Risk Factors For Persistent Disease Research Articles

Comparative study of topical 5-aminolevulinic acid photodynamic therapy (5-ALA-PDT) and surgery for the treatment of high-grade vaginal intraepithelial neoplasia

ObjectiveTo compare the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and local surgical excision in the treatment of high-grade vaginal intraepithelial neoplasia (VAIN). MethodsThis was a retrospective study of a single center. Patients with biopsy-proven high-grade VAIN were counseled on the option of excision or ALA-PDT. After treatment patients were followed up at 3, 6 and 12 months and every 6 months afterwards. Clinical data of two groups were analyzed. ResultsSixty patients were treated with ALA-PDT and 40 patients underwent excision surgery. The clinical characteristics of patients in the two groups were similar. The mean ages of patients treated with ALA-PDT and local surgical excision were 41.93+13.08 (18-70) and 43.25+11.64 (22–61) years old, respectively. The treatment times of PDT for patients in the ALA-PDT group were 5.48±1.41 (2-8) times. At 3–6 months after treatment, the overall complete remission (CR) rate was 93.33% (56/60) in PDT group and 82.5% (33/40) in local surgical excision group. In PDT group, a 12- and 24-month follow-up, the total HPV clearance rate was 68.97% and 77.55%, respectively. At 12-month and 2-year follow-up after local surgical excision, the total HPV clearance rate was 60% and 64.52%, respectively. Further analysis showed that the clinical efficacy was comparable between the two treatments. Patients over 45 years old exhibited a lower HPV clearance rate (P<0.05) than those under 45 years old. It was also observed that persistent HPV infection is a major risk factor for persistent disease. Further comparative analyses showed no significant difference in the CR rate and treatment times between VAINII and VAINIII in ALA-PDT group. Moreover, 4 patients (11.36%) developed recurrent lesions during follow-up after ALA-PDT, whereas 3 patients (8.33%) in the local excision group developed recurrent lesions. In addition, there was no significant difference in the recurrent rate between two groups. ConclusionsALA-PDT shows similar efficacy and less side effects compared to local surgical excision.

Isthmus topography is a risk factor for persistent disease in patients with differentiated thyroid cancer

The risk of differentiated thyroid cancer (DTC) recurrence is widely evaluated according to the 2015 ATA Risk Stratification System. Topography of malignant nodules has been previously reported as an additional risk factor but is not included in the ATA system. Thus, our study aimed to evaluate the relationship between DTC topography and response to initial therapy. We enrolled 401 low- to intermediate-risk patients with DTC who had undergone thyroidectomy and radioiodine therapy. DTC topography was recorded and compared with the response to therapy as assessed 12 months after the end of therapy. Overall, 366/401 (91.3%) patients had an excellent response to initial therapy while 22/401 (5.5%) and 13/401 (3.2%) had incomplete biochemical or structural responses, respectively. Incomplete response occurred in 10/36 (27.8%), 5/125 (4.0%), and 4/111 (3.6%) patients whose unifocal malignant nodules were located in the isthmus, right lobe, or left lobe. Incomplete response was also observed in 4/54 (7.4%) and 12/75 (16%) patients carrying multifocal cancers in one or both lobes, respectively. Patients with isthmic cancer more frequently demonstrated incomplete response compared with those who had cancer in other locations (P = 0.00). No significant relationship was found with age, gender, maximum size of malignant nodule, Hashimoto's thyroiditis, vascular invasion, and extrathyroidal extension (P = 0.78, P = 0.77, P = 0.52, P = 0.19, P = 0.73, and P = 0.26, respectively). The risk of incomplete response was about 65% higher in patients with isthmic lesions compared with other patients (odds ratio = 6.725). A log-rank test demonstrated that disease-free survival (DFS) of patients with isthmic lesions was significantly shorter than that of other patients (P = 0.02). Our data show that isthmus topography of malignant thyroid nodules is a risk factor for having both persistent disease 12 months after primary treatment and reduced DFS.

Differentiated Thyroid Cancer in Children and Adolescents: Long Term Outcome and Risk Factors for Persistent Disease.

Simple SummaryDespite their excellent prognosis, pediatric differentiated thyroid cancers (P-DTC) often undergo aggressive treatment due to the advanced disease presentation. Reliable risk stratification tools to guide management are needed; unfortunately, the current American Thyroid Association (ATA) classification for P-DTC lacks an unequivocal definition of the three risk categories. In line with previous work, our data confirm a favorable long-term outcome in P-DTC including cases with distant metastases. We propose a modified ATA pediatric risk stratification using a cut-off of five lymph nodes as proposed by the 2015 ATA guidelines for adult DTC. The modified pediatric ATA risk class independently predicted short- and long-term outcome. The utility of applying dynamic risk classification was also confirmed as P-DTC with an excellent response seldom experiences relapse. Background: Pediatric differentiated thyroid cancer (P-DTC) frequently presents with advanced disease. The study aim was to evaluate the outcome of P-DTC and a modified 2015 American Thyroid Association risk classification (ATA-R). Methods: A retrospective study of consecutive P-DTC patients was performed. The ATA-R for P-DTC was used with a cut-off of ≤ 5 N1a for low-risk. The outcome could be excellent response (ER) (thyroglobulin < 1 ng/mL and no evidence of disease (EoD) at imaging), biochemical incomplete response (BIR) (thyroglobulin ≥ 1 ng/mL and no EoD at imaging) or structural incomplete response (SIR) (EoD at imaging). Results: We studied 260 P-DTC (70% females; median age at diagnosis 14 years; 93% total thyroidectomy and 82% lymph node dissection). The ATA-R was low in 30% cases, intermediate in 15% and high in 55%, including 31.5% with distant metastases. Radioiodine treatment was administered in 218 (83.8%), and further radioiodine and surgery was performed in 113 (52%) and 76 (29%) patients, respectively. After a median follow-up of 8.2 years, the outcome was ER in 193 (74.3%), BIR in 17 (6.5%) and SIR in 50 (19.2%). Independent predictors of SIR or BIR at first and last visits were ATA-R intermediate or high. Conclusion: P-DTC has an excellent prognosis. Modified ATA-R is a useful prognostic tool in P-DTC to guide management.

The number of risk factors for persistent disease determines the clinical course of early arthritis.

ObjectivesManagement of early arthritis is based upon early recognition of individuals at high risk of developing persistent arthritis. Therefore, this study investigates whether the number of risk factors for persistent disease or treatment determines the clinical course of early arthritis by comparing the chance at (sustained) DMARD-free remission ((S)DFR) after 2 years follow-up.MethodsData from the tREACH trial, a stratified single-blinded multicentre strategy trial with a treat-to-target approach were used. We selected all patients with ≥1 swollen joint who did not fulfil 1987 and/or 2010 criteria for RA. The number of risk factors present; autoantibody-positivity, polyarthritis (>4), erosive disease and elevated acute phase reactants, determined risk group stratification. Multivariate logistic regression analyses were performed with (S)DFR as dependent variables and baseline disease activity score (DAS), treatment, symptom duration and number of risk factors present as independent variables.ResultsIn total, 130 early arthritis patients were included and respectively 31, 66 and 33 had 0, 1 and ≥2 risk factors present. DFR rates were respectively 74%, 48% and 45% for early arthritis patients with 0, 1 and ≥2 risk factors present. In accordance SDFR rates were 61%, 32% and 30%. In our logistic model (S)DFR was not influenced by the initial treatment strategies when stratified for risk groups.ConclusionThe chance at (S)DFR in early arthritis diminishes when more risk factors are present, which is irrespective of the given initial treatment. Our data point out to a stratified management approach in early arthritis based on their risk profile, but validation is needed.Trial registrationISRCTN registry: ISRCTN26791028 (http://www.isrctn.com/ISRCTN26791028).

Alopecia areata as an immune-related adverse event of immune checkpoint inhibitors: A review.

Immune checkpoint inhibitors (ICI) improve the ability of the immune system to target cancer cells by blocking signaling through either the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death (PD-1) receptor, or its ligand (PD-L1). They have been found to cause a variety of immune-related adverse events (irAEs) including a form of nonscarring alopecia that resembles alopecia areata (AA) in presentation and histology. Clinical features of ICI-induced AA are poorly described. We queried the Pubmed database for cases of AA secondary to ICI use reporting on extent of hair loss, treatments attempted, alopecia outcome, and time of follow-up with 13 cases identified. Although most patients had localized hair loss with subsequent regrowth, four of them experienced extensive and persistent AA, lasting up to a year. All but one patient continued ICI after the onset of hair loss. Many used topical corticosteroids with varying outcomes. Possible prognostic factors for severe and persistent disease may include young age and male sex. However, the low number of reported cases limits the generalizability of these findings. Tumor response was positive in every case of immune-induced AA where it was reported. Further investigation will be needed to better characterize clinical features of this irAE, risk factors for persistent disease, and determine its optimal management.

Clinical outcome of high-grade cervical intraepithelial neoplasia during pregnancy: A 10-year experience

ObjectiveTo investigate the clinical outcome of high-grade cervical intraepithelial neoplasia (CIN) diagnosed by colposcopy-directed biopsy during pregnancy and to evaluate the risk factors for persistent disease. Study DesignThis retrospective study included pregnant women who were diagnosed with CIN2+ by colposcopy-directed biopsy from January 2005 to December 2014. The clinical characteristics, histopathologic results, and human papillomavirus (HPV) test results were reviewed. The final histopathologic result after delivery was compared with the initial diagnosis to determine disease progression, persistence, or regression. ResultsDuring the 10-year period, 215 pregnant women were diagnosed with high-grade CIN (75 CIN2, 140 CIN3) by colposcopy-directed biopsy. The mean age of the patients was 30.4 years. A total of 187 patients (87.0%) had high-risk HPV infections, with 76 (35.3%) infections identified as HPV genotype 16 or 18. Excisional procedures for diagnosis and treatment were not performed during pregnancy. The histopathologic results of 160 patients (normal in 43, CIN1 in 10, CIN2 in 15, CIN3 in 89, and invasive cancer in 3) were evaluated during the postpartum period. Multivariate logistic regression analysis was performed, and postpartum high-risk HPV infection (OR 5.09; 95% CI 2.15–12.05; P < 0.001) was identified as a significant independent predictor of CIN2+ persistence. ConclusionsConservative management of CIN2-3 during pregnancy is acceptable. However, persistent high-risk HPV infection is a major risk factor for CIN2+ persistence. Close follow-up with HPV testing, and postpartum colposcopy evaluation are necessary.

Cold urticaria: a 20-year follow-up study.

Chronic cold urticaria results in significant morbidity, yet information on its natural history is limited. We examined the natural history of chronic cold urticaria and its impact on quality of life. We analysed the characteristics of patients diagnosed with cold urticaria at a community-based specialist allergy practice in the Australian Capital Territory (ACT) between 1995 and 2015. Follow-up data were obtained using a mailed questionnaire. Possible predictive factors of disease severity and symptom duration were evaluated. A total of 99 patients were assessed with a median age of 42 (range 5-81 years); 63% were female and the median age of onset of symptoms was 22 years. Of 41 questionnaire responders (14 ± 10.9 years follow-up; median 12 years), 5- and 10-year resolution rates were 17.9% ± 6.2% and 24.5% ± 7.2%, respectively. Whereas 22% reported resolution and 23% described improvement, the remaining 55% reported stable or worsening disease. Most individuals relied on lifestyle modification to ameliorate symptoms rather than medication. Risk factors for persistent disease were intercurrent atopic disease (P = 0.025) and those with longer duration of symptoms at the time of initial assessment (P < 0.001). Secondary causes of cold urticaria were identified in only two patients, both with B-cell malignancy. In a subset of patients, cold urticaria has low rates of spontaneous resolution and results in lifestyle changes and impaired quality of life.

Risk factors for persistent disease in papillary thyroid carcinoma with lymph node metastasis.

It is known that the presence of neck lymph node (LN) metastasis is correlated with persistent disease in papillary thyroid carcinoma (PTC) patients. After appropriate therapy, most patients become disease free, whereas some may still have persistent disease. The present study aimed to determine the potential variables affecting the clinical course of the disease and persistent disease patterns in PTC patients with LN metastasis. The study group included consecutive PTC patients with LN metastasis. Clinicopathological characteristics and persistent disease pattern during the follow-up period were examined to identify risk factors for persistent disease using univariate and multivariate analyses. At the end of a median follow-up of 84 months, 90 (69%) patients became disease free and 40 (31%) patients had persistent disease. Univariate analysis showed that male sex, older age at initial diagnose (≥45 years), larger tumor size (>4 cm), presence of lateral cervical LN metastasis, extrathyroidal invasion, and higher number of metastatic LN (≥10) were significant predictors for persistent disease. Multivariate analysis showed that extrathyroidal involvement, presence of lateral cervical LN metastasis, and older age at initial diagnosis (≥45 years) were independent predictors for persistent disease. Despite the presence of LN involvement, most patients may become disease free with therapy. Patients with extrathyroidal invasion, lateral cervical LN involvement, and those at least 45 years old at initial diagnosis are more likely to have persistent disease. However, disease control can be achieved with close clinical follow-up and therapy.

How reliable is secondary risk stratification with stimulated thyroglobulin in patients with differentiated thyroid carcinoma?

SummaryObjective: Primary risk factors in patients with differentiated thyroid carcinoma (DTC) are well established. In our institution, secondary risk stratification has been performed with stimulated Thyroglobulin (sTg; TSH &gt; 30 mIU/l) within six months after primary therapy since 2001. In this study, we evaluated the predictive value of sTg for long-term disease- free survival (DFS). Patients, methods: Data of 202 consecutive patients with DTC were analyzed retrospectively. Median follow-up time was 6.4 years (12 months to 16.2 years). Patients were staged according to Union International Contre le Cancer (UICC) criteria. Primary risk stratification was carried out according to European Thyroid Association criteria. Initially, 134 patients (66%) were classified as low-risk and 68 patients (34%) as high-risk. The influence of established risk factors and sTg on DFS was analyzed at three different time points, up to 36 months after initial therapy. Results: In total, 169 (84%) of all patients remained in complete remission after surgery followed by radioiodine-therapy. Six patients (3%) developed tumour recurrence after initial complete remission. Primary risk factors for persistent disease were male sex, follicular or oncocytic tumour, primary tumour &gt; 4 cm in diameter, initial lymph node involvement, initial metastatic disease and microscopic or macroscopic residual tumor. sTg ≤ 0.3 ng/ml measured within six months after initial therapy was a highly significant predictor (p ≤ 0.001) for lasting DFS, 99% of patients with sTg ≤ 0.3 ng/ml were in complete remission 36 months after initial therapy. Conclusions: A stimulated Tg ≤ 0.3 ng/ml within six months after initial therapy is a reliable predictor for long-term disease- free survival independent of primary risk stratification.

Persistent disease and recurrence in differentiated thyroid cancer patients with undetectable postoperative stimulated thyroglobulin level

(131)I is given in differentiated thyroid cancer (DTC) without taking into account thyroglobulin (Tg) levels at the time of ablation, whereas 6-18 months later it is a major criterion for cure. This single-center retrospective study assessed the frequency and risk factors for persistent disease on postablation whole body scan (WBS) and postoperative neck ultrasonography (n-US) and for recurrent disease during the subsequent follow-up, in patients with DTC and undetectable TSH-stimulated Tg level (TSH-Tg) in the absence of Tg antibodies (TgAb) at the time of ablation. Among 1031 patients ablated, 242 (23%) consecutive patients were included. Persistent disease occurred in eight cases (3%) (seven abnormal WBS and one abnormal n-US), all with initial neck lymph node metastases (N1). N1 was a major risk factor for persistent disease. Among 203 patients with normal WBS and a follow-up over 6 months, TSH-Tg 6-18 months after ablation was undetectable in the absence of TgAb in 173 patients, undetectable with TgAb in 1 patient and equal to 1.2 ng/ml in 1 patient. n-US was normal in 152 patients and falsely positive in 3 patients. After a mean follow-up of 4 years, recurrence occurred in two cases (1%), both with aggressive histological variants. The only risk factor for recurrence was an aggressive histological variant (P = 0.03). In conclusion, undetectable postoperative TSH-Tg in the absence of TgAb at the time of ablation is frequent. In these patients, repeating TSH-Tg 6-18 months after ablation is not useful. (131)I ablation could be avoided in the absence of N1 and aggressive histological variant.

Identification of Bacteria Enduring Endodontic Treatment Procedures by a Combined Reverse Transcriptase–Polymerase Chain Reaction and Reverse-Capture Checkerboard Approach

Introduction This study identified the bacterial taxa enduring endodontic treatment procedures by using a combined 16S ribosomal RNA-based reverse-transcriptase polymerase chain reaction (RT-PCR) and reverse-capture checkerboard hybridization approach. Methods Samples were taken from infected canals of 15 teeth with apical periodontitis before treatment (S1), after chemomechanical preparation with NaOCl as the irrigant (S2), and after interappointment medication with a calcium hydroxide paste (S3). Bacterial presence was first screened by a DNA-based single PCR assay. RNA extracts were subjected to RT-PCR, and the resulting products were surveyed for the presence of 28 targeted taxa by using the checkerboard method. Results Bacteria were found in all S1 samples. Detectable levels of bacterial ribosomal RNA, used as an indicator of viability, were observed in 60% of the cases after chemomechanical preparation and 53% after intracanal medication. The most prevalent taxa in S1 were Olsenella uli (67%), Pyramidobacter piscolens (60%), Streptococcus species (53%), and Bacteroidetes clone X083 (53%). Streptococcus species (47%), Fusobacterium nucleatum (40%), and O. uli (33%) prevailed in S2, whereas Streptococcus species (47%), Propionibacterium acnes (27%), and O. uli (27%) were the most frequent taxa in S3. Conclusions The present study with a combined molecular approach revealed that bacterial diversity was overall markedly reduced by treatment procedures. Although bacterial taxa more frequently identified in post-treatment samples emerge as potential risk factors for persistent disease, this remains to be determined by longitudinal studies.

Prognostic Factors for Persistent or Recurrent Disease of Papillary Thyroid Carcinoma with Neck Lymph Node Metastases and/or Tumor Extension beyond the Thyroid Capsule at Initial Diagnosis

Reliable prognostic factors are needed in papillary thyroid cancer patients to adapt initial therapy and follow-up schemes to the risks of persistent and recurrent disease. OBJECTIVE AND SETTINGS: To evaluate the respective prognostic impact of the extent of lymph node (LN) involvement and tumor extension beyond the thyroid capsule, we studied a group of 148 consecutive papillary thyroid cancer patients with LN metastases and/or extrathyroidal tumor extension. Initial treatment, performed at the Institut Gustave Roussy between 1987 and 1997, included in all patients a total thyroidectomy with central and ipsilateral en bloc neck dissection followed by radioactive iodine ablation. Uptake outside the thyroid bed, demonstrating persistent disease, was found on the postablation total body scan (TBS) in 22% of the patients. With a mean follow-up of 8 yr, eight patients (7%) with a normal postablation TBS experienced a recurrence. Ten-year disease-specific survival rate was 99% (confidence interval, 97-100%). Significant risk factors for persistent disease included the numbers of LN metastases (>10) and LN metastases with extracapsular extension (ECE-LN >3), tumor size (>4 cm), and LN metastases location (central). Significant risk factors for recurrent disease included the numbers of LN metastases (>10), ECE-LN (>3), and thyroglobulin level measured 6-12 months after initial treatment after T4 withdrawal. We highlight an excellent survival rate and suggest risk classifications of persistent and recurrent disease based on the numbers of LN metastases and ECE-LN, LN metastases location, tumor size, and thyroglobulin level.