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- Neuroendocrine Tumor Imaging With (68)Ga-DOTA-NOC: Physiologic and Benign Variants. [JOURNAL ARTICLE]
- AJR Am J Roentgenol 2014 Dec; 203(6):1317-1323.
OBJECTIVE. Imaging with (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotide analogs has become an important modality in patients with neuroendocrine tumors (NETs). In addition to high uptake in NET lesions, prominent physiologic radiotracer activity has been reported in the pituitary gland, pancreas, adrenal glands, liver, and spleen, and faint activity has been reported in the thyroid and gastrointestinal tract. This article describes previously unknown sites of (68)Ga-DOTA-1-NaI3-octreotide (NOC) uptake unrelated to NETs. MATERIALS AND METHODS. One hundred eighty-two patients (96 female and 86 male patients; age range, 4-89 years) with documented (n = 156) or suspected (n = 26) NETs underwent 207 (68)Ga-DOTA-NOC PET/CT studies. Studies were retrospectively reviewed for the presence, intensity, and localization of foci of increased uptake that were further correlated with findings on additional imaging studies and clinical follow-up for a period of 4-32 months. RESULTS. Uptake of (68)Ga-DOTA-NOC not identified as NET or known physiologic activity was detected in 297 sites with confirmation in 149 of 207 studies (72%). The most common location of non-NET-related (68)Ga-DOTA-NOC-avid sites was in small lymph nodes, followed by prostate, uterus, breasts, lungs, brown fat, musculoskeletal system, and other sites, including oropharynx, pineal body, thymus, aortic plaque, genitalia, surgical bed, and subcutaneous granuloma. Intensity of uptake in non-NET-related (68)Ga-DOTA-NOC-avid sites ranged in maximum standardized uptake value from 0.8 to 10.5. CONCLUSION. Previously unreported benign sites of (68)Ga-DOTA-NOC uptake were found in the majority of studies, suggesting the presence of somatostatin receptors in physiologic variants or processes with no evidence of tumor. Knowledge of increased tracer uptake in non-NET-related sites is important for accurate interpretation and for avoiding potential pitfalls of (68)Ga-DOTA-NOC PET/CT.
- A Novel Acute Necrotizing Pancreatitis Model Induced by L-Arginine in Rats. [JOURNAL ARTICLE]
- Pancreas 2014 Nov 20.
This study developed a novel protocol for creating an acute necrotizing pancreatitis model in rats using L-arginine.Anesthetic laparotomy was performed on the upper abdomen, and the pancreatic parenchyma of Sprague-Dawley rats was injected with 1 mL of sterilized L-arginine solution at 5 different locations in the experimental group. Specifically, 2 different injection points in the head and body of the pancreas were chosen randomly, and 1 injection point in the tail of the pancreas was chosen randomly. The parenchyma of the pancreas was injected with 200 μL of an L-arginine solution at each point. The optimal dose of L-arginine per rat was 0.4 g/kg.Serum amylase activity increased significantly after targeted injection into the parenchyma of the pancreas. Pathological examination of the pancreas 24 hours after L-arginine injection revealed massive interstitial edema, apoptosis, and necrosis of acinar cells with an infiltration of neutrophils, granulocytes, and monocytes.The present study developed an appropriate, workable, and reproducible rat model of acute necrotizing pancreatitis with higher survivability and success rates compared with previously published methods.
- Observations on the use of cidofovir for BK virus infection in renal transplantation. [JOURNAL ARTICLE]
- Transpl Infect Dis 2014 Nov 21.
In renal transplantation, BK virus infection can result in significant graft nephropathy and loss. While reduction in immunosuppression (IS) is considered standard therapy, adjunct agents may be warranted. Data are suggestive of a possible role of cidofovir for the management of BK. This study aims to describe the course of BK viremia (BKV) in a large cohort of renal transplant patients receiving adjunct cidofovir.We evaluated kidney and kidney-pancreas recipients who received cidofovir combined with reduced IS for management of high-level BKV or BK virus nephropathy (BKVN). We examined the rate and timing of BKV clearance, and performed a multivariate analysis to identify risk factors associated with long-term (>6 months) viremia.In total, 75 patients received a median of 13 doses of cidofovir in conjunction with reduced IS; 32 patients (43%) had short-term BKV (≤6 months), and 43 (57%) had long-term BKV. Overall, 53 of 75 patients (71%) eventually cleared BKV at a median of 4.2 months (interquartile range 2.1-9.3 months). Independent factors associated with long-term BKV included older age (odds ratio [OR] 1.1, P = 0.02), delayed graft function (OR 31.4, P = 0.01), and higher peak BKV (OR 12.8, P = 0.02), while BKV reduction by at least 1 log10 copies/mL at 1 month of treatment was associated with clearance within 6 months (OR 49.3, P < 0.01). Patients with earlier clearance maintained stable graft function and no graft losses, while long-term BKV was associated with a 15% decline in estimated glomerular filtration rate.Adjunct cidofovir resulted in preservation of renal function when viral clearance occurred within 6 months of initiation. This retrospective review defines factors predicting response to cidofovir in conjunction with reduced IS for BKVN or high-level BKV. Still, considering cost, frequency of administration, and treatment duration, a randomized trial is necessary to define the exact utility of cidofovir in the setting of BK virus infection.
- Demographic Features and Natural History of Intermediate-Risk Multifocal Versus Unifocal Intraductal Papillary Mucinous Neoplasms. [JOURNAL ARTICLE]
- Pancreas 2014 Nov 19.
This study compares the progression of multifocal (MF) intraductal papillary mucinous neoplasms (IPMNs) to unifocal (UF) lesions.We performed a retrospective review of demographics, risk factors, and cyst characteristics of a prospectively maintained database of 999 patients with pancreatic cysts. Patients included had IPMN under surveillance for 12 months or more. Those with high-risk stigmata were excluded. Cyst size progression and development of worrisome features were compared between MF and UF cohorts. We evaluated whether the dominant cyst in MF-IPMN had more significant growth than did the other cysts.Seventy-seven patients with MF-IPMN and 54 patients with UF-IPMN, with mean follow-up of 27 and 34 months, met the criteria. There were no significant differences between demographics, risk factors, or initial cyst sizes. Fifty-seven percent of MF dominant cysts and 48% of UF cysts increased in size (P = 0.31). Progression in MF was more likely in the dominant cyst (P < 0.05). There were no significant differences in the development of mural nodules or increase in cyst size to more than 3 cm.Demographics of both cohorts were similar, as was the overall incidence of worrisome features. Because meaningful size progression primarily occurred in the dominant cyst, our findings support surveillance based on the dominant cyst in MF disease.
- Bone Metastases in Well-to-Moderately Differentiated Neuroendocrine Tumors: A Single Institutional Review From the Ohio State University Medical Center. [JOURNAL ARTICLE]
- Pancreas 2014 Nov 19.
In this study, we look at the clinical features associated with bone metastasis in patients with well-to-moderately differentiated neuroendocrine tumors (NETs), specifically primary tumor characteristics, complications, elevated hormone levels, and survival.A retrospective study at the Ohio State University was performed on patients diagnosed with well-to-moderately differentiated NETs from 2000 to 2010 who were found to have bone metastases. A control group of patients with metastatic NETs without bone metastases was matched with regard to demographic and clinical data.Of 341 patients with well-to-moderately differentiated NETs, 40 patients were found with bone metastases within the 10-year study period. Patients with bone metastases had shorter survival (median, 52 months) compared to the control group (median, 98 months; P = 0.024). Of 26 patients with bone metastases who died, 6 (23%) patients had a cause of death related to their bone metastatic disease. There were 8 patients with spinal cord compression, and 6 with pathologic fractures.Our study suggests that patients with well-to-moderately differentiated NETs metastatic to bone have larger tumors, more frequently elevated pancreastatin, and shorter survival than patients without bone metastases, with complications of bone metastases significantly contributing to mortality and morbidity.
- In vitro quantitative and relative gene expression analysis of pancreatic transcription factors Pdx-1, Ngn-3, Isl-1, Pax-4, Pax-6 and Nkx-6.1 in trans-differentiated human hepatic progenitors. [JOURNAL ARTICLE]
- J Diabetes Investig 2014 Sep; 5(5):492-500.
Diabetes is a major health concern throughout the world because of its increasing prevalence in epidemic proportions. β-Cell deterioration in the pancreas is a crucial factor for the progression of diabetes mellitus. Therefore, the restoration of β-cell mass and its function is of vital importance for the development of effective therapeutic strategies and most accessible cell sources for the treatment of diabetes mellitus.Human fetuses (12-20 weeks gestation age) were used to isolate human hepatic progenitor cells (hHPCs) from fetal liver using a two-step collagenase digestion method. Epithelial cell adhesion molecule-positive (EpCAM+ve)-enriched hHPCs were cultured in vitro and induced with 5-30 mmol/L concentration of glucose for 0-32 h. Pdx-1 expression and insulin secretion was analyzed using immunophenotypic and chemifluorescence assays, respectively. Relative gene expression was quantified in induced hHPCs, and compared with uninduced and pancreatic cells to identify the activated transcription factors (Pdx-1, Ngn-3, Isl-1, Pax-4, Pax-6 and Nkx-6.1) involved in β-cell production.EpCAM+ve cells derived from human fetal liver showed high in vitro trans-differentiation potential towards the β-cell phenotype with 23 mmol/L glucose induction after 24 h. The transcription factors showed eminent expression in induced cells. The expression level of transcription factors was found significantly high in 23 mmol/L-induced hHPCs as compared with the uninduced cells.The present study has shown an exciting new insight into β-cell development from hHPCs trans-differentiation. Relative quantification of gene expression in trans-differentiated cells offers vast possibility for the production of a maximum number of functionally active pancreatic β-cells for a future cure of diabetes.
- Investigation of the Anti-Inflammatory Effects of Safranal on High-Fat Diet and Multiple Low-Dose Streptozotocin Induced Type 2 Diabetes Rat Model. [JOURNAL ARTICLE]
- Inflammation 2014 Nov 20.
In the present study, it was aimed to investigate the effects of safranal, one of the components of saffron plant, on the inflammation in the rats in which experimental type 2 diabetes and obesity were formed. Type 2 diabetes is a disease characterized by insulin resistance and β-cell dysfunction. Therefore, in the present study, high-fat diet (HFD) and streptozotocin were used for being able to create experimental type 2 diabetes. In the first 6 weeks of the study, experimental groups were formed in five groups, after the stage of creating insulin resistance. The study groups were designed as control, HFD, HFD-Saf, DYB, and DYB-Saf groups. Safranal treatment was applied to the treatment groups for a period of 4 weeks. Throughout the study period (10 weeks), the weight gains and plasma glucose levels of the rats were determined each week and bi-weekly, respectively. At the end of the study, interferon gamma (IFN-γ), interleukin (IL)-1β, IL-6, tumor necrosis factor alpha (TNF-α), TAS and TOS levels in the pancreas and plasma were measured. In addition, the insulin and leptin levels in the plasma were determined. It was ascertained that, compared to the diabetic group, safranal decreased the inflammation both in the plasma and pancreas tissue, by reducing the TNF-α and IL-1β levels in particular. In addition, safranal was also found to decrease the oxidative stress increased due to type 2 diabetes in the plasma and pancreas tissue. It was concluded that safranal might be helpful in terms of reduction of diabetic complications, by means of its effects on both oxidative stress and inflammation, and that further studies should be carried out for this purpose.
- [The relationship and clinicopathological significance of Numb,MDM2 and p53 expression in human pancreatic cancer.] [JOURNAL ARTICLE]
- Zhonghua Wai Ke Za Zhi 2014 Sep; 52(9):675-681.
To study the relationship and clinicopathological significance of Numb,MDM2 and p53 expression in human pancreatic cancer.The expression of Numb,MDM2 and p53 proteins in 65 cases of paired paraffin embedded pancreatic ductal adenocarcinoma (PDAC) specimens and adjacent non-cancerous pancreas was detected by immunohistochemistry (IHC). The relationship among their expression and clinicopathological characters was analyzed.Westem blot was used to examine their expression in 16 paired fresh PDAC specimens and adjacent non-cancerous pancreatic tissues. Meanwhile,Numb expression in Capan-2, PANC-1 and AsPC-1 pancreatic cancer cells with different differentiation were detected by immunofluorescence (IF) , Westem blot and quantitative real-time (qRT) -PCR, respectively. Paired sample t-test, χ(2) test, Kaplan-Meier and Cox regression were used to analyze the results of our experiments, respectively.IHC showed that there was no differential expression of Numb in PDAC and adjacent pancreas (t = 1.746, P = 0.086) , while the expression of MDM2 and p53 was significantly increased in PDAC, compared to that in paired normal pancreas (t = 3.294, P = 0.002;t = 3.152, P = 0.002, respectively) .Numb expression was negatively associated with tumor size (χ(2) = 5.206, P = 0.023), differentiation (χ(2) = 7.802, P = 0.005) and UICC stage (χ(2) = 4.770, P = 0.029), while expression of MDM2 and p53 was positively associated with tumor T and TNM stage, respectively (χ(2) = 5.182, P = 0.023;χ(2) = 6.448, P = 0.011) . Correlation analysis showed a negative association between Numb and MDM2 (r = -0.283, P = 0.023) , but there was no relationship of them with p53 (P > 0.05) .Univariate and multivariate analysis revealed that Numb was a protective prognostic indicator for patients with PDAC (χ(2) = 5.408, P = 0.020). Moreover, patients with Numb positive and MDM2 negative expression had a significantly better overall survival (χ(2) = 5.868, P = 0.015). Western blot showed that Numb expression was much higher in well differentiated PDAC than that in paired normal pancreas (t = 1.092, P = 0.020) , while the expression of MDM2 and p53 was significantly increased in 16 cases of PDAC (t = 3.263, P = 0.005; t = 3.607, P = 0.003, respectively). Numb expression was gradually increased in pancreatic cancer cells with the increasing degree of cell differentiation detected by IF, Westem blot and qRT-PCR.Numb acts as a tumor suppressor gene in the development of PDAC. Numb, MDM2 and p53 might coordinately participate in the development of PDAC.
- [A meta-analysis of surgery treatment of chronic pancreatitis with an inflammatory mass in the head of pancreas: duodenum-preserving pancreatic head resection versus pancreatoduodenectomy.] [JOURNAL ARTICLE]
- Zhonghua Wai Ke Za Zhi 2014 Sep; 52(9):668-674.
To compare the safety and effectiveness of DPPHR with PPPD/PD for treating chronic pancreatitis with an inflammatory mass in the head of pancreas.The relative data bases such as Medline, EMBase, Biosis, COCHRANE Library, Science Citation Index, SinoMed, Chinese Journal Full-text Database, Wangfang, CNKI were searched systematically, researchers selected randomized controlled trials (RCT) and prospective clinical controlled trials (CCT) . The assessment of the bias risk of the included trials was according to the assessing tools suggested by Cochrane Handbook 5.1. The Review Manage 5.2 was used to perform the statistical analysis.In total, 5 RCTs and 2 CCTs were included, 381 patients involved. Comparing with PPPD/PD procedure, DPPHR has no significant difference in terms of the mortality of perioperative period (RD = 0.01, P = 0.51), the incidence of bleeding (RD = -0.01, P = 0.72), pancreatic fistula(RD = -0.01, P = 0.59) and delayed gastric emptying (RD = -0.15, P = 0.10), the ration of complete pain relief after operation (RR = 1.06, P = 0.32) and the score of global quality of life (WMD = 10.31, P = 0.19).While DPPHR had significant superiorities in terms of the total morbidity of perioperative period (RR = 0.60, P = 0.008), the duration of the operations(WMD = -71.60, P = 0.03), the postoperative hospitalization duration(WMD = -3.95, P < 0.01), weight gain(WMD = 3.68, P < 0.01), occupational rehabilitation after the operations (RR = 1.38, P = 0.008).In terms of reducing the morbidity of perioperative period, shortening the duration of the operations and the postoperative hospitalization duration, weight gain, occupational rehabilitation after the operations, the DPPHR is more favorable for improving patients' life qualities comparing with PPPD/PD.
- [A clinical series of 80 patients with adenosquamous carcinoma of pancreas.] [JOURNAL ARTICLE]
- Zhonghua Wai Ke Za Zhi 2014 Sep; 52(9):658-661.
To raise the awareness of adenosquamous carcinoma of pancreas and discuss the treatment of it.Clinical data of 80 cases of pancreas adenosquamous carcinoma patients in the Department of Pancreas Surgery of Changhai Hospital of Second Military Medical University from December 2003 to October 2011 were analyzed. The diagnose and treatment methods were discussed. There were 61 male cases and 19 female cases who aged from 28 to 81 years, with an average age of 60 years. The primary symptoms included 46 cases (57.5%) of abdominal malaise, 6 cases (7.5%) of low back pain, 4 cases (5.0%) of abdominal swelling pain with low back pain, 15 cases (18.8%) of abdominal swelling pain with jaundice, 5 cases (6.3%) of painless jaundice, 3 cases (3.8%) of significantly decreased body-weight and 1 case (1.3%) of no symptom. All the patients had been identified as pancreas tumor suffers by ultrasound, enhanced CT scan or MRI. Totally there were 43 cases of head/unciform process tumors, 15 cases of pancreas body tumors and 22 pancreas tail cases.Health situation of all cases were follow-up observed in the outpatient department or telephoned every 3 months till 24 months after the surgery.Among the 80 patients, 19 patients underwent pancreaticoduodenectomy (PD) , 19 patients received pylorus-preserving PD, with 4 cases of palliative resection and 1 case of total pancreatectomy. The volume of bleeding during the surgery varied from 50 to 3 500 ml with a blood transfusion volume varied from 0 to 4 000 ml. Consumed time for PD procedures was 90 to 260 min with 60 to 150 min for body and (or) tail resection with or without lienectomy. The mean diameter of tumor was (4.9 ± 2.2) cm. Pathological tests showed 35 cases of positive lymph nodes, adjacent organ invasion happened in 35 patients, however, nerve invasion were found in 68 cases.Eighteen cases occurred postoperative complications, including bleeding, pancreatic fistula, gastric emptying, incision fat liquefaction and infection, pleural effusion, ascites and nervous diarrhea. There were only 48 effective follow-up patients, with a loss ratio of follow-up by 40.0%, reasons for the loss includes change of contact information, refuse or unable to provide useful information by the relatives of the patients.Sixteen patients received chemotherapy, and 8 patients received radiotherapy after operation. All patients were dead in the effective follow-ups. The postoperative median survival time was 6 months (0.1 to 23.0 months).Adenosquamous carcinoma of pancreas is a rare kind of malignant tumor, nerve invasion can be found in almost all the cases. Patients with adenosquamous carcinoma of pancreas have an unfavorable prognosis. The principle treatments are surgery, radiotherapy and chemotherapy.