54 research outputs found

    Autotransplantation of parathyroid grafts into the tibialis anterior muscle after parathyroidectomy: a novel autotransplantation site

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    Background: Surgical management of renal secondary hyperparathyroidism (sHPT) is varying. Total parathyroidectomy with heterotopic autotransplantation (TPTX + AT) is one of the standard surgical procedures in sHPT, but there is no consensus about the optimal site for graft insertion. At the surgical department of the University Hospital of Heidelberg we prefer the autotransplantation into the tibialis anterior muscle. The aim of this study was to assess the long-term function of the auto-transplanted parathyroid tissue in this type of surgical procedure. Methods: The function of the autograft of 42 patients was assessed 8.2 ± 2.5 years after surgery, using a modified Casanova-test of the leg bearing the parathyroid tissue. Ischemic blockage was induced by tourniquet and the levels of parathyroid hormone (PTH) were assessed during the test. Results: At the point of assessment, the ischemic blockage led to a significant reduction in the concentration of PTH (≥50 % of the baseline value) in 19 patients (45 %) indicating well-functioning autografts. In 11 patients (26 %), ischemic blockage did not cause any change in the concentration of PTH (≤20 % of the baseline value), indicating functioning residual parathyroid tissue from another site. The source of PTH production was classified as unidentifiable in five patients (12 %). Two patients had developed graft-dependent recurrent HPT (5 %) without therapeutic consequences and three patients suffered from persistent symptomatic hypoparathyroidism (7 %). Conclusions: These results indicate that TPTX + AT into the tibialis anterior muscle is a successful surgical treatment for renal HPT and that the modified Casanova-test is a suitable diagnostic tool for autografts function

    Epithelial to Stromal Re-Distribution of Primary Cilia during Pancreatic Carcinogenesis

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    Background The Hedgehog (HH) pathway is a mediator in pancreatic ductal adenocarcinoma (PDAC). Surprisingly, previous studies suggested that primary cilia (PC), the essential organelles for HH signal transduction, were lost in PDAC. The aim of this study was to determine the presence of PC in human normal pancreas, chronic pancreatitis, and during carcinogenesis to PDAC with focus on both epithelia and stroma. Methods PC were analyzed in paraffin sections from normal pancreas, chronic pancreatitis, intraductal papillary-mucinous neoplasia, and PDAC, as well as in primary human pancreatic stellate cells (PSC) and pancreatic cancer cell lines by double immunofluorescence staining for acetylated alpha-tubuline and gamma-tubuline. Co-staining for the HH receptors PTCH1, PTCH2 and SMO was also performed. Results PC are gradually lost during pancreatic carcinogenesis in the epithelium: the fraction of cells with PC gradually and significantly decreased from 32% in ducts of normal pancreas, to 21% in ducts of chronic pancreatitis, to 18% in PanIN1a, 6% in PanIN2, 3% in PanIN3 and to 1.2% in invasive PDAC. However, this loss of PC in the neoplastic epithelium is accompanied by a gain of PC in the surrounding stroma. The fraction of stromal cells with PC significantly increased from 13% around normal ducts to about 30% around PanIN and PDAC. HH-receptors were detected in tumor stroma but not in epithelial cells. PC are also present in PSC and pancreatic cancer cell lines. Conclusion PC are not lost during pancreatic carcinogenesis but re-distributed from the epithelium to the stroma. This redistribution may explain the re-direction of HH signaling towards the stroma during pancreatic carcinogenesis

    Understanding decision quality through satisfaction

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    "PAAMS 2014 International Workshops, Salamanca, Spain, June 4-6, 2014. Proceedings"One of the most important factors to determine the success of an or-ganization is the quality of decisions made. In order to improve the decisions taken and to strengthen the competitiveness of organizations, systems such as Group Decision Support Systems (GDSSs) have been strongly developed and studied in recent decades. The amount of GDSSs incorporating automatic nego-tiation mechanisms, such as argumentation, is increasing nowadays. The evalu-ation of these mechanisms and the understanding of their real benefits for the organizations is still a hard challenge. In this article, we propose a model that allows a GDSS to measure the participant’s satisfaction with the decision, con-sidering aspects such as problem evaluation, personality, emotions and expecta-tions. This model is intended to enable the understanding of the decision’s qual-ity achieved with an argumentation system and to evaluate its capability to po-tentiate the decision’s quality. The proposed model validates all the assump-tions found in the literature regarding the participant’s satisfaction.This work is supported by FEDER Funds through the “Programa Operacional Fac-tores de Competitividade - COMPETE” program and by National Funds through FCT “Fundação para a Ciência e a Tecnologia” under the project: FCOMP-01-0124-FEDER-PEst-OE/EEI/UI0760/2011 and SFRH/BD/89697/2012

    International Validation of a Nomogram to Predict Recurrence after Resection of Grade 1 and 2 Nonfunctioning Pancreatic Neuroendocrine Tumors

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    Background: Despite the low recurrence rate of resected nonfunctional pancreatic neuroendocrine tumors (NF-pNETs), nearly all patients undergo long-term surveillance. A prediction model for recurrence may help select patients for less intensive surveillance or identify patients for adjuvant therapy. The objective of this study was to assess the external validity of a recently published model predicting recurrence within 5 years after surgery for NF-pNET in an international cohort. This prediction model includes tumor grade, lymph node status and perineural invasion as predictors. Methods: Retrospectively, data were collected from 7 international referral centers on patients who underwent resection for a grade 1-2 NF-pNET between 1992 and 2018. Model performance was evaluated by calibration statistics, Harrel's C-statistic, and area under the curve (AUC) of the receiver operating characteristic curve for 5-year recurrence-free survival (RFS). A sub-analysis was performed in pNETs >2 cm. The model was improved to stratify patients into 3 risk groups (low, medium, high) for recurrence. Results: Overall, 342 patients were included in the validation cohort with a 5-year RFS of 83% (95% confidence interval [CI]: 78-88%). Fifty-eight patients (17%) developed a recurrence. Calibration showed an intercept of 0 and a slope of 0.74. The C-statistic was 0.77 (95% CI: 0.70-0.83), and the AUC for the prediction of 5-year RFS was 0.74. The prediction model had a better performance in tumors >2 cm (C-statistic 0.80). Conclusions: External validity of this prediction model for recurrence after curative surgery for grade 1-2 NF-pNET showed accurate overall performance using 3 easily accessible parameters. This model is available via www.pancreascalculator.com

    Duodenal stump fistula managed with percutaneous drainage, percutaneous transcholecystic biliary diversion and transduodenal glue embolization - A case report

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    Duodenal stump insufficiency is an infrequent but potentially devastating complication of upper gastrointestinal surgery. In the era of image-guided interventions, duodenal stump insufficiency is usually treated rather conservatively or with percutaneous interventions than with surgery. Herein, we present a case of a postsurgical duodenal stump fistula successfully treated in a step-by-step manner with percutaneous drainage of a periduodenal abscess-fistula complex, percutaneous transcholecystic biliary drainage for partial biliary diversion and percutaneous transcatheter fistula embolization via the duodenum with n-butyl-cyanoacrylate

    Chromogranin A and its fragments as regulators of small intestinal neuroendocrine neoplasm proliferation.

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    Chromogranin A is a neuroendocrine secretory product and its loss is a feature of malignant NEN de-differentiation. We hypothesized that chromogranin A fragments were differentially expressed during NEN metastasis and played a role in the regulation of NEN proliferation.Chromogranin A mRNA (PCR) and protein (ELISA/western blot) were studied in 10 normal human mucosa, 5 enterochromaffin cell preparations, 26 small intestinal NEN primaries and 9 liver metastases. Cell viability (WST-1 assay), proliferation (bromodeoxyuridine ELISA) and expression of AKT/AKT-P (CASE ELISA/western blot) in response to chromogranin A silencing, inhibition of prohormone convertase and mTOR inhibition (RAD001/AKT antisense) as well as different chromogranin A fragments were examined in 4 SI-NEN cell lines.Chromogranin A mRNA and protein levels were increased (37-340 fold, p<0.0001) in small intestinal NENs compared to normal enterochromaffin cells. Western blot identified chromogranin A-associated processing bands including vasostatin in small intestinal NENs as well as up-regulated expression of prohormone convertase in metastases. Proliferation in small intestinal NEN cell lines was decreased by silencing chromogranin A as well as by inhibition of prohormone convertase (p<0.05). This inhibition also decreased secretion of chromogranin A (p<0.05) and 5-HT (p<0.05) as well as expression of vasostatin. Metastatic small intestinal NEN cell lines were stimulated (50-80%, p<0.05) and AKT phosphorylated (Ser473: p<0.05) by vasostatin I, which was completely reversed by RAD001 (p<0.01) and AKT antisense (p<0.05) while chromostatin inhibited proliferation (~50%, p<0.05).Chromogranin A was differentially regulated in primary and metastatic small intestinal NENs and cell lines. Chromogranin A fragments regulated metastatic small intestinal NEN proliferation via the AKT pathway indicating that CgA plays a far more complex role in the biology of these tumors than previously considered

    Minichromosome Maintenance Expression Defines Slow-Growing Gastroenteropancreatic Neuroendocrine Neoplasms

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    BACKGROUND: Small intestinal neuroendocrine neoplasm (SI-NEN) proliferation is quantified by Ki67 measurements which capture G1-G2M phases of the cell cycle. G0 and early G1 phases, typical of slow-growing cells, can be detected by minichromosome maintenance protein (MCM) expression. We hypothesized that these replication licensing markers may provide clinically relevant information to augment Ki67 in low-grade neuroendocrine neoplasia. METHODS: Immunohistochemical staining (IHC), Western blot analysis, quantitative polymerase chain reaction, and copy number variations of MCM2, MCM3, and Ki67 were undertaken in SI-NENs (n = 22). MCM and Ki67 expression was compared by Kaplan-Meier survival analysis (tissue microarray, independent set [n = 55]). Forty-three pancreatic NENs and 14 normal tissues were included as controls. RESULTS: In SI-NENs, MCM2 (mean: 21.2%: range: 16%-25%) and MCM3 (28.7%: 22%-34%) were detected in significantly more cells than Ki67 (2.3%: 0%-7%, P < .01). MCM2 mRNA correlated with Ki67 IHC (P < .05). MCM3 protein expression was higher in metastases (38-fold) than in normal small intestine (P = .06) and was largely absent in normal neuroendocrine cells. There was considerable variation at the MCM copy number level (0-4 copies). MCM3 expression in proliferating cells significantly predicted overall survival (P < .002). Combinations of Ki67 and MCM2/3 in algorithms differentiated low and higher proliferative lesions (overall survival: 12 vs 6.1 years, P = .06). MCM expression was not informative in pancreatic NENs. CONCLUSION: MCMs are expressed in a higher proportion of NEN cells than Ki67 in slow-growing small intestinal lesions and correlate with survival. Assessment can be used to augment Ki67 to improve prognostic classification in these low-grade tumors
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