Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic neural ganglia, respectively. ...The heterogeneity in its etiology makes PPGL diagnosis and treatment very complex. The aim of this article was to provide practical clinical guidelines for the diagnosis and treatment of PPGLs from a multidisciplinary perspective, with the involvement of the Spanish Societies of Endocrinology and Nutrition (SEEN), Medical Oncology (SEOM), Medical Radiology (SERAM), Nuclear Medicine and Molecular Imaging (SEMNIM), Otorhinolaryngology (SEORL), Pathology (SEAP), Radiation Oncology (SEOR), Surgery (AEC) and the Spanish National Cancer Research Center (CNIO). We will review the following topics: epidemiology; anatomy, pathology and molecular pathways; clinical presentation; hereditary predisposition syndromes and genetic counseling and testing; diagnostic procedures, including biochemical testing and imaging studies; treatment including catecholamine blockade, surgery, radiotherapy and radiometabolic therapy, systemic therapy, local ablative therapy and supportive care. Finally, we will provide follow-up recommendations.
Neuroendocrine tumors (NETs) are an unusual family of neoplasms with a wide and complex spectrum of clinical behavior. Here, we present the first report of a National Cancer Registry of ...gastroenteropancreatic neuroendocrine tumors from a Southern European country.
Data was provided online at www.retegep.net by participating centers and assessed for internal consistency by external independent reviewers.
The study cohort comprised 907 tumors. The most common tumor types were carcinoids (55%), pancreatic nonfunctional tumors (20%), metastatic NETs of unknown primary (9%), insulinomas (8%) and gastrinomas (4%). Forty-four percent presented with distant disease at diagnosis, most often those from small intestine (65%), colon (48%), rectum (40%) and pancreas (38%), being most unusual in appendix primaries (1.3%). Stage at diagnosis varied significantly according to sex, localization of primary tumor, tumor type and grade. Overall 5-year survival was 75.4% (95% confidence interval 71.3% to 79.5%) and was significantly greater in women, younger patients and patients with hormonal syndrome and early stage or lower grade tumors. Prognosis also differed according to tumor type and primary tumor site. However, stage and Ki-67 index were the only independent predictors for survival.
This national database reveals relevant information regarding epidemiology, current clinical practices and prognosis of NETs in Spain, providing valuable insights that may contribute to understand regional disparities in the incidence, patterns of care and survival of this heterogeneous disease across different continents and countries.
Combination with cabergoline may offer additional benefits to acromegalic patients on pegvisomant monotherapy. We evaluated the safety and efficacy profile of this combination and investigated the ...determinants of response. An observational, retrospective, cross-sectional study. Fourteen acromegalic patients (9 females), who were partially resistant to somatostatin analogs and on pegvisomant monotherapy. Cabergoline was added because of the presence of persistent mildly increased IGF-I. The mean follow-up time was 18.3 ± 10.4 months. The efficacy and safety profile was assessed. The influence of clinical and biochemical characteristics on treatment efficacy was studied. IGF-I levels returned to normal in 4 patients (28%) at the end of the study. In addition, some decline in IGF-I levels was observed in a further 5 patients. The % IGF-I decreased from 158 ± 64% to 124 ± 44% (
p
= 0.001). The average change in IGF-I was −18 ± 27% (range −67 to +24%). Lower baseline IGF-I (
p
= 0.007), female gender (
p
= 0.013), lower body weight (
p
= 0.031), and higher prolactin (PRL) levels (
p
= 0.007) were associated with a better response to combination therapy. There were no significant severe adverse events. Significant tumour shrinkage was observed in 1 patient. Combination therapy with pegvisomant and cabergoline could provide better control of IGF-I in some patients with acromegaly. Baseline IGF-I levels, female gender, body weight, and PRL levels affect the response to this combination therapy.
Purpose
To evaluate the long-term safety of Pegvisomant (PEG) in the Spanish cohort of ACROSTUDY.
Methods
As of July 2013, 199 Spanish patients were included in ACROSTUDY, a global non interventional ...safety PEG surveillance study. Patients were observed for safety, biochemical outcome and magnetic resonance imaging evaluations.
Results
PEG was administered during an average period of 6.7 ± 2.1 years and a mean daily dose of 15.5 ± 7.5 mg. 48.2 % of patients received PEG monotherapy. 90.9 % of patients had received other medical treatment before PEG start. 195 adverse events (AEs) were reported in 88 patients (44.2 %), and serious AEs were described in 31 patients (15.6 %). There were no cases of liver tests >10 ULN, or permanent liver damage. Tumor size changes were locally reported in 61 cases (33.5 %), with increases observed in 11 patients (6 %). In acromegalic patients with diabetes mellitus a decrease in fasting serum glucose value was reported, reaching statistical significance after 1 and 4 years of treatment (−24.6 and −25.9 mg/dl,
p
= 0.04). After 60 months, normal or lower limit of normal (LLN) IGF-I levels were found in 67.9 % of patients. 85.5 % of patients showed an IGF-I normal or <LLN at any time after PEG start. Most patients with uncontrolled IGF-I levels were on submaximal PEG doses.
Conclusions
ACROSTUDY carried out with the Spanish cohort confirmed that PEG has a favorable safety and efficacy profile. The percentage of patients considered under control was similar to data reported globally and in other local ACROSTUDY results.
Asymptomatic pancreatic hypervascular lesions Marín-Serrano, E.; Alvarez-Escola, C.; Rodado-Marina, S. ...
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... et al.,
July 2021, 2021-07-00, 20210701, Letnik:
21
Journal Article
Summary
Apolipoprotein E (ApoE) deficiency promoted an exacerbation of autoimmune arthritis in mice by inducing proinflammatory immune responses. In this study we analysed the contribution of ...hypercholesterolaemia and/or the absence of ApoE anti‐inflammatory properties, unrelated to its function in the control of cholesterol metabolism, towards the acceleration of arthritis in these mutant animals. The induction and severity of collagen type II‐induced arthritis (CIA) were compared for B10.RIII wild‐type (WT), B10.RIII.ApoE+/–, B10.RIII.ApoE–/– and B10.RIII.low‐density lipoprotein receptor (LDLR–/–) mice with different concentrations of circulating ApoE and cholesterol. A 50–70% reduction in serum levels of ApoE was observed in heterozygous B10.RIII.ApoE+/– mice in comparison to B10.RIII.WT, although both strains of mice exhibited similar circulating lipid profiles. This ApoE reduction was associated with an increased CIA severity that remained lower than in homozygous B10.RIII.ApoE–/– mice. An important rise in circulating ApoE concentration was observed in hypercholesterolaemic B10.RIII.LDLR–/– mice fed with a normal chow diet, and both parameters increased further with an atherogenic hypercholesterolaemic diet. However, the severity of CIA in B10.RIII.LDLR–/– mice was similar to that of B10.RIII.WT controls. In conclusion, by comparing the evolution of CIA between several strains of mutant mice with different levels of serum ApoE and cholesterol, our results demonstrate that both hypercholesterolaemia and ApoE regulate the intensity of in‐vivo systemic autoimmune responses.
Our study shows that the levels of ApoE in sera determine the severity of collagen type II‐induced arthritis (CIA) in mice. The intensity of CIA is also modulated by the levels of circulating colesterol. This study highlights the importance of these factors as potential relevant targets for the control of autoimmune disorders.
Duration of previous somatostatin analog therapy, radiotherapy, intra-tumoral growth hormone, and insulin receptor expression are associated with higher risk of tumor growth during pegvisomant ...therapy.
Context:
There is concern that pegvisomant could be associated with a higher risk of tumor growth. The rate and possible determinants of this tumor growth are unknown.
Objective:
The objective of the study was to investigate the clinical, immunohistological, and molecular factors conditioning tumor growth in patients taking pegvisomant.
Design and Setting:
This was a cross-sectional study performed from 2004 to 2010 in four university hospitals in Spain.
Patients:
Seventy-five acromegalic patients with active disease resistant to somatostatin analogs treated with pegvisomant were followed up for a mean of 29 ± 20 months.
Main Outcome Measures:
Magnetic resonance images before initiation of pegvisomant, at 6 months, and then yearly were examined in all patients. Immunohistological and molecular studies were performed in tumors that grew.
Results:
A significant increase in tumor size was observed in five patients (6.7%). Absence of previous irradiation (P = 0.014) and shorter duration of prepegvisomant somatostatin analog therapy (P < 0.001) were associated with an increased risk of tumor growth. A stepwise multivariate linear regression analysis (R2 = 0.334, P < 0.001) identified the duration of somatostatin analog therapy prior to pegvisomant (beta = −4.509, P = 0.014) as the only significant predictor of tumor growth. In those tumors that grew, GH expression and insulin receptor expression were higher (P = 0.033 in both cases) than in the control group.
Conclusions:
No previous radiotherapy, shorter duration of prepegvisomant somatostatin analog therapy, and higher tumor expression of GH and insulin receptor could be risk factors for tumor growth during pegvisomant therapy.
Summary
Kaposi sarcoma (KS) is an angioproliferative tumour that develops as a result of an infection by human herpesvirus 8, which is considered a necessary cause but not sufficient. Other factors – ...genetic, immunological and environmental – might play a role in the development of the disease. We report a case of KS secondary to endogenous Cushing syndrome (ECS) due to a pituitary adenoma, an association that has been reported only once. We also conducted a search through the Medline and PubMed databases for cases involving KS and ECS, finding only three additional cases that shared common clinical and prognostic features with ours. ECS might favour the development of KS due to immunosuppression. Dermatologists and other clinicians should be aware of this association, as it might be an underdiagnosed condition. It also has an important impact on the management of KS, and based on this review it relies on a good prognosis when ECS is well controlled.
What's already known about this topic?
Kaposi sarcoma (KS) is an angioproliferative disorder related to human herpesvirus 8 infection and immune dysfunction.
What does this study add?
We report a case of a multicentric advanced KS secondary to Cushing syndrome due to an adrenocorticotropic hormone‐secreting pituitary microadenoma.
This association has rarely been reported, and this case adds evidence to include endogenous Cushing syndrome as a possible cause of KS.
Purpose
To compare the intraoperative and surgical outcomes of normotensive pheochromocytomas and sympathetic paragangliomas (PPGLs), hypertensive PPGLs and non-PPGL adrenal lesions.
Methods
This a ...retrospective multicenter cohort study of patients with PPGLs from 18 tertiary hospitals. A control group of histologically confirmed adrenocortical adenomas (non-PPGL group) was selected to compare intraoperative and surgical outcomes with of the normotensive PPGLs.
Results
Two hundred and ninety-six surgeries performed in 289 patients with PPGLs were included. Before surgery, 209 patients were classified as hypertensive PPGLs (70.6%) and 87 as normotensive PPGLs. A higher proportion of normotensive PPGLs than hypertensive PPGLs did not receive alpha presurgical blockade (
P
= 0.009). When we only considered those patients who received presurgical alpha blockers (200 hypertensive PPGLs and 76 normotensive PPGLs), hypertensive PPGLs had a threefold higher risk of intraoperative hypertensive crisis (OR 3.0 95% 1.3–7.0) and of hypotensive episodes (OR 2.9 95% CI 1.2–6.7) than normotensive PPGLs. When we compared normotensive PPGLs (
n
= 76) and non-PPGLs (
n
= 58), normotensive PPGLs had a fivefold higher risk of intraoperative complications (OR 5.3 95% CI 1.9–14.9) and a six times higher risk of postoperative complications (OR 6.1 95% CI 1.7–21.6) than non-PPGLs.
Conclusion
Although the risk of intraoperative hypertensive and hypotensive episodes in normotensive PPGLs is significantly lower than in hypertensive PPGLs, normotensive PPGLs have a greater risk of intraoperative and postoperative complications than non-PPGL adrenal lesions. Therefore, it is recommended to follow the standard of care for presurgical and anesthetic management of PPGLs also in normotensive PPGLs.
Purpose
To investigate endocrine function changes after non-functioning pituitary adenomas (NFPA) transsphenoidal surgery and to search for predictors of hypopituitarism resolution and development.
...Methods
We included 117 patients with NFPA who underwent endoscopic transsphenoidal surgery from 2005 to 2019 by two neurosurgeons. Twenty-one patients were excluded because of previous pituitary surgery or radiotherapy. We assessed symptoms at diagnosis, tumour volume, tumour removal, hormonal status at diagnosis, hormonal outcomes at 2- and 12-month follow-up, and complications. Pituitary stalk and gland MRI status (visible or not) were included, and it theirs association to hormonal function was studied for the first time, to our knowledge.
Results
Pituitary gland visualization was more frequent in those patients who showed a smaller number of axes affected at 12 months (
p
= 0.011). Pituitary stalk status showed no association to hormonal function. The hormonal normalization rate at 12 months was 13%. The endocrine improvement rate at 12 months was 16.7%. Worsening of hormonal function occurred in 19.8% of patients. Younger age was associated to hormonal improvement (
p
= 0.004). Higher preoperative tumour volume (p = 0.015) and absence of gross total resection (GTR) (
p
= 0.049) were associated with worsening in at least one hormonal axis after surgery.
Conclusions
Pituitary gland visibility was higher in those patients who showed better hormonal outcomes. Assessment of initial hormonal function and outcome after surgery regarding pituitary stalk status showed no significant association. Higher preoperative tumour volumes and absence of GTR were associated to postoperative endocrine function worsening, while younger age was associated to its improvement.
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