Clinical Outcomes of Biliary Drainage in Patients with Malignant Biliary Obstruction Caused by Colorectal Cancer Metastases.

BACKGROUND AND AIM: Malignant biliary obstruction is an ominous complication of metastatic colorectal cancer (mCRC) that is challenging to solve. Biliary drainage can be performed to relieve symptoms of jaundice, treat cholangitis, or enable palliative systemic therapy. The aim of this study is to evaluate clinical outcomes of biliary drainage of malignant biliary obstruction in mCRC patients. METHODS: Consecutive patients with malignant biliary obstruction due to mCRC who underwent endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography were included. Patient, disease, and procedural characteristics and outcomes were retrospectively collected from electronic medical records. Radiological data were prospectively reassessed. Main outcome was functional success, i.e. achievement of the intended goal of biliary drainage. Prognostic factors for functional success and survival were assessed. RESULTS: Thirty-seven patients were included. Functional success was achieved in 18 (50%) patients. Seventeen (46%) patients experienced adverse events (suspected to be) related to the procedure. Median overall survival after biliary drainage was 61 days (IQR 31-113). No prognostic factors of functional success were identified. Performance status, presence of the primary tumor, ascites, ≥ 5 intrahepatic metastases, estimated hepatic invasion of > 50% and above-median levels of bilirubin and lactate dehydrogenase were significantly associated with poorer survival. Improved survival was seen in patients with technical, functional, or biochemical success, and with subsequent oncologic treatment. CONCLUSIONS: Functional successful biliary drainage was achieved in half of the patients. Adverse events also occurred in nearly half of the patients. We observed a significantly longer survival in whom biliary drainage allowed palliative oncologic therapy.

Fast-track Radioiodine Ablation Therapy After Thyroidectomy Reduces Sick Leave in Patients With Differentiated Thyroid Cancer (FASTHYNA Trial).

BACKGROUND: Recombinant human thyroid stimulating hormone (RhTSH) aided radioiodine ablative therapy (RIT) is current-day practice in the treatment of differentiated thyroid cancer (DTC). It is often planned 4 to 6 weeks after surgery or sometimes even longer (standard protocol). The RhTSH-aided RIT, however, has the advantage that it can be planned shortly after thyroidectomy. The FASTHYNA trial was designed to test the hypothesis that RIT 1 week after thyroidectomy (fast-track protocol) results in a significant reduction of sick leave with lower societal costs and with a better quality of life (QOL) compared with the current standard treatment. METHODS: In a randomized, multicenter trial, we included patients with differentiated thyroid cancer, stage T1-3 N0-1 M0-x, who were treated with a total or completion thyroidectomy, with a paid job of at least 12 hours per week. The primary study end point was days of sick leave reported from time of surgery. Secondary end points were QOL and societal costs associated with absence from work. RESULTS: Twenty patients were eligible for inclusion between November 2013 and May 2016. Significant decreases in mean duration of sick leave in the fast-track group versus the standard care group (115 and 280 hours, respectively, P = 0.02) and in costs associated with productivity losses (&OV0556;4070.77 vs &OV0556;9202.90, P = 0.02) were found. There were no significant differences in QOL between both groups. CONCLUSIONS: The trial showed a significant reduction in sick leave and in societal costs in the fast-track group without a deterioration of QOL. Therefore, fast-track ablation is desirable. TRIAL REGISTRATION: Netherlands trial register: NTR 3933.

Follow-up of patients with thyroglobulin-antibodies: Rising Tg-Ab trend is a risk factor for recurrence of differentiated thyroid cancer.

PURPOSE: Differentiated thyroid cancer is the most common endocrine malignancy. Recurrences (5-20%) are the main reason for follow-up. Thyroglobulin (Tg) has proven to be an excellent disease marker, but thyroglobulin-antibodies (Tg-Ab) may interfere with Tg measurement, leading to over or underestimation. It is proposed that the Tg-Ab trend can be used as a marker for disease recurrence, yet few studies define trend and have a long-term follow-up. The objective of our study was to investigate the value of a well-defined Tg-Ab trend as a surrogate marker for disease recurrence during long-term follow-up. METHODS: We retrospectively studied patients treated at the Nuclear Department of the University Medical Center Utrecht from 1998 to 2010 and the Netherlands Cancer Institute from 2000 to 2009. All patients with Tg-Ab 12 months after treatment were included. The definition of a rise was >50% increase of the Tg-Ab value in a 2 year time period. A decline as >50% decrease of the Tg-Ab value. RESULTS: Twenty-five patients were included. None of the patients with declining or stable Tg-Ab without a concomitant rise in Tg developed a recurrence. Four patients did suffer a recurrence. Three of these patients had a rising Tg-Ab trend, in two of these patients Tg was undetectable. CONCLUSIONS: Tg-Ab trend can be used as a crude surrogate marker for long-term follow-up of Tg-Ab patients. A rising trend in Tg-Ab warrants further investigation to detect recurrent disease. Stable or declining Tg-Ab levels do not seem to reflect a risk for recurrence.

Calibration of PET/CT scanners for multicenter studies on differentiated thyroid cancer with (124)I.

BACKGROUND: Studies on imaging of differentiated thyroid cancer (DTC) using (124)I often require a multicenter approach, as the prevalence of DTC is low. Calibration of participating scanners is required to obtain comparable quantification. As determination of a well-defined range of recovery coefficients is complicated for various reasons, a simpler approach based on the assumption that the iodine uptake is highly focal with a background that significantly lacks radioactivity might be more efficient. For each scanner, a linear conversion between known and observed activity can be derived, allowing quantification that can be traced to a common source for all scanners within one study-protocol. The aim of this paper is to outline a procedure using this approach in order to set up a multicenter calibration of PET/CT scanners for (124)I. METHODS: A cylindrical polyethylene phantom contained six 2-ml vials with reference activities of ~2, 10, 20, 100, 400, and 2000 kBq, produced by dilution from a known activity. The phantom was scanned twice on PET/CT scanners of participating centers within 1 week. For each scanner, the best proportional and linear fit between measured and known activities were derived and based on statistical analyses of the results of all scanners; it was determined which fit should be applied. In addition, a Bland-Altman analysis was done on calibrated activities with respect to reference activities to asses the relative precision of the scanners. RESULTS: Nine Philips (vendor A) and nine Siemens (vendor B) PET/CT scanners were calibrated in a time period of 3 days before and after the reference time. No significant differences were detected between the two subsequent scans on any scanner. Six fitted intercepts of vendor A were significantly different from zero, so the linear model was used. Intercepts ranged from -8 to 26 kBq and slopes ranged from 0.80 to 0.98. Bland-Altman analysis of calibrated and reference activities showed that the relative error of calibrated activities was smaller than that of uncalibrated activities. CONCLUSIONS: A simplified multicenter calibration procedure for PET/CT scans that show highly focal uptake and negligible background is feasible and results in more precise quantification. Our procedure can be used in multicenter (124)I PET scans focusing on (recurrent) DTC.

Characteristics of contralateral carcinomas in patients with differentiated thyroid cancer larger than 1 cm.

PURPOSE: Traditionally, total thyroidectomy has been advocated for patients with tumors larger than 1 cm. However, according to the ATA and NCCN guidelines (2015, USA), patients with tumors up to 4 cm are now eligible for lobectomy. A rationale for adhering to total thyroidectomy might be the presence of contralateral carcinomas. The purpose of this study was to describe the characteristics of contralateral carcinomas in patients with differentiated thyroid cancer (DTC) larger than 1 cm. METHODS: A retrospective study was performed including patients from 17 centers in 5 countries. Adults diagnosed with DTC stage T1b-T3 N0-1a M0 who all underwent a total thyroidectomy were included. The primary endpoint was the presence of a contralateral carcinoma. RESULTS: A total of 1313 patients were included, of whom 426 (32 %) had a contralateral carcinoma. The contralateral carcinomas consisted of 288 (67 %) papillary thyroid carcinomas (PTC), 124 (30 %) follicular variant of a papillary thyroid carcinoma (FvPTC), 5 (1 %) follicular thyroid carcinomas (FTC), and 3 (1 %) Hürthle cell carcinomas (HTC). Ipsilateral multifocality was strongly associated with the presence of contralateral carcinomas (OR 2.62). Of all contralateral carcinomas, 82 % were ≤10 mm and of those 99 % were PTC or FvPTC. Even if the primary tumor was a FTC or HTC, the contralateral carcinoma was (Fv)PTC in 92 % of cases. CONCLUSIONS: This international multicenter study performed on patients with DTC larger than 1 cm shows that contralateral carcinomas occur in one third of patients and, independently of primary tumor subtype, predominantly consist of microPTC.

Thyroid Ultrasound-Guided Fine-Needle Aspiration: The Positive Influence of On-Site Adequacy Assessment and Number of Needle Passes on Diagnostic Cytology Rate.

OBJECTIVE: Nondiagnostic cytology is the most important limitation of thyroid ultrasound-guided fine-needle aspiration (US-FNA). This study aimed to identify factors associated with the adequacy rate of thyroid US-FNA. STUDY DESIGN: Consecutive thyroid US-FNAs (2006-2013) were retrospectively included. Attending radiologists, radiology fellows and radiology residents performed US-FNA, usually involving 2-3 needle passes. In more recent years, rapid on-site adequacy assessment (ROSAA) was performed to ensure specimen adequacy. US characteristics, procedural variations and cytology results were extracted from US and pathology reports and statistically evaluated. RESULTS: Diagnostic cytology was obtained in 64.6% of 1,381 thyroid US-FNAs. Factors associated with nondiagnostic cytology were ROSAA (74.6% diagnostic cytology, OR 0.55, 95% CI 0.42-0.71), ≥3 clinic visits for US-FNA of the same thyroid nodule (54.7%, OR 1.56, 95% CI 1.16-2.10) and increased intranodular vascularization (51.8%, OR 1.73, 95% CI 1.17-2.57). With ROSAA, an increasing number of needle passes demonstrated improving adequacy rates. The adequacy rate was not operator-dependent. CONCLUSION: This study demonstrates that ROSAA improves the adequacy rate of thyroid US-FNA. Without ROSAA, we recommend performing at least 3 needle passes. Less diagnostic cytology is obtained from nodules with increased intranodular vascularization or from those undergoing US-FNA ≥3 times.

SAME-DAY FINE-NEEDLE ASPIRATION CYTOLOGY DIAGNOSIS FOR THYROID NODULES ACHIEVES RAPID ANXIETY DECREASE AND HIGH DIAGNOSTIC ACCURACY.

OBJECTIVE: The time between the moment of referral for the diagnostic workup for thyroid nodules and the outcome can be worrisome for patients. In general, patients experience high levels of anxiety during the evaluation of a lesion suspicious for cancer. Therefore, the implementation of same-day fine-needle aspiration cytology (FNAC) diagnosis is becoming standard-of-care for many solid tumors. Our aim was to assess the feasibility of same-day FNAC diagnosis for thyroid nodules and to assess patient anxiety during the diagnostic process. METHODS: For feasibility of same-day FNAC diagnosis, we assessed the proportion of patients receiving a diagnosis at the end of the visit. Accuracy was measured by comparing histology with the FNAC result. Patient anxiety was measured by the State Trait Anxiety Inventory at 6 moments during the diagnostic workup. RESULTS: Of the 131 included patients, 112 (86%) were female, and the mean age was 53 years. All patients, except those with a nondiagnostic FNAC result (n = 26; 20%), had a diagnosis at the end of the day. There were only two discordant results. Anxiety levels at the beginning of the day were high throughout the group, State Trait Anxiety Inventory (STAI) score 43.1 (SD 2.0) and decreased significantly more in patients with a benign FNAC result (STAI score 30.2), compared to patients with a malignant or indeterminate result (STAI score 39.6). CONCLUSION: Distress of patients with a thyroid nodule undergoing same-day FNAC diagnostics was high. Same-day FNAC diagnosis is feasible and accurate for the evaluation of thyroid nodules. Therefore, same-day FNAC diagnosis seems a safer, more patient-friendly approach to diagnose thyroid nodules.

Quantitative Comparison of 124I PET/CT and 131I SPECT/CT Detectability.

UNLABELLED: Radioiodine therapy with (131)I is used for treatment of suspected recurrence of differentiated thyroid carcinoma. Pretherapeutic (124)I PET/CT with a low activity (~1% of (131)I activity) can be performed to determine whether uptake of (131)I, and thereby the desired therapeutic effect, may be expected. However, false-negative (124)I PET/CT results as compared with posttherapeutic (131)I SPECT/CT have been reported by several groups. The purpose of this study was to investigate whether the reported discrepancies may be ascribed to a difference in lesion detectability between (124)I PET/CT and (131)I SPECT/CT and, hence, whether the administered (124)I activity is sufficient to achieve equal detectability. METHODS: Phantom measurements were performed using the National Electrical Manufacturers Association 2007 image-quality phantom. As a measure of detectability, the contrast-to-noise ratio was calculated. The (124)I activity was expressed as the percentage of (131)I activity required to achieve the same contrast-to-noise ratio. This metric was defined as the detectability equivalence percentage (DEP). RESULTS: Because lower DEPs were obtained for smaller spheres, a relatively low (124)I activity was sufficient to achieve similar lesion detectability between (124)I PET/CT and (131)I SPECT/CT. DEP was 1.5%, 1.9%, 1.9%, 4.4%, 9.0%, and 16.2% for spheres with diameters of 10, 13, 17, 18, 25, and 37 mm, respectively, for attenuation- and scatter-corrected SPECT versus point-spread function (PSF) model-based and time-of-flight (TOF) PET. For no-PSF no-TOF PET, DEP was 3.6%, 2.1%, 3.5%, 7.8%, 15.1%, and 23.3%, respectively. CONCLUSION: A relatively low (124)I activity of 74 MBq (~1% of (131)I activity) is sufficient to achieve similar lesion detectability between (124)I PSF TOF PET/CT and (131)I SPECT/CT for small spheres (≤10 mm), since the reported DEPs are close to 1%. False-negative (124)I PET/CT results as compared with posttherapeutic (131)I SPECT/CT may be ascribed to differences in detectability for large lesions (>10 mm) and for no-PSF no-TOF PET, since DEPs are greater than 1%. On the basis of DEPs of 3.5% for lesion diameters of up to 17 mm on no-PSF no-TOF PET, (124)I activities as high as 170 MBq may be warranted to obtain equal detectability.

124I PET/CT to Predict the Outcome of Blind 131I Treatment in Patients with Biochemical Recurrence of Differentiated Thyroid Cancer: Results of a Multicenter Diagnostic Cohort Study (THYROPET).

UNLABELLED: Patients with suspected recurrence from differentiated thyroid carcinoma, based on an increased thyroglobulin (Tg) level and negative neck ultrasound (US), pose a clinical dilemma. Because standard imaging has a low yield identifying potential recurrence, blind (131)I treatment is often applied. However, a tumor-negative (131)I whole-body scintigraphy (WBS) prevails in 38%-50% of patients. We performed a prospective multicenter observational cohort study to test the hypothesis that (124)I PET/CT can identify the patients with a tumor-negative posttherapy (131)I WBS. METHODS: Our study was designed to include 100 patients with detectable Tg and a negative neck US, who were planned for blind (131)I therapy. All patients underwent (124)I PET/CT after administration of recombinant human thyroid-stimulating hormone. Subsequently, after 4-6 wk of thyroid hormone withdrawal patients were treated with 5.5-7.4 GBq of (131)I, followed by WBS a week later. The primary endpoint was the number of (131)I therapies that could have been omitted using the predicted outcome of the (124)I PET/CT, operationalized as the concordance of tumor detection by (124)I PET/CT, using post-(131)I therapy WBS as the reference test. The study would be terminated if 3 patients had a negative (124)I PET/CT and a positive posttherapy (131)I scan. RESULTS: After inclusion of 17 patients, we terminated the study preliminarily because the stopping rule had been met. Median Tg level at (131)I therapy was 28 µg/L (interquartile range, 129). Eight posttherapy WBS were negative (47%), all of which were correctly predicted by negative (124)I PET/CT. Nine posttherapy WBS showed iodine-avid tumor, of which 4 also had positive (124)I PET/CT findings. Sensitivity, specificity, negative predictive value, and positive predictive value of (124)I PET/CT were 44% (confidence interval [CI], 14%-79%), 100% (CI, 63%-100%), 62% (CI, 32%-86%), and 100% (CI, 40%-100%), respectively. Implementation of (124)I PET in this setting would have led to 47% (8/17) less futile (131)I treatments, but 29% of patients (5/17) would have been denied potentially effective therapy. CONCLUSION: In patients with biochemical evidence of recurrent differentiated thyroid carcinoma and a tumor-negative neck US, the high false-negative rate of (124)I PET/CT after recombinant human thyroid-stimulating hormone (124)I PET/CT as implemented in this study precludes its use as a scouting procedure to prevent futile blind (131)I therapy.

Qualitative elastography can replace thyroid nodule fine-needle aspiration in patients with soft thyroid nodules. A systematic review and meta-analysis.

CONTEXT: Only a minority of thyroid nodules is malignant; nevertheless, many invasive diagnostic procedures are performed to distinguish between benign and malignant nodules. Qualitative ultrasound elastography is a non-invasive technique to evaluate thyroid nodules. OBJECTIVE: To investigate the diagnostic value of qualitative elastography in distinguishing benign from malignant thyroid nodules in patients referred for fine-needle aspiration (FNA). DATA SOURCES: A systematic literature search (PubMed, Embase and Cochrane Library) was performed. STUDY SELECTION: Included studies reported thyroid nodule elastography color scores and the related cytologic or histologic findings in patients with a thyroid nodule referred for FNA. DATA EXTRACTION: Two independent reviewers extracted study data and assessed study quality. Pooled sensitivities and specificities of different populations were calculated using a bivariate Bayesian framework. DATA SYNTHESIS: Twenty studies including thyroid nodules were analyzed. Pooled results of elastography indicate a summary sensitivity of 85% (95% confidence interval [CI], 79-90%) and specificity of 80% (95% CI, 73-86%). The respective pooled negative predictive and positive predictive values were 97% (95% CI, 94-98%) and 40% (95% CI, 34-48%). The pretest probability of a benign nodule was 82%. Only 3.7% of the false-negative nodules was a follicular thyroid carcinoma. A pooled negative predictive value of 99% (95% CI, 97-100%) was found when only complete soft nodules (Asteria elastography 1) were classified as benign, which included 14% of the studied population. CONCLUSIONS: Elastography has a fair specificity and sensitivity for diagnostic accuracy. Its major strength entails the detection of benignity, especially when only completely soft nodules are qualified as benign. The outcomes of our analysis show that FNA could safely be omitted in patients referred for analysis of their thyroid nodule when elastography shows it to be completely soft (Asteria elastography 1). This could prevent unnecessary invasive diagnostic procedures in a substantial portion of patients.

Thyroid incidentalomas in patients with multiple endocrine neoplasia type 1.

OBJECTIVE: Currently, little is known about the prevalence of thyroid tumors in multiple endocrine neoplasia type 1 (MEN1) patients and it is unclear whether tumorigenesis of these thyroid tumors is MEN1-related. The aim of the study was to assess the prevalence of thyroid incidentalomas in MEN1 patients compared with nonMEN1 patients and to verify whether thyroid tumorigenesis is MEN1-related. DESIGN: A cross-sectional study. METHODS: The study included two groups: patients with MEN1 and a matched non-MEN1 control group without known thyroid disease, who underwent an ultrasound of the neck for the localization of parathyroid adenoma. Ninety-five MEN1 patients underwent ultrasound of the neck and were matched on gender and age with non-MEN1 patients. The prevalence of thyroid incidentalomas described in the ultrasound report was scored. Multinodular goiters, solitary nodes, and cysts were scored as incidentalomas. Presence of nuclear menin expression was evaluated by menin immunostaining of the thyroid tumors. RESULTS: In the MEN1 group, 43 (45%) patients had a thyroid incidentaloma compared with 48 (51%) in the non-MEN1 group, of which 14 (15%) and 16 (17%), respectively, were solitary nodes. Menin was expressed in the nuclei of all evaluated thyroid tumors. CONCLUSIONS: MEN1 patients do not have a higher prevalence of thyroid incidentalomas compared with primary hyperparathyroidism patients without the diagnosis of MEN1. Menin was expressed in the thyroid tumors of MEN1 patients.

Recurrent differentiated thyroid cancer: towards personalized treatment based on evaluation of tumor characteristics with PET (THYROPET Study): study protocol of a multicenter observational cohort study.

BACKGROUND: After initial treatment of differentiated thyroid carcinoma (DTC) patients are followed with thyroglobulin (Tg) measurements to detect recurrences. In case of elevated levels of Tg and negative neck ultrasonography, patients are treated 'blindly' with Iodine-131 (131I). However, in up to 50% of patients, the post-therapy scan reveals no 131I-targeting of tumor lesions. Such patients derive no benefit from the blind therapy but are exposed to its toxicity. Alternatively, iodine-124 (124I) Positron Emission Tomography/Computed Tomography (PET/CT) has become available to visualize DTC lesions and without toxicity. In addition to this, 18F-fluorodeoxyglucose (18F-FDG) PET/CT detects the recurrent DTC phenotype, which lost the capacity to accumulate iodine. Taken together, the combination of 124I and 18F-FDG PET/CT has potential to stratify patients for treatment with 131I. METHODS/DESIGN: In a multicenter prospective observational cohort study the hypothesis that the combination of 124I and 18F-FDG PET/CT can avoid futile 131I treatments in patients planned for 'blind' therapy with 131I, is tested.One hundred patients planned for 131I undergo both 124I and 18F-FDG PET/CT after rhTSH stimulation. Independent of the outcome of the scans, all patients will subsequently receive, after thyroid hormone withdrawal, the 131I therapy. The post 131I therapeutic scintigraphy is compared with the outcome of the 124I and 18F-FDG PET/CT in order to evaluate the diagnostic value of the combined PET modalities.This study primary aims to reduce the number of futile 131I therapies. Secondary aims are the nationwide introduction of 124I PET/CT by a quality assurance and quality control (QA/QC) program, to correlate imaging outcome with histopathological features, to compare 124I PET/CT after rhTSH and after withdrawal of thyroid hormone, and to compare 124I and 131I dosimetry. DISCUSSION: This study aims to evaluate the potential value of the combination of 124I and 18F-FDG PET/CT in the prevention of futile 131I therapies in patients with biochemically suspected recurrence of DTC. To our best knowledge no studies addressed this in a prospective cohort of patients. This is of great clinical importance as a futile 131I is a costly treatment associated with morbidity and therefore should be restricted to those likely to benefit from this treatment. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01641679.

[Robot-assisted transaxillary thyroid surgery]. / Robotgeassisteerde transaxillaire schildklieroperatie.

The robot-assisted transaxillary (hemi)thyroidectomy (RATT) is a new surgical technique using the da Vinci S surgery robot. This technique has recently been successfully introduced in the Netherlands. In a RATT a subcutaneous tunnel from the axilla is created to gain access to the thyroid gland. The operation is then carried out with the robot much like an open procedure. Using a RATT, a total thyroidectomy can be performed. However, surgeons at the beginning of the learning curve are advised to start with hemithyroidectomies only. The indication area consists of nodules up to three centimeters and most probably being benign. The major advantage of this technique is the prevention of a potentially disfiguring scar. The most important disadvantage of this technique is its high cost compared with the conventional procedure. In order to successfully introduce the RATT procedure, thorough preparation by both surgeons and operating room personnel is required. A proctoring program is also necessary.