Extent of Resection and Long-Term Outcomes for Appendiceal Adenocarcinoma: a SEER Database Analysis of Mucinous and non-Mucinous Histologies.

BACKGROUND: Mucinous appendiceal adenocarcinomas (MAA) and non-mucinous appendiceal adenocarcinomas (NMAA) demonstrate differences in rates and patterns of recurrence, which may inform the appropriate extent of surgical resection (i.e., appendectomy versus colectomy). The impact of extent of resection on disease-specific survival (DSS) for each histologic subtype was assessed. PATIENTS AND METHODS: Patients with resected, non-metastatic MAA and NMAA were identified in the Surveillance, Epidemiology, and End Results database (2000-2020). Multivariable models were created to examine predictors of colectomy for each histologic subtype. DSS was calculated using Kaplan-Meier estimates and examined using Cox proportional hazards modeling. RESULTS: Among 4674 patients (MAA: n = 1990, 42.6%; NMAA: n = 2684, 57.4%), the majority (67.8%) underwent colectomy. Among colectomy patients, the rate of nodal positivity increased with higher T-stage (MAA: T1: 4.6%, T2: 4.0%, T3: 17.1%, T4: 21.6%, p < 0.001; NMAA: T1: 6.8%, T2: 11.4%, T3: 25.6%, T4: 43.8%, p < 0.001) and higher tumor grade (MAA: well differentiated: 7.7%, moderately differentiated: 19.2%, and poorly differentiated: 31.3%; NMAA: well differentiated: 9.0%, moderately differentiated: 20.5%, and 44.4%; p < 0.001). Nodal positivity was more frequently observed in NMAA (27.6% versus 16.4%, p < 0.001). Utilization of colectomy was associated with improved DSS for NMAA patients with T2 (log rank p = 0.095) and T3 (log rank p = 0.018) tumors as well as moderately differentiated histology (log rank p = 0.006). Utilization of colectomy was not associated with improved DSS for MAA patients, which was confirmed in a multivariable model for T-stage, grade, and use of adjuvant chemotherapy [hazard ratio (HR) 1.00, 95% confidence interval (CI) 0.81-1.22]. CONCLUSIONS: Colectomy was associated with improved DSS for patients with NMAA but not MAA. Colectomy for MAA may not be required.

Identifying the optimal treatment strategy in patients with resectable non-cardia gastric cancer.

BACKGROUND: Multimodal treatment strategy including perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) has been accepted as the standard of care in gastric cancer (GC). The ideal sequence and type of therapy remain undetermined. METHOD: The National Cancer Database was examined from 2006 to 2016 to identify patients with resectable non-cardia gastric cancer. Patient outcomes were compared based on the receipt of PEC, POCR, and POC. This comparison was repeated in a sub-group of patients who received optimal treatment. Optimal treatment was defined as initial chemotherapy within 45 days of diagnosis, resection within 45 days of diagnosis, negative margins, adjuvant chemotherapy within 90 days of resection and standard radiation dose (45 Gy). Kaplan-Meier test, log-rank test, and multivariable analysis (MVA) were performed. RESULTS: We identified 9589 patients. Median survival was greater in the PEC group followed by POCR and POC (60.6, 42.3, and 31.2 months, respectively). On MVA, factors associated with worse overall survival included age above median (≥ 63 years), Charlson-Deyo score of ≥ 1, non-academic/research program, poorly differentiated/undifferentiated grade, positive margins, and positive lymph nodes. Both PEC and POCR were associated with improved survival when compared to POC (HR 0.78 and 0.79; p < 0.001). When compared with PEC, no significant difference was noted with POCR (HR 1.01; p = 0.987). These results were maintained in optimally treated cohort (n = 3418). CONCLUSION: In patients with resectable non-cardia gastric cancer, both perioperative chemotherapy and postoperative chemoradiation therapy were associated with improved survival when compared to postoperative chemotherapy. No difference was noted between perioperative chemotherapy and postoperative chemoradiation therapy. These results were maintained in the optimally treated cohort.

Pancreatectomy for intraductal papillary mucinous neoplasm: has anything changed in North America?

BACKGROUND: Multiple guidelines on the management of intraductal papillary mucinous neoplasm (IPMN) have been published over the past decade. However, practice data are lacking. This study aims to determine whether pancreatectomy procedures, IPMN pathology, or outcomes have changed. METHODS: ACS-NSQIP Procedure Targeted Pancreatectomy database was queried for patients with IPMN from 2014 to 2019. Cases were stratified by pathology, tumor stage/cyst size and procedure. Pancreatectomies for IPMN by year, 30-day morbidity, and clinically relevant postoperative pancreatic fistula (CR-POPF) were quantified. Mann-Kendall trend tests were performed to assess surgical trends and associated outcomes over time. RESULTS: 3912 patients underwent pancreatectomy for IPMN. 21% demonstrated malignancy and 79% were benign. Morbidity and mortality occurred in 29.7% and 1.5% of cases, respectively. Over time, no change was observed in use of pancreatectomy for IPMN (10%) or in benign/malignant pathology, or cyst size. Robotic approach increased from 9.1% to 16.5% with decreases in laparoscopic (19.5%-15.0%) and open interventions (71.5%-68.1%, p = 0.016). No change was observed over time in morbidity or mortality; however, rates of CR-POPF decreased (18.8%-13.8%, p < 0.001). CONCLUSIONS: Practice patterns in treatment of IPMN have not changed significantly in North America. More patients are undergoing robotic pancreatectomy, and postoperative pancreatic fistula rates are improving.

Impact of nodal status in determining multimodal treatment strategies in non-cardia gastric cancer.

BACKGROUND: Patients with resectable noncardia gastric cancer may be subjected to perioperative chemotherapy (PEC), postoperative chemoradiation (POCR), or postoperative chemotherapy (POC). We analyzed these treatment strategies to determine optimal therapy based on nodal status. METHOD: The National Cancer Database was used to identify patients with resected noncardia gastric cancer (2004-2016). Patients were stratified based on clinical nodal status-negative (cLN-), positive (cLN+) and pathological nodal status (pLN-, pLN+). In cLN- patients who underwent upfront resection and were upstaged to pLN+, POC, and POCR were compared. Overall survival (OS) with PEC, POCR, and POC were compared in cLN- and cLN+. RESULTS: We identified 6142 patients (cLN-: 3831; cLN+: 2311). In cLN- patients who underwent upfront resection (N = 3423), 69% were upstaged to pLN+ disease (N = 2499; POCR = 1796, POC = 703). On MVA, POCR was associated with significantly improved OS when compared to POC (hazard ratio [HR]: 0.75; p < 0.001). In patients with cLN- disease (PEC = 408; POCR = 2439; POC = 984), PEC(HR: 0.77; p = 0.01) and POCR(HR: 0.81; p < 0.001) were associated with improved OS compared with POC. In cLN+ group (PEC = 452; POCR = 1284; POC = 575), POCR was associated with improved OS compared with POC (HR: 0.81; p < 0.01), and trend towards improved OS was noted when PEC(HR: 0.83; p = 0.055) was compared with POC. CONCLUSION: Postoperative chemoradiation may be the preferred treatment strategy over postoperative chemotherapy in non-cardia gastric cancer patients who receive upfront resection and are upstaged from clinically node negative to pathologically node positive disease.

Does non-metastatic gastric cancer of the cardia warrant a different treatment strategy?

BACKGROUND: Multimodal treatment strategies with surgery as its centerpiece have been accepted as the standard of care in nonmetastatic cardia gastric cancer (CGC). There remains a lack of consensus regarding the optimal multimodal treatment strategy. METHOD: We queried National Cancer Database from 2004 to 2016 to identify patients with resected nonmetastatic CGC who received perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), or postoperative chemotherapy (POC). A subgroup analysis was performed in optimally treated patients defined as initial chemotherapy within 45 days of diagnosis, resection within 45 days of diagnosis, negative margins, adjuvant chemotherapy within 90 days of resection, and standard radiation dose (45 Gy). Kaplan-Meier, Univariate analysis (UVA), and Multivariable analysis (MVA) were performed. RESULTS: We identified 2387 patients. Median survival was 38.8 months in the PEC group, 36 months in the POCR group, and 32.3 months in the POC group (p = 0.1025). On UVA, patients treated with PEC had an association with improved survival (HR, 0.83; p = 0.037) when compared with POC. On MVA, no significant difference was noted in overall survival (OS) between PEC, POCR, and POC, similar to subgroup analysis of optimally treated cohort. CONCLUSION: OS rate in nonmetastatic CGC is not significantly different between patients receiving PEC, POCR, or POC.

Robotic pancreatoduodenectomy: trends in technique and training challenges.

BACKGROUND: More complex cases are being performed robotically. This study aims to characterize trends in robotic pancreatoduodenectomy (RPD) over time and assess opportunities for advanced trainees. METHODS: Using the ACS-NSQIP database from 2014 to 2019, PD cases were characterized by operative approach (open-OPN, laparoscopic-LAP, robotic-ROB). Proficiency and postoperative outcomes were described by approach over time. RESULTS: 24,268 PDs were identified, with the ROB approach increasing from 2.8% to 7.5%. Unplanned conversion increased over time for LAP (27.7-39.0%, p = 0.003) but was unchanged for ROB cases (14.8-14.7%, p = 0.257). Morbidity increased for OPN PD (35.5-36.8%, p = 0.041) and decreased for ROB PD (38.7-30.3%, p = 0.010). Mean LOS was lower in ROB than LAP/OPN (9.5 vs. 10.9 vs. 10.9 days, p < 0.00001). Approximately, 100 AHPBA, SSO, and ASTS fellows are being trained each year in North America; however, only about 5 RPDs are available per trainee per year which is far below that recommended to achieve proficiency. CONCLUSION: Over a 6-year period, a significant increase was observed in the use of RPD without a concomitant increase in conversion rates. RPD was associated with decreased morbidity and length of stay. Despite this shift, the number of cases being performed is not adequate for all fellows to achieve proficiency before graduation.

Expression of PD-L1 in Patients With Malignant Peritoneal Mesothelioma: A Pilot Study.

INTRODUCTION: Frequency of PD-L1 expression and the role of immunotherapy in malignant peritoneal mesothelioma (MPM) have not been well characterized. The purpose of this study was to determine PD-L1 expression in patients with MPM and perform an exploratory analysis for associations between PD-L1 and its biological behavior in MPM. METHODS: Tumor samples were collected from patients undergoing surgical interventions between January 2018 and June 2020. Specimens were stained with anti-PD-L1 antibodies (Dako 22c3) and positivity was determined by tumor proportion score (TPS) or combined positive score (CPS) being ≥1%. RESULTS: Twenty one samples were obtained from 21 patients. Sixteen of 21 (76%) samples were CPS positive and 9 of 21 (43%) were TPS positive. Three samples had more aggressive biphasic/sarcomatoid histology and a high CPS and TPS (CPS: 3, 75, 95%; TPS: 2, 60, 90%). On an exploratory analysis, as the CPS or TPS threshold increased, there was a trend towards worse survival. CONCLUSIONS: MPM has a high frequency of PD-L1 expression, which may be associated with more aggressive tumor biology. These data provide the foundation for continued evaluation of checkpoint inhibition in patients with MPM.

Conditional survival analysis of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide with an approximate 5-year survival of greater than 50% in patients after surgical resection. Survival estimates have limited utility for patients who have survived several years after initial treatment. We analyzed how conditional survival (CS) after curative-intent surgery for HCC predicts survival estimates over time. METHODS: NCDB (2004-2014) was queried for patients undergoing definitive surgical resection for HCC. Cumulative overall survival (OS) was calculated using the Kaplan-Meier method, and CS at x years after diagnosis was calculated as CS1 = OS (X+5) /OS(X) . RESULTS: The final analysis encompassed 11 357 patients. Age, negative margin status, grade severity and radiation before surgery were statistically significant predictors of cumulative overall conditional survival (P ≤ .0001). Overall unconditional 5-year survival was 65.7%, but CS estimates were higher. A patient who has already survived 3 years has an additional 2-year, or 5-year CS, estimate of 86.96%. CONCLUSION: Survival estimates following hepatic resection in HCC patients change according to survival time accrued since surgery. CS estimates are improved relative to unconditional OS. The impact of different variables influencing OS is likewise nonlinear over the course of time after surgery.

Current Management and Future Opportunities for Peritoneal Metastases: Peritoneal Mesothelioma.

PURPOSE: Diffuse malignant peritoneal mesothelioma (MPM) is a rare and ultimately fatal cancer that was first described just over a century ago. It is a diffuse malignancy arising from the mesothelial lining of the peritoneum; morbidity and mortality from MPM is due to its propensity to progress locoregionally within the abdominal cavity. METHODS: The purpose of this article is to review the current state-of-the-science related to the diagnosis, staging, and treatment of MPM. RESULTS: The condition afflicts men and women equally and the peak incidence is between 55 and 60 years of age although it can arise in the young and elderly. Patients afflicted with MPM most commonly present with nonspecific abdominal symptoms that usually lead to diagnosis when the condition is relatively advanced. Historically, median overall survival for MPM patients without treatment is < 1 year. The couplet of systemic pemetrexed and cisplatin has an overall response rate of approximately 25% and a median overall survival of approximately 1 year. CONCLUSION: The available data, almost all retrospective in nature, have shown that in selected patients, operative cytoreduction (CRS) and regional chemotherapy administered as hyperthermic intraoperative peritoneal chemotherapy (HIPEC) or early postoperative intraperitoneal chemotherapy (EPIC) is associated with long-term survival. Studies on the molecular biology of MPM have yielded new insights relating to the potentially important role of the phosphoinsitide-3-kinase/mammalian target of rapamycin (PI3 K/mTOR) pathways and immune checkpoint inhibitors that may translate into new therapeutic options for patients with diffuse MPM.

Correlation between preoperative endoscopic ultrasound and surgical pathology staging of gastric adenocarcinoma: A single institution retrospective review.

BACKGROUND: Recent evidence validates the effectiveness of neoadjuvant chemotherapy in the treatment of gastric adenocarcinoma. Endoscopic ultrasonographic (EUS) staging has been proposed as a useful adjunct in this setting. METHODS: We performed a retrospective review of patients treated at our institution for gastric adenocarcinoma between July 2005 and January 2014. We identified patients referred for EUS before surgery as part of a prospective treatment plan. Histopathologic staging was compared to EUS staging, with a focus on T- and N-stage. Agreement between the two modalities was examined using kappa-statistics. RESULTS: We identified 614 patients with biopsy-proven gastric adenocarcinoma; 145 underwent curative-intent surgery. Surgical pathology and EUS results were available from 69 patients. The accuracy of EUS for the evaluation of T- and N-stage was 44.9% and 56.5%, respectively. EUS demonstrated greater concordance with histopathology at evaluating T-stage (κ = 0.3469) than N-stage (κ = 0.1316). EUS underestimated T- and N-stage in 40.8% and 30.4% of patients, respectively. CONCLUSION: EUS seems to correlate poorly with pathology in the preoperative staging of gastric adenocarcinoma. In the majority of inaccurate cases, EUS underestimates T-stage and N-stage, limiting its utility in the neoadjuvant setting.

The value of FDG-PET in the staging of gastric adenocarcinoma: A single institution retrospective review.

BACKGROUND: The value of FDG-PET in the staging of gastric adenocarcinoma (GA) has been subject to debate. METHODS: We performed a retrospective review of GA patients between 2006 and 2014 and identified those who had a CT and FDG-PET before initiating treatment. CT and FDG-PET images were analyzed by a blinded body radiologist and nuclear physician, respectively. Disease stage was assessed, looking at primary tumor (PT), locoregional (LLN) and distant lymph node disease (DLN), and metastasis (M). RESULTS: We identified 608 patients who had biopsy-proven GA and 207 (34.0%) had a CT and FDG-PET as part of their staging work-up. Of these, imaging from 166 (27.3%) patients was available for review. CT identified PT, LLN, DLN, and M in 120 (72.3%), 84 (50.6%), 25 (15.1%), and 32 (19.3%) patients, respectively; while FDG-PET identified PT, LLN, DLN, and M in 125 (75.3%), 78 (47.0%), 41 (24.7%), and 27 (16.3%) of patients, respectively. FDG-PET up-staged 31 (18.7%) patients while it down-staged 17 (10.2%) patients. Of patients who were up-staged, 20 (64.5%) developed progressive disease. CONCLUSIONS: Our findings support the use of FDG-PET as a valuable adjunct to CT in the staging of GA, as it changed the stage in 48 (28.9%) patients. J. Surg. Oncol. 2016;113:640-646. © 2016 Wiley Periodicals, Inc.

Accurate staging with internal mammary chain sentinel node biopsy for breast cancer.

BACKGROUND: Although internal mammary chain (IMC) metastases are an independent predictor of prognosis, collecting IMC sentinel nodes (SN) remains controversial. We sought to determine predictors for IMC nodal positivity and the role positive IMC-SNs have on changing staging and management. METHODS: We reviewed a prospectively collected database (1997-2012) to identify patients who had IMC drainage detected on lymphoscintigraphy and underwent biopsy. Chi square tests and logistic regression models were used to determine trends and factors associated with IMC node positivity. RESULTS: A total of 122 patients with cTis-T2cN0M0 breast cancer underwent IMC-SN biopsy. Mean age of the cohort was 53 years, and mean tumor size was 2.0 cm. Identification of IMC nodes was successful in 100% of the cases. There were no complications. Sentinel nodes mapped to the IMC alone in 14 of 122 (11%) patients. Overall, 26% of patients were node positive, with 12 of 122 (10%) patients having a positive IMC-SN. In patients with a positive axilla, IMC-SN was positive in 33% of patients, whereas in patients with a negative axilla, IMC-SN was positive in 3% of cases (P < 0.001). The number of positive axillary nodes was the only independent predictor of IMC positivity (1-3 positive axillary nodes odds ratio 16.9, 95% CI 3.1-91.1; ≥4 positive axillary nodes odds ratio 45.0, 95% CI 4.0-500.7). IMC-SN positivity led to a more advanced nodal category in all patients and more accurate staging in 4 of 12 (33%) patients. CONCLUSIONS: IMC-SN biopsy is predictable and safe. Identification of IMC metastases though IMC-SN biopsy has the potential to alter the stage and adjuvant therapy of breast cancer patients.

Recurrence-free survival dynamics following adjuvant chemotherapy for resected colorectal cancer: A systematic review of randomized controlled trials.

BACKGROUND: Several cytotoxic chemotherapies have demonstrated efficacy in improving recurrence-free survival (RFS) following resection of Stage II-IV colorectal cancer (CRC). However, the temporal dynamics of response to such adjuvant therapy have not been systematically quantified. METHODS: The Cochrane Central Register of Trials, Medline (PubMed) and Web of Science were queried from database inception to February 23, 2023 for Phase III randomized controlled trials (RCTs) where there was a significant difference in RFS between adjuvant chemotherapy and surgery only arms. Summary data were extracted from published Kaplan-Meier curves using DigitizeIT. Absolute differences in RFS event rates were compared at matched intervals using multiple paired t-tests. RESULTS: The initial search yielded 1469 manuscripts. After screening, 18 RCTs were eligible (14 Stage II/III; 4 Stage IV), inclusive of 16,682 patients. In the absence of adjuvant chemotherapy, the greatest rate of recurrence was observed in the first year (mean RFS event rate; 0-0.5 years: 0.22 ± 0.21; 0.5-1 years: 0.20 ± 0.09). Adjuvant chemotherapy was associated with significant decreases in the RFS event rates for the intervals 0-0.5 years (0.09 ± 0.09 vs. 0.22 ± 0.21, p < 0.001) and 0.5-1 years (0.14 ± 0.11 vs. 0.20 ± 0.09, p = 0.001) after randomization, but not at later intervals (1-5 years). In Stage IV trials, RFS event rates significantly differed for the interval 0-0.5 years (p = 0.012), corresponding with adjuvant treatment durations of 6 months. In Stage II/III trials, which included therapies of 6-24 months duration, there were marked differences in the RFS event rates between surgery and chemotherapy arms for the intervals 0-0.5 years (p < 0.001) and 0.5-1 years (p < 0.001) with smaller differences in the RFS event rates for the intervals 1-2 years (p = 0.012) and 2-3 years (p = 0.010). CONCLUSIONS: In a systematic review of positive RCTs comparing adjuvant chemotherapy to surgery alone for Stage II-IV CRC, observed RFS improvements were driven by early divergences that occurred primarily during active cytotoxic chemotherapy. Late recurrence dynamics were not influenced by adjuvant therapy use. Such observations may have implications for the use of chemotherapy for micrometastatic clones detectable by cell-free DNA-based methodologies.

Racial disparities in rates of invasiveness of resected intraductal papillary mucinous neoplasms in the United States.

BACKGROUND: Racial and ethnic disparities have been observed in the multidisciplinary management of pancreatic ductal adenocarcinoma. Intraductal papillary mucinous neoplasm is the most common identifiable precursor to pancreatic ductal adenocarcinoma, where early surgical intervention before the development of an invasive intraductal papillary mucinous neoplasm improves survival. The association of race/ethnicity with the risk of identifying invasive intraductal papillary mucinous neoplasms during resection has not been previously defined. METHODS: The American College of Surgeons National Quality Improvement Program targeted pancreatectomy database (2014-2021) was queried for patients with race/ethnicity data who underwent resection of an intraductal papillary mucinous neoplasm. Backward Wald logistic regression modeling (P ≤ 0.05 for entry; P > .10 for removal) was used to identify independent predictors of invasion. RESULTS: A total of 4,505 cases of resected intraductal papillary mucinous neoplasms were identified, with 923 (20.5%) demonstrating invasive intraductal papillary mucinous neoplasms. The cohort of individuals other than non-Hispanic Whites were significantly more likely to have invasive intraductal papillary mucinous neoplasms (White, 19.9%; Black, 24.2%; Asian, 23.7%; Hispanic, 22.6%; P = .026). Such disparity could not be explained by greater comorbidity, as non-White patients were significantly younger (age <65 years: 41.7% vs 33.2%, P < .001) and had better physical status (American Society of Anesthesiologists score ≤2: 28.8% vs 25.2%, P = .053). After controlling for clinicodemographic variables, being an individual of race/ethnicity other than White was independently associated with higher odds of invasive intraductal papillary mucinous neoplasms (odds ratio, 1.280; 95% confidence interval, 1.046-1.566; P = .017). No differences in postoperative morbidity were observed. CONCLUSION: In a national cohort of patients with resected intraductal papillary mucinous neoplasms, individuals who identified as being of race/ethnicity other than White were significantly more likely to have invasive intraductal papillary mucinous neoplasms during surgical resection.

Laparoscopic radiofrequency ablation for the management of colorectal liver metastases: 10-year experience.

BACKGROUND: Published results addressing the treatment of colorectal liver metastases (CRLM) with radiofrequency ablation (RFA) vary widely with local recurrence rates of 2-40% and 5-year survival of 14-55%. The goal of this study was to analyze our 10-year experience with laparoscopic RFA. METHODS: From January 2000 to July 2010, 130 patients underwent laparoscopic RFA for CRLM. Kaplan-Meier analysis was used to assess survival. Univariate and multivariate analysis were performed to identify factors associated with survival and recurrence. RESULTS: In this cohort, median survival was 40.4 months with 5-year survival of 28.8%. Overall, 9.2% of patients had a local recurrence (3.6% for tumors 3 cm or less). On univariate analysis, factors associated with decreased survival were BMI (P = 0.045), rectal primary (P = 0.005), and increased tumor size (P = 0.002). On multivariate analysis, increased tumor size (HR 1.29 [95% CI: 1.04-1.59]; P = 0.020) and bilobar disease (HR 2.06 [95% CI: 1.02-4.15]; P = 0.044) were associated with decreased survival. On univariate analysis, only BMI was found to be associated with disease recurrence (P = 0.025). CONCLUSIONS: Our data demonstrate that laparoscopic RFA can achieve a median survival of 40.4 months with a low local recurrence rate. Patients with tumors 3 cm or less have a decreased risk of local recurrence.

Assessing an intermittently operated household scale slow sand filter paired with household bleach for the removal of endocrine disrupting compounds.

Endocrine disrupting compounds (EDCs) are a contaminant of emerging concern throughout the world, including developing countries where centralized water and wastewater treatment plants are not common. In developing countries, household scale water treatment technologies such as the biosand filter (BSF) are used to improve drinking water quality. No studies currently exist on the ability of the BSF to remove EDCs. In this experiment, the BSF was evaluated for the removal of three EDCs, estrone (E1), estriol (E3), and 17α-ethinyl estradiol (EE2). Removal results were compared to the slow sand filter (SSF) from the literature, which is similar to the BSF in principal but comparisons have revealed differences in removal of other water quality parameters between SSF and BSF. In general, the BSF minimally removed the compounds from spiked lake water as removal was less than 15% for all three compounds, though mass removal much higher than other studies in which the SSF was used. Household bleach was added to the rate was BSF effluent as suggested in order to achieve different Cl- concentrations (0.67, 2.0, 5.0, and 10.0 mg/L) and subsequent removal of EDCs by oxidation was examined. Concentrations were reduced > 98% for all compounds when the Cl- concentration was greater than 5 mg/L. Removal efficiency was > 50% at the 0.67 mg/L Cl- concentration, while almost 70% removal was observed for all compounds at the 2.0 mg/L Cl- concentration.

Association between SMAD4 Mutations and GATA6 Expression in Paired Pancreatic Ductal Adenocarcinoma Tumor Specimens: Data from Two Independent Molecularly-Characterized Cohorts.

Several molecular biomarkers have been identified to guide induction treatment selection for localized pancreatic ductal adenocarcinoma (PDAC). SMAD4 alterations and low GATA6 expression/modified "Moffitt" basal-like phenotype have each been associated with inferior survival uniquely for patients receiving 5-FU-based therapies. SMAD4 may directly regulate the expression of GATA6 in PDAC, pointing to a common predictive biomarker. To evaluate the relationship between SMAD4 mutations and GATA6 expression in human PDAC tumors, patients with paired SMAD4 mutation and GATA6 mRNA expression data in the TCGA and CPTAC were identified. In 321 patients (TCGA: n = 180; CPTAC: n = 141), the rate of SMAD4 alterations was 26.8%. The rate of SMAD4 alteration did not vary per tertile of normalized GATA6 expression (TCGA: p = 0.928; CPTAC: p = 0.828). In the TCGA, SMAD4 alterations and the basal-like phenotype were each associated with worse survival (log rank p = 0.077 and p = 0.080, respectively), but their combined presence did not identify a subset with uniquely inferior survival (p = 0.943). In the CPTAC, the basal-like phenotype was associated with significantly worse survival (p < 0.001), but the prognostic value was not influenced by the combined presence of SMAD4 alterations (p = 0.960). SMAD4 alterations were not associated with poor clinico-pathological features such as poor tumor grade, advanced tumor stage, positive lymphovascular invasion (LVI), or positive perineural invasion (PNI), compared with SMAD4-wildtype. Given that SMAD4 mutations were not associated with GATA6 expression or Moffitt subtype in two independent molecularly characterized PDAC cohorts, distinct biomarker-defined clinical trials are necessary.

Surgery is Associated With Improved Overall Survival in Patients With Metastatic Gastric Cancer: A National Cancer Database Analysis.

BACKGROUND: The 5-year overall survival (OS) rate for patients with metastatic gastric cancer (mGC) is 5.3%. Surgery for mGC is controversial. METHODS: We identified all mGC patients who received chemotherapy using the National Cancer Database (2004-2015). Patients were grouped according to surgery of: (1) the primary site (PS) only, (2) primary and distant sites (PDS), (3) distant site only (DS), or (4) no surgery (NS). A propensity score adjustment and multivariate regression was used to compare OS. RESULTS: Overall, 18,772 patients met the inclusion criteria: (1) PS (n = 962, 5.1%), (2) PDS (n = 380, 2.1%), (3) DS (n = 984, 5.2%), and 16,446 NS (87.6%). Surgery was associated with improved OS in the PS and PDS groups (hazard ratios: .489 (95% CI: .376-.636); .583 (95% CI: .420-.811), P < .001) (median OS 15.8 and 15.9 months vs 8.6 for NS patients, respectively). CONCLUSIONS: Gastrectomy with or without metastasectomy is associated with improved survival in stage IV gastric cancer patients receiving chemotherapy. This warrants further prospective studies.

Pancreatoduodenectomy: the Metabolic Syndrome is Associated with Preventable Morbidity and Mortality.

BACKGROUND: Patients with metabolic syndrome (MS) may have increased perioperative morbidity and mortality. The aim of this analysis was to investigate the association of MS with mortality, serious morbidity, and pancreatectomy-specific outcomes in patients undergoing pancreatoduodenectomy (PD). METHODS: Patients with MS who underwent PD were selected from the 2014-2018 ACS-NSQIP pancreatectomy-specific database. MS was defined as obesity (BMI ≥ 30 kg/m2), diabetes, and hypertension. Demographics and outcomes were compared by χ2 and Mann-Whitney tests, and adjusted odds ratios from multivariable logistic regression assessed the association between MS and primary outcomes. RESULTS: Of 19,054 patients who underwent PD, 7.3% (n = 1388) had MS. On univariable analysis, patients with MS had significantly worse outcomes (p < 0.05): 30-day mortality (3% vs 1.8%), serious morbidity (26% vs 23%), re-intubation (4.9% vs 3.5%), pulmonary embolism (2.0% vs 1.1%), acute renal failure (1.5% vs 0.9%), cardiac arrest (1.9% vs 1.0%), and delayed gastric emptying (18% vs 16.5%). On multivariable analysis, 30-day mortality was significantly increased in patients with MS (aOR: 1.53, p < 0.01). CONCLUSION: Metabolic syndrome is associated with increased morbidity and mortality in patients undergoing pancreatoduodenectomy. The association with mortality is a novel observation. Perioperative strategies aimed at reduction and/or mitigation of cardiac, pulmonary, thrombotic, and renal complications should be employed in this population given their increased risk.