Does a highly sensitive thyroglobulin (Tg) assay change the clinical management of low‐risk patients with thyroid cancer with Tg on T4 < 1 ng/ml determined by traditional assays?

Objective To evaluate a highly sensitive thyroglobulin (Tg) assay [functional sensitivity (FS): 0·1 ng/ml] (Tg‐ICMA) in low‐risk patients with known Tg on T4 ≤ 1 ng/ml measured by a traditional assay (FS: 1 ng/ml) (Tg‐IRMA). Methods Tg‐ICMA was measured in serum samples stored at –70 °C. Samples were obtained 6 months or more after total thyroidectomy and remnant ablation with ¹³¹I, during L‐T4 therapy (TSH < 0·4 mIU/l). All patients had well‐differentiated and completely resected tumours, no ectopic uptake on post‐therapy whole‐body scans and were considered to be at low risk for recurrence. On the occasion of collection and retesting for this study, Tg‐IRMA was ≤ 1 ng/ml in all samples and no antibody interference was observed. Results Tg‐ICMA ≤ 0·1 ng/ml was observed in 130/178 (73%) patients and recurrence was diagnosed in only 1/130 (0·8%). Tg‐IRMA measured after L‐T4 withdrawal was > 1 ng/ml in 5/130 (3·8%) patients. Forty‐eight (27%) patients had Tg‐ICMA > 0·1 ng/ml (0·12–1·6 ng/ml) and recurrence was diagnosed in 5/48 (10·5%). Tg‐IRMA measured after L‐T4 withdrawal was > 1 ng/ml in 20/48 (41·6%) patients. A negative predictive value of 100% was achieved with Tg‐ICMA on T4 ≤ 0·1 ng/ml combined with neck ultrasonography (US) or with stimulated Tg‐IRMA ≤ 1 ng/ml. Conclusions Patients at low risk for recurrence with undetectable Tg on T4 measured by a highly sensitive assay (FS: 0·1 ng/ml) in the absence of antibody interference and with a negative sensitive neck US do not need to be submitted to Tg stimulation. Recurrence is rare in these cases and only a minority of patients convert to stimulated Tg > 1–2 ng/ml.     

Should ‘low‐risk’ thyroid cancer patients with residual thyroglobulin be re‐treated with iodine 131?

OBJECTIVE: The American consensus statement on patients with low-risk thyroid cancer, published in 2003, suggests repeat (131)I therapy if the thyroglobulin value is elevated at first follow-up. We evaluated this strategy in our practice. METHODS: Among 407 patients with thyroid cancer who had total thyroidectomy and (131)I ablation between January 2000 and December 2003, 12 patients with stage I thyroid cancer (any tumour (T), any node (N), metastasis (M)0 if < 45 years or T1, N0, M0 if > 45 years), were re-treated on the basis of their thyroglobulin level at first follow-up. Mean patient age was 32.8 years. None of them had a T4 tumour. Thyroglobulin levels after thyroid hormone withdrawal 'off-T4' ranged between 4.5 and 251 ng/ml (median 8). One to four courses of 3.7 GBq (131)I were given. RESULTS: Three patients had a negative (131)I therapy scan and an uneventful course. Two patients had slight residual uptake only in the thyroid bed and negative ultrasound examination. Four patients had isolated (131)I uptake in the mediastinal region. No abnormalities were found on complementary mediastinal imaging. This finding was interpreted as benign (131)I thymic uptake. The last three patients also had mediastinal thymic uptake associated with a slight thyroid bed uptake. One patient had a gradual increase in the thyroglobulin level, and underwent resection of nonfunctioning neck lymph nodes. Thyroglobulin levels declined in all other patients. CONCLUSIONS: No distant lesions were found in a group of young 'low-risk' thyroid cancer patients given empirical (131)I therapy for residual thyroglobulin. When blind (131)I therapy shows no uptake, or uptake limited to the thymus, (131)I therapy should not be repeated. The authors also briefly discuss the hypothesis that enhanced thymus might be a source of benign thyroglobulin secretion.     

Is hyperthyroidism often present in patients with thyroid differentiated carcinoma?

The coexistence of thyroid cancer and hyperthyroidism is confirmed by many authors. It appears that the frequency of both disease can be greater as a result of lack of proper and penetrating biopsy diagnosis and of qualification to surgery treatment patients with hyperfunctional goiter and Graves disease, especially coexisting with nodes. The aim of our study was estimation of occurrence of hyperthyroidism in the patients with thyroid differentiated cancer. We examined group of 217 patients with diagnosed thyroid differentiated cancer, 20 patients (9.1%) of them were earlier hyperthyroidism diagnosed. 17 of them were hyperfunctional nodular goiter diagnosed and three as Graves disease, confirmed by presence of anti-TSH receptor antibodies (TRAK). Before thyroidectomy ultrasonography showed nodular goiter in 17 patients and hypoechogenic goiter with nodules in 3 patients. After thyroidectomy at the hyperthyroid patients in 16 papillary thyroid cancer and in 4 follicular thyroid cancers were diagnosed. The frequency of coexistence of cancer and hyperthyroidism in our material amounted for 9.1%. The results of our observation do not diverge from facts given in world literature and is point out the need for precise analysis of patients with hyperthyroidism and of proper qualification to surgery treatments changes suspected to be malignant process.     

Does undetectable basal Tg measured with a highly sensitive assay in the absence of antibodies and combined with normal ultrasonography ensure the absence of disease in patients treated for thyroid carcinoma?

It has been proposed that, in patients treated for well-differentiated thyroid carcinoma, undetectable basal thyroglobulin (Tg) levels measured with a highly sensitive assay in the absence of anti-thyroglobulin antibodies (TgAb) and combined with negative neck ultrasonography (US) ensured the absence of disease. We report a series of five patients with well-differentiated (papillary) carcinoma submitted to total thyroidectomy with apparently complete tumor resection, followed by remnant ablation with (131)I (100-150 mCi), who had no distant metastases upon initial post-therapy whole-body scanning. When tumor recurrence or persistence was detected, these patients presented undetectable basal Tg (0.1 ng/mL) in the absence of TgAb, and US showed no anomalies. Two patients had lymph node metastases, one had mediastinal metastases, bone involvement was observed in one patient, and local recurrence in one. We conclude that further studies are needed to define in which patients undetectable basal Tg (negative TgAb) combined with negative US is sufficient, and no additional tests are required.     

Is familial Mediterranean fever (FMF) common in patients with negative appendectomy?

Objectives

Familial Mediterranean fever (FMF) is an autosomal-recessive disease characterized by recurrent attacks of fever with serositis. Differential diagnosis of a FMF abdominal attack with acute abdomen is difficult. Acute appendicitis is the most common cause of acute abdominal pain that requires surgical treatment. The aim of this study was to investigate frequency of FMF in patients with negative appendectomy.

Methods

We assessed 278 patients (female/male 127/151) who were operated with preoperative diagnosis of acute appendicitis. In 250 of the patients, definitive diagnosis of acute appendicitis was established by histo-pathological examination. Patients with negative appendectomy were assessed for FMF by rheumatologist.

Results

Negative appendectomy was detected in 28 patients (M/F 5/23, mean age 25.3 ± 8.4 years). Negative appendectomy ratio was 10.1 %. Among 28 patients two had FMF (7.7 %).

Conclusions

FMF were established in 7.7 % of patients with negative appendectomy. Our study suggests patients having negative appendectomy should be evaluated for FMF. Further large sample studies are needed to define the real prevalence of FMF among negative appendectomy patients.     

Is push enteroscopy useful in patients with malabsorption of unclear origin?

OBJECTIVE: The aim of this study was to determine the diagnostic value of push enteroscopy in patients with chronic diarrhea and malabsorption of unclear origin. METHODS: From January, 1997, to September, 1999, 16 consecutive patients with chronic diarrhea and biological signs of intestinal malabsorption but no evidence of celiac disease were explored by push enteroscopy. Previous duodenal histological findings had been normal in seven patients and abnormal but inconclusive in nine patients. Endoscopic and histological findings in the duodenum and in the jejunum were compared. RESULTS: Push enteroscopy with jejunal biopsy yielded a diagnosis in comparison with duodenal biopsy in two of 16 (12%) patients, respectively, in two of the nine (22%) patients with abnormal but inconclusive findings on duodenal biopsy, and none of the seven patients with normal duodenal histology. In the two patients in whom jejunal biopsy had diagnostic value but duodenal biopsy did not, the final diagnoses were invasive intestinal lymphoma and microsporidiosis. CONCLUSION: Push enteroscopy had diagnostic value in only 12% of patients with malabsorption of unclear origin, all of whom had had abnormal but inconclusive duodenal histological findings. Push enteroscopy with jejunal biopsy appears to have limited diagnostic value in patients with chronic diarrhea and malabsorption, especially when duodenal biopsies are histologically normal.     

Percutaneous radiofrequency ablation for liver tumors: Is it safer and more effective in low‐risk areas than in high‐risk areas?

Aim: To evaluate the feasibility and safety of ultrasound‐guided radiofrequency ablation (RFA) of hepatic tumors in high‐risk areas (in caudate lobe, adjacent to the hilum, capsular surface, gallbladder or diaphragm) in comparison with those in low‐risk areas. Methods: A total of 526 patients with hepatic tumor treated with ultrasound‐guided cool‐tip RFA between October 2001 and October 2008 were included. The patients were divided into two groups according to the tumor location: group I (high‐risk areas, 163 patients); group II (low‐risk areas, 363 patients). The two groups had similar baseline characteristics. Repeated RFA was adopted if complete ablation (CA) was not achieved. Results: In group I, 20 cases had tumors close to the hilum, 11 in the caudate, 79 adjacent to the capsule, 24 near the gallbladder and 29 cases against the diaphragm. The percentage of patients with primary hepatic tumors in group I was higher than that in group 2 (80.4% vs 56.2%, P < 0.01). More patients in group I felt pain (61.3%, 100/163) than in group II (33.1%, 120/363) (P < 0.01). There was no mortality or major complications in either group. No significant differences were found in the CA rate and the minor complications between the two groups. Conclusion: Results for RFA using cool‐tip electrodes for liver tumors in high‐risk areas are comparable to those in low‐risk areas in the aspects of CA, complications and mortality.     

Does an undetectable rhTSH‐stimulated Tg level 12 months after initial treatment of thyroid cancer indicate remission?

Objectives Routine monitoring after the initial treatment of differentiated thyroid cancer (DTC) includes periodic cervical ultrasonography (US) and measurement of serum thyroglobulin (Tg) during thyrotrophin (TSH) suppression and after recombinant human TSH (rhTSH) stimulation. The aim of our study was to evaluate the utility of repeated rhTSH‐stimulated Tg measurements in patients with DTC who have had no evidence of disease at their initial rhTSH stimulation test performed 1 year after the treatment. Material and methods A retrospective chart review of 278 patients with DTC who had repeated rhTSH stimulation testing after an initial undetectable rhTSH‐stimulated serum Tg level. Results The number of rhTSH stimulation tests performed on individual patients during the follow‐up period (3–12 years, mean 6·3) varied from two to seven. Biochemical and/or cytological evidence of potential persistent/recurrent disease based on detectable second or third rhTSH‐stimulated Tg values and US findings was observed in 11 (4%) patients. Subsequent follow‐up data revealed that in five cases, the results of the second stimulation were false positive, in one case – false negative. Combined with the negative neck US, the negative predictive value for disease‐free survival was 98% after the first undetectable rhTSH‐stimulated Tg and 100% after the second one. Conclusions In patients with DTC, the intensity of follow‐up should be adjusted to new risk estimates evolving with time. The first rhTSH‐stimulated Tg is an excellent predictor for remission, independent of clinical stage at presentation. Second negative rhTSH‐Tg stimulation is additionally reassuring and can guide less aggressive follow‐up by the measurement of nonstimulated Tg and neck US every few years.     

Will the thyroglobulin assay with lower functional sensitivity whilst the patients are on L-T4 treatment replace the TSH-stimulated thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer?

The author reviews the literature on the new assays for serum thyroglobulin (sTg) presenting lower functional sensitivity and demonstrates that its use, whilst the patients are taking L-T4, presents better results than sTg following TSH stimulation in the follow-up of patients with differentiated thyroid carcinoma. Therefore, he suggests a revision on the guidelines for the follow-up of these patients (developed when the available assays present a sensitivity of 1 ng/mL), proposing the use of sTg assays with functional sensitivity of 0.1-0.2 ng/mL with the patients on L-T4 treatment instead of sTg stimulated by TSH.     

Is transient elastography valuable for high‐risk esophageal varices prediction in patients with hepatitis‐B‐related cirrhosis?

Background and Aim: The aim of this study was to evaluate the clinical value of transient elastography (TE) for high‐risk esophageal varices (HREV) prediction in hepatitis‐B‐related cirrhosis patients. Methods: A total of 238 patients with hepatitis B cirrhosis were prospectively enrolled. All patients had undergone TE and upper gastrointestinal endoscopy. Diagnostic value was assessed by the area under ROC curve (AUROC), predictive value and likelihood ratio. Results: The size of esophageal varices correlated with liver stiffness with Kendall's tau_b 0.236 overall and 0.425 in patients with ALT ≥ 5 × upper limit of normal (ULN). The AUROC of TE predicting HREV was 0.73 (95% confidence interval 0.66–0.80) overall and 0.92 (0.82–1.01) for patients with ALT ≥ 5 × ULN. In patients with ALT ≥ 5 × ULN, cut‐off 36.1 kPa predicted HREV with a 100% negative predictive value (NPV), an indefinite negative likelihood ratio (NLR), a 72.7% positive predictive value (PPV) and a positive likelihood ratio (PLR) of 9.3. The AUROC of HREV‐predicting model, constructed by ultrasonography and TE (USLS), was 0.84 (0.77–0.90) in the training set and 0.85 (0.76–0.94) in the validating set. Cut‐off 3.30 excluded HREV with NPV 0.946 and NLR 0.10, and cut‐off 5.98 determined HREV with PPV 0.870 and PLR 10.24. Using USLS, nearly 50% of patients could avoid endoscopic screening. The model's predictive values were maintained at similar accuracy in the validation set. Differences of AUROC in USLS, liver stiffness/spleen diameter to platelet ratio score and ultrasonic score were not significant. Conclusions: TE may predict HREV in patients with ALT ≥ 5 × ULN. Overall, the clinical values of TE and USLS for HREV prediction should be evaluated by further studies.     

Long‐term follow‐up of patients with bone metastases from differentiated thyroid carcinoma – surgery or conventional therapy?

OBJECTIVE: Surgery of bone metastases from differentiated thyroid carcinoma seems indicated in individual patients. This study was performed (1) to analyse retrospectively patients with bone metastases from differentiated thyroid carcinoma and (2) to evaluate the impact of surgery of bone metastases on survival. PATIENTS AND DESIGN: We analysed 41 consecutive patients with bone metastases from differentiated thyroid carcinoma who had undergone thyroid surgery at Vienna University Hospital since 1966. The median follow-up time was 12 years. There were 24 females and 17 males with a mean age of 60 +/- 12 years. Primary tumour histology was follicular in 35 and papillary in six patients. Radioiodine treatment was performed in 32 with a mean administered activity of 27 +/- 24 GBq 131I. Metastases restricted to the skeleton were found in 22 whereas in 19 individuals additional extraskeletal distant metastases were seen. Twenty-seven patients had multiple bone metastases. In 21 individuals, up to five bone metastases were surgically removed with the intention of cure. RESULTS: Univariate analysis identified total thyroidectomy (P = 0.003), lymph node surgery (P = 0.001), radioiodine therapy (P = 0.036), and the absence of extraskeletal distant metastases (P = 0.017) as significant predictors of survival. Multivariate analysis failed to identify significant prognostic factors. In the subgroup of patients with distant metastases limited to the bones, univariate analysis identified, in addition to thyroid and lymph node surgery, the surgical extirpation of the bone metastases as a significant prognostic factor associated with improved survival (P = 0.025). CONCLUSIONS: These findings indicate that in patients without additional extraskeletal distant metastases, the radical surgical extirpation of bone metastases from differentiated thyroid carcinoma might be associated with improved survival.