Abstract
Context
Modern pheochromocytomas (PHEOs) are often discovered by incidental finding on cross-sectional imaging or mutation-based genetic case detection testing. Little is known about how ...these PHEOs behave.
Objective
To describe the characteristics and behavior of PHEOs discovered incidentally on imaging or through mutation-based genetic case detection testing.
Design
Retrospective study.
Setting
Referral center.
Patients
Consecutive patients with pathology-confirmed PHEOs, treated from 2005 to 2016.
Main Outcome Measure(s)
Tumor size, plasma/urine fractionated metanephrines and catecholamines, and preoperative management.
Results
Two hundred seventy-one patients (52% women, median age 52.0 years) presented with 296 PHEOs. Discovery method was most often incidental finding on cross-section imaging (61%) rather than PHEO-related symptoms (27%) or mutation-based case detection testing (12%). Patients with incidentally discovered PHEOs were older than symptomatic and mutation-based case detection testing patients (median age 56.6 vs 43 vs 35 years, P < 0.0001). Mutation-based case detection PHEOs were smaller than those discovered due to symptoms (median size 29.0 vs 50.5 mm, P = 0.0027). Patients with PHEOs discovered due to symptoms had the highest median concentration of 24-hour urinary metanephrines and total plasma metanephrines (P < 0.0001). These patients required a higher cumulative phenoxybenzamine dose than patients with incidental or case detection PHEO (median 450 vs 375 vs 270 mg, P = 0.029).
Conclusions
PHEOs are primarily discovered due to incidental finding on cross-sectional imaging rather than PHEO-related symptoms. PHEOs discovered through mutation-based genetic case detection testing were smaller and required less α-adrenergic blockade preoperatively compared with PHEOs found due to symptoms, which supports routine case detection testing for patients genetically predisposed for PHEOs.
Pheochromocytomas found by mutation-based case detection testing are less biochemically active and require less preoperative α-adrenergic blockade compared with those found due to symptoms.
Surgical approaches to the adrenal gland Sada, Alaa; McKenzie, Travis J
Current opinion in endocrinology, diabetes, and obesity,
06/2023, Letnik:
30, Številka:
3
Journal Article
Recenzirano
Review the literature on the surgical management of adrenal diseases, highlighting the various surgical approaches and their respective pros and cons.
Minimally invasive adrenalectomy is commonly ...used for small and benign adrenal tumors, whereas open adrenalectomy is preferred for larger tumors and primary adrenal malignancy. Although minimally invasive adrenalectomy results in shorter recovery and fewer complications compared with open, the latter offers better oncologic outcomes in the setting of primary adrenal malignancy. Adrenalectomy is performed transabdominally or retroperitoneoscopically, both yielding equivalent results and recovery. Traditional laparoscopic or robotic equipment can be utilized for either minimally invasive approach. Subtotal adrenalectomy may be appropriate for patients with genetically associated pheochromocytoma to preserve cortical function and reduce the risk of adrenal insufficiency. However, the potential benefits of sparing adrenal function must be weighed against the risk of recurrence.
Adrenalectomy is becoming increasingly common worldwide. For benign and small adrenal tumors, minimally invasive adrenalectomy is generally considered the standard approach, while open adrenalectomy is preferred for primary adrenal malignancy and larger tumors. Subtotal adrenalectomy may be appropriate for patients with bilateral adrenal pheochromocytoma, as it can reduce the need for lifelong glucocorticoid dependency.
The lack of reliable, noninvasive methods to diagnose early nonalcoholic steatohepatitis (NASH) is a major unmet need. We aimed to determine the diagnostic accuracy of three‐dimensional magnetic ...resonance elastography (3D‐MRE), with shear stiffness measured at 60 Hz, damping ratio at 40 Hz, and magnetic resonance imaging proton density fat fraction (MRI‐PDFF) in the detection of NASH in individuals undergoing bariatric surgery. Obese adults at risk for NASH were enrolled between 2015 and 2017 (prospective cohort, n = 88) and 2010 and 2013 (retrospective cohort, n = 87). The imaging protocol consisted of multifrequency 3D‐MRE (mf3D‐MRE) with shear waves delivered at different frequencies to explore parameters that best correlated with histologic NASH, and MRI‐PDFF to estimate steatosis. The prospective cohort was used to establish the optimal mf3D‐MRE technical parameters for NASH detection. The two cohorts were then combined to derive predictive models of NASH and disease activity by nonalcoholic fatty liver disease activity score (NAS) using the three imaging parameters that correlated with NASH. A total of 175 patients (median age 45, 81% women, and 81 46% with histologic NASH) were used for model derivation. From the complex shear modulus output generated by mf3D‐MRE, the damping ratio at 40 Hz and shear stiffness at 60 Hz best correlated with NASH. The fat fraction obtained from MRI‐PDFF correlated with steatosis (P < 0.05 for all). These three parameters were fit into a logistic regression model that predicted NASH with cross‐validated area under the receiver operating characteristic curve (AUROC) = 0.73, sensitivity = 0.67, specificity = 0.80, positive predictive value = 0.73 and negative predictive value = 0.74, and disease activity by NAS with cross‐validated AUROC = 0.82. Conclusion: The mf3D‐MRE allows identification of imaging parameters that predict early NASH and disease activity. This imaging biomarker represents a promising alternative to liver biopsy for NASH diagnosis and monitoring. The results provide motivation for further studies in nonbariatric cohorts.
Obesity is a significant public health challenge worldwide and is inextricably linked to adverse cardiovascular outcomes. The relationship between excess adiposity and increased blood pressure is ...well established, and it is estimated that obesity accounts for 65-78% of cases of primary hypertension. The mechanisms through which obesity causes hypertension are complex and include sympathetic nervous system overactivation, stimulation of the renin-angiotensin-aldosterone system, alterations in adipose-derived cytokines, insulin resistance, and structural and functional renal changes. Weight loss is the primary goal of treatment for obesity-related hypertension, although few individuals achieve success with nonpharmacological management alone. Specific considerations apply when selecting the most appropriate pharmacological therapy for obese hypertensive patients. Metabolic surgery has proved to be the most effective means of ensuring substantial and sustained weight loss and has also been shown to confer beneficial effects in type 2 diabetes mellitus. Increasing evidence suggests that metabolic surgery may also be an effective treatment for obesity-related hypertension, although prospective data on long-term blood pressure outcomes are awaited. This review will discuss the pathophysiological mechanisms that link obesity with hypertension and will provide an overview of treatment strategies, with a focus on metabolic surgery.
Comparison of benign and malignant insulinoma Sada, Alaa; Yamashita, Thomas Szabo; Glasgow, Amy E. ...
The American journal of surgery,
February 2021, 2021-02-00, 20210201, Letnik:
221, Številka:
2
Journal Article
Recenzirano
How malignant insulinomas present relative to benign insulinomas is unknown.
A single-institution retrospective study identified patients with insulinoma. Malignancy was defined by distant ...metastases, positive lymph node(s), T stage of 4, direct invasion into surrounding peripancreatic tissue, or presence of lymphovascular invasion. Wilcoxon Rank Sum tests and Kaplan-Meier analysis were used.
A total of 311 patients were identified: 51 malignant and 260 benign. Patients with malignant insulinoma presented with higher levels of insulin, proinsulin, and c-peptide. Malignant lesions were larger: 4.2 ± 3.2 vs 1.8 ± 0.8 cm in benign lesions, p < 0.01. Overall survival at 5 years was 66.8% vs 95.4% for malignant and benign insulinoma respectively, p < 0.01.
Larger size of insulinoma and increased serum β-cell polypeptide concentrations were associated with malignancy. Malignant insulinoma has poorer survival. Further work-up to rule out malignancy may be indicated for larger pancreatic lesions and for patients with higher pre-operative insulin and pro-insulin.
•Malignant and benign insulinoma differ in clinical features at presentation.•Malignant insulinoma is associated with higher serum β-cell polypeptide concentrations.•Malignant insulinoma lesions tend to be larger than benign lesions.•Malignant insulinoma has significantly worse survival compared to benign.
Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with an annual incidence of ~1 case per million population. Differentiating between ACC and benign adrenocortical tumors can be ...challenging in patients who present with an incidentally discovered adrenal mass, due to the limited specificity of standard diagnostic imaging. Recently, urine steroid metabolite profiling has been prospectively validated as a novel diagnostic tool for the detection of malignancy with improved accuracy over current modalities. Surgery represents the only curative treatment for ACC, although local recurrence and metastases are common, even after a margin-negative resection is performed. Unlike other intra-abdominal cancers, the role of minimally invasive surgery and lymphadenectomy in ACC is controversial. Adjuvant therapy with the adrenolytic drug mitotane is used to reduce the risk of recurrence after surgery, although evidence supporting its efficacy is limited; it is also currently unclear whether all patients or a subset with the highest risk of recurrence should receive this treatment. Large-scale pan-genomic studies have yielded insights into the pathogenesis of ACC and have defined distinct molecular signatures associated with clinical outcomes that may be used to improve prognostication. For patients with advanced ACC, palliative combination chemotherapy with mitotane is the current standard of care; however, this is associated with poor response rates (RR). Knowledge from molecular profiling studies has been used to guide the development of novel targeted therapies; however, these have shown limited efficacy in early phase trials. As a result, there is an urgent unmet need for more effective therapies for patients with this devastating disease.
Introduction
Due to the rarity of malignant insulinoma, a lack of the literature describing factors affecting outcomes exists. Our aim was to review malignant insulinoma incidence, characteristics ...and survival trends.
Methods
We identified all patients with malignant insulinoma in the SEER registries from 1973 to 2015. Incidence, neoplasm characteristics and factors affecting cancer-specific survival (CSS) were described.
Results
A total of 121 patients were identified. The crude annual overall incidence was low (range 0.0–0.27 cases per million person years). The largest proportion had localized disease (40%), while 16% had regional disease, 39% distant metastatic disease, and stage was unreported in 5%. Most neoplasms were in the body/tail of the pancreas, followed by the head of the pancreas. Grade was reported in 40% of patients; only a single patient reported as having grade IV with the remainder all grades I/II. Surgical resection was performed in 64% of patients. Within surgical patients, the median primary neoplasm size was 1.8 cm. Regional lymph nodes were examined in 57.1% of surgical patients, while 34% of examined nodes were positive. The median CSS was 183 months. On multivariable analysis, surgical resection, male sex and absence of metastatic disease were associated with superior survival.
Conclusion
While the greatest proportion of patients with malignant insulinoma present with localized disease, regional lymph node involvement was found in 34% of whose nodes were tested. Further studies are needed to assess the role of lymph node dissection in improving survival and preventing recurrence given the observed frequency of lymph node involvement.
Senescent cells, which can release factors that cause inflammation and dysfunction, the senescence-associated secretory phenotype (SASP), accumulate with ageing and at etiological sites in multiple ...chronic diseases. Senolytics, including the combination of Dasatinib and Quercetin (D + Q), selectively eliminate senescent cells by transiently disabling pro-survival networks that defend them against their own apoptotic environment. In the first clinical trial of senolytics, D + Q improved physical function in patients with idiopathic pulmonary fibrosis (IPF), a fatal senescence-associated disease, but to date, no peer-reviewed study has directly demonstrated that senolytics decrease senescent cells in humans.
In an open label Phase 1 pilot study, we administered 3 days of oral D 100 mg and Q 1000 mg to subjects with diabetic kidney disease (N = 9; 68·7 ± 3·1 years old; 2 female; BMI:33·9 ± 2·3 kg/m2; eGFR:27·0 ± 2·1 mL/min/1·73m2). Adipose tissue, skin biopsies, and blood were collected before and 11 days after completing senolytic treatment. Senescent cell and macrophage/Langerhans cell markers and circulating SASP factors were assayed.
D + Q reduced adipose tissue senescent cell burden within 11 days, with decreases in p16INK4A-and p21CIP1-expressing cells, cells with senescence-associated β-galactosidase activity, and adipocyte progenitors with limited replicative potential. Adipose tissue macrophages, which are attracted, anchored, and activated by senescent cells, and crown-like structures were decreased. Skin epidermal p16INK4A+ and p21CIP1+ cells were reduced, as were circulating SASP factors, including IL-1α, IL-6, and MMPs-9 and −12.
“Hit-and-run” treatment with senolytics, which in the case of D + Q have elimination half-lives <11 h, significantly decreases senescent cell burden in humans.
NIH and Foundations.
ClinicalTrials.gov Identifier: NCT02848131. Senescence, Frailty, and Mesenchymal Stem Cell Functionality in Chronic Kidney Disease: Effect of Senolytic Agents.
IMPORTANCE: Adrenalectomy is the definitive treatment for multiple adrenal abnormalities. Advances in technology and genomics and an improved understanding of adrenal pathophysiology have altered ...operative techniques and indications. OBJECTIVE: To develop evidence-based recommendations to enhance the appropriate, safe, and effective approaches to adrenalectomy. EVIDENCE REVIEW: A multidisciplinary panel identified and investigated 7 categories of relevant clinical concern to practicing surgeons. Questions were structured in the framework Population, Intervention/Exposure, Comparison, and Outcome, and a guided review of medical literature from PubMed and/or Embase from 1980 to 2021 was performed. Recommendations were developed using Grading of Recommendations, Assessment, Development and Evaluation methodology and were discussed until consensus, and patient advocacy representation was included. FINDINGS: Patients with an adrenal incidentaloma 1 cm or larger should undergo biochemical testing and further imaging characterization. Adrenal protocol computed tomography (CT) should be used to stratify malignancy risk and concern for pheochromocytoma. Routine scheduled follow-up of a nonfunctional adrenal nodule with benign imaging characteristics and unenhanced CT with Hounsfield units less than 10 is not suggested. When unilateral disease is present, laparoscopic adrenalectomy is recommended for patients with primary aldosteronism or autonomous cortisol secretion. Patients with clinical and radiographic findings consistent with adrenocortical carcinoma should be treated at high-volume multidisciplinary centers to optimize outcomes, including, when possible, a complete R0 resection without tumor disruption, which may require en bloc radical resection. Selective or nonselective α blockade can be used to safely prepare patients for surgical resection of paraganglioma/pheochromocytoma. Empirical perioperative glucocorticoid replacement therapy is indicated for patients with overt Cushing syndrome, but for patients with mild autonomous cortisol secretion, postoperative day 1 morning cortisol or cosyntropin stimulation testing can be used to determine the need for glucocorticoid replacement therapy. When patient and tumor variables are appropriate, we recommend minimally invasive adrenalectomy over open adrenalectomy because of improved perioperative morbidity. Minimally invasive adrenalectomy can be achieved either via a retroperitoneal or transperitoneal approach depending on surgeon expertise, as well as tumor and patient characteristics. CONCLUSIONS AND RELEVANCE: Twenty-six clinically relevant and evidence-based recommendations are provided to assist surgeons with perioperative adrenal care.
BACKGROUND:Surgery is curative for the majority of early-stage endometrial cancers. Postoperatively, patients are actually at much higher risk of mortality from obesity-related comorbidities unless ...they have sustained weight loss.
CASE:A 54-year-old woman with class III obesity, type II diabetes mellitus complicated by neuropathy and retinopathy, hypertension, sleep apnea, and fatty liver disease was diagnosed with grade 1 endometrioid uterine cancer. She underwent dual surgery with laparoscopic bariatric surgery and robotic-assisted laparoscopic hysterectomy. The perioperative period was uncomplicated, and final pathology was consistent with a stage IA grade 1 endometrial cancer. In 12 months, the patient lost 41.3 kg and required less insulin, metformin, and antihypertensive medication.
CONCLUSION:Combined minimally invasive hysterectomy and bariatric surgery for obese women with endometrial cancer can promote sustained weight loss and improve survivorship.
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