Gestione dell’acromegalia in un centro di riferimento: valutazione dei costi diretti di malattia e gestione del paziente durante la pandemia da SARS-CoV-2

Background. Acromegaly is a severe chronic endocrine disease. Achieving biochemical control often needs a multimodal treatment approach, including prolonged medical treatment. The global pandemic due to Coronavirus Disease (COVID-19) represents the toughest challenge faced by the healthcare systems in the modern history and affected the management of many chronic diseases, such as acromegaly. Aim of the study is to evaluate the burden of treatment direct costs with respect to the different therapeutic strategies, disease control, and follow-up length. Besides, it is to report the impact of the pandemic in our Unit of Endocrinology during the 2020. Methods. Single center retrospective study on 73 patients referred to our center between 1st January 2002 and 31st December 2018. Costs of acromegaly treatments were computed based on a detailed revision of patients’ clinical charts. Finally, we evaluated the number of outpatient visits and the disease control rate in 2019 and 2020 of as many patients actively followed. Results. Median total treatment cost/patient was €47393 during the entire follow-up (8.7 years), while median treatment cost/patient/year was €6811. The majority of patients received medical therapy (71/73, 97.3%). Median cost for first-line medical treatment (first-generation somatostatin receptor ligands) was lower compared to second-line treatments (pegvisomant monotherapy or combination therapies), considering both total (€22825 vs €76140; p < 0.001), and yearly cost/patient (€4927 vs €9161; p < 0.001). Sixty patients (82.2%) reached biochemical control at last follow-up (IGF-1 ≤ 1 x upper limit of normality range (ULN)). The yearly cost/patient was comparable between controlled and uncontrolled patients (€6936 vs €6688; p = 0.829). Follow-up duration was significantly longer in controlled patients compared to the uncontrolled ones (8.7 vs 3.5 years; p = 0.019). Finally, we compared data between 31th December 2019 and 31th December 2020. A total of 177 on-site visits were performed in 2019 (median: 2 visits/patient/year), while this number felt down to 118 evaluations in 2020 (median: 1 visit/patient/ year). This 33% reduction of on-site evaluations was partially mitigated performing 21 phone visits. Looking to the patients’ biochemical control, we found that median IGF-1 levels in 2019 were superimposable compared to those observed at the end of 2020 (IGF-1 xULN, median (IQR): 0.735 vs 0.740, p = 0.339). Therefore, we observed that the percentage of biochemically controlled patients did not change significantly between 2019 and 2020, ranging from 75% to 79%. Conclusions. Direct costs for the management of acromegaly have a significant burden on the healthcare systems. However, more than 80% of our patients reached biochemical control using multimodal approaches. Treatment modalities and yearly costs did not significantly differ between controlled and uncontrolled patients, while follow-up length represented a major determinant of biochemical outcome. Cure rate in tertiary centers is high, and patients’ follow-up is usually long enough to build up a strong relationship with the patients, thus improving adherence and persistence to treatment, as well as of self-management. Dealing with a chronic disease has given us the opportunity to mitigate the effects of the pandemic in the short-term

3D CT scan for perioperative identification of anatomical variations of lungs

Aim: The aim of this study is to investigate anatomical lung variations and vascular patterns using volumetric 3D computed tomography (CT) representations. Methods & results: We considered 24 major thoracic surgery performed in our ward. In these, we discovered some interesting anatomical variations of the main pulmonary fissures. These findings were not visible on the plain x-ray or during routine examination of a preoperative CT scan. After re-examination of 3D CT scan reconstruction the anatomical variations were detected. Discussion: General thoracic surgeons must familiarize themselves with anatomical variations in lungs. 3D images may aid the general thoracic surgeon in performing safer surgeries. Conclusion: 3D CT scan should be performed before surgery if possible

Somatostatin and prostate cancer: role of somatostatin receptors in the control of tumor growth

The evidence that prostate cancer (PCa) expresses specific receptors for hormones and neuropeptides, including somatostatin (SRIF) receptors (SSRs) has driven the research towards the identification of new potential diagnostic/therapeutic paths besides the conventional treatment options. Although the first attempts has led to inconclusive results due to the heterogeneity of this tumor and to the complex mechanisms involved in the progression of PCa tumor growth, the potential role of SRIF and its synthetic analogues (SSAs) in the treatment of PCa represents an “open challenge” in the light of the new knowledge about SSR pathophysiology. Indeed, SRIF and SSAs can control tumor cell proliferation by two separate mechanisms: a direct mechanism through the activation of the five specific SSRs or an indirect mechanism through the inhibition of secretion of several growth factors and hormones responsible for tumor cell proliferation. Since new SSAs specific for each receptor subtype, as well as bi-specific compounds and panligands have been synthetized, the identification of alternative SSR targets on PCa cells and the consequent employment of these new specific molecules in the treatment of advanced PCa (alone or in combination with traditional treatment options), could improve the prognosis particularly of those patients not responding to (anti-) hormonal therapy (hormone-refractory PCa patients)

Iniziali esperienze sull'impiego di un dispositivo per l'anastomosi vascolare meccanica per le fistolle arterovenose per l'emodialisi.

INTRODUZIONE ED OBIETTIVI Nella costruzione delle fistole artero-venose, il confezionamento manuale dell’anastomosi è il gold standard.Generalmente questa è realizzata con una o due suture a sopraggitto in continua o talora a punti staccati. La tecnica è abbastanza standardizzata,anche se può richiedere una significativa spesa di tempo, specie in presenza di vasi di piccolo calibro, e una curva di apprendimento anche lunga. Riportiamo la nostra esperienza sull’uso di un dispositivo che permette di rendere l’esecuzione di quest’intervento più rapida, precisa e senza il clampaggio preventivo dell’arteria. MATERIALI E METODI Abbiamo impiegato la suturatrice meccanica per il confezionamento di un’anastomosi vascolare per l’accesso vascolare in due pazienti affetti da IRC. L’anastomosi in entrambi i casi fu confezionata tra l’arteria radiale e la vena cefalica, in anestesia locale e senza il clampaggio preventivo dell’arteria. RISULTATI: La durata complessiva media dell’intervento fu di 25 minuti circa. La connessione tra l’arteria radiale e la vena cefalica fu realizzata prontamente (c.ca 10 secondi), senza dover ricorrere al clampaggio transitorio dell’arteria. Il “thrill”, in entrambi i casi, fu apprezzato immediatamente dopo l’anastomosi senza sanguinamento dai margini di sutura. CONCLUSIONI I vantaggi potenziali dell’uso di questo dispositivo includono la possibilità di realizzare un’anastomosi tecnicamente precisa e con notevole risparmio di tempo, pur ritenendo che esso necessita di ulteriori perfezionamenti. Nei pazienti uremici con patologia aterosclerotica severa, la possibilità di non effettuare il clampaggio preventivo dell’arteria può ridurre il rischio di danni dello strato intimale e la formazione di trombi nel sito di anastomosi. Ovviamente per poter attestare la bontà della tecnica impiegata saranno necessari studi mirati che al momento non sono disponibili

Dosaggio intraoperatorio del paratormone nell'iperparatiroidismo terziario

INTRODUZIONE:L’iperparatiroidismo terziario (THP) è una condizione caratterizzata dalla persistenza di elevati valori di paratormone (PTH) e di conseguente ipercalcemia in soggetti affetti da iperparatiroidismo secondario all’insufficienza renale cui il trapianto di rene non riesce a normalizzare i livelli di PTH. E’ caratterizzata da un’iperplasia autonoma di 1-4 ghiandole paratiroidee. L’unica terapia per questi soggetti è l’escissione di quel tessuto paratiroideo ipersecernente per ridurre i livelli di PTH e di calcemia prevenendo così le possibili conseguenze quali lesioni da calcifilassi, osteoporosi, dolori ossei. Nella nostra esperienza troviamo ausilio tecnico molto utile il dosaggio del paratormone intraoperatorio con saggio immunometrico chemiluminescente su siero per permettere una condotta operatoria meno invasiva e più efficace. METODO/TECNICA:Una popolazione di 15 soggetti (10 donne e 5 uomini) di età compresa tra i 22 e i 60 anni e con alle spalle tra 1 e 13 anni di terapia dialisi, che sviluppata THP in un intervallo tra 1 e 15 mesi dopo un trapianto renale effettuato con successo, è stata sottoposta a paratiroidectomia subtotale del tessuto ghiandolare iperplastico.I livelli di iPTH sono stati dosati all’induzione dell’anestesia (come valore basale per calibrare la macchina), a 10 e a 15 minuti dopo l’asportazione delle paratiroidi ipertrofiche. I pz sono stati studiati con ecotomografia del collo per localizzare le ghiandole e guidare l’aggressione chirurgica ed a scintigrafia paratiroidea con 99mTc-Sestamibi per localizzare eventuali ghiandole ectopiche. RISULTATI: Il range di PTH compreso per i 15 pz tra 670 e 1210 pg/ml, dopo l’intervento si è ridotto tra i 40,67 e i 93,68 pg/ml. La percentuale di decremento rapido dei livelli di PTH è stato del 70,2 % a 10’ e dell’91 % a 15’ dopo l’escissione delle ghiandole iperplastiche ipersecernenti. Un abbattimento dei livelli di PTH del 50% o più a 10’ e/o dell’85% a 15’ è giudicato come predittivo del successo dell’intervento di rimozione di tessuto patologico. Si è avuto pure un miglioramento nel giro di giorni dei sintomi soprattutto per quei soggetti (3) che presentavano lesioni da calcifilassi o dolori ossei (8) e facile faticabilità. I pz sono stati seguiti nel follow-up. Solo in un caso, a distanza di 13 mesi dall’intervento, si sono avuti livelli in crescita di PTH. CONCLUSIONI: La tecnica, abbinata alla ecotomografia del collo e alla scintigrafia con 99mTc-Sestamibi consente al chirurgo di effettuare un intervento mini-invasivo mirato all’isolamento ed alla rimozione del tessuto ritenuto patologico, confortato da un dato sierologico rapido. Nella nostra esperienza il dosaggio intraoperatorio riduce altresì i tempi chirurgici e dà garanzie circa la bontà dell’intervento chirurgico

Epidemiology of acromegaly in Italy: analysis from a large longitudinal primary care database

Purpose: Epidemiological data are pivotal for the estimation of disease burden in populations. Aim: Of the study was to estimate the incidence and prevalence of acromegaly in Italy along with the impact of comorbidities and hospitalization rates as compared to the general population. Methods: Retrospective epidemiological study (from 2000 to 2014) and case control-study. Data were extracted from the Health Search Database (HSD). HSD contains patient records from about 1000 general practitioners (GPs) throughout Italy, covering a population of more than 1 million patients. It includes information about patient demographics and medical data including clinical diagnoses and diagnostic tests. Results: At the end of the study period, 74 acromegaly patients (out of 1,066,871 people) were identified, resulting in a prevalence of 6.9 per 100,000 inhabitants [95% CI 5.4\u20138.5]. Prevalence was higher in females than men (p = 0.004), and showed a statistically significant trend of increase over time (p < 0.0001). Overall, incidence during the study period was 0.31 per 100,000 person-years. Hypertension and type II diabetes mellitus were the comorbidities more frequently associated with acromegaly (31.3 and 14.6%, respectively) and patients were more likely to undergo a high frequency of yearly hospitalization ( 653 accesses/year, p < 0.001) compared to sex-age matched controls. Conclusions: This epidemiological study on acromegaly carried out using a large GP-based database, documented a disease prevalence of about 7 cases per 100,000 inhabitants. As expected, acromegaly was associated with a number of comorbidities (mainly hypertension and type II diabetes mellitus) and a high rate of patients\u2019 hospitalization

Modulatory activity of testosterone on growth pattern and IGF-1 levels in vanishing testis syndrome: a case report during 15 years of follow-up

Abstract Background The vanishing testis syndrome (VTS), is a 46, XY disorder of sex development (46, XY DSD) and is characterized by the absence of testis in a 46, XY subject with male genitalia, gonadal dysgenesis and consequent hypergonadotropic hypogonadism. Case presentation A young man affected by VTS has been followed up for more than 15-year in our center. The patient received different testosterone formulations, which modulated his IGF-1 levels and height velocity, depending on different stimulatory effects, mimicking pubertal spurt until achieving a final height in line with his genetic target. Exogenous testosterone, activating GH/IGF-1 system, can directly influence growth pattern. With this particular case report we demonstrate that an accurate monitoring of patients with VTS, as well as a perfect reproduction of testosterone secretion during pubertal spurt, can guarantee a normal growth and development and, consequently, a high level of quality of life in adulthood. Conclusion Testosterone levels act an important role during pubertal spurt in modulating the GH/IGF-1 axis, besides its well-known impact in sexual development. Very little amount of exogenous testosterone can stimulate IGF-1 secretion and provide to growth velocity the drive that characterizes the initial phases of the growth spurt