CYSTIC TUMORS OF THE PANCREAS

Transcription

1 gstrointestinl trct nd domen CYSTIC TUMORS OF THE PANCREAS Nichols J. Zyromski, MD Cystic tumors (neoplsms) of the pncres re fr more common thn once thought, developing in up to 10% of the generl popultion. Mny cystic pncretic tumors re enign; however, some (prticulrly mucinous tumors) hve distinct mlignnt potentil. Unfortuntely, no idel method currently exists to predict the presence of invsive cncer in n existing cystic tumor or the risk of developing mlignncy if not present lredy. This fct mkes surgicl ptient selection chllenging. In ddition, widespred use of dominl cross-sectionl imging hs incresingly identified symptomtic ptients with incidentl pncretic cysts. For ll of the resons outlined ove, dignosis nd tretment of cystic pncretic tumors represent one of the most exciting nd dynmic topics in pncretic surgery tody. This chpter reviews the pthology, dignosis, nd tretment of the most common pncretic cystic tumors, with specil emphsis on the mngement of intrductl ppillry mucinous neoplsm (IPMN), s well s the evlution of incidentlly discovered pncretic cysts field in ctive evolution. Epidemiology nd Generl Considertions epidemiology The true incidence of pncretic cysts in the generl popultion is difficult to estimte ut likely pproximtes 2%. Rdiologic studies estimte tht the prevlence of pncretic cysts rnges from 1.2 to 19.6% in symptomtic individuls undergoing cross-sectionl imging, including mgnetic resonnce imging (MRI) nd computed tomogrphy (CT). 1 3 Most of these studies confirm n incresing prevlence with ge up to pproximtely 10% y ge 70. Ptients with strong fmily history of pncretic cncer who themselves re t high risk for developing pncretic denocrcinom were found to hve significntly incresed incidence of pncretic cysts (39%) when surveyed with n ggressive screening progrm. 4 One widely quoted utopsy series found pncretic cysts in remrkly high numer, 24%, lthough this high incidence hs yet to e vlidted. 5 pthology The most common neoplstic pncretic cysts re serous cystic neoplsms (SCNs), mucinous cystic neoplsms (MCNs), nd IPMNs. Tle 1 lists ll pncretic cystic lesions, including less common pncretic cystic tumors nd lesions mimicking pncretic cysts [see Tle 1]. Pncretic cysts cn e clssified into those tht re enign (little to no mlignnt potentil) nd those with mlignnt potentil. In generl, potentilly mlignnt cysts include mucincontining pncretic cysts (IPMNs nd MCNs) nd, to lesser extent, solid nd cystic ppillry tumors nd cystic islet cell tumors Decker Intellectul Properties Inc dignosis Due to n increse in the use of cross-sectionl dominl imging, mny pncretic cysts re found incidentlly on cross-sectionl imging performed for seprte indiction (i.e., kidney stone, dominl pin, trum evlution, etc.). Adominl CT is prevlent nd reltively inexpensive nd provides good detil of surrounding structures. MRI with mgnetic resonnce cholngiopncretogrphy (MRCP) provides similr detil of surrounding ntomic structures. The dvntge of MRI/MRCP is more detiled informtion out pncretic ductl ntomy (prticulrly communiction with the cyst), cyst wll, nd lumen (i.e., murl nodules or septtions), nd MRI/MRCP is more sensitive thn CT in terms of detecting smller pncretic cysts [see Figure 1]. In ddition, MRI does not expose the ptient to ionizing rdition nd thus my e etter (leit more expensive) cross-sectionl imging choice for longitudinl surveillnce (i.e., in the cse of IPMN). Trnsdominl ultrsonogrphy (US) hs the dvntges of completely voiding rdition exposure nd eing the lest expensive imging modlity. However, trnsdominl US is opertor dependent nd provides limited ntomic detil, nd its resolution is limited y ptient ody hitus nd the presence of overlying viscer. More invsive imging includes endoscopic ultrsonogrphy (EUS) nd endoscopic retrogrde cholngiopncretogrphy (ERCP). Ech of these specilized tests offers unique dvntges: EUS offers the ility for USdirected spirtion of cyst fluid nd cyst wll structures [see Figure 2], wheres ERCP my identify the chrcteristic fish mouth ppill disgorging mucin often seen in ptients with IPMN [see Figure 3]. Intropertive US is n importnt ddition to the surgeon s pproch to pncretic cysts, prticulrly when the cysts re treted lproscopiclly. Finlly, fluorodeoxyglucose positron emission tomogrphy (FDG-PET) scnning my provide informtion out cysts metolic ctivity nd s such (t lest theoreticlly) my help identify mlignnt cysts [see Figure 4]. The use of FDG-PET scnning is currently investigtionl. 6 Tle 1 Pncretic Cysts Benign (little or no mlignnt potentil) Serous cystdenom Acinr cell cystdenom Simple (congenitl) cyst Pseudocyst Cysts with mlignnt potentil Mucinous cystic neoplsm (MCN) Intrductl ppillry mucinous neoplsm (IPMN) Solid nd cystic pseudoppillry tumor Cystic neuroendocrine tumor Lesions mimicking pncretic cysts Lymphoepithelil cyst Cystic prgnglionom Dermoid inclusion cyst Intestinl dupliction cyst Accessory spleen DOI /

2 gstro cystic tumors of the pncres 2 c Figure 1 () Computed tomogrphic scn of ptient with intrductl ppillry mucinous neoplsm (IPMN) in the uncinte process (rrow). Note the reltive lck of detil even with intrvenous contrst dministrtion. () T 2 -weighted mgnetic resonnce imging study of the sme ptient with IPMN. (c) Mgnetic resonnce cholngiopncretogrphy imging study of the sme ptient with IPMN. The dshed rrow mrks the common ile duct, the solid long rrow shows the cyst, nd the solid short rrows mrk the min pncretic duct. cyst fluid evlution Evlution of pncretic cyst fluid is n re of enthusistic ctive investigtion. Currently, cyst concentrtions of mylse nd crcinoemryonic ntigen (CEA) re the most useful indices pplied to clinicl use. A cyst fluid CEA concentrtion greter thn 192 ng/ml is consistent with mucinous cyst with resonle sensitivity (positive predictive vlue > 90%), lthough the ccurcy of this test is only out 80%. 7,8 Importntly, incresing concentrtions of cyst CEA hve not correlted with incresed risk of mlignncy. A cyst fluid CEA concentrtion greter thn 800 ng/ml is highly sensitive for MCN or mucinous cystdenocrcinom nd thus my influence the decision to operte. 9 A high mylse concentrtion in pncretic cyst fluid simply suggests communiction with the pncretic ductl system, s seen in pseudocyst or IPMN. A cyst fluid mylse less thn 250 IU/mL is typiclly seen with SCN. 9 A gret del of investigtion hs focused on identifying sensitive nd specific mesures of mlignncy in pncretic cysts. Severl studies hve reported cyst fluid DNA nlysis; unfortuntely, none hve een le to distinguish usle

3 gstro cystic tumors of the pncres 3 mngement Mngement of the ptient with pncretic cyst should e tilored sed on how secure clinicins re with ccurte dignosis of the cyst, individul ptient fctors (i.e., fmily history of pncretic cncer, ge, generl medicl comorid stte, fitness for opertive intervention), nd ptient symptoms. Idelly, pncretic cyst ptients re evluted y multidisciplinry group of physicins, including pncretic surgeons, gstroenterologists, nd experienced gstrointestinl/pncretic rdiologists. Mny high-volume pncretic centers hve developed pncres cyst clinics or tumor ords, including ll of these clinicins. A generl mngement lgorithm for pncretic cystic lesions identified on cross-sectionl imging is shown in Figure 5 [see Figure 5]. Figure 2 Endoscopic ultrsound imge. Arrows illustrte fineneedle spirtion iopsy of cyst wll (circled). DNA profile tht successfully predicts cyst mlignncy. 10 Similrly, commercil ssys re ville to test for K-rs muttion, very common genetic muttion seen in pncretic denocrcinom. Clinicl ppliction of these tests hs filed to ccurtely differentite enign from mlignnt or mucinous nd nonmucinous cysts. 11 Current investigtion is focused on identifying novel mrkers in cyst fluid, including shed proteins nd microrna. Cytology otined from the cyst fluid my e dignostic; however, it hs low sensitivity due to limited cell yield nd potentil contmintion y intestinl mucosl cells. opertive indictions Tle 2 summrizes opertive indictions for ptients with pncretic cysts [see Tle 2]. In generl, symptomtic cysts should e resected in ptients fit for surgery. Lrge pncretic cysts my cuse symptoms y mss effect, tht is, erly stiety, nuse, or vomiting from gstric or duodenl ostruction; iliry ostruction; or pin from retroperitonel expnsion. Acute pncretitis cused y pncretic cysts is more common thn generlly pprecited. As mny s 33% of IPMN ptients coming to resection hve hd t lest one out of pncretitis. 12 Finlly, ptient nxiety should not e overlooked s symptomtic indiction for surgery, prticulrly in young ptients who would require long-term surveillnce, s well s in those with personl experience (i.e., reltives) with pncretic cncer. Oviously, the decision to operte for the indiction of nxiety lone is complex nd should e determined only fter extensive counseling on the risk/enefit profile. Figure 3 ( nd ) Endoscopic views of pthognomonic fish mouth ptulous ppill disgorging mucin in ptient with min duct intrductl ppillry mucinous neoplsm.

4 gstro cystic tumors of the pncres 4 Figure 4 () Adominl computed tomogrphic imge of ptient with mucinous cystic neoplsm tht on finl pthologic nlysis proved to hror denocrcinom. () Positron emission tomogrphic (PET) scn of the sme cyst s in. Arrows highlight the PET-vid portion of the cyst wll. The stndrd uptke vlue ws 2.5. Fitness for Opertion Yes No No further evlution or consider intervl imging for cdemic purpose Symptomtic Pin Luminl GI impingement Pncretitis Jundice Imging consistent with: MD-IPMN MCN SPN CNEN Imging consistent with: BD-IPMN Dignosis Uncertin Mngement per Fukuok guidelines 18 [see Figure 8] Consider EUS/FNA Opertion Consider opertion with pproprite counseling Consider short-term follow-up with cross-sectionl imging Figure 5 Algorithm for generl mngement of pncretic cystic neoplsm. BD-IPMN = rnch duct intrductl ppillry mucinous neoplsm; CNEN = cystic neuroendocrine tumor of the pncres; EUS = endoscopic ultrsonogrphy; FNA = fine-needle spirtion; GI = gstrointestinl; MCN = mucinous cystic neoplsms; MD-IPMN = min duct intrductl ppillry mucinous neoplsm; SPN = solid pseudoppillry neoplsm.

5 gstro cystic tumors of the pncres 5 Tle 2 Opertive Indictions for Pncretic Cysts Symptoms Adominl pin Acute pncretitis Erly stiety Nuse/vomiting Biliry ostruction Anxiety Mucinous cysts All mucinous cystic neoplsms (MCNs) Min duct intrductl ppillry mucinous neoplsm (IPMN) Brnch duct intrductl ppillry mucinous neoplsm (IPMN) with worrisome fetures or high-risk stigmt * Mlignnt potentil Mucinous cysts (see ove) Solid nd cystic pseudoppillry tumor Cystic neuroendocrine tumors *Worrisome fetures: cyst greter thn 3 cm, thickened cyst wlls, min pncretic duct (MPD) size 5 to 9 mm, nonenhnced murl nodules, rupt chnge in MPD clier with distl pncretic trophy, lymphdenopthy. 18 High-risk stigmt: ostructive jundice, enhnced solid component, MPD greter thn 10 mm. 18 Pseudocyst By definition, pseudocyst hs no epithelil lining. Pseudocysts form when pncretic duct ecomes disrupted; s the leking pncretic digestive juice is wlled off, firotic cpsule develops [see Figure 6]. Mny older surgicl textooks identify pseudocyst s the most commonly occuring pncretic cystic lesion. Contemporry imging dt hve shown tht neoplstic cysts re more common thn pseudocysts. 3 All ptients with pncretic cysts should e questioned specificlly regrding historicl symptoms of cute pncretitis: epigstric or dominl pin. Most ptients with n episode of cute pncretitis will seek medicl ttention, which lmost lwys includes evlution of serum mylse nd lipse. However, the rre ptient my experience n episode of cute pncretitis without coming to medicl ttention. The dignosis of pseudocyst is often pprent from this clinicl history of cute or chronic pncretitis. Pseudocyst fluid nlysis revels sustntilly high concentrtion of mylse (tens to hundreds of thousnds IU/mL). Detiled discussion of pseudocyst mngement strtegy is eyond the scope of this chpter; however, few slient points deserve mention. In generl (nd regrdless of size), pseudocysts do not require tretment unless they ecome symptomtic. 13 Second, tretment strtegy (percutneous spirtion versus endoscopic versus surgicl) should e dictted sed on the pncretic duct ntomy. 14 Lstly, if surgicl dringe of pncretic pseudocyst is performed, the cyst wll must e iopsied to prove the sence of epithelil lining. Also noteworthy is the fct tht some pseudocysts my e entirely filled with viscid, postinflmmtory deris tht mimics mucin on crosssectionl imging nd EUS evlution. Serous Cystdenom The mjor distinction etween serous nd mucinous pncretic cysts is importnt ecuse serous cystdenoms (SCAs) re predominntly enign lesions. SCAs rise mostly in women (75%) nd re typiclly dignosed in the sixth to Figure 6 () Mgnetic resonnce imging (MRI) study of ptient with clinicl history of severe cute pncretitis. This MRI suggests oth solid (solid rrow) nd fluid (dshed rrow, right in this T 2 -weighted imge) components in the pseudocyst. () Intropertive ultrsound imge of the sme ptient s pseudocyst (circled), which ws found to e composed entirely of mylse-rich fluid. seventh decde of life. 15,16 These cysts my rise in ny portion of the pncres nd re often lrge t the time of dignosis. Ptients with the von Hippel-Lindu syndrome my hve multiple SCAs. Ptients my e symptomtic or my mnifest symptoms relted to mss effect of the cyst, including dominl pin, erly stiety, gstric outlet ostruction, or jundice. It is extremely rre for SCA to cuse cute pncretitis. The typicl SCA is composed of multiple smll cysts lined with cuoidl epithelium; these lesions re well circumscried nd my hve chrcteristic centrl stellte

6 gstro cystic tumors of the pncres 6 firous scr tht lends itself to secure rdiologic dignosis [see Figure 7]. These lesions my lso demonstrte clcifiction of the cyst wll. On the other hnd, oligocystic (i.e., < 5 cysts) or mcrocystic SCAs re less common ut my e confused with mucinous cystic lesions. Cyst fluid nlysis generlly revels low (< 5 ng/ml) CEA concentrtion nd vrile mylse concentrtion; cytology is usully nondignostic. Becuse SCAs re mostly enign, opertive mngement should e dictted y the presence of symptoms. The SCA ptient mnged expectntly should e surveyed t n intervl to exclude rpid cyst growth. The nturl history of SCA is unknown, lthough some uthorities hve suggested tht cysts greter thn 5 cm in size my hve incresed growth rte nd thus tht this size in itself my represent n opertive indiction. 16 Although rre, mlignnt degenertion of SCA to serous cystdenocrcinom does occur. In the lrgest singleinstitution series of resected SCA, 1.3% of ptients hd mlignnt trnsformtion. 15 This numer is likely rtificilly elevted ecuse mny ptients with SCA never come to opertion; tht is, the true denomintor of SCA ptients is not known. In fct, to dte, n ggregte of only 26 ptients with serous cystdenocrcinom hs een reported in the English literture These ptients with mlignnt trnsformtion clerly hve lrger cysts (10.1 cm) nd hd medin survivl of 36 months fter resection. Clinicins should hve n elevted index of suspicion for mlignnt trnsformtion of SCA if new or worsening symptoms develop or if rpid cyst enlrgement is oserved. Mucinous Tumors The recent Fukuok working group consensus guidelines on mucinous cyst (including IPMN nd MCN) mngement delinete opertive indictions for ptients with mucinous pncretic cysts. 18 Fit ptients with secure dignosis of MCN should undergo resection. Similrly, fit ptients with min duct (MD) IPMN should undergo resection. The decision for surgery in ptients with rnch duct (BD) IPMN is more complex. Previous recommendtions suggested opertive resection for fit ptients with BD-IPMN greter thn 3 cm. 19 The more current consensus guidelines no longer recommend opertion sed on size lone nd focus on those cysts with worrisome fetures of greter thn 3 cm, c Figure 7 () Adominl computed tomogrphic scn showing serous cystdenom with typicl chrcteristics: note the centrl stellte firous scr. ( nd c) T 1 - nd T 2 -weighted dominl mgnetic resonnce imge showing multiple smll cysts of serous cystdenom in the pncretic til.

7 gstro cystic tumors of the pncres 7 thickened cyst wll, min pncretic duct (MPD) size of 5 to 9 mm, nonenhncing murl nodules, rupt chnge in MPD clier with distl pncres trophy, nd lymphdenopthy. Additionl high-risk stigmt of jundice, n enhnced solid component, nd MPD greter thn 10 mm re lso indictions for resection sed on the current Fukuok guidelines [see Figure 8]. Mucinous Cystic Neoplsms: Mucinous Cystdenom nd Mucinous Cystdenocrcinom MCNs represent one of two mucin-secreting pncretic cysts (IPMN is discussed elow); it ers repeting tht ll mucinous pncretic neoplsms hve mlignnt potentil. MCNs rise most commonly in women (95%) t men ge of 48 yers. 20,21 Most MCNs re locted in the pncretic ody or til. The clinicl presenttion of MCN rnges from the symptomtic incidentl finding to significnt dominl pin or mss effect from the cyst. Up to 10% of MCN ptients my present with cute pncretitis. Rdiologiclly, MCNs re chrcteristiclly thick wlled nd typiclly pper s single cyst with internl septtion [see Figure 9]. Some MCNs pper rdiologiclly similr to pseudocysts; however, the pncretic prenchym djcent to (prticulrly upstrem from) MCN does not typiclly mnifest chronic pncretitis fetures such s clcifiction nd trophy. Fluid nlysis from MCN commonly revels elevted CEA; the cyst mylse concentrtion is vrile ut is typiclly low s the vst mjority of MCNs do not communicte with the pncretic ductl system. Pthologic nlysis of MCN revels the pthognomonic feture of ovrin strom : hypercellulr stroml lyer lying eneth columnr mucinous epithelium [see Figure 10]. This ovrin strom expresses estrogen nd progesterone receptors (detectle y immunohistochemistry) nd distinguishes these cysts from others, especilly IPMN. The vst mjority of MCNs do not communicte with the pncretic ductl system. Between 10 nd 20% of MCNs in surgicl series demonstrte mlignnt chnges; some uthorities hve suggested tht most MCNs greter thn 4 cm in size hror mlignnt chnge. 20,21 Ptients with mucinous cystdenocrcinom generlly hve lrger cysts nd re older. Ptients mnged with strtegy of wtchful oservtion (i.e., those reluctnt Yes High-risk stigmt* Consider surgery No Yes EUS Worrisome fetures No EUS fetures Murl nodule Min duct involvement Cytology suspicious or No Size of cyst < 1 cm 1 2 cm 2 3 cm > 3 cm CT/MRI in 2 3 yers CT/MRI yerly 2 yers; lengthen intervl if no chnge EUS 3 6 months My lengthen intervl s pproprite Consider surgery in young ptient Close surveillnce MRI/EUS every 3 6 months Consider surgery in young ptient Figure 8 Algorithm for mnging ptients with rnch duct intrductl ppillry mucinous neoplsm sed on recent Fukuok guidelines. 18 Worrisome fetures include cyst size greter thn 3 cm, thickened cyst wll, min pncretic duct (MPD) size of 5 to 9 mm, nonenhncing murl nodules, rupt chnge in MPD clier with distl pncres trophy, nd lymphdenopthy. High-risk stigmt include jundice, n enhnced solid component, nd min pncretic duct size greter thn 10 mm. CT = computed tomogrphy; EUS = endoscopic ultrsonogrphy; MRI = mgnetic resonnce imging.

8 gstro cystic tumors of the pncres 8 Figure 9 () Coronl computed tomogrphic scn showing lrge mucinous cystdenom in the pncretic til. () Mgnetic resonnce imge of the sme ptient s mucinous cystdenom demonstrting thick-wlled single cyst with septtions (rrow). to hve opertion, those in whom the dignosis is not completely secure) should hve routine nd lifelong surveillnce. The idel surveillnce intervl nd modlity remin point of dete. On the other hnd, ptients with resected MCNs tht hve no evidence of mlignnt degenertion do not need routine follow-up. 18 Intrductl Ppillry Mucinous Neoplsm In 1982, Ohhshi nd collegues presented wht is felt to e the first report of wht is now understood to e IPMN. 22 Figure 10 Histologic imge of mucinous cystic neoplsm ovrin strom rchitecture detiling hypercellulr strom lyer (solid rrows) lying eneth columnr mucinous epithelium (dshed rrows). These uthors descried new type of mucinous pncretic cyst tht they termed mucin-secreting pncretic cncer. Of course, the pthologic process of IPMN is not new tht is to sy tht humn eings did not strt developing IPMNs in the 1980s. A forml pthologic review of ll resected pncretic cncers t the Myo Clinic etween 1960 nd 1980 documented much erlier cses of wht is now recognized s IPMN. 23 It is now recognized tht IPMN is the most common cystic pncretic neoplsm. This unique pncretic cyst is interesting for numer of resons. First, IPMN hrors the most significnt mlignnt potentil of ny pncretic cyst. Although most IPMN ptients will not develop mlignnt degenertion, ll IPMNs must e considered premlignnt condition s mlignnt chnges re oserved in s mny s hlf of ll resected IPMNs. 24 Second, IPMNs my develop in the MPD (MD-IPMN), rnch ducts (BD-IPMN), or oth min nd rnch ducts in mixed type [see Figure 11]. Third, s mny s 40% of ptients with IPMN hve multiple cysts in multiple loctions in the pncres, mking opertive plnning mjor chllenge. The ltter fcts re of prticulr interest considering the development nd nturl history of IPMN, rising the intriguing theory of field genetic defect in the pncretic prenchym. 18,24 The fct tht IPMN ptients my develop progressive or recurrent cysts in the pncretic remnnt fter resection lends credence to this field defect theory, mkes opertive decision mking more difficult, nd highlights the need for lifelong surveillnce in these ptients. Both MD-IPMN nd mixed-type IPMN occur more commonly in men thn in women nd re dignosed t men ge of 66 yers. 24,25 Ptients with IPMN present with complints similr to those with other pncretic cysts: dominl pin (50%), weight loss (40%), jundice (15%),

9 gstro cystic tumors of the pncres 9 c Figure 11 () Mgnetic resonnce cholngiopncretogrm of ptient with mixed-type intrductl ppillry mucinous neoplsm (IPMN). Note the min pncretic duct diltion downstrem to the hed from the lrge cystic component nd the ecttic, tortuous pncretic duct with side rnch cinriztion upstrem to the til (similr to chronic pncretitis findings). () Axil computed tomogrphic imge of ptient with min pncretic duct IPMN. Note the min pncretic duct diltion nterior to the superior mesenteric vein (rrow). (c) Mgnetic resonnce cholngiopncretogrm of the sme ptient from showing smooth diltion of the min pncretic duct ll the wy to the til. nd other ostructive symptoms, such s nuse, vomiting, nd erly stiety. In contrst to other cyst types, s mny s 15 to 30% of IPMN ptients my experience cute pncretitis. 12 In most lrge IPMN series, 15 to 20% of ptients re discovered incidentlly. Both CT nd MRI re useful imging modlities in IPMN. The dvntges of CT include its widespred vilility, ese of tolernce for ptients, lower cost, nd resonly stndrdized cquisition protocols. On the other hnd, CT exposes ptients to ionizing rdition; even the reduced rdition dose of contemporry CT scnning protocols must e considered in IPMN ptients, who will most often require lifelong surveillnce. In contrst to CT, MRI is more expensive nd requires longer scnning times in confined tue, which my not e tolerted y some ptients. However, no ionizing rdition exposure is required with MRI. Perhps the most significnt dvntge of MRI lies in the improved visuliztion of internl cyst rchitecture: septe, murl nodulrity, nd pncretic duct cyst communiction. 26,27 Secretin dministrtion stimultes pncretic exocrine secretion, which distends the pncretic ducts. Imging fetures tht rise concern for mlignncy include cyst wll thickening, the presence of cyst wll nodules [s illustrted in Figure 2], nd solid components. Invsion into surrounding structures is n ominous sign. Pncretic prenchyml trophy is commonly seen in ptients with MD-IPMN, sometimes mking this lesion difficult to distinguish from chronic pncretitis. Mlignnt IPMNs mnifest differentil histopthology, which hs een defined y immunohistochemicl stining (prticulrly CDX2 nd MUC2) nd correltes with outcomes. 28,29 Colloid crcinoms hve intestinl-type differentition nd etter reltive prognosis thn tuulr crcinoms. Similrly, different cell linege hs een identified in the ppillry components of IPMN. Gstric, intestinl, pncreticoiliry, nd oncocytic types hve ll een defined.

10 gstro cystic tumors of the pncres 10 Most BD-IPMNs hve gstric-type histology, in which only smll percentge will develop mlignnt degenertion. 30 Mngement strtegies differ sed on the presence of min duct versus side rnch types of IPMN; recent expert consensus conference held in Fukuok, Jpn, hs detiled guidelines for the clinicl pproch to IPMN ptients. 18 min duct ipmn For the ske of mngement decisions, MD-IPMN nd mixed-type IPMN re considered together. The incidence of mlignnt trnsformtion seen in MD-IPMN is high: nerly hlf of resected MD-IPMNs will demonstrte invsive crcinom nd n dditionl 20% will hve high-grde dysplsi or crcinom in situ. 24,25 The mjority (66%) of MD-IPMNs re found in the pncretic hed, wheres up to 10% of these lesions ffect the entire pncretic duct. Cross-sectionl imging typiclly identifies MPD diltion greter thn 6 mm [see Figure 11c]. Endoscopic visuliztion of mucin extruding from ptulous fish mouth ppill is pthognomonic for MD-IPMN [see Figure 3]. ERCP my visulize intrductl filling defects consistent with ppillry extrusions nd is lso useful to otin mucus smples nd duct rushing. More recently, ERCP hs een comined with endoscopic pncretoscopy through smller mother-dughter scope; this dignostic modlity permits visuliztion nd iopsy of discrete intrductl lesions. Specific, trgeted iopsies of murl lesions my lso e otined y EUS-guided iopsy. Cyst spirtion with EUS guidnce lso provides fluid for iochemicl nlysis. Surgicl resection is recommended in ll fit ptients with MD-IPMN nd mixed-type IPMN. A common preopertive chllenge is to loclize the specific tumor in MD-IPMN; some ptients with MD-IPMN my e est served with totl pncretectomy (TP), lthough the decision for TP is complex nd should not e tken lightly (discussed elow). rnch duct ipmn Mngement of ptients with BD-IPMN differs from tht for MD-IPMN in tht surveillnce plys greter role. Current dt suggest tht BD-IPMNs ccount for the mjority of incidentl pncretic cysts tody. 24,25 BD-duct IPMNs re multifocl in 20 to 40% of ptients, fct tht hs mjor implictions in opertive nd screening decision mking. The risk of mlignnt chnge is reltively lower in BD-IPMN thn in MD-IPMN; pproximtely 25% of resected BD-IPMNs re found to hror high-grde dysplsi or frnk mlignncy t resection. 18 This rte of mlignnt degenertion oviously is significnt from the clinicl stndpoint. Dignosis of BD-IPMN my e chllenging, prticulrly in the ptient with single cyst. Communiction with the pncretic ductl system seen y MRI/MRCP or EUS supports the dignosis of BD-IPMN. Cyst fluid high in mucin or CEA content similrly suggests BD-IPMN. However, portion of these ptients with presumed BD-IPMN my e mnged with presumptive ut not definitive dignosis. Previous IPMN mngement guidelines (the Sendi criteri) 19 suggested resection of BD-IPMN with murl nodules, cysts greter thn 3 cm, MPD diltion greter thn 6 mm, or cysts cusing symptoms. These guidelines hve een shown to hve very high negtive predictive vlue ut positive predictive vlue of only out 20%, mening tht nerly four in five resected ptients did not mnifest mlignnt degenertive chnges. The current Fukuok guidelines for BD-IPMN mngement consider the clinicl high-risk stigmt of jundice, n enhncing solid component, or n MPD greter thn 10 mm or worrisome fetures of thickened cyst wlls, cyst greter thn 3 cm, rpid cyst growth, nonenhncing murl nodules, MPD size greter thn 5 to 9 mm, rupt MPD size chnge with distl pncretic trophy, nd peripncretic lymphdenopthy to e more importnt thn size lone. Younger ptients with cysts greter thn 2 cm my e cndidtes for opertion due to the long length of potentil follow-up necessry. 31 Figure 8 illustrtes decision-mking lgorithm for IPMN ptients sed on the most current Fukuok guidelines [see Figure 8]. Ptients with multifocl BD-IPMN should hve decision mking regrding opertion or surveillnce sed on individul cysts rther thn the collection of cysts. Tht is to sy, it my e pproprite to resect one cyst with higherrisk fetures while leving other cysts in situ with plns for longer-term surveillnce. 25,32,33 Therpeutic Considertions in IPMN intropertive mrgin nlysis A mjor surgicl chllenge in IPMN ptients lies in determining the extent of resection. This chllenge is prticulrly pprent in ptients with MD-IPMN. The high incidence of mlignnt degenertion, differentil risk sed on morphology (i.e., min duct versus rnch duct lesions), the presence of skip lesions or field defect, nd the known difficulty in ccurtely identifying dysplsi in the setting of inflmmtion re ll importnt fctors for the surgeon to lnce during the intropertive decision-mking process. Frozensection nlysis of IPMN is extremely difficult even for the most experienced pncretic pthologist. 34 MPD epithelium my e eroded, leding to missed dignosis of dysplsi. Incresed cellulr typi present in severe inflmmtion my mimic dysplsi. Chronic pncretic duct ostruction or chronic pncretitis my lso mimic mlignnt chnge on frozen-section nlysis. The most concerning limittion of frozen-section nlysis is the known presence of skip or discontinuous lesions, which hve een documented in up to 20% of surgicl series. 34,35 Intropertive decision mking must tke into ccount the limittions of frozen-section nlysis nd understnding of underlying pthology (i.e., single cyst, multifocl disese) ut lso, importntly, generl ptient considertions such s ge nd comorid medicl sttus. In generl, if cler high-grde dysplsi or invsive crcinom is present t the mrgin frozen-section nlysis, further resection should e performed. 18 On the other hnd, low-grde or moderte dysplsi my not require further tretment. Thus, preopertive ptient counseling should include discussion with the ptient out the potentil need for TP. Prudent pncretic surgeons lso consult their experienced pncretic surgicl pthologists preopertively to wrn them of n upcoming chllenging IPMN cse. indictions for totl pncretectomy Considertion of TP rises in ptients with MD-IPMN nd in those with multiple, multifocl BD-IPMNs. MD-IPMN

11 gstro cystic tumors of the pncres 11 clerly hs significnt risk of mlignnt chnge, lthough the min tumor focus my e quite difficult to identify even with the most sophisticted imging techniques (oth preopertive nd intropertive US). As noted ove, intropertive frozen-section nlysis of the cut pncretic duct mrgin is not completely ccurte even in the most experienced hnds. Perhps most concerning in the context of the IPMN ptient s glol mngement strtegy is the rel concern for cyst recurrence nd susequent cncer development in the postsurgicl pncretic remnnt. 35,36 The intuitively ttrctive concept of removing ll t-risk pncretic prenchym must e crefully lnced with the physiologic consequences imposed on TP ptients. The clinicin must consider whether ptients hve dequte psychologicl, socil, nd finncil support to survive with resonle qulity of life in n pncretic stte. Pncretic exocrine insufficiency is reltively strightforwrd to tret, lthough exocrine enzymtic replcement is expensive. Pncretic endocrine insufficiency, on the other hnd, remins significnt chllenge for ptients with TP. Even with the etter lnce of contemporry insulin preprtions, TP ptients my experience reltively rittle dietes mellitus. Often the hypoglycemic episodes re more concerning nd chllenging to the ptient thn either shortterm (dietic ketocidosis) or longer-term complictions of hyperglycemi. Some contemporry literture suggests tht TP ptients hve qulity of life similr to tht of those undergoing segmentl pncretectomy. 37 In clinicl prctice, the chllenges of rittle dietes should not e underestimted. One potentil venue to void rittle dietes in ptients undergoing plnned TP involves utologous islet cell trnsplnttion. Experience hs grown ntionlly with totl pncretectomy islet utotrnsplnttion (TP-IAT) for chronic pncretitis ptients. 38 Although most TP-IAT ptients immeditely or eventully require some insulin replcement, their glucose control seems to e much more esily mnged thn tht of ptients with TP lone. The concept of TP-IAT for IPMN ptients is provoctive; however, the specter of reimplnting potentilly mlignnt cells looms lrge in IPMN ptients, nd, to dte, TP-IAP hs not een pplied in IPMN. extrpncretic mlignncy nd ipmn Numerous investigtors hve documented significnt incidence of extrpncretic mlignncy in IPMN ptients. 39,40 Overll, etween 10 nd 50% of IPMN ptients will e dignosed with mlignnt neoplsm outside the pncres. The mjority of these neoplsms involve the gstrointestinl trct; colon polyps nd denocrcinom re most common in Western countries, wheres gstric denocrcinom is most common in Asi. Most extrpncretic neoplsms re dignosed efore or t the time of IPMN dignosis. This oservtion informs the IPMN ptient s evlution: in the West, colonoscopy is indicted during evlution of newly dignosed IPMN, wheres Asin IPMN ptients should lso hve screening upper endoscopy. Screening for other common mlignnt tumors (i.e., rest, uterine cervix, prostte, etc.) should e crried out s recommended for the generl pulic. intervl, type, nd durtion of surveillnce The intervl, type, nd durtion of surveillnce re points of ongoing controversy in IPMN ptients. The controversy revolves round the intervl nd type of surveillnce, either in ptients with primry cysts mnged nonopertively or surveillnce of the pncretic remnnt fter resection. The economic implictions of long-term (in mny cses, lifetime) surveillnce re significnt nd re felt t oth the societl nd the individul ptient level. Not to e overlooked is the nxiety experienced y ptient who hs tumor in his or her pncres. Ptients mnged nonopertively who do not hve highrisk stigmt of jundice, n enhncing solid component, or n MPD greter thn 10 mm should hve initil short-term (3 to 6 months) CT or MRI to estlish cyst stility. After this point, these ptients should undergo n nnul history/ physicl exmintion, lood tumor mrker evlution, nd cross-sectionl imging y CT or MRI/MRCP. Ptients whose cysts develop high-risk stigmt nd those who hve fmily history of hereditry pncretic cncer (i.e., two or more ffected first-degree reltives) should hve shorter intervl surveillnce of 3 to 9 months. Ptients who develop worrisome fetures (i.e., thickened cyst wlls, cyst greter thn 3 cm or rpid cyst growth, nonenhncing murl nodules, MPD size greter thn 5 mm, rupt MPD size chnge with distl pncretic trophy, or peripncretic lymphdenopthy) should e offered surgicl resection if physiclly fit. Ptients with strong fmilil pncretic cncer history represent popultion with significntly elevted risk of developing pncretic cncer. These ptients lso develop pncretic cysts t higher rte thn the generl pulic. 4 This group of ptients should undergo short-intervl surveillnce with CT or MRI/MRCP nd EUS every 3 months. If no chnge is seen in the cyst over 2-yer period, the surveillnce intervl my e lengthened to every 6 months. Screening fter resection should e sed on the pthologic nlysis of the resected specimen nd the presence of other known cysts in the pncretic remnnt. Ptients with noninvsive MCN require no further screening. Ptients with resected noninvsive IPMN nd no residul lesions should hve screening of the pncretic remnnt; however, imging t 2- to 3-yer intervls seems dequte. Ptients with low- or moderte-grde dysplsi in the resected cyst should hve intervl follow-up physicl exmintion, tumor mrker evlution, nd imging on 6-month schedule. Ptients with invsive IPMN should hve follow-up on the sme schedule s those with resected pncretic ductl denocrcinom. role of ltion in ipmn nd other pncretic cysts The fct tht the mjority of ptients with pncretic cysts do not hror mlignnt potentil hs led some investigtors to propose more minimlly invsive tretment, such s cyst ltion. 41 Clinicl experience with cyst ltion is limited, nd ll ptients hve een extremely crefully selected (i.e., single cyst, size < 4 cm, etc.). The cysts re visulized y EUS, mucin is spirted (s completely s possile), nd then ethnol ± chemotherpeutic gent (pclitxel) is

12 gstro cystic tumors of the pncres 12 instilled into the cyst. The gol of this procedure is to chemiclly lte (sclerose) ll of the cyst epithelil lining. Shortterm complictions of this procedure occur infrequently ut include potentilly severe leeding nd pncretitis. In the lrgest series of these ptients reported to dte, 169 ptients hve hd reltively short medin follow-up of 29 months; 52% of ptients were seen to hve complete cyst response with 4% recurrence. 42 This modlity is intuitively ttrctive for ptients with comorid conditions tht mke opertion prohiitively risky, such s ptients with portl vein thromosis nd cvernous trnsformtion [see Figure 12] or those with heptic cirrhosis. Currently, however, cyst ltion should e considered experimentl. Critics of cyst ltion correctly point out three fcts. First, the dignosis of mny pncretic cysts is reltively inccurte without completely resecting the cyst. Second, the technique of intrluminl sclerosnt does not effectively destroy ll of the t-risk epithelium. Finlly, cyst mnipultion hmpers the ility to interpret susequent rdiologic follow-up studies. Further reserch under controlled conditions with dequte long-term follow-up will e necessry efore cyst ltion ecomes prt of routine clinicl prctice. young women (men ge 22 yers) nd re typiclly quite lrge (10+ cm) t the time of dignosis. 43,44 A vriety of nmes hve een pplied to this rre tumor: solid nd cystic tumor, ppillry cystic tumor, solid nd ppillry tumor, Frntz tumor, nd Hmoudi tumor (the ltter two eponyms recognize the pthologists who first descried the tumor). Rdiologiclly, these tumors re predominntly solid, with chrcteristic cystic res relted to tumor necrosis or hemorrhge [see Figure 13]. The fct tht these lesions re predominntly solid distinguishes them from postinflmmtory collections (i.e., wlled-off pncretic necrosis). The cyst wll my contin clcium. Not surprisingly given the typiclly lrge size t dignosis, most ptients present with symptoms relted to the cyst s mss effect [see Figure 14]. Biopsy of SPN is not usully necessry s most ptients will come to resection; however, iopsy (either fine-needle spirtion or core needle iopsy) revels microdenoid cells with pseudoppille rnching round centrl vsculr core. Solid Pseudoppillry Neoplsm Solid pseudoppillry neoplsms (SPNs) re rre, ccounting for less thn 5% of resected pncretic cysts in most lrge series. These tumors lmost universlly occur in Figure 12 Coronl computed tomogrphic scn of ptient with prohiitively complex ntomy. This mn suffered n episode of necrotizing pncretitis tht resulted in portl vein thromosis nd cvernous venous trnsformtion in the port heptis (solid rrows). He hs high-risk min duct intrductl ppillry mucinous neoplsm in the pncretic hed/uncinte process (dshed rrow) tht is eing treted y chemotherpy nd ethnol ltion. Note tht this tretment strtegy is not the stndrd of cre. Figure 13 () T 1 -weighted mgnetic resonnce imge (MRI) of solid pseudoppillry neoplsm. This lrge size is typicl. () T 2 - weighted MRI of the sme tumor.

13 gstro cystic tumors of the pncres 13 Figure 14 Opertive specimen of the solid pseudoppillry neoplsm demonstrted in Figure 13. The ptient presented with pin nd gstric outlet ostruction. Although SPNs re typiclly thought of s enign, recent reltively lrge single-institution series suggest tht s mny s 20 to 25% of these tumors mnifest mlignnt potentil, including lymphtic nd distnt (usully heptic) spred. 44 Tretment of SPN is y resection. Recently, some pncretic surgeons hve emrced enucletion of specific lesions s mesure of pncretic prenchyml preservtion (see elow). It is noteworthy, however, tht SPNs typiclly hve pseudocpsule; thus, even the most enthusistic enucletors do not recommend enucleting SPNs for fer of leving ehind potentilly mlignnt cells. Cystic Neuroendocrine Tumors Pncretic cystic neuroendocrine tumors (CNETs) re rre, ccounting for only 1.2% of ll pncretic resections nd 8% of ll resected cystic pncretic lesions in two lrge series. 45,46 These cysts occur with equl frequency in men nd women, re generlly dignosed in the fifth to sixth decde of life, nd re lmost uniformly discovered incidentlly. Ptients with multiple endocrine neoplsi syndrome type I my hve n incresed risk of developing CNET. 47 The dignosis of pncretic CNET my e suspected on CT or MRI cross-sectionl imging if the cyst wll demonstrtes erly (rteril phse) hyperenhncement [see Figure 15], lthough not ll CNETs hve this feture nd my e indistinguishle from BD-IPMNs. 46 EUS-directed fine-needle spirtion for fluid nlysis my help secure the dignosis; most CNETs will hve cells with positive immunostining for the neuroendocrine mrkers synptophysin nd chromogrnin A. The vst mjority of CNETs re nonfunctionl, lthough ptients with n pproprite clinicl picture should hve iochemicl evlution; few cystic insulinoms hve een reported. The mjority of CNETs re enign, lthough ll of the reltively lrge CNET reports document pproximtely 15% mlignnt potentil (either lymph node or distnt metstses). An re of current controversy in pncretic surgery revolves round pproprite mngement of ptients with nonfunctionl solid smll (< 2 cm) pncretic neuroendocrine tumor. Some uthorities hve suggested strtegy of oservtion with seril imging for these Figure 15 Adominl computed tomogrphic scn of smll cystic neuroendocrine tumor demonstrting hypervsculr erly rteril phse in the cyst wll (rrow). This dignosis ws secured preopertively y endoscopic ultrsonogrphy directed iopsy of the cyst wll. ptients; this rgument hs een proposed y some experts to extend to ptients with CNET. Fine-needle or core-needle iopsy of the cyst wll my inform this discussion; highgrde CNET (i.e., more thn 5 mitoses per high-power field), regrdless of size, my e more likely to metstsize. If ptients elect oservtion, seril cross-sectionl imging is mndtory prt of the follow-up. Acinr Cell Cystdenom/Cystdenocrcinom Acinr cell cystdenoms (ACAs) re rre cysts tht my e uniloculr or multiloculr. These cysts rise more commonly in femles (2:1) nd re lmost universlly enign, lthough the entity of cinr cell cystdenocrcinom hs een reported. 48 Rdiologiclly, pncretic ACAs resemle SCA. Biochemiclly, mny ACAs hve incresed CEA. Histologiclly, these cysts resemle cinr cells oth morphologiclly nd immunohistochemiclly. Ptients with ACA my come to resection ecuse of symptoms (pin, mss effect) or size increse during seril oservtion. Simple Cyst Simple pncretic cysts re uncommon cysts tht re lined y plin cuoidl epithelium. These cysts re usully firly smll nd re universlly enign. Simple pncretic cysts rrely cuse symptoms, lthough some ptients with lrge simple cysts my come to resection for the typicl spectrum of indictions. Mimickers of Cystic Pncretic Tumors A numer of different enign cystic lesions my mimic pncretic serous or mucinous cysts. Most of these cysts re dignosed t the time of pthologic nlysis.

14 gstro cystic tumors of the pncres 14 Lymphoepithelil cysts my occur in ny portion of the pncres nd re usully (ut not lwys) peripncretic s opposed to intrpncretic [see Figure 16]. 49 These cysts re more common in men. Pthologiclly, lymphoepithelil cysts re lined y squmous cells, which re surrounded y rim of lymphoid tissue. The dignosis is firly strightforwrd on frozen-section nlysis; thus, these cysts my e menle to enucletion. Dermoid cysts resemle lymphoepithelil cysts grossly nd rdiologiclly; however, they do not hve the surrounding lyer of lymphoid tissue on microscopic nlysis. These cysts my e filled with seceous glnds or other skin elements. Lymphngioms re lso similr to lymphoepithelil cysts, hving endothelil lining surrounded y lymphoid tissue. These cysts re found predominntly in young women. Figure 16 () Computed tomogrphic scn nd () T 1 -weighted mgnetic resonnce imge of ptient with intrpncretic lymphoepithelil cyst in the pncretic til. Hemngioms nd cystic prgnglionoms djcent to the pncres re extremely unusul. Vrious intestinl dupliction cysts my e locted djcent to the pncres or even within the pncretic prenchym. These cysts re lined y respirtory, intestinl, squmous, or trnsitionl epithelium. Accessory spleens re common (incidence 10 to 15%); these lesions my msquerde s pncretic cyst nd on very rre occsions my even e locted within pncretic prenchym. Accessory spleens re usully recognized s solid lesions on cross-sectionl imging. Approch to the Ptient with Incidentl Pncretic Cyst Ptients with incidentlly discovered pncretic cysts re common in contemporry prctice. A creful history nd physicl exmintion re the initil importnt step in the evlution of these ptients. Symptoms of pin should e chrcterized crefully; initition (i.e., suddenly versus grdul onset), durtion, severity (with chnges, i.e., escltion with time), nd loction re ll importnt. Cysts in the pncretic hed my cuse right upper qudrnt, ck, or shoulder pin, wheres those in the til my loclize pin predominntly to the left side nd left shoulder. Symptoms of mss effect my e sutle nd include erly stiety nd reflux. All ptients should e questioned out history of pncretitis; the dignosis of pseudocyst is supported y historicl episode of cute pncretitis or in ptient with known chronic pncretitis. On the other hnd, mny pncretic cysts (especilly MCN nd IPMN) cn cuse cute pncretitis; lthough the nturl history of this sitution is not entirely cler, mny pncretic surgeons consider n episode of cute pncretitis to e n opertive indiction. Also importnt historiclly is ny fmily history of pncretic mlignncy. The ptient s ge nd generl medicl condition re mjor fctors in tretment plnning. For exmple, prudent pproch to n symptomtic 85-yer-old ptient with mjor crdiopulmonry comoridities nd smll cyst (< 3 cm) my e no further follow-up specific to the cyst s the ptient s overll life spn is unlikely to e ffected y the cyst. On the other end of the spectrum is young, helthy person with n intermedite-sized cyst; even with secure dignosis of enign cyst, considertion must e given to extended follow-up, imging, nd even resection. Specific physicl exmintion findings to e sought include the presence of suprclviculr (Virchow) or umilicl (Sister Mry Joseph) lymphdenopthy or the rre finding of migrtory thromophleitis (Trousseu syndrome) seen with pncretic mlignncy. Sutle findings of mss effect include tympny or succession splsh over the prtilly ostructed stomch or sclerl or uccl jundice. The surgeon should review ll imging studies for type nd qulity nd question the role for supplementl/dditionl imges. For exmple, would dedicted pncretic MRI/MRCP with secretin stimultion provide more informtion out cyst communiction with the pncretic duct or murl nodulrtiy in ptient with suspected IPMN? Does the cyst loction correspond with symptoms? Is the cyst ssocited with peripncretic inflmmtion, upstrem prenchyml trophy, or pncretic duct diltion? Is the cyst menle to the lproscopic pproch or prenchymlspring opertion (enucletion)?

15 gstro cystic tumors of the pncres 15 Finlly, lortory chemistry studies should include complete lood count, comprehensive metolic pnel (to evlute jundice nd nutritionl sttus), nd the tumor mrker CA Idelly, pncres cyst ptient will e mnged coopertively in conjunction with experienced pncretic surgeons, gstroenterologists, rdiologists, nd pthologists. One physicin should ssume responsiility for coordinting follow-up mngement. Figure 5 shows generl lgorithm for mngement of pncretic cysts [see Figure 5]. Specil Opertive Considertions As greter experience with pncretic surgery hs ccrued over the pst severl decdes, the postopertive consequence s of pncretic surgery (i.e., exocrine nd endocrine insufficiency) hve ecome clerer. Efforts towrd pncretic prenchyml preservtion include tiloring pncretectomy to include resecting the miniml mount of pncretic prenchym possile. These opertions include centrl or middle segment pncretectomy nd enucletion [see Figure 17]. 50 Pncretic cysts, prticulrly those tht re most likely enign, represent n excellent pthology to which to pply these opertions. A few cvets deserve considertion. First, no opertion should spre prenchym t the cost of n oncologiclly unsound procedure. Frozen-section nlysis should e performed on ll lesions resected with centrl pncretectomy or enucletion; if mlignncy is suspected or dignosed t intropertive pthology nlysis, these opertions should e converted to trditionl procedure (i.e., pncretoduodenectomy or left-sided pncretectomy) tht permits dequte mrgin nd nodl hrvest. Oviously, this pln demnds thorough preopertive discussion with oth the ptient nd the pthologist. Second, most pncretic surgeons ccept the fct tht centrl pncretectomy nd enucletion re ccompnied y higher incidence of pncretic fistul thn trditionl pncretectomy (in generl, pncretoduodenectomy 15%, distl/left pncretectomy 25%, nd enucletion nd centrl pncretectomy 33%). 50 Preopertive ptient counseling should explin this fct nd discuss fistul mngement strtegy. Most pncretic enucletors re willing to ccept the short-term consequence of reltively higher fistul rte (most of which do not significntly impct the ptient s periopertive course) for the trdeoff of longer-term preservtion of exocrine nd endocrine function. Finlly, the importnce of intropertive US cnnot e overstted. The reltionship of cysts to the min pncretic duct should e closely interrogted with intropertive US; lesions tht re close to or involve the MPD re not menle to enucletion. MPD disruption cretes high-volume pncretic fistuls tht rrely (if ever) hel with nonopertive mngement. Spleen Cyst Stomch DIVISION OF PERITONEUM Body of Pncres Duodenum Figure 17 Centrl pncretectomy () resection nd () reconstruction.

16 gstro cystic tumors of the pncres 16 Conclusion Pncretic cystic tumors re common nd re ecoming more frequently identified with tody s widespred ppliction of cross-sectionl imging. Knowledge of specific pncretic cyst iology (especilly IPMN) is evolving, mking this field dynmic. Understnding the typicl pncretic cyst pthoiology nd dignosis is crucil to inform the individul ptient mngement strtegy. Finncil Disclosures: Nichols J. Zyromski, MD, hs no relevnt finncil reltionships to disclose. References 1. de Jong K, Nio C, Merdji B, et l. Disppointing interoserver greement mong rdiologists for clssifying dignosis of pncretic cysts using mgnetic resohnce imging. Pncres 2012;41: Lffn TA, Horton KM, Klein AP, et l. Prevlence of unsuspected pncretic cysts on MDCT. AJR Am J Roentgenol 2008;191: Spinelli KS, Fromwiller TE, Dniel RA, et l. Cystic pncretic neoplsms: oserve or operte. Ann Surg 2004;239: Cnto MI, Hrun RH, Fishermn EK, et l. Frequent detection of pncretic lesions in symptomtic high-risk individuls. Gstroenterology 2012;142: Kimur W, Ngi, H, Kurod A, et l. Anlysis of smll cystic lesions of the pncres. Int J Pncretol 1995;18: Pedrzzoli S, Sperti C, Psquli C, et l. Comprison of interntionl consensus guidelines versus 18-FDG PET in detecting mlignncy of intrductl ppillry mucinous neoplsms of the pncres. Ann Surg 2011;254: Genevy M, Mino-Kenudson M, Yeger K, et l. Cytology dds vlue to imging studies for risk ssessment of mlignncy in pncretic mucinous cysts. Ann Surg 2011; 254: Brugge WR, Lewndrowski K, Lee-Lewndrowski E, et l. Dignosis of pncretic cystic neoplsms: report of the Coopertive Pncretic Cyst Study. Gstroenterology 2004; 126: Vn der Wij L, Vn Dullemen H, Porte J. Cyst fluid nlysis in the differentil dignosis of pncretic cystic lesions: pooled nlysis. Gstrointest Endosc 2005;62: Shen J, Brugge WR, Dimio CJ, Pitmn MB. Moleculr nlysis of pncretic cyst fluid: comprtive nlysis with current prctice of dignosis. Cncer 2009;117: Swhney MS, Devrjn S, O Frrel P, et l. Comprison of crcinoemryonic ntigen nd moleculr nlysis in pncretic cyst fluid. Gstrointest Endosc 2009;69: Lee SJ, Wters JR, Schmidt CM, Zyromski NJ. Does cute pncretitis chnge the nturl history of intrductl ppillry mucinous neoplsm (IPMN)? Pncretology 2013;13: e Vits GJ, Srr MG. Selected mngement of pncretic pseudocysts: opertive versus expectnt mngement. Surgery 1998;111: Nelon W, Wlser E. Min pncretic ductl ntomy cn direct choice of modlity for treting pncretic pseudocysts (surgery versus percutneous dringe). Ann Surg 2002;235: Glnis C, Zmni A, Cmeron JL, et l. Resected serous cystic neoplsms of the pncres: review of 158 ptients with recommendtions of tretment. J Gstrointest Surg 2007;11: Tseng JF, Wrshw AL, Shni DV, et l. Serous cystdenom of the pncres: tumor growth rtes nd recommendtions for tretment. Ann Surg 2005;242: King JC, Ng TT, White SC, et l. Pncretic serous cystdenocrcinom: cse report nd review of the literture. J Gstrointest Surg 2009;13: Tnk M, Fernández-del Cstillo C, Adsy V, et l. Interntionl consensus guidelines 2012 for the mngement of IPMN nd MCN of the pncres. Pncretology 2012;12: Tnk M, Chri S, Adsy V, et l. Interntionl consensus guidelines for mngement of intrductl ppillry mucinous neoplsms nd mucinous cystic neoplsms of the pncres. Pncretology 2006;6: Cripp S, Slvi R, Wrshw AL, et l. Mucinous cystic neoplsm of the pncres is not n ggressive entity: lessons from 163 resected ptients. Ann Surg 2008;247: Le Bleur Y, Couvelrd A, Vullierme MP, et l. Mucinous cystic neoplsms of the pncres: definition of preopertive imging criteri for high-risk lesions Pncretology 2011; 11: Ohhshi K, Murkmi Y, Tkekoshi T, et l. Four cses of mucin producing cncer of the pncres on specific findings of the ppill of Vter (Jpnese). Prog Dig Endosc 1982; 20: Tollefson MK, Lisch KD, Srr MG, et l. Intrductl ppillry mucinous neoplsm: did it exist prior to 1980? Pncres 2003;26:e Fernández-del Cstillo C, Adsy NV. Intrductl ppillry mucinous neoplsms of pncres. Gstroenterology 2010; 139: Schmidt CM, White PB, Wters JA, et l. Intrductl ppillry mucinous neoplsms: predictors of mlignnt nd invsive pthology. Ann Surg 2007;246:644 51; discussion Kim JH, Eun HW, Prk HJ, et l. Dignostic performnce of MRI nd EUS in the differentition of enign from mlignnt pncretic cyst nd cyst communiction with the min duct. Eur J Rdiol 2012;81: Wters JA, Schmidt CM, Pinchot JW, et l. CT vs. MRCP: optiml clssifiction of IPMN type nd extent. Gstrointest Surg 2008;12: Adsy NV, Merti K, Bsturk O, et l. Pthologiclly nd iologiclly distinct types of epithelium in intrductl ppillry mucinous neoplsms: delinetion of n intestinl pthwy of crcinogenesis in the pncres. Am J Surg Pthol 2004;28: Adsy NV, Merti K, Ande A, et l. The dichotomy in the preinvsive neoplsi to invsive crcinom sequence in the pncres: differentil expression of MUC1 nd MUC2 supports the existence of the two seprte pthwys of crcinogenesis. Mod Pthol 2002;15: Furukw T, Htori T, Fujit I, et l. Prognostic relevnce of morphologicl types of intrductl ppillry mucinous neoplsms of the pncres. Gut 2011;60: Weinerg BM, Spiegel BM, Tomlinson JS, et l. Asymptomtic pncretic cystic neoplsms: mximizing survivl nd