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Background: How obesity has an impact on operative and oncologic outcomes for gastric cancer patients is unclear, and the influence of obesity on response to neoadjuvant chemotherapy (NAC) has not been evaluated., Methods: Patients who underwent curative gastrectomy for primary gastric cancer between 2000 and 2018 were retrospectively identified. After stratification for NAC, operative morbidity, mortality, overall survival (OS), and disease-specific survival (DSS) were compared among three body mass index (BMI) categories: normal BMI (< 25 kg/m 2 ), mild obesity (25-35 kg/m 2 ), and severe obesity (≥ 35 kg/m 2 )., Results: During the study period, 984 patients underwent upfront surgery, and 484 patients received NAC. Tumor stage did not differ among the BMI groups. However, the rates of pathologic response to NAC were significantly lower for the patients with severe obesity (10% vs 40%; p < 0.001). Overall complications were more frequent among the obese patients (44.3% for obese vs 24.9% for normal BMI, p < 0.001). Intraabdominal infections were also more frequent in obese patients (13.9% for obese vs 4.7% for normal BMI, p = 0.001). In the upfront surgery cohort, according to the BMI, OS and DSS did not differ, whereas in the NAC cohort, severe obesity was independently associated with worse OS [hazard ratio (HR) 1.87; 95% confidence interval (CI) 1.01-3.48; p = 0.047] and disease-specific survival (DSS) (HR 2.08; 95% CI 1.07-4.05; p = 0.031)., Conclusion: For the gastric cancer patients undergoing curative gastrectomy, obesity was associated with significantly lower rates of pathologic response to NAC and more postoperative complications, as well as shorter OS and DSS for the patients receiving NAC., (© 2021. Society of Surgical Oncology.)

Background: Patients with medullary thyroid carcinoma (MTC) often receive lateral lymph node dissection with total thyroidectomy when calcitonin levels are elevated, even in the absence of structural disease, but the effect of this intervention on disease-specific outcomes is not known., Patients and Methods: We retrospectively reviewed patients from 1986 to 2017 who underwent thyroidectomy with curative intent for MTC at our institution. The association of disease-specific survival and clinicopathologic features was examined using univariate and multivariate Cox regression., Results: We identified 316 patients who underwent curative resection for MTC. Overall and disease-specific survival were 76% and 86%, respectively, at 10 years. To investigate the effect of prophylactic ipsilateral lateral lymph node dissection, we analyzed 89 patients without known structural disease in the neck lymph nodes at the time of resection and preoperative calcitonin > 200 pg/ml, of whom 45 had an ipsilateral lateral lymph node dissection (LND) and 44 did not. There were no differences in tumor size or preoperative calcitonin levels. There was no difference at 10 years in cumulative incidence of recurrence in the neck (20.9% LND vs. 30.4% no LND, p = 0.46), cumulative incidence of distant recurrence (18.3% vs. 18.4%, p = 0.97), disease-specific survival (86% vs. 93%, p = 0.53), or overall survival (82% vs. 90%, p = 0.6)., Conclusion: Lateral neck dissection in the absence of clinical or radiologic abnormal lymph nodes is not associated with improved survival in patients with MTC., (© 2021. Society of Surgical Oncology.)

Background: This study aimed to analyze timing and sites of recurrence for patients receiving neoadjuvant chemotherapy for gastric cancer. Neoadjuvant chemotherapy followed by surgical resection is the standard treatment for locally advanced gastric cancer in the West, but limited information exists as to timing and patterns of recurrence in this setting., Methods: Patients with clinical stage 2 or 3 gastric cancer treated with neoadjuvant chemotherapy followed by curative-intent resection between January 2000 and December 2015 were analyzed for 5-year recurrence-free survival (RFS) as well as timing and site of recurrence., Results: Among 312 identified patients, 121 (38.8%) experienced recurrence during a median follow-up period of 46 months. The overall 5-year RFS rate was 58.9%, with RFS rates of 95.8% for ypT0N0, 81% for ypStage 1, 77.4% for ypStage 2, and 22.9% for ypStage 3. The first site of recurrence was peritoneal for 49.6%, distant (not peritoneal) for 45.5%, and locoregional for 11.6% of the patients. The majority of the recurrences (84.3%) occurred within 2 years. Multivariate analysis showed that ypT4 status was an independent predictor for recurrence within 1 year after surgery (odds ratio, 2.58; 95% confidence interval, 1.10-6.08; p = 0.030)., Conclusions: The majority of the recurrences for patients with clinical stage 2 or 3 gastric cancer who received neoadjuvant chemotherapy and underwent curative resection occurred within 2 years. After neoadjuvant chemotherapy, pathologic T stage was a useful risk predictor for early recurrence., (© 2021. Society of Surgical Oncology.)

Background: The association between a positive surgical margin and local recurrence after resection of pancreatic adenocarcinoma (PDAC) has been reported. Assessment of the location of the a positive margin and the specific site of local recurrence has not been well described., Methods: A prospectively maintained database was queried for patients who underwent R0/R1 pancreaticoduodenectomy for PDAC between 2000 and 2015. The pancreatic, posterior, gastric/duodenal, anterior peritoneal, and bile duct margins were routinely assessed. Postoperative imaging was reviewed for the site of first recurrence, and local recurrence was defined as recurrence located in the remnant pancreas, surgical bed, or retroperitoneal site outside the surgical bed., Results: During the study period, 891 patients underwent pancreaticoduodenectomy, and 390 patients had an initial local recurrence with or without distant metastases. The 5-year cumulative incidence of local recurrence by site included the remnant pancreas (4%; 95% confidence interval [CI], 3-5%), the surgical bed (35%; 95% CI, 32-39%), and other regional retroperitoneal site (4%; 95% CI, 3-6%). In the univariate analysis, positive posterior margin (hazard ratio [HR], 1.50; 95% CI, 1.17-1.91; p = 0.001) and positive lymph nodes (HR, 1.36; 95% CI, 1.06-1.75; p = 0.017) were associated with surgical bed recurrence, and in the multivariate analysis, positive posterior margin remained significant (HR, 1.40; 95% CI, 1.09-1.81; p = 0.009). An isolated local recurrence was found in 197 patients, and a positive posterior margin was associated with surgical bed recurrence in this subgroup (HR, 1.51; 95% CI, 1.08-2.10; p = 0.016)., Conclusion: In this study, the primary association between site of margin positivity and site of local recurrence was between the posterior margin and surgical bed recurrence. Given this association and the limited ability to modify this margin intraoperatively, preoperative assessment should be emphasized.

Background: This study aimed to compare the clinicopathologic characteristics and stage-specific prognosis of young patients with gastric cancer (GC) after curative resection (R0) in the United States and China., Methods: Data were collected on young patients (age ≤40 years) undergoing R0 resection at one U.S. (n = 79) and one Chinese (n = 257) institution. Patient, surgical, and pathologic variables and stage-specific survival rates were compared. Factors associated with 5-year disease-specific survival (DSS) were determined via multivariate analysis., Results: Tumor location was most often proximal in U.S. patients and distal in Chinese patients. The Chinese patients had more advanced-stage tumors, with a greater number of positive lymph nodes identified. Preoperative chemotherapy was administered more often in the United States. The 5-year overall survival (p = 0.07) and DSS (p = 0.07) did not differ statistically between the U.S. and Chinese cohorts. Among the patients with early GC receiving surgery alone, DSS did not differ significantly between the two cohorts (p = 0.44). Among the patients with advanced GC, DSS was comparable between the U.S. patients receiving preoperative chemotherapy plus surgery and the Chinese patients receiving surgery plus postoperative chemotherapy (p = 0.85). Lauren classification, depth of invasion, number of metastatic lymph nodes, and type of gastrectomy, but not country, were independent predictors of DSS., Conclusions: Tumor features and therapeutic strategies among young patients with GC differ between the United States and China. Survival is comparable between young patients with advanced GC receiving preoperative chemotherapy plus surgery in the United States and those receiving surgery plus postoperative chemotherapy in China, suggesting that the outcomes for young patients with GC are stage dependent but not country specific.

Background: Endoscopic ultrasound (EUS) is a guideline-recommended diagnostic test to estimate pretreatment clinical stage in gastric cancer. The impact of EUS to discriminate long-term outcomes has not been established., Objectives: The objectives of our study were to (1) evaluate the association between EUS and pathologic stage; (2) evaluate the ability of EUS to predict disease-specific survival (DSS); and (3) determine how neoadjuvant chemotherapy (NCT) affects these relationships., Methods: A prospective gastric cancer database at a tertiary care cancer center identified 734 patients who underwent curative intent resection. Patients were separated into EUS low-risk (T1-2, N0) and EUS high-risk (T3-4 Nany, or Tany N+) groups. Agreement statistics and 5-year DSS were estimated stratified by NCT., Results: Between 1987 and 2015, 68% (502/734) of patients were not treated with NCT. Among these patients, percentage agreement between EUS and pathology was moderate (individual T stage: 52%; N stage: 70%; risk group: 73%). EUS accurately estimated pathologic risk group in 73% (365/502) of patients, whereas it overestimated pathologic risk group in 19% (93/502) of patients and underestimated risk in 8% (41/502) of patients. EUS in non-NCT staging was able to discriminate DSS for T stage (hazard ratio [HR] 5.07, p < 0.05), N stage (HR 3.58, p < 0.05), and risk group (HR 6.35, p < 0.05). Among patients treated with NCT, EUS was unable to discriminate DSS for T stage (HR 0.94, p > 0.05), N stage (HR 1.46, p > 0.05) and risk group (HR 0.50, p > 0.05)., Conclusions: Pretreatment clinical staging based on EUS alone could lead to over- or under treatment in 27% of patients and can discriminate DSS in NCT-naive patients. EUS should be used in the context of other validated clinical risk tools.

Purpose: There is an increasing effort in the global public health community to strengthen research capacity in low- and middle-income countries, but there is no consensus on how best to approach such endeavors. Successful consortia that perform research on HIV/AIDS and other infectious diseases exist, but few papers have been published detailing the challenges faced and lessons learned in setting up and running a successful research consortium., Methods: Members of the African Research Group for Oncology (ARGO) participated in generating lessons learned regarding the foundation and maintenance of a cancer research consortium in Nigeria., Results: Drawing on our experience of founding ARGO, we describe steps and key factors needed to establish a successful collaborative consortium between researchers from both high- and low-income countries. In addition, we present challenges we encountered in building our consortium, and how we managed those challenges. Although our research group is focused primarily on cancer, many of our lessons learned can be applied more widely in biomedical or public health research in low-income countries., Conclusions: As the need for cancer care in LMICs continues to grow, the ability to create sustainable, innovative, collaborative research groups will become vital. Assessing the successes and failures that occur in creating and sustaining research consortia in LMICs is important for expansion of research and training capacity in LMICs.

Background: Weight loss following gastrectomy for patients with gastric cancer has not been well characterized. We assessed the impact of patient and procedure-specific variables on postoperative weight loss following gastrectomy for cancer., Methods: A prospectively maintained gastric cancer database identified patients undergoing gastrectomy for cancer. Clinical and pathologic characteristics, baseline body mass index (BMI), and postoperative weights were extracted. Change in weight was analyzed by percent change in weight and absolute change in BMI. Random coefficients models were used to test whether the rate of change in weight over time differed by factors of interest., Results: Of 376 consecutive patients who underwent resection for gastric adenocarcinoma, 55 % were male, median age 66 years, and mean preoperative BMI 27.1 (range 16.2-45.6). Total gastrectomy was associated with more weight loss than subtotal gastrectomy at 1 year (15 vs. 6 %, early stage; 17 vs. 7 %, late stage). Maximum weight change was observed at 6-12 months after operation and remained stable or improved at 2 years. For early- and late-stage patients, median percent weight loss at 1 year was greater for BMI ≥ 30 versus BMI < 30 (14 vs. 8 %, early stage; 15 vs. 9 %, late stage)., Conclusions: The extent of weight loss after gastrectomy for gastric cancer is dependent on preoperative BMI and extent of gastric resection. Maximum weight change is expected by 12 months after operation and will stabilize or improve over time.

Objective: To analyze the natural history of small asymptomatic pancreatic neuroendocrine tumors (PanNET) and to present a matched comparison between groups who underwent either initial observation or resection. Management approach for small PanNET is uncertain., Methods: Incidentally discovered, sporadic, small (<3 cm), stage I-II PanNET were analyzed retrospectively between 1993 and 2013. Diagnosis was determined either by pathology or imaging characteristics. Intention-to-treat analysis was applied., Results: A total of 464 patients were reviewed. Observation was recommended for 104 patients (observation group), and these patients were matched to 77 patients in the resection group based on tumor size at initial imaging. The observation group was significantly older (median 63 vs. 59 years, p = 0.04) and tended towards shorter follow-up (44 vs. 57 months, p = 0.06). Within the observation group, 26 of the 104 patients (25 %) underwent subsequent tumor resection after a median observation interval of 30 months (range 7-135). At the time of last follow-up of the observation group, the median tumor size had not changed (1.2 cm, p = 0.7), and no patient had developed evidence of metastases. Within the resection group, low-grade (G1) pathology was recorded in 72 (95 %) tumors and 5 (6 %) developed a recurrence, which occurred after a median of 5.1 (range 2.9-8.1) years. No patient in either group died from disease. Death from other causes occurred in 11 of 181 (6 %) patients., Conclusions: In this study, no patient who was initially observed developed metastases or died from disease after a median follow-up of 44 months. Observation for stable, small, incidentally discovered PanNET is reasonable in selected patients.

Background: Myxofibrosarcoma and undifferentiated pleomorphic sarcoma (UPS) are aggressive, genetically complex sarcomas. The minimum myxoid component used as a criterion for myxofibrosarcoma varies widely, so we determined the optimal myxoid component cutpoints for stratifying outcomes of UPS and myxofibrosarcoma. We also analyzed clinicopathologic factors associated with outcome., Methods: Review of a prospective, single-institution database identified 197 patients with primary, high-grade extremity/truncal myxofibrosarcoma or UPS resected during 1992-2013. Histology was reviewed and percent myxoid component determined for each tumor. Disease-specific survival (DSS) and distant recurrence-free survival (DRFS) were analyzed using the Kaplan-Meier method, log-rank test, and Cox regression., Results: Median follow-up for survivors was 6.4 years. In minimum p value analysis of myxoid component, the best cutpoint for both DSS and DRFS was 5% (adjusted p ≤ 0.001), followed by 70%. Therefore, sarcomas with <5% myxoid component (n = 69) were classified as UPS and those with ≥5% myxoid component (n = 128) as myxofibrosarcoma. Five-year DRFS was 24% for UPS, 51% for 5-69% myxoid component myxofibrosarcoma, and 65% for ≥70% myxoid component myxofibrosarcoma. Myxoid component, tumor size, and age were independently associated with DSS; myxoid component and tumor size were associated with DRFS. Only tumor site was associated with local recurrence., Conclusions: Percent myxoid component and tumor size are the two most important predictors of DSS and DRFS in high-grade myxofibrosarcoma and UPS. A 5% myxoid component cutpoint is an improved criterion for classifying myxofibrosarcoma. Myxoid component-based classification improves stratification of patient outcome and will aid in selection of patients for systemic therapy and clinical trials.

Introduction: Data on laparoscopic gastrectomy in patients with gastric cancer in the Western hemisphere are lacking. This study aimed to compare outcomes following laparoscopic versus open gastrectomy for gastric adenocarcinoma at a Western center., Methods: Eighty-seven consecutive patients who underwent laparoscopic gastrectomy from November 2005 to April 2013 were compared with 87 patients undergoing open resection during the same time period. Patients were matched for age, stage, body mass index, and procedure (distal subtotal vs. total gastrectomy). Endpoints were short- and long-term perioperative outcomes., Results: Overall, 65 patients (37 %) had locally advanced disease, and 40 (23 %) had proximal tumors. The laparoscopic approach was associated with longer operative time (median 240 vs.165 min; p < 0.01), less blood loss (100 vs.150 mL; p < 0.01), higher rate of microscopic margin positivity (9 vs.1 %; p = 0.04), decreased duration of narcotic and epidural use (2 vs. 4 days, p = 0.04, and 3 vs. 4 days, p = 0.02, respectively), decreased minor complications in the early (27 vs. 16 %) and late (17 vs. 7 %) postoperative periods (p < 0.01), decreased length of stay (5 vs. 7 days; p = 0.01), and increased likelihood of receiving adjuvant therapy (82 vs. 51 %; p < 0.01). There was no difference in the number of lymph nodes retrieved (median 20 in both groups), major morbidity, or 30-day mortality., Conclusions: Laparoscopic gastrectomy for gastric adenocarcinoma is safe and effective for select patients in the West.

Background: Readmission rates have been targeted for cost/reimbursement control. Our goal was to identify causes for readmission and delineate the pattern of early and late readmission., Methods: Between 2011 and 2012, a total of 490 patients underwent pancreaticoduodenectomy, distal pancreatectomy or central pancreatectomy. Logistic regression was used to identify predictors of readmission. K-medoids clustering was performed to identify the major readmission subgroups., Results: Median postoperative length of stay (LOS) was 7 days, and the 30- and 90-day readmission rates were 23 and 29 %, respectively. The most common cause for 30-day readmissions was procedure-related infections (58 %), while the most common cause for 31-90-day readmissions was failure to thrive and chemotherapy-related symptoms (38 %). Independent predictors of 30-day readmissions were central pancreatectomy, discharge with a drain, pancreatic duct <3 mm, previous abdominal surgery, and postoperative LOS. Independent predictors for 31-90-day readmissions were age and preoperative serum carcinoembryonic antigen. Cancer-related covariates were more common in the 31-90-day readmission group. Postoperative carbohydrate antigen 19-9 levels were twofold higher in the 31-90-day readmission group compared with the no readmission group (p = 0.03). K-medoids clustering identified a subgroup where 74 % of readmissions occur at a median of 7 days after discharge., Conclusions: Readmissions after pancreatic operations are procedure-related in the first 30 days, but those after this period are influenced by the natural history of the underlying diagnosis. The readmission penalty policy should account for the timing of readmission and the natural history of the underlying disease and procedure. Early follow-up for patients at high risk for readmission may minimize early readmissions.

Purpose: To compare the characteristics and prognoses of gastric cancers by tumor location in Korean and U.S. subjects after curative-intent (R0) resection for gastric cancer (GC)., Methods: Data were collected for all patients who had undergone R0 resection at one U.S. institution (n = 567) and one South Korean institution (n = 1,620). Patients with gastroesophageal junction tumors or neoadjuvant therapy were excluded. Patient, surgical, and pathologic variables were compared by tumor location. Factors associated with disease-specific survival (DSS) were determined via multivariate analysis., Results: In the Korean cohort, significantly more upper third GC (UTG) patients had undifferentiated, diffuse type, and advanced stage cancers compared to lower third GC (LTG) and middle third GC (MTG) patients. In the U.S. cohort, however, T stage was relatively evenly distributed among UTG, MTG, and LTG patients. The independent predictors of DSS in the Korean cohort were T stage, tumor size, retrieved and positive lymph node counts, and age, but in the U.S. cohort, the only independent predictors were T stage and positive lymph node count. Tumor size significantly affected DSS of Korean UTG patients but not U.S. UTG patients., Conclusions: There were significant differences in tumor characteristics by tumor location within and between both national cohorts. On the basis of these findings, further study to investigate the biological difference between the two countries is needed.

Background: Risk of high-grade dysplasia and invasive carcinoma in intraductal papillary mucinous neoplasms (IPMN) of the pancreas is increased in main duct compared to branch duct lesions. We hypothesized that isolated uncinate duct dilation may also be a radiographic indicator of high-risk disease, as the primary drainage of this portion of the gland originates from a distinct embryologic precursor., Methods: All patients with available preoperative imaging who underwent resection for IPMN between 1994 and 2010 were included (n = 184). Imaging studies were reviewed by an experienced radiologist who was blinded to the pathologic results, and studies were categorized as main duct, branch duct, or combined-duct. The presence of uncinate duct dilation was assessed as a risk factor for tumors which proved to have high-grade dysplasia (HGD) or invasive carcinoma (IC) on pathologic assessment., Results: IPMN with HGD or IC were identified in 82 of 184 cases (45%). Without considering uncinate duct dilation, IPMN with HGD or IC were present in 84% of patients with main duct IPMN (n = 31/37), 58% with combined-duct IPMN (n = 23/40), and 26% with branch \duct IPMN (n = 28/107). Dilation of the uncinate duct was observed in 47 patients, with or without main duct dilation, and 30 of these (64%) contained HGD or IC on pathology. Isolated uncinate duct dilation without main duct dilation was observed in 17 patients, and 11 (65%) had HGD. On multivariate analysis of IPMN without associated main duct dilation, uncinate duct dilation was independently associated with IPMN with HGD or IC (p = 0.002)., Conclusion: Uncinate duct dilation on preoperative radiologic imaging appears to be an additional risk factor for IPMN-associated high-grade dysplasia or adenocarcinoma.

Background: The prognosis of signet ring cell (SRC) gastric adenocarcinoma is regarded as poor, although studies addressing outcomes in relation to non-SRC tumors are conflicting. Our objective was to compare the survival of SRC tumors with stage-matched intestinal-type tumors in a cohort of Western patients., Methods: Review of a prospectively maintained database identified 569 patients undergoing curative resection (R0) from 1990 to 2009. Patients were divided into three histologic groups on the basis of the Lauren classification: SRC (n = 210), intestinal well- or moderately differentiated (WMD, n = 242) disease, and intestinal poorly differentiated (PD, n = 117) disease. Patient demographics, clinicopathologic features, and postoperative outcomes were determined. Stage-stratified disease-specific mortality was calculated and multivariate analysis performed., Results: When compared with WMD and PD tumors, SRC tumors were associated with younger age (63 years SRC vs. 71 years WMD and 72 years PD, p < 0.0001) and with female sex (58 % SRC vs. 40 % WMD and 40 % PD, p = 0.0003). Median follow-up was 115 months. Patients with stage Ia SRC lesions had a better 5-year disease-specific mortality compared with stage-matched intestinal-type tumors (0 % SRC vs. 8 % WMD and 24 % PD, p = 0.001). In contrast, SRC patients with stage III disease fared significantly worse (78 % SRC vs. 54 % WMD and 72 % PD, p = 0.001). On multivariate analysis, the risk of death from gastric cancer comparing all three groups was lowest for SRC in stage I and highest for SRC in stage III disease (stage III hazard ratio: SRC 1 vs. 0.47 WMD and 0.85 PD)., Conclusions: When compared with intestinal-type tumors, SRC tumors at early stages are not necessarily associated with poor outcomes.

Background: Clinical decision making for patients with intraductal papillary mucinous neoplasms (IPMN) of the pancreas is challenging. Even with strict criteria for resection, most resected lesions lack high-grade dysplasia (HGD) or invasive carcinoma., Methods: We evaluated patients who underwent resection of histologically confirmed IPMN and had preoperative imaging available for review. A hepatobiliary radiologist blinded to histopathologic subtype reviewed preoperative imaging and recorded cyst characteristics. Patients with mixed-type IPMN were grouped with main-duct lesions for this analysis. Based on an ordinal logistic regression model, we devised two independent nomograms to predict the findings of adenoma, high-grade dysplasia (HGD-CIS), and invasive carcinoma, separately in both main and branch-duct IPMN. Bootstrap validation was used to evaluate the performance of these models, and a concordance index was derived from this internal validation., Results: There were 219 patients who met criteria for this study. Branch-duct IPMN (bdIPMN) comprised 56 % of the resected lesions. The proportion of HGD-CIS was 15 % for bdIPMN and 33 % for main-duct lesions (mdIPMN); P = 0.003. Invasive carcinoma was identified in 15 % of bdIPMN and 41 % of main-duct lesions (P < 0.001). On multivariate regression, patient gender, history of prior malignancy, presence of solid component, and weight loss were found to be significantly associated with the ordinal outcome for patients with mdIPMN and built into the nomogram (concordance index 0.74). For patients with bdIPMN weight loss, solid component, and lesion diameter were associated with the outcome; (concordance index 0.74)., Conclusion: Based on the analysis of patients selected for resection, two nomograms were created that predict a patient's individual likelihood of harboring HGD or invasive malignancy in radiologically diagnosed IPMN. External validation is ongoing.

Background: Based on review of patient data in case conferences over time, we hypothesized that clinically relevant data are omitted in routine soft tissue sarcoma staging., Methods: We examined subsets of a prospectively collected single institution soft tissue sarcoma database with respect to criteria of the AJCC versions 6 (2002) and 7 (2010) staging systems and examined their clinical outcomes., Results: Relapse-free survival decreases with increasing primary tumor size in four categories, versus two categories used in AJCC 6 and 7 staging. Disease-specific survival decreases over three categories. Conversely, omission of tumor depth as a prognostic factor in version 7 appears supported, since tumor depth is not an independent risk factor for disease-specific survival by multivariate analysis. Patients with nodal disease and no other metastases fare better than patients with other metastases, but have inferior outcomes compared with patients with large high-grade tumors without nodal metastasis. Multivariate analysis identified size, site, grade, age, nodal metastatic disease, and other metastatic disease as independent risk factors for disease-specific survival. Versions 6 and 7 criteria are tacit regarding anatomic site and histology for tumors with identical FNCLCC grade., Conclusions: Improved patient risk assessment may be achieved by staging using a larger number of size categories. Staging system refinements come at the cost of a larger number of staging categories. Histology or site-specific staging systems, nomograms or Bayesian belief networks may provide more accurate means to assess clinical outcomes.

Purpose: To examine the association between positive resection margins and survival and local recurrence in patients with gastric cancer undergoing resection with curative intent., Methods: Patients who underwent curative intent resection for gastric carcinoma from 1985 to 2010 were identified from a prospectively maintained database. Positive margins were defined as disease present at the line of luminal transection. Clinicopathological features and outcome of patients undergoing gastrectomy with negative and positive margins were compared., Results: Among 2384 patients undergoing curative intent resection, 108 (4.5 %) had positive margins. Positive margins were associated with higher American Joint Committee on Cancer (AJCC) stage, T stage, N stage, median number of positive nodes, diffuse Lauren type, and poorly differentiated tumors. Treatment of positive margins consisted of: observation (39 %), chemoradiotherapy (26 %), chemotherapy (20 %), repeat resection (10 %), radiotherapy (4 %), and unknown (1 %). Multivariate analysis of the entire cohort demonstrated margin status, T stage, N stage, grade, and perineural invasion to be independent predictors of survival. Margin status was an independent predictor of survival in patients with ≤3 positive nodes or T1-2 disease but was not in patients with >3 positive nodes or T3-4 disease. Local recurrence occurred in 16 % of patients with a positive margin. We identified no factors predictive of local recurrence in patients with positive margins., Conclusions: Positive resection margin is associated with advanced AJCC stage and aggressive tumor biology but remains an independent predictor of worse survival. The significance of a positive margin in gastric cancer is confined to patients with nontransmural disease and/or limited nodal involvement.

Background: Leiomyosarcoma is a soft tissue sarcoma whose outcome has historically been confounded by the inclusion of gastrointestinal stromal tumors. Thus, we sought to determine the factors that predict survival and recurrence in patients with primary leiomyosarcoma alone., Methods: During 1982-2006, a total of 353 patients with primary resectable leiomyosarcoma were identified from a prospective database. Multivariate analysis was used to assess clinicopathologic factors for association with disease-specific survival (DSS). Competing risk survival analysis was used to determine factors predictive for local and distant recurrence., Results: Of 353 patients, 170 (48 %) presented with extremity, 144 (41 %) with abdominal/retroperitoneal, and 39 (11 %) with truncal tumors. Median age was 57 (range, 18-88) years, and median follow-up was 50 (range, 1-270) months. Most tumors were high grade (75 %), deep (73 %), and completely resected (97 %); median size was 6.0 (range, 0.3-45) cm. Abdominal/retroperitoneal location was associated with worse long-term DSS compared to extremity or trunk (P = 0.005). However, by multivariate analysis, only high grade and size were significant independent predictors of DSS. Overall, 139 patients (39 %) had recurrence: 51 % of those with abdominal/retroperitoneal, 33 % of extremity, and 26 % of truncal disease. Significant independent predictors for local recurrence were size and margin, whereas predictors for distant recurrence were size and grade. Site was not an independent predictor of recurrence; however, late recurrence (>5 years) occurred in 9 % of abdominal/retroperitoneal and 4 % of extremity lesions., Conclusions: Grade and size are significant independent predictors of DSS and distant recurrence. Long-term follow-up in leiomyosarcoma is important, as late recurrence continues in 6-9 % patients.

Background: Survival estimates after curative surgery for gastric cancer are based on AJCC staging, or on more accurate multivariable nomograms. However, the risk of dying of gastric cancer is not constant over time, with most deaths occurring in the first 2 years after resection. Therefore, the prognosis for a patient who survives this critical period improves. This improvement over time is termed conditional probability of survival (CPS). Objectives of this study were to develop a CPS nomogram predicting 5-year disease-specific survival (DSS) from the day of surgery for patients surviving a specified period of time after a curative gastrectomy and to explore whether variables available with follow-up improve the nomogram in the follow-up setting., Methods: A CPS nomogram was developed from a combined US-Dutch dataset, containing 1,642 patients who underwent an R0 resection with or without chemotherapy/radiotherapy for gastric cancer. Weight loss, performance status, hemoglobin, and albumin 1 year after resection were added to the baseline variables of this nomogram., Results: The CPS nomogram was highly discriminating (concordance index: 0.772). Surviving 1, 2, or 3 years gives a median improvement of 5-year DSS from surgery of 7.2, 19.1, and 31.6 %, compared with the baseline prediction directly after surgery. Introduction of variables available at 1-year follow-up did not improve the nomogram., Conclusions: A robust gastric cancer nomogram was developed to predict survival for patients alive at time points after surgery. Introduction of additional variables available after 1 year of follow-up did not further improve this nomogram.

Background: The prevalence of obesity is increasing in the United States. Obesity has been associated with worse surgical outcomes, but its impact on long-term outcomes in gastric cancer is unclear. The aim of this study was to evaluate the effects of being overweight on surgical and long-term outcomes for patients with gastric cancer., Methods: Patients who underwent curative intent resection for gastric carcinoma from 1985 to 2007 were identified from a prospectively collected gastric cancer database. Overweight was defined as a body mass index (BMI) of 25 kg/m(2) or higher. Clinical outcomes of overweight and nonoverweight patients were compared., Results: From the total population of 1,853 patients, 1,125 (60.7%) were overweight. Overweight patients tended to have more proximal tumors and a lower T stage. Accurate complication data were available on a subset of patients from 2000 to 2007. A BMI of ≥25 was associated with increased postoperative complications (47.9 vs. 35.8%, p < 0.001). This was mainly due to an increase in the rate of wound infections (8.9 vs. 4.7%, p = 0.02) and anastomotic leaks (11.8 vs. 5.4%, p = 0.002). Multivariate logistic regression analysis showed that higher BMI, total gastrectomy, and use of neoadjuvant chemotherapy were associated with increased wound infection and anastomotic leak. Overweight patients were less likely to have adequate lymph node staging (73.3 vs. 79.2%, p = 0.047). There was no difference in overall survival or disease-specific survival between the two groups., Conclusions: Increased BMI is a predictor of increased postoperative complications, including anastomotic leak, but it is not a predictor of survival in gastric cancer.

Background: Intraductal papillary mucinous neoplasms (IPMN) may represent a field defect of pancreatic ductal instability. The relative risk of carcinoma in regions remote from the radiographically identified cyst remains poorly defined. This study describes the natural history of IPMN in patients initially selected for resection or surveillance., Methods: Patients with IPMN submitted to resection or radiographic surveillance were identified from a prospectively maintained database. Comparisons were made between these two groups., Results: From 1995 to 2010, a total of 356 of 1,425 patients evaluated for pancreatic cysts fulfilled inclusion criteria. Median follow-up for the entire cohort was 36 months. Initial resection was selected for 186 patients (52 %); 114 had noninvasive lesions and 72 had invasive disease. A total of 170 patients underwent initial nonoperative management. Median follow-up for this surveillance group was 40 months. Ninety-seven patients (57 % of those under surveillance) ultimately underwent resection, with noninvasive disease in 79 patients and invasive disease in 18. Five of the 18 (28 %) invasive lesions developed in a region remote from the monitored lesion. Ninety invasive carcinomas were identified in the entire population (25 %), ten of which developed the invasive lesion separate from the index cyst, representing 11 % with invasive disease., Conclusions: Invasive disease was identified in 39 % of patients with IPMN selected for initial resection and 11 % of patients selected for initial surveillance. Ten patients developed carcinoma in a region separate from the radiographically identified IPMN, representing 2.8 % of the study population. Diagnostic, operative, and surveillance strategies for IPMN should consider risk not only to the index cyst but also to the entire gland.

Background: The immune system has been shown to play an important role in gastrointestinal stromal tumor (GIST). The neutrophil-to-lymphocyte ratio (NLR) in blood is an easily assessable parameter of systemic inflammatory response. The aim of this study was to determine whether the NLR is prognostic in GIST., Methods: A total of 339 previously untreated patients with primary, localized GIST operated at our institution between 1995 and 2010 were identified from a prospectively collected sarcoma database. NLR was assessed preoperatively. Patients who received adjuvant imatinib treatment were excluded from the analysis (n = 64). Cox regression models were calculated and correlation analyses were performed., Results: On univariate analysis, NLR was associated with recurrence-free survival (RFS) (P = 0.003, hazard ratio 3.3, 95 % confidence interval 1.5-7.4). Patients with a low NLR had a 1- and 5-year RFS of 98 and 91 %, compared with 89 and 76 % in those with a high NLR. The median RFS was not reached. Positive correlations were found between NLR and mitotic rate (Pearson correlation coefficient [r] = 0.15, P = 0.03), and NLR and tumor size (r = 0.36, P = 0.0001). RFS in patients with a GIST >5 cm with low NLR was significantly longer compared to patients with high NLR (P = 0.002). Flow cytometry analysis of freshly obtained GISTs revealed that neutrophils constituted a minimal percentage of intratumoral immune cells., Conclusions: NLR is a surrogate for high-risk tumor features. Elevated blood NLR appears to represent systemic inflammation in patients with high-risk GIST.

Introduction: Staging laparoscopy (SL) can identify occult, subradiographic metastatic (M1) disease in patients with gastric or gastroesophageal (G/GEJ) cancer who are unlikely to benefit from gastrectomy. The purpose of this study is to determine the yield of repeat SL following neoadjuvant therapy for G/GEJ adenocarcinoma after initial negative pretreatment SL., Methods: Retrospective review of a prospective database identified patients with locoregionally advanced (T3-4Nany or TanyN+) G/GEJ adenocarcinoma who underwent pretreatment SL. The yield of repeat SL following neoadjuvant therapy was determined., Results: From 1994 to 2010, 276 patients with locoregionally advanced G/GEJ adenocarcinoma were identified, of whom 244 proceeded to operation after neoadjuvant therapy, at a median time of 105 days. One hundred sixty-four patients (67 %) underwent repeat SL, and 80 patients (33 %) proceeded directly to laparotomy. Occult M1 disease was identified in 12 (7.3 %) and 6 (7.5 %) patients, respectively. In the repeat SL cohort, M1 disease was identified at laparoscopy in nine patients (5.5 %). M1 disease not identified by laparoscopy was discovered at laparotomy in three patients (1.8 %). The median follow-up for the study population was 31 months. For patients with M1 disease, median overall survival was 15 months, versus 41 months for patients resected without M1 disease (p < 0.0001)., Conclusions: Occult, subradiographic M1 disease develops in approximately 7 % of patients following neoadjuvant therapy for locoregionally advanced G/GEJ adenocarcinoma. These patients have poor prognosis, and repeat SL can be a valuable tool in selecting patients with locoregionally advanced G/GEJ tumors for potentially curative resection after neoadjuvant therapy.

Background: Malignant peripheral nerve sheath tumors (MPNSTs) occur sporadically, after prior radiation therapy (RT), or in association with neurofibromatosis type 1 (NF1). It is controversial whether patients with NF1-associated MPNST have worse outcomes. We investigated the prognostic significance of sporadic, NF1-associated, and RT-induced MPNST., Methods: Patients with primary high-grade MPNST from 1982 to 2011 were identified from a prospectively maintained database. Patients with sporadic MPNST were included only if the MPNST was not associated with NF1 or a neurofibroma or if it was immunohistochemically S100-positive., Results: We studied 105 patients; 42 had NF1-associated tumors, 49 sporadic, and 14 RT-induced. Median age at diagnosis was 38 years. Median follow-up for surviving patients was 4 years. Mean tumor diameter was 5.5 cm for RT-induced tumors and 9.7 cm for NF1-associated and sporadic tumors (P=0.004). In multivariate analysis, factors associated with worse disease-specific survival (DSS) were larger size (HR 1.08; 95% CI 1.04-1.13; P<0.001) and positive margin (HR 3.30; 95% CI 1.74-6.28; P<0.001). Age, gender, site of disease, and S100 staining were not associated with DSS. The 3-year and median DSS were similar for NF1 and sporadic cases; combined 3-year DSS was 64% and median DSS was 8.0 years. For RT-induced tumors, 3-year DSS was 49% and median DSS was 2.4 years. The relationship between RT association and DSS approached statistical significance (HR 2.29; 95% CI 0.93-5.67; P=0.072)., Conclusions: Margin status and size remain the most important predictors of DSS in patients with MPNST. NF1-associated and sporadic MPNSTs may be associated with improved DSS compared with RT-induced tumors.

Background: Surgical approach is an accepted approach for metastatic neuroendocrine tumors (NET), but the safety and effectiveness of synchronous liver metastases resection with primary and/or locally recurrent NET is unclear., Methods: From 1992 to 2009, a total of 36 patients underwent synchronous resection of primary NET or local recurrence and liver metastases. Patients and tumor characteristics, surgical procedures, and postoperative and long-term outcome were reviewed., Results: Primary lesions were solitary in 28 patients (80 %), with a median size of 25 mm. Liver metastases were multiple in 32 cases (89 %), with a bilobar distribution in 29 patients (81 %) and a median size of 62 mm. Resections included gastroduodenal (n = 5), ileocolonic (n = 18), pancreatic resection (n = 13), and major hepatectomy (n = 15). Resections were R0, R1, and R2 in 13, 11, and 12 cases, respectively, and tumors were classified as G1 in 20 (56 %) and G2 in 15 (42 %). There was 1 postoperative death after a Whipple/right trisectionectomy, and postoperative complication occurred in 16 patients (44 %). With a median follow-up of 56 months, 31 patients (89 %) experienced recurrence, which was confined to the liver in 90 %. Reduction of disease to liver only allowed subsequent liver-directed therapy, such as arterial embolization or percutaneous ablation, in 25 patients (71 %). Five-year symptom-free survival and overall survival were 60 %, and 69 %, respectively., Conclusions: In highly selected patients, an initial surgical approach combining simultaneous resection of liver metastases and primary/recurrent tumors can be performed with low mortality. Most patients develop liver-confined recurrence, which is usually amenable to ablative therapies that offer ongoing disease and symptom control.

Background: It is important to understand the relative importance of prognostic variables in patients with soft tissue sarcomas. The purpose of this study was to describe the hierarchical relationships between features inherent to completely excised, localized high-grade soft tissue sarcomas of the extremity and compare the associations to those previously reported., Methods: Data were collected from the Memorial Sloan-Kettering Cancer Center Sarcoma Database. All adult patients with high-grade extremity soft tissue sarcomas who underwent complete excision (R0 margins) at our institution between 1982 and 2010 were included in the analysis. Bayesian belief network (BBN) modeling software was used to develop a hierarchical network of features trained to estimate the likelihood of disease-specific survival. Important relationships depicted by the BBN model were compared to those previously reported., Results: The records of 1318 consecutive patients met the inclusion criteria, and all were included in the analysis. First-degree associates of disease-specific survival were the primary tumor size; presence of and time to distant recurrence; and presence of and time to local recurrence. On cross-validation, the BBN model was sufficiently robust, with an area under the curve of 0.94 (95 % confidence interval 0.93-0.96)., Conclusions: We successfully described the hierarchical relationships between features inherent to patients with completely excised high-grade soft tissue sarcomas of the extremity. The relationships defined by the BBN model were similar to those previously reported. Cross-validation results were encouraging, demonstrating that BBN modeling can be used to graphically illustrate the complex hierarchical relationships between prognostic features in this setting.

Background: Epidemiologic studies have reported a positive correlation between body mass index (BMI) and pancreatic cancer risk, but clinical relevance of obesity and/or body fat distribution on tumor characteristics and cancer-related outcome remain controversial. We sought to assess the influence of obesity and body fat distribution on pathologic characteristics and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma., Methods: Demographic and biometric data were collected on 328 patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. In a subset of patients, pancreatic fatty infiltration and fibrosis were assessed pathologically, and visceral fat area (VFA) was evaluated. Influence of BMI and body fat distribution on tumor characteristics and survival were evaluated., Results: A significant positive correlation between BMI and VFA was observed, with a wide range of VFA value within each BMI class. According to BMI or VFA distribution, there were no significant differences in patient characteristics, intraoperative or perioperative outcome, or pathologic characteristics, with the exception of significantly higher blood loss in patients with an increased body weight or VFA. Unadjusted overall and disease-free survival between BMI class and VFA quartile were not significantly different., Conclusions: In this study, obesity and body fat distribution were not correlated with specific tumor characteristics or cancer-related outcome.

Purpose: To evaluate the changes in the 7th edition American Joint Committee on Cancer (AJCC) staging system for stomach cancer compared to the 6th edition; to compare the predictive accuracy of the two staging systems., Methods: In a combined database containing 2,196 patients who underwent an R0 resection for gastric adenocarcinoma, differences between the two staging systems were evaluated and stage-specific survival estimates compared. Concordance probability and Brier scores were estimated for both systems to examine the predictive accuracy., Results: Nodal status cutoff values were changed, leading to a more even distribution for the redefined N1, N2, and N3 group. AJCC 6th edition stage II reflected a highly heterogeneous population, which is now adequately subdivided in the AJCC 7th edition into stages IIA, IIB, and IIIA. The predictive accuracy of N classification improved significantly as measured by concordance. Despite increased complexity, the predictive accuracy of AJCC 7th stage grouping was significantly worse than that of the AJCC 6th edition., Discussion: The increased complexity of the 7th edition staging system is accompanied by improvements in the predictive value of nodal staging as compared to the 6th edition, but it was no better in overall stage-specific predictive accuracy. Future refinements of the tumor, node, metastasis staging system should consider whether increased complexity is balanced by improved prognostic accuracy.

Background: Patients with locally unresectable pancreatic cancer (AJCC stage III) have a median survival of 10-14 months. The objective of this study was to evaluate outcome of initially unresectable patients who respond to multimodality therapy and undergo resection., Methods: Using a prospectively collected database, patients were identified who were initially unresectable because of vascular invasion and had sufficient response to nonoperative treatment to undergo resection. Overall survival (OS) was compared with a matched group of patients who were initially resectable. Case matching was performed using a previously validated pancreatic cancer nomogram., Results: A total of 36 patients with initial stage III disease were identified who underwent resection after treatment with either systemic therapy or chemoradiation. Initial unresectability was determined by operative exploration (n = 15, 42%) or by cross-sectional imaging (n = 21, 58%). Resection consisted of pancreaticoduodenectomy (n = 31, 86%), distal pancreatectomy (n = 4, 11%), and total pancreatectomy (n = 1, 3%). Pathology revealed T3 lesions in 26 patients (73%), node positivity in 6 patients (16%), and a negative margin in 30 patients (83%). The median OS in this series was 25 months from resection and 30 months since treatment initiation. There was no difference in OS from time of resection between the initial stage III patients and those who presented with resectable disease (P = .35)., Conclusions: In this study, patients who were able to undergo resection following treatment of initial stage III pancreatic cancer experienced survival similar to those who were initially resectable. Resection is indicated in this highly select group of patients.

Background: Randomized trials have demonstrated a benefit associated with adjuvant therapy for pancreatic cancer, and retrospective studies have demonstrated improvements in postoperative mortality. The purpose of this study was to evaluate whether these improvements could be identified in a cohort of patients who underwent resection for pancreatic cancer at a single institution over three decades., Methods: Short- (30 days), intermediate- (1 year), and long-term survival were compared between decades. Long-term survival focused on patients who survived at least 1 year to minimize the effects of perioperative mortality and patient selection., Results: Between 1983 and 2009, 1147 pancreatic resections were performed for ductal adenocarcinoma, including 123 resections in the 1980s, 399 in the 1990s, and 625 in the 2000s. The 30-day mortality rates were 4.9%, 1.5% (P = 0.03 vs. 1980s), and 1.3% (P = 0.007 vs. 1980s). The 1-year mortality rates were 42%, 31% (P < 0.001 vs. 1980s), and 24% (P < 0.001 vs. 1980s and 1990s). In the group of patients who survived 1 year, the overall survivals were 23.2 months, 25.6 months (P = 0.6 vs. 1980s), and 24.5 months (P = 0.2 vs. 1980s). In a multivariate analysis adjusted for pathologic features, the decade of resection was not a significant predictor of long-term survival (hazard ratio = 1.1, P = 0.3)., Conclusions: Patients who underwent resection for pancreatic cancer between 2000 and 2009 experienced improved operative mortality and 1-year survival compared to those who underwent resection in the 1980s, while the long-term survival was similar over all three decades. These results underscore the need for early detection strategies and more effective adjuvant therapies for patients with pancreatic cancer.

Background: Surgery may have a profound effect on patients' health-related quality of life (QOL). To be optimally useful, trials that seek to guide clinical decision making should measure outcomes that are important to patients and report the results in a clinically meaningful way. We sought to explore how researchers currently measure and interpret QOL in surgical trials, using gastric cancer as a case study., Method: We performed a systematic review of randomized controlled trials (RCTs) of gastric cancer surgery published between 1966 and 2009 that included at least one patient-reported outcome (PRO). Investigators assessed trial eligibility and extracted data in duplicate using standardized forms, then resolved disagreements by consensus., Results: Our search identified 87 RCTs of gastric cancer surgery, of which 11 (13%) included at least one PRO. Ten RCTs measured one or more validated PROs, although six also included ad hoc measures. All manuscripts presented the results as raw scores and nine of the 11 trials identified a statistical difference between groups. All 11 manuscripts prominently reported the PRO results in the abstracts and conclusions, but only one discussed the clinical significance of the differences between groups., Conclusions: Most RCTs of gastric cancer surgery do not include measures of QOL and those that do suffer from important limitations. RCTs would be more useful to surgeons and patients if authors measured PROs and utilized existing approaches to present the results of PROs in ways that provide an intuitive sense of the magnitude of effects.

Introduction: The efficacy of laparoscopic celiac plexus block (CPB) in patients with unresectable pancreatic cancer has not been reported., Methods: Patients with elevated pain scores scheduled for laparoscopy for diagnosis/staging of unresectable pancreatic adenocarcinoma were eligible. The study was designed to evaluate 20 consecutive patients with validated quality of life (EORTC QLQ-C30, QLQ-PAN26) and validated pain assessment tools [Brief Pain Inventory (BPI)]. Questionnaires were obtained preoperatively, and postoperatively at 1, 4, and 8 weeks. Laparoscopic CPB was performed by bilateral injection of 20 cc 50% alcohol utilizing a recently described laparoscopic technique. Functional and symptom scoring was performed by EORTC scoring manual., Results: Median age was 61 years (range 42-80 years), and mean preoperative pain score [worst in 24 h on 0-10 visual analogue scale (VAS)] was 7.8 [standard deviation (SD) 1.6]. Median total operative time (laparoscopy + biopsy + CBP) was 57 min (range 29-92 min), and all patients except one were discharged on day of surgery. No major complications occurred. EORTC functional scales did not change significantly during the postoperative period. EORTC symptomatic pain scores decreased significantly. These findings were also observed in the BPI, with significant decreases in visual analogue score for reported mean (preoperative versus week 4, mean: 5.7 versus 2.7; p < 0.01) and worst (preoperative versus week 4, mean: 7.8 versus 5.1; p < 0.01) pain during a 24-h period., Conclusions: This study documents the efficacy of laparoscopic CPB. The procedure was associated with minimal morbidity, brief operative times, outpatient management, and reduction in pain scores similar to that reported with other approaches to celiac neurolysis.

Background: To study the pathology, treatment, and outcome of patients with gastric remnant cancer (GRC) after resection for peptic ulcer disease (PUD)., Methods: Review of a prospective gastric cancer database identified patients with GRC after gastrectomy for PUD. Clinicopathologic and treatment-related variables were obtained. Multivariate analysis was performed for factors associated with disease-specific survival (DSS)., Results: From January 1985 to April 2010, 4402 patients with gastric adenocarcinoma were treated at our institution and 105 patients (2.4%) had prior gastrectomy for PUD. Prior resections were most often Billroth II (N = 97, 92%). The median time from initial resection to development of GRC was 32 years (3-60 years), and the majority of tumors were located at the gastrointestinal anastomosis (N = 72, 69%). Median DSS was 1.3 years (0.6-2.1 years). Patients who had resection had a significantly better outcome than patients who did not have resection (median DSS 5 vs 0.35 years, P < .0001). Factors associated with DSS on multivariate analysis included advanced T-stage (HR 16.5 (CI 2.2-123.4), P = .0006) and lymph node metastasis (HR 1.1 (CI 1.0-1.2), P < .0001). Stage-specific survival following R0 resection was similar to patients with conventional gastric cancer., Conclusions: Patients have a lifetime risk for the development of GRC following resection for PUD. As with conventional gastric cancer, determinants of survival of patients with GRC include advanced T stage and nodal metastasis. Patients with GRC amenable to curative resection exhibit the best DSS and have stage-specific outcomes similar to patients with conventional gastric cancer.

Background: Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue malignancy that typically presents with local invasion but rarely metastasizes. We examine clinicopathologic factors associated with disease-free survival (DFS) in patients with primary and recurrent DFSP and evaluate responses to multimodality therapy., Materials and Methods: Patients treated for DFSP were identified in a prospectively maintained database. Clinicopathologic factors associated with DFS were analyzed using univariate and multivariate analysis., Results: A total of 244 patients with DFSP were identified. Median follow-up was 50 months. A total of 14 patients had local recurrence (LR), and 2 patients had distant recurrence (DR), with a median time to recurrence of 35 months. At time of last follow-up, 70% and 47% of patients showed no evidence of disease (NED) in the primary (n = 197) and recurrent groups (n = 47), respectively. On univariate analysis, tumor location and depth were associated with DFS in the primary group, while margin status (R1 vs. R0) was associated with DFS in the LR group. On multivariate analysis, only depth (primary group) and margin status (LR group), remained significant. Also, 22 patients had therapy other than surgical resection: 14 radiotherapy, 4 tyrosine kinase inhibitor (TKI) only, 2 conventional chemotherapy only, and 2 chemotherapy plus TKI. Responses to other therapies were variable., Conclusions: DFS after treatment for DFSP is strongly predicted by tumor depth in the primary setting and margin status in recurrent tumors. The treatment for DFSP in the primary or recurrent setting is excision with negative margins, resulting in low recurrence rates and infrequent metastatic spread. Multimodality treatment, especially TKI use, can be effective, but is not curative.

Background: Solid pseudopapillary tumors of the pancreas (SPT) are rare neoplasms, and the natural history is poorly defined. The aim of this study was to define the natural history and compare patient and tumor factors between patients with malignant and non-malignant disease., Methods: Data for all patients with SPT who underwent surgical exploration at MSKCC between 1987 and 2009 were collected and analyzed. Patient, tumor, treatment, and survival variables were examined. Malignant tumors were defined as any tumor that was locally unresectable, metastatic, or recurrent. Differences between groups were analyzed by Fisher's exact, chi-squared, Wilcoxon, and log-rank tests., Results: Forty-five patients had an SPT during the study period. Median age was 38 years (10-63) and 38 (84%) were women. At the time of diagnosis, 38 were symptomatic, with the most common symptom being abdominal pain (n = 35). The most frequent imaging characteristic was a solid and cystic tumor (n = 29), most commonly located in the tail of the pancreas (n = 23). Resection of the primary tumor (n = 41) (41/2,919 = 1.4% of all resections) included distal pancreatectomy in 26, pancreatoduodenectomy in 11, central pancreatectomy in two, and enucleation in two. Nine patients had malignant disease defined by a locally unresectable tumor in three, liver metastases in three, locally unresectable tumor and liver metastases in one, local recurrence and liver metastases in one, and local recurrence in another. Patients with malignant disease presented with larger tumors (7.8 vs. 4.2 cm) (p < 0.005). After median follow-up of 44 months, 34 patients were without evidence of disease, four patients were alive with disease, three patients died of disease, and four patients died of other causes., Conclusions: These results demonstrate that SPT occurs in young women, and the majority of patients will experience long-term survival following resection. The only feature associated with malignant disease was tumor size at presentation. The majority of patients are alive at last follow-up, and a low percentage experienced disease recurrence or death from disease.

Introduction: There are no reliable markers of dysplasia in patients with incidentally discovered intraductal papillary mucinous neoplasms of the pancreas (IPMN). IPMN dysplasia may be associated with mucin protein (MUC) expression and histopathologic subtype. We hypothesize that MUC expression in cyst fluid and serum can identify lesions with high risk of malignancy., Methods: Cyst fluid and serum were collected from 40 patients during pancreatectomy for IPMN between 2005 and 2009. Samples were grouped into low-risk (low-grade or moderate dysplasia, n = 21) and high-risk groups (high-grade dysplasia or carcinoma, n = 19). Mucin expression (MUC1, MUC2, MUC4, and MUC5AC) was assessed utilizing enzyme-linked immunosorbent assays., Results: MUC2 and MUC4 cyst fluid concentrations were elevated in high-risk versus low-risk groups (10 ± 3.0 ng/ml vs. 4.4 ± 1.2 ng/ml, p = 0.03; 20.6 ± 10.6 ng/ml vs. 4.5 ± 1.4 ng/ml, p = 0.03, respectively). Corresponding serum samples revealed higher levels of MUC5AC in high-risk compared with low-risk patients (19.9 ± 9.3 ng/ml vs. 2.2 ± 1.1 ng/ml, p = 0.04). Histopathologic subtype was significantly associated with grade of dysplasia, and the intestinal subtype displayed increased MUC2 cyst fluid concentrations (13.8 ± 6.5 ng/ml vs. 4.1 ± 0.9 ng/ml, p = 0.02)., Conclusions: In this study, high-risk IPMN showed elevated cyst fluid concentrations of MUC2 and MUC4, and increased serum levels of MUC5AC. High-risk IPMN also displayed a distinct mucin expression profile in specific histologic subtypes. These data, if validated, may allow surgeons to more appropriately select patients for operative resection.

Background: Positive peritoneal cytology is a predictor of poor survival in patients with gastric cancer. Our aim is to more clearly define the natural history of this cohort., Methods: Review of a prospectively maintained gastric cancer database of patients who had diagnostic laparoscopy with peritoneal washings. Clinicopathologic and treatment-related variables were obtained. Univariate and multivariate analyses were performed for factors associated with disease-specific survival (DSS)., Results: From January 1993 to April 2009, a total of 1241 patients with gastric cancer underwent laparoscopy with peritoneal washings; 291 (23%) had positive cytology. There were 198 patients (68%) who had visible metastases discovered at laparoscopy (M1), and 93 patients (32%) were without gross evidence of advanced disease (M1 Cyt+). The median DSS for the entire cohort was 1 year; for M1, DSS was 0.8 years, and for M1 Cyt+ , DSS was 1.3 years. At baseline, independent predictors of worse DSS were poor performance status, M1 disease, and diffuse tumors. Among the subset of patients with M1 Cyt+ disease, performance status was the strongest independent predictor of DSS. A total of 48 of the 291 Cyt+ patients had repeat staging laparoscopy after chemotherapy. Compared with patients who had persistently positive cytology (n = 21), those who converted to negative cytology (n = 27) had a significant improvement in DSS (2.5 years vs. 1.4 years, P = 0.0003)., Conclusions: Patients with positive cytology as the only evidence of advanced disease exhibit a poor outcome; however, clearing of Cyt+ disease by chemotherapy is associated with a statistically significant improvement in DSS. The role for gastrectomy in patients with positive peritoneal cytology remains uncertain.

Background: Although cyst fluid carcinoembryonic antigen (CEA; > 192 ng/ml) is the preferred test for identifying mucinous pancreatic cysts, the data are more robust for mucinous cystic neoplasms (MCN) than for intraductal papillary mucinous neoplasms (IPMN). The role of cyst fluid CEA as a marker for either malignancy or malignant progression is uncertain., Methods: All patients with pancreatic cysts who had undergone endoscopic ultrasound with cyst fluid CEA measurement between 2001 and 2009 were identified. Patient outcomes and pathology from operative resections were recorded., Results: Two hundred sixty-seven patients were identified; pathological diagnosis was obtained in 97. Mucinous cysts were identified in 66 of 97 (68%): benign IPMN, n = 42; malignant IPMN, n = 10; benign MCN, n = 12; malignant MCN, n = 2. CEA > 192 ng/mL had a sensitivity and specificity of 73% and 65% for identifying mucinous cysts; cyst fluid CEA was not associated with malignancy (p = 0.85). One hundred seventy-eight patients were managed with an initial non-operative strategy. Eight (4%) developed radiographic changes necessitating surgery; pathology demonstrated seven benign mucinous cysts and one retention cyst. CEA was not associated with radiographic progression (p = 0.37)., Conclusions: Cyst fluid CEA is a useful test for identifying mucinous cysts, including MCN and IPMN. In mucinous cysts, cyst fluid CEA is not associated with malignancy or radiographic progression.

Background: Tissue banking has become a major initiative at many oncology centers. The influence of warm ex-vivo ischemia times, storage times, and biobanking protocols on RNA integrity and subsequent microarray data is not well documented., Methods: A prospective institutional review board-approved protocol for the banking of abdominal neoplasms was initiated at Memorial Sloan-Kettering Cancer Center in 2001. Sixty-four representative pancreas cancer specimens snap-frozen at various ex-vivo procurement times (< or =10 min, 11-30 min, 31-60 min, >1 h) and banked during three time periods (2001-2004, 2004-2006, 2006-2008) were processed. RNA integrity was determined by microcapillary electrophoresis using the RNA integrity number (RIN) algorithm and by results of laser-capture microdissection (LCM)., Results: Overall, 42% of human pancreas cancer specimens banked under a dedicated protocol yielded RNA with a RIN of > or =7. Limited warm ex-vivo ischemia times did not negatively impact RNA quality (percentage of tissue with total RNA with RIN of > or =7 for < or =10 min, 42%; 11-30 min, 58%; 31-60 min, 33%; >60 min, 42%), and long-term storage of banked pancreas cancer biospecimens did not negatively influence RNA quality (total RNA with RIN of > or =7 banked 2001-2004, 44%; 2004-2006, 38%; 2006-2008, 50%). RNA retrieved from pancreatic cancer samples with RIN of > or =7 subject to LCM yielded RNA suitable for further downstream applications., Conclusions: Fresh-frozen pancreas tissue banked within a standardized research protocol yields high-quality RNA in approximately 50% of specimens and can be used for enrichment by LCM. Quality of tissues of the biobank were not adversely impacted by limited variations of warm ischemia times or different storage periods. This study shows the challenges and investments required to initiate and maintain high-quality tissue repositories.

Introduction: Randomized trials, meta-analyses, and guidelines form the basis of clinical decision making. We queried a small sample of surgeons at three academic medical centers to determine whether key elements of surgical practice were concordant with available evidence., Materials and Methods: A French Society of Digestive Surgery (FSDS) questionnaire was submitted to general surgery trainees and faculty at the University of South Florida and University of Chicago and to surgical oncology fellows at the Memorial Sloan-Kettering Cancer Center. Participants were asked to respond "never," "rarely," "often," or "always" to 13 questions involving different aspects of gastrointestinal surgery. For each question, a correct evidence-based answer was available from published studies., Results and Discussion: One hundred ten surgeons (79% of eligible participants) completed the survey. Only 60% of the answers were concordant with existing data. The percentages of correct answers did not differ significantly according to institution or level of experience of participants. The low frequency of correct responses in our subjects paralleled the findings from the 2004 FSDS study. Variability in the quality of evidence and ambiguity in the survey questions may have influenced the responses, but evidence-based medicine does not appear to uniformly influence clinical decision making.

Background: Preoperative biliary drainage (PBD) prior to pancreaticoduodenectomy (PD) continues to be routine in many centers despite retrospective and randomized data showing that PBD increases perioperative infectious complications., Methods: Review of a prospectively maintained database identified 340 consecutive patients with pancreatic adenocarcinoma who underwent PD between 2000 and 2005. From this cohort, 94 PBD and 94 nonstented (no-PBD) patients were matched for age, gender, preoperative albumin, and bilirubin levels (PBD group: prestent bilirubin; no-PBD group: preoperative bilirubin)., Results: The majority of PBD patients (89%) underwent internal endoscopic biliary drainage. Stent-related complications occurred in 46 patients (23%) and resulted in a significant delay in time to resection. In the matched-pair comparison, there was more operative blood loss in PBD patients, but similar operative times, transfusions, and hospital stay. Bile cultures were positive in 82% of PBD patients versus 7% no PBD. There was a statistically significant increase in infectious complications including wound infections and intra-abdominal abscess in PBD patients, but equal incidence of anastomotic leak., Conclusions: In this case-matched control study, PBD was associated with a stent-related complication rate of 23% and resulted in a twofold increase in postpancreatectomy infectious complications. The routine use of PBD remains unjustified.

Background: Most gastric carcinoid tumors (GC) (type I) occur in association with achlorhydria, hypergastrinemia, atrophic gastritis and exhibit low-grade histopathology. The management of this indolent disease is controversial. The aim of this study was to evaluate endoscopic surveillance (ES) compare with surgical resection (SR) for type I GC., Methods: Between 1985 and 2007, 65 patients with type IGC were identified. Data analysis included: demographics, biochemical and endoscopic assessment, type of operation performed, and pathologic evaluation. The primary endpoints were disease-specific survival (DSS) in both groups and recurrence-free survival (RFS) in SR patients., Results: Median follow-up was 30 months (range 1-176 months); most patients were female (83%) with median age of 58 years (range 29-91 years). Type I GC was diagnosed by evidence of hypergastrinemia and/or positive autoimmune antibodies with histopathologic confirmation. Patients underwent ES with polypectomy (n=46) or gastric resection (n=19). SR was performed with larger tumor size, increased depth of invasion, and solitary tumors. Although the 5-year RFS in SR patients was 75%, the DSS in both groups was 100%. However, concomitant adenocarcinoma was identified in 4/19 resected cases; 2/4 were detected on preoperative biopsies. All cases with coexisting gastric adenocarcinoma had larger carcinoid tumors and more advanced carcinoid disease., Conclusions: The DSS is excellent for type I GC patients treated with either ES or SR. SR should be considered with more advanced carcinoid disease given its association with an increased risk of adenocarcinoma. ES is appropriate to assess both the status of carcinoid disease and dysplasia or adenocarcinoma that can develop in association with type I GC.

Objective: The aim of this study is to compare technical feasibility and oncologic efficacy of totally laparoscopic versus open subtotal gastrectomy for gastric adenocarcinoma., Background: Laparoscopic gastrectomy for adenocarcinoma is emerging in the West as a technique that may offer benefits for patients, although large-scale studies are lacking., Methods: This study was designed as a case-controlled study from a prospective gastric cancer database. Thirty consecutive patients undergoing laparoscopic subtotal gastrectomy for adenocarcinoma were compared with 30 patients undergoing open subtotal gastrectomy. Controls were matched for stage, age, and gender via a statistically generated selection of all gastrectomies performed during the same period of time. Patient demographics, tumor-node-metastasis (TNM) stage, histologic features, location of tumor, lymph node retrieval, recurrence, margins, and early and late postoperative complications were compared., Results: Tumor location and histology were similar between the two groups. Median operative time for the laparoscopic approach was 270 min (range 150-485 min) compared with median of 126 min (range 85-205 min) in the open group (p < 0.01). Hospital length of stay after laparoscopic gastrectomy was 5 days (range 2-26 days), compared with 7 days (range 5-30 days) in the open group (p = 0.01). Postoperative pain, as measured by number of days of IV narcotic use, was significantly lower for laparoscopic patients, with a median of 3 days (range 0-11 days) compared with 4 days (range 1-13 days) in the open group (p < 0.01). Postoperative early complications trended towards a decrease for laparoscopic versus open surgery patients (p = 0.07); however, there were significantly more late complications for the open group (p = 0.03). Short-term recurrence-free survival and margin status was similar between the two groups (p = not significant) with adequate lymph node retrieval in both groups., Conclusions: Laparoscopic subtotal gastrectomy for adenocarcinoma is comparable to the open approach with regard to oncologic principles of resection, with equivalent margin status and adequate lymph node retrieval, demonstrating technically feasibility and equivalent short-term recurrence-free survival. Additional benefits of decreased postoperative complications, decreased length of hospital stay, and decreased narcotic use make this a preferable approach for selected patients.

Background: The clinical significance of immunohistochemically detected isolated tumor cells (ITC) in lymph nodes of gastric cancer patients is controversial. This study examined the prognostic impact of ITC on patients with early-stage gastric cancer in two large volume centers in the United States and Japan., Methods: Fifty-seven patients with T2N0M0 gastric carcinoma who underwent gastric resection between January 1987 and January 1997 at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York and 107 patients resected at National Cancer Center Hospital (NCCH) in Tokyo between January 1984 and December 1990 were studied. The sections were newly prepared from each lymph node for immunohistochemical staining for cytokeratin. Lymph nodes and original specimens from MSKCC were examined by pathologists in NCCH. The prognostic significance of the presence of ITC in lymph nodes was investigated in patients of both institutions., Results: ITC were identified in 30 of 57 patients (52.6%) at MSKCC and in 38 of 107 patients (35.5%) at NCCH. In both institutions, there was no significant difference in the prognosis of the studied patients with or without ITC (P= .22, .86 respectively)., Conclusions: The presence of ITC detected by immunohistochemistry in the regional lymph nodes did not affect the prognosis of American and Japanese patients with T2N0M0 gastric carcinoma who underwent gastrectomy with D2 lymph node dissection.

Background: Staging laparoscopy for patients with radiographically resectable pancreatic adenocarcinoma has been reported to yield an 8-15% finding of unresectable disease. Factors associated with the likelihood of subradiographic unresectable disease have not been clearly defined., Methods: A prospectively maintained pancreatic database was reviewed and patients were identified who underwent staging laparoscopy for radiographically resectable pancreatic adenocarcinoma between January 2000 and December 2006. Preoperative carbohydrate antigen 19-9 (CA 19-9) values were assessed for their association with the presence of subradiographic unresectable disease., Results: Four hundred ninety-one patients underwent staging laparoscopy. Resection was performed in 80% (n = 395). Of the 96 patients with unresectable disease, 75 (78%) had metastases either in the liver (n = 60) or peritoneum (n = 15). Preoperative CA 19-9 values were available for 262 of the 491 patients. Fifty-one of these patients had unresectable disease, of which 78% were due to distant disease. The median preoperative CA 19-9 value for patients who underwent resection was 131 U/ml versus 379 U/ml for those patients with unresectable disease (P = 0.003). A receiver operating characteristics (ROC) curve was developed for preoperative CA 19-9 value and tumor resectability. The statistically optimal cutoff value was determined to be 130 U/ml. Unresectable disease was identified in 38 of the 144 patients (26.4%) with a preoperative CA 19-9 >or= 130 U/ml, and in 13 of the 118 patients (11%) with a CA 19-9 < 130 U/ml (P = 0.003). CA 19-9 values greater than 130 U/ml remained a predictor of tumor unresectability on multivariate regression analysis [hazard ratio (HR) 2.70, 95% confidence interval (CI) 1.34-5.44; P = 0.005]., Conclusion: In this study, preoperative CA 19-9 values were strongly associated with the identification of subradiographic unresectable disease. Preoperative CA 19-9 values may allow surgeons to better select patients for staging laparoscopy.