Pheochromocytomas

Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors derived from chromaffin tissue of the adrenal medulla. Such tumors arising from the sympathetic ganglia of the thorax, abdomen, or pelvis are termed “paragangliomas” or “extra-adrenal pheochromocytomas.” The classic symptoms of these tumors are due to excess circulating levels of norepinephrine, epinephrine, or dopamine. Although 21% may be asymptomatic, the most common symptoms associated with pheochromocytomas include sweating, palpitations, and headaches in association with intermittent hypertension. If left untreated, excess catecholamines may result in hypertensive crisis leading to cardiac complications, cerebrovascular stroke, or ultimately sudden death. These catecholamine-secreting tumors are most commonly sporadic, but about 30% of patients have this disease as part of a familial disorder such as multiple endocrine neoplasia type 2 (MEN2) or von Hippel-Lindau (VHL) syndrome. Although most are benign, accurate recognition of pheochromocytomas with malignant potential and distant metastases remains a major diagnostic challenge. Advances in the field of molecular genetics have led to novel diagnostic and therapeutic strategies in an attempt to address this dilemma. Surgical excision of pheochromocytomas and paragangliomas is the mainstay of treatment and offers the only potential for cure. This chapter focuses on recent developments in the diagnosis of pheochromocytomas, encompassing biochemical, radiologic, histologic, and molecular analyzes. In addition, novel therapeutic strategies and advances in individualized targeted therapies for malignant pheochromocytomas will be discussed

Frontal GABA Levels Change during Working Memory

Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but changes in neurotransmitter levels have not been demonstrated in humans during a cognitive task, and the relationship between neurotransmitter dynamics and hemodynamic activity during cognition has not yet been established. We evaluate the concentration of the major inhibitory (GABA) and excitatory (glutamate + glutamine: Glx) neurotransmitters and the cerebral perfusion at rest and during a prolonged delayed match-to-sample working memory task. Resting GABA levels in the dorsolateral prefrontal cortex correlated positively with the resting perfusion and inversely with the change in perfusion during the task. Further, only GABA increased significantly during the first working memory run and then decreased continuously across subsequent task runs. The decrease of GABA over time was paralleled by a trend towards decreased reaction times and higher task accuracy. These results demonstrate a link between neurotransmitter dynamics and hemodynamic activity during working memory, indicating that functional neuroimaging metrics depend on the balance of excitation and inhibition required for cognitive processing

Randomized trial of a phone- and web-based weight loss program for women at elevated breast cancer risk: the HELP study

Excess weight and physical inactivity are modifiable risk factors for breast cancer. Behavioral intervention is particularly important among women with an elevated risk profile. This trial tested an intervention that trained women to use a self-monitoring website to increase activity and lose weight. Women with BMI≥27.5 kg/m(2) at elevated breast cancer risk were randomized to the intervention (N=71) or usual care (N=34). The intervention group received telephone-based coaching and used web-based self-monitoring tools. At 6 months, significant weight loss was observed in the intervention group (4.7% loss from starting weight; SD=4.7%) relative to usual care (0.4% gain; SD=3.0%) (p<.0001). By 12 months, the intervention group had lost 3.7% of weight (SD=5.4%), compared to 1.3% (SD=4.2) for usual care (p=.003). At 12 months, accelerometer-measured moderate-to-vigorous physical activity increased by 12 min/day (SD=24) compared to no change in usual care (p=.04. In summary, this web- and phone-based approach produced modest but significant improvements in weight and physical activity for women at elevated breast cancer risk

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Evolution of breast cancer management in Ireland: a decade of change

Abstract Background Over the last decade there has been a paradigm shift in the management of breast cancer, subsequent to revised surgical oncology guidelines and consensus statements which were derived in light of landmark breast cancer clinical trials conducted throughout the latter part of the 20th century. However the sheer impact of this paradigm shift upon all modalities of treatment, and the current trends in management of the disease, are largely unknown. We aimed to assess the changing practices of breast cancer management over the last decade within a specialist tertiary referral Breast Cancer Centre. Methods Comparative analysis of all aspects of the management of breast cancer patients, who presented to a tertiary referral Breast Cancer Centre in 1995/1996 and 2005/2006, was undertaken and measured against The European Society for Surgical Oncology guidelines for the surgical management of mammographically detected lesions [1998]. Results 613 patients' case profiles were analysed. Over the last decade we observed a dramatic increase in incidence of breast cancer [>100%], a move to less invasive diagnostic and surgical therapeutic techniques, as well as increased use of adjuvant therapies. We also witnessed the introduction of immediate breast reconstruction as part of routine practice Conclusion We demonstrate that radical changes have occurred in the management of breast cancer in the last decade, in keeping with international guidelines. It remains incumbent upon us to continue to adapt our practice patterns in light of emerging knowledge and best evidence.</p

Evolution of breast cancer management in ireland: a decade of change

Background: Over the last decade there has been a paradigm shift in the management of breast cancer, subsequent to revised surgical oncology guidelines and consensus statements which were derived in light of landmark breast cancer clinical trials conducted throughout the latter part of the 20th century. However the sheer impact of this paradigm shift upon all modalities of treatment, and the current trends in management of the disease, are largely unknown. We aimed to assess the changing practices of breast cancer management over the last decade within a specialist tertiary referral Breast Cancer Centre. Methods: Comparative analysis of all aspects of the management of breast cancer patients, who presented to a tertiary referral Breast Cancer Centre in 1995/1996 and 2005/2006, was undertaken and measured against The European Society for Surgical Oncology guidelines for the surgical management of mammographically detected lesions [1998]. Results: 613 patients' case profiles were analysed. Over the last decade we observed a dramatic increase in incidence of breast cancer [&amp;gt;100%], a move to less invasive diagnostic and surgical therapeutic techniques, as well as increased use of adjuvant therapies. We also witnessed the introduction of immediate breast reconstruction as part of routine practice Conclusion: We demonstrate that radical changes have occurred in the management of breast cancer in the last decade, in keeping with international guidelines. It remains incumbent upon us to continue to adapt our practice patterns in light of emerging knowledge and best evidence

Focal thyroid incidentalomas identified with whole-body FDG-PET warrant further investigation.

Fluorodeoxyglucose (FDG) whole body positron emission computed tomography (PET-CT) detects clinically occult malignancy. The aim of this study was to assess the prevalence and significance of focal thyroid 18F - fluorodeoxyglucose uptake. A retrospective review of all patients who had FDG PET-CT examinations, in a single tertiary referral centre was performed. PET scan findings and the final pathological diagnosis were collated. 2105 scans were reviewed. Focal uptake was identified in 35 (1.66%) patients. Final surgical histology was available on eight patients, which confirmed papillary carcinoma in four (20%) patients and lymphoma and metastatic disease in two patients respectively. This gave an overall malignancy rate in focal thyroid uptake of at least 33%. Thyroid incidentalomas occurred with a frequency of 2.13%, with an associated malignancy rate of at least 33% in focal thyroid uptake. The high malignancy rate associated with focal thyroid uptake mandates further investigation in medically fit patients.</p