Wenming Wu

Glucagon-Like Peptide-1 Receptor PET/CT with 68Ga-NOTA-Exendin-4 for Detecting Localized Insulinoma: A Prospective Cohort Study

Preoperative localization of insulinoma is a clinical dilemma. We aimed to investigate whether glucagon-like peptide-1 receptor (GLP-1R) PET/CT with 68Ga-NOTA-MAL-cys40-exendin-4 (68Ga-NOTA-exendin-4) is efficient in detecting insulinoma. Methods: In our prospective cohort study, patients with endogenous hyperinsulinemic hypoglycemia were enrolled. CT, MRI, endoscopic ultrasound, and 99mTc-hydrazinonicotinamide-TOC SPECT/CT were done according to standard protocols. GLP-1R PET/CT was performed 30–60 min after the injection of 68Ga-NOTA-exendin-4. The gold standard for diagnosis was the histopathologic results after surgery. Results: Of 52 recruited patients, 43 patients with histopathologically proven insulinomas were included for the imaging studies. Nine patients did not undergo surgical intervention. 68Ga-NOTA-exendin-4 PET/CT correctly detected insulinomas in 42 of 43 patients with high tumor uptake (mean SUVavg ± SD, 10.2 ± 4.9; mean SUVmax ± SD, 23.6 ± 11.7), resulting in sensitivity of 97.7%. In contrast, 99mTc-hydrazinonicotinamide-TOC SPECT/CT showed a low sensitivity of 19.5% (8/41) in this group of patients; however, it successfully localized the tumor that was false-negative with GLP-1R PET/CT. The sensitivities of CT, MR, and endoscopic ultrasonography were 74.4% (32/43), 56.0% (14/25), and 84.0% (21/25), respectively. Conclusion: 68Ga-NOTA-exendin-4 PET/CT is a highly sensitive imaging technique for the localization 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.

68Ga-NOTA-exendin-4 PET/CT in detection of occult insulinoma and evaluation of physiological uptake

A 52-year-old man who had hypoglycaemia for 8 years was found to have endogenous hyperinsulinism indicating an insulinoma. Abdominal MRI, CT perfusion, endoscopic ultrasonography, and Tc-HYNIC-TOC SPECT/CT were negative. Thus, the patient was referred for Ga-NOTA-exendin-4 PET/CT with the approval of the Institutional Review Board of our hospital. As well as the intense physiological distribution in the kidneys and bladder due to urinary excretion, moderately elevated uptake is apparent in the proximal duodenum (a–c long arrows, SUVmax 5.2) and pancreas (SUVmax 2.9) at 1 h after injection of Ga-NOTAexendin-4. Because visualization of the pancreas tail was significantly influenced by the intense radioactivity in the left kidney, the patient was reimaged at 2 h after injection. A lesion with intense uptake (SUVmax 20.7) was clearly seen in the pancreas tail (d, e short arrows). Interestingly, radioactivity in the proximal duodenum significantly decreased (d, e long arrows, SUVmax 2.3) while the appearance of the normal pancreas remained unchanged. The patient recovered from hypoglycemia after surgical removal of the pancreas tail insulinoma (WHO grade 1). Intraoperative ultrasonography excluded a duodenal tumor. Glucagon-like peptide-1 receptor (GLP-1R) is highly overexpressed in insulinoma [1, 2]. SPECT/CT imaging of GLP-1R using In-labelled or Tc-labelled exendin-4 has been shown to be highly accurate in the detection of insulinoma [2–4]. However, PET/CT imaging of GLP-1R has rarely been reported [5]. We present the first successful use of Ga-NOTA-exendin-4 PET/ CT for the identification of an occult insulinoma that could not be detected by other standard imaging methods. Ga-NOTAexendin-4 also shows great potential for evaluation of pancreatic physiology due to its uptake, presumably, by islet cells. Yaping Luo and Miao Yu contributed equally to the article.

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.

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.

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.

Pancreatic panniculitis associated with pancreatic carcinoma: A case report.

Introduction: Pancreatic panniculitis is a very rare complication of pancreatic cancer, most often accompanying rare acinar cell carcinoma. We herein report a case of pancreatic panniculitis that was associated with pancreatic mucinous adenocarcinoma. Patient information: A 57-year-old male was referred to our hospital for weight loss. A physical examination revealed subcutaneous nodules on his lower extremities. The blood test showed abnormal increases in amylase, lipase, and carbohydrate antigen 19–9 levels. A computed tomography scan detected a hypodense 2 × 1.5 cm solid mass with an unclear margin in the head of the pancreas. The biopsy of subcutaneous nodules on the lower extremities was conducted and revealed lobular panniculitis. Pancreatic cancer and pancreatic panniculitis were strongly suspected. After the administration of octreotide acetate and the Whipple procedure, the serous amylase and lipase levels returned to normal, and the pancreatic panniculitis had almost resolved by 4 weeks later. Conclusion: Pancreatic panniculitis is a rare complication of pancreatic cancer. However, in the presence of a pancreatic mass, as in this case, clinicians should be aware that panniculitis may be the sentinel of pancreatic carcinoma.

Advances in understanding the molecular mechanism of pancreatic cancer metastasis

BACKGROUND Pancreatic cancer (PC) is usually diagnosed at the late-stage and therefore, has widespread metastasis and a very high mortality rate. The mechanisms underlying PC metastasis are not well understood. Recent advances in genomic sequencing have identified groups of gene mutations that affect PC metastasis, but studies elucidating their roles are lacking. The present review was to investigate the molecular mechanisms of PC metastasis. DATA SOURCES Relevant articles on PC metastasis were searched in MEDLINE via PubMed prior to April 2015. The search was limited in English publications. RESULTS PC metastatic cascades are multi-factorial events including both intrinsic and extrinsic elements. This review highlights the most important genetic alterations and other mechanisms that account for PC invasion and metastasis, with particular regard to epithelial-mesenchymal transition, inflammation, stress response, and circulating tumor cells. CONCLUSIONS Analyses of relevant gene functions and signaling pathways are needed to establish the gene regulatory network and to define the pivotal modulators. Another promising area of study is the genotyping and phenotyping of circulating tumor cells, which could lead to a new era of personalized therapy by identifying specific markers and targets.