Sub-adventitial divestment technique for resecting artery-involved pancreatic cancer: a retrospective cohort study.

PURPOSE: To introduce sub-adventitial divestment technique (SDT), a procedure to remove the tumor while preserving the artery during curative pancreatectomy. Peri-operative safety profile was also evaluated. METHODS: In a single center consecutive series of pancreatectomy for pancreatic cancer, the outcome of patients who had pancreatectomy with SDT was compared to standard pancreatic surgery. RESULTS: From June 2014 to June 2016, 72 patients had pancreatectomy with SDT and 235 had standard surgery. Tumor stage was T4 in all 72 (100%) tumors removed using SDT compared to four (2%) with standard pancreatectomy (p < 0.001). All 72 (100%) tumors in the SDT group were stage III compared to 24 (10%) in the standard surgery group (p < 0.001). Both groups had a high proportion of poorly differentiated tumors (52 (72%) and 163 (69%) respectively) and perineural tumor invasion (62 (86%) and 186 (79%) respectively). R1 (< 1 mm) was found in 24 (86%) of 28 tumors in the SDT group, and in 72 (60%) out of 120 standard pancreatectomy tumors (p = 0.01). Complications occurred in 29 (40%) of the SDT group and in 88 (37%) of the standard group. The in-hospital mortality was four (6%) in the SDT group and one (0.4%) in the standard group (p = 0.01), with a 90-day mortality of 5 (8%)/60 and 6 (3%)/209 (p = 0.07) respectively. CONCLUSIONS: The sub-adventitial divestment technique appeared to be an effective surgical technique to remove the tumor while preserving the artery. This approach warrants further validation in prospective studies.

Application of intraoperative transluminal core-biopsy for diagnosis of pancreatic head mass: A single center 15-year experience.

BACKGROUND: Pathology is the gold standard for diagnosis of pancreatic cancer. Preoperative endoscopic ultrasound-guided biopsy is an expensive procedure that is not routine in developing countries, hence a cheap, reliable alternative is required. AIM: To evaluate the effectiveness and safety of a new technique of intraoperative biopsy from pancreatic head mass. METHODS: Patients undergoing intraoperative transluminal core-biopsy (TLCB) for pancreatic head mass from January 2000 to June 2015 were included in this study. Following Kocher's maneuver, a biopsy was taken from the mass through the duodenum transluminally, using a commercial 16G automatic core-biopsy needle. Multiple tissue specimens were obtained for intraoperative frozen section examination. Depending on the pathological results, a decision was taken to either perform pancreaticoduodenectomy, duodenum-preserving pancreatic head resection, bypass surgery, or to just terminate the operation. The malignancy status of the lesion was confirmed by postoperative pathological examination and/or long-term follow-up of the patients. RESULTS: A total of 525 patients were included. Intraoperative pathological reports revealed 436 malignant cases and 89 cases without evidence of malignancy. The sensitivity, specificity, false positive rate, and false negative rate were 97.7%, 100%, 0%, and 2.3%, respectively. Complications occurred in 2 patients. CONCLUSION: TLCB is a quick, safe, effective, and accurate method for intraoperative diagnosis method in patients with pancreatic head mass; it can provide reliable evidence for surgical decision-making.

Comparison of patency rates and clinical impact of different reconstruction methods following portal/superior mesenteric vein resection during pancreatectomy.

INTRODUCTION: Few studies have compared patency rates of the different methods of venous reconstruction (VR) during a pancreatectomy. This study aimed to evaluate the patency rates and the clinical impact of various reconstruction methods. METHODS: For the meta-analysis, databases were systematically searched to identify studies reporting the outcomes of patients who underwent PVR/SMVR. For the retrospective study, clinical data were retrospectively analyzed from patients who underwent a pancreatectomy and VR between Feb. 2009 and Oct. 2015. Patency was assessed by CT and/or ultrasound. RESULTS: For the meta-analysis, the long-term patency rates of the primary repair group and the autologous graft group were significantly higher than that of the synthetic graft group. For the retrospective study, the reconstruction consisted of primary repair in 62 cases (89.8%) and synthetic grafting in 7 cases (10.1%). Synthetic grafting was more likely to cause acute thrombosis compared with primary repair for PVR/SMVR (85.7% versus 16.7%). Acute thrombosis was associated with decreased median survival (12 versus 6 months) and increased hazard of death. Late thrombosis and stenosis were not associated with survival or serious clinical impact. Median survival for the primary repair group and the synthetic grafting group was 12 and 7 months, respectively. CONCLUSION: Primary repair following PVR/SMVR is preferred and can be achieved in most situations. Stenosis should be noted when with risk factors (long segmental and tension), but it produced little clinical impact. Synthetic grafting was associated with a higher thrombosis rate. Acute thrombosis is associated with increased mortality and decreased survival.

[Surgical treatment for pancreatic neuroendocrine neoplasmas].

Pancreatic neuroendocrine neoplasmas (PNENs) are classified into functioning & non-functioning tumors. The radical surgery is the only effective way for the cure & long-term survival. For the locoregional resectable tumors, the surgical resection is the first choice of treatment; the surgical procedures include local resection (enucleation) and standard resection. For the insulinomas and non-functioning tumors less than 2 cm, local resection (enucleation),distal pancreatectomy with spleen-preservation or segmental pancreatectomy are the commonly selected procedures. The radical resections with regional lymph nodes dissection, including pancreaticoduodenectomy, distal pancreatectomy and middle segmental pancreatectomy, should be applied for tumors more than 2 cm or malignant ones. For the locoregional advanced or unresectable functioning tumors, debulking surgery should be performed and more than 90% of the lesions including primary and metastatic tumors should be removed; for the non-functioning tumors, if complicated with biliary & digestive tract obstruction or hemorrhage, the primary tumors should be resected. The liver is the most frequent site of metastases for PNENs and three types of metastases are defined. For typeⅠmetastasis, patients are recommended for surgery if there are no contraindications; For type II metastasis, debulking surgery should be applied and at least 90% of metastatic lesions should be resected, and for patients with primary tumors removed and no extrahepatic metastases, or for patients with well-differentiated (G1/G2) tumors, liver transplantation may be indicated. For the unresectable type Ⅲ metastasis, multiple adjuvant therapies should be chosen.

Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism.

BACKGROUND: Increasing evidence indicates an important role of transcription factor Yin Yang-1 (YY1) in human tumorigenesis. However, its function in cancer remains controversial and the relevance of YY1 to pancreatic ductal adenocarcinoma (PDAC) remains to be clarified. METHODS: In this study, we detected YY1 expression in clinical PDAC tissue samples and cell lines using quantitative RT-PCR, immunohistochemistry and western blotting. We also detected MUC4 and MMP10 mRNA levels in 108 PDAC samples using qRT-PCR and analyzed the correlations between YY1 and MUC4 or MMP10 expression. The role of YY1 in the proliferation, invasion and metastatic abilities of PDAC cells in vitro was studied by CCK-8 assay, cell migration and invasion assays. In vivo pancreatic tumor growth and metastasis was studied by a xenogenous subcutaneously implant model and a tail vein metastasis model. The potential mechanisms underlying YY1 mediated tumor progression in PDAC were explored by digital gene expression (DGE) sequencing, signal transduction pathways blockage experiments and luciferase assays. Statistical analysis was performed using the SPSS 15.0 software. RESULTS: We found that the expression of YY1 in PDACs was higher compared with their adjacent non-tumorous tissues and normal pancreas tissues. However, PDAC patients with high level overexpression of YY1 had better outcome than those with low level overexpression. YY1 expression levels were statistically negatively correlated with MMP10 expression levels, but not correlated with MUC4 expression levels. YY1 overexpression suppressed, whereas YY1 knockdown enhanced, the proliferation, invasion and metastatic properties of BXPC-3 cells, both in vitro and in vivo. YY1 suppresses invasion and metastasis of pancreatic cancer cells by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism. CONCLUSIONS: The present study suggested that YY1 plays a negative role, i.e. is a tumor suppressor, in PDAC, and may become a valuable diagnostic and prognostic marker of PDAC.

Comprehensive analysis of the percentage of surface receptors and cytotoxic granules positive natural killer cells in patients with pancreatic cancer, gastric cancer, and colorectal cancer.

BACKGROUND: Digestive malignancies, especially pancreatic cancer (PC), gastric cancer (GC), and colorectal cancer (CRC), still occur at persistently high rates, and disease progression in these cancers has been associated with tumor immunosurveillance escape. Natural killer (NK) cell dysfunction may be responsible for this phenomenon, however, the exact relationship between tumor immunosurveillance escape in digestive malignancies and NK cell dysfunction remains unclear. METHODS: Percentage of the surface receptors NKG2A, KIR3DL1, NKG2D, NKp30, NKp44, NKp46, and DNAM-1, as well as the cytotoxic granules perforin and granzyme B positive NK cells were determined in patients with pancreatic cancer (n=31), gastric cancer (n=31), and CRC (n=32) prior to surgery and healthy controls (n=31) by multicolor flow cytometry. Independent t-tests or Mann-Whitney U-tests were used to compare the differences between the patient and healthy control groups, as well as the differences between patients with different pathologic features of cancer. RESULTS: Percentage of NKG2D, NKp30, NKp46, and perforin positive NK cells was significantly down-regulated in patients with PC compared to healthy controls, as well as GC and CRC; reduced levels of these molecules was associated with indicators of disease progression in each malignancy (such as histological grade, depth of invasion, lymph node metastasis). On the contrary, percentage of KIR3DL1 positive NK cells was significantly increased in patients with PC, as well as GC and CRC, but was not associated with any indicators of disease progression. CONCLUSIONS: Altered percentage of surface receptors and cytotoxic granules positive NK cells may play a vital role in tumor immunosurveillance escape by inducing NK cell dysfunction in patients with PC, GC, and CRC.

Early Nasojejunal Nutrition Versus Early Oral Feeding in Patients After Pancreaticoduodenectomy: A Randomized Controlled Trial.

OBJECTIVE: The aim of this study was to test the hypothesis that early oral feeding (EOF) is superior to early nasojejunal nutrition (ENN) after pylorus-preserving pancreaticoduodenectomy (PPPD) in terms of delayed gastric emptying (DGE). BACKGROUND: DGE is a common complication after PPPD. Although EOF after PPPD is recommended by several international guidelines, there is no randomized trial to support this recommendation. METHODS: From September 2016 to December 2017, a total of 120 patients undergoing PPPD were randomized into the ENN, EOF, or saline groups at a 1:1:1 ratio (40 patients in each group). The primary endpoint was the rate of clinically relevant DGE. Secondary endpoints included overall morbidity, postoperative pancreatic fistula, post-pancreatectomy hemorrhage, abdominal infection, length of hospital stay, reoperation rate, and in-hospital mortality. RESULTS: The baseline characteristics and operative parameters were comparable between the groups. The incidence of clinically relevant DGE varied significantly among the three groups (ENN, 17.5%; EOF, 10.0%; saline, 32.5%; p =0.038). The saline group had a higher clinically relevant DGE rate than the EOF group (p = 0.014). The saline group also had greater overall morbidities than the ENN and EOF groups (p = 0.041 and p = 0.006, respectively). There were no significant differences in other surgical complication rates or postoperative hospital stay. No mortality was observed in any of the groups. CONCLUSIONS: Nutritional support methods were not related to DGE after PPPD. EOF was feasible and safe after PPPD, and additional ENN should not be routinely administered to patients after PPPD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03150615.

[Establish a gemcitabine-resistant pancreatic cancer cell line SW1990/GZ and research the relationship between SW1990/GZ and pancreatic cancer stem cell].

OBJECTIVES: To establish a gemcitabine-resistant pancreatic cancer cell line SW1990/GZ, and to explore the relationship between drug-resistant cell line SW1990/GZ and pancreatic cancer stem cell. METHODS: Gemcitabine-resistant pancreatic cancer cell line SW1990/GZ was obtained by treating parental cell line SW1990 in vitro with increasing dosage of gemcitabine in culture medium intermittently for 24 weeks. Stable cultures were obtained which were 77.2-fold increased in resistance relative to parental cells. Gene expressions of ABCB1/MDR1, ABCC1/MRP and ABCG2/BCRP were determined by real-time PCR. Tumorigenic potential was performed by nude mice xenograft transplant experiments. Side population analysis and CD24CD44 positive cells explore were determined by flow cytometry to examine cancer stem cell proportion. RESULTS: Gemcitabine-resistant cell line SW1990/GZ underwent obvious morphological and functional changes. Compared with the parental cell line, SW1990/GZ cell was small and turned into round shape. SW1990/GZ had a higher gene expression level of ABCB1/MDR1, ABCC1/MRP and ABCG2/BCRP than SW1990 (P < 0.01). Nude mice xenograft transplant experiments showed that only 1 × 10(5) SW1990/GZ cells were sufficient for tumor formation, whereas an injection of 1 × 10(5) SW1990 cells did not initiate tumors. Flow cytometry analysis showed that SP proportion in SW1990/GZ was (11.0 ± 1.0)%, whereas in parental SW1990 it was (4.6 ± 0.9)%, CD44CD24 positive cells was (8.73 ± 0.81)% in SW1990/GZ, whereas (1.1 ± 0.4)% in SW1990. CONCLUSIONS: Gemcitabine-resistant cell line SW1990/GZ has a higher proportion of pancreatic cancer stem cells compared to its parental cell line SW1990. CD44 is mainly responsible for acquired drug resistance, which can be a potential target to overcome acquired drug resistance in pancreatic cancer.

[Diagnosis and surgical treatment for non-functional islet cell tumor: a retrospective analysis of 44 cases].

OBJECTIVE: To evaluate the methods of diagnosis and surgical treatment for nonfunctional islet cell tumor (NICT). METHODS: Forty-four patients with non-functional islet cell tumor treated at the First Affiliated Hospital of Nanjing Medical University during January 1968 to June 2008 were analyzed retrospectively. There were 9 males and 35 females, aged from 7- to 70-years-old. Clinical manifestation: 15 cases (34.1%) of abdominal masses, 17 patients (38.6%) with epigastric or back pain, 5 cases of jaundice, 5 cases (11.4%) for upper abdominal fullness or vomiting, 10 cases (22.7%) of pancreatic tumor noticed by routine health checkups or imaging examinations. Imaging examination: CT scan, sonography, ERCP, MRI, upper GI series were performed in 33 (75.0%), 16 (36.4%), 6 (13.6%), 2 (4.5%), and 10 cases (22.7%) respectively. Operation methods: 39 patients (88.6%) underwent surgical resection and the other 5 patients did not. COMPLICATIONS: pancreatic fistula in 7 patients (15.9%), intra-abdominal bleeding in 4 (9.1%), gastrojejunal anastomosis outlet obstruction in 1 (2.3%), biliary fistula in 2 (4.5%) and incisional infection in 3 (6.8%). Surgery related mortality happened in 2 patients (4.5%), both treated before 1999. Twenty-five patients underwent operation between January 1999 and June 2008 were followed up for 6 to 108 months. All survive except one died 75 months after the surgery for unknown reason. CONCLUSIONS: No specific clinical manifestation is recognized for non-functional islet cell tumor. Spiral CT is an optimal diagnostic method, while surgery is the first choice for treatment. Middle segmental pancreatectomy has become an alternative surgical protocol for NICT.

Black pleural effusion due to pancreatic pseudocyst: A case report.

RATIONALE: Black pleural effusion (BPE) is an extremely uncommon type of pleural fluid, which can be due to infection, primary or metastatic malignancy, and hemorrhage. As reported in previous studies, BPE is also observed in some patients with pancreatic pseudocyst. PATIENT CONCERNS: We herein reported a case of a 14-year-old female patient who was admitted to our center with a history of cough for 1 and a half months and right chest pain for 1 month. Before this, she was consecutively hospitalized in 3 different hospitals due to the same symptoms. However, the previous treatments were ineffective due to the lack of a definitive diagnosis. Laboratory examination of the pleural effusion showed BPE with a high amylase concentration. Chest x-ray and computed tomography (CT) showed massive pleural effusion, more prominent in the right chest. CT and MRCP of the abdomen showed a cystic lesion located in the tail of the pancreas, which entered the chest cavity via an esophageal hiatal hernia. DIAGNOSES:: pancreatic pseudocyst. INTERVENTIONS: After confirming that the tumor was a pancreatic pseudocyst by intraoperative biopsy, internal drainage to the jejunum was performed. OUTCOMES: The postoperative recovery was rapid and without complications, and the final discharge diagnosis was idiopathic pancreatic pseudocyst (without history of pancreatitis or pancreatic injuries) with BPE of the right chest. LESSONS: This case demonstrates that massive BPE could present as a rare complication of pancreatic pseudocyst, and surgery is a potential treatment for such patients.

Brunner's gland cyst in combination with gastrointestinal stromal tumor: A case report.

Brunner's gland cysts are rare benign lesions that are mainly observed in the first and the second regions of the duodenum. Patients with Brunner's gland cyst demonstrate no specific symptoms. The present study reports the case of a patient with Brunner's gland cyst located in the duodenum in combination with a gastrointestinal stromal tumor (GIST) in the same region. To the best of our knowledge, the present study reports the first case of Brunner's gland cyst with GIST. A 58-year-old female patient was referred to Tianchang Hospital of Traditional Chinese Medicine (Tianchang, China) with a one-month history of upper abdominal discomfort, diarrhea and recurrent vomiting following the intake of food. Upper gastrointestinal endoscopy and a computed tomography scan revealed the presence of a round, cystic-like lesion with internal low density located within the duodenum. Pathological examination revealed that the cyst measured 0.3 cm in diameter and was consistent with a diagnosis of Brunner's gland cyst. Histopathology revealed that the cyst possessed characteristics of GIST. The patient underwent surgical exploration and tumor resection, and was discharged 2 weeks post-surgery. During the 12 month post-operative follow-up period, the outcome of the patient was good. This case study of Brunner's gland cyst combined with GIST enriches the present literature and promotes better understanding of the two diseases. Further investigation is required to explain the mechanism and association between the two rare diseases.

Small amounts of tissue preserve pancreatic function: Long-term follow-up study of middle-segment preserving pancreatectomy.

Middle-segment preserving pancreatectomy (MPP) is a novel procedure for treating multifocal lesions of the pancreas while preserving pancreatic function. However, long-term pancreatic function after this procedure remains unclear.The aims of this current study are to investigate short- and long-term outcomes, especially long-term pancreatic endocrine function, after MPP.From September 2011 to December 2015, 7 patients underwent MPP in our institution, and 5 cases with long-term outcomes were further analyzed in a retrospective manner. Percentage of tissue preservation was calculated using computed tomography volumetry. Serum insulin and C-peptide levels after oral glucose challenge were evaluated in 5 patients. Beta-cell secreting function including modified homeostasis model assessment of beta-cell function (HOMA2-beta), area under the curve (AUC) for C-peptide, and C-peptide index were evaluated and compared with those after pancreaticoduodenectomy (PD) and total pancreatectomy. Exocrine function was assessed based on questionnaires.Our case series included 3 women and 2 men, with median age of 50 (37-81) years. Four patients underwent pylorus-preserving PD together with distal pancreatectomy (DP), including 1 with spleen preserved. The remaining patient underwent Beger procedure and spleen-preserving DP. Median operation time and estimated intraoperative blood loss were 330 (250-615) min and 800 (400-5500) mL, respectively. Histological examination revealed 3 cases of metastatic lesion to the pancreas, 1 case of chronic pancreatitis, and 1 neuroendocrine tumor. Major postoperative complications included 3 cases of delayed gastric emptying and 2 cases of postoperative pancreatic fistula. Imaging studies showed that segments representing 18.2% to 39.5% of the pancreas with good blood supply had been preserved. With a median 35.0 months of follow-ups on pancreatic functions, only 1 patient developed new-onset diabetes mellitus of the 4 preoperatively euglycemic patients. Beta-cell function parameters in this group of patients were quite comparable to those after Whipple procedure, and seemed better than those after total pancreatectomy. No symptoms of hypoglycemia were identified in any patient, although half of the patients reported symptoms of exocrine insufficiency.In conclusion, MPP is a feasible and effective procedure for middle-segment sparing multicentric lesions in the pancreas, and patients exhibit satisfied endocrine function after surgery.

[Combined multiple organ resection in 16 patients with adenocarcinoma of the body or tail of the pancreas].

OBJECTIVE: To investigate the feasibility and therapeutic results of multiple organ resection in patients with tumor of the body and tail of pancreas. METHODS: The clinical and pathological data were analysed in 16 consecutive patients with neoplasm of the body and tail of pancreas from 1999 to 2004 retrospectively. RESULTS: Multiple organ resection was performed in 6 cases of primary pancreatic adenocarcinoma of the body and tail (3 cases of pancreatic cancer, 2 cases of malignant glucagonoma, and 1 case of well-differentiated pancreatic stromal sarcoma) and 10 cases of extrapancreatic malignancy (4 cases of gastric cancer, 2 cases of gastric leiomyosarcoma, 1 case of duodenal cancer, and 3 cases of colon cancer of hepatic flexure). Distal pancreatectomy with splenectomy was performed in all cases. In addition, 10 patients received splenic flexure colectomy, 6 patients received distal gastrectomy, 3 patients received left nephrectomy, left colectomy, total gastrectomy, liver lobe resection, left adrenalectomy, and local diaphragma resection, and 2 patients received transverse colectomy, subtotal colectomy, proximal proctectomy, proximal gastrectomy, and duodenectomy. No perioperative death and severe complications were observed. Patients with primary pancreatic cancer or pancreatic stromal sarcoma died within 1 year. Two patients with malignant glucagonoma died 51 and 39 months later. The 3-year survival rate was 70% in 10 patients with extrapancreatic malignancy, among which 2 patients with enteric cancer have survived 37 and 48 months. CONCLUSION: Radical combined multiple organ resection may be performed actively in appropriately selected patients.

Modified One-layer Duct-to-mucosa Pancreaticojejunostomy Reduces Pancreatic Fistula After Pancreaticoduodenectomy.

Postoperative pancreatic fistula (POPF) is a major source of morbidity after pancreaticoduodenectomy (PD). The purpose of this retrospective study comparing one-layer pancreaticojejunostomy (PJ) with two-layer PJ after PD was to evaluate whether the one-layer duct-to-mucosa PJ after PD can reduce the incidence of POPF.A total of 194 consecutive patients who underwent PD by one surgeon (Y. Miao) from January 2011 to February 2014 were included in this study. Among those patients, 104 underwent one-layer PJ (one-layer group) and 90 patients underwent two-layer PJ (two-layer group), respectively. Preoperative clinicopathologic features, intraoperative parameters, postoperative morbidity with focus on POPF, were compared between the two groups.The overall incidence of POPF was 19.6% (38/194), and clinically relevant grade B/C POPF rates were 8.6% (16/194) and 3.1% (6/194), respectively. There were no differences in patients' demographics and operation related factors between the two groups. However, the incidence of POPF in the one-layer group was significantly lower than in two-layer group (13.5% [14/104 patients] and 26.7% [24/90 patients] respectively; p=0.021). The median postoperative hospital stay was also significantly lower in the one-layer group compared to the two-layer group (13 days vs. 15 days, p=0.035). One patient in two-layer group died due to postoperative hemorrhage.One-layer duct-to-mucosa pancreaticojejunostomy is a simple and easy technique for pancreaticojejunal anastomosis after PD, and can reduce the POPF rate in comparison to the two-layer technique.

Glucagonoma syndrome: A case report.

Necrolytic migratory erythema (NME), diabetes mellitus and glucagon-secreting tumors form the hallmarks of glucagonoma syndrome, and represent the major clinical manifestations of glucagonoma. NME is usually presented as the initial complaint of patients. Due to the rare incidence of glucagonoma, its diagnosis is often delayed, which leads to its progression. Here, we report a case of NME with a typical skin rash, which was misdiagnosed and treated with corticosteroids for two years. Removal of the tumor in the pancreatic body led to the rapid relief of the symptoms. The aim of the present study is to demonstrate the typical characteristics of glucagonoma syndrome to clinicians in order to improve its diagnosis and treatment.

CEACAM6 induces epithelial-mesenchymal transition and mediates invasion and metastasis in pancreatic cancer.

Pancreatic cancer is a disease with an extremely poor prognosis. The acquisition of invasion properties in pancreatic cancer is accompanied by the process of epithelial-mesenchymal transition (EMT). Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is emerging as an important determinant of the malignant phenotype in a range of cancers, including pancreatic cancer. Therefore, the aim of this study was to evaluate the potential involvement of CEACAM6 in the invasion and metastasis of pancreatic cancer cells via EMT regulation. The results of our study showed a positive association between CEACAM6 expression and poor prognosis of pancreatic cancer, differentiation and lymph node metastasis. Elevated levels of CEACAM6 in pancreatic cancer cells promoted EMT, migration and invasion in vitro and metastasis in animal models, whereas shRNA-mediated CEACAM6 knockdown had the opposite effect. Furthermore, we demonstrated that miR-29a/b/c specific for CEACAM6 could regulate its expression at the post-transcriptional level. Collectively, our findings identified CEACAM6, which is regulated by miR-29a/b/c, as an important positive regulator of EMT in pancreatic cancer offering an explanation for how elevated levels of CEACAM6 are likely to contribute to the highly metastatic phenotype of pancreatic cancer.

Galectin-1 secreted by activated stellate cells in pancreatic ductal adenocarcinoma stroma promotes proliferation and invasion of pancreatic cancer cells: an in vitro study on the microenvironment of pancreatic ductal adenocarcinoma.

OBJECTIVES: This study aimed to clarify that the activated pancreatic stellate cells (PaSCs) are the origin of the highly expressed galectin-1 in the stroma of pancreatic ductal adenocarcinoma (PDAC) tissue and to evaluate the effect of the secreted galectin-1 on proliferation and invasion ability of pancreatic cancer cell line CFPAC-1 in vitro. METHODS: Different kinds of PaSCs were isolated from the normal or cancerous pancreatic tissues and cultured. Immunohistochemistry study, quantitative polymerase chain reaction, and Western blot were carried out to check the cellular origin of galectin-1 in PDAC tissue. By using modified Boyden chambers, in vitro coculture system of PaSCs was established with the pancreatic cancer cell line CFPAC-1 and based on which we assessed the proliferation and invasion ability of CFPAC-1 with or without galectin-1 antagonists. RESULTS: We identified PaSCs as the primary source of the highly expressed galectin-1 in PDAC stroma. Galectin-1 secreted by PaSCs increased CFPAC-1 proliferative rate in the proliferation assay and facilitated CFPAC-1 infiltration in the invasion assay. CONCLUSIONS: Under malignant circumstances, PaSCs express and secret galectin-1, which could further promote the proliferation and invasion of cancer cells.

Side population in the pancreatic cancer cell lines SW1990 and CFPAC-1 is enriched with cancer stem-like cells.

In this study, we first sought to determine the existence of side population (SP) cells in pancreatic cancer cell lines. Furthermore, we compared the biological characteristics of SP and non-SP cells. The presence of side population cells in pancreatic cancer cell lines was detected by Hoechst 33342 staining and FACS analysis. Cell cycle distribution was analyzed using flow cytometry. SP and non-SP cells were exposed to various concentrations of gemcitabine; drug sensitivity was examined using the MTT assay and flow cytometry using Annexin-V and PI staining. To compare the tumorigenic ability in vivo, groups of nude mice were orthotopically inoculated with varying numbers of SP and non-SP cells. The percentages of CD44+CD24+ and CD133+ in SP and non-SP cells were also detected by FACS analysis. The SP fraction was detected in BxPc-3, CFPAC-1, MIA PaCa-2, PANC-1 and SW1990 pancreatic cancer cell lines. Cell cycle analysis revealed that the SP cells contained more cells in the G1 phase and fewer cells in the S phase when compared with the non-SP cells. The SP cells exhibited increased tumorigenetic ability following in vivo transplantation into BALB/C nude mice and increased chemoresistance following in vitro exposure to gemcitabine. FACS analysis showed that the SP cells contained more CD44+CD24+ and CD133+ cells than the non-SP cells. In conclusion, these observations suggest that SP cells in the pancreatic cancer cell lines possess the property of cancer stem cells. SP cells may therefore be novel specific targets for the effective treatment of pancreatic cancer.