Mutation and Expression of Gene YY1 in Pancreatic Neuroendocrine Tumors and Its Clinical Significance.

OBJECTIVE: The clinical significance of the YY1 gene mutation and expression in pancreatic neuroendocrine tumors (PNETs) remains unknown. Therefore, this study aimed to comprehensively analyze the somatic mutation of YY1 in the different subtypes of PNETs. METHODS: A total of 143 PNETs were assessed by Sanger sequencing to identify the somatic mutation of YY1 gene in various subtypes of PNETs. YY1 protein expression was examined in 103 PNETs by immunohistochemical staining and western blot. Gene mutation and its protein expression were correlated with clinicopathologic features. RESULTS: A recurrent mutation (chr14:100743807C>G) in the YY1 gene was identified in 15 of 83 insulinomas (18%) and in only 1 of 60 noninsulinoma PNETs (1.7%) (P = .0045). The YY1 mutation was not found in MEN1-associated insulinomas. The YY1 mutation in insulinomas was correlated with older age and lower serum glucose levels (age, 57 vs 42.5 years, P = .006; blood glucose, 25.2 vs 33.6 mg/dL, P = .008). YY1 protein expression was found in 100 of 103 PNETs, although expression was weaker in metastases than in localized tumors (P = .036). The stronger expression of YY1 protein was associated with favorable disease-free survival of patients with PNETs (log-rank, P = .011; n = 70). Multivariable statistical analysis showed that YY1 protein expression could be an independent predictor of prognosis. CONCLUSION: The hotspot YY1 mutation mostly occurred in insulinomas and rarely in noninsulinoma PNETs. The stronger YY1 protein expression was correlated with the better prognosis of PNETs patients.

Dynamic hematological changes in patients undergoing distal pancreatectomy with or without splenectomy: a population-based cohort study.

BACKGROUND: The clinical outcomes of patients who received distal pancreatectomy with splenectomy (DPS) and spleen-preserving distal pancreatectomy (SPDP) have been generally investigated. However, postoperative hematological changes after distal pancreatectomy with or without splenectomy are poorly understood. METHODS: Information from patients undergoing distal pancreatectomy (DP) between January 2014 and June 2019 at a single institution was reviewed. A linear mixed-effects model was used to compare dynamic hematological changes between different groups. RESULTS: A total of 302 patients who underwent DP were enrolled. In the long term, most postoperative hematological parameters remained significantly higher than preoperative levels in the DPS group, while postoperative lymphocyte, monocyte, basophil, and platelet levels returned to preoperative levels in the SPDP group. All postoperative hematological parameters except for red blood cell count and serum hemoglobulin level were significantly higher in the DPS group than in the SPDP group. There were no significant differences in hematological changes between the splenic vessel preservation (SVP) and Warshaw technique (WT) groups. CONCLUSIONS: Postoperative hematological changes were significantly different between the DPS and SPDP groups. Compared to DPS, SPDP reduced abnormal hematological changes caused by splenectomy. SVP and WT were comparable in terms of postoperative hematological changes.

Surgeons' knowledge regarding the diagnosis and management of pancreatic cancer in China: a cross-sectional study.

BACKGROUND: Pancreatic cancer is rare but highly malignant. Studies have shown that surgeons' knowledge closely links to the correct diagnosis and treatment outcomes of pancreatic cancer. The purpose of this study was to survey current surgeons' knowledge regarding pancreatic cancer. METHODS: A cross-sectional study was conducted among 705 surgeons who attended the 2011 China Surgical Week's meeting in Beijing. A questionnaire regarding the risk factors, clinical manifestations, diagnosis, and treatment of pancreatic cancer was used. Surgeons' answers were analyzed and compared among different regions, levels of hospital, and professional ranks. RESULTS: Most surgeons had a correct knowledge toward the risk factors, diagnosis, and management of pancreatic cancer. However, several knowledge gaps were identified. They include "The association between type 2 diabetes and pancreatic cancer", "The most common histologic type of pancreatic neoplasm", "the typical clinical symptoms of pancreatic cancer", "The accuracy of ultrasound in screening pancreatic cancer", "Enhanced CT in the diagnosis of pancreatic cancer", and "Which is more superior between MRI and CT in the diagnosis of pancreatic cancer". We also found that overall surgeons' responses did not depend on their geographic locations, but on hospital levels and professional ranks. Surgeons working at level three hospitals had better knowledge than others in certain areas and resident surgeons had fewer correct answers in some areas. CONCLUSIONS: Although most surgeons have a good knowledge in most areas related to the diagnosis and treatment of pancreatic cancer in China, certain knowledge gaps exist, particularly among trainees and those from low level hospitals. Continuing medical education programs to improve these knowledge gaps should be implemented.

Pancreatic metastasis of renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is a common cancer, but pancreatic metastasis of RCC is unusual. Because of the rarity and peculiarity, pancreatic lesions from RCC metastasis were described mostly in case reports which highlight the importance of a systematic analysis of this clinical condition. DATA SOURCES: Data of 7 patients with pancreatic metastasis of RCC treated in the Peking Union Medical College Hospital were extracted and 193 similar patients reported in the past 10 years from the literature were analyzed. Epidemiological, pathological and follow-up information were investigated. Potential prognostic factors were compared with corresponding data reported 10 years ago. RESULTS: Multivariate Cox regression showed that asymptomatic metastasis and surgical procedure were independent factors associated with better survival. Compared with the data reported 10 years ago, follow-up of RCC patients has been emphasized in recent years, and atypical surgery is frequently used since it has similar effect as typical surgery on tumor resection while it is able to preserve more pancreatic function. CONCLUSION: Surgical treatment should be an option as long as the pancreatic metastasis of RCC is resectable.

Chromogranin A is a reliable serum diagnostic biomarker for pancreatic neuroendocrine tumors but not for insulinomas.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are a group of rare tumors. Chromogranin A (CgA) was considered as the most practical and useful serum tumor marker in PNET patients. But peripheral blood levels of CgA are not routinely tested in Chinese patients with PNETs. This study was to assess the diagnostic value of CgA in Chinese patients with PNETs especially in patients with insulinomas. METHODS: Eighty-nine patients with PNETs including 57 insulinomas and 32 non-insulinoma PNETs as well as 86 healthy participants were enrolled in this study between September 2003 and June 2013. Serum levels of CgA were measured by ELISA method. Expression of CgA protein was detected in 26 PNET tissues including 14 insulinomas by immunohistochemical staining. RESULTS: Serum levels of CgA in 89 PNET patients were significantly higher than that in healthy controls (P = 7.2 × 10-9). Serum levels of CgA in 57 patients with insulinomas (median 64.8 ng/ml, range 25-164) were slightly higher than the levels in healthy controls (median 53.4 ng/ml, range 39-94) but much lower than the levels in 32 patients with non-insulinoma PNETs (median 193 ng/ml, range 27-9021), P = 0.001. The serum CgA levels were reduced in 16 of 17 patients with insulinomas after tumor resection. ROC curve showed that CgA values at 60 ng/ml distinguished patients with insulinomas from healthy controls but its sensitivity and specificity were 66.7% and 73.3%, respectively. In contrast, CgA values at 74 ng/ml distinguished patients with non-insulinoma PNETs from healthy controls, and the sensitivity and specificity were 65.6% and 91.9%, respectively. Except for two insulinomas with negative staining of CgA, 12 insulinoma tissues showed positive staining of CgA. CONCLUSION: CgA is a reliable serum diagnostic biomarker for PNETs but not for insulinomas.

N-wasp in pancreatic ductal adenocarcinoma: associations with perineural invasion and poor prognosis.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has long been acknowledged to have a dismal prognosis. Therefore, prognostic markers, especially molecular ones, are of interest. So far, expression of Neural Wiskott-Aldrich syndrome protein (N-WASP) and its associations with clinicopathologic variables and prognosis for patients with PDAC remain unknown. METHODS: N-WASP expression was detected by immunohistochemical staining in a tissue microarray consisted of tumor and nontumor samples from 86 patients with PDAC. The correlations of N-WASP expression with clinicopathologic features and overall survival were evaluated. In addition, risk factors of perineural invasion (PNI) were identified. RESULTS: High expression of N-WASP was more frequent in tumor than in nontumor tissues of PDAC patients (45.3 vs. 19.8%, p < 0.001). The rank of N-WASP grading was significantly higher in tumor tissues than in nontumor tissues (p = 0.048). Also, high expression of N-WASP in tumor tissues was significantly associated with PNI, and lymph node status had a marginally significant relation to tumoral N-WASP expression. Univariate analyses showed that, in addition to conventional clinicopathologic variables, including sex, histologic grade, PNI and lymph node metastasis, high tumoral N-WASP expression was an independent marker of PNI and served as a significant predictor of poor overall survival. The prognostic implication of N-WASP expression was not proven In the multivariate analysis. CONCLUSIONS: Our data showed highly up-regulated expression of N-WASP in PDAC tissues, its correlations with PNI, and its association with an unfavorable prognosis.

Prognostic significance of epidermal growth factor-like domain 7 in pancreatic cancer.

BACKGROUND: Recent studies have shown the clinical significance of epidermal growth factor-like domain 7 (EGFL7) in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer (PC) remains unclear. The present study was undertaken to investigate the role of EGFL7 in the prognosis of PC. METHODS: The expression of EGFL7 in nine PC cell lines was first determined by Western blotting analysis. Tissue microarray-based immunohistochemical staining was performed in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 83 patients with PC. Finally, correlations between EGFL7 expression and clinicopathological variables as well as overall survival were evaluated. RESULTS: EGFL7 was widely expressed in all PC cell lines tested. EGFL7 expression in tumor tissues was significantly higher than that in non-tumor tissues (P=0.040). In addition, univariate analysis revealed that high EGFL7 expression in tumor tissues was significantly associated with poor overall survival, accompanied by several conventional clinicopathological variables, such as gender, histological grade and lymph node metastasis. In a multivariate Cox regression test, EGFL7 expression was identified as an independent marker for long-term outcome of PC. CONCLUSION: Our data showed that EGFL7 is extensively expressed in PC and that EGFL7 is associated with poor prognosis.

Notch1 contributes to chemoresistance to gemcitabine and serves as an unfavorable prognostic indicator in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) carries frequent chemoresistance and extremely dismal prognosis. The underlying mechanisms remain to be further elucidated. We here report the role of Notch1 in gemcitabine resistance and its prognostic significance in PC. METHODS: A small interfering RNA (siRNA) specifically targeting Notch1 was transiently transfected into three PC cell lines (AsPC-1, BxPC-3, and MIA PaCa-2), followed by examination of chemosensitivity to gemcitabine. On the other hand, Notch1 expression was evaluated immunohistochemically and correlated with clinicopathological and prognostic variables. RESULTS: Successful knockdown of Notch1 by specific siRNA induced increased chemosensitivity to gemcitabine in all three cell lines. Immunohistochemical staining revealed that Notch1 was highly expressed in PC tissues (54.8 %), in contrast to that in para-tumor tissues (16.4 %). In addition, Notch1 positivity was significantly correlated with early-term metastasis and shortened overall survival. Multivariate Cox regression identified Notch1 as an independent prognostic factor. CONCLUSIONS: Notch1 contributes to chemoresistance to gemcitabine, and serves as a significant indicator of unfavorable prognosis in PC.

Human equilibrative nucleoside transporter 1 (hENT1) predicts the Asian patient response to gemcitabine-based chemotherapy in pancreatic cancer.

BACKGROUND/AIMS: Individualized chemotherapy is important in the treatment of pancreatic cancer. Therefore, markers for predicting a patient response to treatment must be identified. We studied the relationship between human equilibrative nucleoside transporter 1 (hENT1) expression in tumor cells and the Asian patient response to gemcitabine-based chemotherapy. The aim of the study was to identify markers for individualized chemotherapy in Asian patients with pancreatic cancer. METHODOLOGY: Specimens from 44 Asian patients diagnosed with pancreatic adenocarcinoma were analyzed by immunohistochemistry for hENT1 expression in tumor cells. The correlations between hENT1 expression and various clinicopathological factors, including survival status, were studied. RESULTS: The overall survival (OS) and disease-free survival (DFS) in the hENT1 high-expression group were significantly longer than those of the hENT1 low or no-expression group: OS 21.75 months (95%CI=18.45-25.04 months) vs. 12.48 months (95%CI=10.12-14.85 months); DFS 15.44 months (95%CI=11.26-19.62 months) vs. 8.24 months (95%CI=8.69-9.78 months), respectively. CONCLUSIONS: Our studies suggest that hENT1 expression is related to the patient response to gemcitabine-based chemotherapy in Asian patients with pancreatic cancer. Therefore, hENT1 may be a valuable prognostic marker for individualized chemotherapy in pancreatic cancer.

Diagnostic accuracy of K-ras mutation for pancreatic carcinoma: a meta-analysis.

BACKGROUND: The conventional tests for the diagnosis of early stage pancreatic carcinoma are not acceptable. This meta-analysis is to evaluate the accuracy of K-ras mutation for the diagnosis of pancreatic carcinoma. DATA SOURCES: A systemic search of all relevant literature was performed in Web of Science, EMBASE, Cochrane Database, and MEDLINE (PubMed as the search engine) prior to June 1, 2011. Thirty-four studies fulfilled the inclusion criteria and data were pooled for analysis. RESULTS: The pooled estimates for K-ras mutation in diagnosis of pancreatic carcinoma were as follows: sensitivity 0.68 (95% CI: 0.66-0.71), specificity 0.87 (95% CI: 0.85-0.88), positive likelihood ratio 4.54 (95% CI: 3.47-5.94), negative likelihood ratio 0.37 (95% CI: 0.30-0.44) and diagnostic odds ratio 14.90 (95% CI: 10.02-22.15). Summary receiver operating characteristic analysis demonstrated that the maximum joint sensitivity and specificity was 0.79, and the overall area under the curve was 0.86. CONCLUSIONS: Diagnostic accuracy of K-ras mutation was not superior to that of conventional tests. Therefore, K-ras mutation analysis alone is not recommended for the diagnosis of pancreatic carcinoma.

Risk factors for the occurrence of insulinoma: a case-control study.

BACKGROUND: The etiology of insulinoma is poorly understood. Few studies investigated the possible roles of environmental factors and lifestyle in the pathogenesis of insulinoma. The aim of this study is to identify risk factors associated with occurrence of insulinoma in the Chinese population. METHODS: This study consisted of 196 patients with insulinoma and 233 controls. Demographic information of the patients and controls and risk factors of the disease were analyzed. Univariate and unconditional multivariable logistic regression analyses were made to estimate odds ratios (ORs) and possible risk factors. RESULTS: Approximately 68.88% (135/196) of the patients were from rural areas in contrast to 10.30% (24/233) of the controls (P<0.0001). This difference was confirmed by the multivariate analysis (OR=4.950; 95% CI: 2.928-8.370). Family history of pancreatic endocrine tumor (OR=16.754; 95% CI: 2.125-132.057) and other cancers (OR=2.360; 95% CI: 1.052-5.291) was also related to a high-risk population of insulinoma. CONCLUSION: Rural residents or people who have a family history of pancreatic endocrine tumor and other cancers are a high-risk population of insulinoma.

[Pancreatic acinar cell carcinoma: diagnostic and surgical treatment strategy].

OBJECTIVE: To investigate the clinical features, diagnostic and therapeutic strategy of pancreatic acinar cell carcinoma. METHODS: The data of pancreatic acinar cell carcinoma patients who underwent surgical operations from January 2002 to January 2012 were retrospectively reviewed. RESULTS: Six cases of pancreatic acinar cell carcinoma, identified with pathology were collected, including 3 males and 3 females with the average of 47.8 yeas old. Upper abdominal pain was present in 5 cases, weight loss was present in 4 cases with the average of 12.5 kg. Other symptoms included nausea/vomiting, back pain and obstructive jaundice. The serum CA19-9 and CA24-2 level were significantly elevated in 2 cases. CT scan, MRI and DSA were the main imaging methods to diagnose this disease. However, no case was diagnosed as pancreatic acinar cell carcinoma before operation. All cases were confirmed by the pathological examination. Relatively high rates of surgical resection, long operative time, more blood loss and combined multi-organ resection were the characteristics of this disease's operative surgical procedures. The average period of postoperative follow-up process was 60 months, and the mean survival time was (32 ± 8) months. CONCLUSIONS: The clinical features and biological behavior of pancreatic acinar cell carcinoma are different from those of ductal adenocarcinoma, while the relatively specific clinical manifestations and imaging changes will be helpful for qualitative diagnosis before operation. As it has high rate of resection and better prognosis, more radical surgical strategies should be carried out for patients of this disease.

[The role of perioperative enteral and parenteral nutrition treatment in pancreatic cancer: a multicenter, prospective randomized controlled trial].

OBJECTIVE: To compare the two different nutritional supports, enteral nutrition and parenteral nutrition in the aspects of nutritional conditions, immune status, the incidence of perioperative complications and quality of life impacts in pancreatic cancer. METHODS: For the pancreatic cancer patients which pancreaticoduodenectomy were performed from January 2007 to December 2008 in five high-volume medical centres, prospective, randomized controlled study was carried out. The enrolled patients were randomly divided into enteral nutritional group (EN group) and parenteral nutritional group (PN group). Related indicators, such as nutritional conditions, immune status, incidence of complications, general status and quality of life were assessed. RESULTS: The 200 patients were enrolled, while 178 cases which 90 patients in EN group and 88 patients in PN group were qualified to evaluate. The 22 cases were dropped out. For the mean hospital stay ((23 ± 13) days and (27 ± 24) days respcectively), Karnofsky score and the life quality scoring, there are no statistical differences between the two groups. In post-operation day 7 and day 10, the prealbumin was (69 ± 16) mg/L and (80 ± 22) mg/L in EN group and it was (67 ± 19) mg/L and (70 ± 11) mg/L in PN group, which are all significantly decreased than preoperational levels ((186 ± 38) mg/L for enteral group and (179 ± 37) mg/L for parenteral group, t = -2.24, -2.13, -2.23, -2.20, all P < 0.05), but there was no statistically significant between the 2 groups (P > 0.05). Other general indicators such as the albumin, hemoglobin, total bilirubin, blood urea nitrogen, serum creatinine, serum potassium and serum sodium, revealed no statistical differences in the 2 groups (P > 0.05); The total lymphocytes, CD(+)3CD(+)4 and CD(+)3CD(+)8 lymphocytes in PN group was (0.687 ± 0.065)×10(9)/L, (0.363 ± 0.029)×10(9)/L, and (0.183 ± 0.018)×10(9)/L respectively in post-operation day 10, which they are significantly decreased than in preoperational levels of PN group and the respective counterpart of EN group in post-operation day10 (t = -2.04-2.83, P < 0.05). The 35 patients were suffered from different complications in the 2 groups, but there was no statistical differences among them (P > 0.05). CONCLUSIONS: Enteral nutritional support could not decrease the incidence of perioperative complications in pancreatic cancer patient, but it can improve the immunonutrition status in comparison with parenteral nutrition.

Medullary thyroid carcinoma with nodular goiter carries an excellent prognosis.

BACKGROUND: In our institution, patients with medullary thyroid carcinoma (MTC) concurrent with nodular goiter (NG) have a nearly 100% survival rate, but the reasons and characteristics are unclear. METHODS: Eighty patients with MTC who underwent surgery in our center between 1971 and 2011 were reviewed. RESULTS: A total of 21 MTC/NG and 59 MTC only patients were identified. The stage of the two groups had no significant difference (P = 0.13). The MTC/NG group had lower preoperative serum calcitonin (CT) levels (914.7 ng/L vs. 1162.6 ng/L, P = 0.003), lower postoperative serum CT levels (371.4 ng/L vs. 582.5 ng/L, P < 0.001), lower carcinoembryonic antigen levels (18.3 ng/ml vs. 130.5 ng/ml, P < 0.001), a lower propensity toward lymph node metastasis (40.0% vs. 66.7%, P = 0.07), and a lower proportion of multifocality (19.1% vs. 42.4%, P = 0.06), capsular invasion (9.5% vs. 25.4%, P = 0.21), and vascular invasion (4.8% vs. 10.1%, P = 0.67). The mean tumor diameter of the two groups was similar (20.3 mm vs. 22.1 mm, P = 0.6). Overall 15-year survival in MTC/NG versus MTC only groups was 100% versus 57.0% (P = 0.03). CONCLUSIONS: MTC with NG is an indolent disease and has an excellent prognosis. The only independent predictor of survival was the TNM stage of disease.

Activated mTOR/P70S6K signaling pathway is involved in insulinoma tumorigenesis.

BACKGROUND: Insulinoma was a rare tumor and its pathogenesis was poorly understood. There had no study that focused on the role of mTOR signaling pathway in insulinoma tumorigenesis. MATERIALS AND METHODS: Expression of p-mTOR and its downstream p-P70S6K in insulinoma and normal pancreatic tissue was evaluated by immunohistochemical staining and Western blotting. In vitro study, an insulinoma cell line (INS-1) was treated with inhibitors of mTOR (rapamycin) or dual PI3K/mTOR inhibitor (NVP-BEZ235), RT-PCR, and Western blotting were applied to evaluate their influence on the expression of mTOR and P70S6K. Cell proliferation was evaluated by MTT test, cell cycle and apoptosis were analyzed by flow cytometry, insulin secretion level was evaluated by GSIS method. RESULTS: Positive expression of p-mTOR and p-P70S6K was much higher in insulinoma tumor specimens than the normal pancreatic islet (P < 0.05). mTOR inhibitors can induce decreased expression of mTOR and P70S6K, which resulting in inhibiting INS-1 cell proliferation, insulin secretion and inducing apoptosis. NVP-BEZ235 had better influence on inhibiting the cell proliferation and inducing apoptosis than rapamycin. CONCLUSION: mTOR/P70S6K signaling pathway is involved in tumorigenesis of insulinoma, NVP-BEZ235 and rapamycin offer a promising role as novel drugs in treatment of insulinoma.

Metabolic syndrome components and risk factors for pancreatic adenocarcinoma: a case-control study in China.

BACKGROUND: Metabolic syndrome is a complex collection of interrelated conditions. Recent data have shown that metabolic syndrome may play a role in several cancers. Pancreatic adenocarcinoma is the fourth most common cause of death from cancer in the United States and the fifth in Europe. Despite the increasing numbers of published studies, the etiology of pancreatic adenocarcinoma is incompletely defined. Therefore, this paper aims to evaluate the risk factors for pancreatic adenocarcinoma. METHODS: This was a case-control study of pancreatic adenocarcinoma patients who were referred to the Peking Union Medical College Hospital. Controls were randomly selected from an existing database of healthy individuals at the Health Screening Center. Data on metabolic syndrome, pancreatic diseases, liver diseases, and a history of diabetes and history of hypertension were collected either by conducting a retrospective review of the patients' records and health examination reports or by interview. RESULTS: A history of smoking (OR = 2.981), diabetes (OR = 2.421), cholecystolithiasis (OR = 5.453), or chronic pancreatitis (OR = 28.264) as well as the levels of fasting blood glucose (OR = 4.241), total cholesterol (OR = 1.793), and apolipoprotein A (OR = 36.065) were significantly related to pancreatic adenocarcinoma. CONCLUSIONS: Cholelithiasis, chronic pancreatitis, and certain metabolic syndrome components are potential risk factors for the development of pancreatic adenocarcinoma.

Risk factors for postoperative pancreatic fistula in patients with insulinomas: analysis of 292 consecutive cases.

BACKGROUND: Pancreatic fistula (PF) remains the most challenging complication in pancreatic surgery, yet few published studies have focused on the risk factors for postoperative PF in patients undergoing surgery for insulinomas. METHODS: From January 1990 to February 2010, a total of 292 patients with insulinomas underwent surgery at Peking Union Medical College Hospital. Demographic data, intraoperative procedures, and postoperative data were collected. Particular attention was paid to variables associated with PF as defined by the International Study Group of Pancreatic Fistula (ISGPF). Univariate and multivariate analyses were used to identify possible risk factors for PF. RESULTS: PF was found in 132 (45.2%) patients, of whom 90 were classified into ISGPF grade A, 33 grade B, and 9 grade C. Multivariate analysis showed that male patients (OR=2.56; P=0.007) and operative time >180 minutes (OR=3.756; P<0.0001) were independent risk factors for clinical PF. Pancreatic resection with stapler was a protective factor for both total PF (OR=0.022; P=0.010) and clinical PF (OR=0.097; P=0.007). CONCLUSIONS: Male gender and operative time >180 minutes were independent risk factors for clinical PF, while pancreatic resection with a stapler was a protective factor. Whether body mass index (BMI) and other variables during operation are risk factors of PF needs further study.

Induction, modulation and potential targets of miR-210 in pancreatic cancer cells.

BACKGROUND: MiR-210 is induced by hypoxia and plays different roles in the development of certain cancers. However, little is known about its role in pancreatic cancer (PC). This study aimed to explore the induction and modulation of PC by miR-210 and its potential molecular targets. METHODS: PC cells were cultured under normoxic and hypoxic conditions. Expression of miR-210 and hypoxia-inducible factor (HIF)-1alpha was detected using quantitative reverse-transcription polymerase chain reaction. Cancer cells were transiently transfected with HIF-1alpha small interfering RNA (siRNA) and miR-210 mimics, and cell proliferation was measured using the CCK-8 assay. Potential targets for miR-210 were then identified using a dual luciferase reporter assay. RESULTS: Hypoxic conditions induced miR-210 expression in six PC cell lines (AsPC-1, BxPC-3, MIAPaCa-2, PANC-1, Su86.86 and SW1990), but not in Capan-1 or T3M4 cells. Transfection of HIF-1alpha siRNA into PANC-1 cells markedly inhibited HIF-1alpha expression, and subsequently down-regulated miR-210 expression under hypoxic conditions. MiR-210 had no observable impact on the proliferation of PANC-1 or Su86.86 cells and dual luciferase reporter assays showed significantly reduced luciferase activity in the wild-type E2F3, EFNA3, GIT2, MNT, ZNF462 and EGR3 constructs, compared to the corresponding mutants, but not in HOXA3. CONCLUSIONS: These results suggest that miR-210 expression in PC cells is induced by hypoxia through a HIF-1alpha-dependent pathway, but does not influence PC cell proliferation. Also, E2F3, EFNA3, GIT2, MNT, ZNF462 and EGR3 may be potential miR-210 targets in PC.

Laparoscopic distal pancreatectomy with or without splenectomy: spleen-preservation does not increase morbidity.

BACKGROUND: The indications for laparoscopic spleen-preserving distal pancreatectomy (LSPDP) and its morbidity compared with laparoscopic distal pancreatectomy with splenectomy (LDPS) are ill-defined. This study aimed to share the indications for spleen-preservation and investigate the safety and outcome of LSPDP at our institution. METHODS: A retrospective review of patients who were scheduled to receive laparoscopic surgery for distal pancreatic lesions was conducted. The indications, surgical procedures, intra-operative data, and outcomes of the two procedures were collected and compared by statistical analysis. RESULTS: LDPS and LSPDP were successfully performed in 16 and 21 patients respectively, whereas they were converted to open surgery in 9 patients. There were no significant differences in age, gender, operation time, blood loss, and conversion rate between the LDPS and LSPDP groups. The mean tumor size showed an inter-group difference (5.05 vs 2.53 cm, P<0.001). There were no significant differences in complication and morbidity rates between the two groups. All patients remained alive without recurrence during a follow-up of 9 to 67 months (median 35). CONCLUSION: LSPDP has a morbidity and outcome comparable to LDPS.

Clinical characteristics of hereditary and sporadic medullary thyroid carcinoma.

OBJECTIVE: To study the clinical characteristics and outcomes of the hereditary medullary thyroid carcinoma (HMTC) and the sporadic medullary thyroid carcinoma (SMTC). METHODS: The clinical data of 78 patients with medullary thyroid carcinoma who underwent surgery in our hospital between July 1980 and May 2011 were retrospectively analyzed. RESULTS: Of these 78 patients, there were 23 HMTC cases and 55 SMTC cases. The HMTC group was significantly younger age of onset [(36.4±13.5) years vs. (46.6±11.2) years, P<0.01] and a lower pre/post-operative serum calcitonin levels [(850.4±110.20) ng/L vs. (1450.4±118.3) ng/L, P<0.01 and (410.8±133.2) ng/L vs. (1585.4±129.5) ng/L, P<0.01] than the SMTC group. In addition, the mean tumor diameter was also significantly smaller in the HMTC group (14.3 mm vs. 21.0 mm in SMTC group, P<0.05). Tumor multifocality was seen in a significantly higher proportion of HMTC cases compared with the SMTC cases (56.6% vs. 29.1%, P<0.05). The overall 10-year survival was 100% in HMTC group and 80.2% in SMTC group (P<0.05). CONCLUSION: HMTC has a better prognosis than SMTC.