High frequency of alternative splicing variants of the oncogene Focal Adhesion Kinase in neuroendocrine tumors of the pancreas and breast / 医学前沿

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK6/7 in cells. These results suggested that FAK6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.

The influence of bacterial outer membrane vesicles tumor vaccine on tumor cell proliferation and CD8 + T cell infiltration of mouse with pancreatic cancer / 中华消化外科杂志

Objective:To investigate the influence of bacterial outer membrane vesicles (OMVs) tumor vaccine on tumor cell proliferation and CD8 + T cell infiltration of mouse with pancreatic cancer. Methods:The experimental study was conducted. The ovalbumin (OVA) lentivirus vector plasmid pLV-EF1a-hluc-P2A-mNeongreen-CMV-OVA-3Xflag-P2A-puro was used to construct the mouse pancreatic cancer Pan02-OVA cells. The ClyA-Catchers-OMVs (CC-OMVs) originated from Escherichia coli and labeled antigenic peptide SpyTag-OVA were used to construct the OMVs tumor vaccine. Mouse CD8 + T cells were stimulated by OMVs tumor vaccine, and the effects of OMVs tumor vaccine on inhibiting pancreatic cancer cells proliferation and stimulating CD8 + T cell infiltration were analy-zed by in vitro cell killing assay, including the OMVs tumor vaccine stimulated T cell group and the control T cell group, subcutaneous pancreatic cancer model, including the OMVs tumor vaccine group and the control group, and immunohistochemical staining. Observation indicators: (1) identification of mouse pancreatic cancer Pan02-OVA cells; (2) morphological observation of CC-OMVs; (3) inhibi-tion of mouse pancreatic cancer Pan02-OVA cells by OMVs tumor vaccine specific T cells; (4) inhibi-tion of mouse pancreatic cancer by OMVs tumor vaccine; (5) CD8 + T cell infiltration in pancreatic cancer tissue of mouse stimulated by OMVs tumor vaccine. Measurement data with normal distribu-tion were represented as Mean± SD, and comparison between groups was analyzed using the t test. Count data were described as absolute numbers or percentages. Results:(1) Identification of mouse pancreatic cancer Pan02-OVA cells. Results of laser scanning confocal microscopy showed that the mNeongreen fluorescence was expressed in Pan02-OVA cells infected with the OVA lentivirus vector plasmid of pLV-EF1a-hluc-P2A-mNeongreen-CMV-OVA-3Xflag-P2A-puro. Results of Flow cytometry showed that using the mouse pancreatic cancer Pan02 cells as references, the protein expression rate of Flag on the Pan02-OVA cells was 90.7%. (2) Morphological observation of CC-OMVs. Results of transmission electron microscopy analysis showed that the CC-OMVs were in spherical shape, with a diameter <50 nm. (3) Inhibition of mouse pancreatic cancer Pan02-OVA cells by OMVs tumor vaccine specific T cells. Results of cell proliferation toxicity test showed that the absorbance at 450 nm of mouse pancreatic cancer Pan02-OVA cells was 0.41±0.12 and 1.05±0.15 in the OMVs tumor vaccine-stimulated T cell group and the control T cell group, respectively, showing a significant difference between the two groups ( t=9.54, P<0.05). (4) Inhibition of mouse pancreatic cancer by OMVs tumor vaccine. The weight of subcutaneous tumor tissue in the back of mouse was (81±10)g and (153±17)g in the OMVs tumor vaccine group and the control group, respectively, showing a significant difference between the two groups ( t=8.26, P<0.05). (5) CD8 + T cell infiltration in pancreatic cancer tissue of mouse stimulated by OMVs tumor vaccine. Results of immuno-histochemical staining showed that the numbers of CD8 + T cells staining in the mouse back subcu-taneous tumor tissues was 28.7±3.5 and 9.3±1.5 in the OMVs tumor vaccine group and the control group, respectively, showing a significant difference between the two groups ( t=8.74, P<0.05). Conclusion:Bacterial OMVs tumor vaccine can inhibit proliferation of pancreatic cancer cells and increase the numbers of CD8 + T cells infiltrated in pancreatic cancer tissue of mouse.

Epidemiological characteristics, diagnosis, treatment and prognosis of gallbladder cancer in China: a report of 6 159 cases / 中华消化外科杂志

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Research progress of B7-H3 in tumor immunity / 国际生物医学工程杂志

Immunotherapy plays an important role in tumor biology research, and there has been significant progress in target therapy for cancer. B7-H3(CD276) is an immune checkpoint from the B7 family of molecules, many of whom interact with known checkpoint markers including CTLA4, PD-1, and CD28. This molecule is over-expressed in many kinds of tumors, although the receptor of B7-H3 has not been characterized. Initially, B7-H3 was thought to co-stimulate the immune response, but recent studies have shown that it has a co-inhibitory role on T-cells, contributing to cancer cell immune evasion. Therefore, its over-expression has been linked to poor prognosis in human patients and to invasive and metastatic potential of tumors in in vitro models. Moreover, recent evidence has shown that B7-H3 influences cancer progression beyond the immune regulatory roles. In this review, we aim to characterize the roles of B7-H3 in different cancers, its relationship with other immune checkpoints, and its non-immunological function in cancer progression. Targeting B7-H3 in cancer treatment can reduce cell proliferation, progression, and metastasis, which may lead to improved therapeutic options and better clinical outcomes.

Advances in research of E26 transforming specific homologous factor EHF/ESE3 in tu-mors / 中国肿瘤临床

EHF [ETS ( E26 transformation-specific) homologous factor/epithelium-specific ETS factor family member 3, ESE3] is a mem-ber of the ETS superfamily. EHF is mainly located in cell nuclei. It is a transcription factor that can directly bind to the promoter region of genes or form a transcription complex with other molecules to enhance or inhibit the transcription of downstream target genes. EHF is involved in multiple cell processes including cell proliferation, differentiation, apoptosis, and senescence. EHF plays a role as a tumor suppressor in cancers such as prostate, pancreatic, esophageal, and colon cancers. However, it acts as an oncogene in oral squa-mous cell carcinoma, gastric cancer, ovarian cancer, thyroid cancer, head and neck squamous cell carcinoma, and breast cancer. In the immune microenvironment, EHF can regulate the expression of some important immune factors and further affect the infiltration and function of the regulatory T cells, myeloid derived suppressor cells, and dendritic cells. In recent years, the pathophysiological function of EHF in tumors and their immune microenvironment has attracted increasing attention. This article reviews the research progress concerning the structure, function, and mechanism of EHF for the identification of new targets and molecular predictive markers for tumor therapy.

Prognostic value of tumor infiltration immune cells in pancreatic cancer / 中华外科杂志

Objective@#To investigate the prognostic effect of tumour-infiltrating immune cell, including CD8+ T cell, regulatory T-cell (Treg) and myeloid-derived suppressor cells (MDSC) on pancreatic patients.@*Methods@#This study retrospectively collected the data of 80 patients who were histologically diagnosed of pancreatic cancer and underwent classical R0 surgical resection at Tianjin Medical University Cancer Institute and Hospital from January 2010 to May 2012. All patients survival were followed up until the cut-off date of January 2015. Clinicopathological features including immunohistochemical staining of FOXP3, CD8 and CD33 were reviewed as indice for evaluating the prognosis of pancreatic patients.The prognostic effect of tumour-infiltrating immune cells were analysed by Kaplan-Meier and Log-rank test. Multiple-factor analysis was conducted with the Cox regression model. The correlation between tumour-infiltrating immune cells and clinicopathological features was analysed by χ2 test. The C57BL/6 mouse model was used to evaluate the efficacy of Treg and MDSC depletion therapy in vivo. Student′s t-test was applied to assess the difference of the tumour volume, Ki-67 positive rate and CD8+ T-cell infiltration proportion between depletion group and control group.@*Results@#Eventually, 80 patients were included and no patient was lost during the follow-up period. The median follow-up time was 33.2 months (7.4-59.9 months). Patients with high level of tumour-infiltrating CD8+ T cells had longer overall survival (OS) time ((21.6±11.9)months vs. (13.6±7.4)months, χ2=4.647, P = 0.031) than those with low level of tumour-infiltrating CD8+ T cells. Tumor infiltration FOXP3+ cells were strongly associated with reduced OS((20.9±8.5)months vs.(13.4±8.8)months, χ2=10.528, P=0.001), reduced relapse free survival (RFS) ((15.2±9.0)months vs. (9.5±8.8)months, χ2=6.288, P=0.012) and larger tumor size(χ2=4.073, r=0.226, P=0.044). The high intratumoural MDSC group showed a significantly shorter OS((23.5±11.8)months vs. (13.8±7.6)months, χ2=5.724, P=0.017), RFS((17.9±11.3)months vs. (10.2±7.5)months, χ2=7.430, P=0.006) and more advanced N stage (χ2=4.714, r=0.243, P=0.030) than the low intratumoural MDSC group. Multivariate Cox analysis revealed that pTNM (P=0.008), tumour-infiltrating Treg density (P=0.009) and intratumoural MDSC density (P=0.034) were independent and negative prognostic factors for OS; pTNM(P=0.003) and tumour-infiltrating MDSC level(P=0.018) were independent and negative factors for RFS. The experiment in vivo revealed that Treg and MDSC depletion therapy significantly decreased tumour volume in the C57BL/6 mouse model of subcutaneous tumours((1 396.3±442.5)mm3 vs. (3 356.9±533.5)mm3, t=4.986, P=0.018). Tumour Ki-67 positive rate significantly decreased (23%±5% vs. 55%±10%, t=3.130, P=0.011) in Treg and MDSC depletion group, whereas, the proportion of tumour-infiltrating CD8+ T cells significantly increased in depletion groups (3.25%±0.69% vs. 0.76%±0.25%, t=3.393, P=0.007).@*Conclusions@#Tumour-infiltrating Treg, MDSC level and pTNM stage are independent prognostic factors for patients with pancreatic cancer. Treg and MDSC depletion therapy can significantly retard tumour growth and increase the level of tumour-infiltrating CD8+ T-cells in the C57BL/6 mouse model of subcutaneous tumours.

The expression of PTK7 in pancreatic ductal adenocarcinoma and its clinical significance / 中国肿瘤临床

Objective: To explore the expression of PTK7 in pancreatic ductal adenocarcinoma and its clinical significance. Methods: The clinical and follow-up data of 85 patients with pancreatic ductal adenocarcinoma who underwent radical surgery at Tianjin Medical University Cancer Institute and Hospital from May 2011 to January 2016 were analyzed. The expression of PTK7 in 85 pancreatic cancer tissues and the corresponding para-cancer tissues was detected by immunohistochemistry, and the relationship between PTK7 expression level and the clinical pathological features and prognosis was analyzed. Results: Positive expression of PTK7 was observed mainly in the cytoplasm, presenting as brownish yellow granules. It was noted that expression of PTK7 in pancreatic ductal adenocarcinoma tissues and para-carcinoma tissues was 70.6% (60/85) and 52.9% (45/85), respectively, and the positive rate in pancreatic ductal adenocarcinoma tissues was significantly higher than that in para-carcinoma tissues; the difference was statistically significant (P<0.05). The abnormal expression of PTK7 was correlated with the tumor stage, lymph node metastasis, and the vascular tumor embolus (P<0.05). The survival analysis suggested that the survival time or recurrence-free time of patients with PTK7 high expression in pancreatic duct adenocarcinoma was significantly shorter than in those with low expression (P<0.05, respectively). ShRNA interference of PTK7 was successfully established in the cell stabilizing system, verified by MTT and clone formation. Results indicated that cell survival was significantly lower in the shRNA experimental group compared to the control group (P<0.05), the number of colonies formed was significantly smaller in the shRNA experimental group compared to the control group (P<0.05), and the expression of proliferation-related proteins Ki-67 and PCNA was significantly lower in the shRNA experimental group compared to the control group (P<0.05, respectively). Conclusions: The up-regulation of PTK7 expression in pancreatic ductal ad-enocarcinoma tissues was associated with the tumor stage, lymph node metastasis, and the vascular tumor thrombus, suggesting poor prognosis. It was also found that in pancreatic cancer cell lines, PTK7 could promote the proliferation of pancreatic cancer cells by regulating the levels of proliferative factors Ki-67 and PCNA.

The efficacy and safety of 125I particle intraoperative implantation combined with chemotherapy in the treatment of locally advanced pancreatic cancer / 中华肝胆外科杂志

The effect of the treatment of 112I particle therapy in solid tumor is remarkable and with less side effect.This study retrospectively analyzed the clinical data of 125I particles implantation combined systemic chemotherapy in the treatment of locally advanced pancreatic cancer patients.Main observation indexes included:the overall median survival,1 year survival rate,pain relief rate,the postoperative complications.Intraoperative 125I particles implantation combined with postoperative chemotherapy in treatment of locally advanced pancreatic cancer patient was safety,which can effectively prolong patient survival and relieve patients' pain.

Selection of pancreaticojejunostomy in pancreaticoduodenectomy / 中华肝胆外科杂志

The proper selection of pancreaticojejunostomy in pancreaticoduodenectomy is very important factor for patients'postoperative recovery.The method of pancreaticojejunostomy should be performed individually on the basis of the pancreatic texture,size of pancreatic residue,duct size,duct location,jejunal size,et al.The paper presents a review of widely used pancreaticojejunostomv and our experience.

50 cases of clinical diagnosis and treatment of solid-pseudopapillary tumor of pancreas / 中国肿瘤临床

Objective:This study explored the clinical characteristics, imaging features, biological characteristics, treatment, and prog-nosis of solid-pseudopapillary tumor of the pancreas (SPT). Methods:We collected clinical data of 50 cases of SPT in Tianjin Medical University Cancer Istitute and Hospital from January 2011 to October 2016. We then retrospectively reviewed and analyzed clinical and pathological features of these patients. We conducted follow-up consultations and summarized data on patient characteristics, pathological features, diagnosis, treatment, and prognosis. Results:Among 50 SPT patients, mean age was 33.0±12.00 years, and male-to-female ratio was 1:5.25. Clinical presentation was mostly an abdominal placeholder diagnosed by physical examination, and tumor was usually located in the head or body and tail of the pancreas. All patients received surgery;procedures included pancreaticoduode-nectomy, and distal pancreatectomy plus spleen resection. SPT was clearly diagnosed with postoperative histopathological examina-tion. Hospital stay lasted for 13.9±5.16 days. All 50 cases were followed up, with consultation period lasting for 3-70 months. No recur-rence or metastasis appeared in 49 cases, and perioperative death was not noted in our patients. Conclusion:SPT is a rare, potential low-grade malignant tumor, which mostly affects young females. There is no obvious specificity in the clinical manifestation and labora-tory examination. Tumor marker levels are almost within normal range. Surgery for SPT provides good prognosis and long survival dura-tion.

Clinical efficacy of modified FOLFIRINOX as neoadjuvant chemotherapy for borderline resectable pancreatic cancer / 中华消化外科杂志

Objective To investigate the clinical efficacy of modified FOLFIRINOX as neoadjuvant chemotherapy for borderline resectable pancreatic cancer.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 28 patients diagnosed as borderline resectable pancreatic cancer who were admitted to the Tianjin Medical University Cancer Institute and Hospital between April 2013 and October 2015 were collected.Twenty-eight patients were treated with modified FOLFIRINOX (irinotecan 135 mg/m2,oxaliplatin 64 mg/m2,leucovorin 400 mg/m2,5-FU 2 400 mg/m2,repeat the regimen every 2 weeks) as neoadjuvant chemotherapy.After the completion of neoadjuvant chemotherapy,patients were evaluated operation feasibility and developed surgical planning in 3 weeks.Observation indicators:(1) Efficacy of neoadjuvant chemotherapy;(2) adverse events of neoadjuvant chemotherapy;(3) surgical and postoperative situations;(4)follow-up situations.Follow-up using outpatient examination,telephone interview and we-chat was performed to detect survival of patients up to January 2017.Measurement data with skewed distribution were described as median (range).The survival curve was drawn by Kaplan-Meier method and the survival analysis was done by Log-rank test.Results (1) Efficacy of neoadjuvant chemotherapy:28 patients received chemotherapy with a median cycle of 6 cycles (range,3-12 cycles).Chemotherapy reaction of 28 patients:14 had partial remission,10 had stable disease and 4 had progressive disease.(2) Adverse events of neoadjuvant chemotherapy:there were 22 adverse events of 28 patients during chemotherapy,including 15 with grade1-2 and 7 with grade 3-4.(3)Surgical and postoperative situations:of 28 patients,18 received radical resection for pancreatic cancer including 11 receiving pancreaticoduodenectomy,7 receiving distal pancreatectomy with splenectomy.Surgeries included 6 with portal vein and superior mesenteric vein resection and reconstruction,1 with coeliac trunk resection.Ten patients received R0 resection and 8 received R1 resection.Of 18 patients,8 with postoperative complications were improved by conservative treatment,including 2 with pancreatic fistula,1 with biliary fistula,3 with delayed gastric empty,1 with anastomotic hemorrhage,1 with lympha fistula.No patient received re-operation or died within 30 days postoperatively.Pathological TNM staging:2 patients were detected in stage Ⅰ-Ⅱ,14 in stage Ⅲ and 2 in stage Ⅳ.All the 18 patients received chemotherapy after operation.Ten patients without operation continued chemotherapy.(4) Following up:28 patients were followed up for 5-21 months with a median time of 13 months.Of the 15 died patients,5 received operation and 10 received no operation.The median progressionfree survival time and median overall survival time were 14 months and 19 months in the 18 operative patients,7 months and 11 months in the 10 non-operative patients,respectively,with statistically significant differences (x2=7.335,9.950,P＜0.05).Conclusions Modified FOLFIRINOX as neoadjuvant chemotherapy for borderline resectable pancreatic cancer is safe and effective,and patients can tolerate mild adverse reactions.Operable patients undergo surgeries after chemotherapy have relatively good outcome.

Clinical efficacy of modified FOLFIRINOX as neoadjuvant chemotherapy for borderline resectable pancreatic cancer / 中华消化外科杂志

Objective To investigate the clinical efficacy of modified FOLFIRINOX as neoadjuvant chemotherapy for borderline resectable pancreatic cancer.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 28 patients diagnosed as borderline resectable pancreatic cancer who were admitted to the Tianjin Medical University Cancer Institute and Hospital between April 2013 and October 2015 were collected.Twenty-eight patients were treated with modified FOLFIRINOX (irinotecan 135 mg/m2,oxaliplatin 64 mg/m2,leucovorin 400 mg/m2,5-FU 2 400 mg/m2,repeat the regimen every 2 weeks) as neoadjuvant chemotherapy.After the completion of neoadjuvant chemotherapy,patients were evaluated operation feasibility and developed surgical planning in 3 weeks.Observation indicators:(1) Efficacy of neoadjuvant chemotherapy;(2) adverse events of neoadjuvant chemotherapy;(3) surgical and postoperative situations;(4)follow-up situations.Follow-up using outpatient examination,telephone interview and we-chat was performed to detect survival of patients up to January 2017.Measurement data with skewed distribution were described as median (range).The survival curve was drawn by Kaplan-Meier method and the survival analysis was done by Log-rank test.Results (1) Efficacy of neoadjuvant chemotherapy:28 patients received chemotherapy with a median cycle of 6 cycles (range,3-12 cycles).Chemotherapy reaction of 28 patients:14 had partial remission,10 had stable disease and 4 had progressive disease.(2) Adverse events of neoadjuvant chemotherapy:there were 22 adverse events of 28 patients during chemotherapy,including 15 with grade1-2 and 7 with grade 3-4.(3)Surgical and postoperative situations:of 28 patients,18 received radical resection for pancreatic cancer including 11 receiving pancreaticoduodenectomy,7 receiving distal pancreatectomy with splenectomy.Surgeries included 6 with portal vein and superior mesenteric vein resection and reconstruction,1 with coeliac trunk resection.Ten patients received R0 resection and 8 received R1 resection.Of 18 patients,8 with postoperative complications were improved by conservative treatment,including 2 with pancreatic fistula,1 with biliary fistula,3 with delayed gastric empty,1 with anastomotic hemorrhage,1 with lympha fistula.No patient received re-operation or died within 30 days postoperatively.Pathological TNM staging:2 patients were detected in stage Ⅰ-Ⅱ,14 in stage Ⅲ and 2 in stage Ⅳ.All the 18 patients received chemotherapy after operation.Ten patients without operation continued chemotherapy.(4) Following up:28 patients were followed up for 5-21 months with a median time of 13 months.Of the 15 died patients,5 received operation and 10 received no operation.The median progressionfree survival time and median overall survival time were 14 months and 19 months in the 18 operative patients,7 months and 11 months in the 10 non-operative patients,respectively,with statistically significant differences (x2=7.335,9.950,P＜0.05).Conclusions Modified FOLFIRINOX as neoadjuvant chemotherapy for borderline resectable pancreatic cancer is safe and effective,and patients can tolerate mild adverse reactions.Operable patients undergo surgeries after chemotherapy have relatively good outcome.

Role of insulin-like growth factor binding protein 2 in tumor malignant biological be-havior and its clinical application / 中国肿瘤临床

Insulin-like growth factor binding proteins (IGFBPs) are crucial to cell growth, development, proliferation, and apoptosis in humans. Among IGFBPs, IGFBP2 is recognized as a regulator of insulin-like growth factor (IGF). Besides binding with IGF, IGFBP2 also interacts with extracellular matrix through its specific structure. IGFBP2 promotes the malignant phenotype of tumor by activating several important intracellular signal pathways. IGFBP2 is specifically overexpressed in several malignant tumors, and this overexpression is correlated with patient prognosis. IGFBP2 is regarded as a potential biomarker and a therapeutic target. This review briefly summarizes the latest progress of research on the role of IGFBP2 in tumor malignant biological behavior and its clinical application.

Diagnosis and treatment analysis of 15 pancreatic acinar cell carci-noma patients / 中国肿瘤临床

Objective:To discuss the clinical feature, diagnosis, and treatment course of pancreatic acinar cell carcinoma (ACC) to guide clinical practice and improve prognosis of patients. Methods:Clinical data of 15 patients with pathologically confirmed pancreatic acinar cell carcinoma between December 1994 and March 2014 in Tianjin Medical University Cancer Institute and Hospital were retro-spectively studied. Results:The patients include eight males and seven females with a median age of 44. Tumors in these patients appeared in different parts of the pancreas. Eight patients had tumor in the head, six in the body and tail, and one in the uncinate process. The tumor size ranged from 3 cm to 18 cm, with an average diameter of 6.67 cm. The patients presented less jaundice and the tumor markers remained constant, specifically, no increase was reported. Six patients had metastasis before their operation. Twelve patients received radical resection, while the other three received palliative treatment. The preoperative and intraoperative diagnoses were not exact. The final diagnosis depended on pathologic confirmation after surgery or puncture. The immunohistochemical results of trypsin and chymotrypsin were positive in the patients who were examined. The postoperative chemotherapy was usually based on gemcitabine. The average survival time was 20.6 months. Conclusion:Pancreatic acinar cell carcinoma has special clinical features, and clinicians tend to regard it as low-grade malignancy. The attitude towards ACC should be positive.

Effects of dioscin on apoptosis in pancreatic cancer MiaPaCa-2 cells and its mechanism / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to observe the effects of dioscin on apoptosis and on expression of PRDX1 in pancreatic cancer MiaPaCa-2 cells in vitro.</p><p><b>METHODS</b>MTT assay was used to detect the growth rate among the medication groups treated with different concentrations of dioscin. The apoptosis rate was determined by annexin V-fluorescein isothiocyanate/propidium iodide double staining and flow cytometry. Western blot analysis was used to assay the expression of PRDX1 and apoptotic proteins in the cells. Reactive oxygen species (ROS) formation was measured by 2'7'-dichlorofluorescein diacetate (DCFH-DA).</p><p><b>RESULTS</b>Dioscin considerably inhibited the proliferation of MiaPaCa-2 cells in vitro. The inhibitory action was enhanced in a dose-dependent manner. The levels of intracellular ROS detected with DCFH-DA were highly increased after dioscin treatment. The flow cytometry analysis using annexin V-PI staining showed that compared with the apoptotic rate of control group [(3.5 ± 0.7)%], 2.5 µmol/L and 5 µmol/L dioscin induced apoptosis in (28.4 ± 0.9)% and (49.6 ± 2.7)% MiaPaCa-2 cells, and Western blot analysis showed that apoptotic proteins Bax and cleaved caspase-3 expressions were increased and antiapoptotic protein Bcl-2 expression was decreased. In addition, these effects could be blocked by antioxidant N-acetylcysteine (NAC) administration, and the apoptotic rates decreased to (10.8 ± 2.3)% and (18.8 ± 3.0)%, respectively. We further observed the decrease of PRDX1 expression after dioscin treatment. Moreover, after PRDX1 overexpression, dioscin treatment no longer induced high levels of ROS and apoptosis, and the apoptotic rate was decreased to (21.3 ± 5.9)%.</p><p><b>CONCLUSION</b>Dioscin can down-regulate the PRDX1 expression, and then induces ROS-mediated apoptosis in cancer cells.</p>

Role of HIF-1αin hypoxic microenvironment of tumor and the targeted therapy / 中国肿瘤临床

Hypoxia is a common characteristic in solid tumors. With the regulation of the transcription of multiple target genes, HIF-1αplays an important role in the energy metabolism, proliferation, and apoptosis of tumor cells. HIF-1αcontributes to the adapta-tion of tumor cells and tissue to hypoxia stress through these processes. It also promotes tumor angiogenesis and increases their inva-sive ability and the resistance to radio and chemotherapy. Cancer treatment targeting on HIF-1αis an important potential therapy.

Clinical significance of coagulation parameters in patients with pancreatic cancer / 中华肝胆外科杂志

Objective To investigate the coagulation disorder status of patients with pancreatic cancer and to explore its role in tumor formation,progression and metastasis.Method The present study involved 114 patients with pancreatic cancer diagnosed by surgery or biopsy,and 40 healthy volunteers.For each individual,nine plasma coagulation parameters were tested using the STAGO Compact automated.Results The levels of plasma antithrombin Ⅲ (AT-Ⅲ) and protein C of the pancreatic cancer group were significantly reduced compared with the control group,while the levels of plasma PT,APTT,INR,FIB,F-Ⅷ,D-dimer (D-D) were significantly elevated.The level of plasma D-D increased with increase in clinical stage,while the level of AT-Ⅲ decreased.The level of plasma D-D became higher with worsening in histological grade.Conclusions Patients with pancreatic cancer were in a state of hypercoagulation,with reduced anticoagulation function and secondary hyperfibrinolysis.The level of Plasma D-D was significantly associated with the clinical stage,histological grade and distant metastasis.These together with AT-Ⅲ could be used as indicators to monitor patients with pancreatic cancer.

Signet ring cell carcinoma of pancreas: a report of 4 cases / 中华肝胆外科杂志

Objective To analyze the investigation and treatment of signet ring cell carcinoma of pancreas.Method The clinical data of patients with histopathologically confirmed signet ring cell carcinoma of pancreas were analyzed retrospectively.Results There were 4 patients with signet ring cell carcinoma.There was no patient who presented with a typical carcinoid syndrome.Most patients presented with upper abdominal pain,backache or jaundice caused by bile duct obstruction.In one patient CA19-9 and CEA were raised.All patients received palliative biliary bypass and needle biopsy of the tumour.The median survival was 2.8 months.Conclusions Pancreatic signet ring cell carcinoma is a rare disease with poor prognosis.Surgery is the only effective treatment but the resectability rate is low.Whether this tumour responds to chemotherapy requires further studies.

Clinical characteristics and treatment of 57 patients with serous cystadenoma of pancreas / 中华肝胆外科杂志

Objective To analyse the diagnosis and treatment options of serous cystadenoma of the pancreas.Method The clinical data of 57 patients operated in the Tianjin Medical University Cancer Institute & Hospital from August 1996 to December 2011 with pathologically confirmed serous cystadenoma of pancreas after the operation were retrospectively studied.Results There were 13 males (22.8％) and 44 females (77.2％).The median age was 56.8 years.The patients were asymptomatic in 31.6％.CT was accurate in the diagnosis in 70.6％.All patients received surgical resection,inluding pancreaticoduodenectomy (n =17,29.8％),distal pancreatectomy (n =38,66.7％),palliative resection (n=1),and tumor enucleation (n=1).Postoperative complications developed in 6 patients.Histopathologically,there were 50 cases of serous microcystic adenoma (87.7％) and 7 cases of serous oligocystic adenoma (12.3 ％).One of these patients had developed into serous cystadenocarcinoma.At a follow-up of 12 months to 15 years,one patient with serous cystadenocarcinoma died 13 months after the operation.The remaining patients were all alive.Statistical analysis was performed based on the postoperative histopathological type and tumor size.The mean postoperative hospital stay of the group of patients with serous microcystic adenoma were significantly longer than the patients with serous oligocystic adenoma [(17.39±7.61) d vs (19.43±0.98) d,P=0.002].The incidence of patients with clinical symptoms was higher in the group of patients with tumor size ≥4 cm when compared with the patients with tumour size ＜4 cm.There was no significant difference on the other parameters.Conclusions Pancreatic serous cystadenoma is a rare pancreatic tumor,and it often happens in elderly women.Indications for surgical resection included symptomatic tumours,tumor diameter more than 4 cm,malignant biological behavior,malignancy could not be ruled out,and potentially malignant tumors.For asymptomatic patients and tumor size less than 4 cm,surgical resection should also be considered if the tumour progresses on follow-up.

Mucinous cystic neoplasms of pancreas: an analysis of 42 patients / 中华肝胆外科杂志

Objective To study the clinicopathological characteristics,diagnosis and treatment of patients with mucinous cystic neoplasms (MCNs) of the pancreas.Methods The clinical data of 42 patients with mucinous cystic neoplasms of pancreas were retrospectively analyzed.Chi-square test and independent sample t-test were used for statistical analysis.Results The mean age of the patients was 53.1 yeas (ranged from 29 to 78 y).There were 32 female (76.2％).The patients were divided into two groups according to symptoms (the symptomatic group and the asymptomatic group).There were significant differences in tumor size,tumor location,operation type,operation time and adhesions with the surrounding tissues between the 2 groups of patients.The patients were then divided into three groups according to pathological type.There were significant differences in age,tumor marker,tumor location,operation type,operation time,adhesions with the surrounding tissues,operative blood loss,and postoperative hospital stay among the 3 groups of patients.There was no tumour recurrence in the patients with cystadenoma.Patients with cystadenocarcinoma developed tumor recurrence at a mean of 16.4 months (range,0-50) and died of tumor recurrence even after radical surgery at a mean of 22.9 months (range,3-58).Conclusion MCNs were seen most commonly in middleaged women.The presence of symptoms was a sign of malignancy.Resection of the tumor in the early stage is the key in dealing with MCNs.