Nazanene H. Esfandiari

The Effect of Extent of Surgery and Number of Lymph Node Metastases on Overall Survival in Patients with Medullary Thyroid Cancer

CONTEXT Total thyroidectomy with central lymph node dissection is recommended in patients with medullary thyroid cancer (MTC). However, the relationship between disease severity and extent of resection on overall survival remains unknown. OBJECTIVE The aim of the study was to identify the effect of surgery on overall survival in MTC patients. METHODS Using data from 2968 patients with MTC diagnosed between 1998 and 2005 from the National Cancer Database, we determined the relationship between the number of cervical lymph node metastases, tumor size, distant metastases, and extent of surgery on overall survival in patients with MTC. RESULTS Older patient age (5.69 [95% CI, 3.34-9.72]), larger tumor size (2.89 [95% CI, 2.14-3.90]), presence of distant metastases (5.68 [95% CI, 4.61-6.99]), and number of positive regional lymph nodes (for ≥16 lymph nodes, 3.40 [95% CI, 2.41-4.79]) were independently associated with decreased survival. Overall survival rate for patients with cervical lymph nodes resected and negative, cervical lymph nodes not resected, and 1-5, 6-10, 11-16, and ≥16 cervical lymph node metastases was 90, 76, 74, 61, 69, and 55%, respectively. There was no difference in survival based on surgical intervention in patients with tumor size ≤ 2 cm without distant metastases. In patients with tumor size > 2.0 cm and no distant metastases, all surgical treatments resulted in a significant improvement in survival compared to no surgery (P < .001). In patients with distant metastases, only total thyroidectomy with regional lymph node resection resulted in a significant improvement in survival (P < .001). CONCLUSIONS The number of lymph node metastases should be incorporated into MTC staging. The extent of surgery in patients with MTC should be tailored to tumor size and distant metastases.

Preablation 131-I Scans With SPECT/CT Contribute to Thyroid Cancer Risk Stratification and 131-I Therapy Planning

CONTEXT The use of preablation diagnostic radioiodine scans for risk stratification and radioiodine therapy planning for differentiated thyroid cancer (DTC) remains controversial. OBJECTIVE The objective was to assess the contribution of preablation diagnostic 131-I scans with SPECT/CT (Dx 131-I scan) to (1) the risk stratification and (2) the postoperative management of DTC. DESIGN The study was designed as a prospective sequential patient series. SETTING The study was conducted at a University hospital. PATIENTS Three hundred twenty patients (pts) with DTC (219F; 101M, mean age 47.3 ± 16.4 y, range 10-90) were studied. INTERVENTION Using clinical and histopathology information an endocrinologist performed risk stratification and determined postoperative management with respect to radioiodine therapy (RAI) planning. The decision to withhold or to administer RAI, and the recommended low, medium or high therapeutic 131-I activity were recorded. Dx 131-I scans were performed and interpreted by two nuclear medicine physicians as showing thyroid remnant, cervical nodal, or distant metastases. The endocrinologist then reperformed risk stratification and reformulated management after consideration of Dx 131-I scans and stimulated thyroglobulin (Tg) information. MAIN OUTCOME MEASURE Main outcome measures were changes in risk stratification and management after Dx 131-I scans. RESULTS Detection of unsuspected nodal and distant metastases and elevated stimulated Tg levels resulted in a change in the estimated risk of recurrence in 15% of patients, and management in 31% of patients, as compared to initial risk stratification and management based on histopathology alone. CONCLUSIONS Both imaging data and stimulated thyroglobulin levels acquired at the time of Dx 131-I scans are consequential for 131-I therapy planning, providing information that changes risk stratification in 15% of patients as compared to recurrence risk estimation based on histopathology alone. Dx 131-I scans contribute to risk stratification by defining residual nodal and distant metastatic disease, changing clinical management in 29.4% of patients.

Courses of malignant pheochromocytoma: implications for therapy.

Abstract:  Survival of patients with metastatic pheochromocytoma that have exceeded 30 years without therapy to reduce tumors have been reported. We reviewed the records of 38 patients with malignant pheochromocytoma who had received 131I‐metaiodiobenzylguanidine (131I‐MIBG) treatments between 1981 and 1996 to evaluate longevity. Survival from diagnosis to last follow‐up exceeded 5 years in 21 of 38 (55%) and ≥10 years in 50%. In 17 of 21, the interval from diagnosis to 131I‐MIBG therapy was greater than 5 years. Survival following 131I‐MIBG was ≥5 years in 12 of 17 and ≥10 years in 7 of 17 patients despite continued evidence of excessive circulating catecholamines. Objective responses to 131I‐MIBG therapy were seen in about 30% and were usually of a few years, duration, but one individual exhibited marked reductions in volume and function of tumors that have persisted for 21 years. No feature, including a remission of >5 years following surgical excision, was found to predict prolonged survival. In summary, many patients with malignant pheochromocytoma will follow a course extending over many years. The role of 131I‐MIBG therapy in longevity is uncertain, but this radiopharmaceutical reduces evidence of tumors in some patients. Criteria for selecting patients who will benefit from treatment remain to be determined.

Evaluating Positron Emission Tomography Use in Differentiated Thyroid Cancer.

BACKGROUND Using the Surveillance, Epidemiology, and End Results-Medicare database, a substantial increase was found in the use of positron emission tomography (PET) scans after 2004 in differentiated thyroid cancer (DTC) patients. The reason for the increased utilization of the PET scan was not clear based on available the data. Therefore, the indications for and outcomes of PET scans performed at an academic institution were evaluated. METHODS A retrospective cohort study was performed of DTC patients who underwent surgery at the University of Michigan Health System from 2006 to 2011. After identifying patients who underwent a PET scan, indications, rate of positive PET scans, and impact on management were evaluated. For positive scans, the location of disease was characterized, and presence of disease on other imaging was determined. RESULTS Of the 585 patients in the cohort, 111 (19%) patients had 200 PET scans performed for evaluation of DTC. Indications for PET scan included: elevated thyroglobulin and negative radioiodine scan in 52 scans (26.0%), thyroglobulin antibodies in 13 scans (6.5%), rising thyroglobulin in 18 scans (9.0%), evaluation of abnormality on other imaging in 22 scans (11.0%), evaluation of extent of disease in 33 scans (16.5%), follow-up of previous scan in 57 scans (28.5%), other indications in two scans (1.0%), and unclear indications in three scans (1.5%). The PET scan was positive in 124 studies (62.0%); positivity was identified in the thyroid bed on 25 scans, cervical or mediastinal lymph nodes on 105 scans, lung on 28 scans, bone on four scans, and other areas on 14 scans. Therapy following PET scan was surgery in 66 cases (33.0%), chemotherapy or radiation in 23 cases (11.5%), observation in 110 cases (55.0%), and palliative care in one case (0.5%). Disease was identifiable on other imaging in 66% of cases. PET scan results changed management in 59 cases (29.5%). CONCLUSIONS In this academic medical center, the PET scan was utilized in 19% of patients. Indications for the PET scan included conventional indications, such as elevated thyroglobulin with noniodine avid disease, and more controversial uses, such as evaluation of extent of disease or abnormalities on other imaging tests. PET scan results changed management in about 30% of cases.

Controversies in the Management of Low-Risk Differentiated Thyroid Cancer

Controversy exists over optimal management of low-risk differentiated thyroid cancer. This controversy occurs in all aspects of management, including surgery, use of radioactive iodine for remnant ablation, thyroid hormone supplementation, and long-term surveillance. Limited and conflicting data, treatment paradigm shifts, and differences in physician perceptions contribute to the controversy. This lack of physician consensus results in wide variation in patient care, with some patients at risk for over- or undertreatment. To reduce patient harm and unnecessary worry, there is a need to design and implement studies to address current knowledge gaps.

Diabetes and Stress Hyperglycemia in the Intensive Care Unit: Outcomes After Cardiac Surgery

Abstract Background: Hyperglycemia is common in the post–cardiac surgery population and has been associated with increased mortality rates, surgical length of stay, and infection rates. Although hospitalized patients with diabetes are known to have more complications, recent studies in various hospital settings have reported worse outcomes in patients with stress hyperglycemia than in those with diabetes. Aim: The primary objective of this study was to analyze 30- and 90-day mortality rates in post–cardiac surgery patients with stress hyperglycemia and diabetes who were managed to achieve similar moderate blood glucose goals using the University of Michigan Hospital (Ann Arbor, MI) insulin protocol between 2005 and 2008. The secondary outcomes were rates of postoperative complications, including hypoglycemia. Methods: A standardized glucose management program was followed to treat all patients in the cardiac intensive care unit, with a blood glucose goal of 100 to 140 mg/dL. Data from 1973 patients with either diabetes or stress hyperglycemia were analyzed to identify associations between mean postoperative blood glucose levels and mortality, incidence of hypoglycemia, and complication rates. Results: Mortality rates did not differ between patients with diabetes and stress hyperglycemia (3.4 and 2.3%; P = 0.2). Rates of severe hypoglycemia were low (1%) for both groups and were not associated with an increase in mortality (P = 0.95). Other complication rates were similar between patients with diabetes and stress hyperglycemia. Conclusion: Maintaining a blood glucose range between 100 to 140 mg/dL in post–cardiac surgery patients was associated with a low mortality rate, low risk of hypoglycemia, and with complications rates that were similar in patients with diabetes and stress hyperglycemia.

Retrospective Study of Sirolimus and Cyclophosphamide in Patients with Advanced Differentiated Thyroid Cancers.

BACKGROUND We hypothesize that the combination of an mTOR inhibitor, sirolimus, with a well-known cytotoxic agent, cyclophosphamide, provides a well-tolerated and promising alternative treatment for advanced, differentiated thyroid cancers (DTC). METHODS This retrospective review extracted data from patients treated for advanced DTC at the University of Michigan Comprehensive Cancer Center from 1995 through 2013. Fifteen patients treated with combination sirolimus and cyclophosphamide were identified as the sirolimus+cyp group. Seventeen patients treated with standard of care and enrolled in clinical trials were identified as the comparison group. RESULTS The one-year progression free survival rate (PFS) was 0.45, 95% CI [0.26, 0.80] in the sirolimus+cyp population and 0.30, 95% CI [0.13, 0.67] in the comparison population. The hazard ratio for PFS from initiation of treatment was 1.47, 95% CI [0.57, and 3.78]. In patients treated as first line, one-year PFS rate was 0.57, 95% CI [0.30, 1.00] in the sirolimus+cyp group and relatively unchanged at 0.29, 95% CI [0.11, 0.74] in the comparison group. The hazard ratio for PFS for first line patients was 1.10, 95% CI[ 0.4, and 3.5]. In patients with 3 or fewer sites of metastases, the one year PFS was 0.58, 95% CI [0.33, 1.00] in the sirolimus+cyp group, and 0.37, 95% CI [0.17, 0.80] in the comparison group. The average number of toxicities was 0.87 in the sirolimus+cyp patients and 1.71 in the comparison group. CONCLUSIONS The combination of sirolimus and cyclophosphamide was generally well tolerated with similar progression free survival, highlighting its applicability in patients with limited options.

Impact of left ventricular assist device on diabetes management: an evaluation through case analysis and clinical impact

Abstract Background: Diabetes is a major risk factor for the development of heart failure (HF). In patients with advanced HF, left ventricular assist devices (LVADs) are increasingly used as a bridge to heart transplantation and destination therapy. It has been our observation that, post-LVAD implantation, diabetes management improves dramatically. Objective: We evaluated insulin requirements in a group of type 2 diabetes patients after LVAD implantation, compared them to a small control group, and performed a pertinent literature review. Methods: Relevant clinical and biochemical data were collected by chart review of 11 patients with known type 2 diabetes mellitus and HF who underwent LVAD implantation. Patients treated only with insulin were evaluated and compared with 5 control patients undergoing other cardiac procedures. Results: Insulin requirement decreased by 73% at 6 months from the pre-LVAD dose despite no significant changes in weight or glomerular filtration rate. Mean hemoglobin A1c reduced post-LVAD to 6.4% from 8.6%. Patients undergoing other cardiac procedures showed no significant changes in hemoglobin A1c or insulin requirements. Conclusion: Patients with diabetes undergoing LVAD implantation demonstrated a significant reduction in insulin requirements. This finding underscores the importance of HF in the progression of insulin resistance.

Roux-en-Y gastric bypass versus sleeve gastrectomy: risks and benefits.

INTRODUCTION Roux-en-Y gastric bypass (GB) and sleeve gastrectomy (SG) are the most commonly performed metabolic surgeries and are highly effective for the treatment of obesity and related comorbidities. In this narrative review, recent studies of at least two years of follow-up directly comparing outcomes between GB and SG are reviewed to assess the efficacy of each procedure in weight loss and diabetes remission, as well as resulting quality of life (QoL) assessment and micronutrient deficiencies. EVIDENCE ACQUISITION A systematic search of the literature of PubMed using MeSH terms and key words was performed. EVIDENCE SYNTHESIS Forty recent studies comparing GB and SG including 208,556 patients are included in this narrative review. Most studies demonstrate significantly greater weight loss after GB compared to SG. There is some evidence that GB may lead to greater proportion of remission of diabetes mellitus (DM), but the majority of studies found no significant difference at longer follow-up. There is some evidence of greater rates of vitamin D and B12 deficiencies following GB. There were no significant differences in QoL assessments between SG and GB. CONCLUSIONS A review of moderate and long-term studies directly comparing SG and GB suggests a greater degree of weight loss with GB. There is some but limited evidence the GB is more likely to induce DM remission, while increasing the risk of specific micronutrient deficiencies.

Fatty Liver Disease, Women, and Aldosterone: Finding a Link in the Jackson Heart Study

Context: Fatty liver disease is one of the most common forms of chronic liver disease. The renin-angiotensin-aldosterone system has been implicated in the pathogenesis of fatty liver. Objective: Determine the relationship between fatty liver and aldosterone in a large cohort study. Design: Community-based, observational cohort study of African Americans. Setting: The original Jackson Heart Study cohort enrolled African American participants from the Jackson, Mississippi, metropolitan area in Hinds, Madison, and Rankin Counties. Participants: Our study population consisted of 2507 Jackson Heart Study participants (1625 women and 882 men) who had liver attenuation measured per computed tomography scans, had aldosterone measurements, and were not taking angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or mineralocorticoid receptor antagonists. Intervention: There was no intervention. Main outcome measure: Liver attenuation on computed tomography scans. Results: Univariate regression analysis demonstrated a statistically significant correlation between aldosterone levels and liver attenuation. Each doubling of aldosterone was associated with 1.08 Hounsfield unit decrease (95% confidence interval, 1.47 to −0.69, P < 0.001). A multivariable model adjusted for body mass index, age, alcohol intake, and homeostatic model assessment of insulin resistance determined that the association was statistically significant only for women. Conclusion: Our data demonstrate a positive association between aldosterone levels and fatty liver in African American women.