Faculty Bibliography

BACKGROUND & AIMS/OBJECTIVE:In the West, early gastric cancer is increasingly managed with endoscopic resection (ER). This is, however, based on the assumption that the low prevalence and risk of lymph node metastases observed in Asian patients is applicable to patients in the United States. We sought to evaluate the frequency of and factors associated with metastasis of early gastric cancers to lymph nodes, and whether the Japanese ER criteria are applicable to patients in the US. METHODS:We performed a retrospective study of 176 patients (mean age 68.5 years; 59.1% male; 58.5% Caucasian) who underwent surgical resection with lymph node dissection of T1 and Tis gastric adenocarcinomas, staged by pathologists, at 7 tertiary care centers in the US from January 1, 1999 through December 31, 2016. The frequency of lymph node metastases and associated risk factors were determined. RESULTS:The mean size of gastric adenocarcinomas was 23.0±16.6 mm-most were located in the lower-third of the stomach (67.0%), invading the submucosa (55.1%), and moderately differentiated (31.3%). Lymphovascular invasion was observed in 18.2% of lesions. Overall, 20.5% of patients had lymph node metastases. Submucosal invasion (odds ratio, 3.9; 95% CI 1.4-10.7) and lymphovascular invasion (odds ratio, 4.6; 95% CI, 1.8-12.0) were independently associated with increased risk of metastasis to lymph nodes. The frequency of lymph node metastases among patients fulfilling standard and expanded Japanese criteria for ER were 0 and 7.5%, respectively. CONCLUSION/CONCLUSIONS:The frequency of lymph node metastases among patients with early gastric cancer in a US population is higher than that of published Asian series. However, early gastric cancer lesions that meet the Japanese standard criteria for ER are associated with negligible risk of metastasis to lymph nodes, so ER can be recommended for definitive therapy. Expanded criteria cancers appear to have a higher risk of metastasis to lymph nodes, so ER may be considered for select cases.

Introduction: Many patients who undergo Roux-en-Y gastric bypass (RYGB)surgery experience weight regain after initial weight loss, particularly patients who develop dilation of the gastrojejunal (GJ)anastomosis. Transoral outlet reduction (TORe)is a minimally invasive endoscopic procedure which has demonstrated efficacy in inducing weight loss in patients who have experienced weight regain after RYGB. Prior literature has described total weight loss of 8.4-8.6kg or 25% excess weight loss. However, there is limited published information on patient reported experiences with the TORe procedure. We aimed to evaluate clinical and patient-reported experience outcomes in patients who have undergone TORe.
Result(s): A total of 18 patients who underwent TORe procedure within the last 1.5 years at a large, urban medical center were requested to participate in a survey-based study. A total of 7 subjects agreed to participate. All were older than age 18, had undergone RYGB, and had a mean GJ diameter prior to TORe of 27mm. All patients underwent TORe with reduction of the GJ to a diameter of 8mm sized by a CRE balloon, and 5 out of 7 received supporting sutures to reduce the gastric pouch. The average weight loss was 6.8kg, with average excess weight loss of 7.5% with median follow-up of 4 months after TORe. Metabolic parameters including hemoglobin A1c and lipid panels were evaluated pre- and post-TORe, and all were reduced, however the differences were not statistically significant (table 1). Survey results indicated that 4 out of 7 subjects were satisfied with their weight loss after TORe, and were notable for a higher perceived than actual weight loss after TORe (self-reported average 8.6kg or 9.6% excess weight loss). Only 1 patient reported significant adverse event following TORe, with epigastric pain requiring hospitalization for two days for pain control. Subjects, on average, reported high quality of life following TORe with use of Moorehead-Ardelt Quality of Life Questionnaire. 6 of 7 subjects stated they were willing to undergo repeat TORe for further weight loss.
Conclusion(s): Our study demonstrates that patients who have undergone TORe tolerated the procedure well and experienced excess weight loss. Most patients reported satisfaction with their weight loss following TORe, and we found that patients reported a higher perceived weight loss than objectively measured. Clinically our cohort demonstrated a reduction in metabolic parameters, but this was not statistically significant, likely given small sample size. Most patients reported high quality of life scores following TORe and were willing to undergo repeat TORe based on their experiences. These findings support the use of TORe given general positive patient-reported outcomes, however further evaluation is needed to predict which patients are most likely to clinically benefit from this procedure. [Figure presented]
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Background: Prior data from Asian countries showed comparable outcomes of endoscopic submucosal dissection (ESD)vs surgery in patients with early gastric cancer (EGC)meeting standard and expanded criteria. Data from comparative studies using strict criteria in North American population are lacking.
Method(s): We conducted a multicenter retrospective study from 16 North American centers. All patient underwent ESD and/or gastrectomy for EGC between 12/2004 and 2/2018, with follow-up until 10/2018. Patients who did not meet either standard or expanded criteria, those with evidence of lymph node or distant metastasis at time of diagnosis, those without curative resection, and those with follow-up time of less than 6 months were excluded. Primary outcomes were overall survival (OS), cancer-specific survival (CSS)and recurrence-free survival (RFS). Kaplan-Meier using log-rank analysis was used to compare outcomes between ESD and surgery groups. Factors associated with outcomes were analyzed using Cox hazards regression and linear regression analyses.
Result(s): There were 393 patients with EGC who underwent ESD or gastrectomy from 14 US and 2 Canadian centers. Of these, 318 patients were excluded due to unfulfilled standard or expanded criteria (n=254), evidence of lymph node metastasis (n=1), no data on lymphovascular invasion (n=1), non-R0 resection (n=17)and follow-up time of less than 6 months (n=45). A total of 75 patients were analyzed (38 treated with ESD and 37 treated with surgery). Patients treated with surgery had a higher proportion of pedunculated lesions (P=0.02), undifferentiated tumors (P =0.01), EGCs fulfilling expanded criteria (P <0.0001)and longer follow-up time (P=0.0004)(Table 1). OS (P= 1.00), CSS (P=1.00)and RFS (P=1.00)were not statistically different between ESD vs surgery groups. There was no subsequent nodal or distant metastasis in either group. A single patient in the surgery group died of an etiology not related to gastric cancer at 7.9 years after gastrectomy. There were no deaths in the ESD group. One patient with moderately differentiated adenocarcinoma in the gastric antrum, treated with curative ESD, developed a gastric cardiac neuroendocrine tumor at 7.2 years (Table 2). The metachronous lesion was treated with a repeat curative endoscopic resection. There was no demographic, procedural or histological factor associated with OS, CSS or RFS.
Conclusion(s): The standard and expanded criteria for gastric ESD are clinically applicable to a North American population. ESD provides comparable oncologic outcomes and is thus an alternative treatment option to surgery. Recurrence after ESD is uncommon, and can be managed successfully using follow-up and repeat endoscopic treatment. [Figure presented][Figure presented]
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BACKGROUND:Pathogenic germline mutations in the CDKN2A tumor suppressor gene are rare and associated with highly-penetrant familial melanoma and pancreatic cancer (PC) in non-Hispanic Whites (NHWs). To date, the prevalence and impact of CDKN2A rare coding variants (RCV) in racial minority groups remain poorly characterized. We examined the role of CDKN2A RCVs on risk of PC among minority subjects. METHODS:We sequenced CDKN2A in 220 African American (AA) PC cases, 900 non-cancer AA controls, and 183 Nigerian controls. RCV frequencies were determined for each group and compared with that of 1,537 NHW PC patients. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for both a case-case comparison of RCV frequencies in AAs versus NHWs, and case-control comparison between AA cases versus non-cancer AA controls plus Nigerian controls. Smaller sets of Hispanic and Native American cases and controls also were sequenced. RESULTS:One novel missense RCV and one novel frameshift RCV were found among AA patients: 400G>A and 258_278del. RCV carrier status was associated with increased risk of PC among AA cases (11/220; OR=3.3, 95%CI: 1.5-7.1;p=0.004) compared with AA and Nigerian controls (17/1083). Further, AA cases had higher frequency of RCVs, 5.0% (OR=13.4, 95%CI 4.9-36.7;p<0.001) compared to NHW cases(0.4%). CONCLUSIONS:CDKN2A RCVs are more common in AA than in NHW PC patients, and associated with moderately increased PC risk among AAs. IMPACT/CONCLUSIONS:RCVs in CDKN2A are frequent in AAs and are associated with risk for PC.

BACKGROUND: Per-oral endoscopic myotomy (POEM) has emerged as an endoscopic treatment of achalasia. There are no pre-procedural imaging modalities to predict the safest and the most efficacious approach. AIM: To evaluate the use of optimal coherence tomography (OCT) in providing a pre-procedural esophageal assessment. METHODS: Patients undergoing POEM from July 2013 to November 2015 were captured in a multicenter, international registry. Patients who underwent OCT pre-POEM ("OCT arm") were compared to patients without pre-POEM OCT ("control arm"). OCT images were assessed for the degree of vascularity and the thickness of the circular muscular layer, and an approach was determined. RESULTS: A total of 84 patients were captured in the registry. Fifty-one patients underwent pre-POEM OCT. Using OCT as a guide, 24 (47 %) of patients underwent anterior POEM while 27 (53 %) underwent posterior POEM. Technical success was achieved in 96 % of patients. Significantly less bleeding occurred in the OCT arm when compared to the control group [4 (8 %) vs. 14 (43 %), p = 0.0001]. As a result, procedural time was significantly lower in the OCT group as compared to the control group (85.8 vs. 121.7 min, p = 0.000097). CONCLUSION: Pre-POEM OCT results in a reduction in procedural bleeding which contributes to a reduction in overall procedural time. CLINICAL TRIAL REGISTRATION: NCT01438385.

The purpose of our study is to determine if Gadofosveset trisodium-enhanced magnetic resonance angiography (MRA) could be used for detection and localization of acute lower gastrointestinal (LGI) bleed. Four patients underwent MRA (4 females, mean age of 65 years) for suspected LGI bleeding. MRA detected an active rectal bleed in one patient. All other patients did not demonstrate active bleeding and these true negatives were confirmed by computed tomography angiography, endoscopy, and tagged-red blood cell scan or digital subtraction angiography. Preliminary results suggest that MRA may serve as an alternative technique for detecting acute LGI bleeding when nuclear scintigraphy is unavailable or in the younger radiosensitive population but further investigation in a larger cohort is required.