Impact of Nonalcoholic Fatty Liver Disease (NAFLD) on Weight Loss After Bariatric Surgery.

OBJECTIVE: Obesity and associated comorbidities, such as NAFLD, impose a major healthcare burden worldwide. Bariatric surgery remains the most successful approach for sustained weight loss and the resolution of obesity-related complications. However, the impact of preexisting NAFLD on weight loss after bariatric surgery has not been previously studied. The goal of this study is to assess the impact of preexisting NAFLD on weight loss outcomes up to 5 years after weight loss surgery. RESEARCH DESIGN AND METHODS: Data from the Michigan Bariatric Surgery Cohort (MI-BASiC) was extracted to examine the effect of baseline NAFLD on weight loss outcomes. The cohort included a total of 714 patients older than 18 years of age undergoing gastric bypass (GB; 380 patients) or sleeve gastrectomy (SG; 334 patients) at the University of Michigan between January 2008 and November 2013. Repeated measure analysis was used to determine if preexisting NAFLD was a predictor of weight loss outcomes up to 5 years post-surgery. RESULTS: We identified 221 patients with an established clinical diagnosis of NAFLD at baseline. Multivariable repeated measure analysis with adjustment for covariates shows that patients with preexisting NAFLD had a significantly lower percentage of total and excess weight loss compared to patients without preexisting NAFLD. Furthermore, our data show that baseline dyslipidemia is an indicator of the persistence of NAFLD after bariatric surgery. CONCLUSIONS: Our data show that patients' body weight loss in response to bariatric surgery is impacted by factors such as preexisting NAFLD. Additionally, we show that NAFLD may persist or recur in a subset of patients after surgery, and thus careful continued follow-up is recommended.

Impact of diabetes on weight loss outcomes after bariatric surgery: Experience from 5-year follow-up of Michigan Bariatric Surgery Cohort.

OBJECTIVE: For patients with obesity and diabetes, bariatric surgery can lead to the remission of both diseases. However, the possible impact of diabetes on the magnitude of weight loss outcomes after bariatric surgery has not been precisely quantified. RESEARCH DESIGN AND METHODS: Data from Michigan Bariatric Surgery Cohort (MI-BASiC) was extracted to examine the effect of baseline diabetes on weight loss outcomes. Consecutive patients older than 18 years of age undergoing gastric bypass (GB) or sleeve gastrectomy (SG) for obesity at University of Michigan between January 2008 and November 2013 were included. Repeated measures analysis was used to determine if diabetes was a predictor of weight loss outcomes over 5 years postsurgery. RESULTS: Out of the 714 included patients, 380 patients underwent GB [mean BMI 47.3 ± 0.4 kg/m2 , diabetes 149 (39.2%)] and 334 SG [mean BMI 49.9 ± 0.5 kg/m2 , diabetes 108 (32.3%)]. Multivariable repeated measures analysis showed, after adjusting for covariates, that individuals with diabetes had a significantly lower percentage of total (p = .0023) and excess weight loss (p = .0212) compared to individuals without diabetes. CONCLUSIONS: Our data demonstrate that patients with diabetes undergoing bariatric surgery would experience less weight loss than patients without diabetes.

Predicting Early Weight Loss Failure Using a Bariatric Surgery Outcomes Calculator and Weight Loss Curves.

CONTEXT: Weight loss after bariatric surgery can be accurately predicted using an outcomes calculator; however, outliers exist that do not meet the 1 year post-surgery weight projections. OBJECTIVE: Our goal was to determine how soon after surgery these outliers can be identified. DESIGN: We conducted a retrospective cohort study. SETTING, PATIENTS, AND INTERVENTION: Using a bariatric surgery outcomes calculator formulated by the Michigan Bariatric Surgery Collaborative (MBSC), predicted weight loss at 1 year post-surgery was calculated on all patients who underwent primary bariatric surgery at a single-center academic institution between 2006 and 2015 who also had a documented 1-year follow-up weight (n = 1050). MAIN OUTCOME MEASURES: Weight loss curves were compared between high, low, and non-outliers as defined by their observed-to-expected (O:E) weight loss ratio based on total body weight loss (TBWL) %. RESULTS: Mean predicted weight loss for the study group was 39.1 ± 9.9 kg, while mean actual weight loss was 39.7 ± 17.1 kg resulting in a mean O:E 1.01 (± 0.35). Based on analysis of the O:E ratios at 1 year post-surgery, the study group was sub-classified. Low outliers (n = 188, O:E 0.51) had significantly lower weight loss at 2 months (13.1% vs 15.6% and 16.5% TBWL, p < 0. 001) and at 6 months (19% vs 26% and 30% TBWL, p < 0.001) when compared to non-outliers (n = 638, O:E 1.00) and high outliers (n = 224, O:E 1.46), respectively. CONCLUSIONS: Weight loss curves based on individually calculated outcomes can help identify low outliers for additional interventions as early as 2 months after bariatric surgery.

Metreleptin therapy for nonalcoholic steatohepatitis: Open-label therapy interventions in two different clinical settings.

BACKGROUND: Recombinant leptin therapy reverses nonalcoholic steatohepatitis (NASH) in leptin-deficient lipodystrophy. We inquired if leptin therapy would improve nonalcoholic steatohepatitis in more common forms of this heterogeneous condition. METHODS: Nine male patients with relative leptin deficiency (level < 25th percentile of body mass index- and gender-matched United States population) and biopsy-proven NASH and 23 patients with partial lipodystrophy and NASH were recruited for two distinctive open-label trials. Participants received leptin therapy in the form of metreleptin for 12 months. The primary endpoints were the global nonalcoholic steatohepatitis scores from paired liver biopsies scored blindly. FINDINGS: Of 9 participants recruited in the relative leptin deficiency treatment study, 7 completed 12-months of therapy. Mean global NASH scores were reduced from 8 ± 3 to 5 ± 2 (range: from 1 to 6, P = 0.004). In the partial lipodystrophy study, 19 of 22 subjects completed 12 months of treatment, and 18 completed a second liver biopsy. Global NASH scores also reduced significantly from 6 ± 2 to 5 ± 2 (range: from -2 to 4, P = 0.008). In both studies, the predominant changes were in steatosis and hepatic injury scores. CONCLUSION: Our findings show that patients with NASH associated with both relative leptin deficiency and partial lipodystrophy have reductions in hepatic steatosis and injury in response to exogenous leptin therapy. Moreover, leptin deficiency may have regulatory effects in mediating fat deposition and ensuing injury in the liver.TRIAL REGISTRATION. ClinicalTrials.gov NCT00596934 and NCT01679197.

Immediate and partial neural dysfunction after thyroid and parathyroid surgery: Need for recognition, laryngeal exam, and early treatment.

BACKGROUND: Laryngeal dysfunction after thyroid and parathyroid surgery requires early recognition and a standardized approach for patients that present with voice, swallowing, and breathing issues. The Endocrine Committee of the American Head and Neck Society (AHNS) convened a panel to define the terms "immediate vocal fold paralysis" and "partial neural dysfunction" and to provide clinical consensus statements based on review of the literature, integrated with expert opinion of the group. METHODS: A multidisciplinary expert panel constructed the manuscript and recommendations for laryngeal dysfunction after thyroid and parathyroid surgery. A meta-analysis was performed using the literature and published guidelines. Consensus was achieved using polling and a modified Delphi approach. RESULTS: Twenty-two panelists achieved consensus on five statements regarding the role of early identification and standardization of evaluation for patients with "immediate vocal fold paralysis" and "partial neural dysfunction" after thyroid and parathyroid surgery. CONCLUSION: After endorsement by the AHNS Endocrine Section and Quality of Care Committee, it received final approval from the AHNS Council.

Cancer incidence and mortality following treatment of hyperthyroidism with radioactive iodine.

PURPOSE OF REVIEW: Hyperthyroidism is a commonly encountered clinical issue. Radioactive iodine is one of the treatment modalities employed over the last 80 years. Prior studies are conflicting as to whether radioactive iodine is associated with an increased risk of subsequent malignancy and associated mortality. The present article reviews recent publications on this subject. RECENT FINDINGS: Two recent studies make meaningful contributions to the existing literature; however, data remain inconsistent. The first, conducted using the Clalit Health Services database, evaluated solid tumor incidence after radioactive iodine and found no association with increased risk of solid tumor malignancy. The second, which is an updated analysis of the Cooperative Thyrotoxicosis Therapy Follow-up Study, concluded that there is a dose-dependent increased risk of solid tumor mortality using a novel method of estimating organ-specific radiation exposure. SUMMARY: In patients with hyperthyroidism, radioactive iodine is a popular and effective treatment option. Prior studies reach conflicting conclusions on the potential relationship between radioactive iodine and both subsequent cancer incidence and mortality. We review recent publications that add to our understanding of this important clinical question.

Patient Report of Recurrent and Persistent Thyroid Cancer.

Background: Despite the excellent survival of most patients with differentiated thyroid cancer (DTC), recurrent and persistent disease remain major concerns for physicians and patients. However, studies on patient report of recurrent and persistent disease are lacking. Methods: Between February 1, 2017, and October 31, 2018, we surveyed eligible patients who were diagnosed with DTC between 2014 and 2015 from the Georgia and Los Angeles Surveillance, Epidemiology, and End Results cancer registries (N = 2632; response rate, 63%). Patients who reported current disease status were included in this study (n = 2454). Patient-reported data were linked to registry data. A multivariable, multinomial logistic regression analysis was conducted to determine patient and tumor characteristics associated with recurrent and persistent thyroid cancer. Quality of life was evaluated using the Patient-Reported Outcomes Measurement Information System-Global Health v1.2 questionnaire. Meaningful change in global health was defined as a minimal difference of a half standard deviation or 5 points compared with the mean (T score = 50) of a sample population matching the United States 2000 General Census. Results: Of the 2454 patients completing the survey, 95 (4.1%) reported recurrent disease and 137 (5.8%) reported persistent disease. In multinomial analyses, T3/T4 classification and cervical lymph node involvement (N1) were associated with both report of recurrent (adjusted relative risk ratio [RRR] 1.99, 95% confidence interval [CI 1.16-3.42]; adjusted RRR 2.03 [CI 1.29-3.21], respectively) and persistent disease (adjusted RRR 3.48 [CI 1.96-6.20]; adjusted RRR 3.56 [CI 2.41-5.24], respectively). Additionally, Hispanic ethnicity was associated with report of recurrent disease (adjusted RRR 1.99 [CI 1.23-3.24]). Regarding quality of life, the median scores in patients with persistent disease met criteria for meaningful change in global physical health (T-score = 44.9) and global mental health (T-score = 43.5) when compared with the general population norms. Median scores in patients with cured or recurrent disease did not meet criteria for meaningful change. Conclusions: Patient report is a reasonable method of assessing recurrent and persistent disease. Impact on quality of life is more marked for patients with reported persistent disease. Our findings will help personalize treatment and long-term follow-up in these patients.

Bariatric Surgery in the Treatment of Type 2 Diabetes.

PURPOSE OF REVIEW: We seek to characterize the impact of bariatric surgery on diabetes mellitus by recalling its history, examining the clinical data, exploring the putative mechanisms of action, and anticipating its future. RECENT FINDINGS: Results of clinical trials reveal that bariatric surgery induces remission of diabetes in 33-90% of individuals at 1-year post-treatment versus 0-39% of medically managed. Remission rates decrease over time but remain higher in surgically treated individuals. Investigations have revealed numerous actions of surgery including effects on intestinal physiology, neuronal signaling, incretin hormone secretion, bile acid metabolism, and microbiome changes. Bariatric surgery improves control of diabetes through both weight-dependent and weight-independent actions. These various mechanisms help explain the difference between individuals treated surgically vs. medically. They also explain differing effects of various bariatric surgery procedure types. Understanding how surgery affects diabetes will help optimize utilization of the therapy for both disease prevention and treatment.

Factors Associated With Diagnosis and Treatment of Thyroid Microcarcinomas.

CONTEXT: Nearly one-third of all thyroid cancers are ≤1 cm. OBJECTIVE: To determine diagnostic pathways for microcarcinomas vs larger cancers. DESIGN/SETTING/PARTICIPANTS: Patients from Georgia and Los Angeles Surveillance, Epidemiology, and End Results (SEER) registries with differentiated thyroid cancer diagnosed in 2014 or 2015 were surveyed. Survey data were linked to SEER data on tumor and treatment characteristics. Multivariable logistic regression analysis was performed. MAIN OUTCOME MEASURES: Method of nodule discovery; reason for thyroid surgery. RESULTS: Of patients who underwent surgery, 975 (38.2%) had cancers ≤1 cm, and 1588 cancers (61.8%) were >1 cm. The reported method of nodule discovery differed significantly between patients with cancers ≤1 cm and those with cancers >1 cm (P < 0.001). Cancer ≤1 cm was associated with nodule discovery on thyroid ultrasound (compared with other imaging, OR, 1.59; 95% CI, 1.21 to 2.10), older patient age (45 to 54 years vs ≤44, OR, 1.45; 95% CI, 1.16 to 1.82), and female sex (OR, 1.51; 95% CI, 1.22 to 1.87). Hispanic ethnicity (OR, 0.71; 95% CI, 0.57 to 0.89) and Asian race (OR, 0.67; 95% CI, 0.49 to 0.92) were negative correlates. Cancers ≤1 cm were associated with lower likelihood of surgery for a nodule suspicious or consistent with cancer (OR, 0.48; 95% CI, 0.40 to 0.57). CONCLUSION: Thyroid microcarcinomas are more likely to be detected by ultrasound and less likely to be associated with surgery scheduled for known thyroid cancer. Understanding diagnostic pathways allows for targeted interventions to decrease overdiagnosis and overtreatment.

Diagnosis of acquired generalized lipodystrophy in a single patient with T-cell lymphoma and no exposure to Metreleptin.

BACKGROUND: Metreleptin, a recombinant methionyl -human -leptin, was approved to treat patients with generalized lipodystrophy (GL) in February 2014. However, leptin therapy has been associated with the development of lymphoma. We present a unique case of a patient with prior history of T cell lymphoma in remission, who was diagnosed with Acquired Generalized Lipodystrophy (AGL) during the following year after a clinical remission of her lymphoma without receiving leptin therapy. CASE PRESENTATION: A 33-year-old woman with a diagnosis of stage IV subcutaneous panniculitis like T-cell lymphoma in 2011, underwent chemotherapy. Shortly after completion therapy, she had a relapse and required more chemotherapy with complete response, followed by allogenic stem cell transplant on June 28, 2012. Since that time, she has been on observation with no evidence of disease recurrence. Subsequent to the treatment, she was found to have high triglycerides, loss of fat tissue from her entire body and diagnosis of diabetes. Constellation of these findings led to the diagnosis of AGL in 2013. Her leptin level was low at 3.4 ng/mL (182 pmol/mL). She is currently not receiving any treatment with Metreleptin for her AGL. CONCLUSIONS: Causal association between exogenous leptin therapy and T-cell lymphoma still remains unclear. We hereby present a case of a young woman who was diagnosed with AGL after going into remission from T-cell lymphoma and who has never been treated with Metreleptin. Steroid therapy and chemotherapy might have masked the diagnosis of AGL in this patient. We believe that patients can develop these 2 conditions independent of each other.

Differentiated Thyroid Cancer Outcomes After Surgery and Activity-Adjusted 131I Theragnostics.

PURPOSE: The aim of this study was to determine clinical outcomes in patients with differentiated thyroid cancer after surgery and activity-adjusted I therapy informed by diagnostic I scans with SPECT/CT (Dx scan). METHODS: Single-institution retrospective cohort study analysis of clinical outcomes after 1 to 5 years (mean, 39.6 ± 23.4 months) of follow-up in 350 patients with differentiated thyroid cancer associated with histopathologic risk factors, nodal metastases, and/or distant metastases. Postoperatively, all patients underwent Dx scans for completion of staging and risk stratification, and I therapy was based on integration of information from histopathology, stimulated thyroglobulin and scintigraphy. RESULTS: Twenty-three patients (6.6%) underwent reoperative neck dissection for removal of unsuspected residual nodal metastases identified on Dx scans. Clinical outcomes were as follows: 84.3% complete response, 1.4% biochemical incomplete response, 2.3% indeterminate response, and 12% structural incomplete response. Of the entire cohort, only 8 patients (2.3%) had persistent iodine-avid metastatic disease, which required repeated I therapy. Of 31 patients with iodine-avid distant metastases identified on Dx scans, 13 patients (42%) achieved complete response with a single I treatment. CONCLUSIONS: Detection of regional and distant metastases on postoperative Dx scans permits adjustment of prescribed I activity for targeted treatment, as compared with fixed-activity ablation. This approach resulted in complete response after a single I treatment in 88% patients with histopathologic risk factors and regional metastases and 42% patients with distant metastases. Most patients with structural incomplete response (81%) had elevated thyroglobulin levels with negative follow-up I scans and positive PET/CT and/or CT scans consistent with altered tumor biology (non-iodine-avid disease).

Metabolic Parameters, Weight Loss, and Comorbidities 4 Years After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy.

BACKGROUND: Sleeve gastrectomy (LSG) is now the predominant bariatric surgery performed, yet there is limited long-term data comparing important outcomes between LSG and Roux-en-Y gastric bypass (RYGB). This study compares weight loss and impact on comorbidities of the two procedures. METHODS: We retrospectively evaluated weight, blood pressure, hemoglobin A1c, cholesterol, and medication use for hypertension, diabetes, and hyperlipidemia at 1-4 years post-operatively in 380 patients who underwent RYGB and 334 patients who underwent LSG at the University of Michigan from January 2008 to November 2013. Follow-up rates from 714 patients initially were 657 (92%), 556 (78%), 507 (71%), and 498 (70%) at 1-4 years post-operatively. RESULTS: Baseline characteristics were similar except for higher weight and BMI in LSG. There was greater weight loss with RYGB vs. LSG at all points. Hemoglobin A1c and total cholesterol improved more in RYGB vs. LSG at 4 years. There was greater remission of hypertension and discontinuation of all medications for hypertension and diabetes with RYGB at 4 years. CONCLUSIONS: Weight loss, reduction in medications for hypertension and diabetes, improvements in markers of diabetes and hyperlipidemia, and remission rates of hypertension were superior with RYGB vs. LSG 4 years post-operatively. Choice of bariatric procedures should be tailored to surgical risk, comorbidities, and weight loss goals.

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.

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.

Struma Ovarii With Hyperthyroidism.

We report the case of a 61-year-old woman with persistent thyrotoxicosis for 7 years despite low thyroidal radioiodine uptake and methimazole treatment. Her initial I whole-body scan (WBS) was read as negative. Upon evaluation in our institution, she remained hyperthyroid after discontinuation of methimazole. Repeat WBS with SPECT/CT revealed low 24-hour thyroidal uptake (RAIU = 2%) and intensely focal radioiodine uptake in a large heterogeneous left pelvic mass, consistent with left adnexal struma ovarii. Resection of this mass confirmed benign struma ovarii. This case illustrates the advantage of fusion SPECT/CT imaging with planar I-WBS for diagnosis of extrathyroidal thyrotoxicosis.

Milestone Weight Loss Goals (Weight Normalization and Remission of Obesity) after Gastric Bypass Surgery: Long-Term Results from the University of Michigan.

BACKGROUND: Rates of weight normalization and obesity remission after Roux-en-Y gastric bypass (GB) are unknown. This study evaluated weight loss, rates of achieving body mass index (BMI) <25 or 30 kg/m2, recidivism, and predictors of success following GB. METHODS: We retrospectively studied weight and BMI at baseline, 2 and 6 months, and annually at 1-7 years in 219 patients undergoing GB at the University of Michigan from January 2008 to November 2010. RESULTS: Follow-up was excellent for a population traditionally associated with high attrition rates with data availability of 157/219, 145/219, 144/219, 134/219, 123/219, 82/161, and 29/64 patients at 1-7 years, respectively. Mean baseline BMI was 47.0 kg/m2. Weight normalization (BMI <25 kg/m2) occurred in 2.3-6.8% of patients. More importantly, 47% of patients achieved remission of obesity (BMI <30 kg/m2) at some time point and 24% (52/219) at the last observed time point. BMI <30 kg/m2 was associated with a lower initial BMI and follow-up for more than 2 years. CONCLUSIONS: Rates of weight normalization are low after GB; however, a large number of patients achieved BMI <30 kg/m2. While the percent total weight loss and excess weight loss are both quite high in the entire cohort and this is likely associated with significant health benefits, our results still underscore the need to address obesity with intensive clinical attention earlier in its course.

Roux-En-Y Gastric Bypass Vs. Sleeve Gastrectomy: Balancing the Risks of Surgery with the Benefits of Weight Loss.

BACKGROUND: The purpose of the study was to compare weight loss, metabolic parameters, and postoperative complications in patients undergoing Roux-en-Y gastric bypass (GB) and sleeve gastrectomy (SG). METHODS: We retrospectively studied 30-day postoperative complications as well as change in weight, blood pressure, cholesterol, hemoglobin, hemoglobin A1C, and creatinine from baseline to 2, 6, 12, and 24 months postoperatively in 383 patients undergoing GB and 336 patients undergoing SG at the University of Michigan from January 2008 to November 2013. For a study population which typically has high attrition rates, there were excellent follow-up rates (706/719 at 2 months, 566/719 at 6 months, 519/719 at 12 months, and 382/719 at 24 months). RESULTS: Baseline characteristics were similar in both groups except for higher weight and BMI in the SG group. The GB group experienced greater total body weight loss at 6, 12, and 24 months (41.9 vs. 34.6 kg at 24 months, p < 0.0001). Excess weight loss was 69.7 and 51.7 % following GB and SG respectively at 24 months (p < 0.0001). BP improved significantly in both groups. Surgical complication rates were greater after GB (10.1 vs. 3.5 %, p = 0.0007) with no significant difference in life-threatening or potentially life-threatening complications. CONCLUSIONS: Weight loss was greater following GB compared to SG at 2 years. The risk for surgical complications was greater following GB. Surgical intervention should be tailored to surgical risk, comorbidities, and desired weight loss.

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.

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.

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.