Context:
Pheochromocytoma-paraganglioma syndrome is caused by mutations in SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase (SDH), and in SDHAF2, required for flavination of SDHA. A ...recent report described a patient with an abdominal paraganglioma, immunohistochemically negative for SDHA, and identified a causal germline mutation in SDHA.
Objective:
In this study, we evaluated the significance of SDHA immunohistochemistry in the identification of new patients with SDHA mutations.
Setting:
This study was performed in the Erasmus Medical Center in Rotterdam (The Netherlands) and the Université Paris Descartes in Paris (France).
Methods:
We investigated 316 pheochromocytomas and paragangliomas for SDHA expression. Sequence analysis of SDHA was performed on all tumors that were immunohistochemically negative for SDHA and on a subset of tumors immunohistochemically positive for SDHA.
Results:
Six tumors were immunohistochemically negative for SDHA. Four tumors from Dutch patients showed a germline c.91C→T SDHA gene mutation (p.Arg31X). Another tumor (from France) carried a germline SDHA missense mutation c.1753C→T (p.Arg585Trp). Loss of the wild-type SDHA allele was confirmed by loss of heterozygosity analysis. Sequence analysis of 35 SDHA immunohistochemically positive tumors did not reveal additional SDHA mutations.
Conclusions:
Our results demonstrate that SDHA immunohistochemistry on paraffin-embedded tumors can reveal the presence of SDHA germline mutations and allowed the identification of SDHA-related tumors in at least 3% of patients affected by apparently sporadic (para)sympathetic paragangliomas and pheochromocytomas.
Somatostatin receptor imaging (SRI) with (111)In-DTPA(0)octreotide has proven its role in the diagnosis and staging of gastroenteropancreatic neuroendocrine tumors (GEPNETs). Newer radiolabeled ...somatostatin analogs which can be used in positron emission tomography (PET) imaging, and which have a higher affinity for the somatostatin receptor, especially receptor subtype-2, have been developed. It would be desirable, however, if one radiolabeled analog became the new standard for PET imaging, because the current application of a multitude of analogs implies a fragmented knowledge on the interpretation of the images that are obtained in clinical practice. In our view, the most likely candidates for such a universal PET tracer for SRI are (68)Ga-DOTA(0),Tyr(3)octreotate or (68)Ga-DOTA(0),Tyr(3)octreotide. Treatment with radiolabeled somatostatin analogs is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumors. Symptomatic improvement may occur with all (111)In-, (90)Y-, or (177)Lu-labeled somatostatin analogs that have been used for peptide receptor radionuclide therapy (PRRT). The results that were obtained with (90)Y-DOTA(0),Tyr(3)octreotide and (177)Lu-DOTA(0),Tyr(3)octreotate are very encouraging in terms of tumor regression. Also, if kidney protective agents are used, the side effects of this therapy are few and mild, and the median duration of the therapy response for these radiopharmaceuticals is 30 and 40 months respectively. The patients' self-assessed quality of life increases significantly after treatment with (177)Lu-DOTA(0),Tyr(3)octreotate. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with (177)Lu-DOTA(0),Tyr(3)octreotate. These data compare favorably with the limited number of alternative treatment approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable GEPNETs.
Approach to the Patient: Insulinoma Hofland, Johannes; Refardt, Julie C; Feelders, Richard A ...
The journal of clinical endocrinology and metabolism,
2024-Mar-15, 2024-03-15, 20240315, Letnik:
109, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Abstract
Insulinomas are hormone-producing pancreatic neuroendocrine neoplasms with an estimated incidence of 1 to 4 cases per million per year. Extrapancreatic insulinomas are extremely rare. Most ...insulinomas present with the Whipple triad: (1) symptoms, signs, or both consistent with hypoglycemia; (2) a low plasma glucose measured at the time of the symptoms and signs; and (3) relief of symptoms and signs when the glucose is raised to normal. Nonmetastatic insulinomas are nowadays referred to as “indolent” and metastatic insulinomas as “aggressive.” The 5-year survival of patients with an indolent insulinoma has been reported to be 94% to 100%; for patients with an aggressive insulinoma, this amounts to 24% to 67%. Five percent to 10% of insulinomas are associated with the multiple endocrine neoplasia type 1 syndrome. Localization of the insulinoma and exclusion or confirmation of metastatic disease by computed tomography is followed by endoscopic ultrasound or magnetic resonance imaging for indolent, localized insulinomas. Glucagon-like peptide 1 receptor positron emission tomography/computed tomography or positron emission tomography/magnetic resonance imaging is a highly sensitive localization technique for seemingly occult, indolent, localized insulinomas. Supportive measures and somatostatin receptor ligands can be used for to control hypoglycemia. For single solitary insulinomas, curative surgical excision remains the treatment of choice. In aggressive malignant cases, debulking procedures, somatostatin receptor ligands, peptide receptor radionuclide therapy, everolimus, sunitinib, and cytotoxic chemotherapy can be valuable options.
Purpose
There is no evidence-based systemic therapy for patients with progressive meningiomas for whom surgery or external radiotherapy is no longer an option. In this study, the efficacy and safety ...of peptide receptor radionuclide therapy (PRRT) in patients with progressive, treatment-refractory meningiomas were evaluated.
Methods
Retrospective analysis of all meningioma patients treated with
177
LuLu-DOTA-TATE from 2000 to 2020 in our centre. Primary outcomes were response according to RANO bidimensional and volumetric criteria and progression-free survival (PFS). Overall survival (OS) and tumour growth rate (TGR) were secondary endpoints. TGR was calculated as the percentage change in surface or volume per month.
Results
Fifteen meningioma patients received
177
LuLu-DOTA-TATE (7.5–29.6 GBq). Prior to PRRT, all patients had received external radiotherapy, and 14 patients had undergone surgery. All WHO grades were included WHO 1 (
n
=3), WHO 2 (
n
=5), and WHO 3 (
n
=6). After PRRT, stable disease was observed in six (40%) patients. The median PFS was 7.8 months with a 6-month PFS rate of 60%. The median OS was 13.6 months with a 12-month OS rate of 60%. All patients had progressive disease prior to PRRT, with an average TGR of 4.6% increase in surface and 14.8% increase in volume per month. After PRRT, TGR declined to 3.1% in surface (
p
=0.016) and 5.0% in volume (
p
=0.013) per month.
Conclusion
In this cohort of meningioma patients with exhaustion of surgical and radiotherapeutic options and progressive disease, it was shown that PRRT plays a role in controlling tumour growth.
Nonfunctioning pancreatic neuroendocrine tumors (NF-pNETs) are highly prevalent and constitute an important cause of mortality in patients with multiple endocrine neoplasia type 1 (MEN1). Still, the ...optimal age to initiate screening for pNETs is under debate.
The aim of this work is to assess the age of occurrence of clinically relevant NF-pNETs in young MEN1 patients.
Pancreatic imaging data of MEN1 patients were retrieved from the DutchMEN Study Group database. Interval-censored survival methods were used to describe age-related penetrance, compare survival curves, and develop a parametric model for estimating the risk of having clinically relevant NF-pNET at various ages. The primary objective was to assess age at occurrence of clinically relevant NF-pNET (size ≥ 20 mm or rapid growth); secondary objectives were the age at occurrence of NF-pNET of any size and pNET-associated metastasized disease.
Five of 350 patients developed clinically relevant NF-pNETs before age 18 years, 2 of whom subsequently developed lymph node metastases. No differences in clinically relevant NF-pNET-free survival were found for sex, time frame, and type of MEN1 diagnosis or genotype. The estimated ages (median, 95% CI) at a 1%, 2.5%, and 5% risk of having developed a clinically relevant tumor are 9.5 (6.5-12.7), 13.5 (10.2-16.9), and 17.8 years (14.3-21.4), respectively.
Analyses from this population-based cohort indicate that start of surveillance for NF-pNETs with pancreatic imaging at age 13 to 14 years is justified. The psychological and medical burden of screening at a young age should be considered.
Objective
To evaluate the impact of multidisciplinary team (MDT) meetings on the management of patients with neuroendocrine neoplasms (NENs).
Methods
All newly referred gastro‐entero‐pancreatic ...(GEP)‐NEN patients discussed from 1 April to 1 October 2017 in the MDT of seven European expert centres were prospectively included. The impact on patients' management was defined as a change in diagnosis, grade, stage or treatment.
Results
A total of 292 patients were included, mainly small intestinal (siNENs) (32%) and pancreatic NENs (28%), with distant metastases in 51%. Patients had received prior surgery in 43% of cases and prior medical treatment in 32%. A significant change occurred in 61% of NENs: 7% changes in diagnosis, 8% in grade and 16% in stage. The MDT recommended a new treatment for 51% of patients, mainly surgery (9%) or somatostatin analogues (20%). A significant change was most frequently observed in patients with Stage IV disease (hazard ratio HR 3.6, 95% confidence interval CI: 1.9–6.9 vs. Stage I) and G2 NENs (vs. G1, HR 2.1 95% CI: 1.2–3.8).
Conclusion
NEN‐dedicated MDT discussion in expert centres yields significant management changes in over 60% of patients and thus represents the gold standard for the management of these patients.
Lanreotide autogel/depot (LAN) is a somatostatin analog used in first‐line treatment for neuroendocrine tumors (NETs). The aim of HomeLAN was to evaluate the satisfaction with injection experience ...among patients with NETs receiving at‐home LAN injection via patient support programs (PSPs). This was an international, non‐interventional, cross‐sectional, online survey in adults with NETs enrolled in PSPs, receiving LAN injections at home, administered by a healthcare professional (HCP) or administered independently (self or caregiver administering injection). The primary endpoint was satisfaction with the most recent LAN injection. Secondary endpoints included the level of anxiety prior to injection, impact on daily life, and the extents to which participants felt in control of their life and agreed that home administration met their medical needs. In total, 111 participants from Belgium, Greece, the Netherlands, and Spain completed the survey (50.5% male; mean age, 63.6 years; most common primary tumor site was intestine 47.7%). For 99 participants, their most recent injection was administered by an HCP. Overall, 95.5% of all participants were satisfied with their most recent injection experience (95% confidence interval: 89.89%–98.06%); 67% reported experiencing no anxiety prior to injection, 91.0% reported that home injection had a “great deal” or “quite a bit” of positive impact on their daily life, and 85.6% strongly agreed that the PSP met their medical needs. In the HCP injection subgroup, 71.7% reported that this mode of administration helped them to feel in control of their lives. In this patient survey, satisfaction levels were high among patients with NETs receiving LAN injections at home via a LAN PSP. Most patients did not experience anxiety prior to their most recent injection and acknowledged that thanks to their treatment they had a good quality of life despite their disease. Most strongly agreed that the PSP met their medical needs, which highlights the valuable service that LAN PSPs provide for patients with NETs.
HomeLAN was an international, non‐interventional, online survey of adults with neuroendocrine tumors (NETs) enrolled in lanreotide autogel (LAN) patient support programs (PSP). Patients were receiving LAN injections at home, administered either by a healthcare professional or independently. The findings indicate a very high level of satisfaction with their injection experience among patients with NETs who are receiving LAN injections at home via a LAN PSP, highlighting the importance of LAN PSPs for optimizing the treatment experience of patients with NETs.
Purpose
We present a historical overview on neuropathic ulcers in patients with acromegalic gigantism.
Materials and methods
The case histories of 6 famous patients with acromegalic gigantism and ...living in the twentieth century were analyzed. The combined final height and maximum weight of these giants were: 272 cm. & 215.9 kg., 218.4 cm. & 125 kg., 242 cm. & 165 kg., 220.5 cm. & 135 kg., 235 cm. & 136 kg. and 224.8 cm. & 174 kg.
Conclusions
Neuropathic foot ulcers leading to hospital admissions and surgical and medical interventions were reported in 6 patients with acromegalic gigantism. These ulcers significantly impaired the daily activities of these individuals. Neuropathies of the sural nerve in patients with acromegalic gigantism can lead to hypoesthesia and hypoalgesia of the lower legs and feet. Potential contributing factors for the development of neuropathic ulcers of the feet in patients with acromegalic gigantism and neuropathy might be leg and foot deformities, muscle weakness and poor quality footwear. Diabetes mellitus, or impaired glucose intolerance does not necessarily seem to play a role.
This expert consensus document represents an initiative by the European Neuroendocrine Tumor Society (ENETS) to provide guidance for synoptic reporting of radiological examinations critical to the ...diagnosis, grading, staging and treatment of neuroendocrine neoplasms (NENs). Template drafts for initial tumor staging and follow‐up by computed tomography (CT) and magnetic resonance imaging (MRI) were established, based on existing institutional and organisational reporting templates relevant for NEN imaging, and applying the RadLex lexicon of radiological information (Radiological Society of North America), for consistency regarding the radiological terms. During the ENETS Scientific Advisory Board meeting 2018, the template drafts were subject to iterative interdisciplinary discussions among experts in imaging, surgery, gastroenterology, oncology and pathology. Members of the imaging group stated a strong preference for a combination of limited and standardised options by way of drop‐down menus. Separate templates were produced for the initial work‐up and for follow‐up, respectively. To provide a detailed description of the radiological findings of the primary tumor and its local extension and spread, different templates were developed for bronchial, pancreatic and gastrointestinal NENs for CT and MRI, respectively. Each template was structured in 10 sections: clinical details, comparative imaging modality, acquisition technique, primary tumor findings, regional lymph node metastases, distant metastases, TNM classification, reference lesions according to RECIST 1.1, additional findings and conclusion. Two templates were developed for follow‐up, for CT and MRI, respectively, and were specifically focused on assessment of therapy response. These included a qualitative response assessment, such as decrease of vascularisation and presence of necrosis, and a quantitative assessment according to RECIST 1.1 and the modified RECIST (mRECIST) for assessing tumor response following transarterial chemoembolisation.
These guidelines are an initiative by the European Neuroendocrine Tumor Society (ENETS) to provide guidance for synoptic reporting of radiological examinations critical to the diagnosis, grading, staging and treatment of neuroendocrine neoplasms (NENs). Template drafts for initial tumor staging and follow‐up by computed tomography and magnetic resonance imaging were established.
BACKGROUND
Clinical pathways are care plans established to describe essential steps in the care of patients with a specific clinical problem. They translate (inter)national guidelines into local ...applicable protocols and clinical practice. The purpose of this article is to establish a multidisciplinary integrated care pathway for specialists and allied health care professionals in caring for individuals with von Hippel–Lindau (VHL) disease.
METHODS
Using a modified Delphi consensus‐making process, a multidisciplinary panel from 5 Dutch University Medical Centers produced an integrated care pathway relating to the provision of care for patients with VHL by medical specialists, specialized nurses, and associated health care professionals. Patient representatives cocreated the pathway and contributed quality criteria from the patients' perspective.
RESULTS
The panel agreed on recommendations for the optimal quality of care for individuals with a VHL gene mutation. These items were the starting point for the development of a patient care pathway. With international medical guidelines addressing the different VHL‐related disorders, this article presents a patient care pathway as a flowchart that can be incorporated into VHL expertise clinics or nonacademic treatment clinics.
CONCLUSIONS
Medical specialists (internists, urologists, neurosurgeons, ophthalmologists, geneticists, medical oncologists, neurologists, gastroenterologists, pediatricians, and ear‐nose‐throat specialists) together with specialized nurses play a vital role alongside health care professionals in providing care to people affected by VHL and their families. This article presents a set of consensus recommendations, supported by organ‐specific guidelines, for the roles of these practitioners in order to provide optimal VHL care. This care pathway can form the basis for the development of comprehensive, integrated pathways for multiple neoplasia syndromes.
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