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.

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.

Evaluation of Acute Supplementation With the Ketone Ester (R)-3-Hydroxybutyl-(R)-3-Hydroxybutyrate (deltaG) in Healthy Volunteers by Cardiac and Skeletal Muscle 31P Magnetic Resonance Spectroscopy.

In this acute intervention study, we investigated the potential benefit of ketone supplementation in humans by studying cardiac phosphocreatine to adenosine-triphosphate ratios (PCr/ATP) and skeletal muscle PCr recovery using phosphorus magnetic resonance spectroscopy (31P-MRS) before and after ingestion of a ketone ester drink. We recruited 28 healthy individuals: 12 aged 23-70 years for cardiac 31P-MRS, and 16 aged 60-75 years for skeletal muscle 31P-MRS. Baseline and post-intervention resting cardiac and dynamic skeletal muscle 31P-MRS scans were performed in one visit, where 25 g of the ketone monoester, deltaG®, was administered after the baseline scan. Administration was timed so that post-intervention 31P-MRS would take place 30 min after deltaG® ingestion. The deltaG® ketone drink was well-tolerated by all participants. In participants who provided blood samples, post-intervention blood glucose, lactate and non-esterified fatty acid concentrations decreased significantly (-28.8%, p ≪ 0.001; -28.2%, p = 0.02; and -49.1%, p ≪ 0.001, respectively), while levels of the ketone body D-beta-hydroxybutyrate significantly increased from mean (standard deviation) 0.7 (0.3) to 4.0 (1.1) mmol/L after 30 min (p ≪ 0.001). There were no significant changes in cardiac PCr/ATP or skeletal muscle metabolic parameters between baseline and post-intervention. Acute ketone supplementation caused mild ketosis in blood, with drops in glucose, lactate, and free fatty acids; however, such changes were not associated with changes in 31P-MRS measures in the heart or in skeletal muscle. Future work may focus on the effect of longer-term ketone supplementation on tissue energetics in groups with compromised mitochondrial function.

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.

Inclusion of Wheat Dried Distillers' Grains with Solubles from Bioethanol Plants in Diets for Dairy Cows.

Dried distillers' grains with solubles (DDGS) from bioethanol production can replace soya in diets for dairy cows, but the optimum inclusion level of European wheat DDGS (wDDGS) is unknown. Two batches of wDDGS from different UK bioethanol plants were fed to 44 (Experiment 1) and 40 (Experiment 2) cows in a Latin square design. Each wDDGS replaced soya and rapeseed at four inclusion levels (g/kg of diet dry matter (DM): 0, 80, 160 and 240-Experiment 1; 0, 75, 150 and 225-Experiment 2). Diets were balanced for metabolisable energy (ME) and protein (MP), and for minimum starch and saturated fat in Experiment 2. In Experiment 1, DM intake (29 kg/day) and milk yield (42.3 kg/day) were unaffected by wDDGS inclusion up to 160 g/kg but were lower than control with 240 g/kg inclusion, which was attributed to the low proportion of solubles in this wDDGS batch. In Experiment 2, DM intake (22.4 kg/day) and milk yield (32.1 kg/day) were unaffected by wDDGS inclusion up to 225 g/kg. ME content of wDDGS, determined in vivo (MJ/kg DM) was 12.1 (Experiment 1) and 13.4 (Experiment 2). It is concluded that the optimum inclusion level of wDDGS is at least 225 g/kg DM in diets balanced for minimum starch and saturated fat as well as ME and MP supplies.

Neuropsychologic changes in primary hyperparathyroidism after parathyroidectomy from a dual-institution prospective study.

BACKGROUND: The impact of parathyroidectomy on neuropsychiatric symptoms in primary hyperparathyroidism remains poorly defined. The validated scales Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 can be used to assess depression and anxiety, respectively. Our aim was to prospectively characterize the changes in neuropsychiatric symptoms after parathyroidectomy. METHODS: Patients undergoing parathyroidectomy and thyroidectomy (control) from two institutions between 2014 and 2019 were prospectively administered a questionnaire assessing neuropsychiatric symptoms before and after surgery. Paired t tests compared preoperative with postoperative neuropsychiatric symptoms and t tests compared differences in neuropsychiatric symptoms between parathyroidectomy and thyroidectomy. RESULTS: A total of 244 patients underwent parathyroidectomy and 161 underwent thyroidectomy. We observed improvement in neuropsychiatric symptoms after parathyroidectomy (6.2 [5.0-7.4], P < .01). Preoperatively, neuropsychiatric symptoms were more prevalent in patients undergoing parathyroidectomy when compared with thyroidectomy (11.2 ± 11.5 vs 7.5 ± 8.2, P < .01); however, after surgery there was no difference between the two groups (5.1 ± 7.1 vs 5.4 ± 7.2, P = .59). Preoperatively, 27.5% and 18.0% of patients endorsed moderate to severe depression and anxiety, which fell to 8.2% and 5.3%, respectively, (P < .01) after surgery. CONCLUSION: Patients undergoing parathyroidectomy showed significant improvement in neuropsychiatric symptoms after surgery. Neuropsychiatric symptoms are more prevalent in patients with primary hyperparathyroidism. Neuropsychiatric symptoms should be assessed in all patients with primary hyperparathyroidism and should be considered a relative indication for parathyroidectomy.

Environmental chemicals and metabolic disruption in primary and secondary human parathyroid tumors.

BACKGROUND: The incidence of primary hyperparathyroidism has increased 300% in the United States in the past 30 years, and secondary hyperparathyroidism is almost universal in patients with end-stage renal disease. We assessed the presence of environmental chemicals in human hyperplastic parathyroid tumors as possible contributing factors to this increase. METHODS: Cryopreserved hyperplastic parathyroid tumors and normal human parathyroids were analyzed by gas chromatography and liquid chromatography coupled to ultra-high-resolution mass spectrometry, bioinformatics, and biostatistics. RESULTS: Detected environmental chemicals included polychlorinated biphenyls, polybrominated diphenyl ethers, dichloro-diphenyl-trichloroethane derivatives, and other insecticides. A total of 99% had p,p'-dichlorodiphenyldichloroethylene. More than 50% contained other environmental chemicals, and many classified as endocrine disruptors. Polychlorinated biphenyl-28 and polychlorinated biphenyl-49 levels correlated positively with parathyroid tumor mass. Polybrominated diphenyl ether-47 concentrations in tumors were inversely correlated with patients' serum calcium levels. Cellular metabolites in pathways of purine and pyrimidine synthesis and mitochondrial energy production were associated with tumor growth and with p,p'-dichlorodiphenyldichloroethylene in primary hyperparathyroidism tumors. In normal parathyroids, p,p'-dichlorodiphenyldichloroethylene , polychlorinated biphenyl-28, polychlorinated biphenyl-74, and polychlorinated biphenyl-153, but not p,p'-dichlorodiphenyldichloroethylene or polychlorinated biphenyl-49, were detected. CONCLUSION: Environmental chemicals are present in human parathyroid tumors and warrant detailed epidemiologic and mechanistic studies to test for causal links to the growth of human parathyroid tumors.

Geographical and seasonal variation in iodine content of cow's milk in the UK and consequences for the consumer´s supply.

BACKGROUND: Dairy products provide a crucial source of dietary iodine for the majority of the UK population, contributing approximately 30-40 % of daily intake. Fluctuations in the iodine content of purchased milk both seasonally and annually implies potential fragility of iodine supply likely through fluctuating supplementation practices in cow herds. We set out to establish the level of national variation in herds and identify factors which might impact milk iodine content. METHODS: Milk samples were obtained from 98 herds across the UK via the National Milk Laboratories in August and December 2016. Iodine concentration of samples was measured using ICP-MS. Milk samples and feed intake data were additionally taken from 22 cows from the University of Nottingham (UON) dairy herd. RESULTS: There was considerable variation in milk iodine content from < 0.012 (Limit of Detection) to 1558 µg L-1, with a summer median of 197 µg L-1 and winter median 297 µg L-1. Overall, winter values were higher than summer counterparts (P < 0.001) and this held true for samples taken from the North West (P = 0.002) and South West (P = 0.006) but not for other regions studied. Data from the UON herd showed a negative relationship between iodine content and milk yield (P = 0.03) and we found that milk iodine content varied considerably despite apparently similar iodine intakes. CONCLUSIONS: Regional differences in milk iodine concentration between summer and winter suggests that feeding practices are far from uniform across the country. The negative association observed between iodine concentration and milk yield in UON samples, suggests that reduced summer values may be influenced by dilution in addition to seasonal differences in concentrate feed provision.

Multimodal Preoperative Localization Improves Outcomes in Reoperative Parathyroidectomy: A 25-Year Surgical Experience.

Reoperative parathyroid surgery (REOPS) is often associated with lower cure rates and greater risk of nerve injury and hypoparathyroidism. The aim of this study was to evaluate cure rates, pathology, complications, and the efficacy of preoperative localization in patients requiring REOPS. Between 1992 and 2017, 2491 consecutive patients underwent parathyroidectomy for primary hyperparathyroidism. With Institutional Review Board approval, our prospectively collected parathyroidectomy outcomes database was queried for operative findings, outcomes, pathology, and localization methodology. Three hundred forty-six patients had REOPS (111 men/32% and 235 women/68%), with an overall cure rate of 91 per cent and a mean follow-up of 1.9 ± 0.7 years. The average preoperative serum calcium and parathyroid hormone were 11 ± 1 mg/dL and 373 ± 796 pg/mL, respectively. Normalization of intraoperative parathyroid hormone occurred in 248 patients and it was predictive of cure in 98.8 per cent of patients. A single adenoma was resected in 253 patients (75%), and the superior gland location was most common at 57 per cent. Ectopic glands were identified in only 33 patients. When preoperative imaging localized a lesion, a tumor was identified in that location in 75.4 per cent of sestamibi or SPECT/CT scans, 57.8 per cent of CT, 61.2 per cent of MRI, and 46.2 per cent of US. When at least two imaging modalities were concordant, sensitivity improved to 91.6 per cent (P < 0.001). Complication rates of permanent hypoparathyroidism and recurrent nerve palsy occurred in 0.03 per cent of patients. REOP for recurrent or persistent primary hyperparathyroidism has a cure rate of 91 per cent. Most missed parathyroid tumors are in the neck, and multimodal imaging improves preoperative localization and success.

Avoiding Pitfalls in Insulinomas by Preoperative Localization with a Dual Imaging Approach.

Insulinomas are rare endocrine malignancies of the pancreas that require surgical resection but can be difficult to localize preoperatively. We sought to review and improve the accuracy of preoperative localization techniques at our institution. We retrospectively reviewed all insulinomas that underwent resection at our institution between 1998 and 2016. Localization techniques include selective arterial calcium stimulation (CaStim), CT, MRI, angiography, and somatostatin receptor scintigraphy. Thirty-eight patients had pathologically proven insulinomas on surgical resection. Localization accuracies of CaStim, CT, and MRI were 89 per cent (31/35), 67 per cent (22/33), and 46 per cent (11/24), respectively. When compared with CT alone and CaStim alone, the combination of these two modalities resulted in 100 per cent preoperative localization (30/30), whereas the use of CaStim alone resulted in 80 per cent (4/5) localization and the use of CT alone resulted in 66 per cent (2/3) localization. Four of our patients had both negative CT and MRI. Among these patients, CaStim was 100 per cent localizing and the only positive modality for these patients. These data confirm that CaStim is accurate in preoperatively identifying single and multiple insulinomas; and when combined with CT, this accuracy is increased to 100 per cent. Based on these data, we propose that a dual imaging approach is a superior means of preoperative localization.

A heritable subset of the core rumen microbiome dictates dairy cow productivity and emissions.

A 1000-cow study across four European countries was undertaken to understand to what extent ruminant microbiomes can be controlled by the host animal and to identify characteristics of the host rumen microbiome axis that determine productivity and methane emissions. A core rumen microbiome, phylogenetically linked and with a preserved hierarchical structure, was identified. A 39-member subset of the core formed hubs in co-occurrence networks linking microbiome structure to host genetics and phenotype (methane emissions, rumen and blood metabolites, and milk production efficiency). These phenotypes can be predicted from the core microbiome using machine learning algorithms. The heritable core microbes, therefore, present primary targets for rumen manipulation toward sustainable and environmentally friendly agriculture.

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.

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.

Accuracy of the ACS NSQIP Online Risk Calculator Depends on How You Look at It: Results from the United States Gastric Cancer Collaborative.

The objective of this study is to assess the accuracy of the American College of Surgeons National Surgical Quality Improvement Program online risk calculator for estimating risk after operation for gastric cancer using the United States Gastric Cancer Collaborative. Nine hundred and sixty-five patients who underwent resection of gastric adenocarcinoma between January 2000 and December 2012 at seven academic medical centers were included. Actual complication rates and outcomes for patients were compared. Most of the patients underwent total gastrectomy with Roux-en-Y reconstruction (404, 41.9%) and partial gastrectomy with gastrojejunostomy (239, 24.8%) or Roux-en-Y reconstruction (284, 29.4%). The C-statistic was highest for venous thromboembolism (0.690) and lowest for renal failure at (0.540). All C-statistics were less than 0.7. Brier scores ranged from 0.010 for venous thromboembolism to 0.238 for any complication. General estimates of risk for the cohort were variable in terms of accuracy. Improving the ability of surgeons to estimate preoperative risk for patients is critically important so that efforts at risk reduction can be personalized to each patient. The American College of Surgeons National Surgical Quality Improvement Program risk calculator is a rapid and easy-to-use tool and validation of the calculator is important as its use becomes more common.

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.

Impact of lymph node ratio in selecting patients with resected gastric cancer for adjuvant therapy.

BACKGROUND: The impact of adjuvant chemotherapy and chemo-radiation therapy in the treatment of resectable gastric cancer remains varied. We sought to define the clinical impact of lymph node ratio on the relative benefit of adjuvant chemotherapy or chemo-radiation therapy among patients having undergone curative-intent resection for gastric cancer. METHODS: Using the multi-institutional US Gastric Cancer Collaborative database, 719 patients with gastric adenocarcinoma who underwent curative-intent resection between 2000 and 2013 were identified. Patients with metastasis or an R2 margin were excluded. The impact of lymph node ratio on overall survival among patients who received chemotherapy or chemo-radiation therapy was evaluated. RESULTS: Median patient age was 65 years, and the majority of patients were male (56.2%). The majority of patients underwent either subtotal (40.6%) or total gastrectomy (41.0%), with the remainder undergoing distal gastrectomy or wedge resection (18.4%). On pathology, median tumor size was 4 cm; most patients had a T3 (33.0%) or T4 (27.9%) lesion with lymph node metastasis (59.7%). Margin status was R0 in 92.5% of patients. A total of 325 (45.2%) patients underwent resection alone, 253 (35.2%) patients received 5-FU or capecitabine-based chemo-radiation therapy, whereas the remaining 141 (19.6%) received chemotherapy. Median overall survival was 40.9 months, and 5-year overall survival was 40.3%. According to lymph node ratio categories, 5-year overall survival for patients with a lymph node ratio of 0, 0.01-0.10, >0.10-0.25, >0.25 were 54.1%, 53.1 %, 49.1 % and 19.8 %, respectively. Factors associated with worse overall survival included involvement of the gastroesophageal junction (hazard ratio 1.8), T-stage (3-4: hazard ratio 2.1), lymphovascular invasion (hazard ratio 1.4), and lymph node ratio (>0.25: hazard ratio 2.3; all P < .05). In contrast, receipt of adjuvant chemo-radiation therapy was associated with an improved overall survival in the multivariable model (versus resection alone: hazard ratio 0.40; versus chemotherapy: hazard ratio 0.45, both P < .001). The benefit of chemo-radiation therapy for resected gastric cancer was noted only among patients with lymph node ratio >0.25 (versus resection alone: hazard ratio R 0.34; versus chemotherapy: hazard ratio 0.45, both P < .001). In contrast, there was no noted overall survival benefit of chemotherapy or chemo-radiation therapy among patients with lymph node ratio ≤0.25 (all P > .05). CONCLUSION: Adjuvant chemotherapy or chemo-radiation therapy was utilized in more than one-half of patients undergoing curative-intent resection for gastric cancer. Lymph node ratio may be a useful tool to select patients for adjuvant chemo-radiation therapy, because the benefit of chemo-radiation therapy was isolated to patients with greater degrees of lymphatic spread (ie, lymph node ratio >0.25).

Neuropsychological Changes in Primary Hyperparathyroidism after Parathyroidectomy.

Neuropsychiatric symptoms (NPSs) of sporadic primary hyperparathyroidism (PHPT) are often subtle and effects of parathyroidectomy (PTX) on symptoms remains poorly characterized. Our aim was to evaluate effects of PTX on NPS in patients with PHPT. A prospective questionnaire was distributed to all patients undergoing PTX and to a thyroidectomy (TX) control group. The questionnaire included the validated scales Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) to assess for depression and anxiety respectively, as well as questions modified from Pasieka's Parathyroid Assessment of Symptoms (M-PAS). Point values were assigned to questionnaire answers to create a score, with a maximum of 63. Fifty-eight patients underwent PTX (58.6%) and 41 TX (41.4%). Mean preoperative scores were greater in PTX versus TX patients in total score, PHQ-9, GAD-7, and M-PAS (all P < 0.05). Post-PTX scores were lower than pre-PTX in total score, PHQ-9, GAD-7, and M-PAS (all P < 0.05), but not in pre- and post-TX. Post-PTX 69.0 and 82.8 per cent of patients showed no symptoms of depression and anxiety, respectively, compared with 37.9 and 56.9 per cent pre-PTX. A total of 16.2 and 10.3 per cent of patients had moderately severe to severe depression and anxiety, which fell to 0 per cent post-PTX. NPSs are more common in patients with PHPT when compared with TX. Patients undergoing PTX have improvements in NPS. NPS scoring should occur in all patients with PHPT and severity of NPS should be considered a relative indication for PTX.

Readmission Following Gastric Cancer Resection: Risk Factors and Survival.

BACKGROUND: This study utilized a multi-institutional database to evaluate risk factors for readmission in patients undergoing curative gastrectomy for gastric adenocarcinoma with the intent of describing both perioperative risk factors and the relationship of readmission to survival. METHODS: Patients who underwent curative resection of gastric adenocarcinoma from 2000 to 2012 from seven academic institutions of the US Gastric Cancer Collaborative were analyzed. In-hospital deaths and palliative surgeries were excluded, and readmission was defined as within 30 days of discharge. Univariate and multivariable logistic regression analyses were employed and survival analysis conducted. RESULTS: Of the 855 patients, 121 patients (14.2 %) were readmitted. Univariate analysis identified advanced age (p < 0.0128), American Society of Anesthesiology status ≥3 (p = 0.0045), preexisting cardiac disease (p < 0.0001), hypertension (p = 0.0142), history of smoking (p = 0.0254), increased preoperative blood urea nitrogen (BUN; p = 0.0426), concomitant pancreatectomy (p = 0.0056), increased operation time (p = 0.0384), estimated blood loss (p = 0.0196), 25th percentile length of stay (<7 days, p = 0.0166), 75th percentile length of stay (>12 days, p = 0.0256), postoperative complication (p < 0.0001), and total gastrectomy (p = 0.0167) as risk factors for readmission. Multivariable analysis identified cardiac disease (odds ratio (OR) 2.4, 95 % confidence interval (CI) 1.6-3.3, p < 0.0001), postoperative complication (OR 2.3, 95 % CI 1.6-5.4, p < 0.0001), and pancreatectomy (OR 2.2, 95 % CI 1.1-4.1, p = 0.0202) as independent risk factors for readmission. There was an association of decreased overall median survival in readmitted patients (39 months for readmitted vs. 103 months for non-readmitted). This was due to decreased survival in readmitted stage 1 (p = 0.0039), while there was no difference in survival for other stages. Stage I readmitted patients had a higher incidence of cardiac disease than stage I non-readmitted patients (58 vs. 24 %, respectively, p = 0.0002). CONCLUSIONS: Within this multi-institutional study investigating readmission in patients undergoing curative resection for gastric cancer, cardiac disease, postoperative complication, and concomitant pancreatectomy were identified as significant risk factors for readmission. Readmission was associated with decreased overall median survival, but on further analysis, this was driven by differences in survival for stage I disease only.

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.