Person: Yoon, Sam
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Yoon
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Sam
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Yoon, Sam
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Publication D2 Lymphadenectomy with Surgical Ex Vivo Dissection into Node Stations for Gastric Adenocarcinoma Can Be Performed Safely in Western Patients and Ensures Optimal Staging(Springer Nature, 2013) Schmidt, Benjamin; Chang, Kevin; Maduekwe, Ugwuji N.; Look-Hong, Nicole; Rattner, David; Lauwers, Gregory Y.; Mullen, John; Yang, Han-Kwang; Yoon, SamBACKGROUND: The AJCC recommends examination of >16 nodes to stage gastric adenocarcinoma. D2 lymphadenectomy (LAD) followed by surgical ex vivo dissection (SEVD) into nodal stations is standard at many high-volume Asian centers, but potential increases in morbidity and mortality have slowed adoption of D2 LAD in some Western centers. METHODS: A total of 331 patients with gastric adenocarcinoma who underwent surgical resection at one Western institution from 1995 to 2010 were examined. RESULTS: Median age of patients was 69 years old, 65% were male, and 84% were white. D1 LAD was performed in 285 patients (86%) and D2 LAD in 46 patients (14%), with SEVD being performed in 17 patients (37%) in the D2 group. D2 LAD with or without SEVD was performed much more commonly between 2006 and 2010. For the D1, D2 without SEVD, and D2 with SEVD groups, the median number of examined nodes and percentage with >16 examined nodes were 16 and 51%, 27 and 93%, and 40 and 100%, respectively. Major complications occurred in 16% of the D1 group and 17% of the D2 group (p>0.05), and 30-day mortality was 3% for the D1 group and 0% for the D2 group. D2 LAD was a positive prognostic factor for overall survival on univariate (p=0.027) and multivariate analyses (p=0.005), but there were several possible confounding variables. CONCLUSIONS: D2 LAD at our Western institution was performed with low morbidity and no mortality. Optimal staging occurred after D2 LAD combined with SEVD, where a median of 40 nodes were examined and all patients had >16 examined nodes.Publication Prophylactic total gastrectomy for individuals with germline CDH1 mutation(Elsevier BV, 2011) Pandalai, Prakash K.; Lauwers, Gregory Y.; Chung, Daniel; Patel, Devanshi; Yoon, SamBACKGROUND: Germline mutation of the CDH1 gene, which encodes for the E-cadherin adhesion protein, is rare but confers an estimated lifetime risk of hereditary diffuse gastric cancer of 87%. Fewer than 100 prophylactic total gastrectomies have been reported for this condition. METHODS: Patients with germline CDH1 mutation who underwent multidisciplinary counseling followed by prophylactic total gastrectomy were reviewed. RESULTS: Ten patients (6 male, 4 female) with a median age of 42 years (range, 26-51) underwent prophylactic total gastrectomy between 2006 and 2009. Of the 6 families represented, there were 4 missense, 1 frameshift, and 1 splice site mutation. Median time from genetic testing to surgery was 3 months (range, 1-7). All patients had an upper endoscopy before surgery, identifying only 1 patient with a focus of diffuse gastric cancer. After prophylactic total gastrectomy, extensive pathologic analysis demonstrated that 9 patients had up to 77 foci of noninvasive cancer, and 2 of these patients had 4-12 foci of T1 invasive cancer. Median operative time was 213 minutes; there were no anastomotic leaks, and the length of stay was 7-8 days. One patient had a complication within 30 days (pulmonary embolism), and 3 patients had late complications (2 small bowel obstructions and 1 anastomotic stricture). Median weight loss at 6 months was 19%. CONCLUSION: The majority of patients with germline CDH1 mutation have foci of noninvasive or invasive gastric cancer by middle age. Serial upper endoscopies provide inadequate screening. Prophylactic total gastrectomy is the procedure of choice for definitive treatment.Publication Endoscopic Surveillance of Patients With Hereditary Diffuse Gastric Cancer: Biopsy Recommendations After Topographic Distribution of Cancer Foci in a Series of 10 CDH1-mutated Gastrectomies(Ovid Technologies (Wolters Kluwer Health), 2012) Fujita, Hiroshi; Lennerz, Jochen K.M.; Chung, Daniel; Patel, Devanshi; Deshpande, Vikram; Yoon, Sam; Lauwers, Gregory Y.The management of hereditary diffuse-type gastric cancer revolves around surveillance biopsies and the timing of prophylactic gastrectomy. In the absence of a validated surveillance biopsy protocol, we modeled bioptic diagnostic yield on the basis of the topographic distribution of cancer foci in a series of 10 gastrectomies in CDH1-mutation carriers. Complete histologic examination was performed in all cases, and 1817 slides were evaluated for the presence of in situ, intramucosal, or submucosal diffuse-type carcinoma. Detailed maps determined the density of cancer foci. On the basis of the number of sampled glands per biopsy in routine surveillance preoperative endoscopy, we estimated the theoretical number of biopsies necessary for a 90% rate of detection of neoplastic foci, and we evaluated this number, taking into account the regional distribution of these foci. A total of 96 m of gastric mucosa with ∼1,193,453 gastric glands yielded 302 cancer foci [in situ (n=89), intramucosal (n=209), and submucosal (n=4)] spanning the width of a total of 1820 glands (8 to 1205 per case; average 182±115). On the basis of the number of glands per stomach and the average number of glands sampled during surveillance biopsy (28.7±1.7; range, 0 to 79; n=112), the theoretical number of biopsies necessary to capture at least 1 cancer focus was estimated to be 1768 (range, 50 to 5832) to assure a 90% detection rate. Mapping of cancer foci showed the highest density in the anterior proximal fundus (37%) and cardia/proximal fundus (27%). Our results argue for the incorporation of cancer focus distribution into any biopsy protocol, although detection is likely to remain extremely low, and they call into question the validity of endoscopic surveillance.Publication New Metastatic Lymph Node Ratio System Reduces Stage Migration in Patients Undergoing D1 Lymphadenectomy for Gastric Adenocarcinoma(Springer Science + Business Media, 2010) Maduekwe, Ugwuji N.; Lauwers, Gregory Y.; Fernandez-del-Castillo, Carlos; Berger, David; Ferguson, Charles M.; Rattner, David; Yoon, SamBackground: The American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) staging system for gastric cancer incorporates the absolute number of metastatic lymph nodes (N status) and is optimally used when ≥15 nodes are examined. The ratio of metastatic to examined nodes (N ratio) is an effective prognostic tool, but has not been examined in Western patients undergoing primarily D1 lymphadenectomy. Methods: Two hundred and fifty seven patients with gastric adenocarcinoma who underwent gastric resection between 1995 and 2005 at our institution were examined. Novel N ratio intervals were determined using the best cutoff approach (Nr0: N ratio = 0 and ≥15 nodes examined; Nr1: 0 ≤ N ratio ≤ 0.3; Nr2: 0.3 < N ratio ≤ 0.7; and Nr3: N ratio > 0.7). Overall survival was examined according to N status and N ratio. Results: 83% of patients underwent D1 lymphadenectomy with a median of 14 lymph nodes examined. Overall survival stratified by N status was significantly different in patients with <15 nodes examined compared with those with ≥15 nodes examined. When we stratified by N ratio intervals, there was no significant difference in overall survival in patients with <15 versus ≥ 15 nodes examined. On multivariate analysis, N ratio but not N status was retained as an independent prognostic factor. Conclusions: The use of N status for staging patients undergoing primarily D1 lymphadenectomy results in significant stage migration due to varying numbers of nodes examined. Use of N ratio reduces stage migration and may be a more reliable method of staging these patients.Publication Noncurative Gastrectomy for Gastric Adenocarcinoma Should only be Performed in Highly Selected Patients(Springer Nature, 2013) Schmidt, Benjamin; Look-Hong, Nicole; Maduekwe, Ugwuji N.; Chang, Kevin; Hong, Theodore; Kwak, Eunice Lee; Lauwers, Gregory Y.; Rattner, David; Mullen, John; Yoon, SamBackground: The benefit of surgical resection in patients with incurable gastric adenocarcinoma is controversial. Methods: A total of 289 patients who presented with advanced or metastatic gastric cancer from 1995 to 2010 were retrospectively reviewed. Results: Ten patients (3.5 %) required emergent surgery at presentation and were excluded from further analyses. Patients who underwent nonemergent surgery at presentation (n = 110, 38.1 %) received either gastric resection (group A, n = 46, 42 %) or surgery without resection (group B, n = 64, 58 %). Procedures in group A included distal gastrectomy (n = 25, 54 %), total gastrectomy (n = 17, 37 %), and proximal/esophagogastrectomy (n = 4, 9 %). Procedures in group B included laparoscopy (n = 17, 27 %), open exploration (n = 25, 39 %), gastrostomy and/or jejunostomy tube (n = 12, 19 %), and gastrojejunostomy (n = 10, 16 %). Group A required a stay in the intensive care unit or additional invasive procedure significantly more often than group B (15 vs. 2 %, p = 0.009). Four patients in group A (8.7 %) and three patients in group B (4.7 %) died within 30 days of surgery (p = 0.45). When the 110 patients who underwent nonemergent surgery (groups A and B) were compared to nonoperatively managed patients (group C, n = 169, 58 %), median overall survival did not significantly differ (8.6 vs. 9.2 vs. 7.7 months; p > 0.05). Three patients in group B (4.7 %) and three in group C (1.8 %) ultimately required an operation for their primary tumor. Conclusions: Patients with gastric adenocarcinoma who present with advanced or metastatic disease not amenable to curative resection infrequently require emergent surgery. Noncurative resection is associated with significant perioperative morbidity and mortality as well as limited overall survival, and should therefore be performed judiciously.Publication Comparison of a Lymph Node Ratio–Based Staging System With the 7th AJCC System for Gastric Cancer(Ovid Technologies (Wolters Kluwer Health), 2012) Wang, Jiping; Dang, Ping; Raut, Chandrajit; Pandalai, Prakash K.; Maduekwe, Ugwuji N.; Rattner, David; Lauwers, Gregory Y.; Yoon, SamOBJECTIVES: The American Joint Committee on Cancer (AJCC) staging system for gastric cancer bases N status on absolute number of metastatic nodes, regardless of the number of examined nodes. We examined a modified staging system utilizing node ratio (Nr), the ratio of metastatic to examined nodes. METHODS: A total of 18,043 gastric cancer patients who underwent gastrectomy were identified from the US Surveillance, Epidemiology, and End Results (SEER) database. A training set was divided into 5 Nr groups, and a TNrM staging system was constructed. Median survival and overall survival, based on 7th edition AJCC and TNrM staging systems, were compared, and the analysis was repeated in a validation set. RESULTS: Median examined nodes were 10 to 11. For the training set, overall survival for all 5 AJCC N categories was significantly different when subgrouped into 15 or fewer versus more than 15 examined nodes, but overall survival was similar regardless of the number of examined nodes in 4 of 5 Nr categories. Seven AJCC stages had statistically different overall survival between subgroups, whereas only 1 TNrM stage had statistically different overall survival between subgroups. When misclassification was defined as any subgroup in which median survival fell outside the 95% confidence interval of the group's overall median survival, AJCC staging misclassified 57% of patients and TNrM staging misclassified only 12%. Similar results were found in the validation set. CONCLUSIONS: The AJCC system classifies SEER gastric cancer patients into stages in which subgroups often have wide variations in survival. For patients undergoing limited lymph node analysis, the proposed TNrM system may predict survival more accurately.Publication Cross Species Genomic Analysis Identifies a Mouse Model as Undifferentiated Pleomorphic Sarcoma/Malignant Fibrous Histiocytoma(Public Library of Science, 2009) Mito, Jeffrey K.; Riedel, Richard F.; Dodd, Leslie; Lahat, Guy; Lazar, Alexander J.; Dodd, Rebecca D.; Stangenberg, Lars; Eward, William C.; Brigman, Brian E.; Jacks, Tyler; Lev, Dina; Mukherjee, Sayan; Kirsch, David G.; Aziz, Syed A.; Hornicek, Francis; Yoon, SamUndifferentiated pleomorphic sarcoma/Malignant Fibrous Histiocytoma (MFH) is one of the most common subtypes of human soft tissue sarcoma. Using cross species genomic analysis, we define a geneset from the \(LSL\)-\(Kras^{G12D}\); \(Trp53^{Flox/Flox}\) mouse model of soft tissue sarcoma that is highly enriched in human MFH. With this mouse geneset as a filter, we identify expression of the RAS target FOXM1 in human MFH. Expression of \(Foxm1\) is elevated in mouse sarcomas that metastasize to the lung and tissue microarray analysis of human MFH correlates overexpression of FOXM1 with metastasis. These results suggest that genomic alterations present in human MFH are conserved in the \(LSL\)-\(Kras^{G12D}\); \(p53^{Flox/Flox}\) mouse model of soft tissue sarcoma and demonstrate the utility of this pre-clinical model.