INTERESSAMENTO GHIANDOLARE
4 – ANALISI STATISTICA
Le variabili continue sono espresse come media ± DS. Il test di correlazione di Pearson è stato utilizzato per valutare la correlazione tra FE-1 ed età e FE-1 e dimensioni della cisti maggiore. La correlazione tra FE-1 e grado di compromissione ghiandolare è stata valutata mediante il test di correlazione di Spearman, così come la correlazione tra età e grado di compromissione ghiandolare. Eventuali differenze del valore medio di FE-1 in relazione al grado di compromissione ghiandolare sono
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state valutate con l'analisi della varianza (ANOVA). Un livello di p < 0.05 è stato considerato statisticamente significativo.
5 – RISULTATI
L’età media dei pazienti era pari a 66.04 ± 9.57 anni. Nessun paziente ha mostrato valori di FE-1 < 200 µg/g, indicativi di PEI. Il valore medio di FE-1 è risultato essere di 539.39 ± 111.55 µg/g. Il valore medio di FE-1 e l’età media per ogni grado di compromissione ghiandolare è riportato in Tabella 5.
Tabella 5 Valori medi di FE-1 ed età per grado di compromissione ghiandolare da IPMN
E’ risultata una correlazione inversa statisticamente significativa del valore della FE-1 con l'età (ρ = -0.465; p = 0.017) (Figura 29) e con il grado di compromissione ghiandolare (ρs = -0.478; p = 0.013) (Figura 30). Il valore medio di FE-1 è risultato significativamente più basso nei pazienti con grado di compromissione ghiandolare
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pari a 4 e 5 rispetto ai pazienti con grado 1, 2 e 3 (p = 0.003) (Figura 31), mentre non sono state evidenziate differenze statisticamente significative in relazione ai singoli gradi di compromissione ghiandolare (p = 0.052). E' stata inoltre osservata una correlazione diretta tra età e grado di compromissione ghiandolare, seppur non statisticamente significativa (ρs = 0.371; p = 0.062). Per quanto sia stata evidenziata una tendenza alla correlazione inversa tra valore di FE-1 e dimensione della cisti maggiore questa non è risultata statisticamente significativa (ρ = -0.307; p = 0.127).
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Figura 30 Elastasi Fecale-1 in relazione al grado di compromissione ghiandolare da IPMN (Spearman: ρs = -0.478; p = 0.013).
Figura 31 Valore di Elastasi Fecale-1 in pazienti con compromissione ghiandolare di grado 1, 2 e 3 rispetto a pazienti con grado 4 e 5 (ANOVA: p = 0.003).
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6 – DISCUSSIONE
Studi postmortem su soggetti anziani hanno documentato la presenza di alterazioni anatomopatologiche pancreatiche quali fibrosi, iperplasia epiteliale duttale, dilatazioni duttali e depositi di materiale proteico intraluminale (213-215). Queste alterazioni sono presumibilmente responsabili della compromissione della funzionalità esocrina del pancreas che sopraggiunge con l’aumentare dell’età.
Herzig et al. hanno studiato questo aspetto e hanno dosato la FE-1 in soggetti di età superiore a 60 anni, e con anamnesi negativa per altre possibili cause di PEI quali malattie gastrointestinali e diabete; i valori riscontrati sono stati confrontati con quelli di soggetti giovani di età compresa tra 20 e 28 anni. Lo studio ha dimostrato una riduzione della FE-1 statisticamente significativa in soggetti di età superiore ai 70 anni rispetto ai controlli. Tra gli over 60 è stato riscontrato un valore di FE-1 < 200 µg/g nel 21.7% dei soggetti, evidenziando quindi la presenza di PEI. Nel gruppo dei soggetti con PEI, circa la metà presentava valori di FE-1 < 100 µg/g indicando quindi la presenza di PEI di grado severo (216).
Dal punto di vista anatomopatologico, il pancreas dei pazienti con IPMN presenta alterazioni in parte simili a quelle descritte nel pancreas dei soggetti anziani, ovvero proliferazione di cellule epiteliali secernenti mucina all’interno dei dotti pancreatici, ostruzione duttale da parte del muco prodotto e conseguente dilatazione dei dotti secondari e/o del dotto principale (79, 111).
Sono inoltre ben definiti l’aspetto radiologico e quello ultrasonografico dell’IPMN. Le immagini RM, TC ed ecoendoscopiche mostrano dilatazioni cistiche dei dotti
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secondari, dilatazione del dotto principale, estroflessioni polipoidi nel dotto pancreatico principale e calcificazioni (148, 217, 218).
Simili alterazioni radiologiche e ultrasonografiche sono presenti nella pancreatite cronica, e in pazienti con questa patologia sono state messe in relazione con la PEI. Dominguez-Munoz et al. hanno dimostrato che la probabilità di PEI, diagnosticata mediante breath test ai trigliceridi misti, risulta significativamente aumentata in presenza di calcificazioni e dilatazione del dotto principale (187).
Bilgin et al. hanno messo in relazione la FE-1 con le alterazioni pancreatiche visibili alla RM in pazienti con pancreatite cronica dimostrando una correlazione statisticamente significativa tra valori di FE-1 e dimensioni pancreatiche, e tra valori di FE-1 e alterazioni del dotto pancreatico principale valutate secondo la classificazione di Cambridge (190).
Il nostro studio ha dimostrato che esiste una correlazione inversa statisticamente significativa (ρs = -0.478; p = 0.013) tra il grado di compromissione ghiandolare pancreatica e i valori di FE-1. I pazienti con compromissione ghiandolare di grado più severo (grado 4 e 5), pur non mostrando valori al di sotto dei limiti previsti per la diagnosi di PEI, presentano una riduzione statisticamente significativa (p = 0.003) dei valori di FE-1 rispetto ai pazienti con compromissione ghiandolare di grado meno severo (grado 1, 2 e 3). In linea con i dati del lavoro di Herzig anche il presente studio ha dimostrato una correlazione inversa statisticamente significativa tra i valori di FE-1 e l’età dei pazienti (ρ = -0.465; p = 0.017). Pur essendo stata evidenziata una tendenza alla correlazione inversa tra il diametro della cisti maggiore e il valore di FE-1, tale correlazione non risulta statisticamente significativa (ρ = -0.307; p = 0.127).
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Questi dati mostrano una chiara relazione tra il grado di compromissione ghiandolare da IPMN e la funzionalità esocrina del pancreas. Tuttavia i valori di FE-1, anche nei casi di IPMN con compromissione ghiandolare di grado più severo (grado 4 e 5) non raggiungono, nel nostro campione, valori < 200 µg/g e non giustificano, secondo le linee guida, un trattamento enzimatico sostitutivo.
7 – CONCLUSIONI
La correlazione inversa statisticamente significativa tra valori di FE-1 e il grado di compromissione ghiandolare da IPMN induce a ipotizzare che una minoranza dei pazienti con compromissione ghiandolare severa (grado 4 e 5), possa essere affetta da PEI e presentare deficit nutrizionali clinicamente evidenti o subclinici potenzialmente curabili con la terapia enzimatica sostitutiva. Al fine di verificare questa ipotesi sono necessari studi su campioni di pazienti più numerosi e selezionati in base ad un grado severo di compromissione ghiandolare pancreatica da IPMN.
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