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Article: Non-Interventional Management of Advanced Pancreatic Neuroendocrine Neoplasms in Patients with von Hippel-Lindau Disease.

Halperin, Reut / Tirosh, Amit

2023 Volume 15, Issue 6

Abstract: Von Hippel-Lindau (VHL) is a rare autosomal dominant hereditary cancer predisposition syndrome. Patients with VHL have a high risk for developing retinal and central nervous system hemangioblastoma, pheochromocytoma, renal cell carcinoma, and pancreatic ... ...

Abstract	Von Hippel-Lindau (VHL) is a rare autosomal dominant hereditary cancer predisposition syndrome. Patients with VHL have a high risk for developing retinal and central nervous system hemangioblastoma, pheochromocytoma, renal cell carcinoma, and pancreatic neuroendocrine neoplasms (PNEN). About a fifth of patients with VHL will develop PNEN, and only a tenth of them will develop metastatic or unresectable (advanced) PNEN requiring medical intervention. In this review, we performed a literature search for studies, written in English, on the medical interventions for VHL-related localized and advanced PNENs and their clinical outcomes. We detail the various medical interventions for this rare group of patients, including their mode of action and potential efficacy and toxicity. Finally, based on the current literature, we delineate a possible management algorithm for patients with VHL and advanced PNEN. We can conclude that data on the efficacy of various vascular endothelial growth factor (VEGF) receptor inhibitors, and on the efficacy of belzutifan, a novel hypoxia-inducible factor 2 inhibitor, for the management of advanced PNEN in VHL, are scarce. Hence, deduction from the management of sporadic PNEN is required, and is implemented in the proposed management algorithm provided within this review.
Language	English
Publishing date	2023-03-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15061739
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Article ; Online: A Case of Metastatic Thymoma Responsive to Treatment With 177 Lu-DOTATATE.

Halperin, Reut / Urban, Damien / Tirosh, Amit

Clinical nuclear medicine

2023 Volume 48, Issue 4, Page(s) e190–e192

Abstract: Abstract: We describe a case of a 74-year-old woman with germline BRCA2 mutation, with an incidental diagnosis of metastatic thymoma presenting as a mediastinal mass with cardiac muscle and lymph node involvement. Despite surgical and radiotherapy ... ...

Abstract	Abstract: We describe a case of a 74-year-old woman with germline BRCA2 mutation, with an incidental diagnosis of metastatic thymoma presenting as a mediastinal mass with cardiac muscle and lymph node involvement. Despite surgical and radiotherapy treatment, there was marked advancement with new lung and liver metastases. All lesions demonstrated 68 Ga-DOTATATE PET/CT uptake, and the patient received 4 peptide receptor radionuclide therapy cycles with 177 Lu-DOTATATE, with pronounced reduction in the size of the liver, cardiac, and pleural lesions. This is the first case to demonstrate partial response to peptide receptor radionuclide therapy in metastatic thymoma, thus suggesting possible treatment option to refractory and advancing metastatic thymoma.
MeSH term(s)	Aged ; Female ; Humans ; Neuroendocrine Tumors/pathology ; Octreotide ; Organometallic Compounds ; Positron Emission Tomography Computed Tomography ; Receptors, Peptide ; Thymoma ; Thymus Neoplasms
Chemical Substances	copper dotatate CU-64 ; Octreotide (RWM8CCW8GP) ; Organometallic Compounds ; Receptors, Peptide ; Lutetium-177 (BRH40Y9V1Q)
Language	English
Publishing date	2023-01-14
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	197628-x
ISSN	1536-0229 ; 0363-9762
ISSN (online)	1536-0229
ISSN	0363-9762
DOI	10.1097/RLU.0000000000004553
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Zs.A 1276: Show issues

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Article: Unique Characteristics of Patients with Von Hippel-Lindau Disease Defined by Various Diagnostic Criteria.

Halperin, Reut / Arnon, Liat / Eden-Friedman, Yehudit / Tirosh, Amit

Cancers

2023 Volume 15, Issue 6

Abstract: Von Hippel-Lindau (VHL) disease diagnosis is based on two criteria sets: International criteria (IC, two hemangioblastomas, one hemangioblastoma plus one visceral lesion, or VHL family history/pathogenic variant plus hemangioblastoma/visceral lesion); or ...

Abstract	Von Hippel-Lindau (VHL) disease diagnosis is based on two criteria sets: International criteria (IC, two hemangioblastomas, one hemangioblastoma plus one visceral lesion, or VHL family history/pathogenic variant plus hemangioblastoma/visceral lesion); or Danish criteria (DC, two clinical manifestations, or VHL family history/pathogenic variant plus hemangioblastoma/visceral lesion). We aimed to compare the characteristics of patients with VHL-related pancreatic neuroendocrine tumor (vPNET) meeting either the clinical Danish criteria only (DOC) or IC to those with sporadic PNET (sPNET). The cohort included 33 patients with VHL (20 vPNETs) and 65 with sPNET. In terms of genetic testing and family history of VHL, 90.0% of the patients with vPNET in the IC group had a germline
Language	English
Publishing date	2023-03-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15061657
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Article: Genetic and epigenetic alterations in pancreatic neuroendocrine tumors.

Tirosh, Amit / Kebebew, Electron

Journal of gastrointestinal oncology

2020 Volume 11, Issue 3, Page(s) 567–577

Abstract: Neuroendocrine tumors (NETs) are a heterogenous group of tumors that originate from neuroendocrine cells, mainly in the pancreas and the gastrointestinal and bronchopulmonary tracts. There has been considerable progress in our understanding of the ... ...

Abstract	Neuroendocrine tumors (NETs) are a heterogenous group of tumors that originate from neuroendocrine cells, mainly in the pancreas and the gastrointestinal and bronchopulmonary tracts. There has been considerable progress in our understanding of the genetic and epigenetic changes associated with pancreatic NETs (PNETs). The main genetic alterations that drive PNETs include genetic alterations in
Language	English
Publishing date	2020-06-30
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2594644-4
ISSN	2219-679X ; 2078-6891
ISSN (online)	2219-679X
ISSN	2078-6891
DOI	10.21037/jgo.2020.03.11
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Article ; Online: Towards Federated Learning with Byzantine-Robust Client Weighting

Amit Portnoy / Yoav Tirosh / Danny Hendler

Applied Sciences, Vol 12, Iss 8847, p

2022 Volume 8847

Abstract: Federated learning (FL) is a distributed machine learning paradigm where data are distributed among clients who collaboratively train a model in a computation process coordinated by a central server. By assigning a weight to each client based on the ... ...

Abstract	Federated learning (FL) is a distributed machine learning paradigm where data are distributed among clients who collaboratively train a model in a computation process coordinated by a central server. By assigning a weight to each client based on the proportion of data instances it possesses, the rate of convergence to an accurate joint model can be greatly accelerated. Some previous works studied FL in a Byzantine setting, in which a fraction of the clients may send arbitrary or even malicious information regarding their model. However, these works either ignore the issue of data unbalancedness altogether or assume that client weights are a priori known to the server, whereas, in practice, it is likely that weights will be reported to the server by the clients themselves and therefore cannot be relied upon. We address this issue for the first time by proposing a practical weight-truncation-based preprocessing method and demonstrating empirically that it is able to strike a good balance between model quality and Byzantine robustness. We also establish analytically that our method can be applied to a randomly selected sample of client weights.
Keywords	federated learning ; machine learning ; robustness ; Technology ; T ; Engineering (General). Civil engineering (General) ; TA1-2040 ; Biology (General) ; QH301-705.5 ; Physics ; QC1-999 ; Chemistry ; QD1-999
Subject code	006
Language	English
Publishing date	2022-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Impact of Pancreatic Neuroendocrine Tumor on Mortality in Patients With von Hippel-Lindau Disease.

Arnon, Liat / Halperin, Reut / Tirosh, Amit

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

2021 Volume 27, Issue 10, Page(s) 1040–1045

Abstract: Objective: The main causes for morbidity and mortality in von Hippel-Lindau (VHL) disease are central nervous system hemangioblastoma and clear cell renal cell carcinoma, but the effect of VHL-related pancreatic neuroendocrine tumors (PNET) on patient ... ...

Abstract	Objective: The main causes for morbidity and mortality in von Hippel-Lindau (VHL) disease are central nervous system hemangioblastoma and clear cell renal cell carcinoma, but the effect of VHL-related pancreatic neuroendocrine tumors (PNET) on patient outcome is unclear. We assessed the impact of PNET diagnosis in patients with VHL on all-cause mortality (ACM) risk. Methods: We used the Surveillance, Epidemiology, and End Results database. Of 16 344 patients, 170 had VHL based on clinical diagnostic criteria, and 510 patients had PNET (91 VHL-related and 419 sporadic). Results: Survival analysis demonstrated a lower ACM among patients with VHL-related PNET compared to patients with sporadic PNET (log-rank test, P = .011). Among patients with VHL, ACM risk was higher with vs without PNET (P = .029). The subgroup analysis revealed a higher ACM risk with metastatic PNET (sporadic P = .0031 and VHL-related P = .08) and a similar trend for PNET diameter ≥3 cm (P = .06 and P = 0.1 in sporadic and VHL-related PNET, respectively). In a multivariable analysis of patients with VHL, diagnosis with PNET by itself was associated with a trend of lower risk for ACM, while presence of metastatic PNET was independently associated with increased ACM risk. Conclusion: Diagnosis with PNET is not associated with a higher ACM risk in VHL by itself. The independent association of advanced PNET stage with higher mortality risk emphasizes the importance of active surveillance for detecting high-risk PNET at an early stage to allow timely intervention.
MeSH term(s)	Carcinoma, Renal Cell/epidemiology ; Hemangioblastoma/epidemiology ; Humans ; Kidney Neoplasms/epidemiology ; Pancreatic Neoplasms/epidemiology ; von Hippel-Lindau Disease/complications
Language	English
Publishing date	2021-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	1473503-9
ISSN	1530-891X
ISSN	1530-891X
DOI	10.1016/j.eprac.2021.03.005
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Zs.A 5034: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 508: Show issues

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Article ; Online: Low risk for all-cause mortality among patients with lung neuroendocrine tumors co-diagnosed with pituitary adenomas.

Peltz-Sinvani, Naama / Percik, Ruth / Uri, Inbal / Kfir, Sapir Kon / Tirosh, Amir / Tirosh, Amit

Endocrine

2021 Volume 73, Issue 3, Page(s) 745–751

Abstract: Purpose: Lung neoplasms often co-occur with pituitary adenoma (PA). However, whether co-diagnosis of lung neuroendocrine tumors (LNETs) and PA constitute a unique entity and the impact of such co-diagnosis on patients' outcome is yet to be defined. The ... ...

Abstract	Purpose: Lung neoplasms often co-occur with pituitary adenoma (PA). However, whether co-diagnosis of lung neuroendocrine tumors (LNETs) and PA constitute a unique entity and the impact of such co-diagnosis on patients' outcome is yet to be defined. The study objective was to compare patients' clinical characteristics with LNET to patients co-diagnosed with PA. Methods: A Retrospective, case-control study based on the Surveillance, Epidemiology, and End Results (SEER) registry database between 2000 and 2016. A total of 2947 patients with LNET, including 2913 with LNET alone ("Sporadic") and 34 patients with both LNET and PA ("LNET-PA"). Results: PA preceded LNET diagnosis in 85.3% of patients and had higher rates among LNET patients (34/2947) than with any cancer (p < 0.00001) and compared to patients with non-small cell lung cancer (NSCLC) (15/2378, p = 0.047). LNET-PA patients were younger at diagnosis compared with NSCLC patients and PA (p = 0.04). Among patients <60 years with LNET, co-diagnosis with PA was associated with lower all-cause mortality (ACM) risk (Log-rank test, p = 0.03). Adjusted ACM risk of patients with LNET-PA was lower than sporadic LNET (hazard ratio 0.553, 95% confidence interval 0.309-0.99, p = 0.046), especially among Caucasians, and lower overall-mortality risk in patients <60 years with borderline statistical significance (p = 0.071). Conclusions: Patients with both LNET and PA constitute a distinct morbidity and mortality profile than sporadic LNET, possibly suggesting an undefined MEN syndrome. Additional studies to further investigate patients' natural course and genetic profile with these neoplasms are needed.
Language	English
Publishing date	2021-05-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	1194484-5
ISSN	1559-0100 ; 1355-008X ; 0969-711X
ISSN (online)	1559-0100
ISSN	1355-008X ; 0969-711X
DOI	10.1007/s12020-021-02740-y
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Zs.A 3884: Show issues

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Article: Trabecular Bone Score Change Is Not Predicted by Bone Turnover: Short-term Sequential Follow-up.

Aharon-Hananel, Genya / Zacay, Galia / Tau, Noam / Levy-Shraga, Yael / Tirosh, Amit / Vered, Iris / Tripto-Shkolnik, Liana

The Israel Medical Association journal : IMAJ

2023 Volume 25, Issue 6, Page(s) 438–442

Abstract: Background: Trabecular bone score (TBS) reflects vertebrae microarchitecture and assists in fracture risk assessment. The International Society of Clinical Densitometry postulates that the role of TBS in monitoring antiresorptive therapy is unclear. ... ...

Abstract	Background: Trabecular bone score (TBS) reflects vertebrae microarchitecture and assists in fracture risk assessment. The International Society of Clinical Densitometry postulates that the role of TBS in monitoring antiresorptive therapy is unclear. Whether changes in TBS correlate with bone resorption measured by bone turnover markers is not known. Objectives: To determine whether longitudinal changes in TBS correlate with C-terminal telopeptide (CTX) of type I collagen. Methods: Examinees with two bone mineral density (BMD) measurements were detected via the institutional database. Over 5.8% change in TBS was considered least significant and patients were grouped accordingly (increment, decrement, or unchanged). CTX, BMD, co-morbidities, incident fractures, and medication exposure were compared between the groups by Kruskal-Wallis. The correlation between TBS and BMD change and CTX in a continuous model was analyzed by Pearson's correlation coefficient. Results: In total, 110 patients had detailed medical records. In 74.5%, TBS change was below least significant change. Two other TBS categories, fracture incidence or medication exposure, did not differ by CTX. In the continuous model, BMD and TBS change was positively correlated (r = 0.225, P = 0.018). A negative correlation was observed between BMD change and CTX. The decrease in BMD level was associated with higher CTX (r = -0.335, P = 0.004). No correlation was observed between CTX and TBS. Conclusions: No correlation between TBS dynamics and bone resorption marker was found. Clinical interpretation and implication of longitudinal TBS changes should be further explored.
MeSH term(s)	Humans ; Cancellous Bone/diagnostic imaging ; Follow-Up Studies ; Bone Remodeling ; Bone Resorption ; Fractures, Bone
Chemical Substances	sudan III (ND733RX3JN)
Language	English
Publishing date	2023-06-29
Publishing country	Israel
Document type	Journal Article
ZDB-ID	2008291-5
ISSN	1565-1088 ; 0021-2180
ISSN	1565-1088 ; 0021-2180
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Zs.A 5470: Show issues

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Article ; Online: Complications of acromegaly: thyroid and colon.

Tirosh, Amit / Shimon, Ilan

Pituitary

2017 Volume 20, Issue 1, Page(s) 70–75

Abstract: Introduction: In acromegaly the long-term exposure to high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels may result in specific complications in different human organs, including the thyroid gland and the colon.: Materials and ... ...

Abstract	Introduction: In acromegaly the long-term exposure to high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels may result in specific complications in different human organs, including the thyroid gland and the colon. Materials and methods: We will review here the evidence available regarding the characteristic thyroid and colon complications in acromegaly. Results: This review summarizes the published data observing noncancerous structural abnormalities (thyroid nodules, colonic polyps) and thyroid and colon cancer in patients diagnosed with acromegaly. Conclusion: Thyroid micro-carcinomas are probably over-diagnosed among acromegalic patients. In regard to colon cancer, there is no sufficient data to suggest that colon cancer risk is higher in acromegaly compared to the general population.
MeSH term(s)	Acromegaly/complications ; Acromegaly/metabolism ; Animals ; Colon/metabolism ; Colon/pathology ; Colonic Neoplasms/etiology ; Colonic Neoplasms/metabolism ; Humans ; Thyroid Gland/metabolism ; Thyroid Gland/pathology ; Thyroid Neoplasms/etiology ; Thyroid Neoplasms/metabolism
Language	English
Publishing date	2017-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1385151-2
ISSN	1573-7403 ; 1386-341X
ISSN (online)	1573-7403
ISSN	1386-341X
DOI	10.1007/s11102-016-0744-z
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Zs.A 6139: Show issues

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Article ; Online: The utility of

Tirosh, Amit / Kebebew, Electron

Future oncology (London, England)

2017 Volume 14, Issue 2, Page(s) 111–122

Abstract: Neuroendocrine tumors (NETs) are rare neoplasms that emerge mainly from the GI tract, pancreas and respiratory tract. The incidence of NETs has increased more than sixfold in the last decades. NETs typically express somatostatin receptors on their cell ... ...

Abstract	Neuroendocrine tumors (NETs) are rare neoplasms that emerge mainly from the GI tract, pancreas and respiratory tract. The incidence of NETs has increased more than sixfold in the last decades. NETs typically express somatostatin receptors on their cell surface, which can be targeted by 'cold' somatostatin analogs for therapy or by 'hot' radiolabeled somatostatin analogs for tumor localization and treatment. 68-Gallium-DOTA peptides (DOTATATE, DOTATOC, DOTANOC) positron emission tomography/computed tomography is a highly accurate imaging modality for NETs that has been found to be more sensitive for NET detection than other imaging modalities. In the current review, we will discuss the clinical utility of 68-Gallium-DOTATATE positron emission tomography/computed tomography for the diagnosis and management of patients with NETs.
MeSH term(s)	Gastrointestinal Tract/pathology ; Humans ; Neuroendocrine Tumors/diagnosis ; Neuroendocrine Tumors/diagnostic imaging ; Neuroendocrine Tumors/pathology ; Neuroendocrine Tumors/therapy ; Organometallic Compounds/therapeutic use ; Positron Emission Tomography Computed Tomography/trends ; Prognosis
Chemical Substances	Organometallic Compounds ; gallium Ga 68 dotatate (9L17Y0H71P)
Language	English
Publishing date	2017-10-26
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2274956-1
ISSN	1744-8301 ; 1479-6694
ISSN (online)	1744-8301
ISSN	1479-6694
DOI	10.2217/fon-2017-0393
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