The early detection of recurrent differentiated thyroid carcinoma (DTC) cells in the post surgery DTC patients relies on the sensitivity of measuring both the level of thyroglobulin (Tg) and 131-Iodine distribution by Whole Body Scan (WBS). Undetectable level of Tg associated with negative WBS or elevated levels of Tg associated with positive WBS ("concordant") is ordinarily indicative of either absence or presence of disease. At times, elevated level of Tg with negative WBS or low levels of Tg with positive WBS ("discordant") could also occur. In the present study, we retrospectively reviewed series of 573 patients with DTC followed in the Diagnostic Imaging and Radiotherapy of the University "Federico II" of Naples between 1993 and 1997. We focused on 9 out of 573 patients (1.56%) who had a discordant pattern with low level of Tg/positive WBS in the post-surgical follow-up. Four patients were metastatic at presentation while 5 patients with metastasis during follow-up still remained in persistently low levels of Tg (<5 ng/mL). This result does point to some flaw in the evaluation of "discordant" cases. Reviewing data previously described series by resetting cut-off values of Tg <1 ng/ml as undetectable changed the apparent "discordant" subgroup of patients into "concordant". Recent introduction of recombinant human TSH (rhTSH) to enhance the expression level of Tg brought significant increase in the sensitivity of diagnostic evaluation of thyroid cancer patients. The role of burdensome WBS in the follow up evaluation of DTC patients is significantly reduced over time especially in low-risk patients while the relevance of Tg assay is steadily increased. Sensitive Tg assays, significantly improved our ability to assess disease status in follow-up of DTC. Given the possibility of late disease relapses, the need for long-term follow-up, and reduced delay in treatment of persistent disease, there is still need for greater sensitive diagnostic tools for DTC.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biological Markers/blood ; Biomedical Technology ; Carcinoma/*diagnosis/drug therapy/radionuclide imaging ; Female ; Follow-Up Studies ; Humans ; Iodine Radioisotopes/diagnostic use ; Male ; Middle Aged ; Recombinant Proteins/diagnostic use ; Research Support, Non-U.S. Gov't ; Thyroglobulin/*blood ; Thyroid Neoplasms/*diagnosis/drug therapy/radionuclide imaging ; Thyrotropin/*diagnostic use ; Whole-Body Counting

Objective: To show the effectiveness of goal-oriented proprioceptive training in subacute stroke for balance, autonomy, and fall risk. Methods: Out a total of 35 patients, consistent in age (75.31±8.65 years), type of stroke (ischemic, 3 to 11 weeks before), and motor impairment, 18 patients underwent solely proprioceptive rehabilitation, the other 17 dual task exercises. The study assessed autonomy using Barthel Index, fall risk with Timed Up and Go Test (TUG), balance through Berg Balance Scale (BBS) and Tinetti test. Results: After two months, significant improvements were recorded in Barthel Index, BBS (p<0.0001), Tinetti test (p<0.0001 in dual task group, p=0.0029 in single task group), and TUG (p=0.0052 in dual task group, p=0.0020 in single task group) in both groups. Comparing the two groups, dual task group showed a significant difference in Tinetti balance assessment (p=0.0052), between the total score of Tinetti test and TUG in single (p=0.0271), and dual task (p=0.0235). Likewise, Tinetti gait test was significantly related to TUG in single (p=0.0536), and dual task (p=0.0466), while Tinetti balance test to Barthel Index (p=0.0394), BBS (p<0.0001), and TUG in single (p=0.0219), and dual task (p=0.0196). Lastly, there is a positive correlation of the use of aids with BBS (p=0.0074), and total score of Tinetti test (p=0.0160). Conclusion In subacute stroke, goal-oriented proprioceptive training improved balance, but only partially autonomy. Furthermore, the use of aids after dual-task exercises improved recovery of balance, but did not reduced falls.

Purpose: This study prospectively assessed the performance of liver stiffness measurements using point shear-wave elastography (p-SWE) in comparison with transient elastography (TE) in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). Methods: Fifty-six consecutive adult patients with a histological diagnosis of NAFLD prospectively underwent TE and p-SWE on the same day. The median of 10 measurements (SWE-10), the first five (SWE-5), and the first three (SWE-3) measurements were analyzed for p-SWE. Liver biopsy was considered as the reference standard for liver fibrosis grade. Receiver operating characteristic (ROC) curves and areas under the ROC curves (AUROCs) were calculated to assess the performance of TE and p-SWE for the diagnosis of significant (F2-F4) and advanced fibrosis (F3-F4). Results: Forty-six patients (27 men, 19 women; mean age, 54.7±9.1 years) had valid p-SWE and TE measurements. Twenty-seven patients (58.7%) had significant fibrosis and 18 (39.1%) had advanced fibrosis. For significant fibrosis, both SWE-10 (AUROC, 0.787; P=0.002) and SWE- 5 (AUROC, 0.809; P=0.001) provided higher diagnostic performance than TE (AUROC, 0.719; P=0.016) and SWE-3 (AUROC, 0.714; P=0.021), albeit without statistical significance (P=0.301). For advanced fibrosis, SWE-5 showed higher diagnostic performance (AUROC, 0.809; P<0.001) than TE (AUROC, 0.799; P<0.001), SWE-10 (AUROC, 0.797; P<0.001), and SWE-3 (AUROC, 0.736; P=0.003), although the differences were not statistically significant (P=0.496). The optimal SWE-10 and SWE-5 cutoff values were ≥8.4 and ≥7.8 for significant fibrosis, and ≥9.1 and ≥8.8 for advanced fibrosis, respectively. Conclusion TE and p-SWE showed similar performance for the diagnosis of significant and advanced fibrosis in NAFLD patients.

Epiduroscopy is defined as a percutaneous, minimally invasive endoscopic investigation of the epidural space. Periduroscopy is currently used mainly as a diagnostic tool to directly visualize epidural adhesions in patients with failed back surgery syndrome (FBSS), and as a therapeutic action in patients with low back pain by accurately administering drugs, releasing inflammation, washing the epidural space, and mechanically releasing the scars displayed. Considering epiduroscopy a minimally invasive technique should not lead to underestimating its potential complications. The purpose of this review is to summarize and explain the mechanisms of the side effects strictly related to the technique itself, leaving aside complications considered typical for any kind of extradural procedure (e.g. adverse reactions due to the administration of drugs or bleeding) and not fitting the usual concept of epiduroscopy for which the data on its real usefulness are still lacking. The most frequent complications and side effects of epiduroscopy can be summarized as non-persistent post-procedural low back and/or leg discomfort/pain, transient neurological symptoms (headache, hearing impairment, paresthesia), dural puncture with or without post dural puncture headache (PDPH), post-procedural visual impairment with retinal hemorrhage, encephalopathy resulting in rhabdomyolysis due to a dural tear, intradural cyst, as well as neurogenic bladder and seizures. We also report for first time, to our knowledge, a case of symptomatic pneumocephalus after epiduroscopy, and try to explain the reason for this event and the precautions to avoid this complication.
Brain Diseases ; Cicatrix ; Epidural Space ; Failed Back Surgery Syndrome ; Hearing Loss ; Humans ; Inflammation ; Leg ; Low Back Pain ; Paresthesia ; Pharmaceutical Preparations ; Pneumocephalus ; Post-Dural Puncture Headache ; Punctures ; Retinal Hemorrhage ; Rhabdomyolysis ; Seizures ; Tears ; Tissue Adhesions ; Urinary Bladder, Neurogenic ; Vision Disorders

Angelman syndrome (AS) is a severe neurobehavioural disorder caused by failure of expression of the maternal copy of the imprinted domain located on 15q11-q13. There are different mechanisms leading to AS: maternal microdeletion, uniparental disomy, defects in a putative imprinting centre, mutations of the E3 ubiquitin protein ligase (UBE3A) gene. However, some of suspected cases of AS are still scored negative to all the latter mutations. Recently, it has been shown that a proportion of negative cases bear large deletions overlapping one or more exons of the UBE3A gene. These deletions are difficult to detect by conventional gene-scanning methods due to the masking effect by the non-deleted allele. In this study, we have used for the first time multiplex ligation-dependent probe amplification (MLPA) and comparative multiplex dosage analysis (CMDA) to search for large deletions affecting the UBE3A gene. Using this approach, we identified a novel causative deletion involving exon 8 in an affected sibling. Based on our results, we propose the use of MLPA as a fast, accurate and inexpensive test to detect large deletions in the UBE3A gene in a small but significant percentage of AS patients.
Angelman Syndrome/*genetics ; Child ; Female ; Gene Deletion ; Gene Dosage ; Genetic Testing ; Humans ; Male ; Ubiquitin-Protein Ligases/*genetics

PURPOSE: This study was conducted to investigate the role of four polymorphic variants of DNA methyltransferase genes as risk factors for radiation-induced fibrosis in breast cancer patients. We also assessed their ability to improve prediction accuracy when combined with mitochondrial haplogroup H, which we previously found to be independently associated with a lower hazard of radiation-induced fibrosis. MATERIALS AND METHODS: DNMT1 rs2228611,DNMT3A rs1550117,DNMT3A rs7581217, and DNMT3B rs2424908 were genotyped by real-time polymerase chain reaction in 286 Italian breast cancer patients who received radiotherapy after breast conserving surgery. Subcutaneous fibrosis was scored according to the Late Effects of Normal Tissue–Subjective Objective Management Analytical (LENT-SOMA) scale. The discriminative accuracy of genetic models was assessed by the area under the receiver operating characteristic curves (AUC). RESULTS: Kaplan-Meier curves showed significant differences among DNMT1 rs2228611 genotypes in the cumulative incidence of grade ≥ 2 subcutaneous fibrosis (log-rank test p-value= 0.018). Multivariate Cox regression analysis revealed DNMT1 rs2228611 as an independent protective factor for moderate to severe radiation-induced fibrosis (GG vs. AA; hazard ratio, 0.26; 95% confidence interval [CI], 0.10 to 0.71; p=0.009). Adding DNMT1 rs2228611 to haplogroup H increased the discrimination accuracy (AUC) of the model from 0.595 (95% CI, 0.536 to 0.653) to 0.655 (95% CI, 0.597 to 0.710). CONCLUSION: DNMT1 rs2228611 may represent a determinant of radiation-induced fibrosis in breast cancer patients with promise for clinical usefulness in genetic-based predictive models.
Breast Neoplasms* ; Breast* ; Discrimination (Psychology) ; DNA* ; Fibrosis* ; Genotype ; Humans ; Incidence ; Mastectomy, Segmental ; Models, Genetic ; Polymorphism, Single Nucleotide ; Protective Factors ; Radiation Tolerance ; Radiotherapy ; Real-Time Polymerase Chain Reaction ; Risk Factors ; ROC Curve ; Skin*

Purpose: This study is to use a simple algorithm based on patient’s age to reduce the overall biological detriment associated with PET/CT. Materials and Methods: A total of 421 consecutive patients (mean age 64 ± 14 years) undergoing PET for various clinical indications were enrolled. For each scan, effective dose (ED in mSv) and additional cancer risk (ACR) were computed both in a reference condition (REF) and after applying an original algorithm (ALGO). The ALGO modified the mean dose of FDG and the PET scan time parameters; indeed, a lower dose and a longer scan time were reported in the younger, while a higher dose and a shorter scan time in the older patients. Moreover, patients were classified by age bracket (18–29, 30–60, and 61–90 years). Results: The ED was 4.57 ± 0.92 mSv in the REF condition. The ACR were 0.020 ± 0.016 and 0.0187 ± 0.013, respectively, in REF and ALGO. The ACR for the REF and ALGO conditions were significantly reduced in males and females, although it was more evident in the latter gender (all p < 0.0001). Finally, the ACR significantly reduced from the REF condition to ALGO in all three age brackets (all p < 0.0001). Conclusion Implementation of ALGO protocols in PET can reduce the overall ACR, mainly in young and female patients.

Purpose: The aim of this study was to assess whether new-generation shear wave elastography (SWE) is suitable for the characterization of lung subpleural lesions. Methods: In total, 190 consecutive patients with subpleural lung lesions received ultrasonography and SWE. Patients with suspected malignancy underwent ultrasound-guided transthoracic needle biopsy. Final diagnoses were made on the basis of patients’ clinical course, microbiological studies, and histological results. SWE was also performed in 25 healthy volunteers. Results: We found no statistically significant differences in stiffness between lung carcinomas, lung metastases, and pneumonia (P=0.296) or between different histological types of lung cancer (P=0.393). Necrosis was associated with reduced stiffness in pneumonia. Excluding necrotic lesions, pneumonia showed higher stiffness than lung carcinomas (2.95±0.68 m/s vs. 2.60±0.54 m/s, P=0.006). Chronic pneumonia showed increased stiffness (3.03±0.63 m/s), probably due to the presence of fibrotic tissue on histology. Pleural effusion was associated with a statistically significant reduction in stiffness, both in lung carcinomas (P=0.004) and lung metastases (P=0.002). The presence of air in healthy lung tissue may lead to incorrect speed estimates due to shear wave reflection (very high values, 14.64±2.19 m/s). Conclusion Transthoracic SWE could not distinguish lung malignancy from pneumonia, or between different histological types of lung carcinomas. In particular, SWE seems unable to resolve the clinical dilemma of chronic subpleural consolidations.

PURPOSE: The purpose of this study was to evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate endpoints of overall survival (OS) in modern clinical trials investigating the efficacy of targeted agents in the second-line treatment of metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: A systematic search of literature pertaining to randomized phase II and III trials evaluating targeted agents as second-line treatments for mCRC was performed. The strength of the correlation between both PFS and ORR and OS was assessed based on the Pearson's correlation coefficient (R) and the coefficient of determination (R²). RESULTS: Twenty trials, including a total of 7,571 patients, met the search criteria. The median duration of post-progression survival (PPS) was 7.6 months. The median differences between experimental and control arms were 0.65 months (range, –2.4 to 3.4) for the median PFS and 0.7 months (range, –5.8 to 3.9) for the median OS. PFS and ORR showed moderate (R=0.734, R²=0.539, p < 0.001) and poor correlation (R=0.169, R²=0.029, p=0.476) with OS, respectively. No differences between anti-angiogenic agents and other drugs were evident. CONCLUSION: Targeted agents investigated in the second-line treatment of mCRC provided minimal PFS gains translating into modest OS improvements. Considering both the moderate correlation between PFS and OS and the short duration of PPS, the OS should remain the preferred primary endpoint for randomized clinical trials in the second-line treatment of mCRC.
Arm ; Biomarkers* ; Colorectal Neoplasms* ; Disease-Free Survival ; Humans ; Molecular Targeted Therapy ; Translating