Objective: To determine whether primary tumor resection in patients with metastatic pheochromocytoma or paraganglioma (PPG) is associated with longer overall survival (OS).Background: Patients with metastatic PPG have poor survival outcomes. The impact of surgical resection of the primary tumor on OS is not known.Methods: We retrospectively studied patients with metastatic PPG treated at the University of Texas, MD Anderson Cancer Center from January 2000 through January 2015. Kaplan-Meier analysis with log-rank tests was used to compare OS among patients undergoing primary tumor resection and patients not treated surgically. Propensity score method was applied to adjust for selection bias using demographic, clinical, biochemical, genetic, imaging, and pathologic information.Results: A total of 113 patients with metastatic PPG were identified. Eighty-nine (79%) patients had surgery and 24 (21%) patients did not. Median OS was longer in patients who had surgery than in patients who did not [148 months, 95% confidence interval (CI) 112.8–183.2 months vs 36 months, 95% CI 27.2–44.8 months;P< 0.001].Fifty-three (46%) patients had synchronous metastases; of these patients, those who had surgery had longer OS than those who did not (85 months, 95% CI 64.5–105.4 months vs 36 months, 95% CI 29.7–42.3 months;P< 0.001). Patients who had surgery had a similar ECOG performance status to the ones who did not (P= 0.1798, two samplettest;P= 0.2449, Wilcoxon rank sum test). Univariate and propensity score analysis confirmed that patients treated with surgery had longer OS than those not treated surgically irrespective of age, race, primary tumor size and location, number of metastatic sites, and genetic background (log-rankP< 0.001).In patients with hormonally active tumors (70.8%), the symptoms of catecholamine excess improved after surgery. However, the tumor burden was a more important determinant of OS than hormonal secretion.Conclusions: Primary tumor resection in patients with metastatic PPG appeared to be associated with improved OS. In patients with hormonally active tumors, surgical resection led to better blood pressure control.

Purpose of review: Pheochromocytomas and paragangliomas (PPGs) are rare neuroendocrine tumors. Over the last 15 years, substantial progress has been made toward understanding the clinical aspects and molecular origins of this disease. Nevertheless, predicting and managing malignancy remains the biggest challenge in clinical practice. The natural history of patients with malignant PPGs has not yet been described, and their prognosis varies. Currently, the diagnosis of malignant PPGs relies on the presence of metastases, by which time the disease is usually advanced. Better understanding of the clinical and molecular characteristics of patients with malignant PPGs has spurred several prospective clinical trials. Recent findings: Several molecular targeted therapies, a novel radiopharmaceutical medication that targets the catecholamine transporter, and immunotherapy are under evaluation for the treatment of patients with malignant PPGs. Furthermore, the identification of clinical predictors of malignancy and survival has led to the first TNM staging classification for PPGs. Summary: Prospective clinical trials are providing patients with therapeutic options beyond systemic chemotherapy. The knowledge derived from these trials and from the evaluation of the TNM staging in clinical practice will help to clarify how to most effectively treat malignant PPGs.

Objective: Pheochromocytomas (PHs) and sympathetic paragangliomas (PGs) are tumors that produce catecholamines, predisposing patients to cardiovascular disease and gastrointestinal effects such as constipation. Objectives: i) determine the prevalence of constipation, its risk factors, and its impact on survival; ii) identify whether a systematic combination of fiber, water, and laxatives was effective for treatment of constipation.Design and methods: We retrospectively studied 396 patients with PH/PG diagnosed in 2005–2014. The study population was patients with constipation as a presenting symptom; the control group was patients without constipation as a presenting symptom. The MD Anderson Symptom Inventory was used to assess constipation and quality of life.Results: Twenty-three patients (6%) had constipation. Constipation was associated with headaches, palpitations, diaphoresis, weight loss, and excessive noradrenaline production (P<0.0001). Eighteen of these patients had non-metastatic primary tumors larger than 5 cm and/or extensive metastases. No statistically significant differences in age, sex, and genotype were noted between the study and control groups. In patients without metastases, resection of the primary tumor led to symptom disappearance. A systematic combination of fiber, water, and laxatives was associated with symptom improvement. Two patients who presented unmanaged constipation died because of sepsis from toxic megacolon.Conclusions: Constipation is a rare and potentially lethal complication in patients with PH/PGs. Severe constipation can be prevented by recognizing and treating mild symptoms.

Reconstructing regional to hemispheric-scale climate variability requires the application of spatially representative and climatically sensitive proxy archives. Large spatial networks of dendrochronologies have facilitated the reconstruction of atmospheric variability and inferred variability in the Atlantic Ocean system. However, the marine environment has hitherto lacked the direct application of the spatial network approach because of the small number of individual absolutely-dated marine archives. In this study we present the first analyses of a network of absolutely-dated annually-resolved growth increment width chronologies from the marine bivalves Glycymeris glycymeris and Arctica islandica. The network contains eight chronologies spanning >500km along the western British continental shelf from the southern Irish Sea to North West Scotland. Correlation analysis of the individual chronologies and a suite of climate indices, including the Atlantic Multidecadal Oscillation (AMO), Central England surface air temperature (CET), northeast Atlantic sea surface temperatures (SST's) and the winter North Atlantic Oscillation (wNAO), demonstrates that, despite the large geographical distances been sites and the heterogeneous nature of the marine environment, the increment width variability in these series contains an element of coherence likely driven by a common response to changing environmental forcing. A nested Principal component analysis (PCA) was used to construct five composite series which explain between 31% and 74% of the variance across the individual chronologies. Linear regression analyses indicate that the composite series explain up to 41% of the variance in Northeast Atlantic SSTs over the calibration period (1975–2000). Calibration verification (reduction of error [RE] and coefficient of efficiency [CE]) statistics indicate that the composite series contains significant skill at reconstructing multi-decadal northeast Atlantic SST variability over the past two centuries (1805–2010). These data suggest that composite series derived from sclerochronology networks can facilitate the robust reconstruction of marine climate over past centuries to millennia providing invaluable baseline records of natural oceanographic variability

Background Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors. Metastases develop in 15-20%. The American Joint Committee on Cancer (AJCC) established inaugural guidelines for PPGL tumor-node-metastasis (TNM) staging. The objective of this analysis is to investigate the associations between TNM staging and overall survival (OS). Methods We retrospectively applied the TNM staging at the time of diagnosis of the primary tumor. The primary outcome was OS. Unadjusted survival rates were estimated by the Kaplan-Meier method. Cox proportional hazards regression models were used to evaluate the associations between OS and covariates of interest. Results The study included 458 patients. Median OS was 18.0 (95% CI: 15.6-not reached) years. At diagnosis, 126 (27.5%) tumors were stage I, 213 (46.5%) were stage II, 47 (10.3%) were stage III, and 72 (15.7%) were stage IV. The 10-year OS probabilities were 0.844 (95% CI: 0.768-0.928) for patients with stage I tumors, 0.792 (95% CI: 0.726-0.865) for stage II, 0.595 (95% CI: 0.435-0.813) for stage III, and 0.221 (95% CI: 0.127-0.384) for stage IV. Compared with stage I, the hazard ratios (HR) for death were 1.50 (0.87-2.57) for stage II, 2.85 (1.45-5.63) for stage III, and 8.88 (5.16-15.29) for stage IV (p < 0.001). Compared with patients with no germline mutations, those with RET 634/918 had better OS (HR: 0.28, 95% CI: 0.12-0.69). Other germline mutations, including SDHB, did not exhibit worse OS than patients with metastasis and sporadic disease. Conclusions OS rates correlated with the recently developed AJCC TNM staging and was not worse in hereditary disease. Stage IV disease exhibited a significantly shorter OS compared with stages I-III. Future staging systems could be adjusted to better separate stages I and II.