Improved Adherence to ATA Medullary Thyroid Cancer Treatment Guidelines.

BACKGROUND: The 2009 American Thyroid Association (ATA) guidelines for medullary thyroid cancer (MTC) were created to unify national practice patterns. Our aims were to (1) evaluate national adherence to ATA guidelines before and after 2009, (2) identify factors that are associated with concordance with guidelines, and (3) evaluate whether there is an association between survival and concordant treatment. PATIENTS AND METHODS: Patients with MTC were identified from the 2009 to 2015 National Cancer Database. Adherence to ATA recommendations regarding extent of surgery (R61-R66) was analyzed. Logistic regression was used to determine predictors of discordance and propensity score matching was used to compare concordant treatment rates between time periods. Kaplan-Meier survival analysis was used to determine association between survival and concordant treatment. RESULTS: There were 3421 patients with MTC, and of these 3087 had M0 disease and 334 had M1 disease. We found that 72% of M0 cases adhered to R61-66, and 68% of M0 cases without advanced local disease were adherent to R61-63. Following propensity score matching, the adherence rate was 67% before 2009 and 74% after. Patient factors associated with discordant treatment were female gender, older age, treatment at a nonacademic facility, and living within 50 miles of the treatment facility. Adherence to guidelines was associated with improved overall survival (OS) (p < 0.01). CONCLUSIONS: Treatment of MTC was discordant from guidelines in 26% of cases from 2009 to 2015 compared with 33% prior to 2009 in a propensity matched analysis, and was most often in cases with localized, noninvasive disease. Improved adherence to guidelines may improve overall survival.

Environmental Chemicals and their Association with Hyperparathyroidism.

BACKGROUND: The incidence of hyperparathyroidism has increased in the USA. The previous work from our institution detected environmental chemicals (EC) within hyperplastic parathyroid tumors. The National Health and Nutrition Examination Survey (NHANES) is a program designed to assess the health status of people in the USA and includes measurements of EC in serum. Our aim was to determine which EC are associated with elevated parathyroid hormone (PTH) and calcium levels within NHANES. METHODS: NHANES was queried from 2003-2016 for our analysis with calcium. A separate subgroup was queried from 2003-2006 that included PTH levels. Subjects with elevated calcium, and elevated PTH and normal Vitamin D levels were identified. Wilcoxon rank sum tests were used to analyze levels of EC in those with elevated calcium, and those with elevated PTH in the subgroup. All EC with p < 0.05 were then included in separate multivariate models adjusting for serum vitamin D and creatinine for PTH and albumin for calcium. RESULTS: There were 51,395 subjects analyzed, and calcium was elevated in 2.1% (1080) of subjects. Our subgroup analysis analyzed 14,681 subjects, and PTH was elevated without deficient Vitamin D in 9.4% (1,377). Twenty-nine different polychlorinated biphenyls and the organochlorine pesticides hexachlorobenzene, transnonachlor, oxychlordane, and p,p'-dichlorodiphenyldichloroethylene (DDE) were found to be associated with elevated calcium and separately with elevated PTH (all p < 0.05). CONCLUSION: In NHANES, 33 ECs were found to be associated with elevated calcium as well as elevated PTH levels on our subgroup analysis. These chemicals may lead us toward a causal link between environmental factors and the development of hyperparathyroidism and should be the focus of future studies looking at chemical levels within specimens.

Development of a Prognostic Nomogram and Nomogram Software Application Tool to Predict Overall Survival and Disease-Free Survival After Curative-Intent Gastrectomy for Gastric Cancer.

BACKGROUND: We sought to derive and validate a prediction model of survival and recurrence among Western patients undergoing resection of gastric cancer. METHODS: Patients who underwent curative-intent surgery for gastric cancer at seven US institutions and a major Italian center from 2000 to 2020 were included. Variables included in the multivariable Cox models were identified using an automated model selection procedure based on an algorithm. Best models were selected using the Bayesian information criterion (BIC). The performance of the models was internally cross-validated via the bootstrap resampling procedure. Discrimination was evaluated using the Harrell's Concordance Index and accuracy was evaluated using calibration plots. Nomograms were made available as online tools. RESULTS: Overall, 895 patients met inclusion criteria. Age (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.17-1.84), presence of preoperative comorbidities (HR 1.66, 95% CI 1.14-2.41), lymph node ratio (LNR; HR 1.72, 95% CI 1.42-2.01), and lymphovascular invasion (HR 1.81, 95% CI 1.33-2.45) were associated with overall survival (OS; all p < 0.01), whereas tumor location (HR 1.93, 95% CI 1.23-3.02), T category (Tis-T1 vs. T3: HR 0.31, 95% CI 0.14-0.66), LNR (HR 1.82, 95% CI 1.45-2.28), and lymphovascular invasion (HR 1.49; 95% CI 1.01-2.22) were associated with disease-free survival (DFS; all p < 0.05) The models demonstrated good discrimination on internal validation relative to OS (C-index 0.70) and DFS (C-index 0.74). CONCLUSIONS: A web-based nomograms to predict OS and DFS among gastric cancer patients following resection demonstrated good accuracy and discrimination and good performance on internal validation.

Prognostic Impact of Serum Pancreastatin Following Chemoembolization for Neuroendocrine Tumors.

PURPOSE: The objective of this study was to investigate the prognostic impact of the biomarker serum pancreastatin in patients with metastatic neuroendocrine tumors (NETs) treated with transarterial chemoembolization (TACE). METHODS: Patients with metastatic NET treated with TACE at a single institution from 2000 to 2013 were analyzed. Patient demographics, response to therapy, and long-term survival were compared with baseline pancreastatin level and changes in pancreastatin levels after TACE. RESULTS: A total of 188 patients underwent TACE during the study period. An initial pancreastatin level greater than 5000 pg/mL correlated with worse overall survival (OS) from time of first TACE (median OS, 58.5 vs. 22.1 months, p < 0.001). A decrease in pancreastatin level by 50% or more after TACE treatment correlated with improved OS (median OS 53.8 vs. 29.9 months, p = 0.032). Patients with carcinoid syndrome were more likely to have a subsequent increase in pancreastatin after initial drop post-TACE (78.1 vs. 55.2%, p = 0.002). Patients with an increase in pancreastatin levels after initial drop post-TACE were more likely to have liver progression on imaging (70.7 vs. 40.7%, p = 0.005) and more likely to need repeat TACE (21.1 vs. 6.7%, p = 0.009). CONCLUSIONS: For patients with liver metastases from NET treated with TACE, pancreastatin measurement may be a useful prognostic indicator. Extreme high levels before TACE can predict poor outcomes, whereas significant drops in pancreastatin after TACE correlate with improved survival. An increase in levels after initial decrease may predict progressive liver disease requiring repeat TACE. As such, pancreastatin levels should be measured throughout the TACE treatment period.

Neutrophil Lymphocyte Ratio and Transarterial Chemoembolization in Neuroendocrine Tumor Metastases.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has been shown to be predictive of outcomes in various cancers, including neuroendocrine tumors (NETs), and cancer-related treatments, including transarterial chemoembolization (TACE). We hypothesized that NLR could be predictive of response to TACE in patients with metastatic NET. METHODS: We reviewed 262 patients who underwent TACE for metastatic NET at a single tertiary medical center from 2000 to 2016. NLR was calculated from blood work drawn 1 d before TACE, as well as 1 d, 1 wk, and 6 mo after treatment. RESULTS: The median post-TACE overall survival (OS) of the entire cohort was 30.1 mo. Median OS of patients with a pre-TACE NLR ≤ 4 was 33.3 mo versus 21.1 mo for patients with a pre-TACE NLR >4 (P = 0.005). At 6 mo, the median OS for patients with post-TACE NLR > pre-TACE NLR was 21.4 mo versus 25.8 mo for patients with post-TACE NLR ≤ pre-TACE NLR (P = 0.007). On multivariate analysis, both pre-TACE NLR and 6-mo post-TACE NLR were independent predictors of survival. NLR values from 1-d and 1-wk post-TACE did not correlate with outcome. CONCLUSIONS: An elevated NLR pre-TACE and an NLR that has not returned to its pre-TACE value several months after TACE correlate with outcomes in patients with NET and liver metastases. This value can easily be calculated from laboratory results routinely obtained as part of preprocedural and postprocedural care, potential treatment strategies.

Genetic and Pathological Assessment of hnRNPA1, hnRNPA2/B1, and hnRNPA3 in Familial and Sporadic Amyotrophic Lateral Sclerosis.

BACKGROUND: Mutations in the genes encoding the heterogeneous nuclear ribonucleoproteins hnRNPA1 and hnRNPA2/B1 have been reported in a multisystem proteinopathy that includes amyotrophic lateral sclerosis (ALS) and inclusion body myopathy associated with Paget disease of the bone and frontotemporal dementia. Mutations were also described in the prion-like domain of hnRNPA1 in patients with classic ALS. Another hnRNP protein, hnRNPA3, has been found to be associated with the ALS/frontotemporal dementia protein C9orf72. OBJECTIVE: To further assess their role in ALS, we examined these hnRNPs in spinal cord tissue from sporadic (SALS) and familial ALS (FALS) patients, including C9orf72 repeat expansion-positive patients, and controls. We also sought to determine the prevalence of HNRNPA1, HNRNPA2B1, and HNRNPA3 mutations in Australian ALS patients. METHODS: Immunostaining was used to assess hnRNPs in ALS patient spinal cords. Mutation analysis of the HNRNPA1, HNRNPA2B1, and HNRNPA3 genes was performed in FALS and of their prion-like domains in SALS patients. RESULTS: Immunostaining of spinal motor neurons of ALS patients with the C9orf72 repeat expansion showed significant mislocalisation of hnRNPA3, and no differences in hnRNPA1 or A2/B1 localisation, compared to controls. No novel or known mutations were identified in HNRNPA1, HNRNPA2B1, or HNRNPA3 in Australian ALS patients. CONCLUSIONS: hnRNPA3 pathology was identified in motor neurons of ALS patients with C9orf72 repeat expansions, implicating hnRNPA3 in the pathogenesis of C9orf72-linked ALS. hnRNPA3 warrants further investigation into the pathogenesis of ALS linked to C9orf72. This study also determined that HNRNP mutations are not a common cause of FALS and SALS in Australia.

Interaction of Postoperative Morbidity and Receipt of Adjuvant Therapy on Long-Term Survival After Resection for Gastric Adenocarcinoma: Results From the U.S. Gastric Cancer Collaborative.

BACKGROUND: Postoperative complications (POCs) can negatively impact survival after oncologic resection. POCs may also decrease the rate of adjuvant therapy completion. We evaluated the impact of complications on gastric cancer survival and analyzed the combined effect of complications and adjuvant therapy on survival. METHODS: We analyzed 824 patients from 7 institutions of the U.S. Gastric Cancer Collaborative who underwent curative resection for gastric adenocarcinoma between 2000 and 2012. POC were graded using the modified Clavien-Dindo system. Survival probabilities were estimated using the method of Kaplan and Meier and analyzed using multivariate Cox regression. RESULTS: Median follow-up was 35 months. The overall complication rate was 41 %. The 5-year overall survival (OS) and recurrence-free survival (RFS) of patients who experienced complications were 27 and 23 %, respectively, compared with 43 and 40 % in patients who did not have complications (p < 0.0001 for OS and RFS). On multivariate analysis, POC remained an independent predictor for decreased OS and RFS (HR 1.3, 95 % CI 1.1-1.6, p = 0.03 for OS; HR 1.3, 95 % CI 1.01-1.6, p = 0.03 for RFS). Patients who experienced POC were less likely to receive adjuvant therapy (OR 0.5, 95 % CI 0.3-0.7, p < 0.001). The interaction of complications and failure to receive adjuvant therapy significantly increased the hazard of death compared with patients who had neither complications nor adjuvant therapy (HR 2.3, 95 % CI 1.6-3.2, p < 0.001). CONCLUSIONS: Postoperative complications adversely affect long-term outcomes after gastrectomy for gastric cancer. Not receiving adjuvant therapy in the face of POC portends an especially poor prognosis following gastrectomy for gastric cancer.

Preoperative Helicobacter pylori Infection is Associated with Increased Survival After Resection of Gastric Adenocarcinoma.

BACKGROUND: Limited data exist on the prognosis of preoperative Helicobacter pylori (H. pylori) infection in gastric adenocarcinoma (GAC). METHODS: Patients who underwent curative-intent resection for GAC from 2000 to 2012 at seven academic institutions comprising the United States Gastric Cancer Collaborative were included in the study. The primary end points of the study were overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS). RESULTS: Of 559 patients, 104 (18.6 %) who tested positive for H. pylori were younger (62.1 vs 65.1 years; p = 0.041), had a higher frequency of distal tumors (82.7 vs 71.9 %; p = 0.033), and had higher rates of adjuvant radiation therapy (47.0 vs 34.9 %; p = 0.032). There were no differences in American Society of Anesthesiology (ASA) class, margin status, grade, perineural invasion, lymphovascular invasion, nodal metastases, or tumor-node-metastasis (TNM) stage. H. pylori positivity was associated with longer OS (84.3 vs 44.2 months; p = 0.008) for all patients. This relationship with OS persisted in the multivariable analysis (HR 0.54; 95 % CI 0.30-0.99; p = 0.046). H. pylori was not associated with RFS or DSS in all patients. In the stage 3 patients, H. pylori was associated with longer OS (44.5 vs 24.7 months; p = 0.018), a trend of longer RFS (31.4 vs 21.6 months; p = 0.232), and longer DSS (44.8 vs 27.2 months; p = 0.034). CONCLUSIONS: Patients with and without preoperative H. pylori infection had few differences in adverse pathologic features at the time of gastric adenocarcinoma resection. Despite similar disease presentations, preoperative H. pylori infection was independently associated with improved OS. Further studies examining the interaction between H. pylori and tumor immunology and genetics are merited.

VariantSpark: population scale clustering of genotype information.

BACKGROUND: Genomic information is increasingly used in medical practice giving rise to the need for efficient analysis methodology able to cope with thousands of individuals and millions of variants. The widely used Hadoop MapReduce architecture and associated machine learning library, Mahout, provide the means for tackling computationally challenging tasks. However, many genomic analyses do not fit the Map-Reduce paradigm. We therefore utilise the recently developed SPARK engine, along with its associated machine learning library, MLlib, which offers more flexibility in the parallelisation of population-scale bioinformatics tasks. The resulting tool, VARIANTSPARK provides an interface from MLlib to the standard variant format (VCF), offers seamless genome-wide sampling of variants and provides a pipeline for visualising results. RESULTS: To demonstrate the capabilities of VARIANTSPARK, we clustered more than 3,000 individuals with 80 Million variants each to determine the population structure in the dataset. VARIANTSPARK is 80 % faster than the SPARK-based genome clustering approach, ADAM, the comparable implementation using Hadoop/Mahout, as well as ADMIXTURE, a commonly used tool for determining individual ancestries. It is over 90 % faster than traditional implementations using R and Python. CONCLUSION: The benefits of speed, resource consumption and scalability enables VARIANTSPARK to open up the usage of advanced, efficient machine learning algorithms to genomic data.

Prognostic Performance of Different Lymph Node Staging Systems After Curative Intent Resection for Gastric Adenocarcinoma.

OBJECTIVE: To compare the prognostic performance of American Joint Committee on Cancer/International Union Against Cancer seventh N stage relative to lymph node ratio (LNR), log odds of metastatic lymph nodes (LODDS), and N score in gastric adenocarcinoma. BACKGROUND: Metastatic disease to the regional LN basin is a strong predictor of worse long-term outcome following curative intent resection of gastric adenocarcinoma. METHODS: A total of 804 patients who underwent surgical resection of gastric adenocarcinoma were identified from a multi-institutional database. The relative discriminative abilities of the different LN staging/scoring systems were assessed using the Akaike's Information Criterion (AIC) and the Harrell's concordance index (c statistic). RESULTS: Of the 804 patients, 333 (41.4%) had no lymph node metastasis, whereas 471 (58.6%) had lymph node metastasis. Patients with ≥N1 disease had an increased risk of death (hazards ratio = 2.09, 95% confidence interval: 1.68-2.61; P < 0.001]. When assessed using categorical cutoff values, LNR had a somewhat better prognostic performance (C index: 0.630; AIC: 4321.9) than the American Joint Committee on Cancer seventh edition (C index: 0.615; AIC: 4341.9), LODDS (C index: 0.615; AIC: 4323.4), or N score (C index: 0.620; AIC: 4324.6). When LN status was modeled as a continuous variable, the LODDS staging system (C index: 0.636; AIC: 4304.0) outperformed other staging/scoring systems including the N score (C index: 0.632; AIC: 4308.4) and LNR (C index: 0.631; AIC: 4225.8). Among patients with LNR scores of 0 or 1, there was a residual heterogeneity of outcomes that was better stratified and characterized by the LODDS. CONCLUSIONS: When assessed as a categorical variable, LNR was the most powerful manner to stratify patients on the basis of LN status. LODDS was a better predicator of survival when LN status was modeled as a continuous variable, especially among those patients with either very low or high LNR.

Factors Associated With Recurrence and Survival in Lymph Node-negative Gastric Adenocarcinoma: A 7-Institution Study of the US Gastric Cancer Collaborative.

OBJECTIVES: To determine pathologic features associated with recurrence and survival in patients with lymph node-negative gastric adenocarcinoma. STUDY DESIGN: Multi-institutional retrospective analysis. BACKGROUND: Lymph node status is among the most important predictors of recurrence after gastrectomy for gastric adenocarcinoma. Pathologic features predictive of recurrence in patients with node-negative disease are less well established. METHODS: Patients who underwent curative resection for gastric adenocarcinoma between 2000 and 2012 from 7 institutions of the US Gastric Cancer Collaborative were analyzed, excluding 30-day mortalities and stage IV disease. Competing risks regression and multivariate Cox regression were used to determine pathologic features associated with time to recurrence and overall survival. Differences in cumulative incidence of recurrence were assessed using the Gray method (for univariate nonparametric analyses) and the Fine and Gray method (for multivariate analyses) and shown as subhazard ratios (SHRs) and adjusted subhazard ratios (aSHRs), respectively. RESULTS: Of 805 patients who met inclusion criteria, 317 (39%) had node-negative disease, of which 54 (17%) recurred. By 2 and 5 years, 66% and 88% of patients, respectively, experienced recurrence. On multivariate competing risks regression, only T-stage 3 or higher was associated with shorter time to recurrence [aSHR = 2.7; 95% confidence interval (CI), 1.5-5.2]. Multivariate Cox regression showed T-stage 3 or higher [hazard ratio (HR) = 1.8; 95% CI, 1.2-2.8], lymphovascular invasion (HR = 2.2; 95% CI, 1.4-3.4), and signet ring histology (HR = 2.1; 95% CI, 1.2-3.6) to be associated with decreased overall survival. CONCLUSIONS: Despite absence of lymph node involvement, patients with T-stage 3 or higher have a significantly shorter time to recurrence. These patients may benefit from more aggressive adjuvant therapy and postoperative surveillance regimens.

Conditional survival after surgical resection of gastric cancer: a multi-institutional analysis of the us gastric cancer collaborative.

BACKGROUND: Survival estimates following surgical resection of gastric adenocarcinoma are traditionally reported as survival from the date of surgery. Conditional survival (CS) estimates, however, may be more clinically relevant by accounting for time already survived. We assessed CS following surgical resection for gastric adenocarcinoma. METHODS: We analyzed 807 patients who underwent resection for gastric adenocarcinoma from 2000 to 2012 at seven participating institutions in the U.S. Gastric Cancer Collaborative. Cox proportional hazards models were used to evaluate factors associated with overall survival. Three-year CS estimates at "x" year after surgery were calculated as follows: CS3 = S(x+3)/S(x). RESULTS: Overall 1-, 3-, and 5-year overall survival rates after gastric resection were 42, 34, and 30 %, respectively. Using CS estimates, the probability of surviving an additional 3 years given that the patient had survived at 1, 3, and 5 years were 56, 71, and 82 %, respectively. Patients with higher risk at baseline (i.e., stage III or IV disease, lymphovascular invasion) demonstrated the greatest increase in CS over time. CONCLUSIONS: Survival estimates following surgical resection of gastric adenocarcinoma is dynamic; the probability of survival increases with time already survived. Patients with worse prognostic features at the time of surgery had the greatest increases in CS over time. Conditional survival estimates provide important information about the changing probability of survival over time and should be used among patients with resected gastric adenocarcinoma to guide subsequent follow-up strategies.

A nomogram to predict overall survival and disease-free survival after curative resection of gastric adenocarcinoma.

BACKGROUND: The American Cancer Society projects there will be over 22,000 new cases, resulting in nearly 11,000 deaths, related to gastric adenocarcinoma in the US in 2014. The aim of the current study was to find clinicopathologic variables associated with disease-free survival (DFS) and overall survival (OS) following curative resection of gastric adenocarcinoma, and create a nomogram for individual risk prediction. METHODS: A nomogram to predict DFS and OS following surgical resection of gastric adenocarcinoma was constructed using a multi-institutional cohort of patients who underwent surgery for primary gastric adenocarcinoma at seven major institutions in the US between January 2000 and August 2013. Discrimination and calibration of the nomogram were tested by C-statistic, Kaplan-Meier curves, and calibration plots. RESULTS: A total of 719 patients who underwent surgery for primary gastric adenocarcinoma were included in the study. Using the backward selection of clinically relevant variables with Akaike information criteria, age, sex, tumor site, depth of invasion, and lymph node ratio (LNR) were selected as factors predictive of OS, while age, tumor site, depth of invasion, and LNR were incorporated in the prediction of DFS. A nomogram was constructed to predict OS and DFS using these variables. Discrimination and calibration of the nomogram revealed good predictive abilities (C-index, DFS 0.711; OS 0.702). CONCLUSION: Independent predictors of recurrence and death following surgery for primary gastric adenocarcinoma were used to create a nomogram to predict DFS and OS. The nomogram was able to stratify patients into prognostic groups, and performed well on internal validation.

Value of Peritoneal Drain Placement After Total Gastrectomy for Gastric Adenocarcinoma: A Multi-institutional Analysis from the US Gastric Cancer Collaborative.

BACKGROUND: The effect of routine drainage after abdominal surgery with enteric anastomoses is controversial. In particular, the role of peritoneal drain (PD) placement after total gastrectomy for adenocarcinoma is not well established. METHODS: Patients who underwent total gastrectomy for gastric adenocarcinoma (GAC) at seven institutions from the US Gastric Cancer Collaborative, from 2000 to 2012, were identified. The association of PD placement with postoperative outcomes was analyzed. RESULTS: Overall, 344 patients were identified and 253 (74 %) patients received a PD. The anastomotic leak rate was 9 %. Those with PD placement had similar American Society of Anesthesiologists score, tumor size, TNM stage, and the need for additional organ resection when compared with their counterparts. No difference was observed in the rate of any complication (54 vs. 48 %; p = 0.45), major complication (25 vs. 24 %; p = 0.90), or 30-day mortality (7 vs. 4 %; p = 0.51) between the two groups. In addition, no difference in anastomotic leak (9 vs. 10 %; p = 0.90), the need for secondary drainage (10 vs. 9 %; p = 0.92), or reoperation (13 vs. 8 %; p = 0.28) was identified. On multivariate analysis, PD placement was not associated with decreased postoperative complications. Subset analysis, stratified by patients who did not undergo concomitant pancreatectomy (n = 319) or those who experienced anastomotic leak (n = 31), similarly demonstrated no association of PD placement with reduced complications or mortality. CONCLUSIONS: PD placement after total gastrectomy for GAC is associated with neither a decrease in the frequency and severity of adverse postoperative outcomes, including anastomotic leak and mortality, nor a decrease in the need for secondary drainage procedures or reoperation. Routine use of PDs is not warranted.

The Prognostic Value of Signet-Ring Cell Histology in Resected Gastric Adenocarcinoma.

BACKGROUND: Conflicting data exist on the prognostic implication of signet-ring cell (SRC) histology in gastric adenocarcinoma (GAC). METHODS: All patients who underwent curative-intent resection of GAC from the seven institutions of the U.S. Gastric Cancer Collaborative between 2000 and 2012 were included. Primary end points were recurrence-free survival (RFS) and overall survival (OS). Stage-specific analyses were performed. RESULTS: A total of 768 patients met the inclusion criteria. SRC was present in 40.6 % of patients and was associated with female sex (52.9 vs. 38.6 %; p < 0.001), younger age (61 vs. 67 years; p < 0.001), poor differentiation (94.8 vs. 50.3 %; p < 0.001), perineural invasion (PNI) (41.4 vs. 23 %; p < 0.001), microscopically positive resection margins (R1, 24.7 vs. 8.6 %; p < 0.001), distal location (82.2 vs. 70.1 %; p < 0.001), receipt of adjuvant therapy (63 vs. 51.2 %; p = 0.002), and more advanced stage (stage 3: 55.2 vs. 36.5 %; p < 0.001). SRC was associated with earlier recurrence (56.7 months vs. median not reached; p = 0.009) and decreased OS (33.7 vs. 46.6 months; p = 0.011). When accounting for other adverse pathologic features, PNI (hazard ratio [HR] 1.57; p = 0.016) and higher stage (HR 2.64; p < 0.001) were associated with decreased RFS, but SRC was not. Although PNI (HR 1.52; p = 0.007), higher stage (HR 2.11; p < 0.001), greater size (HR 1.05; p = 0.016), and adjuvant therapy (HR 0.50; p < 0.001) were associated with OS, SRC was not. Similarly, when accounting for adverse pathologic factors on multivariate analysis, stage-specific analyses showed no association between SRC and RFS or OS. CONCLUSIONS: SRC histology is associated with adverse pathologic features including poor differentiation, higher stage, and microscopically positive resection margins but is not independently associated with reduced RFS or OS. Identification of signet-ring histology during preoperative evaluation should not, in isolation, dictate treatment strategy.

Is it time to abandon the 5-cm margin rule during resection of distal gastric adenocarcinoma? A multi-institution study of the U.S. Gastric Cancer Collaborative.

BACKGROUND: A proximal margin distance of 5 cm is advocated for resection of gastric adenocarcinoma (GAC). We assessed the prognostic value of proximal margin (PM) distance on survival outcomes after resection of distal GAC. METHODS: All patients who underwent resection of distal GAC (antrum/body) from 2000 to 2012 at seven institutions of the U.S. Gastric Cancer Collaborative were included. Patients with positive distal margins or macroscopic residual disease were excluded. The prognostic value of PM distance (assessed in 0.5-cm increments) on overall (OS) and recurrence-free survival (RFS) was assessed by Kaplan-Meier and multivariate regression analysis. RESULTS: A total of 465 patients underwent resection of distal GAC. Of these, 435 had R0 resections; 30 patients had a positive PM. 143 patients had stage I, and 322 had stage II-III tumors. Median follow-up was 44 months. Average PM distance was 4.8 cm. Median OS for patients with PM of 3.1-5.0 cm (n = 110) was superior to patients with PM ≤ 3.0 cm (n = 176) (48.1 vs. 29.3 months; p = 0.01), while a margin >5.0 cm (n = 179) offered equivalent survival to PM 3.1-5.0 cm (50.6 months, p = 0.72). The prognostic value of margin distance was stage specific. On multivariate analysis of stage I patients, PM 3.1-5.0 cm remained associated with improved OS [hazard ratio (HR), 0.16; 95 % confidence interval (95 % CI), 0.04-0.60; p = 0.01]. In stage II-III, neither PM 3.1-5.0 cm nor PM > 5.0 cm was significantly associated with OS; OS was dictated by T stage and nodal involvement. CONCLUSIONS: The prognostic value of proximal margin distance after resection of distal gastric cancer appears stage specific. In stage I, a 3.1- to 5.0-cm proximal margin is associated with the same improved OS as a > 5.0-cm margin. In stage II-III disease, other adverse pathologic factors more strongly impact survival than proximal margin distance.

The importance of the proximal resection margin distance for proximal gastric adenocarcinoma: A multi-institutional study of the US Gastric Cancer Collaborative.

BACKGROUND: A 5 cm margin is advocated for distal gastric adenocarcinoma (GAC). The optimal proximal resection margin (PM) length for proximal GAC is not established. METHODS: Patients who underwent curative-intent resection for proximal GAC from 2000 to 2012 at 7 centers in the US Gastric Cancer Collaborative were included. PM length was sequentially dichotomized and analyzed at 0.5 cm increments (0.5-6.5 cm). Outcomes after negative margin (R0) and positive microscopic margin (R1) resections were compared. Primary endpoints were local recurrence (LR) and overall survival (OS). RESULTS: All patients (n = 162) had R0 distal margins. 151 (93.2%) had an R0-PM with mean length of 2.6 cm (median:1.7 cm; range:0.1-15 cm). A greater PM distance was not associated with LR or OS. An R1-PM was associated with higher N-stage (N3:73% vs. 26%; P = 0.007) and increased LR (HR6.1; P = 0.009) but not associated with decreased OS. On multivariate analysis, an R1-PM was also not independently associated with LR. CONCLUSIONS: For resection of proximal gastric adenocarcinoma, proximal margin length is not associated with local recurrence or overall survival. An R1 margin is associated with advanced N-stage but is not independently associated with recurrence or survival. When performing resection of proximal gastric adenocarcinoma, efforts to achieve a specific margin distance, especially if it necessitates an esophagectomy, should be abandoned.

An assessment of feeding jejunostomy tube placement at the time of resection for gastric adenocarcinoma: A seven-institution analysis of 837 patients from the U.S. gastric cancer collaborative.

BACKGROUND: Jejunostomy feeding tubes (J-tubes) are often placed during resection for gastric adenocarcinoma (GAC). Their effect on postoperative complications and receipt of adjuvant therapy is unclear. METHODS: Patients who underwent curative-intent resection of GAC at seven institutions of the U.S. Gastric Cancer Collaborative from 2000 to 2012 were identified. The associations of J-tubes with postoperative complications and receipt of adjuvant therapy were determined. RESULTS: Of 837 patients, 265 (32%) received a J-tube. Patients receiving J-tubes demonstrated greater incidence of preoperative weight loss, lower BMI, greater extent of resection, and more advanced TNM stage. J-tube placement was associated with increased infectious complications (36% vs. 19%; P < 0.001), including surgical-site (14% vs. 6%; P < 0.001) and deep intra-abdominal (11% vs. 4%; P < 0.001) infections. On multivariate analysis, J-tubes remained independently associated with increased risk of infectious complications (all: HR = 1.93; P = 0.001; surgical-site: HR = 2.85; P = 0.001; deep intra-abdominal: HR = 2.13; P = 0.04). J-tubes were not associated with increased receipt of adjuvant therapy (HR = 0.82; P = 0.34). Subset analyses of patients undergoing total and subtotal gastrectomy similarly demonstrated an association of J-tubes with increased risk of infectious outcomes and no association with increased receipt of adjuvant therapy. CONCLUSIONS: J-tube placement after resection of gastric adenocarcinoma is associated with increased postoperative infectious outcomes and is not associated with increased receipt of adjuvant therapy. Selective use of J-tubes is recommended.

Utility of the proximal margin frozen section for resection of gastric adenocarcinoma: a 7-Institution Study of the US Gastric Cancer Collaborative.

BACKGROUND: The proximal gastric margin dictates the extent of resection for gastric adenocarcinoma (GAC). The value of achieving negative margins via additional gastric resection after a positive proximal margin frozen section (FS) is unknown. METHODS: The US Gastric Cancer Collaborative includes all patients who underwent resection of GAC at seven institutions from 2000-2012. Intraoperative proximal margin FS data and final permanent section (PS) data were classified as R0 or R1, respectively; positive distal margins were excluded. The primary aim was to evaluate the impact on local recurrence of converting a positive proximal FS-R1 margin to a PS-R0 final margin by additional resection. Secondary endpoints were recurrence-free survival (RFS) and overall survival (OS). RESULTS: Of 860 patients, 520 had a proximal margin FS and 67 were positive. Of these, 48 were converted to R0 on PS by additional resection. R0 proximal margin was achieved in 447 patients (86 %), PS-R1 in 25 (5 %), and converted FS-R1-to-PS-R0 in 48 (9 %). The median follow-up was 44 months. Local recurrence was significantly decreased in the converted FS-R1-to-PS-R0 group compared to the PS-R1 group (10 vs. 32 %; p = 0.01). Median RFS was similar between the FS-R1-to-PS-R0 and PS-R1 cohorts (25 vs. 20 months; p = 0.49), compared to 37 months for the PS-R0 group. Median OS was similar between the FS-R1-to-PS-R0 conversion and PS-R1 groups (36 vs. 26 months; p = 0.14) compared to 50 months for the PS-R0 group. On multivariate analysis, increasing T-stage and N-stage were associated with worse OS; the FS-R1-to-PS-R0 proximal margin conversion was not significantly associated with improved RFS (p = 0.68) or OS (p = 0.44). CONCLUSION: Conversion of a positive intraoperative proximal margin frozen section during gastric cancer resection may decrease local recurrence, but it is not associated with improved RFS or OS. This may guide decisions regarding the extent of resection.