Xiafei Hong

Targeted next-generation sequencing as a comprehensive test for patients with and female carriers of DMD/BMD: a multi-population diagnostic study

Duchenne and Becker muscular dystrophies (DMD/BMD) are the most commonly inherited neuromuscular disease. However, accurate and convenient molecular diagnosis cannot be achieved easily because of the enormous size of the dystrophin gene and complex causative mutation spectrum. Such traditional methods as multiplex ligation-dependent probe amplification plus Sanger sequencing require multiple steps to fulfill the diagnosis of DMD/BMD. Here, we introduce a new single-step method for the genetic analysis of DMD patients and female carriers in real clinical settings and demonstrate the validation of its accuracy. A total of 89 patients, 18 female carriers and 245 non-DMD patients were evaluated using our targeted NGS approaches. Compared with traditional methods, our new method yielded 99.99% specificity and 98.96% sensitivity for copy number variations detection and 100% accuracy for the identification of single-nucleotide variation mutations. Additionally, this method is able to detect partial deletions/duplications, thus offering precise personal DMD gene information for gene therapy. We detected novel partial deletions of exons in nine samples for which the breakpoints were located within exonic regions. The results proved that our new method is suitable for routine clinical practice, with shorter turnaround time, higher accuracy, and better insight into comprehensive genetic information (detailed breakpoints) for ensuing gene therapy.

Propensity score‐matched analysis of robotic versus open surgical enucleation for small pancreatic neuroendocrine tumours

Enucleation of pancreatic neuroendocrine tumours (pNETs) via robotic surgery has rarely been described. This study sought to assess the safety and efficiency of robotic surgery for the enucleation of small pNETs.

Catechol-O-methyltransferase, a new target for pancreatic cancer therapy

Catechol‐O‐methyltransferase (COMT) is an important molecule in different types of cancers. Its biological effect and therapeutic significance, however, rarely been investigated fully in pancreatic cancer. Immunohistologically, high COMT expression was significantly correlated with the longer overall survival of patients (P < 0.05), indicating its protective nature. The effects of COMT on cell growth, apoptosis, and invasion were evaluated using overexpression and silencing methods. In detail, we carried out experiments using one stably transduced and two transiently transfected pancreatic cancer cell lines in vitro, and one stably transduced cell line in vivo mice xenograft models. In vitro experiments showed that COMT inhibited cell proliferation, enhanced gemcitabine‐induced apoptosis, and inhibited cell invasion in stably transduced and transiently transfected cell lines by regulating the PI3K/Akt pathway, p53, and E‐cadherin. The COMT overexpressed and silenced cell lines showed significantly inhibited and enhanced growth capacities in in vivo xenograft models, respectively. In conclusion, COMT suppressed pancreatic cancer and its high expression predicted longer survival time. The interaction of COMT with the PI3K/Akt pathway makes it a potential target for therapy.

The Effect of Body Mass Index on Surgical Outcomes in Patients Undergoing Pancreatic Resection: A Systematic Review and Meta-Analysis.

Objectives Previous studies that investigated the association between body mass index (BMI) and pancreatectomy outcomes have produced conflicting conclusions. We conducted this meta-analysis to assess the association between them. Methods We searched PubMed, EMBASE, and Cochrane Library databases up to December 28, 2014. Patients were divided into high-BMI group (BMI ≥ 25 kg/m2) and normal-BMI group (BMI < 25 kg/m2). Postoperative and intraoperative outcomes were evaluated. Meta-regression and subgroup analysis were performed to evaluate any factors accountable for the heterogeneity. Meta-analysis was performed using a random-effect model. Results We included 22 studies involving 8994 patients. Patients in the high-BMI group had significantly increased postoperative pancreatic fistula rate (odds ratio [OR],1.96; 95% confidence interval [CI], 1.43–2.67), delayed gastric emptying rate (OR, 1.62; 95% CI, 1.15–2.29), wound infection rate (OR, 1.43; 95% CI, 1.07–1.93), operation time (mean difference [MD],15; 95% CI, 13.40–16.60), blood loss (MD, 270.71; 95% CI, 248.93–292.49), and length of hospital stay (MD, 2.87; 95% CI, 1.51–4.24). For modest heterogeneity in postoperative pancreatic fistula, regional distribution tended to be the contributor. Conclusions High BMI not only increased the surgical difficulty but also decreased the surgical safety for pancreatectomy.

Catechol-O-Methyltransferase Inhibits Colorectal Cancer Cell Proliferation and Invasion

BACKGROUND AND AIMS Catechol-O-methyltransferase (COMT) has been reported as an important molecule in various types of cancers. The biological function of COMT in colorectal cancer (CRC) has not yet been fully investigated. METHODS We constructed a transient transfection of a CRC cell lines to up- and downregulate COMT expression level and tested the proliferative, invasion ability in vitro. We also constructed a stable transduced CRC cell line and conducted tumor-forming capacity experiment in mouse xenograft model in vivo. RESULTS In vitro experiment showed that COMT inhibited the cell proliferation by regulating p-Akt, PTEN and inhibited G1 to S phase transition by regulating p53, p27, and cyclinD1. COMT inhibited invasion by regulating E-cadherin. In vivo experiment showed decreased tumor growth in COMT overexpressing cell line. CONCLUSIONS COMT has tumor-suppressive functions for CRC cell lines in vitro and in vivo experiments.

The effect of pylorus removal on delayed gastric emptying after pancreaticoduodenectomy: a meta-analysis of 2,599 patients.

Background Delayed gastric emptying is a serious complication of pancreaticoduodenectomy. The effect of pylorus removal on delayed gastric emptying has not been well evaluated. Study Design We searched five databases (PubMed, EMBASE and the Cochrane Central Register of Controlled Trials, Scopus and Web of Science) up to July 2014. The meta-regression analysis was performed to evaluate any factors accountable for the heterogeneity. Publication bias was assessed by Eggers test, and corrected by Duvals trim and fill method. Subgroup analyses were conducted for different surgical techniques of pyloric removal. Other intraoperative and postoperative parameters were compared between two groups. Results We included 27 studies involving 2,599 patients, with a moderate-high heterogeneity for primary outcome (I2 = 63%). Meta-regression analysis showed that four variables primarily contributed to the heterogeneity, namely nasogastric tube intubation time, solid food start time, preoperative diabetes percentage and the number of patients in pylorus-preserving group. After excluding four studies, the remaining twenty-three studies showed reduced heterogeneity (I2 = 51%). Then we used Duvals trim and fill method to correct publication bias. The corrected MH odds ratio was 0.78 (95% CI: 0.52–1.17). A subgroup analysis showed that pylorus removal tends to reduce delayed gastric emptying incidence for subtotal stomach-preserving pancreaticoduodenectomy or pylorus-resecting pancreaticoduodenectomy, compared with pylorus-preserving group. However, standard Whipple procedure failed to show any significant reduction of DGE compared with pylorus-removal group. No significant differences were observed in terms of length of hospital stay, infection and pancreatic fistula; however, pylorus removal resulted in longer operation time, more blood loss and higher mortality. Conclusion The pylorus removal does not significantly reduce the overall incidence of delayed gastric emptying. Subtotal stomach-preserving pancreaticoduodenectomy or pylorus-resecting pancreaticoduodenectomy tends to reduce delayed gastric emptying incidence, but needs further validation.

Solid Serous Cystadenoma of the Pancreas: A Case Report of 2 Patients Revealing Vimentin, β-Catenin, α-1 Antitrypsin, and α-1 Antichymotrypsin as New Immunohistochemistry Staining Markers

AbstractSolid serous cystadenoma (SCA) of the pancreas is a rare type of pancreatic solid tumors. Postoperative pathological evaluation is of particular importance for distinguishing solid SCA of the pancreas from other pancreatic solid tumors.Here we present 2 cases of solid SCA of the pancreas, both preoperatively diagnosed with pancreatic neuroendocrine tumors. One case had positive OctreoScan test.Surgical resections were done for both cases. Postoperative immunohistochemistry assays were conducted with marker panels for SCA and 2 types of pancreatic solid tumors, which were neuroendocrine tumor (pNET) and solid pseudopapillary tumor (SPT).Two cases showed typical staining patterns for SCA markers. Notably, both cases showed positivity for 4 SPT markers (vimentin, &bgr;-catenin, &agr;-1 antitrypsin, and &agr;-1 antichymotrypsin).Emphasis should be paid to those 4 new markers for future pathological diagnosis of solid SCA of the pancreas.

An increased total resected lymph node count benefits survival following pancreas invasive intraductal papillary mucinous neoplasms resection: an analysis using the surveillance, epidemiology, and end result registry database.

Background The therapeutic effect of lymph node dissection for pancreas invasive intraductal papillary mucinous neoplasms (IPMN) remains unclear. The study investigated whether cancer-specific survival (CSS) and overall survival (OS) rates among invasive IPMN patients improve when more lymph nodes are harvested during surgery. Study Design The study cohort was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The lymph node count was categorized into quartiles. The relationship between lymph node count and survival was analyzed using Kaplan–Meier curves and a Cox proportional-hazards model. The stage migration was assessed by Chi-square tests. Propensity score matching (PSM) was used to minimize confounding variables between groups. Results In total, 1,080 patients with resected invasive IPMNs from 1992 to 2011 were included. Univariate and multivariate Cox models indicated that an increased lymph node count independently improves survival. The Kaplan-Meier and log-rank tests identified 16 nodes as an optimal cut-off value that yielded a significant survival benefit for all invasive IPMN patients. The stage migration effect existed in this cohort. After PSM, the 5-year CSS increased from 36% to 47%, and the median survival rate increased from 30 months to 40 months by increasing the lymph node count to over 16, alone. The 5-year OS rate also provided additional support for this result. Conclusion Increased lymph node counts were associated with improved survival in invasive IPMN patients. One cut-off value of lymph node count was 16 for this improvement.

The prognostic impact of primary tumor resection in pancreatic neuroendocrine tumors with synchronous multifocal liver metastases

BACKGROUND Whether primary tumor resection benefits patients with synchronous multifocal liver metastases from pancreatic neuroendocrine tumors remains controversial. We investigated whether primary tumor resection significantly affects survival in this study. METHODS A retrospective study of patients with synchronous multifocal liver metastases from pancreatic neuroendocrine tumors between 1998 and 2016 was performed. Patient demographics, operation details, adjuvant treatment, and pathological and survival information were collected, and relevant clinical-pathological parameters were assessed in univariate and multivariate survival analyses. RESULTS Sixty-three patients were included in this study, including 35 who underwent primary tumor resection. The median survival time and 5-year survival rate of this cohort were 50 months and 44.5%, respectively. Median survival time in the resected group was significantly longer at 72 months than that of 32 months in the nonresected group (p = 0.010). Multivariate analysis showed that primary tumor surgery was a significant independent prognostic factor (HR 0.312, 95% CI: 0.128-0.762, p = 0.011). CONCLUSIONS Primary tumor resection significantly benefits patients with synchronous multifocal liver metastases from pancreatic neuroendocrine tumors.

Surgery in overweight patients with insulinoma: effects on weight loss

Abstract Objective: Weight loss induced by the complete resection of insulinoma is controversial in overweight patients. The study sought to explore postoperative weight loss and metabolic changes in overweight insulinoma patients. Methods: A retrospective study was conducted to review the follow-up data of insulinoma patients with a BMI ≥25kg/m2 who underwent complete lesion resection between May 2010 and May 2015. Body mass index (BMI), weight loss (WL) and percentage weight loss (%WL) were main outcomes. Results: Fifty-one patients were included with a median follow-up of 28 months. The BMI at 3 months, 1 year, 2 years and 3 years postoperatively were significantly lower than the preoperative BMI values (p < .01). The WL% was 12.9% at 3 months postoperatively without significant changes throughout the 3-year follow-up. WL and the %WL were significantly higher in the high BMI group (BMI≥ 27.5 kg/m2). Multivariate analysis indicated that higher initial BMI was associated with increased weight loss (p = .001). 63.8% of patients with hypertension recovered and improved sleep quality was evident in all patients with obstructive sleep apnea syndrome within 1 year postoperatively. Conclusions: Weight significantly decreased postoperatively in overweight insulinoma patients, which was more evident in patients with higher BMI and metabolic comorbidities were largely improved.