Prediction of Mediastinal Lymph Node Metastasis in Papillary Thyroid Cancer

Because of the rarity of mediastinal lymph node metastasis, no evidence exists regarding risk factors indicating its presence. This study aimed to identify risk factors representing potential triggers of imaging for mediastinal lymph node metastasis. Carried out was an analysis of 392 consecutive patients with node-positive papillary thyroid cancer referred to a tertiary surgical center. Significant univariate associations (P ≤ 0.001) existed, after correction for multiple testing, between mediastinal lymph node metastasis and poor tumor differentiation (24% versus 2%), number of positive lymph nodes (mean 14.4 versus 7.3 nodes), and distant metastasis (43% versus 11%). Only nominally significant were age at first tumor diagnosis (47.7 versus 39.1 years; P = 0.042), extrathyroidal tumor extension (76% versus 53%; P = 0.044), and bilateral lymph node metastasis (81% versus 49%; P = 0.006). In the initial and optimized multivariate logistic regression models, which included all significant variables from the above analysis, only poor tumor differentiation (odds ratio 11.6–14.6) and distant metastasis (odds ratio 5.4–6.1) represented significant (P ≤ 0.005) predictors of mediastinal lymph node metastasis. These two variables featured excellent negative predictive values of 96%. Regarding prediction of mediastinal lymph node metastasis, poor tumor differentiation was more discriminatory than distant metastasis, as reflected in a better accuracy (94% versus 86%) and positive predictive value (42% versus 18%). We conclude that, subject to validation in independent series, patients with poorly differentiated papillary thyroid cancers, which are rare, should be ideal candidates for mediastinal imaging because 5 of 12 patients (42%) having this condition in the present investigation harbored mediastinal lymph node metastasis.     

Age-related penetrance of endocrine tumours in multiple endocrine neoplasia type 1 (MEN1): a multicentre study of 258 gene carriers

OBJECTIVE: In multiple endocrine neoplasia type 1 (MEN1), age-related tumour penetrance according to the type of MEN1 germline mutation has not been investigated in-depth. This study was conducted to examine whether carriers of out-of-frame/truncating and in-frame MEN1 mutations differ in age-related tumour penetrance. DESIGN: A multicentre study with biochemical, hormonal and radiological screening for MEN1-associated tumours. PATIENTS: A total of 258 MEN1 carriers from six major German tertiary referral centres averaging 43 years of age at last follow-up. MEASUREMENTS: Main outcome measure was time to first diagnosis of MEN1-associated tumours. RESULTS: Independent of the year of birth and observation period, time to first tumour diagnosis did not vary much by the type of MEN1 germline mutation or endocrine organ system, and perhaps not even by the type of endocrine tumour when the amount of time was considered by which the diagnosis probably has been advanced through the manifestation of hormonal symptoms. Parathyroid hyperplasia and adenomas developed almost twice as often as enteropancreatic and pituitary tumours (77%vs. 49-32%), and more than five to sevenfold as often as adrenal cortical tumours and carcinoids (77%vs. 15-10%), reaching penetrance rates of up to 90%, 60%, 40%, 26% and 17%, respectively. The heterogeneity of tumour penetrance was marked, ranging from 9 years to 25 years for the earliest, and from 68 years to 77 years for the latest tumour manifestation. CONCLUSIONS: Because of our inability of predicting tumour penetrance and malignant transformation individually, life-long follow-up of MEN1 carriers is warranted to prevent tumour morbidity.     

Abnormal carcinoembryonic antigen levels and medullary thyroid cancer progression: a multivariate analysis

HYPOTHESIS: Medullary thyroid cancer cells are capable of secreting carcinoembyronic antigen (CEA). An abnormal preoperative CEA level may have important implications for the management of this condition. DESIGN: Retrospective analysis. SETTING: Tertiary referral center at a university hospital. PATIENTS: One hundred fifty patients with a histopathologic diagnosis of medullary thyroid cancer and preoperative CEA measurements using the same assay. Main Outcome Measure We used univariate and multivariate analyses to quantify the relationship between preoperative CEA level and tumor progression. RESULTS: On multivariate analysis, abnormal preoperative CEA levels were significantly associated with the initial operation rather than reoperation, larger primary tumors, positive lymph nodes, and distant metastasis. When analyses were limited to the 54 patients with increased CEA levels before the initial operation, there was a respective significant association between successive CEA levels (4.7-10.0, 10.1-30.0, 30.1-100.0, and >100.0 ng/mL) and lymph node metastases (>10 positive nodes: 0%, 9%, 53%, and 69% [P<.001]), involvement of cervical lymph node compartments (central: 33%, 36%, 73%, and 93% [P=.002]; lateral [ipsilateral]: 20%, 27%, 67%, and 88% [P=.001]; and lateral [contralateral]: 22%, 10%, 36%, and 73% [P=.008]), and distant metastasis (0%, 27%, 13%, and 75% [P<.001]). When CEA levels exceeded 30.0 ng/mL, surgical cure was exceptional. CONCLUSIONS: In medullary thyroid cancer, an abnormal CEA level heralds advanced disease. Carcinoembryonic antigen levels greater than 30.0 ng/mL indicate central and lateral (ipsilateral) lymph node metastases, whereas CEA levels greater than 100.0 ng/mL signify lateral (contralateral) lymph node metastases and distant metastasis.     

Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases

Introduction

Seven SNPs in five genomic loci were recently found to confer a mildly increased risk of breast cancer.

Methods

We have investigated the correlations between disease characteristics and the patient genotypes of these SNPs in an unselected prospective cohort of 1,267 consecutive patients with primary breast cancer.

Results

Heterozygote carriers and minor allele homozygote carriers for SNP rs889312 in the MAP3K1 gene were less likely to be lymph node positive at breast cancer diagnosis (P = 0.044) relative to major allele homozygote carriers. Heterozygote carriers and minor allele homozygote carriers for SNP rs3803662 near the TNCR9 gene were more likely to be diagnosed before the age of 60 years (P = 0.025) relative to major allele homozygote carriers. We also noted a correlation between the number of minor alleles of rs2981582 in FGFR2 and the average number of first-degree and second-degree relatives with breast cancer and/or ovarian cancer (P = 0.05). All other disease characteristics, including tumour size and grade, and oestrogen or progesterone receptor status, were not significantly associated with any of these variants.

Conclusion

Some recently discovered genomic variants associated with a mildly increased risk of breast cancer are also associated with breast cancer characteristics or family history of breast cancer and ovarian cancer. These findings provide interesting new clues for further research on these low-risk susceptibility alleles.     

Intraoperative Monitoring of the Recurrent Laryngeal Nerve in Thyroid Surgery

BACKGROUND: Recurrent laryngeal nerve (RLN) palsy ranks among the leading reasons for medicolegal litigation of surgeons because of its attendant reduction in quality of life. As a risk minimization tool, intraoperative nerve monitoring (IONM) has been introduced to verify RLN function integrity intraoperatively. Nevertheless, a systematic evidence-based assessment of this novel health technology has not been performed. METHODS: The present study was based on a systematic appraisal of the literature using evidence-based criteria. RESULTS: Recurrent laryngeal nerve palsy rates (RLNPR) varied widely after thyroid surgery, ranging from 0%-7.1% for transient RLN palsy to 0%-11% for permanent RLN palsy. These rates did not differ much from those reported for visual nerve identification without the use of IONM. Six studies with more than 100 nerves at risk (NAR) each evaluated RLNPR by contrasting IONM with visual nerve identification only. Recurrent laryngeal nerve palsy rates tended to be lower with IONM than without it, but this difference was not statistically significant. Six additional studies compared IONM findings with their corresponding postoperative laryngoscopic results. Those studies revealed high negative predictive values (NPV; 92%-100%), but relatively low and variable positive predictive values (PPV; 10%-90%) for IONM, limiting its utility for intraoperative RLN management. CONCLUSIONS: Apart from navigating the surgeon through challenging anatomies, IONM may lend itself as a routine adjunct to the gold standard of visual nerve identification. To further reduce the number of false negative IONM signals, the causes underlying its relatively low PPV require additional clarification.     

Routine monitoring in patients with free tissue transfer by laser-doppler flowmetry

The use of laser Doppler flowmetry (LDF) was tested in 108 consecutive patients, who underwent free tissue transfer at our institution between December, 1988, and June, 1990. Sixteen patients (14.8%) suffered vascular complications, which could be detected in all cases earlier by LDF than by clinical examination alone. LDF therefore prompted faster surgical intervention in these cases, allowing flap salvation in 9.3% (n = 10). Difficulties had to be noted in diagnosing venous thrombosis by means of the LDF due to sometimes unspecific alterations in LDF signals. Technical improvement of LDF might lead to a higher diagnostic accuracy if venous thrombosis occurs.