Pancreatic cancer is a one of the most malignant digestive cancer.Because the lack of effective methods for early diagnosis,most patients have been ineligible for surgical resection when diagnosed.Kallikrein family is a group of serine proteases,because of its ability to decompose the extracellular matrix proteins,it may be closely related to the invasion and metastasis of various cancers.And some members of kallikrein family may become cancer diagnostic biomarkers.This paper reviews all the recent articles about kallikrein family study in pancreatic cancer.

OBJECTIVETo evaluate the impact of downstaging factors on oncologic outcomes in a cohort of patients with rectal cancer after intensified neoadjuvant chemoradiotherapy.

METHODSClinical and follow-up data of 135 patients with mid-low rectal cancer receiving intensified neoadjuvant chemoradiotherapy in our hospital from 2005 to 2012 were analyzed retrospectively. Tumor stages before chemoradiotherapy (uTNM) and after surgery (ypTNM) were compared. The therapeutic regimen consisted of 25 fractions of totaled 50 Gy radiation and 2-3 cycles of combination chemotherapy with 5-Fu/capecitabine plus oxaliplatin. Association of 3-year disease-free survival (DFS) with T-stage, N-stage and TNM-stage was examined through the comparison of uTNM and ypTNM.

RESULTSThe mean follow-up of 135 patients was 37.1 (12 to 87) months. The 3-year DFS was 85.2%. The 3-year DFS of patients with downstaging of T-stage (n=76) was 90.8%, which was significantly better compared to those without downstaging (n=48, 75.0%, P=0.040). The 3-year DFS of patients with downstaging of N-stage (n=54) was 98.1%, which was n=53, better compared to those without downstaging (significantly 77.4%) and those with progressive disease (n=16, 75.0%) (P=0.009). Multivariate analysis showed downstaging in N-stage was a prognostic factor for DFS (HR=0.793, 95%CI:0.626-1.004, P=0.054).

CONCLUSIONSPatients with pathologic downstaging in T-stage, N-stage and TNM classification after intensified neoadjuvant chemoradiotherapy may improve patient survival. Downstaging in N-stage may be an independent predictor of survival.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Chemoradiotherapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Rectal Neoplasms ; therapy ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVEThe present study assessed the pathological staging features of rectal cancer after neoadjuvant chemoradiotherapy, and its relation to prognosis.

METHODSPathologic data related to TNM classification were analyzed on the surgical specimens of 135 patients with mid-low rectal cancer after neoadjuvant themoradiotherapy from 2005 to 2012. Tumor invasion, nodal status, local invasive factors (including cancer deposit, radial margin, perivascular or perineural invasion) were investigated with patients' 3-year disease-free survival (DFS).

RESULTSThe overall 3-year DFS was 85.2%, with a pathological complete response (pCR) rate of 19.26%. Three out of 29 patients (10.4%) with ypT0 were found to have positive lymph nodes. There was a trend towards decreased survival as the ypT category and ypTNM staging increased (χ(2) = 14.296 and 52.643, P = 0.006 and 0.000). ypT0-T2 in T category and yp0-I in TNM staging showed a favorable survival above 92%, while the patients with ypT3, or ypIIIB had a comparable lower DFS of 70.2% and 46.7%. DFS in patients with negative lymph node were significantly improved than those with positive nodes (93.5% vs. 66.7%, χ(2) = 34.125, P = 0.000). Patients with or without local invasive factor significantly differed in DFS (42.9% vs. 90.1%, χ(2) = 32.666, P = 0.000) . Cox regression analyze showed that the nodal status (RR = 12.312, 95%CI: 2.828-39.258, P = 0.000) and local invasive factors (RR = 5.422, 95%CI: 1.202-8.493, P = 0.020) were independent risk factors to 3-year survival. As the concept of clinical complete response (cCR) is obscure, there were 27.6% of patients with ypT0 had normal mucosa or no evidence of tumor by EUS or MRI tests before surgery.

CONCLUSIONPostoperative pathologic staging features were closely associated with patient's prognosis. The increasing of ypT or ypTNM staging was correlated to decreasing of DFS. Nodal status, positive radial margin, perivascular and perineural invasion were independent risk factors to DFS. Since cCR did not correlate and could not predict pCR, the ongoing radical surgery could not be avoided even there was no evidence of tumor existing before operation.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Chemoradiotherapy, Adjuvant ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Postoperative Period ; Prognosis ; Rectal Neoplasms ; diagnosis ; mortality ; pathology ; Young Adult

Objective To explore the short-term outcome of laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) for pancreatic head cancer.Methods The retrospective cohort study was conducted.The clinicopathological data of 108 patients with pancreatic head cancer who were admitted to the Affiliated Tongji Hospital of Huazhong University of Science and Technology between July 2014 and July 2015 were collected.Among 108 patients,47 and 61 who respectively underwent LPD and OPD were allocated into LPD and OPD groups.Observation indicators:(1) intraoperative situations;(2) postoperative situations;(3) postoperative pathological situations;(4) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect chemotherapy and postoperative survival situations at 1 and 3 years postoperatively up to June 2018.Measurement data with normal distribution were represented as x±s and comparison between groups was analyzed using the t test.Comparison between groups of count data was analyzed using the chi-square test.Results (1) Intraoperative situations:operation time in the LPD and OPD groups was respectively (288±24)minutes and (265±29)minutes,with no statistically significant difference between groups (t=5.138,P＞0.05).Volume of intraoperative blood loss in the LPD and OPD groups was respectively (136±14)mL and (388±21)mL,with a statistically significant difference between groups (t=-7.297,P＜0.05).Cases with blood transfusion were respectively 3 and 7 iu the LPD and OPD groups,with no statistically significant difference between groups (x2 =0.325,P ＞ 0.05).(2) Postoperative situations:of 47 patients in the LPD group,16 with postoperative complications were improved by conservative treatment,including 7 with pancreatic fistula (5 with biochemical pancreatic fistula and 2 with grading B and C of pancreatic fistula);4 with delayed gastric emptying were cured by gastrointestinal decompression and gastric motility promoting treatment;2 with postoperative bleeding were improved by conservative treatment;2 with intraabdominal infection were improved by enhanced antibiotic therapy and transabdominal percutaneous drainagc;1 with biliary fistula was improved by transabdominal percutaneous drainage;there was no wound infection and perioperative death.Of 61 patients in the OPD group,28 with postoperative complications were improved by conservative treatment,including 12 with pancreatic fistula (9 with biochemical pancreatic fistula and 3 with grading B and C of pancreatic fistula);8 with delayed gastric emptying were cured by gastrointestinal decompression and gastric motility promoting treatment;3 with intra-abdominal infection were improved by enhanced antibiotic therapy and transabdominal percutaneous drainage;2 with postoperative bleeding were improved by conservative treatment;2 with wound infection were c ured by conservative treatment;1 with biliary fistula was improved by transabdominal percutaneous drainage;there was no perioperative death.There was no statistically significant difference in the cases with postoperative complications between groups (x2 =1.546,P＞ 0.05).Duration of hospital stay in the LPD and OPD groups was (13.6±2.1)days and (19.3 ±4.4)days,respectively,with a statistically significant difference (t =-4.354,P＜0.05).(3) Postoperative pathological situations:R0 resection rate was respectively 100.0％ (47/47) and 98.4％ (60/61) in the LPD and OPD groups,with no statistically significant difference (x2 =0,P＞0.05),and there was 1 patient with R1 resection in the OPD group.The total number of lymph node dissected in the LPD and OPD groups was respectively 19±4 and 13±4,with a statistically significant difference (t=-4.126,P＜0.05).The cases with high-and moderate-differentiated tumor and low-differentiated tumor (tumor differentiation),staging T1-T2 and T3-T4 (T stage),staging N0 and N1 (N stage),staging Ⅰ and Ⅱ-Ⅲ (TNM staging) and nerve or vascular invasion were respectively 35,12,28,19,20,27,16,31,21 in the LPD group and 50,11,36,25,36,25,14,47,32 in the OPD group,with no statistically significant difference (x2=0.891,0.003,2.882,1.628,0.643,P＞0.05).(4) Follow-up and survival situations:44 and 55 patients in the LPD and OPD group respectively underwent postoperative adjuvant therapy during the follow-up,with no statistically significant difference (x2=0,P＞0.05).The postoperative 1-year follow-up:47 patients in the LPD group were followed up,37 survived and 10 died;of 61 patients in the OPD group,3 lost to follow-up,and 58 were followed up (43 survived and 15 died);there was no statistically significant difference in survival between groups (x2=0.301,P＞0.05).The postoperative 3-year follow-up:of 47 patients in the LPD group,3 lost to follow-up,and 44 were followed up (21 survived and 23 died);of 61 patients in the OPD group,6 lost to follow-up,and 55 were followed up (23 survived and 32 died);there was no statistically significant difference in survival between groups (x2 =0.346,P＞0.05).Conclusion LPD is safe and feasible for pancreatic head cancer,with advantages of less bleeding,shorter duration of hospital stay and more total number of lymph node dissected,and its survival effect is equivalent to that of OPD.

Objective: To semi-quantify the postoperative complications occurred after laparoscopic pancreaticoduodenectomy(LPD) using Clavien-Dindo score, thereafter exploring its impact factors. Methods: In this retrospective cohort study, the clinical data of 124 patients who had undergone LPD for periampullary tumor from June 2016 to June 2017 at Department of Biliary Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were collected.Malignancy was confirmed based on postoperative pathological reports.Postoperative complications were semi-quantitated using Clavien-Dindo score.Multivariable logistic regression model was applied to explore the factors related to severe complications(Clavien-Dindo Ⅲb-Ⅴ). Results: Of the 124 patients, there were 64 males(51.6%) and 60 females(48.4%), with age of 57 years(range, 23-82 years). In total, postoperative complications occurred in 30 patients(24.2%). Among the 30 patients, 4 patients suffered Clavien-Dindo grade Ⅰ, 18 patients(14.5%) suffered Clavien-Dindo grade Ⅱ, 6 patients(4.8%) suffered Clavien-Dindo grade Ⅲa, 1 patient(0.1%) suffered Clavien-Dindo grade Ⅳb, and 1 patient(0.1%) suffered Clavien-Dindo grade Ⅴ.Intraabdominal hemorrhage occurred in 8 patients, pancreatic fistula was found in 10 patients(7 patients had biochemical leakage and 3 of them had grade B pancreatic fistula), both biliary fistula and gastrointestinal fistula were found in 1 patient.Abdominal infection occurred in 10 patients, both liver failure and renal failure occurred in one patient.Moreover, arrhythmia was found in two patients, and mortality occurred in one patient.Five patients suffered multiple complications.Univariable analysis showed that postoperative complications were associated with body mass index, American Society of Anesthesiologists(ASA) score, intraoperative blood transfusion, and pancreatic texture(P<0.05). In multivariable logistic regression, ASA grade Ⅲ, intraoperative blood transfusion, and pancreatic softness were independently related to postoperative complications after LPD(P<0.05). Conclusions Clavien-Dindo score is feasible to be applied in management of patients with LPD.ASA score, texture of pancreas, and intraoperative blood transfusion were independently associated with postoperative complications.

Objective: To investigate the expression of KLK7 in pancreatic cancer and its clinical significance. Methods: Immunohistochemistry was used to detect the expression of KLK7 protein in pancreatic cancer tissue microarray with 92 samples. Statistical analysis of the relationship between KLK7 and clinicopathological characteristics was finished. Pancreatic cancer cell lines were infected with lentiviuses in order to get cells with KLK7 stable overexpression.KLK7-siRNA was transfected into pancreatic cancer cells to knock down KLK7.Cell proliferation and chemosensitivity were detected by CCK-8 assay; Cell invasion and migration abilities were detected by Transwell assay. At the same time, subcutaneous xenograft tumor models were established in nude mice to observe the effect of KLK7 on tumor growth in nude mice. Data were statistically analyzed by rank sum test, χ² test and Logistic regression analysis. Results: The expression level of KLK7 in pancreatic cancer tissues was higher than that in paired adjacent tissues (P<0.05). KLK7 expression was correlated with vascular invasion(χ²=7.535, P<0.05). Further univariate and multivariate analysis showed that KLK7 expression was an independent risk factor for vascular invasion of pancreatic cancer(χ²=7.535, P<0.05). The overexpression of KLK7 in pancreatic cancer cell lines BxPC-3 and CFPAC can increase their proliferation abilities, reduce the chemosensitivity and promote their migration and invasion behaviour; The results of in vivo experiments showed that the volume of subcutaneously transplanted tumors in the overexpressing KLK7 group was significantly larger than that in the control group (t=4.479, P<0.05). The group of overexpressing KLK7 showed greater tumor weight than the control group(t=2.831, P<0.05). Conclusions The expression level of KLK7 in pancreatic ductal adenocarcinoma was higher than that in paired adjacent tissues and it is an independent risk factor for vascular invasion of pancreatic cancer.KLK7 can promote the proliferation of pancreatic cancer cells, reduce the chemosensitivity and increase the invasion and migration of pancreatic cancer cells.

Objectives To examine the expression of the long coding RNA GSTM3TV2 in pancreatic cancer tissues and to examine its role and mechanism in chemoresistance of pancreatic cancer cells. Methods The expression of lncRNA GSTM3TV2 in 15 pancreatic cancer specimens and corresponding adjacent to cancer tissue samples diagnosed by Department of Pathology, Peking Union Medical College Hospital was detected by real?time PCR.And the expressions of GSTM3TV2 in pancreatic cancer cell AsPC?1,BxPC?3,MIAPaCa?2,PanC?1,SU86.86,T3M4,and chemoresistant cells AsPC?1/GR and MIAPaCa?2/GR, and human pancreatic nestin?expressing cells hTERT?HPNE were detected. Pancreatic cancer cell lines were transfected with GSTM3TV2?pcDNA3.1(+)in order to get cells with GSTM3TV2 overexpression.GSTM3TV2?siRNA was transfected into pancreatic cancer cells to knock down GSTM3TV2. The cell chemoresistance was measured by CCK?8 and flow cytometry assay when incubated with nab?paclitaxel. At the same time, subcutaneous xenograft tumor models were established in nude mice to observe the effect of GSTM3TV2 on chemoresistance of tumor growth in nude mice.Western blot assay was also performed to detect the molecular mechanism of chemoresistance of GSTM3TV2. Results Comparing toadjacent tissues(0.084 ± 0.019), GSTM3TV2 expression was significantly upregulated in the pancreatic cancer tissues(0.493 ± 0.084) (t=5.146, P<0.05). GSTM3TV2 expression were higher in the chemotherapy resistance pancreatic cancer cells AsPC?1/GR(210.799±19.788) and MIAPaCa?2/GR(122.408±23.419) than that in the AsPC?1(3.793±0.615) and the MIAPaCa?2(5.179±1.095)(t=21.800,P<0.05;t=-18.490,P<0.05). The results of in vivo experiments showed that the volume of subcutaneously transplanted tumors in the overexpressing GSTM3TV2 group ((1 059.609±102.498)mm3) was significantly larger than that in the control group((566.414±81.087) mm3) by treated with nab?paclitaxel(t=4.230,P<0.05).Meanwhile,GSTM3TV2 could promote the expression of Cyclin D1, CDK6, Cyclin E1, Vimentin, N?cadherin, ZEB1, Snail and Slug; but decrease cleaved caspase?3,cleaved PARP in pancreatic cancer cells.Conclusions The expression level of GSTM3TV2 in pancreatic canceris higher than that in paired adjacent tissues. GSTM3TV2 may act as an oncogene to promote chemoresistance in pancreatic cancer through regulation of cell proliferation,apoptosis, and epithelial?mesenchymal transition.

Objectives To examine the expression of the long coding RNA GSTM3TV2 in pancreatic cancer tissues and to examine its role and mechanism in chemoresistance of pancreatic cancer cells. Methods The expression of lncRNA GSTM3TV2 in 15 pancreatic cancer specimens and corresponding adjacent to cancer tissue samples diagnosed by Department of Pathology, Peking Union Medical College Hospital was detected by real?time PCR.And the expressions of GSTM3TV2 in pancreatic cancer cell AsPC?1,BxPC?3,MIAPaCa?2,PanC?1,SU86.86,T3M4,and chemoresistant cells AsPC?1/GR and MIAPaCa?2/GR, and human pancreatic nestin?expressing cells hTERT?HPNE were detected. Pancreatic cancer cell lines were transfected with GSTM3TV2?pcDNA3.1(+)in order to get cells with GSTM3TV2 overexpression.GSTM3TV2?siRNA was transfected into pancreatic cancer cells to knock down GSTM3TV2. The cell chemoresistance was measured by CCK?8 and flow cytometry assay when incubated with nab?paclitaxel. At the same time, subcutaneous xenograft tumor models were established in nude mice to observe the effect of GSTM3TV2 on chemoresistance of tumor growth in nude mice.Western blot assay was also performed to detect the molecular mechanism of chemoresistance of GSTM3TV2. Results Comparing toadjacent tissues(0.084 ± 0.019), GSTM3TV2 expression was significantly upregulated in the pancreatic cancer tissues(0.493 ± 0.084) (t=5.146, P<0.05). GSTM3TV2 expression were higher in the chemotherapy resistance pancreatic cancer cells AsPC?1/GR(210.799±19.788) and MIAPaCa?2/GR(122.408±23.419) than that in the AsPC?1(3.793±0.615) and the MIAPaCa?2(5.179±1.095)(t=21.800,P<0.05;t=-18.490,P<0.05). The results of in vivo experiments showed that the volume of subcutaneously transplanted tumors in the overexpressing GSTM3TV2 group ((1 059.609±102.498)mm3) was significantly larger than that in the control group((566.414±81.087) mm3) by treated with nab?paclitaxel(t=4.230,P<0.05).Meanwhile,GSTM3TV2 could promote the expression of Cyclin D1, CDK6, Cyclin E1, Vimentin, N?cadherin, ZEB1, Snail and Slug; but decrease cleaved caspase?3,cleaved PARP in pancreatic cancer cells.Conclusions The expression level of GSTM3TV2 in pancreatic canceris higher than that in paired adjacent tissues. GSTM3TV2 may act as an oncogene to promote chemoresistance in pancreatic cancer through regulation of cell proliferation,apoptosis, and epithelial?mesenchymal transition.

Objective To evaluate the impact of downstaging factors on oncologic outcomes in a cohort of patients with rectal cancer after intensified neoadjuvant chemoradiotherapy. Methods Clinical and follow-up data of 135 patients with mid-low rectal cancer receiving intensified neoadjuvant chemoradiotherapy in our hospital from 2005 to 2012 were analyzed retrospectively. Tumor stages before chemoradiotherapy(uTNM) and after surgery(ypTNM) were compared. The therapeutic regimen consisted of 25 fractions of totaled 50 Gy radiation and 2-3 cycles of combination chemotherapy with 5-Fu/capecitabine plus oxaliplatin. Association of 3-year disease-free survival (DFS) with T-stage, N-stage and TNM-stage was examined through the comparison of uTNM and ypTNM. Results The mean follow-up of 135 patients was 37.1(12 to 87) months. The 3-year DFS was 85.2%. The 3-year DFS of patients with downstaging of T-stage ( n=76 ) was 90 . 8%, which was significantly better compared to those without downstaging (n=48, 75.0%, P=0.040). The 3-year DFS of patients with downstaging of N-stage (n=54) was 98.1%, which was n=53, better compared to those without downstaging (significantly 77.4%) and those with progressive disease (n=16, 75.0%)(P=0.009). Multivariate analysis showed downstaging in N-stage was a prognostic factor for DFS (HR=0.793, 95%CI:0.626-1.004, P=0.054). Conclusions Patients with pathologic downstaging in T-stage, N-stage and TNM classification after intensified neoadjuvant chemoradiotherapy may improve patient survival. Downstaging in N-stage may be an independent predictor of survival.

Objective To evaluate the impact of downstaging factors on oncologic outcomes in a cohort of patients with rectal cancer after intensified neoadjuvant chemoradiotherapy. Methods Clinical and follow-up data of 135 patients with mid-low rectal cancer receiving intensified neoadjuvant chemoradiotherapy in our hospital from 2005 to 2012 were analyzed retrospectively. Tumor stages before chemoradiotherapy(uTNM) and after surgery(ypTNM) were compared. The therapeutic regimen consisted of 25 fractions of totaled 50 Gy radiation and 2-3 cycles of combination chemotherapy with 5-Fu/capecitabine plus oxaliplatin. Association of 3-year disease-free survival (DFS) with T-stage, N-stage and TNM-stage was examined through the comparison of uTNM and ypTNM. Results The mean follow-up of 135 patients was 37.1(12 to 87) months. The 3-year DFS was 85.2%. The 3-year DFS of patients with downstaging of T-stage ( n=76 ) was 90 . 8%, which was significantly better compared to those without downstaging (n=48, 75.0%, P=0.040). The 3-year DFS of patients with downstaging of N-stage (n=54) was 98.1%, which was n=53, better compared to those without downstaging (significantly 77.4%) and those with progressive disease (n=16, 75.0%)(P=0.009). Multivariate analysis showed downstaging in N-stage was a prognostic factor for DFS (HR=0.793, 95%CI:0.626-1.004, P=0.054). Conclusions Patients with pathologic downstaging in T-stage, N-stage and TNM classification after intensified neoadjuvant chemoradiotherapy may improve patient survival. Downstaging in N-stage may be an independent predictor of survival.