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Tu1087

The Yield of Endoscopic Surveillance Following Excision of Rectal CarcinoidsFerga C. Gleeson, Michael J. Levy, Eric J. Dozois, David W. Larson, Louis M. Wong KeeSong, Lisa Boardman

Background: Endoscopic ultrasound (EUS) is often performed to evaluate patients withrectal carcinoid tumor to evaluate tumor size, depth of invasion and lymph node status. Arecently proposed surveillance protocol calls for an EUS examination at 3 months followinglocal therapy and then every 6 months for 3 years. The need and utility for surveillanceprograms in this setting have not been validated. Aims: In patients who have undergoneresection of a rectal carcinoid to determine the potential utility of endoscopic surveillancefor identifying disease recurrence. Method: A histopathology database was reviewed toidentify patients with an endoscopic diagnosis of a well-differentiated rectal carcinoid tumorfrom 1/1/00-1/9/12. Clinical, radiologic, endoscopic, EUS, and follow-up outcome datawere analyzed. Results: Among 87 patients who met inclusion criteria, local excision wasperformed in 75 (86%) to include: hot snare polypectomy n=56, transanal excision (TAE)n=13, endoscopic mucosal resection (EMR) n=5 and endoscopic submucosal dissection(ESD) n=1. Of 70 patients with local disease management, 55 (79%) underwent postintervention surveillance, 20 (36%) of whom included EUS [1 (IQR 1-2.5)]. Colonoscopyalone was performed in n=23, colonoscopy and non-invasive imaging n=7, non-invasiveimaging alone n= 5, colonoscopy and EUS n=4, colonoscopy and EUS and non-invasiveimaging n=1. Fifteen (21%) patients had no specific rectal carcinoid surveillance on site buthad ongoing on site separate clinical evaluations. Disease progression was identified in 6(8.6%) patients at 1.4 (IQR 0.38-2.7) years from initial diagnosis. All 6 cases reflected distantmetastatic locations (n=4 liver, n=1 pancreas, n=1 lung and liver) rather than that of localrecurrence or a combination of local and distant disease. All were identified by non-invasiveimaging at 35 (IQR 4.7-33) months following initial therapy. At no point during their coursewas local recurrence identified. Disease specific mortality (n=3) occurred at 13 (IQR 9-69)months following initial therapy. Conclusions: Our data suggest the lack of local recurrenceof rectal carcinoid following local disease management. These data call into question theutility of any endoscopic surveillance program. Additional study is needed to more firmlyestablish the natural course of disease in such patients to help devise a more accurate andtailored approach to disease surveillance.

Tu1088

Prediction of Tumor Recurrence in Patients With Gastrointestinal StromalTumors Following Resection by the Modified NIH CriteriaJi Eun Kwon, Sang Gyun Kim, Joo Hyun Lim, Jaeyoung Chun, Jeongmin Choi, Jong PilIm, Joo Sung Kim, Hyun Chae Jung

Background/Purpose : Risk of recurrence of gastrointestinal stromal tumors (GISTs) hasbeen assessed using the National Institutes of Health (NIH) consensus criteria. The modifiedNIH criteria is currently widely accepted; it includes both tumor site and tumor rupture asadditional prognostic factors. However, a majority of the studies regarding this modificationhave been conducted in Western nations. The aims of this study were to clarify the clinicalusefulness of the modified NIH criteria for risk stratification in Korea and to determine theassociation of the prognostic factors for GIST recurrence. Methods : From January 2000through September 2012, 261 patients who underwent curative resection for primary GISTwere included in this study. Those who received adjuvant chemotherapy after surgery wereexcluded. The enrolled patients were divided into two groups according to primary tumorsite; each group was stratified to predict recurrence by the original NIH criteria and modifiedNIH criteria. Clinical and pathologic data were collected and analyzed retrospectively. Results: A total of 172 patients had gastric GISTs; 89 patients had non-gastric GISTs. The meanage was 58.9 years (range: 22-89 years). The median follow-up duration was 4.26 years(range: 0.04-12.75 years). In the gastric GIST group, both risk stratification systems yieldedthe identical classification. Only 1 patient (1.9%) in the intermediate category and 8 patients(19%) in the high risk category experienced tumor recurrence. In the non-gastric GISTgroup, all patients who were placed in the intermediate risk category by the original NIHcriteria were reclassified into the high risk category according to the modified NIH criteria.Among the 22 reclassified patients, 6 patients suffered a recurrence during the observationalperiod. Under the modified NIH criteria, 4 patients (8.8%) in the low risk category and 14patients (35.9%) in the high risk category experienced tumor recurrence. The five-yearrecurrence free survival of gastric GIST group and non-gastric GIST group were 93.3% and

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73.2%, respectively. The primary tumor site, tumor size, mitotic count, presence of micro-scopic tumor necrosis and presence of tumor hemorrhage were significantly associated withthe risk of tumor recurrence with univariate analysis. With multivariate analysis, the primarytumor site, tumor size, mitotic count, and presence of tumor hemorrhage were statisticallysignificant variables. Conclusions : The high risk category by the modified NIH criteria wasfound to have a high recurrence rate of GIST; furthermore, the non-gastric GIST group hada worse prognosis than gastric GIST group. Therefore, the modified NIH criteria accuratelypredicted the recurrence of GISTs after curative resection. In addition, the presence ofbleeding might be considered to be an additional prognostic factor for GIST.Association of clinicopathologic factors with tumor recurrence

* : Log-rank test † : Cox regression hazard model ‡ : Available cases only

Recurrence free survival of non-gastric GIST group (a) by the NIH criteria and (b) by themodified NIH criteria

Tu1089

Somatostatin and the Slow-Growing Nature of Small IntestinalNeuroendocrine TumorsRosalie T. Zwiggelaar, Reidar Fossmark, Mark Kidd, Marianne W. Furnes, Arne K.Sandvik, Helge Waldum, Bjorn I. Gustafsson

Background: Small intestinal neuroendocrine tumors (SI-NETs) are usually slow-growingwell-differentiated tumors. The reason for this indolent behavior is not understood. Somato-statin (SST) analogues inhibit tumor growth. We aimed to investigate whether SST producingcells are present in SI-NETs. Our hypothesis was that locally produced SSTmay be responsiblefor the indolent behavior of SI-NETs by direct inhibition of tumor proliferation. Materialand Methods: 13 paraffin embedded primary, and 31 fresh frozen SI-NETs (15 primary and16 liver metastases) were used. Quantification and localization of SST were determinedusing in situ hybridization (ISH), immunohistochemistry (IHC), RT-PCR and Western Blot(WB) analyses. Results: IHC demonstrated SST expression in 12/13 (92.3 %) while ISH wasonly positive in 7/13 (53.8 %). Tumors from SSA treated patients showed less SST positivity(IHC: 7/8 (87.5 %), ISH: 3/8 (37.5 %) compared to untreated (IHC: 5/5 (100 %), ISH: 4/5 (80 %)) (Table 1). RT-PCR and WB demonstrated significantly (.30 times, p=0.05) higherSST expression in SI-NETs with Ki-67 ,1 % compared to those with Ki-67.1 % (Fig A).Additionally, SST expression was significantly (5 times, p ,0.05) higher in primaries thanin liver metastases (Fig B). Conclusion: SST is highly expressed in SI-NETs while SSAtreatment seems to decrease endogenous SST production. SST expression is higher in slowlyproliferating tumors and primaries compared to lesions with higher proliferative activity

and metastases. These findings indicate that naturally occurring SST may at least be partlyresponsible for the generally slow growth rate of SI-NETs.Protein expression (IHC) vs. mRNA expression (ISH)

A. SI-NETs: Ki-67 index ,1% vs. .1%. B. Primary SI-NETs vs. Liver Mets

Tu1090

19-Year Single Center Experience in the Management of Patients With PrimaryGastrointestinal (GI) LymphomaWolfgang Fischbach, Nicole Müller

Introduction: Primary GI lymphoma are a rare disease. Multicenter studies were, therefore,initiated in the 90ies with various published results in subgroups of GI lymphoma. We herereport our long-term findings in patients with any primary GI lymphoma who were nottreated within a controlled clinical trial. Method: As a German reference center patients withGI lymphoma are regulary presented to our institution. From 1993 on, we saw 102 consecu-tive patients (59 male and 43 female, age 31-89 years) with primary GI lymphoma: gastricMALT lymphoma = 76 (63 stage I, 6 stage II, 7 stage III/IV); secondary high grade MALTlymphoma = 3; diffuse large B-cell lymphoma (DLBCL) = 14 (Stage I/II/III-IV = 8/4/2);Burkitt lymphoma = 1; intestinal follicular lymphoma (FL) grade I/II = 8 (stage I/II/III-IV =5/1/2). Treatment strategies were as follows:MALT-lymphoma: H. pylori eradication, radiation(RTx) and/or chemotherapy (CTx) in stages . II or in case of eradication failure; DLBCL:CTx except in 3 cases treated by H. pylori eradication only; FL: no therapy, CTx or RTx.Results: 26/47 patients (55%) with MALT lymphoma achieved complete remission (CR)after exclusive H. pylori eradication. Application of all therapeutic procedures resulted inCR = 53/76 (70%) and PR with watch-and-wait = 22/76 (29%). There was only 1 patientrevealing progression. In DLBCL, 12 (86%) achieved CR after 1-3 line therapies. In FL,watch-and-wait resulted in long-term stable disease in n=5, CR after RTx in 1 case, andstable disease after CTx in 2 cases. Conclusion: Despite a negative selection of patients beingpresented to our reference center the overall treatment results in all subgroups of GI lym-phoma are excellent when all treatment options are offered in a sequential therapy strategy.Watch-and-wait is a promising approach in MALT lymphoma with residual disease followingH. pylori eradication and in FL.

Tu1091

Gastrointestinal Stromal Tumors Show Strong Association With Synchronousor Metachronous Other MalignanciesRicha Jain, Ihab Lamzabi, Paolo Gattuso, Shriram Jakate

Background: Gastrointestinal stromal tumor (GIST) is the most common malignant mesen-chymal tumor of the GI tract. GISTs most commonly develop from mutations in KIT (80-85%), less often in PDGFRA (5-10%) and rarely from other sites. While germline mutationsoccur rarely, the overwhelming majority of these mutations are somatic, in which settingmulti-organ cancers are less likely to occur. We reviewed GIST cases from last 19 years toevaluate association of GIST with other malignancies. Design: From our Medical Center'spathology and clinical databases we retrieved 103 cases of C-kit positive GISTs from 1993-2011 (Female:54, Male:49; mean age 63). We investigated if these patients had othermalignancies that occurred synchronously or metachronously. We also assessed the distribu-tion of second malignancies and their relationships if any with the location, size and highmitoses (.10/50 hpf) of GIST. Results: 62/103 (60%) of GISTs were located in the stomach(mean size 2.9 cm) followed by small bowel (27/103 or 26%, mean size 6.3 cm). Only 9/103 cases had highmitoses. 42/103 (40%) cases had other malignancies, the majority of which(27/42 or 64%) were gastrointestinal carcinomas and occurred synchronously (colorectal6/27, gastric 5/27, distal esophageal 4/27). In 15/42 cases, other malignancies occurredmetachronously, most of which (12/15) preceded GIST by mean of 1.2 years and the

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majority were breast carcinomas (6/15). GISTs associated with other malignancies showedno differences in location, size and mitoses compared with GISTs without other malignancies.Conclusions: GISTs show high incidence (40%) of other malignancies despite known pre-dominant somatic and not germline mutations. The majority of other malignancies occursynchronously and are gastrointestinal carcinomas. Metachronously occurring GISTs aremost often preceded by breast carcinomas, often within 2 years. The rate of second malignan-cies appears to be sufficiently high to consider surveillance studies (colonoscopy and esopha-gogastroduodenoscopy, mammography) and genetic studies for additional undiscoveredmutations.

Tu1092

Nonsurgical Treatment for Intestinal Follicular Lymphoma: A RetrospectiveAnalysis of 43 PatientsShotaro Nakamura, Takayuki Matsumoto, Koji Ikegami, Ema Washio, Motohiro Esaki,Keisuke Kawasaki, Koichi Kurahara, Minako Hirahashi, Takanari Kitazono, MakotoHashizume

Background: Double-balloon endoscopy (DBE) and capsule endoscopy (CE) have increasedthe detection of the jejunoileal lesions of intestinal follicular lymphoma (FL). However,optimal therapeutic strategy for this disease has not been established. Methods: The clinico-pathologic features and efficacy of nonsurgical treatments of intestinal FL were retrospectivelyanalyzed in 43 Japanese patients (21 men and 22 women; median age, 60 years). In allpatients, DBE and/or CE were performed. The presence of t(14;18)/ IgH-BCL2 was determinedby fluorescence in situ hybridization. Results: The site of the involvement was the duodenum(84%), the jejunum (74%), the ileum (51%), and the colorectum (19%). Involvement ofmultiple segments of the gastrointestinal (GI) tract was found in 81%. Macroscopically, 91%of cases showed polyposis type. The histologic grade 1-2 was seen in 93% of cases, whilet(14;18) was detected in 95%. Clinical stage by Lugano classification was as follows; stageI in 25 patients, stage II1 in 2, stage II2 in 4, stage IIE in 2 and stage IV in 10. Initialtreatment modalities included watch and wait/antibiotics (n=13), rituximab monotherapy(R alone group; n=18), and rituximab plus chemotherapy (R-CHOP group; n=12). Completeremission (CR) of FL was achieved in 27 patients (63%) and partial remission in 7 (16%),while 9 patients (21%) showed no change. During the follow-up periods ranging from 0.5to 8.0 years (median 3.3 years), one patient died of causes unrelated to FL, while 11 (26%)showed relapse or progression of FL. The progression-free survival (PFS) rate after 3 and5 years was 81% and 59%, respectively. Patients with involvement of multiple GI segmentstended to have worse PFS than those of single segments ( P=0.054). Patients with stage II-IV were less frequent in R alone group (28%) than in R-CHOP group (92%). After thetherapy, CR was achieved in 78% in R alone group, while in 100% in R-CHOP group ( P=0.13). The relapse/progression equally occurred (both 33%), and the PFS rate after 3-yearsdid not differ between R alone (65%) and R-CHOP groups (82%, P=0.75). Conclusions:Intestinal FL frequently involves the duodenum and the jejunum. Therefore, assessment ofsmall bowel using DBE and/or CE is mandatory. Both rituximab monotherapy and R-CHOPtherapy are effective. Careful follow-up is required especially for patients who have FL inthe multiple GI portions.

Tu1093

EUS Guided Keyhole Biopsy: Simple and Successful Histologic Diagnosis ofSubmucosal GI TumorsPeter Grubel

BACKGROUND: EUS guided FNA is often hampered by the lack of sufficient tissue to allowhistology and immunohistochemistry and Tru-Cut biopsy is technically difficult when theendoscope is angulated. EUS guided keyhole biopsy technique (EUS-KB) is a novel techniqueto sample submucosal tumors (SMT). METHODS: Patients with SMT were prospectivelyexamined over a 2-year period. Following EUS evaluation, a needle knife was used to cuta small mucosal keyhole over the center of the lesion (A). A biopsy forceps was thenintroduced through the hole into the center of the lesion and samples were obtained andplaced in formalin (B). RESULTS: 23 patients (mean age 69 years) with SMT underwentEUS-KB. The anatomic sites of the lesions were as follows: Esophagus in 1, stomach in 16,duodenum in 5, and rectum in 1 patient. The mean procedural time was 21 minutes.There was one bleeding complication (4%) controlled with epinephrine injection. Adequatespecimens for histology, mitotic rate and immunohistochemistry were obtained in all patientsallowing a diagnosis in all patients. The tissue specimens measured 2-15 mm and showedno cautery artifacts. Pathology showed 14 benign lesion and 9 neoplastic lesions (8 GIST,1 gastrinoma). Surgical resection was performed in three patients and confirmed the EUS-KB diagnosis of GIST and gastrinoma. CONCLUSIONS: EUS-KB is an easy, quick and safetechnique. It provides abundant histological tissue to accurately diagnose SMT.

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