ2 =115.325,P<0.001) and earlier clinical staging (χ2 =24.788, P<0.001 ).In SBRT +CT group, patients had advanced staging (χ2 =159.759,P<0.001) and lymph node metastasis(χ2 =40.925,P<0.001).Only 1 patient experienced grade 3 radiotherapy associated duodenitis .The adverse events of patients who were first treated by chemotherapy included grade 3 neutropenia in 4 patients and grade 3 gastrointestinal reaction in 5 patients.The adverse events of patients who were first treated by radiotherapy included grade 3 neutropenia or/and leucopenia in 18 patients and grade 3 abdominal pain, nausea or vomit in 16 patients.The adverse events of CT +SBRT+CT patients included grade 3 neutropenia or/and leucopenia in 4 patients and grade 3 abdominal pain or nausea in 5 patients.There was no grade ≥4 adverse events.Conclusions For very elderly patients with LAPC , the survival of patients who received pre-SBRT chemotherapy , post-SBRT chemotherapy and pre-and post-SBRT chemotherapy was comparable , but SBRT+CT group and CT +SBRT+CT group had longer PFS than CT +SBRT group.

Objective To propose the method of dose distribution calculated by one-step optimization with 7 shells (Cao method) and compare with that by three-step optimization with 4 shells (Blanck method) and CyberKnife treatment plans for pancreatic cancer. Methods 20 cases of pancreatic cancer who underwent CyberKnife treatment were retrospectively analyzed,and CT was performed to localize and delineate the target area and endangering organs. Dosage was optimized and evaluated with Blanck method and Cao method. The planning target volume (PTV) conformity index (CI), new conformity index (nCI), homogeneity index (HI),gradient index (GI), coverage, dose-volume and doses to organs at risk were compared. Results Compared with Blanck method, CI (1.11 ± 0.05 vs 1.15 ± 0.05), nCI (1.20 ± 0.06 vs 1.23 ± 0.06), coverage [(92.48 ± 1.85)% vs (93.53 ± 2.15)%], volumes encompassed by 100% and 30% prescription dose line (36.46 ± 16.64 vs 38.19 ± 17.68; 286.19 ± 126.52 vs 320.93 ± 154.82) and monitor unit (56 369 ± 20 019 vs 57 814 ± 20 531) were significantly decreased,while GI was increased (3.22 ± 0.19 vs 3.11 ± 0.19), and all the differences were statistically significant (P<0.05). Additionally, Dmax of the intestine (21.17 ± 2.90 vs 20.63 ± 3.13), D10cc of the stomach (12.78 ± 2.57 vs 13.11 ± 2.43), D5ccof the duodenum (11.01 ± 3.45 vs 11.50 ± 3.25), D10ccof the duodenum (9.30 ± 3.31 vs 9.78 ± 3.07) and D0.35ccof the spinal cord (6.09 ± 0.98 vs 6.59 ± 0.92) were all significantly decreased (P<0.05). No significant differences were found on other parameters. Conclusions Better dose distributions are accessible by one-step optimization with 7 shells in CyberKnife treatment plans for pancreatic cancer.

Objective To investigate the safety and efficacy of re-irradiation with stereotactic body radiotherapy(SBRT) for treating locally recurrent advanced pancreatic cancer.Methods From 2014 to 2017,7 patients with stage Ⅲ pancreatic cancer were treated by re-irradiated with SBRT at Shanghai Changhai Hospital.SBRT was delivered via the G4 type cyberknife robotic stereotactic radiosurgery system in all the patients.The median dose of the first SBRT was 35Gy/5-7 fx,and the median dose of re-irradiation with SBRT was 31 Gy/5-8 fx.6 patients had undergone sequential chemotherapy either with gemcitabine or S-1 based therapy except one patient who refused the chemotherapy.Results There were 5 male and 2 female patients.The median overall survival (OS) of 7 patients was 30 months.Patients were re-irradiated with SBRT after a median interval of 10 months after the first SBRT.Median OS and locally relapse-free survival (LFRS) from re-irradiation were 13 months and 11 months,respectively.Three months after re-irradiation,3(42.9％) patients had partial remission and 4 patients had stable disease.Pain disappeared in 4 patients at the end of reirradiation and significant pain was alleviated in 2 patients 1 month after re-irradiation.There were no toxicities of grade 3 or higher grade during two courses of SBRT.Conclusions For patient with locally recurrent advanced pancreatic cancer,SBRT re irradiation regimen was associated with acceptable toxicity,which can effectively alleviate the pain,prolong the survival and improve the life quality.

Objective To investigate the efficacy and safety of stereotactic body radiation therapy (SBRT) for very elderly patients with pancreatic cancer.Methods The clinical data of a total of 149 patients aged from 75 to 90 years with locally advanced or metastatic pancreatic cancer treated by SBRT in Changhai Hospital from January 2012 to December 2016 were retrospectively reviewed.Prescription doses ranged from 3.6-9Gy/fractions,and the total doses were 19.5-49Gy in 3-8 fractions.The level of serum cancer antigen 19-9(CA19-9) before and 3 months after treatment was compared and the radiotherapy biological effective dose (BED10) was calculated.The adverse events of the radiotherapy were observed.Overall survival (OS) and progression-free survival (PFS) were recorded through follow-up,and the factors influencing the patients' survival were investigated by univariate and multivariate analysis.Results All the patients' median OS and PFS were 12.9and 8.3 months,respectively.One-year OS and PFS rate were 55.9％ and 19.5％,respectively.Tumor stage and the decrease of CA19-9 levels ＞50％ at 3 months after treatment and BED10 were independent factors of OS and PFS.No grade 3 or higher toxicities were recorded in all the patients.Conclusions SBRT is safe and effective for very elderly patients with locally advanced or medically inoperable pancreatic cancer.Tumor stage,the decrease of CA19-9 levels after treatment and BED10 were associated with prognosis.

OBJECTIVE： To prepare Ursolic acid （UA）/Pluronic F127 （PF127）/TPGS-doxorubicin （DOX） mixed nanomicelles， and to characterize it and study its in vitro release behavior. METHODS： UA/PF127/TPGS nanomicelles were prepared by thin film hydration method. Using encapsulation efficiency of UA as index， combined with the results of single factor tests， L9（34） orthogonal test was used to optimize drug dosage of UA， molar ratio of PF127 to TPGS， hydration temperature and hydration volume， validation test was performed. On the basis of succinylated TPGS， TPGS-DOX was synthesized and mixed with UA/PF127/TPGS to prepare UA/PF127/TPGS-DOX mixed nanomicelles， the appearance， particle size and critical micelle concentration （PF127/TPGS） were investigated. The drug release behavior was examined by dialysis bag diffusion method. RESULTS： The optimal preparation technology of UA/PF127/TPGS nanomicelles was as follows as drug dosage of UA 8 mg， molar ratio of PF127 to TPGS 3 ∶ 7， hydration temperature 50 ℃， hydration volume 4 mL. Average encapsulation efficiency of UA in nanomicelles was 89.00％ （RSD＝0.43％， n＝3）. The prepared UA/PF127/TPGS-DOX mixed nanomicelles solution was clear with opalescence. The nanomicelles were spherical and uniform in size； average particle size was （115.00±9.42） nm； critical micelle concentration of PF127/TPGS （molecular ratio 3 ∶ 7） was 0.001 3％. The in vitro drug release of UA and DOX in the mixed nanomicelles was significantly slowed down， compared with raw materials or substance control. The drug release process of the two drugs in the nanomicelles conformed to Weibull equation. CONCLUSIONS： UA/PF127/TPGS-DOX mixed nanomicelles are successfully prepared with uniform particle size， good stability and good sustained-release effect.

Objective: To investigate the clinicopathological characteristics of cardial mixed adenoneuroendocrine carcinoma (MANEC) and analyze its prognostic factors. Methods: The retrospective and descriptive study was conducted. The clinicopathological data of 34 patients with primary cardial MANEC who were admitted to the Changzhou No.2 People′s Hospital of Nangjing Medical University from January 2008 to January 2018 were collected. There were 20 males and 14 females, aged from 39 to 81 years, with an average age of 66 years. All the 34 patients underwent resection of cardia cancer and postoperative pathological examination. Observation indicators: (1) surgery and treatment; (2) clinical manifestations and pathological conditions; (3) pathological examination of surgical resection specimens; (4) follow-up and survival; (5) analysis of prognostic factors. Follow-up using outpatient examination and telephone interview was conducted to detect the survival of patients and tumor recurrence and metastasis up to December 2018. Measurement data with normal distribution were represented as Mean±SD. Measurement data with skewed distribution were expressed as M (range). Count data were expressed as absolute numbers or percentages. Kaplan-Merier method was used to calculate the survival time and rate and draw the survival curve, and log-rank test was used for the survival analysis. Univariate and multivariate analyses were performed using the COX proportional risk model. Results: (1) Surgery and treatment: all the patients underwent surgery successfully and postoperative systemic chemotherapy based on cisplatin + etoposide. (2) Clinical manifestations and pathological conditions: patients had epigastric discomfort, abdominal pain and abdominal distension as the first symptoms. Of 34 patients, number of males, cases with age ≥60 years, cases with esophageal involvement, cases with stable microsatellite, cases with higher CA19-9, cases with elevated cancer embryonic antigen, cases of tumor pathologic TNM stage Ⅲ-Ⅳ, cases with tumor diameter ≥5 cm, cases with vascular tumor emboli, cases with positive lymph node metastasis, cases with nerve invasion were 20, 29, 31, 28, 4, 3, 29, 30, 27, 30, 29, respectively. (3) Pathological examination of surgical excision specimens: the masses of patients were mainly ulcer-type, with the diameter of 3.0-8.4 cm. Of the 34 patients, 1 had tumor infiltrated into submucosa, 5 infiltrated into muscle layer, 18 infiltrated into serosal layer, and 10 infiltrated into extra-serous fibrous adipose tissues. Microscopy examination showed that all tumors were composed of two components including adenocarcinoma and neuroendocrine carcinoma, and the two components accounted for more than 30%. Among adenocarcinoma components of the 34 patients, 14 were poorly differentiated tubular adenocarcinoma, 6 were mucinous adenocarcinoma, 6 were moderately differentiated tubular adenocarcinoma, 5 were low-adhesion carcinoma, 1 was highly differentiated tubular adenocarcinoma, and 2 were papillary adenocarcinoma. Among the neuroendocrine carcinoma components of the 34 patients, 10 were small cell type and 24 were large cell type. Of the 34 patients, 10 had adenocarcinoma and neuroendocrine carcinoma closely adjacent but not confused, and 24 had adenocarcinoma and neuroendocrine carcinoma cross-mixed. Immunohistochemistry examination of 34 patients showed that the components of neuroendocrine carcinoma were positive for synaptophysin, pheochromoin A and nerve cell adhesion molecule. The components of adenocarcinoma were positive for broad-spectrum cytokeratin, cytokeratin 8/18 and cytokeratin 7. (4) Follow-up and survival: 34 patients were followed up for 8.0-68.0 months, with a median time of 53.7 months. The 34 patients had survived for 21-49 months, with a median time of 35 months. The 1-, 3-, 5-year survival rates were 93.31%, 53.60%, and 20.62%. (5) Ananlysis of prognostic factors: results of univariate analysis showed that CA19-9, tumor diameter, intravascular tumor thrombus, tumor pathological TNM stage, lymph node metastasis, microsatellite detection, and histological classification were the related factors affecting the prognosis of patients with cardial MANEC (risk ratio =1.724, 0.327, 1.401, 1.612, 1.542, 1.876, 0.945, 95% confidence interval: 1.226-3.467, 0.218-0.776, 1.171-4.432, 0.694-4.054, 0.987-3.776, 1.217-4.341, 0.614-2.115, P<0.05). Results of multivariate analysis showed that the tumor pathological TNM stage Ⅲ-Ⅳ, positive lymph node metastasis, stable microsatellite, neuroendocrine carcinoma as the main histological classification were independent risk factors affecting the prognosis of patients with cardial MANEC (odds ratio=1.667, 1.441, 1.306, 3.501, 95% confidence interval: 1.013-4.915, 1.035-5.746, 1.006-6.213, 2.076-8.528, P<0.05). Conclusions Cardial MANEC is composed of two components including adenocarcinoma and neuroendocrine carcinoma, and the two components account for more than 30%. The tumors in the neuroendocrine cacinoma area present as solid nest-like pattern, rosettes-shaped or organ-like pattern, with high nuclear-to-plasma ratio and fine chromatin, and it is easy to see mitotic figures. Adenocarcinoma components are tubular adenocarcinoma, mucinous adenocarcinoma, papillary adenocarcinoma with various differentiation. The adenocarcinoma and neuroendocrine carcinoma components can be cross-mixed, and also can be closely adjacent but not confused. Tumor pathological TNM stage Ⅲ-Ⅳ, positive lymph node metastasis, stable microsatellite, neuroendocrine carcinoma as the main histological classification are independent risk factors affecting the prognosis of patients with cardial MANEC.