Insulinoma Research Articles

68Ga-exendin-4 PET/CT for the localization of insulinomas

Objective To determine whether glucagon-like peptide-1 (GLP-1) receptor PET/CT with 68Ga-exendin-4 is accurate in localizing insulinomas, by comparing with conventional imaging techniques. Methods In this prospective cohort study, patients with biochemically proven endogenous hyperinsulinemic hypoglycemia from March 2014 to November 2016 were recruited consecutively. 68Ga-exendin-4 PET/CT, CT, MRI, endoscopic ultrasound (EUS), and SSTR imaging were performed before elective surgery. Surgical pathology results were considered as the gold standard. Sensitivity based on patient-analysis and positive predictive value (PPV) based on lesion-analysis were calculated and compared using χ2 test and generalized score test. Results A total of 109 patients were recruited (47 males, 62 females; average age (45.1±14.8) years), and 96 of them with insulinomas proved pathologically were included in the main assessment. Thirteen patients with positive 68Ga-exendin-4 PET/CT findings did not undergo surgical intervention. Based on patient-analysis, the sensitivities of 68Ga-exendin-4 PET/CT, CT, MRI, EUS and SSTR imaging for detecting insulinomas were 98.96%(95/96), 81.25%(78/96), 79.41%(54/68), 81.40%(35/43) and 21.84%(19/87), respectively. Based on lesion-analysis, the PPV of the above 5 methods were 100%(102/102), 97.56%(80/82), 95.16%(59/62), 83.72%(36/43) and 90.48%(19/21), respectively. 68Ga-exendin-4 PET/CT showed the highest diagnostic sensitivity than others (all P<0.01) and higher PPV than MRI, EUS and SSTR imaging (all P<0.05). Conclusion 68Ga-exendin-4 PET/CT is a highly sensitive imaging technique for detection of insulinoma. Key words: Insulinoma; Positron-emission tomography; Tomography, X-ray computed; Glucagon-like peptide 1; Gallium radioisotopes

Radiofrequency ablation for pancreatic insulinoma: an accident or not

Insulinoma is the most common functional pancreatic neuroendocrine tumor. Surgical removal or enucleation is the most commonly used treatment. Insulinomas are usually benign, solitary and small. So they are theoretically the good indication for radiofrequency ablation (RFA) treatment. In 2009, Limmer et al ever reported the first case of insulinoma who were successfully treated by RFA. To date, 5 similar articles in English have been published, reporting 7 cases in total. In the recent year, we successfully treated 2 cases with insulinoma (one in pancreatic cauda and the other in pancreatic body). All the 2 cases got complete remission with quick alleviation of clinical symptoms and without complications. The data of these 9 cases showed that RFA is a safe and effective treatment for insulinoma, and for selected patients, it can be recommended as a treatment of first choice. Key words: Insulinoma; Radiofrequency ablation; Laparoscopy; Safety; Efficacy

Application of dynamic glucose monitoring in the diagnosis and differential diagnosis of hypoglycemia

Objective To analyze the characteristics of dynamic blood glucose in hypoglycemia patients with different causes and explore the application value of dynamic glucose monitoring system (DGMS) in the diagnosis and differential diagnosis of hypoglycemia. Methods We used DGMS to monitor the blood glucose levels of 20 hypoglycemia patients for 3-6 days, including 6 cases of insulinoma, 7 cases of reactive hypoglycemia, 2 cases of autoimmune hypoglycemia, 3 cases of islet cell hyperplasia, 1 case of drug-induced hypoglycemia, 1 case of congenital hyperinsulinism. The blood glucose profiles of hypoglycemia patients with different causes were compared. Results The average monitoring duration was (88.9±10.8)hours. 38-936 points of hypoglycemia were detected in these patients with hypoglycemia. The average blood glucose of patients of each cause, in the order from low to high, were: congenital hyperinsulinism [(2.97±0.59)mmol/L], islet cell hyperplasia [(4.83±1.32)mmol/L], insulinoma [(4.87±1.37)mmol/L], drug-induced hypoglycemia [(5.98±0.8)mmol/L], reactive hypoglycemia [(6.38±1.99)mmol/L], and autoimmune hypoglycemia [(7.63±2.67)mmol/L]. The constituent ratio of hypoglycemia from low to high were: autoimmune hypoglycemia and drug-induced hypoglycemia (0%), reactive hypoglycemia [0.5% (0.0%, 1.6%), insulinoma [9.0% (5.2%, 16.3%), islet cell hyperplasia [9.5% (1.1%, 14.2%), congenital hyperinsulinism (58.5%). In terms of the blood glucose profiles in day and night, the night blood glucose levels were lower than those in daytime in insulinoma [(5.16±1.37)mmol/L vs. (4.44±1.24)mmol/L], reactive hypoglycemia [(6.93±2.19)mmol/L vs. (5.57±1.25)mmol/L], autoimmune hypoglycemia [(8.08±2.79)mmol/L vs. (6.95±2.31)mmol/L], islet cell hyperplasia [(5.23±1.31)mmol/L vs. (4.11±1.00)mmol/L] and congenital hyperinsulinism [(3.06±0.57)mmol/L vs. (2.83±0.59)mmol/L] (all P<0.05); while the daytime blood glucose level was lower than that at night in drug-induced hypoglycemia [(5.90±0.81)mmol/L vs. (6.11±0.77)mmol/L, P<0.05]. 62.2% and 78.9% of the hypoglycemia episodes happened at night in patients with insulinoma and islet cell hyperplasia, and 43.2% at night in patients with congenital hyperinsulinism. The highest standard deviation of blood glucose (2.67 mmol/L), largest amplitude of glycemic excursions (9.2 mmol/L)and coefficient of variation (35%) were found in patients with autoimmune hypoglycemia. The largest range of blood glucose (20.4 mmol/L) was found in patients with reactive hypoglycemia. The day-night differences in coefficient of variation (31.6% vs. 22.4%) and range of blood glucose (20.4 mmol/L vs. 6.8 mmol/L) were most prominent in patients with reactive hypoglycemia. Conclusion The dynamic monitoring of blood glucose and the analysis of the parameters such as average blood glucose, blood glucose profiles and variability of blood glucose may be helpful for the diagnosis of hypoglycemia and differential diagnosis of causes of hypoglycemia. Key words: Hypoglycemia; Insulinoma; Dynamic glucose monitoring system; Continuous glucose monitoring system; Reactive hypoglycemia; Differential diagnosis

Application of comprehensive nursing intervention on the management of blood su-gar of the patients with insulinoma

Objective To explore the application value of comprehensive nursing intervention on the management of blood sugar of the patients with insulinoma. Methods A total of 50 cases of patients with insulinoma in our hospital from August 2010 to December 2015 were selected as the research objects and were divided into observation group and control group according to their orders of admission, 25 cases in each group.The control group received conventional nursing intervention, while the observation group received comprehensive nursing intervention.The mean of blood sugar for 24 hours, the standard deviation, the maximum of blood sugar, the minmum of blood sugar, the maximum amplitude range, the occurance of hypoglycemia and the duration time of the two groups were recorded by CGMS. Results The average blood sugar of the observation group was (4.94±1.39)mmol/L, which was significantly higher than that (t=4.263, P<0.05)of the control group.The standard deviation and the maximum amplitude range of the observation group was (1.36±0.45) and (6.58±3.14)mmol/L respectively, which were signicantly lower than that of the control group(t=4.179、6.924, P<0.05). Conclusion The blood sugar can be better controlled by providing comprehensive nursing intervention to insulinoma patients on the basis of conventional nursing. Key words: Insulinoma; The management of blood sugar; Comprehensive nursing intervention; Hypoglycemia

The application of dynamic blood glucose monitoring on patients with insulinoma

Objective To explore the application value of dynamic blood glucose monitoring in the blood glucose monitoring for patients with insulinoma. Methods A total of 16 patients with insulinoma treated in our hospital from October 2013 to December 2015 were taken as the observation group.While 15 cases with hypoglycemia caused by the type 2 diabetic reaction were taken as the diabetic group and 15 cases of normal healthy volunteers as control group.Three groups all received 72 hours dynamic blood glucose monitoring.The general information, the mean value of 24 hours blood glucose, the standard deviation of the blood glucose, the maximum of the blood sugar, the minimum of the blood sugar, the maximum fluctuation range and the frequency and duration of hypoglycemia were compared. Results The BMI index and insulin releasing index of the observation group were significantly higher than that of the diabetic group and the control group (P<0.05). The HbAlc of diabetic group was significantly higher than that of the observation group and control group (t=4.615, 4.273, P<0.05), while the MAD of the diabetic group was significantly lower than that of the observation group and control group (t=5.124, 5.238, P<0.05). The 72-hour starvation-exercise test found 13 positive cases and 3 negative cases in the observation group.The average blood glucose and blood glucose of the observation group were (4.69 + 1.53) mmol/L and (2.46 + 0.29) mmol/L respectively, which were significantly lower than that of the diabetic group and the control group (P<0.05). The maximum blood glucose level and the maximum fluctuation range of the observation group were significantly lower than that of the diabetic group, which were significantly higher than that of the control group (P<0.05). The frequency of hypoglycemia of observation group was significantly higher than that of the diabetic group and the duration of hypoglycemia was significantly longer than that of the diabetic group (P<0.05). Conclusion Dynamic blood glucose monitoring can better reflect the dynamic changes of blood glucose of patients with insulinoma, which shows a strong application value. Key words: Insulinoma; Blood glucose monitoring; Dynamic blood glucose monitoring; Application value

Insulinoma misdiagnosed as alcohol induced hypoglycaemia

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Palpitation, tremble, sweaty, and weight gain——Localization of insulinoma

A 47 years old female presented with palpitation, tremble, sweaty, and weight gain. Insulinoma was suspended and confirmed with hypoglycemia caused by endogenous hyperinsulinemia. The CT scan was failed to localize the tumor. MRI and ASVS showed inconsistent results. A nutrient arterial was found by arterial angiography and explained the different results. Robert assistant surgery successfully removed the tumor and the patient was well recovered. (Chin J Endocrinol Metab, 2016, 32: 696-699) Key words: Insulinoma; Localization diagnosis; Selective Arterial Calcium Stimulation hepatic Venous Sampling; Arterial angiography

Identification of CD90 as Putative Cancer Stem Cell Marker and Therapeutic Target in Insulinomas.

The long-term prognosis after surgical resection of malignant insulinoma (INS) is poor. Novel adjuvant therapies, specifically targeting cancer stem cells (CSCs), are warranted. Therefore, the goal of this study was to characterize and target putative INS CSCs. Using fluorescence-activated cell sorting, human INS cell line CM and pancreatic carcinoid cell line BON1 were screened for the presence of stem cell-associated markers. CD90, CD166, and GD2 were identified as potential CSC markers. Only CD90(+) INS cells had an increased tumor-initiating potential in athymic nude mice. Anti-CD90 monoclonal antibodies decreased the viability and metastatic potential of injected cells in a zebrafish embryo INS xenograft model. Primary INS stained positive for CD90 by immunohistochemistry, however also intratumoral fibroblasts and vascular endothelium showed positive staining. The results of this study suggest that anti-CD90 monoclonals form a potential novel adjuvant therapeutic modality by targeting either INS cells directly, or by targeting the INS microenvironment.

Efficacy of EUS-guided ethanol ablation in the treatment of insulinoma

Objective To evaluate the safety and efficacy of endoscopic ultrasonography (EUS) guided ethanol ablation in patients with insulinoma. Methods The data of 10 patients with insulinoma treated at the First Affiliated Hospital of Guangxi Medical University from December 2013 to January 2015 were prospectively analyzed. Results The patients were given EUS-guided ethanol ablation with dose of 0.10 to 2.00 ml (average 0.70 ± 0.62 ml) in pancreatic lesions for 15 times. No complications were observed during and after the procedure. The blood glucose improved after the procedure [4.8(3.9-5.5) mmol/L VS 2.4(1.9-2.5) mmol/L, P<0.05] and the serum insulin level significantly decreased[83.7(40.1-143.5) pmol/L VS 177.3(66.5-200.6) pmol/L, P<0.05]. The average hospital stay was (4.3±1.5) days. The patients were followed up for 6-12 months. EUS indicated that the echo of pancreatic lesions changed from high to low. CE-EUS revealed low enhancement and lack of blood supply. Conclusion EUS-guided ethanol ablation may become a promising minimally invasive treatment for insulinoma because of its safety, efficacy and low price. Trail registration Clinical Trial.gov, NCT02121366 Key words: Insulinoma; EUS; Alcohol injection; Efficacy

Combination of intraoperative ultrasonography for localizing insulinoma under Da Vinci robotic surgical system: experience of a single center in 50 cases

To evaluate the effect and safety of enucleation of insulinoma under the Da Vinci robotic surgical system combination with intraoperative ultrasonography(IOUS) for the localization. The clinical materials of 50 insulinoma cases which underwent IOUS and assisted by the robotic surgical system from September 2012 to September 2014 in Peking Union Medical College Hospital were reviewed retrospectively. The patients were followed up by outpatient review and telephone until October 2014. The diagnostic accuracy rate, operation time, blood loss, complications and cure rate were analyzed by t-test. The locations of tumors were 13 in the head, 21 in the body and 13 in the tail of pancreas, 2 were multiple insulinoma, 1 was ectopic to mesenterium.The average operation time was 142 minutes; the average blood loss was 165 ml.Three(6.0%) patients were transformed to open.One patient experienced postoperative bleeding about 300 ml on the 7(th) day after operation and no infection and perioperative death.Thirty-five cases were of class A and 14 of class B according to the clinical grading of postoperative pancreatic fistula.The blood glucose 60 minutes after tumor dissection was significantly elevated than that before operation ((6.2±1.8)mmol/L vs.(3.7±1.2)mmol/L)(t=-6.89, P<0.01). The cure rate was 100% as all the patients' symptoms were disappeared during follow-up time. Combination IOUS is a highly sensitive method for the localization of insulinoma, which is helpful in localizing tumors precisely in insulinoma cases assisted by robotic surgical system and shortening operation time.It is safe and effective for insulinoma enucleation.

Diagnosis and management of insulinoma: current best practice and ongoing developments

Insulinoma is a predominantly benign and rare neuroendocrine tumor. Patients with insulinoma typically present with neurologic symptoms from hypoglycemia, such as confusion, dizziness, and behavioral changes, as well as symptoms from a surge in catecholamine levels, such as palpitations, diaphoresis, and tachycardia. Symptomatic patients usually have glucose levels below 55 mg/dL and are relieved of their symptoms when carbohydrate is administered. The 48-hour test, performed by measuring blood glucose levels of insulin, C peptide, and proinsulin collected every 4-6 hours in fasting patients, accurately confirms the diagnosis of insulinoma in the majority of the patients. Once the diagnosis is confirmed, the next step in management involves identifying the location of the tumor and successfully removing it surgically. In the last two decades, clinicians have moved away from invasive angiography for preoperative localization. A multiphase computed tomography (CT) can be used to localize the lesion and evaluate for metastasis. If CT does not detect the lesion, selective arterial calcium stimulation test is recommended to identify the region of the lesion in the pancreas. Some argue that all preoperative localization techniques are superfluous. The combination of intraoperative ultra - sound and operative palpation has led to a nearly 100% success rate. Recently, in select cases, laparoscopic enucleations and resections of insulinomas have been performed with shorter length of stay and faster recovery time. Despite advances in imaging, a little over 10% of insulinoma patients undergo reexploration for missing lesions. Patients who are not candidates for tumor resections or awaiting surgery have had symptomatic relief from diazoxide and somatostatin analogs among various medical therapies. In patients with metastatic insulinoma, progression- free survival and overall survival are reported from newly approved chemotherapeutic agents. Liver-directed therapies, such as ablation and selective radiation, and cytoreductive surgery have also been performed for symptom control and prolonging survival.

A Man With Whipple’s Triad Secondary to a Malignant Insulinoma

Insulinomas are neuroendocrine tumors of the pancreas that are derived from the beta cells and secrete insulin. They are rare and most are benign growths within the pancreas. We present a patient who had a long history of symptoms suggestive of recurrent fasting hypoglycemia and was subsequently found to have a small malignant insulinoma within his pancreas requiring extensive surgery. J Med Cases. 2015;6(7):307-308 doi: http://dx.doi.org/10.14740/jmc2175w

Diagnosis and treatment of space-occupying lesions of the head of pancreas

Objective To investigate the experiences in the diagnosis and treatment of space-occupying lesions of the head of pancreas.Methods The clinical data of 247 patients with space-occupying lesions of the head of pancreas who were admitted to the First Affiliated Hospital of Chinese Medical University from January 2011 to April 2014 were retrospectively analyzed.All the patients received enhanced computed tomnography and (or) magnetic resonance imaging of the pancreas.The levels of alpha-fetal protein (AFP),CA19-9,CA125 and carcinoembryonic antigen (CEA) were detected,and the serum level of IgG4 was detected in patients who were suspected of autoimmune pancreatitis.Intraoperative pathological examination was applied to patients who were diagnosed as with cancer of the head of pancreas.Pancreaticoduodenectomy,extended pancreaticoduodenectomy or bilio-jejunostomy or (and) gastrointestinal anastomosis were applied to patients according to the stage and infiltration of the tumor.Duodenum-preserving pancreatic head resection or pancreaticoduodenectomy could be selected after informed consent.The adjacent tissues and organs should be preserved on the premise of complete tumor resection for patients with benign and low-grade malignancy.Results A total of 194 patients had solid spaceoccupying lesions of the head of pancreas,including 125 with pancreatic head cancer,45 with mnass in the head of pancreas,9 with chronic pancreatitis with mass in the head of pancreas,11 with autoimmune pancreatitis,4 with insulinoma.Fifty-three patients were with cystic space-occupying lesions,including 12 with mucinous cystadenoma,8 with serous cystadenoma,17 with pancreatic cyst,12 with solid-pseudopapillary tumor of pancreas and 4 with intraductal papillary mucinous neoplasm.The positive rates of AFP,CA19-9,CA125 and CEA of the 71 patients who were confirmed as with pancreatic cancer by pathological examination were 7.0％ (5/71),94.4％ (67/71),42.3％ (30/71) and 0,respectively.The positive rates of AFP,CA19-9,CA125 and CEA of the 12 patients with chronic pancreatitis with mass in the head of pancreas were 1/12,4/12,1/12 and 0,respectively.Seventynine patients with pancreatic head cancer,mass in the head of pancreas and chronic pancreatitis with mass in the head of pancreas received intraoperative pathological examination.A total of 119 patients received operation,including 71 with pancreatic head cancer,7 with chronic pancreatitis with mass in the head of pancreas,4 with insulinoma,1 with pancreatic tuberculosis,8 with mucinous cystadenoma,4 with serous cystadenoma,6 with pancreatic pseudocyst,1 with huge lymphangioma,1 with lymphoepithelial cyst,12 with solid-pseudopapillary tumor of pancreas and 4 with intraductal papillary mucinous neoplasm.Of the 247 patients with space-occupying lesions of the head of pancreas,61 received pancreaticoduodenectomy,4 received duodenum-preserving pancreatic head resection,4 received pancreatic head and neck resection,2 received partial resection of the uncinate process of the pancreas,9 received enucleation of the tumor,38 received bilio-jejunostomy or (and) gastrointestinal anastomosis,22 received endoscopic retrograde cholangio-pancreatography + stent installation,18 received percutaneous transhepatic cholangial drainage + stent installation,1 received exploratory lapartomy and the other 88 patients were untreated.Conclusions The diagnosis and differential diagnosis of the space-occupying lesions of the head of pancreas depend on the clinical presentation,medical history,laboratory examination,sonography,computed tomography or magnetic resonance imaging.Individualized treatment plan based on the feature of the tumor and kinds of the lesions combined with intraoperative pathological examination is helpful for selecting the surgical procedures. Key words: Space-occupying lesions of the head of pancreas; Carcinoma of the head of pancreas; Chronic pancreatitis with mass in the head of pancreas; Diagnosis; Treatment

Value of the combination of multi-slice spiral computed tomography perfusion scan and intraoperative ultrasonography for localizing insulinoma in the da Vinci robotic surgical system

Objective To investigate the value of the multi-slice spiral computed tomograpby (MSCT) perfusion scan and intraoperative ultrasonography (IOUS) for localizing insulinoma in the da Vinci robotic surgical system.Methods The clinical data of 20 patients with insulinoma who were admitted to the Peking Union Hospital from July 2013 to July 2014 were retrospectively analyzed.The condition of the patients was evaluated by MSCT perfusion scan before operation,and the tumor was located by uhrasonograhy during the operation.The operation methods were selected according to the location of the tumors.The diagnostic accuracy of the MSCT perfusion scan and IOUS for locating insulinoma was analyzed,and the operation time,volume of intraoperative blood loss,perioperative complications,pre-and postoperative levels of blood glucose were recorded.Patients were followed up via out-patient cxamination and phone call till July 31,2014.The count data were presented by x ± s and were analyzed using the t test.Results Twenty-one insulinomas were detected in the 20 patients.The accurate rate of the MSCT perfusion scan was 90.0％ (18/20) in locating the tumor,and the accurate rate of the MSCT perfusion scan and intraoperative ultrasonography was 100.0％ (20/20).The blood flow,blood volume,permeability were (97 ±37)mL/(100 mL · min),(20 ± 14)mL/100 mL and (38 ±22)mL/(100 mL · min) in the normal pancreatic tissues,and (170 ±50)mL/(100 mL · min),(26 ± 14) mL/100 mL and (51 ±42)mL/(100 mL · min)in the tumor tissues.The blood flow of the tumor tissues was significantly higher than that of the normal pancreatic tissues (t =5.58,P ＜0.05),while no significant difference was detected in the blood volume and permeability between the tumor tissues and the normal pancreatic tissues (t =1.31,1.18,P ＞ 0.05).Eleven insulinomas were located at the head of the pancreas,6 at the body of the pancreas and 4 at the tail of the pancreas.Of the 20 patients,19 received enucleation of the insulinoma in the da Vinci robotic surgical system (1 of the them was converted to open surgery),and 1 patient received spleen-preserving distal pancreatectomy in the da Vinci robotic surgical system.The operation time and median volume of blood loss were (146 ±54) minutes and 50 mL (range,20-1 000 mL),respectively.No complications such as bleeding,infection or death occurred after the operation.Eleven patients were complicated with grade A pancreatic fistula and 9 with grade B pancreatic fistula.The levels of blood glucose before operation and at 60 minutes after the operation were (3.8 ± 1.0) mmol/L and (6.4 ± 1.8) mmol/L,with significant difference (t =6.69,P ＜ 0.05).The symptoms were dismissed at the deadline of the follow-up,with the remission rate of 100.0％ (20/20).Conclusion Combination of MSCT perfusion scan and IOUS could improve the diagnostic rate of insulinoma,and significantly increase the efficacy of da Vinci robotic surgical system for treating insulinoma. Key words: Insulinoma; Multislice spiral computed tomography perfusion scan; Intraoperative ultrasonography; Da Vinci robotic system

Insulinomatosis: a case report and review of literature

Objective To analyze the clinical and pathological characteristics of insulinomatosis,and to improve the awareness of the disease.Methods The clinical and pathological characters of a case of insulinomatosis diagnosed in Chinese PLA General Hospital and the pertinent literatures were analyzed and summarized.Results (1) Insulinomatosis mostly occurs in females and rarely develops metastases,the patients are considerably younger at diagnosis.The rate of recurrent hyper-insulinemic hypoglycemia episodes in insulinomatosis is higher than that in sporadic solitary insulinoma and MEN related insulinoma.(2) The typical character of insulinomatosis is the synchronous and metachronous occurrence of insulinomas.Micro-adenoma,macro-adenoma and insulin-expressing monohormonal endocrine cell clusters (IMECCs) can be found in the pathological photograph.(3) Total pancreatectomy was the bcst choice to treat insulinomatosis.(4) The etiology of insulinomatosis was still unclear,no MEN-1 mutation was found.Conclusion Insulinomatosis is characterized by the synchronous and metachronous occurrence of insulinomas,multiple insulinoma precursor lesions,and recurrent hypoglycemia. Key words: Insulinomatosis ; Hyperinsulinemic hypoglycemia; Insulinoma

The left anterior pararenal space approach in laparoscopic distal pancreatectomy with splenic preservation

Objective To explore the safety of the left anterior pararenal space approach in laparoscopic distal pancreatectomy with splenic preservation.Methods 30 patients operated between August 2008 and September 2013 were retrospectively reviewed.Results Of the 30 patients,28 underwent laparoscopic distal pancreatectomy with preservation of splenic artery and vein,2 underwent laparoscopic distal pancreatectomy with division of the splenic artery and vein and preservation of the short gastric vessels.All the 30 patients had their operations carried out successfully with an average operative time of (55 ± 38) min,blood loss (100 ± 48) ml and duration of hospitalization 7.8 d.Pancreatic fistula occurred in 2 patients and it healed spontaneously on drainage.Partial splenic infarction occurred in 1 patient.The pathological lesions were serous cystadenoma in 6 patients,mucinous cystadenoma in 6 patients,insulinoma in 5 patients,solid pseudopapillary tumor in 6 patients,chronic pancreatitis presenting as a mass in 3 patients,and pancreatic cyst in 4 patients.Conclusions The left anterior pararenal space approach was safe and efficacious in distal pancreatectomy with splenic preservation.If the pancreatic lesion was big and compressed the splenic artery and vein,laparoscopic distal pancreatectomy with division of the splenic artery and vein and preservation of the short gastric vessels was the procedure of choice. Key words: Pancreatic neoplasms ; Pancreatectomy; Preservation of spleen; Operating approach

Suppressor of cytokine signaling 1 protects rat pancreatic islets from cytokine-induced apoptosis through Janus kinase/signal transducers and activators of transcription pathway.

Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathway involved in negative feedback loops. Although SOCS1 is an important intracellular suppressor of apoptosis in a variety of cell types, its role in cytokine-induced pancreatic β-cell apoptosis remains unclear. The present study investigated potential effects of SOCS1 on the cytokine-induced pancreatic β-cell apoptosis. After successfully transfected with SOCS1/pEGFP-C1 or pEGFP-C1 plasmids to overexpress SOCS1, RINm5F (rat insulinoma cell line) cells were exposed to cytokines, interferon (IFN)-γ alone, IFN-γ+interleukin (IL)-1β, IFN-β+IL-1β+tumor necrosis factor (TNF)-α respectively. Pancreatic β-cell apoptosis was assessed by using MTT, FACS, and caspase-3 activity assays. Protein phosphorylation of Janus kinase 2 (JAK2) and signal transducers and activators of transcription 1 (STAT1) were verified by Western blotting and mRNA expression of inducible nitric oxide synthase (iNOS), NF-κB and Fas were analyzed by RT-PCR. Overexpression of SOCS1 in RINm5F cells was shown to attenuate IFN-γ alone, IFN-γ+IL-1β and IFN-γ+TNF-α+IL-1β mediated apoptosis. Phosphorylation of JAK2 and STAT1 significantly decreased in RINm5F cells which overexpressed SOCS1 protein. Overexpression of SOCS1 significantly suppressed cytokine-induced iNOS mRNA levels. Overexpression of SOCS1 protects pancreatic islets from cytokine-induced cell apoptosis via the JAK2/STAT1 pathway.

Emerging therapies for pancreas neuroendocrine cancers.

Neuroendocrine tumors (NET) are rare malignancies, with the most common site of origin being from the gastrointestinal tract, particularly the pancreas, small bowel and appendix. Pancreatic neuroendocrine tumors can be functional, i.e., hormone secreting tumors, e.g., insulinoma, gastrinoma or VIPoma, and can have distinctive symptoms leading to the diagnosis. In contrast nonfunctional tumors, the majority of PNET's, usually present later either incidentally or due to tumor bulk symptoms. The recent WHO classification system in 2010 classified PNET's into different stages and grades depending on the mitotic activity and Ki-67 labeling index. PNET's have a broad range of prognoses depending on the histologic grade, differentiation and biologic behavior. Computerized tomographic scanning (CT), magnetic resonance imaging (MRI) and octreoscan are imaging tools used to diagnose PNET, in addition to a confirmatory tissue diagnosis with immunohistochemical stains, typically obtained by either cytologic or histologic assessment. Symptomatic advanced PNET's can be treated with a long-acting somatostatin analogue for those tumors with somatostatin receptor positivity and which may also have antiproliferative activity. Another treatment modality is peptide receptor radionucleotide therapy (PRRT) in somatostatin receptor-positive tumors, albeit as yet with limited availability in the United States. Systemic therapies with combination cytotoxic agents e.g., streptozocin, anthracyclines, and capecitabine and temozolomide, all have established activity in PNET's. Biologic agents targeting the VEGF and mTOR signaling pathways, e.g., sunitinib, bevacizumab or everolimus are becoming integrated as treatments for PNET's. Poorly differentiated, high grade PNETs with a very high mitotic rate are treated with platinum-based chemotherapy regimens similar to treatment paradigms for small cell carcinoma of the lung. For liver confined or predominant disease, strategies such as cytoreductive surgery, hepatic artery embolization or radioembolization are treatment modalities to effect locoregional tumor control. The next generation of studies in PNET will help define optimal sequencing strategies of available therapies and also will attempt to use biomarker-guided approaches to select therapies.

Etiologies of patients admitted to emergency department with hypoglycemia

Hypoglycemia is the most common endocrinologic problem seen in emergency departments. To explore its causes in patients who admitted to the emergency department with symptoms resembling hypoglycemia, 225 hypoglycemia cases were evaluated from January 2000 to May 2008. Of 225 hypoglycemia cases, 158 (70.2%) were receiving treatment for diabetes mellitus, which was the most common group (94 patients were using insulin, 55 were receiving oral anti-diabetics (OAD) and 9 patients both OAD and insulin). The other causes for hypoglycemia were as follows: reactive hypoglycemia cases (11.6%), insulinoma (2.7%), malignancies (2.2%), Sheehan syndrome (0.9%), chronic liver disease (0.9%), gestational diabetes mellitus (0.4%), OAD use by mistake (3.6%), and use of OAD for suicidal purposes (13%). In eight of the cases, the reason could not be identified. The study revealed that diabetes mellitus constitute the most common reason for hypoglycemia among the patients seen in emergency departments. Efforts should be made to prevent hypoglycemia by giving the patients better education. Key words: Emergency department, hypoglycemia, endocrine emergency.

Expression and distribution of N-myc downstream regulated gene 2 in pancreatic diseases

The pancreatic tissues from patients with islet cell hyperplasia,insulinoma,and pancreatic adenocarcinoma,as well as normal pancreatic tissues were embedded with paraffin,serial sections were cut and mounted on glass slides.Immunohistochemical staining was carried out with N-myc down-stream regulated gene 2 (Ndrg2) monoclonal antibody by means of ABC method,and Western blotting was carried out to detect the expression and distribution of Ndrg2.The results showed that Ndrg2 positive immunoreactivity was mainly localized in the cytoplasm of islet cell,being similar to the localization of insulin positive immunoreactivity.The number and volume of pancreatic islets were increased in the patients with islet cell hyperplasia,and Ndrg2 expression was also increased.Western blotting results showed that the expression of Ndrg2 in the pancreas of patients with islet cell hyperplasia was increased compared with normal group.The above results suggest that Ndrg2 may play an important role in performing physiological function of islet cells. Key words: N-myc downstream regulated gene 2 ; Pancreatic islet cells; Insulin; Immunohistochemistry