La chirurgia del surrene Dipartimento dell’Emergenza e dei Trapianti d’Organo Sezione di Urologia e Trapianto di Rene Università di Bari La chirurgia del surrene Pasquale Ditonno Michele Battaglia Seminari di Fisiopatologia Chirurgica Bari – 10-11 Novembre 2011

A SURGICAL HISTORY 1927 1936 1991 1992 1.Cagner 2.Mercan ADRENALECTOMY ANTERIOR APPROACH 1927 1563– Eustachius describes the anatomy of the adrenal Gland 1855 – Addison correlates clinical features of adrenal disease with pathology found in autopsies 1886 – Frankel describes pheochromocytoma 1912 – Cushing presents clinical features of Hypercortisolism 1955 – Conn describes hyperaldosteronism ROUX in Lausane MAYO in Rochester ADRENALECTOMY POSTERIOR APPROACH 1936 YOUNG TRANSABDOMINAL LAPAROSCOPIC ADRENALECTOMY Snow 1991 1.LATERAL TRANSABD. 2.POSTERIOR RETROPER. LAPAROSCOPIC 1.Cagner 2.Mercan 1992

Scint.Scan. US,CT,MR, 58,2% Interdisciplinary collaboration Advances during the last fifteen years have completely changed our understanding of and approach… In the past the diagnosis was complex, time consuming and, sometimes, frustating process, especially with regard to localization Scint.Scan. US,CT,MR, Interdisciplinary collaboration Incidentaloma’s increased incidence 36,6% 58,2% 1986 2010

Indicazioni alla chirurgia “Surgery of the adrenal gland consists of operative procedures to ‘correct endocrine abnormalities’ or to ‘treat malignant disease’. When medical therapy is ineffective or does not exist for a particular adrenal disease, surgery becomes necessary.” IS IT MALIGNANT? IS IT METASTATIC? IS IT FUNCTIONAL? Chow and Blute, Surgery of the adrenal glands, Campbell Urology, 9th Ed

386 Surrenectomie 188 dx – 188 sx – 10 Bilaterali SURRENECTOMIA: LA NOSTRA ESPERIENZA (Gennaio 1978-Ottobre 2011) 386 Surrenectomie 188 dx – 188 sx – 10 Bilaterali 184 M – 202 F – Età media: 54 aa (r: 14-82) Distribuzione per tipo di accesso lombotomico: 160 Anteriore: 26 Toraco-addominale: 5 Laparoscopico: 195 Laparoscopic adrenalectomy the “platinum standard” Cestari et al. Curr Opin Urol. 2005 Mar;15(2):69

Major Causes Benign Adenoma 50% Cyst 10% Myelolipoma 10% Pheochromocytoma 10% Metastases 6-30% Adrenal Cancer 0.01% The incidental adrenal mass. Am J Med 1996

Posizione: Non sul rene, ma mediale al rene, sottodiaframmatica, dinanzi al pilastro laterale Quadrilatero di Albarran Fegato - Milza Margine med. polo super. del rene Cava Aorta Peduncolo renale E’ contenuto in una propria loggia, inclusa in quella renale, senza tuttavia stretti rapporti Tale loggia e’ separata dal polo superiore del rene da tessuto fibroadiposo ancorato al diaframma

Vie di accesso al surrene transperitoneale addominale extraperitoneale lombotomica toraco-freno-laparotomica posteriore laparoscopica ( trans- e retroperitoneale) 9

Approccio laparoscopico: i vantaggi Soddisfazione del paziente Cosmesi Analgesici Hospital stay Recovery Time

Elementi da considerare qualunque sia tipo di accesso Tipo di patologia (Carcinoma) Sede (mono, bilaterale, ectopica) Volume della lesione Body Mass Index Friabilità dell’organo Attenta emostasi Esperienza del chirurgo Ampiezza del campo operatorio Dominio dei vasi Possibilità di estensione dell’accesso

La chirurgia del surrene L’approccio chirurgico Patologia Patients 1004 Non-Secretory 854 (85%) Pheochromocytoma 42 (4.2%) Sub-Clinical Cushings Syndrome 92 (9.2%) Aldosterone-Producing Adenoma 15(1.6%) Journal of Clinical Endocrinology & Metabolism 85 (2) 637-644, 2000

L’incidentaloma surrenalico “ Yes, doctor, the abdominal scan was negative for the problem you were worried about, but we found another one of those adrenal masses” A.I.D.S. Adrenal incidentaloma discovered serendipitously Su 87.065 autopsie in 24 studi è riportata una incidenza del 6%. Nelle ecografie addominali una incidenza dello 0,6-1.3 % Kloss RT et al. Endocr Rev 1995; 16:460 La probabilità della diagnosi correla con l’età: 0.2 % in soggetti di età tra 20 e 29 aa 7 % in soggetti di età superiore ai 70 aa

Qual è l’approccio diagnostico ottimale? Non esiste uno specifico algoritmo diagnostico L’approccio diagnostico si basa su: esperienza clinica del medico indagini di laboratorio e di imaging Young WF, NEJM 2007; 356

Sindrome di Cushing subclinica Il termine subclinico si riferisce alla presenza di una secrezione autonoma di cortisolo in pazienti che non presentano i caratteristici segni dell’ipercortisolismo per un nodulo iperfunzionante capace di sopprimere il surrene controlaterale senza elevare il cortisolo sierico e determinare la classica sindrome Se lo stato di soppressione ormonale non viene riconosciuto, dopo la surrenectomia può comparire una crisi addisoniana Tuttavia questi pazienti spesso presentano gli effetti della persistente secrezione endogena di cortisolo: ipertensione obesità diabete mellito osteoporosi Emral R. Endocr J 2003;50:399-408

Sindrome di Cushing subclinica Strategie terapeutiche Pazienti giovani Pazienti sintomatici Chirurgia Wait and see Pazienti anziani Pazienti asintomatici

FEOCROMOCITOMA E’ un tumore raro con caratteristiche cliniche peculiari allo stesso tempo una condizione curabile e potenzialmente letale Per curare la malattia: Diagnosi precoce Localizzazione precisa Appropriata preparazione anestesiologica pre and post-operatoria Rimozione chirurgica completa Fattori di rischio: Rilascio di catecolamine imprevisto ed incontrollabile Possibilità di malattia multifocale e comportamento maligno

FEOCROMOCITOMA • Attacks of Headaches (80%) • Palpitations (64%) Hypertension In Pheochromocytoma • Paroxysmal in 48%--episodically secreted • Persistent in 29%-- continually secreted • Normal in 13% • Attacks of Headaches (80%) • Palpitations (64%) • Diaphoresis (57%) Symptomatic Triad Of Headache, Sweating, And Tachycardia In A Hypertensive Patient Sensitivity 90.9% And Specificity 93.8%

Feocromocitoma clinicamente silente circa il 5% degli incidentalomi surrenalici Dosaggio delle metanefrine frazionate e catecolamine nelle urine delle 24 ore Imaging phenotype Imaging Alta densità alla TAC Elevata vascolarizzazione Ritardato washout del MC Alta intensità nelle sequenze T2-pesate (RMN)

Approccio Transperitoneale Approccio lombotomico Surrenectomia per Feocromocitoma 1959-2011 Pz Bambini 12 Adulti 101 Totale 113 Sede surrenalica 100 Sede extra-surr. 8 Bilaterale 6 Maligni 16 Approccio Transperitoneale 53 Approccio lombotomico 47 Laparoscopia (dal 2000) 13

Adrenal carcinoma Rare tumor (0.5-2 case per million) An extraordinarily aggressive malignancy with an overall poor prognosis Despite aggressive surgical therapy, the actuarial 5-year survival for patients who undergo complete resection ranges 23% to 48% Incomplete resection (including removal of adjacent, involved organs) is associated with a median survival of less than 1 year Dackiw AP, World J Surg 2001;25:914–926

The Mayo Clinic Study • 342 Patients With Adrenal Incidentaloma Retrospectively Evaluated • Tumor Diameter Averaged 2.5 cm • Most Malignant Tumors Measured > 5 cm • Removing All Tumors > 4 cm Would Have Removed Eight Benign Tumors For Every Carcinoma Incidentally discovered adrenal tumors: an institutional perspective. Herrera MF; Grant CS; van HeerdenJA; Sheedy PF; Ilstrup DM. Surgery 1991 Dec;110(6):1014-21

Mass • Masses > 6 cm Usually Are Treated Surgically • Masses < 4 cm Are Generally Monitored • Masses Between 4 And 6 cm: Criteria Other Than Size Should Be Considered In Making The Decision To Monitor Or Proceed To Surgery • Experienced investigators now recommend excision of all tumors >4 cm National Institutes Of Health Management Of The Clinically Inapparent Adrenal Mass (Incidentaloma) 2002

Assessment del potenziale maligno In uno studio condotto su 2005 pazienti con incidentaloma surrenalico un carcinoma era presente nel 4,7% dei soggetti e il 2,5% risultava affetto da malattia metastatica Young WF, Endocrinol Metab CNA 2000; 29:159 >4 cm 90% sensibilità Bassa specificità Dimensioni Imaging phenotype Forma irregolare Densità mista alla TAC Elevata vascolarizzazione Ritardato washout del MC Alta intensità nelle sequenze T2-pesate (RMN)

Distribuzione delle neoplasie maligne in rapporto alle dimensioni 386 Surrenectomie 19 Malignancy Diametro (cm)

When enthusiasm for laparoscopy turns to tragedy An incidentally discovered primary Adrenal Carcinoma Applicability of laparoscopy, with the possibility of tumor fracture or inadequate resection of adjacent organs, has been questioned Initial case reports: early postop development of carcinomatosis in all 5 pts with an incidentally discovered primary AC undergone laparoscopy for a presumed benign adrenal mass (Conn’s [2]; Cushing’s [2]; virilizing tumor[1]). 3 of 5 suffered local recurrence, and 1 port-site recurrence, after 4-14 months after laparoscopy Ushiyama T, J Urol 1997;157:2239. Hofle G, Horm Res 1998;50:237–241. Hamoir E, Ann Chir 1998;52:364–368. Deckers S, Horm Res 1999; 52:97–100. Foxius A, Surg Endosc 1999;13:715–717. When enthusiasm for laparoscopy turns to tragedy

MD Anderson Cancer Center: at a median follow up of 28 months, comparison of recurrence rates for laparoscopic and open resection of AC. Open group: 86% of patients recurred with 62% dying of mets and 24% alive with disease. Of these, 35% with local rec, 8% carcinomatosis, and remaining with mets. Lap group: 6 pts 100% recurred, with higher percentage (83%) carcinomatosis At a follow up of 15 months, 66% pts died from mets, and 33% alive with disease Open group: 6 pts with tumors <6 cm 4 of 6 were disease-free at 21 months Lap group: 5 pts with tumors <6 cm developed local rec, distant, and/or peritoneal mets In 2 of 6 cases, tumor fracture, rupture, or uncontrolled hemorrhage reported Gonzalez RJ, Laparoscopic resection of adrenal cortical carcinoma: a cautionary note. Surgery 2005;138:1078–1086.

The overall local recurrence rate was 23%. Gill recently described 31 pts undergone lap adrenalectomy for malignancy; 26 isolated adrenal mets, 6 primary incidental adrenal ca, and 1 malignant pheo. The overall local recurrence rate was 23%. 5 of 26 (19%) patients with adrenal mets 2 of 6 (33%) with adrenal ca. Patients with local rec also recurred at other (systemic) sites Pts with local rec had a lower 3-year survival than pts without local recurrence (17% vs 66%, P 0.016). Overall 5-year actuarial survival was 40% at a median follow up of 26 months. Moinzadeh A, Gill IS. J Urol 2005;173:519–525.

Local recurrence and/or intraperitoneal dissemination occurred in A contemporary review of the literature between 1998 to 2004 reveals 25 cases of AC resected laparoscopically Local recurrence and/or intraperitoneal dissemination occurred in 10 of 25 (40%) pts The disease-free interval averaged 34.1 months. Henry JF, World J Surg 2002;26:1043–1047. Prager G, Arch Surg 2004;139:46–4961. Zeh HJ 3rd, Udelsman R.Ann Surg Oncol 2003;10:1012–1017. Suzuki K. Biomed Pharmacother 2002; 56(suppl):139s-144s. Kebebew E, Arch Surg 2002;137:948–951. Belldegrun A, Surg Gynecol Obstet 1986;163:203–208. Valeri A, Surg Endosc 2002;16:1274–1279.

Despite arguments in favor of applying minimally invasive approaches to the majority of adrenal lesions the laparoscopic resection of primary adrenal malignancies remains controversial. Gonzalez RJ, Surgery 2005;138:1078–1086.

Adrenal Metastasis Adrenal glands are common sites for mets in a number of primary cancers, but an isolated metastasis is rare Resection of isolated adrenal mets of melanoma, lung, kidney, colon, and breast cancer may improve survival In series of open adrenalectomy for mets, median survival of 30 months vs historical survival of 6-8 months without resection Higashiyama M, Int Surg1994;79:124–129 Adrenalectomy for mets from RCC are associated with the most favorable results Lo CY, Br J Surg 1996;83:528–53

DFS ranged from 42% to 91% over a mean followup interval Recognition that most malignancies metastasize to the medullary portion, rather than cortex, rarely penetrate the capsule of the gland laparoscopic resection less likely to result in tumor fracture,which predispose to local recurrence or intraperitoneal dissemination To date, 8 series totaling 98 patients have reported the use of lap adrenalectomy for mets with no port-site recurrences and only 1 patient (1%) developing peritoneal dissemination DFS ranged from 42% to 91% over a mean followup interval of 8 to 26 months Greene FL, CA Cancer J Clin 2007;57:130–146

Diverse considerazioni fanno tendere verso una aggressione laparoscopica nelle metastasi surrenaliche Aumentata esperienza del chirurgo Migliore visione Immediato controllo dei vasi Possibilità di esplorare la cavità peritoneale per eventuali metastasi Completo controllo del tumore primitivo Metastasi isolata al surrene Possibilità di resezione completa del surrene interessato

Chirurgia laparoscopica “organ sparing” Accurata emostasi (coagulazione bipolare, colla di fibrina, EndoGIA, bisturi ad ultrasuoni) Indicazioni: Piccoli Adenomi Sindrome di Cushing Feocromocitoma bilaterale

Conclusioni Migliore accuratezza delle tecniche diagnostiche Incremento incidentalomi Neoplasie maligne anche in piccole masse La chirurgia rimane il gold standard nella cura delle masse surrenaliche ma con: minori costi di degenza migliori risultati estetici minore morbidita’ minori tempi operatori sostituendo l’ approccio chirurgico tradizionale con quello laparoscopico L’approccio multidisciplinare permette di ottenere i migliori risultati