The Selective Arterial Calcium Injection Test is a Valid Diagnostic Method for Invisible Gastrinoma with Duodenal Ulcer Stenosis: A Case Report

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1 Hiroshim J. Med. Sci. Vol. 65, No. 1, 13~17, Mrch, 2016 HIJM The Selective Arteril Clcium Injection Test is Vlid Dignostic Method for Invisile Gstrinom with Duodenl Ulcer Stenosis: A Cse Report Kenjiro OKADA 1), Tkeshi SUDO 1), Ktsunri MIYAMOTO 1), Yujiro YOKOYAMA 1), Yoshihiro SAKASHITA 1), Ysushi HASHIMOTO 1), Hironori KOBAYASHI 1), Hiroyuki OTSUKA 1), Tkuy SAKODA 1) nd Fumio SHIMAMOTO 2) 1) Deprtment of Surgery, Hiroshim Memoril Hospitl, Honkw-cho 1-4-3, Nk-ku, Hiroshim , Jpn 2) Deprtment of Pthology, Hiroshim Memoril Hospitl, Honkw-cho 1-4-3, Nk-ku, Hiroshim , Jpn ABSTRACT The locliztion nd dignosis of microgstrinoms in ptient with multiple endocrine neoplsi type 1 is difficult preopertively. The selective rteril clcium injection (SACI) test is vlid dignostic method for the preopertive dignosis of these invisile microgstrinoms. We report rre cse of multiple invisile duodenl microgstrinoms with severe duodenl stenosis dignosed preopertively y using the SACI test. A 50-yer-old mn ws dmitted to our hospitl with recurrent duodenl ulcers. His serum gstrin level ws elevted to 730 pg/ml. It ws impossile for gstrointestinl endoscopy to pss through to visulize the inferior prt of the duodenum, ecuse recurrent duodenl ulcers hd resulted in severe duodenl stenosis. The duodenl stenosis lso prevented dditionl endoscopic exmintions such s endoscopic ultrsonogrphy. Computed tomogrphy did not show ny tumors in the duodenum nd pncres. The SACI test provided the evidence for gstrinom in the vsculr territory of the inferior pncretic-duodenl rtery. We dignosed gstrinom in the peri- mpullry lesion, so we performed Sutotl Stomch-Preserving Pncretico- duodenectomy with regionl lymphdenectomy. Histopthologicl findings showed multiple duodenl gstrinoms with lymph node metstsis nd nonfunctioning pncretic neuroendocrine tumors. Twenty months fter surgery, the ptient is live with no evidence of recurrence nd norml gstrin level. In conclusion, the SACI test cn enhnce the ccurcy of preopertive locliztion nd dignosis of invisile microgstrinoms, especilly in the setting of severe duodenl stenosis. Key words: Selective rteril clcium injection test, Gstrinom, Duodenl stenosis, Multiple endocrine neoplsi type 1 Gstrinom is the most common neuroendocrine tumor in ptients with multiple endocrine neoplsi type 1 (MEN 1) 6,10,11). Gstrinoms in ptient with MEN 1 tend to e multiple nd too smll for imging methods to show them, mking the locliztion nd dignosis of these microgstrinoms difficult preopertively. Endoscopic ultrsonogrphy (EUS) is useful method for showing nd dignosing sumucosl microgstrinoms, ut in cse of severe stenosis cused y recurrent ulcers, it ws impossile for EUS to pss through the stenosis nd show the microgstrinoms. Some hve recommended the use of the selective rteril clcium injection (SACI) test s vlid dignostic method for the locliztion of these invisile microgstrinoms preopertively 4,8,12). We report rre cse of multiple invisile duodenl microgstrinoms nd pncretic neuroendocrine tumors in ptient with MEN 1 with severe duodenl stenosis dignosed preopertively y using the SACI test. CASE PRESENTATION A 50-yer-old mn ws dmitted to our hospitl with recurrent duodenl ulcers cusing epigstric pin, nuse nd vomiting. He hd een treted with proton pump inhiitors for duodenl ulcers for 2 yers. Despite continuous proton pump List of revitions SACI: Selective rteril clcium injection, MEN 1: Multiple endocrine neoplsm type 1 EUS: Endoscopic ultrsonogrphy, GIS: Gstrointestinl endoscopy, CT: Computed tomogrphy IPDA: Inferior pncretic-duodenl rtery, MRI: Mgnetic resonnce imging SSPPD: Sutotl Stomch-Preserving Pncreticoduodenectomy, DNETs: Duodenl neuroendocrine tumors PNETs: Pncretic neuroendocrine tumors, CgA: Chromogrnin A

2 14 K. Okd et l inhiitor tretment, his dominl symptoms did not improve. There ws no other pst medicl history except for the duodenl ulcers. His fther hd died of n unspecified pncretic tumor. Lortory tests showed elevted levels of serum clcium (12.8 mg/dl), gstrin (730 pg/ml), nd prthyroid hormone (2,000 pg/ml), ut prolctin ws norml (18.3 ng/ml). Gstrointestinl endoscopy (GIS) showed gint ulcer filling one third of the lumen of the duodenum. It ws impossile to pss the en do scope through this lesion to view the inferior prt, ecuse recurrent duodenl ulcers hd resulted in severe duodenl stenosis. In ddition, the duodenl stenosis prevented dditionl endoscopic exmintions such s EUS from showing sumucosl tumors such s gstrinoms nd otining specimens y fine-needle spirtion of the tumors. The tissue iopsied from these ulcertive lesions ws negtive for duodenl crcinom. Contrst-enhnced computed tomogrphy (CT) showed duodenl wll thickening nd edem of the descending prt of the duodenum, ut did not show tumors in the duodenum nd pncres (Fig. 1). Only one lymph node sized within 16 mm in dimeter in the posterior prt of the hed of pncres ws enhnced (Fig. 1). Angiogrphy nd the SACI test were performed to identify the rteril supply of the gstrinom. The gstroduodenl rtery, inferior pncreticduodenl rtery (IPDA), proper heptic rtery nd splenic rtery were selectively ctheterized. This test provided the evidence for gstrinom in the vsculr territory of the IPDA, the peri-mpullry lesion, nd the sence of heptic metstses (Fig. 2). In ddition, prthyroid nd pituitry glnd evlution were conducted to dignose the MEN 1. Thyroid ultrsonogrphy showed suspected prthyroid denom, ut rin mgnetic resonnce imging (MRI) showed norml pituitry glnd. We dignosed gstrinom in the peri-mpullry lesion with MEN 1, so we performed Sutotl Stomch-Preserving Pncreticoduodenectomy (SSPPD) with regionl lymphdenectomy (Fig. 3). Histopthologicl findings showed 4 smll neuroendocrine tumors sized within 3 mm in the duodenum (DNETs) (Fig. 4-c), 4 smll neuroen docrine tumors sized within 3mm in the hed of pncres (PNETs) (Fig. 5-c) nd 1 lymph node metstsis in the posterior prt of the hed of pncres (Fig. 6-). Immunohistochemicl exmintion found tht the DNETs nd the lymph node metstsis were positive for chromogrnin A (CgA), synptophysin nd gstrin. On the other hnd, the PNETs were positive for CgA nd synptophysin, ut negtive for gstrin. The Ki-67 leling index of the DNETs nd the metsttic lymph node were out 10%, nd tht of the PNETs ws < 2%. By WHO clssifiction 2010, the DNETs were NET G2, nd the PNETs were NET G1. The ptient ws dignosed with multiple duodenl gstrinoms with lymph node metstsis nd nonfunctioning PNETs with MEN 1. In the postopertive course, the pncretic fistul s compliction ws treted with conservtive mesures. He ws dischrged from the hospitl on the 51st postopertive dy. Ten months fter the surgery, prthyroidectomy ws performed for the suspected prthyroid denom. Histopthologicl findings showed the prthyroid denom. Now twenty months fter the first surgery, SSPPD, the ptient is live with norml gstrin level nd without ny evidence of recurrence. Fig. 1. Computed tomogrphy. () Arrow indictes duodenl wll thickening nd edem. () Arrow indictes enhnced lymph node sized within 16 mm in dimeter in the posterior prt of the hed of pncres.

3 SACI Test for Invisile Gstrinom with DU Stenosis gstrin (pg/ml) sec 60sec 90sec GDA IPDA PHA SPA proximl SPA distl Fig. 2. Results of the SACI test. The gstroduodenl rtery, inferior pncreticduodenl rtery (IPDA), proper heptic rtery nd splenic rtery were selected. Injection of clcium into IPDA resulted in shrp rise in this rtery gstrin levels (efore: 1400 pg/ml, fter 60s: 3600 pg/ml). Fig. 3. We performed Sutotl Stomch-Preserving Pncreticoduodenectomy with regionl lymphdenectomy. Histopthologicl findings of the resected specimen. c Fig. 4. Smll duodenl neuroendocrine tumors. () H.E stining. Arrow indictes one of 4 smll sumucosl tumors sized within 3 mm. () Immunohistochemicl stining for CgA. The tumors were positive for CgA. They were duodenl neuroendocrine tumors (DNETs). (c) Immunohistochemicl stining for gstrin. The DNETs were positive for gstrin. They were dignosed s duodenl gstrinoms.

4 16 K. Okd et l c Fig. 5. Smll pncretic neuroendocrine tumors. () H.E stining. Arrow indictes one of 4 smll pncretic tumors sized within 3 mm. () Immunohistochemicl stining for CgA. The tumors were positive for CgA. They were pncretic neuroendocrine tumors (PNETs). (c) Immunohistochemicl stining for gstrin. The PNETs were negtive for gstrin. They were dignosed s nonfunctioning PNETs. Fig. 6. The metsttic lymph node. () Immunohistochemicl stining for CgA. The lymph node ws positive for CgA. It ws metsttic lymph node of NETs. () Immunohistochemicl stining for gstrin. The metsttic lymph node ws positive for gstrin. It ws dignosed s the metsttic lymph node of duodenl gstrinoms. DISCUSSION The SACI test is highly ccurte nd sfe method for the preopertive locliztion nd dignosis of gstrinoms with MEN 1 in the duodenum or/nd pncres nd is especilly helpful in cse of duodenl stenosis. More thn hlf of duodenl gstrinoms with MEN 1 tend to e smller thn 1 cm in dimeter 3,12). Imging studies such s GIS, contrst-enhnced CT, nd MRI re used for preopertive dignosis of microgstrinoms, ut these imging studies my fil to show them. EUS is lso useful method for detecting sumucosl smll tumors s smll s 2-3 mm in dimeter 1) ut, in our cse, severe duodenl stenosis prevented creful exmintion with ny stndrd modlity. The SACI test ws the only vlid method for locliztion nd dignosis of the invisile microgstrino-

5 SACI Test for Invisile Gstrinom with DU Stenosis 17 ms. The tretment strtegy for gstrinoms with MEN 1 hs een controversil. We recommend erly nd ggressive surgicl resection of gstrinoms, ecuse recently pulished rticles suggest tht this improves survivl rtes nd the long term iomedicl cure of gstrinoms s well s decresing the rte of heptic metstses 2,5,7,9). The preopertive dignosis in our cse ws invisile gstrinoms in the peri-mpullry lesion, so we selected totl duodenectomy rther thn prtil duodenectomy. In ddition, ny regionl lymph nodes round the hed of the pncres nd heptic rtery should e dissected, ecuse duodenl gstrinoms reportedly metstsize to regionl lymph nodes independent of size 7,8). In our cse, the preopertive CT showed one highly enhnced lymph node sized within 16 mm in dimeter in the posterior prt of the hed of the pncres. Pncres preserving totl duodenectomy to sve the hed of the pncres offered less invsive surgery compred with SSPPD, ut this procedure did not llow for regionl lymph node dissection nd the resection of microgstrinoms in the hed of the pncres. With totl duodenectomy, regionl lymph node dissection nd the possiility of microgstrinoms in the hed of pncres, we performed SSPPD. As result, pthologicl findings showed tht one highly enhnced metsttic lymph node ws lrger thn the primry duodenl microgstrinoms, so it ws possile for the metsttic lymph node to secrete more gstrin thn the duodenl microgstrinoms nd to e fed from IPDA, identified y the SACI test s the rteril supply of the gstrinom. Proper preopertive dignosis y the SACI test nd erly nd ggressive surgicl resection contriuted to curtive R0 resection nd recurrence-free survivl. CONCLUSION The SACI test cn enhnce the ccurcy of preopertive locliztion nd dignosis of invisile microgstrinoms, especilly in the setting of severe duodenl stenosis. Consent Written informed consent ws otined from the ptient for puliction of this Cse Report nd ny ccompnying imges. Competing interests The uthors declre tht they hve no competing interests. Authors contriution TS conceived of this cse presenttion nd drfted the presenttion. KM, YY, YS, YH, HK, HO nd TS prticipted in the design of this cse presenttion. FS crried out the pthologicl studies. All uthors red nd pproved the finl mnuscript. (Received Jnury 22, 2016) (Accepted Ferury 23, 2016) REFERENCES 1. Anderson, M.A., Crpenter, S., Thompson, N.W., Nostrnt, T.T., Elt, G.H. nd Scheimn, J.M Endoscopic ultrsound is highly ccurte nd directs mngement in ptients with neuroendocrine tumors of the pncres. Am. J. Gstroenterol. 95: Brtsch, D.K., Frendrich, V., Lnger, P., Celik, I., Knn, P.H. nd Rothmund, M Outcome of duodenopncretic resections in ptients with multiple endocrine neoplsi type 1. Ann. Surg. 242: Frendrich, V., Lnger, P., Wldmnn, J., Brtsch, D.K. nd Rothmund, M Mngement of spordic nd multiple endocrine neoplsi type 1 gstrinoms. Br. J. Surg. 94: Fujihr, S., Mori, H., Nishiym, N., Koyshi, M., Kor, H. nd Mski, T Multiple gint duodenl ulcers ssocited with duodenl gstrinom. Clin. J. Gstroenterol. 5: Giril, F., Venzon, D.J., Ojeuru, J.V., Bshir, S. nd Jensen, R.T Prospectivestudy of the nturl history of gstrinom in ptients with MEN 1: definition of n ggressive nd nonggressive form. J. Clin. Endocrinol. Met. 86: Goudet, P., Murt, A., Binquet, C., Crdot- Buters, C., Cost, A., Ruszniewski, P., et l Risk fctors nd cuses of deth in MEN 1 disese. A GTE (Groupe d Etude des Tumeurs Endocrines) cohort study mong 758 ptients. World J. Surg. 34: Immur, M., Komoto, I., Doi, R., Onoder, H., Koyshi, H. nd Kwi, Y New pncrespreserving totl duodenectomy technique. World J. Surg. 29: Immur, M., Komoto, I., Ot, S., Hirtsuk, T., Kosugi, S., Doi, R., et l Biochemiclly curtive surgery for gstrinom in multiple endocrine neoplsi type 1 ptient. World J. Gstroenterol. 17: Norton, J.A., Frker, D.L., Alexnder, H.R., Giril, F., Liewehr, D.J., Venzon, D.J., et l Surgery increses survivl in ptients with gstrinom. Ann. Surg. 244: Skuri, A., Suzuki, S., Kosugi, S., Okmoto, T., Uchino, S., Miy, A., et l Multiple endocrine neoplsi type 1 in Jpn: Estlishment nd nlysis of multicenter dtse. Clin. Endoclinol. (Oxf) 76: Thkker, R.V., Newey, P.J., Wlls, G.V., Bilezikin, J., Drlle, H., Eeling, H., et l Clinicl prctice guidelines for multiple endocrine neoplsi type 1 (MEN1). J. Clin. Endocrinol. Met. 97: Thompson, C. nd Courtney, M Townsend: endocrine pncres, p Siston textook of surgery. 18 th ed. Sunders Elsevier, Phildelphi.

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