Pre-operative thyroglobulin measurement for thyroid cancer risk of recurrence and response to therapy.

BACKGROUND: Thyroid cancer has an overall favorable prognosis, but no pre-operative biochemical marker has been shown to distinguish between low and high-risk disease or predict response to therapy. METHODS: We retrospectively reviewed 162 patients that underwent thyroid surgery for thyroid cancer between 2006 and 2022 in whom a pre-operative thyroglobulin level (Tg) was measured. We subdivided patients into low, intermediate and high-risk thyroid cancer and based on their response to therapy per ATA guidelines. RESULTS: We showed that as pre-operative Tg level increased, patients were more likely to have high-risk disease (p â€‹< â€‹0.01). We found a linear association between the primary tumor size and high-risk histology with pre-operative Tg (p â€‹< â€‹0.01). Pre-operative Tg level was significantly associated with response to therapy following initial surgical management. Specifically, as pre-operative Tg increases, patients were less likely to achieve an excellent response (p â€‹< â€‹0.01). CONCLUSIONS: Our retrospective analysis demonstrated that pre-operative Tg is significantly associated with ATA structural risk of recurrence and response to therapy and may have the potential to guide initial therapy and follow-up management.

Thyroid Cancer Polygenic Risk Score Improves Classification of Thyroid Nodules as Benign or Malignant.

CONTEXT: Thyroid nodule ultrasound-based risk stratification schemas rely on the presence of high-risk sonographic features. However, some malignant thyroid nodules have benign appearance on thyroid ultrasound. New methods for thyroid nodule risk assessment are needed. OBJECTIVE: We investigated polygenic risk score (PRS) accounting for inherited thyroid cancer risk combined with ultrasound-based analysis for improved thyroid nodule risk assessment. METHODS: The convolutional neural network classifier was trained on thyroid ultrasound still images and cine clips from 621 thyroid nodules. Phenome-wide association study (PheWAS) and PRS PheWAS were used to optimize PRS for distinguishing benign and malignant nodules. PRS was evaluated in 73 346 participants in the Colorado Center for Personalized Medicine Biobank. RESULTS: When the deep learning model output was combined with thyroid cancer PRS and genetic ancestry estimates, the area under the receiver operating characteristic curve (AUROC) of the benign vs malignant thyroid nodule classifier increased from 0.83 to 0.89 (DeLong, P value = .007). The combined deep learning and genetic classifier achieved a clinically relevant sensitivity of 0.95, 95% CI [0.88-0.99], specificity of 0.63 [0.55-0.70], and positive and negative predictive values of 0.47 [0.41-0.58] and 0.97 [0.92-0.99], respectively. AUROC improvement was consistent in European ancestry-stratified analysis (0.83 and 0.87 for deep learning and deep learning combined with PRS classifiers, respectively). Elevated PRS was associated with a greater risk of thyroid cancer structural disease recurrence (ordinal logistic regression, P value = .002). CONCLUSION: Augmenting ultrasound-based risk assessment with PRS improves diagnostic accuracy.

Computer-Assisted Levothyroxine Dose Selection for the Treatment of Postoperative Hypothyroidism.

Background: Thyroid hormone replacement with levothyroxine (LT4) is a recommended treatment for patients undergoing thyroidectomy. The starting LT4 dose is frequently calculated based on the patient's weight. However, the weight-based LT4 dosing performs poorly in clinical practice, with only ∼30% of patients achieving target thyrotropin (TSH) levels at the first thyroid function testing after treatment initiation. A better way to calculate the LT4 dose for patients with postoperative hypothyroidism is needed. Methods: In this retrospective cohort study we used demographic, clinical, and laboratory data for 951 patients after thyroidectomy and several regression and classification machine learning methods to develop an LT4 dose calculator for treating postoperative hypothyroidism targeting the desired TSH level. We compared the accuracy with the current standard-of-care practice and other published algorithms and evaluated generalizability with fivefold cross-validation and out-of-sample testing. Results: The retrospective clinical chart review showed that only 285/951 (30%) patients met their postoperative TSH goal. Obese patients were overtreated with LT4. An ordinary least squares regression based on weight, height, age, sex, calcium supplementation, and height:sex interaction predicted prescribed LT4 dose in 43.5% of all patients and 45.3% of patients with normal postoperative TSH (0.45-4.5 mIU/L). The ordinal logistic regression, artificial neural networks regression/classification, and random forest methods achieved comparable performance. LT4 calculator recommended lower LT4 doses to obese patients. Conclusions: The standard-of-care LT4 dosing does not achieve the target TSH in most thyroidectomy patients. Computer-assisted LT4 dose calculation performs better by considering multiple relevant patient characteristics and providing personalized and equitable care to patients with postoperative hypothyroidism. Prospective validation of LT4 calculator performance in patients with various TSH goals is needed.

A novel biosynthetic scaffold mesh reinforcement affords the lowest hernia recurrence in the highest-risk patients.

INTRODUCTION: Patients with higher postoperative infection risk undergoing ventral hernia repair (VHR) have limited options for mesh use. Biosynthetic mesh is intended to utilize the durability of synthetic mesh combined with the biocompatibility of biologic mesh. We sought to assess the outcomes of a novel biosynthetic scaffold mesh for VHR in higher risk patients over a 12-month postoperative period. METHODS: Two cohorts of 50 consecutive patients who underwent VHR with TELA Bio OviTex biosynthetic or synthetic mesh were retrospectively compared. Endpoints included surgical site occurrence (SSO), readmission rate, and hernia recurrence following VHR at 12 months postoperatively. RESULTS: OviTex mesh placement was associated with higher risk Ventral Hernia Working Group (VHWG) distribution and more contaminated CDC wound class distribution compared to synthetic mesh placement (VHWG grade 3: 68% vs. 6%, p < 0.001; CDC class > I: 70% vs. 6%, p < 0.001). Additionally, concomitant procedures were performed more often with OviTex mesh placement than synthetic mesh placement (70% vs 10%, p < 0.001). The OviTex mesh performed comparably to synthetic mesh in terms of incidences of SSO (36% vs 22%, p = 0.19), readmission rates (24% vs 14%, p = 0.31), and hernia recurrence (6% vs 12%, p = 0.74). On further evaluation, patients who developed SSO with OviTex mesh (n = 18) had a 17% hernia recurrence whereas those with synthetic mesh (n = 11) had an associated 55% hernia recurrence (p = 0.048). CONCLUSIONS: The OviTex biosynthetic mesh was used in higher risk patients and performed similarly to synthetic mesh in regards to rate of SSO, readmissions, and hernia recurrence. Furthermore, patients who developed SSO with Ovitex mesh were significantly less likely to have hernia recurrence than those with synthetic mesh. Overall, the data suggest that biosynthetic mesh is a more desirable option for definitive hernia repair in higher risk patients.

Mucinous cystic neoplasms of the liver: presence of biliary communication.

A 35-year-old woman was referred for a symptomatic liver mass. Diagnostic workup detected a septated cyst located centrally in the liver measuring 10 × 7 cm. The cyst had gradually increased in size from previous studies with new intrahepatic biliary dilation. Due to concern for malignancy and symptomatic presentation of the patient, a partial central hepatectomy was performed. Pathology revealed a smooth-walled, multiloculated cyst lined with mucinous epithelium and ovarian-type stroma. The diagnosis of low-grade mucinous cystic neoplasm of the liver (MCN-L) was made. Characteristics of MCN-L have not been elucidated due to its rarity.

Diagnosing microscopic pancreatic neuroendocrine tumor using 68-Ga-DOTATATE PET/CT: case series.

Neuroendocrine tumors (NETs) are an uncommon diagnosis which often present asymptomatically or with vague symptoms. They can originate from many different organs such as the GI tract, lungs, pancreas and others. 68Gallium DOTATATE positron emission topography/computed topography has been shown to be an effective imaging modality for diagnosing NET and evaluating management options for patients. Here, we present two cases of positive findings in the distal pancreas on the DOTATATE PET/CT scans without any morphological lesion found to be NET in a healthy 48-year-old male and 68-year-old male.

The Impact of Somatostatin Receptor-Directed PET/CT on the Management of Patients with Neuroendocrine Tumor: A Systematic Review and Meta-Analysis.

Somatostatin receptor (SSTR) imaging is widely used for guiding the management of neuroendocrine tumor (NET) patients. 68Ga-DOTATATE approval by the U.S. Food and Drug Administration has triggered widespread clinical interest in SSTR PET/CT throughout the United States. Here, we performed a systematic review and meta-analysis to evaluate the impact of SSTR PET/CT on the management of patients with NETs. Methods: A comprehensive literature search was performed using The National Center for Biotechnology Information PubMed online database, applying the following key words: "management" AND "PET" AND "neuroendocrine". Fourteen of 190 studies were deemed suitable based on the following inclusion criteria: original research, cohort study, number of patients 10 or more, and reported change in management after SSTR PET/CT. Change in management across studies was determined by a random-effects model. Results: A total of 1,561 patients were included. Overall, change in management occurred in 44% (range, 16%-71%) of NET patients after SSTR PET/CT. In 4 of 14 studies, SSTR PET/CT was performed after an 111In-Octreotide scan. In this subgroup, additional information by SSTR PET/CT led to a change in management in 39% (range, 16%-71%) of patients. Seven of 14 studies differentiated between inter- and intramodality changes, with most changes being intermodality (77%; intramodality, 23%). Conclusion: The management was changed in more than one third of patients undergoing SSTR PET/CT even when performed after an 111In-Octreotide scan. Intermodality changes were 3 times more likely than intramodality changes, underlining the clinical impact of SSTR PET/CT.

Human Biodistribution and Radiation Dosimetry of 18F-Clofarabine, a PET Probe Targeting the Deoxyribonucleoside Salvage Pathway.

18F-clofarabine, a nucleotide purine analog, is a substrate for deoxycytidine kinase (dCK), a key enzyme in the deoxyribonucleoside salvage pathway. 18F-clofarabine might be used to measure dCK expression and thus serve as a predictive biomarker for tumor responses to dCK-dependent prodrugs or small-molecule dCK inhibitors, respectively. As a prerequisite for clinical translation, we determined the human whole-body and organ dosimetry of 18F-clofarabine. Methods: Five healthy volunteers were injected intravenously with 232.4 ± 1.5 MBq of 18F-clofarabine. Immediately after tracer injection, a dynamic scan of the entire chest was acquired for 30 min. This was followed by 3 static whole-body scans at 45, 90, and 135 min after tracer injection. Regions of interest were drawn around multiple organs on the CT scan and copied to the PET scans. Organ activity was determined and absorbed dose was estimated with OLINDA/EXM software. Results: The urinary bladder (critical organ), liver, kidney, and spleen exhibited the highest uptake. For an activity of 250 MBq, the absorbed doses in the bladder, liver, kidney, and spleen were 58.5, 6.6, 6.3, and 4.3 mGy, respectively. The average effective dose coefficient was 5.1 mSv. Conclusion: Our results hint that 18F-clofarabine can be used safely in humans to measure tissue dCK expression. Future studies will determine whether 18F-clofarabine may serve as a predictive biomarker for responses to dCK-dependent prodrugs or small-molecule dCK inhibitors.

68Ga-DOTATATE PET/CT Interobserver Agreement for Neuroendocrine Tumor Assessment: Results of a Prospective Study on 50 Patients.

We evaluated observer agreement for 68Ga-DOTATATE PET/CT interpretations in patients with neuroendocrine tumor (NET). METHODS: 68Ga-DOTATATE PET/CT was performed on 50 patients with known or suspected NET of the small bowel (n = 19), pancreas (n = 14), lung (n = 4), or other location (n = 13). The images were reviewed by 7 observers, who used a standardized interpretation approach. The observers were classified as having a low level of experience (<500 scans or <5 y experience with 68Ga-DOTATATE PET/CT; n = 4) or a high level of experience (≥500 scans or ≥5 y experience with 68Ga-DOTATATE PET/CT; n = 3). Interpretation by the primary nuclear medicine physician, who had access to all clinical and imaging data, served as the reference standard. Interobserver agreement was determined by the Cohen κ statistic and intraclass correlation coefficient (ICC) with corresponding 95% confidence interval (95%CI). RESULTS: Interobserver agreement was substantial, and the median number of false findings was low for the overall scan result: that is, positive versus negative scan result (κ = 0.80; 95%CI, 0.74-0.86; false findings, 3), organ involvement (κ = 0.70; 95%CI, 0.64-0.76; false findings, 5), and lymph node involvement (κ = 0.71; 95%CI, 0.65-0.78; false findings, 6). Interobserver agreement was substantial to almost perfect, and the average absolute difference (Δ) from the reference observer was low for number of organ and lymph node metastases (organ: ICC, 0.84; 95%CI, 0.77-0.89; Δ = 0.45; lymph node: ICC, 0.77; 95%CI, 0.69-0.84; Δ = 0.45), tumor SUVmax (ICC, 0.99; 95%CI, 0.97-0.99; Δ = 0.44), and reference SUV (spleen: ICC, 0.81; Δ = 1.10; liver: ICC, 0.79; Δ = 0.62). Interpretations of appropriateness for peptide-receptor radionuclide therapy varied more significantly among observers (κ = 0.64; 95%CI, 0.57-0.70), and a higher frequency of false-positive recommendations for peptide-receptor radionuclide therapy occurred in observers with low experience than in those with high experience (range, 7-12 vs. 4-8). CONCLUSION: The interpretation of 68Ga-DOTATATE PET/CT images for NET staging is consistent among observers with low and high levels of experience. However, image-based recommendations for or against peptide-receptor radionuclide therapy require experience and training.

Prostate specific membrane antigen (PSMA) ligands for diagnosis and therapy of prostate cancer.

INTRODUCTION: Prostate specific membrane antigen (PSMA) has become an attractive diagnostic and therapeutic target for small molecule ligands. Radionuclide-chelating ligands can be labeled with either 68Ga for positron-emission-tomography (PET) or 177Lu for radionuclide therapy. Areas covered: In this literature review we evaluate the diagnostic value of 68Ga PSMA PET/CT and the therapeutic potential of 177Lu PSMA radioligand therapy (RLT) in patients with prostate cancer. 68Ga PSMA PET/CT is more accurate than CT for nodal staging and superior to conventional imaging in patients with biochemical recurrence, translating into major changes in clinical management. The preliminary data for 177Lu PSMA indicates >50% reduction of PSA levels in up to 59% of patients. Severe adverse events occurred <10% of patients after RLT. Expert commentary: PSMA ligands for diagnostic and therapeutic purpose will significantly impact the management of patients with prostate cancer.

The incidence of thyroid cancer in focal hypermetabolic thyroid lesions: an 18F-FDG PET/CT study in more than 6000 patients.

BACKGROUND: The clinical significance of incidental thyroid abnormalities discovered in fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) (FDG PET/CT) studies remains controversial. The aim of this large retrospective study was to (a) determine the prevalence of focal F-FDG thyroid uptake on whole-body F-FDG PET/CT studies carried out for nonthyroid cancers and (b) to test whether intense focal F-FDG thyroid uptake is associated with malignancy. MATERIALS AND METHODS: A total of 11 921 F-FDG PET/CT studies in 6216 patients carried out at our institution between January 2012 and December 2014 were analyzed. We retrospectively reviewed the medical records of these patients. Eight hundred and forty-five/6216 (13.6%) patients had a thyroid incidentaloma on the basis of the clinical F-FDG PET/CT report. One hundred and sixty/845 (18.9%) of these underwent ultrasound and 98 (61.3%) of these underwent a fine-needle aspiration (FNA). Twenty-six of these 98 (26.5%) patients underwent thyroidectomy. Thyroid lesion and background standardized uptake value (SUVs) for each patient were measured upon review of the F-FDG PET/CT study. We measured maximum standardized uptake value (SUVmax), thyroid to background TL/TBG, thyroid to bloodpool TL/BP and thyroid to liver TL/L ratios in benign and malignant lesions. Receiver operating curves were calculated to determine optimal cut-off values between malignant and benign lesions. RESULTS: Twenty-one of the 98 patients who underwent FNA biopsy or thyroidectomy had malignant disease (21.4%). Malignant lesions had significantly higher thyroid lesion SUVmax, TL/TBG, TL/BP, and TL/L than benign nodules. The receiver operating curves derived cut-off ratio TL/TBG of more than 2.0 differentiated benign from malignant lesions best with a specificity and sensitivity of 0.76 and 0.88, respectively. CONCLUSION: The incidence of malignancy in biopsied focal hypermetabolic thyroid lesions is 21.4%. Lesions on F-FDG PET/CT studies, with a ratio TL/TBG more than 2.0, warrant further work-up with ultrasound and FNA to exclude malignancy.

Incidence of abnormal positron emission tomography in patients with unexplained cardiomyopathy and ventricular arrhythmias: The potential role of occult inflammation in arrhythmogenesis.

BACKGROUND: The incidence of myocardial inflammation in patients with unexplained cardiomyopathy referred for ventricular arrhythmias (VAs) is unknown. OBJECTIVE: The purpose of this study was to report fasting positron emission tomographic (PET) scan findings in consecutive patients referred with unexplained cardiomyopathy and VA. METHODS: Fluorine-18 fluoro-2-deoxyglucose (18-FDG) PET/computed tomographic (CT) scans with a >16-hour fasting protocol were prospectively ordered for patients referred for VA and unexplained cardiomyopathy (ejection fraction <55%). Patients with focal myocardial FDG uptake were labeled as arrhythmogenic inflammatory cardiomyopathy (AIC) and classified into 4 groups based on the presence of lymph node uptake (AIC+) and perfusion abnormalities (early vs late stage). RESULTS: Over a 3-year period, 103 PET scans were performed, with 49% (AIC+ 17, AIC 33) exhibiting focal FDG uptake. Mean patient age was 52 ± 12 years (ejection fraction 36% ± 16%). Patients with AIC were more likely to have a history of pacemaker (32% vs 6%, P = .002) compared to those with normal PET. When biopsy was performed, histologic diagnosis revealed nongranulomatous inflammation in 6 patients and sarcoidosis in 18 patients. Ninety percent of patients with AIC/AIC+ were prescribed immunosuppressive therapy, and 58% underwent ablation. Correlation between low voltage regions on electroanatomic mapping and FDG uptake was observed in 74%. Magnetic resonance imaging findings matched abnormal PET regions in only 40%. CONCLUSION: Nearly 50% of patients referred with unexplained cardiomyopathy and VA demonstrate ongoing focal myocardial inflammation on FDG PET. These data suggest that a significant proportion of patients labeled "idiopathic" may have occult AIC, which may benefit from early detection and immunosuppressive medical therapy.

Impact of 68Ga-DOTATATE PET/CT on the management of neuroendocrine tumors: the referring physician's perspective.

UNLABELLED: Somatostatin receptor imaging with (68)Ga-DOTATATE PET/CT (DOTATATE) is increasingly used for managing patients with neuroendocrine tumors. The objective of this study was to determine referring physicians' perspectives on the impact of DOTATATE on the management of neuroendocrine tumors. METHODS: A set of 2 questionnaires (pre-PET and post-PET) was sent to the referring physicians of 100 consecutive patients with known or suspected neuroendocrine tumors, who were evaluated with DOTATATE. Questionnaires on 88 patients were returned (response rate, 88%). Referring physicians categorized the DOTATATE findings on the basis of the written PET reports as negative, positive, or equivocal for disease. The likelihood for metastatic disease was scored as low, moderate, or high. The intended management before and changes as a consequence of the PET study were indicated. RESULTS: The indications for PET/CT were initial and subsequent treatment strategy assessments in 14% and 86% of patients, respectively. Referring physicians reported that DOTATATE led to a change in suspicion for metastatic disease in 21 patients (24%; increased and decreased suspicion in 9 [10%] and 12 [14%] patients, respectively). Intended management changes were reported in 53 of 88 (60%) patients. Twenty patients (23%) scheduled to undergo chemotherapy were switched to treatments without chemotherapy, and 6 (7%) were switched from watch-and-wait to other treatment strategies. Conversely, 5 patients (6%) were switched from their initial treatment strategy to watch-and-wait. CONCLUSION: This survey of referring physicians demonstrates a substantial impact of DOTATATE on the intended management of patients with neuroendocrine tumors.

[Prevention of thromboembolism in bariatric surgery]. / Prevencíon del tromboembolismo en cirugía bariátrica.

Disease thromboembolic (ETEV) is one of the major complications that can occur after surgery, and is the leading cause of death in the postoperative period of Bariatric Surgery. Among other factors, should be aware that these patients are at additional risk of ETEV due to own obesity (IMC > 30). After Bariatric Surgery the risk of thromboembolic events varies according to the surveyed series. In general, it is estimated that danger EP (pulmonary embolism) is 0.8% and DVT (deep vein thrombosis) of 1.7%. ETEV global mortality estimates of 0.1 to 2%.

[Morbid obesity]. / Obesidad mórbida.

Morbid obesity (MO) is a serious disease caused by genetic and environmental factors, which is associated with multiple comorbid factors that impact very significantly on the amount and life quality. Obesity surgery is a complex surgery but not without complications, which objective is to achieve an ideal weight or cure obesity reducing comorbidities and improving the welfare of patients. The Spanish Society for the Study of Obesity (SEED) and the Spanish Society of Obesity Surgery (SECO) have developed a consensus document that allows the various professionals involved in the treatment of OM practical guidance in developing their own protocols in their work environment. In this context, the general and digestive service of the HUB team developed the clinical course of this surgical procedure because it is a tool that facilitates systematic care and multidisciplinary group of patients with a predictable clinical course, such as whether morbidly obese patients operated by laparotomy or laparoscopy.

[Thromboembolic prophylaxis in bariatric surgery. A multidisciplinary protocol]. / Cirugía bariátrica. Profilaxis tromboembólica.

Severe or morbid obesity is one of the 21st century epidemics. Surgery is the most important and cost-effective treatment. Bariatric procedures are becoming very common in our Hospitals. Thromboembolic events such us deep venous thrombosis or pulmonary embolism (PE) are the most common medical cause of death after these procedures. Incidence of PE may arise to 3% after surgery and its mortality is about 75%. Prophylactic protocols have not been clearly defined until now. These protocols have to consider special patients, such as morbid obese ones; different kind of procedures, most of the laparoscopic; and patients' comorbidities. By the other hand, treatment for morbid obesity has to be considered by a multidisciplinary approach. Here we present the protocol that has been initiated at our Institution. After a long and high experience in bariatric procedures, we have defined a multidisciplinary protocol to prevent thromboembolic events after surgery where nurses and surgeons play a leading role. The combination of physical, pharmaceutical and educational measures all together are the key for the adequate prevention in these patients.