Correlazione tra dati istologici e profili immunofenotipici in pazienti affetti da Mieloma Multiplo, sottoposti a chemioterapia e trapianto di midollo

Il Mieloma multiplo costituisce il 10- 15% delle neoplasie ematologiche. I criteri diagnostici e di risposta terapeutica sono stati stabiliti dall'International Myeloma Working Group. Di recente, sebbene l’esame morfologico rimanga un gold standard sia nell’iter diagnostico che post-terapeutico, si sta sempre più affermando il ruolo dell’immunofenotipizzazione mediante citofluorimetria multiparametrica. In particolare, rapidità di analisi e capacità di discriminazione tra plasmacellule normali e patologiche, fanno di questa tecnica un mezzo vantaggioso soprattutto nella definizione della risposta al trattamento e della malattia minima residua. Questo lavoro ha confrontato 92 controlli contemporanei di profili immunofenotipici e referti istologici, suddivisi in 3 gruppi in base al tipo di trattamento ricevuto dai rispettivi pazienti (chemioterapia, trapianto autologo di cellule staminali e trapianto allogenico), allo scopo di stabilire la percentuale di concordanza tra referto istologico e profilo immunofenotipico nella definizione della risposta al trattamento. Nel primo gruppo, istologia ed immunofenotipo hanno dimostrato una concordanza pari al 100%, nel secondo dell’89,9% e nel terzo dell’80%.In generale, istologia e citofluorimetria, hanno dato esiti discordanti in 6 controlli: in 5 controlli (gruppo HDT-ASCT), l’analisi citofluorimetrica si è dimostrata superiore a quella morfologica nel definire la risposta terapeutica. Per uno di essi, la disponibilità di un controllo successivo, ha dimostrato la capacità dell’analisi immunofenotipica di anticipare la risposta. Solo in un caso (gruppo Allo-SCT), l’esito dell’analisi immunofenotipica si è discostato dalla risposta ottenuta, ma la concordanza si è comunque verificata al controllo successivo. Alla luce dei risultati ottenuti, è doveroso rivalutare il ruolo ancillare della citofluorimetria multiparametrica nella gestione del Mieloma Multiplo, dal momento che le sue potenzialità potrebbero promuoverla a mezzo diagnostico e prognostico imprescindibile

Moving Toward Continuous Therapy in Multiple Myeloma

The introduction of novel agents, characterized by favorable toxicity profiles and higher manageability compared to conventional drugs employed in the past, has considerably changed the treatment paradigm for multiple myeloma. Continuous therapy currently represents the standard approach for myeloma patients both at diagnosis and at relapse. In younger patients, long-term maintenance after autologous transplantation significantly improved progression-free survival and overall survival compared to observation. Also in transplant-ineligible patients, continuous treatment with combinations of newer agents and maintenance treatment following a more intense induction phase proved to be superior as compared to fixed-duration therapy. Maintenance and continuous therapy at diagnosis have shown to deepen responses and suppress minimal residual disease. At relapse, continuous therapy allowed better disease control over time. This review covers the main evidence supporting the use of continuous therapy in multiple myeloma as well as the open issues, such as the optimal agents to be used and the optimal candidates for receiving them

Fisiopatologia e trattamento dell'iperparatiroidismo primario

Abstract non disponibil

Pseudoipoparatiroidismo di tipo 1A: evidenza radiologica delle alterazioni appendicolari

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Day case parathyroidectomy: is this the right way for the patients?

Minimally-invasive video-assisted parathyroidectomy (MIVAP) can be considered as the primary treatment of choice for single parathyroid adenoma. Often, this technique is performed in a day surgery setting and is associated with regional anaesthesia (RA). Many studies have already reported the feasibility and safety of MIVAP in day surgery. Here our focus has been on the patient's personal experience with these procedures through an assessment of their recovery at home

Normocalcemic primary hyperparathyroidism: a survey in a small village of Southern Italy

We investigated the prevalence of normocalcemic primary hyperparathyroidism (NPHPT) in the adult population living in a village in Southern Italy. All residents in 2010 (n=2045) were invited by calls and 1046 individuals accepted to participate. Medical history, calcium intake, calcium, albumin, creatinine, parathyroid hormone (PTH) and 25OHD were evaluated. NPHPT was defined by normal albumin-adjusted serum calcium, elevated plasma PTH, and exclusion of common causes of secondary hyperparathyroidism (SHPT) (serum 25OHD <30 ng/ml, estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m(2) and thiazide diuretics use), overt gastrointestinal and metabolic bone diseases. Complete data were available for 685 of 1046 subjects. Twenty subjects did not meet the inclusion criteria and 341 could not be evaluated because of thawing of plasma samples. Classical PHPT was diagnosed in four women (0.58%). For diagnosing NPHPT the upper normal limit of PTH was established in the sample of the population (n=100) who had 25OHD ≥30 ng/ml and eGFR ≥60 ml/min per 1.73 m(2) and was set at the mean+3s.d. Three males (0.44%) met the diagnostic criteria of NPHPT. These subjects were younger and with lower BMI than those with classical PHPT. Our data suggest, in line with previous studies, that NPHPT might be a distinct clinical entity, being either an early phenotype of asymptomatic PHPT or a distinct variant of it. However, we cannot exclude that NPHPT might also represent an early phase of non-classical SHPT, since other variables, in addition to those currently taken into account for the diagnosis of NPHPT, might cumulate in a normocalcemic subject to increase PTH secretion

Genetic and Clinical Features of Multiple Endocrine Neoplasia Types 1 and 2

Multiple endocrine neoplasia (MEN) are clinical inherited syndromes affecting different endocrine glands. Three different patterns of MEN syndromes can occur (MEN 1, MEN 2A, and MEN 2B). MEN syndromes are very rare, affect all ages and both sexes are equally affected. MEN 1 is characterized by the neoplastic transformation of the parathyroid glands, pancreatic islets, anterior pituitary, and gastrointestinal tract. Heterozygous MEN 1 germline mutations have been detected in about 70–80% of patients with MEN 1. The mutations are scattered throughout the entire genomic sequence of the gene. MEN 1 patients are characterized by variable clinical features, thus suggesting the lack of a genotype-phenotype correlation. Therapeutical approaches are different according to the different endocrinopathies. The prognosis is generally good if adequate treatment is provided. In MEN 2 syndromes, the medullary thyroid cancer (MTC) is almost invariably present and can be associated with pheochromocytoma (PHEO) and/or multiple adenomatosis of parathyroid glands with hyperparathyroidism (PHPT). The different combination of the endocrine neoplasia gives origin to 3 syndromes: MEN 2A, MEN 2B, and FMTC. The clinical course of MTC varies considerably in the three syndromes. It is very aggressive in MEN 2B, almost indolent in the majority of patients with FMTC and with variable degrees of aggressiveness in patients with MEN 2A. Activating germline point mutations of the RET protooncogene are present in 98% of MEN 2 families. A strong genotype-phenotype correlation has been observed and a specific RET mutation may be responsible for a more or less aggressive clinical course. The treatment of choice for primary MTC is total thyroidectomy with central neck lymph nodes dissection. Nevertheless, 30% of MTC patients, especially in MEN 2B and 2A, are not cured by surgery. Recently, developed molecular therapeutics that target the RET pathway have shown very promising activity in clinical trials of patients with advanced MTC. MEN 2 prognosis is strictly dependent on the MTC aggressiveness and thus on the success of the initial treatment

A patient with MEN1 and end‑stage chronic kidney disease due to Alport syndrome: Decision making on the eligibility of transplantation

Absence of neoplastic disease in the organ‑recipient is required in order to allow organ transplantation. Due to its rarity, no data regarding management of patients with Multiple endocrine neoplasia type 1 (MEN1) and end‑stage renal failure candidates for kidney transplantation are available. A 36 year‑old man was referred to the present hospital with MEN1, with a neuroendocrine pancreatic tumor and primary hyperparathyroidism and associated Alport syndrome with end stage renal failure. The present study aimed to establish the eligibility of the patient for a kidney transplantation. The neuroendocrine tumor had been treated with duodenopancreatectomy two years earlier and hyperparathyroidism by parathyroidectomy. The review of the literature did not provide data regarding the eligibility for kidney transplantation of patients harboring a neuroendocrine pancreatic tumor in the context of MEN1. Due to the end‑stage renal failure, neuroendocrine markers were unreliable and the investigation therefore relied on imaging studies, which were unremarkable. Young age, low‑grade tumor, low expression of Ki67, absence of metastatic lymph nodes, onset in the setting of a MEN1 were all positive prognostic factors of the neuroendocrine tumor. Normal serum calcium ruled out persistent primary hyperparathyroidism. Overall, hemodyalisis is known to significantly reduce life expectancy. Benefits of kidney transplantation overcome the risk of neuroendocrine tumor recurrence in a young patient bearing MEN1