Prognostic validation of the WHO 2010 grading system in pancreatic insulinoma patients.

The purpose of this study was to evaluate the prognostic potential of the World Health Organization (WHO) 2010 grading system in patients with pancreatic insulinomas. This was a retrospective study that analyzed the overall survival of 85 pancreatic insulinoma patients treated at our Institute between May 2002 and March 2013. The mean age of our patient cohort was 44.26 ± 13.82 years, with the gender split at 30 males and 55 females. Median survival time of the cohort, post-surgery, was 100.23 ± 18.18 months. Among the 85 patients, histopathological analyses revealed 52 Low Grade (G1) neuroendocrine tumors (NET), 23 Intermediate Grade (G2) NET, and 10 High Grade (G3) Neuroendocrine carcinomas (NEC) according to the WHO 2010 grading classification. Significant difference for overall survival was observed between the NET G1 and NEC G3 groups (P<0.01), and the NET G2 and NEC G3 groups (P<0.019). In addition, our data showed that overall survival was significantly correlated with the European Neuroendocrine Tumor Society (ENETS) tumor-node-metastasis (TNM) staging system, and in multivariate analysis, the diameter of tumor was found to be significantly correlated with survival (P=0.038). These findings provide additional validation for the prognostic value of using the WHO 2010 grading system, specifically with regard to pancreatic insulinomas.

Cushing Syndrome Caused by a Pancreatic Neuroendocrine Tumour and Its Pelvic Metastases.

Cushing's syndrome caused by an ectopic tumour secreting adrenocorticotropic hormone (ACTH) is not common. Furthermore, an ACTH-secreting panreatic neoplasm is extremely rare. We present a 27-year old female patient suffering from a pancreatic neuroendocrine tumour (p-NET) with extensive pelvic metastases, which could secrete ACTH and cause Cushing's syndrome. The postoperative pathologic examinations of this patient prompted pancreatic poorly differentiated neuroendocrine tumour with extensive metastases of bilateral ovarian, uterus and pelvic peritoneum. The immunohistochemical staining of her tumour tissues was positive for Chromogranin A, Synaptophysin and ACTH. The main aim of this article is to share the experience of her diagnosis and treatment and to review the relevant literature, with an emphasis on discussing the possible transfer modes. Moreover, we strongly suggest that a careful examination of pelvic cavity during the follow-up of patients diagnosed as ACTH-secreting p-NET should also be carried out.

Induction of diabetes in rhesus monkeys and establishment of insulin administration strategy.

OBJECTIVES: The diabetic rhesus monkey seems to be a useful model for preclinical investigations of islet transplantation and new drug treatments for type 1 diabetes mellitus (T1DM). Information is limited regarding a standard technique to induce and assess diabetes in rhesus monkeys as well as the strategy to apply insulin administration. Herein, we have established and characterized a model of diabetic rhesus macaques. METHODS: Four monkeys were divided into 2 groups of 2 each: group 1, total pancreatectomy; and group 2, partial pancreatectomy (75%) with low-dose streptozotocin (STZ) administration. Pancreatic function was measured using intravenous glucose tolerance tests before the operation. Spiral computed tomography (CT) scans of the pancreas were obtained before and after pancreatectomy. Fasting blood glucose and postprandial blood glucose levels were monitored twice daily using blood samples from the fingers or toes. Various types and doses of insulin were administered twice daily. We performed regular assessments of hematological and serum biochemical parameters, insulin, and C-peptide. RESULTS: Both total pancreatectomy and partial pancreatectomy (75%) with STZ administration induced T1DM in rhesus monkeys; there was interindividual variation in the STZ dose. Excluding C-peptide and insulin, the hematological and serum biochemical parameters did not differ significantly from normal values postoperatively. The various insulin treatment strategies are achieved stable blood glucose (BG) levels. CONCLUSIONS: STZ injection after partial pancreatectomy may be a safe, reproducible method to induce T1DM. Porcine insulin administration was a safe, economical method to control BG levels in a diabetic rhesus monkey before islet transplantation.

Evaluation of POSSUM in predicting post-operative morbidity in patients undergoing pancreaticoduodenectomy.

The Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) is a predictive scoring system for post-operative morbidity. The present study assessed the value of POSSUM in predicting post-operative morbidity following pancreaticoduodenectomy (PD). POSSUM scores were prospectively calculated for 265 consecutive cases of PD performed between 2005 and 2007. Expected morbidity was estimated based on POSSUM scores and was compared with observed morbidity. Patients were also stratified into one of four groups based on their individual POSSUM scores and subsequent risk of morbidity. Mean expected morbidity was 43.81% (116 cases) and mean observed morbidity was 39.62% (105 cases) (no statistically significant difference). It is concluded that the POSSUM scoring system has high value for predicting the risk of morbidity in PD patients.

Anti-CD25 mAb, anti-IL2 mAb, and IL2 block tolerance induction through anti-CD154 mAb and rapamycin in xenogeneic islet transplantation.

BACKGROUND: We have used anti-CD154 monoclonal antibody (mAb; MR1) and rapamycin (rapa) to induce tolerance to islet xenografts. The aim of this study was to investigate whether classical anergy and/or regulation by interleukin (IL)2-dependent CD25+ T regulatory cells played roles in the induction and maintenance of tolerance in this model. METHODS: Streptozotocin-induced diabetic mice were transplanted with rat islets. We performed the following groups: control group, islet transplantation without therapy; rapamycin group, 0.2 mg/kg by oral gavage on days 0, 1, 2, and every other day to day 14; anti-CD154 mAb (MR1) group, 0.5 mg intraperitoneally on days 0, 2, and 4; combination therapy group with rapa and MR1. We then administered in addition to the combination therapy with early (from days 0 to 14 [for IL2] or to 28 [for anti-IL2 mAb and anti-CD25 mAb] post-transplantation) or late (from days 100 to 114 [for IL2] or to 128 [for anti-IL2 mAb and anti-CD25 mAb] posttransplantation) recombinant IL2 (2000 U, intraperitoneally twice a day), a neutralizing anti-IL2 mAb (S4B6-1, 0.3 mg intraperitoneally twice weekly), and a depleting anti-CD25 mAb (PC61, 0.3 mg intraperitoneally twice weekly), respectively. Histology was performed at time of rejection. RESULTS: Rapa and MR1 therapy alone significantly prolonged xenograft survival compared to the control group: median graft survival was 34 days versus 17 days (P<.05) and 98 days versus 17 days (P<.05), respectively, but rejection still occurred. Combination therapy with MR1 and rapa allowed indefinite graft survival (median graft survival [MGS]>200 days, P<.001). When exogenous IL2 was administered early with MR1 and rapa, rapid rejection developed in 18 of 18 mice (MGS 7 days), whereas when IL2 was given late, only 3 of 10 developed rejection. Early administration of anti-IL2 mAb led to rejection in 10 of 10 mice (MGS 42 days), whereas late administration led to rejection in only one of four mice. Early administration of anti-CD25 mAb led to rejection in eight of nine mice (MGS 49 days), whereas late administration led to rejection in only three of seven mice. CONCLUSIONS: Rapa and MR1 allowed indefinite graft survival of islet xenografts. Classical anergy and regulation by IL2-dependent CD25+ T regulatory cells were critical in the induction of tolerance in the immediate posttransplantation period and less important for maintenance of tolerance.

Positron emission tomography modalities prevent futile radical resection of pancreatic cancer: A meta-analysis.

BACKGROUND: Numerous distant metastases were not detected preoperatively. Positron emission tomography (PET) has been used for oncology diagnosis recently. However, it remains controversial whether PET modality is a more efficient way in detecting unresectable features for radical resection of pancreatic cancer (PC). This meta-analysis aims to validate the efficiency of PET modalities (including PET and PET/CT) in preoperative assessment of PC, and compare them with computed tomography (CT). METHODS: PubMed, EMBASE, Science Citation Index and The Cochrane Library were searched to identify relevant studies. Both PET modality and CT had been performed for all the included patients. A meta-analysis was performed to compare the ability of PET modalities in detecting occult distant metastases and regional lymph nodes invasion with that of CT. RESULTS: 17 clinical studies that recruited 1343 patients were included. This meta-analysis indicated that PET modalities were more efficient in detecting true positive distant metastases compared with CT (OR = 1.52, 95%CI: 1.23-1.88). In subgroup analysis, when compared with CT alone, PET/CT also showed greater utility in detecting distant metastases (OR = 1.66, 95%CI: 1.31-2.08). There was no definite difference in detecting regional lymph nodes invasion between PET modalities and CT (OR = 0.97, 95%CI: 0.63-1.47). CONCLUSION: Compared with CT, PET/CT provides extensive possibility to avoid futile radical resection by detecting occult metastases of PC preoperatively. Surgeons, especially in developing countries, should take PET modalities as a routine preoperative assessment before making operative plan for PC patients.

Pancreatic Castleman's Disease: Studies of Three Cases And A Cumulative Review of the Literature.

Castleman's disease (CD) is a relatively rare and benign disorder. Pancreatic localization of CD is even more rare and is usually indistinguishable from pancreatic neoplasms. We report three cases of CD in which pancreas was all involved. One located in the tail of the pancreas, who accepted distal pancreatectomy, and the others in the head accepted enucleation. In addition, we review current data on its pathogenesis, imaging findings, diagnosis, differential diagnosis, and treatment.

The expression of ADAM12 (meltrin alpha) in human giant cell tumours of bone.

AIMS: To examine the expression of ADAM12 (meltrin alpha), a member of the disintegrin and metalloprotease (ADAM) family, in human giant cell tumours of the bone, skeletal muscle tissue from human embryos, and human adult skeletal muscle tissue. METHODS: ADAM12 mRNA was detected by reverse transcription polymerase chain reaction and in situ hybridisation. RESULTS: ADAM12 mRNA was detected in 14 of the 20 giant cell tumours of bone and in three of the six tumour cell cultures. The expression of ADAM12 in cells cultured from the tumour was linked to the presence of multinucleated giant cells. ADAM12 mRNA could not be detected in the five adult skeletal muscle tissue samples, although it was found in the two embryonic skeletal muscle tissue samples. ADAM12 mRNA was localised to the cytoplasm of multinucleated giant cells and some mononuclear stromal cells. CONCLUSIONS: These results indicate that multinucleated giant cells are formed by the cell fusion of mononuclear stromal cells in giant cell tumours of bone and that ADAM12 is involved in the cell fusion process.