Aberrant expression of CKS2 induced by ELK1 contributes to malignant progression of pancreatic cancer.

Cyclin-dependent kinase subunit 2 (CKS2) has been reported to promote various malignancies. This study investigated the functional role of CKS2 in pancreatic cancer (PC). An analysis of abnormally expressed genes and their prognostic value for PC was performed by using the Gene Expression Profiling Interactive Analysis (GEPIA) database and performing immunohistochemical staining on 64 samples of tumor tissue. CCK-8 assays, EdU staining, colony formation assays, flow cytometry, and a xenograft tumor model were used to analyze the biological function of CKS2 in PC. Our results revealed that CKS2 was expressed at significantly higher levels in PC tissues than in adjacent normal tissues, and a high level of CKS2 expression was associated with a poor prognosis for patients with PC. Moreover, functional assays revealed that CKS2 knockdown suppressed cell proliferation, induced cell cycle S phase, G2/M phase arrest, and apoptosis in vitro, and also reduced tumor growth in vivo. In addition, CKS2 knockdown increased the levels of Bax, caspase-3, P53, P21, and GADD45α expression, but decreased Bcl-2, Cyclin B1, CDK1, Cyclin A, and Cdc25C expression. CKS2 overexpression produced the opposite effects of CKS2 knockdown. Furthermore, we found that ELK1 protein regulated transcription of the CKS2 gene. In conclusion, our findings suggest that CKS2 expression is regulated by ELK1, which could possibly serve as prognostic indicator and therapeutic target for PC.

Perioperative safety and prognosis following parenchyma-preserving surgery for solid pseudopapillary neoplasm of the pancreas.

BACKGROUND/OBJECTIVES: To evaluate perioperative safety and outcome of parenchyma-preserving pancreatectomy and risk factors of metastasis and recurrence for patients with solid pseudopapillary neoplasm (SPN). METHODS: Demographic data, operative and pathological parameter, follow-up data of patients with SPN undergoing their first operation were collected in our single center from May 2016 to October 2021 and compared between regular pancreatectomy group and parenchyma-preserving surgery group. Risk factors for metastasis and recurrence were investigated. RESULTS: A total of 194 patients were included, 154 of whom were female and the average age of all patients was 33 years old. Most patients were asymptomatic, with the most common complaint being abdominal pain or discomfort. Of them, 62 patients underwent parenchyma-preserving pancreatectomy including middle segment pancreatectomy and enucleation, and 132 patients underwent regular pancreatectomy including pancreaticoduodenectomy, distal pancreatectomy and total pancreatectomy. Patients in the parenchyma-preserving surgery group had a shorter duration of operation, less intraoperative bleeding, and decreased risk of combined organ removal and blood transfusion, with no statistical significance yet. The two groups exhibited a similar incidence of postoperative complications including grade B and C pancreatic fistula, delayed gastric emptying, postoperative pancreatic hemorrhage, and other complications, as well as radiological intervention, relaparotomy and the length of postoperative hospital stay. There were no perioperative deaths. All the patients, except 18 of those who discontinued follow-up, were alive with a median follow-up time of 31 months. Three patients in the regular pancreatectomy group were observed to have liver metastasis, and no metastasis was observed in the parenchyma-preserving surgery group. Significant risk factors for tumor metastasis and recurrence were tumor size, angioinvasion, and nerve infiltration. CONCLUSIONS: Parenchyma-preserving surgery did not significantly increase the frequency of perioperative complications or recurrence and might be preferable if comprehensive conditions allow.

Curcumin promotes skin wound healing by activating Nrf2 signaling pathways and inducing apoptosis in mice.

Background/aim: Curcumin may have potential as a therapy for wound healing, but the underlying mechanism remains unclear. It is not known whether curcumin can promote wound healing by activating Nrf2 signaling pathway and inducing apoptosis. This study determined the role of Nrf2 signaling pathway and apoptosis in curcumin-promoting skin wound healing. Materials and methods: The full-thickness skin defect model of mice was made and randomly divided into a control group and a curcumin group. The mice in the curcumin group and in the control group received respectively a daily topical treatment of Vaseline cream with or without 5 mg curcumin. The wound healing of mice was observed daily. The mice in two groups were killed respectively on postinjury days 3, 7, and 14, and the wound tissues were collected, with 5 mice in each group. Pathological change and formation of collagen fibers were observed by HE and Masson staining respectively. The expression of caspase-3 was observed by immunohistochemistry. Western blot was used to examine the protein levels of Nrf2 and HO-1, and ELISA assay and colorimetry assay were used to check the contents of ROS, MDA, SOD, and GSH. Results: The wound healing rates of curcumin group were higher than those of control group (p < 0.05), and the pathological changes were also significantly better than those in the control group (p < 0.05). Collagen fiber synthesis in curcumin group was higher than that in control group (p < 0.05). Moreover, the expression of caspase-3 in curcumin group was higher than that in control group on 7th day post wound (p < 0.05). Furthermore, the levels of ROS and MDA in curcumin were lower than those in control group (p < 0.05), and the level of Nrf2, HO-1, SOD and GSH were higher than those in control group (p < 0.05). Conclusion: Curcumin improves skin wound healing by activating the Nrf2 signaling pathway and inducing apoptosis in mice.

Efficacy comparison of optimal treatments for hepatocellular carcinoma patients with portal vein tumor thrombus.

INTRODUCTION AND OBJECTIVES: Optimal treatment of hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT) remains controversial. MATERIALS AND METHODS: A total of 627 HCC patients with PVTT after initial treatment with one of the following at Affiliated Tumor Hospital of Guangxi Medical University: liver resection (LR, n = 225), transarterial chemoembolization (TACE, n = 298) or sorafenib (n = 104) were recruited and randomly divided into the training cohort (n = 314) and internal validation cohort (n = 313). Survival analysis were repeated after stratifying patients by Cheng PVTT type. RESULTS: Resection led to significantly higher OS than the other two treatments among patients with type I or II PVTT. TACE worked significantly better than the other two treatments for patients with type III. All three treatments were associated with similar OS among patients with type IV. These findings were supported by the internal validation cohort. CONCLUSIONS: Our results suggest that the optimal treatment for HCC involving PVTT depends on the type of PVTT. LR may be more appropriate for type I or II PVTT; TACE, for type III Sorafenib may be more appropriate than invasive treatments for patients with type IV PVTT.

Surgical revision for pancreatojejunostomy stricture: a case series of 14 patients.

BACKGROUND: Pancreatojejunostomy stricture (PJS) is a rare long-term complication of pancreaticojejunal anastomosis. This study aimed to investigate the role of surgery in the management of pancreatojejunostomy strictures. METHODS: The database of the Pancreas Center of Nanjing Medical University was retrospectively screened for patients who underwent a surgical revision for PJS between June 2012 and August 2019, and their clinical characteristics and management modalities were reviewed. RESULTS: Fourteen consecutive cases were retrieved, the median age at index operation was 41.1 years (19-71). The average time between the two operations was 70.6 months (8-270 months). Index procedures included pancreaticoduodenectomy (PD) (7/14, 50%), pylorus-preserving PD (4/14, 28.6%), Berger procedure (2/14, 14.3%), and middle pancreatectomy (1/14, 7.1%). The diameter of the main pancreatic duct was < 4 mm in all 14 cases, and nine underwent pancreaticojejunostomy (PJ) stenting during the index operation. The most frequent complaints were abdominal pain (6/14, 42.9%), recurrent acute pancreatitis (6/14, 42.9%), pancreatic fistula (1/14, 7.1%), and abdominal distention (1/14, 7.1%). The diagnosis of PJ stricture was confirmed by computed tomography or magnetic resonance imaging in all cases. All patients had a main duct diameter > 5 mm before surgical revision. All patients underwent wedge excision with interrupted one-layer suturing with absorbable sutures and without stent placement. In this series, only one patient required reoperation. Upon follow-up, 11 of 12 patients had complete resolution of the PJ stricture. CONCLUSION: PJS is a long-term complication of pancreatojejunostomy. Surgical revision of the anastomosis is a safe and effective treatment modality.

Separation and Purification of Two Saponins from Paris polyphylla var. yunnanensis by a Macroporous Resin.

An effective method for separating and purifying critical saponins (polyphyllin II and polyphyllin VII) from a Paris polyphylla var. yunnanensis extract was developed in this study which was environmentally friendly and economical. Static adsorption kinetics, thermodynamics, and the dynamic adsorption-desorption of macroporous resins were investigated, and then the conditions of purification and separation were optimized by fitting with an adsorption thermodynamics equation and a kinetic equation. Effective NKA-9 resin from seven macroporous resins was screened out to separate and purify the two saponins. The static adsorption and dynamic adsorption were chemical and physical adsorption dual-processes on the NKA-9 resin. Under the optimum parameters, the contents of polyphyllin II and polyphyllin VII in the product were 17.3-fold and 28.6-fold those in plant extracts, respectively. The total yields of the two saponins were 93.16%. This research thus provides a theoretical foundation for the large-scale industrial production of the natural drugs polyphyllin II and polyphyllin VII.

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.

Prognostic Nomogram for Resected Pancreatic Adenocarcinoma: A TRIPOD-Compliant Retrospective Long-Term Survival Analysis.

BACKGROUND: Prognostic prediction had been widely used in various cancer entities, from early screening to end-stage patient caring. Currently, there is hardly any well-validated nomogram which exists for long-term survival prediction in pancreatic adenocarcinoma (PC) patients in a post-surgery setting. Our objectives are to identify possible prognostic factors in PC patients following radical resection and to develop a prognostic nomogram based on independent survival predictors. METHODS: From 2009 to 2014, a total of 432 PC patients who underwent curative intended surgeries with complete follow-up data were included in this current retrospective long-term survival analysis. Clinicopathological data were extracted from medical records, and all missing values (percentage 0.9-8.3%) were imputed five times with the "PMM" method. Cox proportional hazards models were utilized. A nomogram was formulated based on results from the multivariate regression model so as to predict OS at 1-, 2- and 3-year as well as median OS. Validations, including discrimination and calibration, were carried out with 1000 bootstrap resamples. External validation was conducted in order to verify the accuracy of our nomogram at 1 and 2 years by utilizing the clinicopathological data of 122 PC patients who underwent curative intended surgeries in 2015 in our centre. RESULTS: Age, abdominal pain, back pain, tumour location, preoperative neutrophil-lymphocyte ratio, preoperative CA19-9, tumour differentiation, microscopic nerve invasion, microscopic vascular invasion, T stage, lymph node ratio, M stage and adjuvant chemotherapy were all assembled into nomogram. The concordance index (C-index) of internal and external validation was 0.702 and 0.688, respectively. The C-index of the TNM staging system was 0.572 (P < 0.001 vs. nomogram). CONCLUSION: Our prognostic nomogram based on clinicopathological parameters shows good performance in long-term survival prediction in PC patients following radical surgery and could play a role in further clinical utilization.

Central pancreatectomy for early-stage pancreatic ductal adenocarcinoma: a single-center case-control study.

PURPOSE: Central pancreatectomy (CP) has been applied for treating benign and low-grade malignant tumors in pancreatic neck, but studies regarding CP for pancreatic ductal adenocarcinoma (PDAC) are quite limited. We aimed to investigate the role of central pancreatectomy in the treatment of PDAC in the neck of the pancreas. METHODS: Patients who underwent CP at our hospital between 2009 and 2016 were identified. Patients treated by distal pancreatectomy (DP) were matched according to the tumor size, location, and staging. The surgical and survival outcomes were compared between the CP and DP groups. RESULTS: Nine patients had CP. Five (56%) had postoperative complications and three (33%) had clinically significant (grade B + C) fistula. No significant difference was found between the CP and DP groups for the rate of overall morbidity, pancreatic fistula, reoperation, and readmission. Tumor size was smaller in the CP group compared to the DP group. The mortality of both groups was zero. The median postoperative survival was similar between the two groups (20.4 months for CP vs 19.4 months for DP, P = 0.842). CONCLUSIONS: CP is safe for patients with small PDAC at the neck of the pancreas. Considering the good preservation of pancreatic endocrine and exocrine functions, CP could be considered as an alternative procedure for single small PDAC in pancreatic neck.

Exposure to jet lag aggravates depression-like behaviors and age-related phenotypes in rats subject to chronic corticosterone.

Our previous finding demonstrated that chronic corticosterone (CORT) may be involved in mediating the pathophysiology of premature aging in rats. Frequent jet lag increases the risk for many diseases, including obesity and type 2 diabetes, and is associated with the aging processes. However, the effect of jet lag on CORT-induced depression and its association with aging phenotypes remain unclear. In this study, the rats were exposed to both CORT and jet lag treatment, and the differences were analyzed and compared to rats with single CORT treatment. Our results showed that jet lag treatment aggravated CORT-induced depression-like behavior evidenced by sucrose intake test, forced swimming test, and open field test. Additionally, this treatment aggravated the shortening of telomeres, which possibly resulted in decreased telomerase activity, and downregulated the expression of telomere-binding factor 2 (TRF2) and telomerase reverse transcriptase compared to that in CORT rats, as revealed by quantitative real-time-polymerase chain reaction and western blot analysis, respectively. The shortening of telomeres may have been caused by increased oxidative stress, which was associated with the inhibition of sirtuin 3. Exposure to jet lag also aggravated the degeneration of mitochondrial functions, as shown by the decreases in the mRNA expression of COX1, ND1, and Tfam. Our findings provide physiological evidence that jet lag exposure may worsen stress-induced depression and age-related abnormalities.

Diagnosis and treatment of solid-pseudopapillary tumors of the pancreas: A single institution experience with 97 cases.

BACKGROUND/OBJECTIVES: We evaluated the diagnoses and surgical management of solid pseudopapillary tumors of the pancreas (SPTP) in a single center setting. METHODS: Demographic details, clinical presentations, imaging features, surgical strategies, and pathological findings of 97 consecutive patients who underwent surgery for pathologically confirmed SPTP between 2008 and 2016 were analyzed retrospectively. RESULTS: A total of 97 patients with SPTP accounted for 2.15% of total pancreatic surgeries (N = 4508). The mean age at diagnosis was 31.6 ±â€¯13.92 years (range: 7-83 years), and males:females were 85:12. Chief complaints were abdominal pain or discomfort (n = 50). The mean transverse tumor diameter was 53.2 ±â€¯2.76 mm (range: 14-170 mm). Tumors were localized to the pancreatic head (38.1%; 37/97), neck (12.4%; 12/97), body and tail (49.5%; 48/97). There were no significant differences in age of onset, presenting symptoms, and sites between males and females. A significant difference was found in the maximum diameter of SPTP across different age groups. Partial pancreatectomy was performed for patient with tumor ≥ 5 cm, and enucleation was performed when tumor was smaller than 5 cm. Pancreatic fistula was the main complication. Immunohistochemical markers for endocrine, exocrine and epithelial factors were used for a final diagnosis. During a median follow-up of 54 months (range: 7-121 months), 84 patients were alive without evidence of recurrence, and 13 patients were lost to follow-up. CONCLUSION: SPTP surgical resection is a safe procedure with low morbidity and mortality, which is also effective even in the presence of invasiveness and metastases. Accurate initial diagnoses and follow up are essential.

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.

Predictors of distant metastasis on exploration in patients with potentially resectable pancreatic cancer.

BACKGROUND: Patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC) are frequently found to be unresectable on exploration due to small distant metastasis. This study was to investigate predictors of small distant metastasis in patients with potentially resectable PDAC. METHODS: Patients who underwent surgical exploration for potentially resectable PDAC from 2013 to 2014 were reviewed retrospectively and divided into two groups according to whether distant metastases were encountered on exploration. Then, univariate and multivariate logistic regression analyses were used to identify predictors of distant metastasis. A scoring system to predict distant metastasis of PDAC on exploration was constructed based on the regression coefficient of a multivariate logistic regression model. RESULTS: A total of 235 patients were included in this study. Mean age of the study population was 61.7 ± 10.4 years old. Upon exploration, distant metastases were found intraoperatively in 62 (26.4%) patients, while the remaining 173 were free of distant metastases. Multivariate logistic regression analysis identified that age ≤ 62 years old (p < 0.001), male sex (p = 0.011), tumor size ≥4.0 cm (p < 0.001), alanine aminotransferase level (ALT) < 125 U/L (p < 0.001), and carbohydrate antigen (CA19-9) level ≥ 385 U/mL (p < 0.001) were independent risk factors for occult distant metastasis of PDAC. A preoperative scoring system (0-8 points) for distant metastasis on exploration was constructed using these five factors. The receiver operating characteristic curves showed that the area under the curve of this score was 0.85. A score of 6 points was suggested to be the optimal cut-off value, and the sensitivity and specificity were 85% and 69%, respectively. CONCLUSIONS: Distant metastasis is still frequently encountered on exploration for patients with potentially resectable PDAC. Younger age, male sex, larger tumor size, low ALT level and high CA19-9 level are independent predictors of unexpected distant metastasis on exploration.

Afferent Loop Decompression Technique is Associated with a Reduction in Pancreatic Fistula Following Pancreaticoduodenectomy.

OBJECTIVES: Postoperative pancreatic fistula (POPF) is a major complication and main cause of mortality after pancreaticoduodenectomy (PD). Afferent loop decompression technique (ALDT) has theoretical feasibility to reduce the rate of POPF. The aim of this study is to determine whether ALDT is a protective factor for POPF. METHODS: A total of 492 consecutive patients who underwent PD between January 2012 and December 2014 were identified from a prospective database. All data were extracted and events were judged based on medical records. Propensity score matching was conducted to balance several variables. Univariate and multivariate analyses were performed, respectively, to investigate the independent risk factors for pancreatic fistula. ALDT required a nasogastric tube with multiple side holes to be placed deep into the afferent jejunal limb. The rationale for this technique was to prevent pancreatic fistula by decreasing intraluminal pressure in the afferent jejunal loop by placement of the nasogastric tube and the application of continuous low-pressure suction after surgery. RESULTS: The total rate of POPF for the entire cohort was 30.7%, and ISGPS grade-A/B/C POPF rates were 18.1, 10.6 and 2.0%, respectively. In-hospital mortality was 1.6%. Among the 331 patients who received ALDT, 89 developed pancreatic leakage (26.9 vs. 38.5% for non-ALDT; P = 0.009) and eight developed biliary leakage (2.4 vs. 6.2% for non-ALDT; P = 0.035). Apart from ALDT, decreased preoperative ALT, soft pancreas, long operative time and tumour presence in the lower common bile duct (as opposed to the pancreas) were identified as other independent risk factors for POPF following multivariate logistic regression analysis. CONCLUSIONS: ALDT may reduce the incidence of POPF after PD.

Genetic diversity of K-antigen gene clusters of Escherichia coli and their molecular typing using a suspension array.

Capsular polysaccharides (CPSs), or K-antigens, are the major surface antigens of Escherichia coli. More than 80 serologically unique K-antigens are classified into 4 groups (Groups 1-4) of capsules. Groups 1 and 4 contain the Wzy-dependent polymerization pathway and the gene clusters are in the order galF to gnd; Groups 2 and 3 contain the ABC-transporter-dependent pathway and the gene clusters consist of 3 regions, regions 1, 2 and 3. Little is known about the variations among the gene clusters. In this study, 9 serotypes of K-antigen gene clusters (K2ab, K11, K20, K24, K38, K84, K92, K96, and K102) were sequenced and correlated with their CPS chemical structures. On the basis of sequence data, a K-antigen-specific suspension array that detects 10 distinct CPSs, including the above 9 CPSs plus K30, was developed. This is the first report to catalog the genetic features of E. coli K-antigen variations and to develop a suspension array for their molecular typing. The method has a number of advantages over traditional bacteriophage and serum agglutination methods and lays the foundation for straightforward identification and detection of additional K-antigens in the future.

Effect of antecolic or retrocolic route of gastroenteric anastomosis on delayed gastric emptying after pancreaticoduodenectomy: A meta-analysis of randomized controlled trials.

BACKGROUND: Delayed gastric emptying (DGE) is one of the most troublesome complications after classical pancreaticoduodenectomy (PD) or pylorus-preserving PD. Whether the route of gastroenteric reconstruction has any influence on DGE remains controversial. The aim of this study was to investigate the influence of different types of gastroenteric anastomosis on DGE after PD/PPPD. METHODS: A systematic search of literature databases (Cochrane Library, PubMed, EMBASE, and Web of Science) was performed to identify eligible studies. Cochrane collaboration's tool for assessing risk of bias was utilized to evaluate the quality of included studies. The primary outcome was DGE incidence rate. Further outcomes included mortality, morbidity, and other operation related events. Random-effect or fix-effect models were used as appropriate. RESULTS: Five randomized controlled trials (RCTs) including a total of 530 patients were identified and included in the analysis. Based on these studies, no difference was found in DGE incidence between antecolic and retrocolic groups (relative risk [RR], 0.82; 95% confidence interval [CI], 0.51-1.32; P = 0.41). Mortality, morbidity, and operation related events were not significantly different between groups. CONCLUSIONS: Results of the meta-analysis reveal that DGE occurrence is not affected by route of gastroenteric anastomosis. Anastomosis approach should be chosen according to the surgeons' preference.

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.

Diagnosis and surgical management of insulinomas in 33 consecutive patients at a single institution.

PURPOSE: The purpose of this study was to evaluate the diagnosis and surgical management of insulinomas in a single-center setting. METHODS: Demographic details, clinical presentation, preoperative diagnosis, surgical strategy, and outcomes of 33 consecutive patients who underwent surgery for insulinoma were analyzed retrospectively. RESULTS: The median time from the first onset of symptoms to diagnosis was 24 months (range 3 days to 50 years). All cases presented with Whipple's triad and had a fasting insulin to glucose ratio higher than 0.33. The preoperative detection rates of transabdominal ultrasonography, CT, MRI, and EUS were 22 % (2/9), 72 % (23/32), 75 % (9/12), and 80 % (4/5), respectively. Intraoperative manual palpation localized all cases. Enucleation was performed in 58 % of cases (19/33), partial pancreatic resection in 39 % (13/33), and enucleation plus partial resection in 3 % (1/33). Pancreatic fistula was the most common complication and occurred in 15 patients (45 %), including seven grade A, five grade B, and three grade C fistulas. There was no mortality. When compared with partial pancreatectomy, enucleation held a significant advantage in operative time and operative bleeding, with no significant differences in demographic data and postoperative complications. During a median follow-up period of 32 months, two patients were lost to follow-up and the remaining 31 patients were without evidence of recurrence. CONCLUSIONS: A fasting insulin release index larger than 0.3 is a reliable indicator for the diagnosis of insulinoma. Intraoperative palpation by an experienced surgeon can effectively complement an uncertain preoperative localization. Compared with partial pancreatic resection, enucleation showed significant benefit in terms of intraoperative blood loss and operation time.

[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.