Reducing Infection Rates with Enhanced Preoperative Diabetes Mellitus Diagnosis and Optimization Processes.

OBJECTIVES: Hyperglycemia and increased preoperative hemoglobin A1c (HbA1c) are associated with perioperative morbidity and death. For nonurgent operations, adequate glycemic control before surgery is recommended. Our surgical practice needed a process for preoperative diabetes mellitus (DM) diagnosis and glycemic optimization. METHODS: Our review of the existing preoperative evaluation process found that patients without a DM diagnosis but with random plasma glucose ≥200 mg/dL received no additional screening. Patients with DM routinely receive neither preoperative HbA1c screening nor DM management when HbA1c is ≥8.0%. RESULTS: A new preoperative evaluation process was designed. HbA1c screening was automatically performed for patients with random plasma glucose ≥200 mg/dL. For patients with a DM diagnosis, an HbA1c test was performed. Specialty consultation was prompted for patients with known DM and HbA1c ≥8.0% and those with no DM diagnosis but HbA1c ≥6.5%. In the first year postimplementation, 9320 patients received a basic metabolic panel; 263 had random plasma glucose ≥200 mg/dL that triggered an HbA1c check. In total, 123 patients (99 with and 24 without a DM diagnosis) were referred to endocrinology; 13 received a new DM diagnosis. Twenty patients had surgery delayed for DM treatment. All of the patients received individualized medication instructions for the perioperative period. Among patients with random plasma glucose ≥200 mg/dL, incidence rates for surgical site infection pre- and postimplementation were 47.8/1000 and 3.8/1000 population. CONCLUSIONS: The implemented process benefited patients scheduled for nonurgent procedures by optimizing glucose control and lowering infection rates through earlier preoperative DM diagnosis, glycemic management, and standardized patient medication instruction.

A case of celiac plexus block causing iatrogenic Cushing's syndrome.

Treatment with corticosteroids can lead to iatrogenic Cushing's syndrome when used for longer intervals and in high doses. Less common administration routes may conceal the exposure, raising the possibility of misdiagnosis and mismanagement.

Impact of Body Mass Index ≥35 kg/m2 on Minimally Invasive Adrenalectomy.

Introduction: Obesity is associated with numerous chronic conditions and an increased risk for surgical complications. Laparoscopic and robotic adrenalectomy have proven effective in the resection of adrenal tumors. This study analyzes the outcomes of severely obese patients (body-mass index [BMI] ≥35 kg/m2) following minimally invasive adrenalectomy. Materials and Methods: A retrospective analysis of patients who underwent minimally invasive adrenalectomy at our institution between 2010 and 2023 was conducted. Two matching analyses were performed. The first analysis compared patients with BMI greater versus lower than 35 kg/m2. The second analysis compared outcomes between robotic and laparoscopic adrenalectomy in patients with a BMI ≥35 kg/m2. Results: A total of 278 patients were included in the study. The median tumor size was 29 mm. Adrenal tumors had similar laterality, and most were hormonally active (66.2%). The most common pathological diagnosis was pheochromocytoma (25.5%). No statistical difference was found in peri- and postoperative outcomes between patients with BMI ≥35 and <35 kg/m2 who underwent minimally invasive adrenalectomy. When the surgical approach was compared in severely obese patients, robotic adrenalectomy was associated with shorter hospital length of stay with similar operative time as the laparoscopic approach. Conclusions: Minimally invasive adrenalectomy is safe and feasible in patients with BMI ≥35 kg/m2. Robotic and laparoscopic approaches are both safe and efficient for the resection of adrenal tumors in severely obese patients.

Anaplastic thyroid cancer: An update.

Anaplastic thyroid cancer (ATC) is one of the most lethal of all cancers. It is more common in women and occurs primarily in older patients. ATC has a median overall survival of 3-5 months and a nearly 100% disease-specific mortality. It is known to spread rapidly to locoregional structures as well as outside the neck to distant sites, hence ATC is always considered stage IV. With better understanding of the disease at a molecular level, the introduction of newer treatment strategies has been possible and is part of the multimodal (surgery, radiation, and systemic therapy) therapeutic approach. However, there is extensive work needed to achieve better survival outcomes.

Eleven-Year Experience with Selective Adrenal Vein Sampling in Management of Primary Adrenal Hormonal Hypersecretion.

Introduction: Nearly half of the adult population in the United States has been diagnosed with hypertension. Adrenal hormonal hypersecretion is a leading cause of secondary hypertension. Adrenal vein sampling (AVS) may assist in differentiating between unilateral and bilateral adrenal hormonal hypersecretion to identify patients who are candidates for adrenalectomy. We reviewed the use of AVS at our institution along with associated outcomes after adrenalectomy. Materials and Methods: A retrospective chart review was conducted of patients with a diagnosis of primary hyperaldosteronism (PA) or adrenocorticotropic hormone-independent Cushing syndrome (AICS) and who underwent adrenalectomy between January 1, 2010, and December 1, 2021. Patient data of baseline characteristics, preoperative workup, including AVS, and postoperative outcomes were collected and analyzed. Results: Seventy-one patients were identified in the study period (48 PA and 23 AICS). Computed tomography scan identified unilateral adrenal nodules in 52 patients (29 left; and 23 right), bilateral nodules in 13 patients, and no nodules in 6 patients. AVS was performed in 45 patients with PA (93%) and 5 patients with AICS (21%). After surgery, the number of PA patients with hypokalemia or requiring potassium supplementation significantly decreased after adrenalectomy (before surgery: 33 [68.7%]; and after surgery: 5 [10.4%], P < .01). The number of medications required for hypertension in AICS patients also significantly decreased. No major adverse events were noted. Conclusions: Our long-term experience demonstrates the ongoing use of AVS during workup of patients with primary hyperaldosteronism and for select patients with adrenocorticotropic hormone-independent Cushing syndrome. However, a low level of discordance between imaging and AVS findings in PA patients suggests that there may be a subset of patients in whom preoperative AVS is not necessary.

Lenvatinib as a Therapeutic Option in Unresectable Metastatic Pheochromocytoma and Paragangliomas.

Context: Metastatic pheochromocytomas and paragangliomas (mPPGL) are rare vascular neuroendocrine tumors that highly express vascular growth factors. Systemic treatment options in cases of unresectable multisite disease are limited. Multikinase inhibitors that inhibit angiogenesis, such as lenvatinib, have proven effective in several other malignancies, and may be a viable option for mPPGL. Objective: We aimed to evaluate the efficacy of lenvatinib as salvage therapy in mPPGLs. Methods: This was a retrospective analysis of mPPGL patients ≥ 18 years of age who received lenvatinib from 2015 to 2020 at a tertiary referral center. Patients were started on lenvatinib 20 mg daily and dose was adjusted according to tolerance or disease progression. Results: Eleven patients were included. Median treatment duration was 14.7 months (95% CI, 2.3-NE). Treatment was discontinued due to disease progression, adverse events, or death. Overall survival at 12 months was 80.8% (95% CI, 42.3-94.9%) but its median was not reached. Median progression-free survival was 14.7 months (95% CI, 1.7-NE). Among the 8 patients with measurable disease, overall response rate was 63%, as 5/8 experienced a partial response and 3/8 had stable disease. Worsening hypertension and anemia were the most common adverse events. Conclusion: Lenvatinib may be a viable treatment option for mPPGL, although at the potential risk of worsening hypertension. Larger, multicenter studies are needed to better characterize treatment efficacy.

Cytoreductive Surgery of the Primary Tumor in Metastatic Adrenocortical Carcinoma: Impact on Patients' Survival.

CONTEXT: The role of cytoreduction of adrenocortical carcinoma (ACC) remains poorly understood. OBJECTIVE: To analyze the impact of cytoreductive surgery of the primary tumor in patients with metastatic ACC. DESIGN AND SETTING: We performed a multicentric, retrospective paired cohort study comparing the overall survival (OS) in patients with metastatic ACC who were treated either with cytoreductive surgery (CR group) or without cytoreductive surgery (no-CR group) of the primary tumor. Data were retrieved from 9 referral centers in the American-Australian-Asian Adrenal Alliance collaborative research group. PATIENTS: Patients aged ≥18 years with metastatic ACC at initial presentation who were treated between January 1, 1995, and May 31, 2019. INTERVENTION: Performance (or not) of cytoreductive surgery of the primary tumor. MAIN OUTCOME AND MEASURES: A propensity score match was done using age and the number of organs with metastasis (≤2 or >2). The main outcome was OS, determined from the date of diagnosis until death or until last follow-up for living patients. RESULTS: Of 339 patients pooled, 239 were paired and included: 128 in the CR group and 111 in the no-CR group. The mean follow-up was 67 months. Patients in the no-CR group had greater risk of death than did patients in the CR group (hazard ratio [HR] = 3.18; 95% CI, 2.34-4.32). Independent predictors of survival included age (HR = 1.02; 95% CI, 1.00-1.03), hormone excess (HR = 2.56; 95% CI, 1.66-3.92), and local metastasis therapy (HR = 0.41; 95% CI, 0.47-0.65). CONCLUSION: Cytoreductive surgery of the primary tumor in patients with metastatic ACC is associated with prolonged survival.

Do Molecular Profiles of Primary Versus Metastatic Radioiodine Refractory Differentiated Thyroid Cancer Differ?

Management of metastatic radioiodine refractory differentiated thyroid cancer (DTC) can be a therapeutic challenge. Generally, little is known about the paired molecular profile of the primary tumor and the metastases and whether they harbor the same genetic abnormalities. The present study compared the molecular profile of paired tumor specimens (primary tumor/metastatic sites) from patients with radioiodine refractory DTC in order to gain insight into a possible basis for resistance to radioiodine. Twelve patients with radioiodine refractory metastases were studied; median age at diagnosis of 61 years (range, 25-82). Nine patients had papillary TC (PTC), one had follicular TC (FTC), and two had Hürthle cell TC (HTC). Distant metastases were present in the lungs (n = 10), bones (n = 4), and liver (n = 1). The molecular profiling of paired tumors was performed with a panel of 592 genes for Next Generation Sequencing, RNA-sequencing, and immunohistochemistry. Digital microfluidic PCR was used to investigate TERT promoter mutations. The genetic landscape of all paired sites comprised BRAF, NRAS, HRAS, TP53, ATM, MUTYH, POLE, and NTRK genes, including BRAF and NTRK fusions. BRAF V600E was the most common point mutation in the paired specimens (5/12). TERT promoter mutation C228T was detected in one case. PD-L1 expression at metastatic sites was highly positive (95%) for one patient with HTC. All specimens were stable for microsatellite instability testing, and the tumor mutation burden was low to intermediate. Therefore, the molecular profile of DTC primary and metastatic lesions can show heterogeneity, which may help explain some altered responses to therapeutic intervention.

Indeterminate thyroid nodules in the era of molecular genomics.

BACKGROUND: Indeterminate thyroid nodules are diagnosed in up to 30% of fine-needle aspirations and the risk of malignancy in these cases are highly variable. Consequently, managing these nodules has been a challenge. While a diagnostic thyroidectomy would help clarify the pathology, there is the risk of developing surgical-related complications for a procedure that may not have been necessary and associated high costs. Genomic testing of indeterminate thyroid nodules may help better guide management. METHODS: We present an unbiased comprehensive review of available molecular testing for classifying indeterminate thyroid nodules, as well as their strengths and limitations, with the objective to allow practitioners to choose the best testing modality for their patients. RESULTS: Molecular testing of these nodules provided a platform to help distinguish benign versus malignant nodules, providing more confidence to rule in or rule out the likelihood of thyroid cancer in indeterminate nodules. CONCLUSION: Genomic testing has evolved to more comprehensive panels to better stratify indeterminate nodules, including Hürthle cell neoplasms and noninvasive follicular neoplasm with papillary-like nuclear features. Understanding the methodology of each available test improves patient care and reduces unnecessary costs.

Brain Metastases From Differentiated Thyroid Carcinoma: Prevalence, Current Therapies, and Outcomes.

BACKGROUND AND OBJECTIVE: The brain is an unusual site for distant metastases of differentiated thyroid carcinoma (DTC). The aim of this study was to document the prevalence of brain metastases from DTC at our institutions and to analyze the current therapies and the outcomes of these patients. METHODS: We performed a retrospective chart review of patients with DTC and secondary neoplasia of the brain. RESULTS: From 2002 to 2016, 9514 cases of thyroid cancer were evaluated across our institutions and 24 patients met our inclusion criteria, corresponding to a prevalence of 0.3% of patients with DTC. Fourteen (58.3%) were female and 10 (41.7%) were male. Fifteen patients had papillary thyroid cancer (PTC) (62.5%). Brain metastases were diagnosed 0 to 37 years (mean ± SD, 10.6 ± 10.4 years) after the initial diagnosis of thyroid cancer. Patients undergoing surgery had a median survival time longer than those that did not undergo surgery (27.3 months vs 6.8 months; P = 0.15). Patients who underwent stereotactic radiosurgery (SRS) had a median survival time longer than those that did not receive SRS (52.5 months vs 6.7 months; P = 0.11). Twelve patients (50%) were treated with tyrosine kinase inhibitors (TKIs), and they had a better survival than those who have not used a TKI (median survival time, 27.2 months vs 4.7 months; P < 0.05). CONCLUSION: The prevalence of brain metastases of DTC in our institutions was 0.3% over 15 years. The median survival time after diagnosis of brain metastases was 19 months. In our study population, the use of TKI improved the survival rates.

Navigating Systemic Therapy in Advanced Thyroid Carcinoma: From Standard of Care to Personalized Therapy and Beyond.

Thyroid cancer, with the exception of anaplastic thyroid cancer, typically has very favorable outcomes with the standard therapy. However, those that persist, recur, or metastasize are associated with a worse prognosis. Targeted therapy with kinase inhibitors has shown promise in advanced cases of thyroid cancer, and currently five drug regimens are approved for use in clinical practice in the treatment of differentiated, medullary, and anaplastic thyroid cancer, with more options in the pipeline. However, one of the greatest dilemmas is when and how to initiate one of these drugs, and this is discussed herein.

Mantle Cell Lymphoma in the Thyroid: A Rare Presentation.

BACKGROUND: While 2% of all extranodal Non-Hodgkin Lymphomas present in the thyroid, there exists insufficient data to describe the incidence of mantle cell lymphoma in the thyroid. A case series of 1400 patients revealed that <1% of thyroid lymphomas may be MCL; hence better understanding of the disease course is essential. PATIENT FINDINGS: A 65-year-old female was referred for a multinodular goiter. Multiple fine needle aspirations from the dominant right nodule were consistent with Hashimoto's thyroiditis and flow cytometry was negative. Due to progressing dysphagia, she underwent total thyroidectomy. SUMMARY: Pathology revealed MCL with mantle zone growth pattern in the right thyroid. Flow cytometry showed monoclonal B cells comprising 9% of total cells. The Ki-67 index was 10%. She was diagnosed as having stage IIE MCL and offered conservative management by medical oncology, given that she had no B symptoms. CONCLUSION: Though chemotherapy is the treatment of choice in MCL, a subset of patients with low-grade disease may be observed. As in our patient, mantle zone growth pattern and a Ki-67 index < 10% suggest a favorable prognosis. A diagnosis of primary MCL in the thyroid remains rare and staging modalities as well as treatment options continue to evolve.

Patterns of Treatment Failure in Anaplastic Thyroid Carcinoma.

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most lethal forms of cancer with a high mortality rate. Current guidelines support surgery for resectable ATC followed by external beam radiation therapy (EBRT) with or without chemotherapy. Treatment for those who are unresectable is palliative. Our goal was to examine first-line therapies as well as the role of genomic profiling in an effort better understand how to approach ATC. METHODS: This is a retrospective study of ATC patients who were seen at our institution from January 2013 to October 2015. Median overall survival (OS) and time to treatment failure (TTF) were calculated by the Kaplan-Meier method. RESULTS: Fifty-four patients were included. Median age at diagnosis was 63 years and 29/54 (54%) were women. The majority had stage IVC disease at diagnosis (50%), followed by IVB (32%), and IVA (18%). Approximately 93% had somatic gene testing. Initial treatment was surgery in 23 patients, EBRT with or without radiosensitizing chemotherapy in 29 patients, and systemic chemotherapy in 2 patients. Nineteen patients had all three treatment modalities. For the entire cohort, median OS was 11.9 months with 39% survival at 1 year and median TTF was 3.8 months. The majority of patients (74%) developed new distant metastasis or progression of existing metastatic disease. Patients who received trimodal therapy consisting of surgery, EBRT, and chemotherapy had a median OS of 22.1 months versus 6.5 months in those who received dual therapy with EBRT and chemotherapy (p = 0.0008). The TTF was the same in the two groups (7.0 and 6.5 months, respectively). Men were three times more likely to die from ATC than women (p = 0.0024). No differences in OS or TTF were noted based on tumor size (5 cm cutoff), age (60 years cutoff), or presence of any mutation. There was a trend toward shorter TTF in patients with somatic mutations in TP53. CONCLUSION: Patients with ATC amenable to aggressive tri-modal therapy demonstrate improved survival. The short TTF, due primarily to distant metastatic disease, highlights the potential opportunity for improved outcomes with earlier initiation of systemic therapy including adjuvant or neoadjuvant therapy.

5th International ACC Symposium: Old Syndromes with New Biomarkers and New Therapies with Old Medications.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with variable but often aggressive clinical course. Hormonal overproduction can be seen in about half of all ACC cases. When present, the hormonal excess leads to a wide range of metabolic, musculoskeletal, cardiovascular, and infectious complications and adds multiple layers of complexity to the management of ACC. To improve the outcome of patients with hormonally functioning ACC, an effective approach should include parallel efforts to achieve oncologic and hormonal control. An experienced multidisciplinary team is crucial to deliver and coordinate care to manage the specific aspects of this condition. In this review, we summarized the clinical features and management of hormonally functioning ACCs to assist practicing physicians in addressing the complex medical issues that can be seen in the context of this clinical entity.

Bone Metastases and Skeletal-Related Events in Medullary Thyroid Carcinoma.

CONTEXT: Bone metastases (BM) can lead to devastating skeletal-related events (SREs) in cancer patients. Data regarding medullary thyroid carcinoma (MTC) with BM are lacking. OBJECTIVE: We evaluated the natural history of BM and SREs in MTC patients identified by a cancer center tumor registry. SETTING: The study was conducted at a tertiary cancer center. PATIENTS AND MAIN OUTCOME MEASURES: We retrospectively reviewed the charts of MTC patients with BM who received care from 1991 to 2014 to characterize BM and SREs. RESULTS: Of 1008 MTC patients treated, 188 were confirmed to have BM (19%), of whom 89% (168 of 188) had nonosseous distant metastases. Median time from MTC to BM diagnosis was 30.9 months (range 0-533 mo); 25% (45 of 180) had BM identified within 3 months of MTC diagnosis. Median follow-up after detecting BM was 1.6 years (range 0-23.2 y). Most patients (77%) had six or more BM lesions, most often affecting the spine (92%) and pelvis (69%). Many patients (90 of 188, 48%) experienced one or more SREs, most commonly radiotherapy (67 of 90, 74%) followed by pathological fracture (21 of 90, 23%). Only three patients had spinal cord compression. Patients with more than 10 BM lesions were more likely to experience SREs (odds ratio 2.4; P = .007), with no difference in 5-year mortality after MTC diagnosis between patients with (31%) and without SREs (23%) (P = .11). CONCLUSIONS: In this large retrospective series, BM in MTC was multifocal, primarily involving the spine and pelvis, supporting screening these regions for metastases in at-risk patients. SREs were common but spinal cord compression was rare. Antiresorptive therapies in this population should be investigated further with prospective trials.

Recurrent Mutations of Chromatin-Remodeling Genes and Kinase Receptors in Pheochromocytomas and Paragangliomas.

PURPOSE: Pheochromocytomas and paragangliomas (PPGL) are genetically heterogeneous tumors of neural crest origin, but the molecular basis of most PPGLs is unknown. EXPERIMENTAL DESIGN: We performed exome or transcriptome sequencing of 43 samples from 41 patients. A validation set of 136 PPGLs was used for amplicon-specific resequencing. In addition, a subset of these tumors was subjected to microarray-based transcription, protein expression, and histone methylation analysis by Western blotting or immunohistochemistry. In vitro analysis of mutants was performed in cell lines. RESULTS: We detected mutations in chromatin-remodeling genes, including histone-methyltransferases, histone-demethylases, and histones in 11 samples from 8 patients (20%). In particular, we characterized a new cancer syndrome involving PPGLs and giant cell tumors of bone (GCT) caused by a postzygotic G34W mutation of the histone 3.3 gene, H3F3A Furthermore, mutations in kinase genes were detected in samples from 15 patients (37%). Among those, a novel germline kinase domain mutation of MERTK detected in a patient with PPGL and medullary thyroid carcinoma was found to activate signaling downstream of this receptor. Recurrent germline and somatic mutations were also detected in MET, including a familial case and sporadic PPGLs. Importantly, in each of these three genes, mutations were also detected in the validation group. In addition, a somatic oncogenic hotspot FGFR1 mutation was found in a sporadic tumor. CONCLUSIONS: This study implicates chromatin-remodeling and kinase variants as frequent genetic events in PPGLs, many of which have no other known germline driver mutation. MERTK, MET, and H3F3A emerge as novel PPGL susceptibility genes. Clin Cancer Res; 22(9); 2301-10. ©2015 AACR.

Metastatic mesothelioma to the thyroid.

A 69 year-old male patient with a history of malignant mesothelioma treated with chemotherapy and surgical resection with removal of the right lung and right pleural pneumonectomy was clinically in remission for 1 ½ years. A positron emission tomography (PET) scan revealed limited uptake in the right pleural space, thought to represent post-surgical changes, and uptake in the left thyroid lobe. Thyroid ultrasound revealed a solid left lobe nodule with peripheral vascularity and absent microcalcifications. Fine needle aspiration cytology showed a microfollicular arrangement of cytologically bland cells with variable Hürthle cell changes initially interpreted as suspicious for Hürthle cell neoplasm. Review at multidisciplinary conference raised the possibility of metastatic mesothelioma, supported by immunohistochemical studies in the cell block. The patient opted for left hemithyroidectomy with isthmusectomy which confirmed malignant mesothelioma. Repeat PET scan 6 months later revealed no further uptake in the thyroid bed, with limited uptake in the right pleural space. Metastatic tumors to the thyroid are uncommon with only one previous description of metastasis to the thyroid by mesothelioma. Metastasis of cytologically low grade tumors such as mesothelioma present problems for cytology due to the potential for overlap with the variable appearances of thyroid neoplasms. The value (if any) of ancillary tests, including mutation testing, expression profiling and immunohistochemistry is discussed.