Journal articles: 'PanNEN'

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Wen, Junmiao, Jiayan Chen, Di Liu, Xinyan Xu, Min Fan, and Zhen Zhang. "The Eighth Edition of the American Joint Committee on Cancer Distant Metastases Stage Classification for Metastatic Pancreatic Neuroendocrine Tumors Might Be Feasible for Metastatic Pancreatic Ductal Adenocarcinomas." Neuroendocrinology 110, no. 5 (July 30, 2019): 364–76. http://dx.doi.org/10.1159/000502382.

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Background: Significant modifications have been made to the 8th edition of the American Joint Committee on Cancer (AJCC) distant metastases (M) stage classification for metastatic pancreatic neuroendocrine tumors (PanNETs). We aimed to validate this revised classification among metastatic PanNET patients using the Surveillance, Epidemiology, and End Results database. We further sought to evaluate the feasibility of applying this classification to metastatic pancreatic neuroendocrine carcinoma (PanNEC) and pancreatic ductal adenocarcinoma (PDAC) patients. Methods: Stage IV pancreatic neuroendocrine neoplasm (PanNEN, including G1/G2 PanNET and G3 PanNEC classified according to the World Health Organization [WHO] 2010 grading scheme) and PDAC patients with metastatic disease diagnosed between 2010 and 2015 were identified and restaged according to the revised M stage classification for PanNET. Overall survival (OS) was compared using Kaplan-Meier analysis and log-rank test. Uni- and multivariate Cox regression models were utilized to identify prognostic factors. Results: A total of 1,371 stage IV PanNEN and 634 PDAC patients were included. Among PanNEN patients, liver (75.0%) was the most common metastatic site, followed by distant lymph nodes (8.5%), lung (8.4%), bone (7.3%), and brain (1.0%). The 5-year OS for PanNET patients with M1a, M1b, and M1c stage was 44.15, 53.32, and 19.70%, respectively. However, survival comparison showed no significant difference between M1a and M1b stages among PanNET patients. Similar findings were noted after applying this classification to PanNEC patients. Multivariate analysis showed that the age at diagnosis and the number of distant metastatic sites were independent prognostic factors for metastatic PanNEN patients. Interestingly, excellent survival discrimination by M stage among stage IV PDAC patients was noted (M1a vs. M1b vs. M1c, 5-year OS: 5.42, 2.46, and 0%, respectively). Conclusion: Our study is the first large sample-based validation of the AJCC 8th M stage classification for PanNET. The revised classification did not effectively stratify metastatic PanNEN patients. However, further study is warranted to validate this classification for PanNET patients according to the WHO 2017 classification. Interestingly, the revised M stage classification might be feasible for PDAC patients with metastatic disease.

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Azar, Ibrahim, Omid Yazdanpanah, Shiva Swaroop Bongu, Mohammed Najeeb Al Hallak, W. Michael Korn, Anthony Frank Shields, and Philip Agop Philip. "Molecular profiling of pancreatic neuroendocrine neoplasms (panNENs): A single-institution experience." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e16207-e16207. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e16207.

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e16207 Background: PanNENs are rare with a heterogeneous pathophysiology and widely differing clinical course. Despite a recent update of the grading system, prognostication and prediction of response to therapy remain challenging. Somatostatin receptor aside, there are currently no predictive biomarkers or targeted agents for panNENs. Molecular profiling offers an opportunity to develop new drugs and personalize treatments. Methods: We compiled data from patients diagnosed with panNENs from Karmanos Cancer Institute between 2014 and 2020. Of the 35 patients with panNENs, 33 underwent Next Generation Sequencing (Caris Molecular Intelligence). Two tumor biopsies were insufficient for molecular analysis. Results: Of the 35 tumors analyzed, 11 were grade 1, 18 were G2, 2 were well-differentiated G3 and 4 were poorly differentiated pancreatic neuroendocrine carcinomas (panNEC). Median age at diagnosis was 61. 21 patients identified as White, 6 as Black and 8 as other. 21 were men. 28 patients were metastatic at diagnosis. The most frequently detected molecular alteration was MEN1 mutations (11 G1, 1 G1 and 1 G3). 3 G2 and 2 G3 tumors expressed PTEN mutations. All 3 p53 mutations were G3, 2 of them panNEC. An FGFR3 amplification was detected in a single G1 panNEN. Her2/Neu amplification was detected in a G2 tumor. Other frequent alterations were MGMT (4), TOP2A (4), ARID1A (3), TUBB3 (3) and TSC2 (3). 3 tumors were PD-L1 positive. All tumors were TMB non-high and MMR-proficient. Conclusions: Molecular profiling of panNEN can detect targetable alterations with currently validated commercial agents. panNENs are immunologically cold. Further genomic and epigenomic profiling studies can help understand the molecular underpinnings of pathophysiology and aid in the development of biology-driven targeted therapies.

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April-Monn, Simon Leonhard, Valentina Andreasi, Marco Schiavo Lena, Martin Carl Sadowski, Corina Kim-Fuchs, Michelle Claudine Buri, Avanee Ketkar, et al. "EZH2 Inhibition as New Epigenetic Treatment Option for Pancreatic Neuroendocrine Neoplasms (PanNENs)." Cancers 13, no. 19 (October 7, 2021): 5014. http://dx.doi.org/10.3390/cancers13195014.

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Pancreatic neuroendocrine neoplasms are epigenetically driven tumors, but therapies against underlying epigenetic drivers are currently not available in the clinical practice. We aimed to investigate EZH2 (Enhancer of Zest homolog) expression in PanNEN and the impact of EZH2 inhibition in three different PanNEN preclinical models. EZH2 expression in PanNEN patient samples (n = 172) was assessed by immunohistochemistry and correlated with clinico-pathological data. Viability of PanNEN cell lines treated with EZH2 inhibitor (GSK126) was determined in vitro. Lentiviral transduction of shRNA targeting EZH2 was performed in QGP1 cells, and cell proliferation was measured. Rip1TAG2 mice underwent GSK126 treatment for three weeks starting from week 10 of age. Primary cells isolated from PanNEN patients (n = 6) were cultivated in 3D as islet-like tumoroids and monitored for 10 consecutive days upon GSK126 treatment. Viability was measured continuously for the whole duration of the treatment. We found that high EZH2 expression correlated with higher tumor grade (p < 0.001), presence of distant metastases (p < 0.001), and shorter disease-free survival (p < 0.001) in PanNEN patients. Inhibition of EZH2 in vitro in PanNEN cell lines and in patient-derived islet-like tumoroids reduced cell viability and impaired cell proliferation, while inhibition of EZH2 in vivo in Rip1TAG2 mice reduced tumor burden. Our results show that EZH2 is highly expressed in high-grade PanNENs, and during disease progression it may contribute to aberrations in the epigenetic cellular landscape. Targeting EZH2 may represent a valuable epigenetic treatment option for patients with PanNEN.

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Nakano, Kenzo, Toshihiko Masui, Akitada Yogo, Yuichiro Uchida, Asahi Sato, Yosuke Kasai, Kazuyuki Nagai, Takayuki Anazawa, Yoshiya Kawaguchi, and Shinji Uemoto. "Chloroquine induces apoptosis in pancreatic neuroendocrine neoplasms via endoplasmic reticulum stress." Endocrine-Related Cancer 27, no. 7 (July 2020): 431–39. http://dx.doi.org/10.1530/erc-20-0028.

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Although pancreatic neuroendocrine neoplasms (PanNENs) are generally indolent, patients with distant metastasis have a dismal prognosis. Recently, the autophagy inhibitor chloroquine (CQ) has been shown to suppress the tumour growth of PanNENs, but the detailed mechanisms have not been elucidated. Furthermore, these results were obtained from poorly differentiated cell lines rather than well-differentiated cell lines, which is the most prevalent type in this tumour. To explore the mechanism and efficacy of CQ on PanNENs, we applied CQ to cell lines and evaluated the resulting apoptosis and endoplasmic reticulum (ER) stress. CQ treatment induced ER stress, and an unfolded protein response was activated through the PERK-eIF2α-ATF4 pathway, resulting in the expression of the pro-apoptotic protein C/EBP homologous protein (CHOP), which reflects ER-stress-mediated apoptotic cell death. Furthermore, hydroxychloroquine (HCQ) was effective in Men1 heterozygous-deficient (Men1+/ΔN3-8) mice, a mouse PanNEN model that is considered to correspond to human low-grade PanNEN. HCQ administration decreased tumour size in Men1+/ΔN3-8 mice. In the HCQ group, histological analyses revealed that proliferative activity was unchanged, but apoptosis was accelerated, accompanied by CHOP expression. These results suggest that autophagy inhibition by CQ/HCQ could be used for the treatment of PanNEN, including the well-differentiated type.

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van den Bold, Ingeborg. "Pannen en paprika’s." TBV – Tijdschrift voor Bedrijfs- en Verzekeringsgeneeskunde 22, no. 7 (September 2014): 319. http://dx.doi.org/10.1007/s12498-014-0138-y.

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Müringer, Alfred. "Pannen beim Versichererwechsel." Versicherungsmagazin 50, no. 10 (October 2003): 54–57. http://dx.doi.org/10.1007/bf03244419.

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Otto, Raik, Katharina M. Detjen, Pamela Riemer, Melanie Fattohi, Carsten Grötzinger, Guido Rindi, Bertram Wiedenmann, Christine Sers, and Ulf Leser. "Transcriptomic Deconvolution of Neuroendocrine Neoplasms Predicts Clinically Relevant Characteristics." Cancers 15, no. 3 (February 1, 2023): 936. http://dx.doi.org/10.3390/cancers15030936.

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Pancreatic neuroendocrine neoplasms (panNENs) are a rare yet diverse type of neoplasia whose precise clinical–pathological classification is frequently challenging. Since incorrect classifications can affect treatment decisions, additional tools which support the diagnosis, such as machine learning (ML) techniques, are critically needed but generally unavailable due to the scarcity of suitable ML training data for rare panNENs. Here, we demonstrate that a multi-step ML framework predicts clinically relevant panNEN characteristics while being exclusively trained on widely available data of a healthy origin. The approach classifies panNENs by deconvolving their transcriptomes into cell type proportions based on shared gene expression profiles with healthy pancreatic cell types. The deconvolution results were found to provide a prognostic value with respect to the prediction of the overall patient survival time, neoplastic grading, and carcinoma versus tumor subclassification. The performance with which a proliferation rate agnostic deconvolution ML model could predict the clinical characteristics was found to be comparable to that of a comparative baseline model trained on the proliferation rate-informed MKI67 levels. The approach is novel in that it complements established proliferation rate-oriented classification schemes whose results can be reproduced and further refined by differentiating between identically graded subgroups. By including non-endocrine cell types, the deconvolution approach furthermore provides an in silico quantification of panNEN dedifferentiation, optimizing it for challenging clinical classification tasks in more aggressive panNEN subtypes.

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Tsoli, Marina, Maria-Eleni Spei, Göran Wallin, Gregory Kaltsas, and Kosmas Daskalakis. "Association of a Palliative Surgical Approach to Stage IV Pancreatic Neuroendocrine Neoplasms with Survival: A Systematic Review and Meta-Analysis." Cancers 12, no. 8 (August 11, 2020): 2246. http://dx.doi.org/10.3390/cancers12082246.

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The role of primary tumor resection in patients with pancreatic neuroendocrine neoplasms (PanNENs) and unresectable distant metastases remains controversial. We aimed to evaluate the effect of palliative primary tumor resection (PPTR) on overall survival (OS) in this setting. We searched the MEDLINE, Embase, Cochrane Library, Web of Science and SCOPUS databases up to January 2020 and used the Newcastle–Ottawa scale (NOS) criteria to assess quality/risk of bias. A total of 5661 articles were screened. In 10 studies, 5551 unique patients with stage IV PanNEN and unresectable metastases were included. The five-year OS for PanNEN patients undergoing PPTR in stage IV was 56.6% vs. 23.9% in the non-surgically treated patients (random effects relative risk (RR): 1.70; 95% CI: 1.53–1.89). Adjusted analysis of pooled hazard ratios (HR) confirmed longer OS in PanNEN patients undergoing PPTR (random effects HR: 2.67; 95% CI: 2.24–3.18). Cumulative OS analysis confirmed an attenuated survival benefit over time. The complication rate of PPTR was as high as 27%. In conclusion, PPTR may exert a survival benefit in stage IV PanNEN. However, the included studies were subject to selection bias, and special consideration should be given to PPTR anchored to a multimodal treatment strategy. Further longitudinal studies are warranted, with long-term follow-up addressing the survival outcomes associated with surgery in stage IV disease.

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Gulde, Sebastian, Alessia Foscarini, Simon L. April-Monn, Edoardo Genio, Alessandro Marangelo, Swapna Satam, Daniel Helbling, et al. "Combined Targeting of Pathogenetic Mechanisms in Pancreatic Neuroendocrine Tumors Elicits Synergistic Antitumor Effects." Cancers 14, no. 22 (November 8, 2022): 5481. http://dx.doi.org/10.3390/cancers14225481.

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Pancreatic neuroendocrine neoplasms (PanNENs) are the second most common malignancy of the pancreas. Surgery remains the only curative treatment for localized disease. For patients with inoperable advanced or metastatic disease, few targeted therapies are available, but their efficacy is unpredictable and variable. Exploiting prior knowledge on pathogenetic processes involved in PanNEN tumorigenesis, we tested buparlisib (PI3K inhibitor) and ribociclib (CDK4/6 inhibitor), as single agents or in combination, in different preclinical models. First, we used cell lines representative of well-differentiated (INS-1E, NT-3) and poorly differentiated (BON-1) PanNENs. The combination of buparlisib with ribociclib reduced the proliferation of 2D and 3D spheroid cultures more potently than the individual drugs. Buparlisib, but not ribociclib, induced apoptosis. The anti-proliferative activity of the drugs correlated with downstream target inhibition at mRNA and protein levels. We then tested the drugs on primary islet microtissues from a genetic PanNET animal model (Men1-defective mice) and from wild-type mice: the drug combination was effective against the former without altering islet cell physiology. Finally, we treated PanNET patient-derived islet-like 3D tumoroids: the combination of buparlisib with ribociclib was effective in three out of four samples. Combined targeting of PI3K and CDK4/6 is a promising strategy for PanNENs spanning various molecular and histo-pathological features.

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IZUMO, WATARU, RYOTA HIGUCHI, TORU FURUKAWA, TAKEHISA YAZAWA, SHUICHIRO UEMURA, YUTARO MATSUNAGA, MASAHIRO SHIIHARA, et al. "Evaluation of the Significance of Lymphatic, Microvascular and Perineural Invasion in Patients With Pancreatic Neuroendocrine Neoplasms." Cancer Diagnosis & Prognosis 2, no. 2 (March 3, 2022): 150–59. http://dx.doi.org/10.21873/cdp.10089.

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Background: Some prognostic factors for pancreatic neuroendocrine neoplasms (PanNENs) have been reported; however, the significance of lymphatic, microvascular, and perineural invasion remains unclear. We aimed to clarify the role of these factors in PanNEN recurrence. Patients and Methods: We analyzed 138 patients who underwent curative pancreatectomy and were pathologically diagnosed with PanNEN. We evaluated the association between clinicopathological factors and the recurrence of PanNENs. Results: The numbers of patients with lymphatic, microvascular, and perineural invasion were 34 (25%), 43 (31%) and 17 (12%), respectively. Twenty-four patients (17%) had recurrences, and the 3, 5, and 10-year recurrence-free survival (RFS) rates were 88%, 84%, and 76%, respectively. The recurrence sites (with duplication) were mainly the liver (twenty-two patients), followed by the lymph nodes (seven patients), and bone (two patients). In multivariate analyses, grade 2-3 and the presence of microvascular invasion were significant risk factors for RFS (hazard ratio=7.5 and 7.9, respectively). When examining outcomes according to these factors, the 5-year RFS rates of patients with risk scores of 0, 1, and 2 were 100%, 91%, and 32%, respectively (p<0.001). Even in patients with grade 1 (n=97) or limited resection (enucleation, splenic-preserving distal pancreatectomy, central pancreatectomy, and duodenum-preserving pancreatic head resection, n=62), the presence of microvascular invasion was a significant risk factor for RFS (hazard ratio=13.4 and 18.0, respectively). Conclusion: The presence of microvascular invasion is an independent risk factor for recurrence in patients with PanNEN.

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Maurer, S. "“…es wird fortwährend Pannen geben.”." Germanistische Mitteilungen 43, no. 2 (2018): 171–88. http://dx.doi.org/10.33675/gm/2017/2/5.

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Oberhofer, Elke. "Checkliste soll Impf-Pannen vermeiden." MMW - Fortschritte der Medizin 158, no. 10 (May 2016): 8. http://dx.doi.org/10.1007/s15006-016-8244-7.

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Cech, Michael, Anne Drogand, Klaus Pavkovic, and Helmuth Schweitzer. "Sozialpleiten — nur Pech und Pannen?" Sozial Extra 30, no. 1 (January 2006): 8–13. http://dx.doi.org/10.1007/s12054-006-0153-z.

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Marotta, Alessandro, Jordan P. Reynolds, Thomas P. Plesec, E. Rene Rodriguez, Sunguk N. Jang, Maria Luisa C. Policarpio-Nicolas, Bridgette Springer, and Charles D. Sturgis. "Fibrous Extracellular Spheroids in an Endoscopic Ultrasound-Guided Pancreatic Fine Needle Aspiration Correlating to a Gyriform Pancreatic Endocrine Tumor with a Unique Cobblestone Pavement Growth Pattern." Case Reports in Pathology 2019 (October 17, 2019): 1–8. http://dx.doi.org/10.1155/2019/1701072.

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Pancreatic neuroendocrine neoplasms (PanNENs) are uncommon tumors. Fine needle aspiration (FNA) samples from PanNENs are typically of high cellularity and lack necrosis. In cytology slides from these tumors, dyscohesive cells are usually reported with variably round to oval to plasmacytoid forms exhibiting coarsely granular chromatin and showing immunoreactivity for synaptophysin. We present an unusual, and to our knowledge not previously described, example of an FNA of a PanNEN with large extracellular fibrous spheroids containing intrinsic fibroblasts and rimmed by small to intermediate sized neoplastic epithelial cells with high nuclear cytoplasmic ratios. The cytomorphology of the PanNEN in this case was in some ways reminiscent of that expected in adenoid cystic carcinomas of the salivary glands that most often contain large extracellular globules of basement membrane material and a somewhat biphasic population of lesional cells. The cytomorphology in this case was found to correlate well with the resection specimen histomorphology of an exaggerated gyriform pattern of growth resulting in a unique cobblestone-pavement like microscopic appearance. Knowledge of this potential cytomorphology will aid the cytology community through recognition and reporting of this previously undescribed pattern in an uncommon disease.

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Redaktion, CS. "Schneller Werkstofftest reduziert Pannen und Ausschuss." maschinenbau 1, no. 5 (October 2021): 12–13. http://dx.doi.org/10.1007/s44029-021-0084-2.

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Pipinikas, Christodoulos P., Alison M. Berner, Teresa Sposito, and Christina Thirlwell. "The evolving (epi)genetic landscape of pancreatic neuroendocrine tumours." Endocrine-Related Cancer 26, no. 9 (August 2019): R519—R544. http://dx.doi.org/10.1530/erc-19-0175.

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Neuroendocrine neoplasms (NENs) are a relatively rare group of heterogeneous tumours originating from neuroendocrine cells found throughout the body. Pancreatic NENs (PanNENs) are the second most common pancreatic malignancy accounting for 1–3% of all neoplasms developing in the pancreas. Despite having a low background mutation rate, driver mutations in MEN1, DAXX/ATRX and mTOR pathway genes (PTEN, TSC1/2) are implicated in disease development and progression. Their increased incidence coupled with advances in sequencing technologies has reignited the interest in PanNEN research and has accelerated the acquisition of molecular data. Studies utilising such technological advances have further enriched our knowledge of PanNENs’ biology through novel findings, including higher-than-expected presence of germline mutations in 17% of sporadic tumours of no familial background, identification of novel mutational signatures and complex chromosomal rearrangements and a dysregulated epigenetic machinery. Integrated genomic studies have progressed the field by identifying the synergistic action between different molecular mechanisms, while holding the promise for deciphering disease heterogeneity. Although our understanding is far from being complete, these novel findings have provided the optimism of shaping the future of PanNEN research, ultimately leading to an era of precision medicine for NETs. Here, we recapitulate the existing knowledge on pancreatic neuroendocrine tumours (PanNETs) and discuss how recent, novel findings have furthered our understanding of these complex tumours.

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Xie, Hao, Junjia Liu, Siddhartha Yadav, Xavier M. Keutgen, Timothy J. Hobday, Jonathan R. Strosberg, and Thorvardur R. Halfdanarson. "The Role of Perioperative Systemic Therapy in Localized Pancreatic Neuroendocrine Neoplasms." Neuroendocrinology 110, no. 3-4 (May 24, 2019): 234–45. http://dx.doi.org/10.1159/000501126.

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Background: The role of perioperative systemic therapy (PST) in the management of localized pancreatic neuroendocrine neoplasms (PanNEN) is unclear. Objectives: We aimed to evaluate the benefit of PST compared to surgery alone (SA) in patients with localized PanNEN. Method: We selected patients with stages I–III PanNEN who underwent curative-intent surgical resection in National Cancer Database from 2006 to 2014. Patients who had both PST and surgical resection were matched with patients who received SA by propensity score at 1-to-1 ratio with nearest neighbor method. Results: Four thousand eight hundred and ninety-two patients were included in this study with median age of 60 years. Factors associated with significant more use of PST compared to SA included age <65 years, community medical facilities, grade 3 tumor, tumor in the pancreatic head, T34 tumor, and N1 tumor. Three hundred and one PST patients were matched with 301 SA patients. In the matched cohort, the PST group had significantly shorter overall survival (OS) compared to the SA group (median overall both not reached, p = 0.037). This finding was confirmed by multivariable Cox proportional hazards regression in the original cohort (hazard ratio [HR] 1.45, 95% CI 1.11–1.89, p = 0.006). Subgroup analyses showed that adjuvant therapy was not associated with improved OS in grades 1–2 PanNEN (HR 2.03, 95% CI 1.31–3.16, p = 0.002). Conclusions: PST stratified by grade and neoadjuvant or adjuvant therapy compared to SA was not associated with improved OS in patients with localized PanNEN. PST for localized PanNEN should be used with caution until prospective data are available.

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Jadhav, N. C., and D. L. Gang. "Multifocal Pancreatic Neuroendocrine Neoplasms In Tuberous Sclerosis: A Rare Case." American Journal of Clinical Pathology 154, Supplement_1 (October 2020): S77. http://dx.doi.org/10.1093/ajcp/aqaa161.168.

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Abstract Casestudy: Pancreatic neuroendocrine neoplasms (PanNEN) are rare accounting for 2-5% of pancreatic tumors. Although mostly sporadic, 10-20% are associated with inherited syndromes, notably MEN-1, Von Hippel- Lindau disease, neurofibromatosis type 1, and tuberous sclerosis (TS). When compared to sporadic cases, PanNEN in hereditary syndromes occur at a younger age, are often multifocal, cystic, and may show characteristic microscopic patterns. TS is an autosomal dominant multi-system disorder with mutations involving TSC1 or TSC2 genes which function as tumor suppressors by inhibiting mTORC1 kinase. PanNEN is observed in 1.5-1.8% of patients with TS and no surveillance guidelines for the assessment of pancreatic lesions are established. Compared to other syndromes, PanNEN associated with TS are solitary. To our knowledge, only two cases of multifocal PanNEN in TS patients have been reported. We present a case of a 67-year-old gentleman with a history of TS also affecting two daughters. He presented to the emergency department with severe abdominal pain. Abdominal ultrasound suggested acute appendicitis and an incidental 2.0 cm solid lesion was noted in the head of the pancreas. Follow-up MRI revealed two additional non-cystic masses in the pancreatic tail. Endoscopic ultrasound-guided biopsy of a tail lesion revealed monomorphic tumor cells with stippled chromatin without cytologic atypia. Immunohistochemical staining was positive for synaptophysin and chromogranin. Ki-67 labelling index was under 1%. Diagnosis of a well-differentiated neuroendocrine tumor (G1) was made. The patient denied symptoms of the carcinoid syndrome and no biologically active hormones were detected. Gallium PET scan revealed multiple foci of radiotracer uptake throughout the pancreas in addition to those described on MRI. Although PanNEN are rare in TS, malignant behavior has been reported. This case reinforces the importance of early detection through active surveillance, especially as surgical options may be limited in multifocal disease.

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Andreasi, Partelli, Capurso, Muffatti, Balzano, Crippa, and Falconi. "Long-Term Pancreatic Functional Impairment after Surgery for Neuroendocrine Neoplasms." Journal of Clinical Medicine 8, no. 10 (October 3, 2019): 1611. http://dx.doi.org/10.3390/jcm8101611.

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Radical surgery represents the only curative treatment for pancreatic neuroendocrine neoplasms (PanNEN). The aim of this study was to evaluate the postoperative onset of diabetes mellitus (DM) and/or pancreatic exocrine insufficiency (PEI) in surgically treated PanNEN. Consecutive PanNEN patients, without preoperative DM, who underwent partial pancreatic resection, were included. After a median follow-up of 72 months, overall 68/276 patients (24%) developed DM. Patients who developed DM were significantly older (p = 0.002) and they had a higher body mass index (BMI) (p < 0.0001) than those who did not; they were more frequently male (p = 0.017) and with nonfunctioning neoplasms (p = 0.019). BMI > 25 Kg/m2 was the only independent predictor of DM (p = 0.001). Overall, 118/276 patients (43%) developed a PEI, which was significantly more frequent after pancreaticoduodenectomy (p < 0.0001) and in patients with T3-T4 tumors (p = 0.001). Pancreaticoduodenectomy was the only independent predictor of PEI (p < 0.0001). Overall, 54 patients (20%) developed disease progression. Patients with and without DM had similar progression free survival (PFS), whereas patients without PEI had better five-year-PFS (p = 0.002), although this association was not confirmed in multivariate analysis. The risk of DM and PEI after surgery for PanNEN is relatively high but it does not affect PFS. BMI and pancreatic head resection are independent predictors of DM and PEI, respectively.

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Palmieri, Lola-Jade, Solène Dermine, Amélie Barré, Marion Dhooge, Catherine Brezault, Anne-Ségolène Cottereau, and Romain Coriat. "Medical Treatment of Advanced Pancreatic Neuroendocrine Neoplasms." Journal of Clinical Medicine 9, no. 6 (June 15, 2020): 1860. http://dx.doi.org/10.3390/jcm9061860.

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Pancreatic neuroendocrine neoplasms (panNENs) are relatively rare but their incidence has increased almost sevenfold over the last four decades. Neuroendocrine neoplasms are classified according to their histologic differentiation and their grade. Their grade is based on their Ki-67 proliferation index and mitotic index. Their prognosis is highly variable according to these elements and treatments also vary according to their classification. Surgery is the only curative treatment for localized and advanced panNENs and offers a better prognosis than non-surgical treatments. In the case of an advanced panNEN without the possibility of resection and/or ablation, medical treatment remains the cornerstone for improving survival and preserving quality-of-life. PanNENs are considered as chemosensitive tumors, unlike midgut neuroendocrine tumors. Thus, panNENs can be treated with chemotherapy, but targeted therapies and somatostatin analogs are also treatment options. The scarcity and heterogeneity of NENs make their management difficult. The present review aims to clarify the medical treatments currently available for advanced panNENs, based on their characteristics, and to propose a treatment algorithm.

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Müller, Stefan, and Jan-W. Vesting. "DNA-Analyse und Recht: Pleiten Pech und Pannen?" Kritische Justiz 29, no. 4 (1996): 466–83. http://dx.doi.org/10.5771/0023-4834-1996-4-466.

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Calabrò, Diletta, Giulia Argalia, and Valentina Ambrosini. "Role of PET/CT and Therapy Management of Pancreatic Neuroendocrine Tumors." Diagnostics 10, no. 12 (December 7, 2020): 1059. http://dx.doi.org/10.3390/diagnostics10121059.

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Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous neoplasms with neuroendocrine differentiation that show peculiar clinical and histomorphological features, with variable prognosis. In recent years, advances in knowledge regarding the pathophysiology and heterogeneous clinical presentation, as well as the availability of different diagnostic procedures for panNEN diagnosis and novel therapeutic options for patient clinical management, has led to the recognition of the need for an active multidisciplinary discussion for optimal patient care. Molecular imaging with positron emission tomography/computed tomography (PET/CT) has become indispensable for the management of panNENs. Several PET radiopharmaceuticals can be used to characterize either panNEN receptor expression or metabolism. The aim of this review is to offer an overview of all the currently used radiopharmaceuticals and of the new upcoming tracers for pancreatic neuroendocrine tumors (panNETs), and their clinical impact on therapy management. [68Ga]Ga-DOTA-peptide PET/CT (SSA-PET/CT) has high sensitivity, specificity, and accuracy and is recommended for the staging and restaging of any non-insulinoma well-differentiated panNEN cases to carry out detection of unknown primary tumor sites or early relapse and for evaluation of in vivo somatostatin receptors expression (SRE) to select patient candidates for peptide receptor radiometabolic treatment (PRRT) with 90Y or 177Lu and/or cold analogs. SSA-PET/CT also has a strong impact on clinical management, leading to a change in treatment in approximately a third of the cases. Its role for treatment response assessment is still under debate due to the lack of standardized criteria, even though some semiquantitative parameters seem to be able to predict response. [18F]FDG PET/CT generally shows low sensitivity in small growing and well-differentiated neuroendocrine tumors (NET; G1 and G2), while it is of utmost importance in the evaluation and management of high-grade NENs and also provides important prognostic information. When positive, [18F]FDG PET/CT impacts therapeutical management, indicating the need for a more aggressive treatment regime. Although FDG positivity does not exclude the patient from PRRT, several studies have demonstrated that it is certainly useful to predict response, even in this setting. The role of [18F]FDOPA for the study of panNET is limited by physiological uptake in the pancreas and is therefore not recommended. Moreover, it provides no information on SRE that has crucial clinical management relevance. Early acquisition of the abdomen and premedication with carbidopa may be useful to increase the accuracy, but further studies are needed to clarify its utility. GLP-1R agonists, such as exendin-4, are particularly useful for benign insulinoma detection, but their accuracy decreases in the case of malignant insulinomas. Being a whole-body imaging technique, exendin-PET/CT gives important preoperative information on tumor size and localization, which is fundamental for surgical planning as resection (enucleation of the lesion or partial pancreatic resection) is the only curative treatment. New upcoming tracers are under study, such as promising SSTR antagonists, which show a favorable biodistribution and higher tumor-to-background ratio that increases tumor detection, especially in the liver. [68Ga]pentixafor, an in vivo marker of CXCR4 expression associated with the behavior of more aggressive tumors, seems to only play a limited role in detecting well-differentiated NET since there is an inverse expression of SSTR2 and CXCR4 in G1 to G3 NETs with an elevation in CXCR4 and a decrease in SSTR2 expression with increasing grade. Other tracers, such as [68Ga]Ga-PSMA, [68Ga]Ga-DATA-TOC, [18F]SiTATE, and [18F]AlF-OC, are also under investigation.

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Gehrlein, Markus. "Pannen/Riedemann/Smid (Hrsg.), Unternehmensstabilisierungs- und -restrukturierungsgesetz (StaRUG), Kommentar." Deutsche Zeitschrift für Wirtschafts- und Insolvenzrecht 31, no. 11 (October 8, 2021): 641. http://dx.doi.org/10.1515/dwir-2021-0135.

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Ley, Ralph. "Stefan Pannen: Die Weiterleiter. Funktion und Selbstverständnis ostdeutscher Journalisten." GDR Bulletin 19, no. 2 (October 17, 1993): 32–33. http://dx.doi.org/10.4148/gdrb.v19i2.1111.

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Mapelli, Paola, Stefano Partelli, Matteo Salgarello, Joniada Doraku, Francesca Muffatti, Marco Schiavo Lena, Stefano Pasetto, et al. "Dual Tracer 68Ga-DOTATOC and 18F-FDG PET Improve Preoperative Evaluation of Aggressiveness in Resectable Pancreatic Neuroendocrine Neoplasms." Diagnostics 11, no. 2 (January 28, 2021): 192. http://dx.doi.org/10.3390/diagnostics11020192.

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Purpose: To define an imaging risk profile in a population of patients affected by Pancreatic neuroendocrine neoplasms (PanNENs) candidates to surgery, by assessing the predictive role of 68Ga-DOTATOC and 18F-FDG PET/CT and PET/MR derived parameters in risk stratification, particularly regarding histological features of aggressive behaviour. Patients and methods: Retrospective study including 83 patients (53 males, 30 females; median age: 60 years, interquartile range 52–66.5), who underwent to 68Ga-DOTATOC (PET/CT: n = 77; PET/MR: n = 6) and, 68/83 patients, also to 18F-FDG PET (PET/CT: n = 65; PET/MR: n = 3) before surgery for PanNEN between 2011 and 2019, with available histological and follow-up data. The PET scans were interpreted with both qualitative (positive vs. negative) and semiquantitative measurements as follows: maximum and mean standardized uptake value (SUVmax and SUVmean) for both 18F-FDG and 68Ga-DOTATOC scans, metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG) for 18F-FDG scans and somatostatin receptor density (SRD) and total lesion somatostatin receptor density (TLSRD) for 68Ga-DOTATOC PET. Receiver Operating Characteristics (ROC) curve analysis was used to investigate the performance of several PET parameters in predicting tumour stage or characteristic. For each PET parameter, the optimal cut-off was derived. Logistic regression analysis was used to assess if the PET parameters, categorized with the optimal cut-off values, were able to predict significantly the corresponding tumour stage or characteristic. Results: Overall, 29 (35%) patients had G1, 49 (59%) a G2 and five (6%) had a G3 PanNEN. The median Ki-67 index was 4% (interquartile range: 1–8%). SRD and TLSRD significantly discriminated between pT3 or pT4 PanNEN versus pT1 or pT2, as well as 18F-FDG MTV and TLG. 68Ga-DOTATOC SUVmax was able to significantly predict the presence of distant metastases with a threshold of 51.27 (sensitivity and specificity of 85.7 and 68.1%, respectively). 18F-FDG MTV and TLG were predictors of angioinvasion. The cut-off threshold for MTV was 7.98 (sensitivity and specificity of 69.7 and 82.4%, respectively) (p = 0.0004) whereas the cut-off for TLG was 32.4 (sensitivity and specificity of 69.7% and 82.4%, respectively) (p = 0.0004). Conclusion: Dual tracer 68Ga-DOTATOC and 18F-FDG PET scans provide relevant information regarding tumour behaviour and aggressiveness, implementing the diagnostic preoperative work-up.

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Prosperi, Daniela, Guido Gentiloni Silveri, Francesco Panzuto, Antongiulio Faggiano, Vincenzo Marcello Russo, Damiano Caruso, Michela Polici, et al. "Nuclear Medicine and Radiological Imaging of Pancreatic Neuroendocrine Neoplasms: A Multidisciplinary Update." Journal of Clinical Medicine 11, no. 22 (November 18, 2022): 6836. http://dx.doi.org/10.3390/jcm11226836.

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Pancreatic neuroendocrine neoplasms (panNENs) are part of a large family of tumors arising from the neuroendocrine system. PanNENs show low–intermediate tumor grade and generally high somatostatin receptor (SSTR) expression. Therefore, panNENs benefit from functional imaging with 68Ga-somatostatin analogues (SSA) for diagnosis, staging, and treatment choice in parallel with morphological imaging. This narrative review aims to present conventional imaging techniques and new perspectives in the management of panNENs, providing the clinicians with useful insight for clinical practice. The 68Ga-SSA PET/CT is the most widely used in panNENs, not only fr diagnosis and staging purpose but also to characterize the biology of the tumor and its responsiveness to SSAs. On the contrary, the 18F-Fluordeoxiglucose (FDG) PET/CT is not employed systematically in all panNEN patients, being generally preferred in G2–G3, to predict aggressiveness and progression rate. The combination of 68Ga-SSA PET/CT and 18F-FDG PET/CT can finally suggest the best therapeutic strategy. Other radiopharmaceuticals are 68Ga-exendin-4 in case of insulinomas and 18F-dopamine (DOPA), which can be helpful in SSTR-negative tumors. New promising but still-under-investigation radiopharmaceuticals include radiolabeled SSTR antagonists and 18F-SSAs. Conventional imaging includes contrast enhanced CT and multiparametric MRI. There are now enriched by radiomics, a new non-invasive imaging approach, very promising to early predict tumor response or progression.

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Wessel, Andrea. "Druck auf Landgard nimmt zu." Lebensmittel Zeitung 73, no. 23 (2021): 18. http://dx.doi.org/10.51202/0947-7527-2021-23-018.

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Für Landgard wird die Lage immer verzwickter. Nicht nur die Kündigung einer großen Erzeugergruppe lastet schwer auf der Genossenschaft, auch beim Start der Obst-und-Gemüse-Plattform für Aldi Süd soll es Pannen gegeben haben.

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Tamura, Takashi, Yuto Sugihara, Hirofumi Yamazaki, Hiromu Koutani, Takaaki Tamura, Ikuhisa Tsuda, Tomoya Emori, et al. "Contrast-Enhanced Harmonic Endoscopic Ultrasound for Diagnosis of the Aggressiveness of Pancreatic Neuroendocrine Neoplasm." Diagnostics 12, no. 12 (November 29, 2022): 2988. http://dx.doi.org/10.3390/diagnostics12122988.

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The purpose of this study is to clarify the associations between the enhancement patterns on contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) and the aggressiveness and prognosis of pancreatic neuroendocrine neoplasms (PanNENs). Patients who underwent CH-EUS and were pathologically diagnosed with PanNEN were included in this study. Patients were divided into three groups according to contrast-enhancement patterns on early-phase and late-phase imaging: “Group A”, vascular rich in both phases; “Group B”, vascular rich and vascular poor in early and late phases, respectively; “Group C”, vascular poor in both phases. Of 39 patients, 25 were assigned to Group A, 7 to Group B, and 7 to Group C. The median overall survival was not reached in Groups A and B and was 335 days in Group C (p < 0.001). The 1-year survival rates were 100% in Group A, 60% in Group B, and 43% in Group C. Patients in Group C showed the shortest overall survival among the three groups. The vascular-poor pattern on late-phase CH-EUS had the highest sensitivity, specificity, and accuracy for aggressive PanNENs among the patterns analyzed on CH-EUS and CECT (84.6%, 91.7%, and 89.2%, respectively). CH-EUS is useful for the diagnosis of and predicting the prognosis of PanNENs.

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Grolmusz, Vince Kornél, Annamária Kövesdi, Katalin Borka, Peter Igaz, and Attila Patócs. "Prognostic relevance of proliferation-related miRNAs in pancreatic neuroendocrine neoplasms." European Journal of Endocrinology 179, no. 4 (October 2018): 219–28. http://dx.doi.org/10.1530/eje-18-0305.

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ObjectivePancreatic neuroendocrine neoplasms (PanNENs) are rare tumors arising from the endocrine pancreas; however, their prognosis differs significantly upon their proliferative state, which is characterized by histopathological grading. MiRNAs are small, noncoding RNAs posttranscriptionally regulating gene expression. Our aim was to identify miRNAs with altered expression upon proliferation which can be used as prognostic biomarkers in PanNENs.MethodsMiRNA expression profiles of 40 PanNENs were downloaded from Gene Expression Omnibus and were reanalyzed upon tumor grades (discovery cohort). Results of the reanalysis were confirmed by qRT-PCR analysis of five miRNAs on an independent validation cohort of 63 primary PanNEN samples. Cox proportional hazards survival regression models were fit for both univariate and multivariate analysis to determine the miRNAs’ effect on progression-free and overall survival.ResultsNineteen miRNAs displayed differential expression between tumor grades. The altered expression of three out of five chosen miRNAs was successfully validated; hsa-miR-21, hsa-miR-10a and hsa-miR-106b were upregulated in more proliferative PanNENs compared to Grade 1 tumors. In univariate analysis, higher expression of tissue hsa-miR-21, hsa-miR-10a and hsa-miR-106b of primary PanNENs predicted worse progression-free and overall survival; however, multivariate analysis only confirmed the expression of hsa-miR-21 as an independent prognostic factor.ConclusionsThe expression of hsa-miR-106b, hsa-miR-10a and especially hsa-miR-21 has prognostic relevance regarding progression-free and overall survival in patients with PanNENs.

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Zehnder, Adalbert. "Das Gesetz bin ich." kma - Klinik Management aktuell 11, no. 06 (June 2006): 40–42. http://dx.doi.org/10.1055/s-0036-1573783.

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Mit einem selbstherrlichen Führungsstil setzt der Geschäftsführer einer 1000-Betten-Klinik in Oberfranken Ruf und Fortbestand seines Hauses aufs Spiel. Pannen und Skandale häufen sich, das Personal ist frustriert. Jetzt verlangt eineungewöhnliche Protestbewegung aus mundtot gemachten Mitarbeitern, niedergelassenen Ärzten, Honoratioren und Patienten seine Entfernung aus dem Amt.

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Cowzer, Darren, Ronak H. Shah, Sippy Punn, Laura Fiedler, April DeMore, Joanne F. Chou, Marinela Capanu, Michael F. Berger, Diane Reidy-Lagunes, and Nitya Prabhakar Raj. "Next-generation sequencing (NGS) of circulating cell-free DNA (cfDNA) in advanced pancreatic neuroendocrine neoplasms (PanNENs)." Journal of Clinical Oncology 41, no. 4_suppl (February 1, 2023): 653. http://dx.doi.org/10.1200/jco.2023.41.4_suppl.653.

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653 Background: PanNENs represent 1-2% of all pancreatic neoplasms. The genomic landscape derived from PanNEN tumor tissue has been described previously. There are little data detailing the frequency of genetic alterations identified in cfDNA in an advanced PanNEN population, the plasma-tissue concordance of detected alterations, and the clinical utility of cfDNA. Methods: Patients (pts) with metastatic PanNENs underwent collection of cfDNA for NGS using the MSK-IMPACT 505 gene assay between March 2017 and April 2020. Matched tissue based NGS with the FDA authorized MSK-IMPACT gene assay was completed when tumor tissue was available. For some pts, plasma and tumor tissue were sequenced at multiple time points. Clinical actionability of sequence variants was annotated by OncoKB. Clinicopathologic characteristics were extracted, and data are herein reported. Results: 25 unique pts with metastatic PanNENs had 32 plasma samples analyzed. The majority had well differentiated (22/25; 88%), intermediate grade disease (13/25; 52%). 6 (24%) pts had well differentiated high grade disease and 3 (12%) had poorly differentiated neuroendocrine carcinomas. After extraction, median cfDNA yield per sample was 23.98ng (range: 3.2 to 500.1). Mutations were detected in 21(66%) of 32 samples (10 pre systemic therapy, 10 at progression, 12 post response to therapy or while stable on therapy). The most frequently mutated genes occurring in >10% of patients were DAXX (28%), TSC2 (24%), MEN1 (24%), ARID1B (20%), ARID1A (12%) and ATRX (12%). 23 (92%) pts underwent tumor tissue sequencing with MSK-IMPACT with a median time of 6.9 (range: 0.5-33.4) months between tissue collection and time of plasma analysis. NGS of cfDNA identified the most common mutations observed in tumor tissue for: DAXX (5/6; 83%), TSC2 (3/6; 50%), MEN1 (5/12; 42%), ARID1A (3/5; 60%) and ATRX (3/6; 50%). In 21/23 (91%) paired samples, additional mutations not seen in tissue were detected in plasma and included TSC2, TP53, EGFR, VHL, and BRCA2. Potentially actionable mutations were identified in sequenced cfDNA in 8/25 (32%) patients including 4 TSC2 mutations (level 3b), 1 ATM mutation (level 3b), 2 ARID1A mutations (level 4) and 1 KRAS mutation (level 4). One patient who was treated with larotrectinib for an ETV6:NTRK3 fusion detected on tumor sequencing ultimately developed resistance with a NRTK3 G623R alteration identified through sequencing of cfDNA at radiographic disease progression. Conclusions: NGS of cfDNA in metastatic PanNENs, across the spectrum of WHO-defined tumor grade/differentiation, revealed tumor-associated genetic alterations in 66% of plasma samples. Clonal evolution, actionable alterations, and resistance mechanisms can be detected through circulating cfDNA genotyping and may serve as a powerful tool to better understand disease biology of a disease that often changes over time and through therapy.

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Doelfs, Guntram. "Kommentar: Der rastlose Minister." kma - Klinik Management aktuell 26, no. 09 (September 2021): 40. http://dx.doi.org/10.1055/s-0041-1736062.

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Die Bilanz von vier Jahren Jens Spahn als Gesundheitsminister fällt gemischt aus. Einerseits durchbrach er die jahrelange Blockade im Gesundheitswesen, brachte mit Gesetzen im gefühlten Wochentakt vor allem die Digitalisierung und die Pflege voran. Andererseits blieb so manches Stückwerk – und in der Corona-Krise leistete sich der Minister einige Pannen. Spahn ficht das nicht an, Kritik perlt an ihm einfach ab.

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Frilling, Andreja, Ashley Clift, Adil Al-Nahhas, Richard P. Baum, and Daniel Kaemmerer. "Surgery and peptide receptor radionuclide therapy: An effective multimodal approach for metastatic neuroendocrine tumors." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 4113. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.4113.

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4113 Background: Neuroendocrine neoplasia (NEN) of the pancreas (PanNEN) or small bowel (SBNEN) frequently present with metastases at initial diagnosis, undermining the efficacy of surgical treatment. Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues, 90Y-DOTATOC and 177Lu-DOTATATE, has been shown to achieve prolonged progression-free survival (PFS) and overall survival (OS) in a substantial number of non-surgical patients with advanced NEN. Our aim was to prospectively determine the efficacy of a combination of radical loco-regional surgery and 177Lu PRRT in patients with metastasised NEN. Methods: A set of inclusion criteria was defined (e.g. PanNEN or SBNEN, G1/G2 NEN, initial tumour diagnosis, treatment naïve patient, stage IV NEN, positivity on 68Ga DOTATATE or DOTATOC PET/CT, eligibility for surgery and PRRT). Patients underwent PRRT within 3 months following surgery. Follow-up included biochemistry and imaging. Outcome measures included 1-, 3-, and 5-year OS and PFS from initial diagnosis. Results: Forty-one patients met eligibility criteria and were included. There were 26 males (63.4%) and median age at surgery was 58.8 years (range 32.1-78.3). All patients with SBNEN underwent right hemicolectomy, terminal ileal resection and mesenteric lympadenectomy. In PanNEN patients either Whipple procedure or distal pancreatectomy and peripancreatic lymphadenectomy were performed. The median number of PRRT cycles was 4 (range 2-6). Post-treatment mortality was 0%. Surgical morbidity was 12% (all grade 1 according Clavien-Dindo) and transient grade 1 toxicity occurred post PRRT in 40%. There was no grade 3 toxicity. Median follow-up was 5.48 years (range 0.53 – 11.98). Median PFS and OS were 3.33 years and 9.07 years, respectively. Progression-free survival (with 95% CI) was at 1-, 3-, and 5-years 80% (68.7-92.6), 60.9% (45.9-75.9) and 43.3% (27.4-59.3), respectively. Overall survival (with 95% CI) at 1-, 3-, and 5-years was 97.6% (93-100), 97.6% (93-100), and 95% (87-100), respectively. Conclusions: Radical loco-regional surgery for primary tumours combined with PRRT provides a novel, highly efficacious approach in metastasised NEN.

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Mori, Martina, Giulia Benedetti, Stefano Partelli, Carla Sini, Valentina Andreasi, Sara Broggi, Maurizio Barbera, et al. "Ct radiomic features of pancreatic neuroendocrine neoplasms (panNEN) are robust against delineation uncertainty." Physica Medica 57 (January 2019): 41–46. http://dx.doi.org/10.1016/j.ejmp.2018.12.005.

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Bračič, Stojan. "Sornig, Karl (1993): Sprache: Spiel. (Das agonale Prinzip in der Kommunikation) (lrr ttimer, Irreführungen, Spiel der Gestalten). Grazer Linguistische Monographien 9. Graz. 416 Seiten." Linguistica 35, no. 2 (December 1, 1995): 347–51. http://dx.doi.org/10.4312/linguistica.35.2.347-351.

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Das besprochene Heft 9 aus der Serie "Grazer Linguistische Monographien" ist eigentlich das fünfte Faszikel einer umfangreicheren Studie des Autors, die bis jetzt bereits folgende Themata behandelte: Vom Ur-Schweigen ins Reden (fasc. I), Am biguitäten (fasc. II), Metapher (fasc. III), Sprachmagische Strategien (fasc. IV). Im vor liegenden fünften Faszikel ist die Rede von lrrtümern (Pannen), Irreführungen und dem Spiel der Gestalten, die alle dem Spiel der Sprache und mit der Sprache zugrunde liegen.

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Shimura, Mitsuhiro, Masamichi Mizuma, Tatsuyuki Takadate, Yasutake Katoh, Takashi Suzuki, Masahiro Iseki, Tatsuo Hata, et al. "A novel liver metastasis-correlated protein of pancreatic neuroendocrine neoplasm (PanNEN) discovered by proteomic analysis." Oncotarget 9, no. 36 (May 11, 2018): 24291–303. http://dx.doi.org/10.18632/oncotarget.25110.

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Primavesi, Florian, Valentina Andreasi, Frederik J. H. Hoogwater, Stefano Partelli, Dominik Wiese, Charlotte Heidsma, Benno Cardini, et al. "A Preoperative Clinical Risk Score Including C-Reactive Protein Predicts Histological Tumor Characteristics and Patient Survival after Surgery for Sporadic Non-Functional Pancreatic Neuroendocrine Neoplasms: An International Multicenter Cohort Study." Cancers 12, no. 5 (May 14, 2020): 1235. http://dx.doi.org/10.3390/cancers12051235.

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Background: Oncological survival after resection of pancreatic neuroendocrine neoplasms (panNEN) is highly variable depending on various factors. Risk stratification with preoperatively available parameters could guide decision-making in multidisciplinary treatment concepts. C-reactive Protein (CRP) is linked to inferior survival in several malignancies. This study assesses CRP within a novel risk score predicting histology and outcome after surgery for sporadic non-functional panNENs. Methods: A retrospective multicenter study with national exploration and international validation. CRP and other factors associated with overall survival (OS) were evaluated by multivariable cox-regression to create a clinical risk score (CRS). Predictive values regarding OS, disease-specific survival (DSS), and recurrence-free survival (RFS) were assessed by time-dependent receiver-operating characteristics. Results: Overall, 364 patients were included. Median CRP was significantly higher in patients >60 years, G3, and large tumors. In multivariable analysis, CRP was the strongest preoperative factor for OS in both cohorts. In the combined cohort, CRP (cut-off ≥0.2 mg/dL; hazard-ratio (HR):3.87), metastases (HR:2.80), and primary tumor size ≥3.0 cm (HR:1.83) showed a significant association with OS. A CRS incorporating these variables was associated with postoperative histological grading, T category, nodal positivity, and 90-day morbidity/mortality. Time-dependent area-under-the-curve at 60 months for OS, DSS, and RFS was 69%, 77%, and 67%, respectively (all p < 0.001), and the inclusion of grading further improved the predictive potential (75%, 84%, and 78%, respectively). Conclusions: CRP is a significant marker of unfavorable oncological characteristics in panNENs. The proposed internationally validated CRS predicts histological features and patient survival.

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Jiménez, Beatriz, Mei Ran Abellona U, Panagiotis Drymousis, Michael Kyriakides, Ashley K. Clift, Daniel S. K. Liu, Eleanor Rees, et al. "Neuroendocrine Neoplasms: Identification of Novel Metabolic Circuits of Potential Diagnostic Utility." Cancers 13, no. 3 (January 20, 2021): 374. http://dx.doi.org/10.3390/cancers13030374.

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The incidence of neuroendocrine neoplasms (NEN) is increasing, but established biomarkers have poor diagnostic and prognostic accuracy. Here, we aim to define the systemic metabolic consequences of NEN and to establish the diagnostic utility of proton nuclear magnetic resonance spectroscopy (1H-NMR) for NEN in a prospective cohort of patients through a single-centre, prospective controlled observational study. Urine samples of 34 treatment-naïve NEN patients (median age: 59.3 years, range: 36–85): 18 had pancreatic (Pan) NEN, of which seven were functioning; 16 had small bowel (SB) NEN; 20 age- and sex-matched healthy control individuals were analysed using a 600 MHz Bruker 1H-NMR spectrometer. Orthogonal partial-least-squares-discriminant analysis models were able to discriminate both PanNEN and SBNEN patients from healthy control (Healthy vs. PanNEN: AUC = 0.90, Healthy vs. SBNEN: AUC = 0.90). Secondary metabolites of tryptophan, such as trigonelline and a niacin-related metabolite were also identified to be universally decreased in NEN patients, while upstream metabolites, such as kynurenine, were elevated in SBNEN. Hippurate, a gut-derived metabolite, was reduced in all patients, whereas other gut microbial co-metabolites, trimethylamine-N-oxide, 4-hydroxyphenylacetate and phenylacetylglutamine, were elevated in those with SBNEN. These findings suggest the existence of a new systems-based neuroendocrine circuit, regulated in part by cancer metabolism, neuroendocrine signalling molecules and gut microbial co-metabolism. Metabonomic profiling of NEN has diagnostic potential and could be used for discovering biomarkers for these tumours. These preliminary data require confirmation in a larger cohort.

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Miura, T., T. Aoki, H. Ohtsuka, S. Aoki, T. Hata, M. Iseki, T. Takadate, et al. "Preoperative neutrophil‐to‐lymphocyte ratio (NLR) predicts recurrence after surgery in patient with pancreatic neuroendocrine neoplasm (PanNEN)." Annals of Oncology 30 (November 2019): ix59. http://dx.doi.org/10.1093/annonc/mdz422.049.

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Tang, Laura H. "Pancreatic Neuroendocrine Neoplasms: Landscape and Horizon." Archives of Pathology & Laboratory Medicine 144, no. 7 (April 16, 2020): 816–28. http://dx.doi.org/10.5858/arpa.2019-0654-ra.

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Context.— Since the initial description of pancreatic endocrine physiology and the recognition of islet cell tumors in the 1800s, there have been noteworthy advances in the pathobiology of pancreatic neuroendocrine neoplasms (PanNENs), and definition of the important distinction between well-differentiated neuroendocrine tumor (PanNET) and poorly differentiated neuroendocrine carcinoma (PanNEC). The evolving knowledge has resulted in a continuous update in terminology, classification, and grading system for this group of neoplasms. Pancreatic neuroendocrine tumors associated with hereditary conditions have been linked to unique molecular and genetic events, and sporadic PanNETs have specific gene signatures. Based on accumulative experience and knowledge, therapeutic strategies have been defined for this group of neoplasms. Objective.— To review the evolution and description of the pathologic-genomic evolution of PanNENs, and to facilitate accurate pathologic interpretation for the corresponding clinical management. Data Sources.— Literature review of published studies and author's own work. Conclusions.— Evolving experience and knowledge have established subtypes of pancreatic neuroendocrine neoplasms, based on their genotype and phenotype. Accurate pathologic interpretation of the specific neoplasm has significant implications for therapy and prognosis.

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Beheshti, Kathryn, Charlie Endris, Peter Goodwin, Annabelle Pavlak, and Kerstin Wasson. "Burrowing crabs and physical factors hasten marsh recovery at panne edges." PLOS ONE 17, no. 1 (January 5, 2022): e0249330. http://dx.doi.org/10.1371/journal.pone.0249330.

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Salt marsh loss is projected to increase as sea-level rise accelerates with global climate change. Salt marsh loss occurs along both lateral creek and channel edges and in the marsh interior, when pannes expand and coalesce. Often, edge loss is attributed to erosive processes whereas dieback in the marsh interior is linked to excessive inundation or deposition of wrack, but remains poorly understood. We conducted a two-year field investigation in a central California estuary to identify key factors associated with panne contraction or expansion. Our study explored how an abundant burrowing crab, shown to have strong negative effects on marsh biomass near creek edges, affects panne dynamics. We also explored which physical panne attributes best predicted their dynamics. To our knowledge, ours is the first study of panne dynamics in a California marsh, despite how ubiquitous pannes are as a feature of marshes in the region and how often extensive marsh dieback occurs via panne expansion. Overall, we found that pannes contracted during the study period, but with variable rates of marsh recovery across pannes. Our model incorporating both physical and biological factors explained 86% of the variation in panne contraction. The model revealed a positive effect of crab activity, sediment accretion, and a composite of depth and elevation on panne contraction, and a negative effect of panne size and distance to nearest panne. The positive crab effects detected in pannes contrast with negative effects we detected near creek edges in a previous study, highlighting the context-dependence of top-down and bioturbation effects in marshes. As global change continues and the magnitude and frequency of disturbances increases, understanding the dynamics of marsh loss in the marsh interior as well as creek banks will be critical for the management of these coastal habitats.

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Rahma, Ira, Sistiana Windyariani, and Suhendar. "Profil Kemampuan Pemecahan Masalah Siswa SMA Pada Materi Ekosistem." BIODIK 6, no. 3 (September 4, 2020): 277–87. http://dx.doi.org/10.22437/bio.v6i3.9551.

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This study aims to describe the profile of problem-solving abilities on each indicator according to Pannen (in Rusmono, 2012). The research used is descriptive method. The sample used is 35 students who have studied the ecosystem material. The sample selection technique used in this study was purposive sampling, which is a sample collection technique with certain considerations, subject taking is not based on strata, random or regional but is based on the existence of certain objectives. This research was conducted in FEBRUARY 4th week of 2020. The instrument used was a test question for the description of problem-solving abilities, amounting to 12 questions. The results showed that the problem-solving ability profile had a percentage of 59% in the sufficient category. The results include three categories, namely; 1) the good category consists of indicators of identifying problems by 75% and collecting 66% of data, 2) sufficient categories consisting of indicators of solving problems based on data by 55%, choosing ways to solve problems by 61%, and planning to implement problems by 57% . 3) the less category consists of indicators of analyzing data / problems by 40%. Abstrak. Penelitian ini bertujuan untuk mendeskripsikan profil kemampuan pemecahan masalah pada setiap indikator menurut Pannen (dalam rusmono, 2012). Penelitian yang digunakan ialah metode deskriptif. Sampel yang digunakan sebanyak 35 siswa yang telah mempelajari materi ekosistem. Teknik pemilihan sampel yang di gunakan dalam penelitian ini adalah menggunakan purposive sampling, yaitu teknik pengumpulan sampel dengan pertimbangan tertentu, pengambilan subjek bukan di dasarkan atas strata, random atau daerah tetapi di dasarkan atas adanya tujuan tertentu. Penelitian ini dilaksanakan pada bulan FEBRUARI minggu ke-4 tahun 2020. Instrumen yang digunakan berupa soal tes uraian kemampuan pemecahan masalah yang berjumlah 12 soal. Hasil penelitian menunjukkan profil kemampuan pemecahan masalah memiliki persentase sebesar 59% dengan kategori cukup. Adapun hasil tersebut mencakup tiga ketegori ialah; 1) Kategori baik terdiri dari indikator mengidentifikasi masalah sebesar 75% dan mengumpulkan data 66%, 2) Kategori cukup terdiri dari indikator memecahkan masalah berdasarkan data sebesar 55%, memilih cara untuk memecahkan masalah masalah sebesar 61%, dan merencanakan penerapan masalah sebesar 57%. 3) Kategori kurang terdiri dari indikator menganalisis data/masalah sebesar 40%.

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43

Grau, Andreas. "Der Rücktritt von Bundeskanzler Willy Brandt im Mai 1974 aus Sicht der Union: „Eine Summe von Pannen“ und „mäßiges Krisenmanagement“." Historisch-Politische Mitteilungen 22, no. 1 (December 2015): 153–70. http://dx.doi.org/10.7788/hpm-2015-0106.

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Sadid, Agus. "MODEL DESA TERPADU PAUDNI MEWUJUDKAN MASYARAKAT PEMBELAJAR SEPANJANG HAYAT." JIV-Jurnal Ilmiah Visi 9, no. 1 (June 30, 2014): 56–67. http://dx.doi.org/10.21009/jiv.0901.7.

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The pattern of rural development should move towards an integral-concept of development. Early childhood education program, (PAUDNI) has a huge potential to enhance peopleâ€™s welfare. The village model of PAUDNI would be the best alternative solution of empowering community. The problem is how to develop the integrated village model that establishes a life-long learning community. This article describes, discusses, and explores the integrated village model of PUDNI. The conclusion is (1) the PAUDNI village is constructed by the andragogy theory by Knowles and Pannen, emphasizing the community empowerment on integral and integrated aspects; (2) the construction of PAUDNI village model includes community participations, cooperation, commitment, and integrity; (3) the implementation of the model should consider data and analysis, community participation, PAUDNI Units such as PKBM, LKP, PAUD and other non-formal and informal groups; (4) in supervision and guidance process, the model of PAUNI village should involve some related people or institutions. Implementing such a village model properly would create a life-long learning community and enhance the social welfare and the life quality of the community.

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Saponjski, Jelena, Dragana Sobic-Saranovic, Djuro Macut, Tatjana Isailovic, Nikola Bogosavljevic, Darko Jovanovic, and Vera Artiko. "The role of somatostatin receptor scintigraphy in the diagnosis and follow-up of the pancreatic neuroendocrine neoplasms." Nuclear Technology and Radiation Protection 35, no. 3 (2020): 261–67. http://dx.doi.org/10.2298/ntrp2003261s.

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The aim of investigation was to assess the role of somatostatin receptor scintigraphy in diagnosis and follow-up of pancreatic neuroendocrine neoplasms. Somatostatin receptor scintigraphy was performed with 740 MBq 99mTc-EDDA/HYNIC TOC for diagnosis of primary tumors and follow-up after the therapy. There were 63 true positive, 24 true negative, 4 false positive, and 6 false negative findings. Sensitivity was 91.3 %, specificity 85.7 %, positive predictive value 94.0 %, negative predictive value 80.0 %, accuracy 89.7 %. The SPECT contributed diagnosis in 28 true positive findings. In 32 patients (33 %) somatostatin receptor scintigraphy significantly changed the management of the patients (10 had surgery, in 17 somatostatin analogues, and in 5 peptide receptor radionuclide therapy was introduced). Mean Ki-67 index in true positive patients was 13.8 ?5.0 % while in true negative 7.1 ? 3.4% which is significantly lower at p < 0.05. There was significantly (p < 0.01) higher number of increased chromogranin A values in true positive than in true negative patients (p = 0.000857). Our results confirmed the value of SRS in the diagnosis and follow-up of the patients with pancreatic neuroendocrine neoplasms PanNEN if primary tumors, recurrences or metastases are suspected, as well as for appropriate choice of the therapy.

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Permatasari, Anak Agung Ayu Putri, Ni Kadek Yunita Sari, and I. Made Endra Puniawan. "PKM PEMANFAATAN LIMBAH TANAMAN PANDAN WANGI DI DESA CEPAKA, KEDIRI, TABANAN." JURNAL WIDYA LAKSANA 11, no. 1 (February 19, 2022): 55. http://dx.doi.org/10.23887/jwl.v11i1.32530.

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Tanaman pandan wangi tumbuh subur di negara beriklim tropis, yang biasanya dimanfaatkan sebagai campuran bahan masakan untuk membuatnya wangi dan enak. Daun pandan wangi mengandung zat alkaloida, polifenol, flavonoida, tannin, saponin dan juga zat warna alami. Senyawa tersebut dapat berperan sebagai anti bakteri, mengontrol kadar gula darah, mencegah kanker, mengatasi masalah gigi dan gusi, mengatasi kram, mengurangi rambut rontok dan masalah sakit kepala.. Salah satu perkebunan pandan wangi yang terdapat di Bali yaitu UD. Melonila, yang terletak di Jalan Raya Munggu Desa Cepaka, Tabanan Bali. Hasil perkebunan pandan wangi biasanya dipasarkan ke pasar tradisional. Setelah dipanen tanaman ini harus segera didistribusikan agar tetap segar. Sedangkan tanaman yang merupakan sisa hasil panen memiliki kualitas yang hampir sama, tumbuh dengan cepat akan tetapi tidak mudah untuk dipasarkan. Oleh karena itu banyaknya hasil panen dari tanaman pandan wangi ini yang selalu tumbuh dengan cepat dan mudah menjadi permasalahan yang dialami oleh mitra, sehingga mitra ingin berinovasi mengembangkan produk dari limbah tanaman kemangi menjadi desinfektan alami. Oleh karena itu dilakukan pengembangan terhadap produk dengan menentukan merk dagang dan desain kemasan serta pemasaran produk yang dilakukan melalui sosial media. Berdasarkan hasil PKM didapatkan bahwa kelompok tani mengalami rata-rata peningkatan pengetahuan mengenai pemanfaatan limbah pandan wangi sebesar 83%. Kata Kunci : Desa Cepaka, desinfektan alami, inovasi, pemasaran

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Wigmore, Annemieke. "Fry panned?" New Scientist 203, no. 2724 (September 2009): 27. http://dx.doi.org/10.1016/s0262-4079(09)62338-1.

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48

Dube, M. P. "Panculture panned." JAMA: The Journal of the American Medical Association 270, no. 16 (October 27, 1993): 1934b—1934. http://dx.doi.org/10.1001/jama.270.16.1934b.

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Dubé, Michael P. "Panculture Panned." JAMA: The Journal of the American Medical Association 270, no. 16 (October 27, 1993): 1934. http://dx.doi.org/10.1001/jama.1993.03510160052023.

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Singhi, Aatur D., Philip J. Stephens, Jeffrey S. Ross, Vincent A. Miller, Siraj Mahamed Ali, and Alexa Betzig Schrock. "Utility of comprehensive genomic profiling (CGP) to distinguish neoplasms pathologically diagnosed as PanNETs and PanNECs and identify potentially actionable genomic alterations (GA)." Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 274. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.274.

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274 Background: The majority of pancreatic neuroendocrine neoplasms are classified as pancreatic neuroendocrine tumors (PanNETs) or carcinomas (PanNECs). These are distinct entities with respect to clinical presentation, prognosis and treatment; however, locally advanced/metastatic cases may exhibit overlapping histopathologic features and, thus are challenging to differentiate and may result in inappropriate management. Recent sequencing studies have identified key differences between PanNETs and PanNECs. PanNECs often harbor recurrent GA in RB1, and members of the RAS/MAPK and TGF-β pathways. In contrast, PanNETs frequently exhibit GA in chromatin remodeling genes (e.g., MEN1, DAXX and ATRX). The purpose of this study was to evaluate the utility of CGP in the pathologic assessment of locally advanced/metastatic pancreatic neuroendocrine neoplasms. Methods: Hybrid-capture based CGP was performed for up to 315 cancer-related genes and intronic regions of up to 28 genes rearranged in cancer on 318 locally advanced/metastatic pancreatic neuroendocrine neoplasms. Results were correlated with submitting histopathologic diagnoses. Results: Among 50 pathologically-classified PanNETs, 41 (82%) and 9 (18%) cases harbored GA consistent with a PanNET and PanNEC, respectively. In comparison, among 268 pathologically-classified PanNECs, 209 (78%) and 59 (22%) cases had GA compatible with a PanNET and PanNEC, respectively. Commonly altered genes in CGP-classified PanNETs include: MEN1 (37%), DAXX (21%), CDKN2A/B (20%), ATRX (11%), TSC2 (10%), TP53 (8%), PTEN (8%), ARID1A (7%) and SETD2 (5%). Defects in the BRCA pathway were seen in 10% of PanNETs. Conversely, CGP-classified PanNECs had GA in TP53 (54%), RB1 (49%), KRAS (46%), CDKN2A/B (21%), GNAS (10%), PTEN (9%), SMAD4 (7%), MYC (7%) and ARID1A (6%). Conclusions: Pathologic discrimination between PanNETs and PanNECs can be difficult, but incorporating CGP improves the classification of these neoplasms. Further, the identification of recurrent GA in members of the BRCA family highlights a potential therapeutic target for locally advanced/metastatic PanNETs.

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Journal articles on the topic 'PanNEN'

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