Clinicopathologic Analysis of Micropapillary Urothelial Carcinoma of the Upper Urinary Tract: Implications for HER2-Targeted Therapy.

Introduction/Background To determine the clinical significance of micropapillary urothelial carcinoma (MPUC) of the upper urinary tract (UTUC) and a potential therapeutic strategy. Patients and Methods A retrospective cohort study was conducted to examine the incidence of micropapillary UTUC from 2010 to 2018 and its clinicopathological characteristics. Clinical outcomes and cancer-specific survival (CSS) were compared between MPUC and conventional UTUC matched by stage within a 6-month variation of receiving surgery. Results A total of 24 MPUC cases were identified out of 901 cases (2.7%) of urothelial carcinoma (UC) of the renal pelvis and ureter. MPUC was significantly smaller (<3 cm) and associated with nodal metastasis compared with conventional UTUC (P = .017 & 0.021, respectively); however, no significant difference was observed for lymphovascular invasion, distant metastasis, or CSS (P > 0.50, respectively) compared with match controls. Six MPUC patients (25%) developed metastasis to the liver, lymph nodes, and lung during follow-up. Patients with HER2-positive MPUC (3 of 4) had a significantly higher risk of metastasis compared with HER2-negative MPUC (3 of 20; P = 0.035). Conclusions MPUC is an aggressive variant of UTUC and usually presents as a small locally advanced disease. HER2 immunohistochemistry may identify the subset of patients with micropapillary UTUC that are candidates for targeted therapy.

Should Contralateral Nodules Be an Indication of Total or Completion Thyroidectomy for Patients With Unilateral Papillary Thyroid Carcinoma?

Objective: To determine whether papillary thyroid carcinoma (PTC) patients with benign or nonsuspicious nodules in the contralateral lobe have a higher rate of recurrence or worse survival after lobectomy compared to those without nodules in the contralateral lobe. Methods: Adult patients who underwent lobectomy and were diagnosed with unilateral PTC (2013-2015), were identified from an institutional database. Patients who previously had cytologically benign nodules or nonsuspicious nodules in the contralateral lobe comprised the contralateral nodule (CN) group. Patients who did not have nodules in the contralateral lobe comprised the unilateral nodule (UN) group. Results: 370 patients were included: 242 in the UN group and 128 in the CN group. After a median follow-up of 62 months (range, 16-85 months), recurrence was confirmed in 4.1% patients in the UN group and 5.5% patients in the CN group (p = 0.559). Clinical contralateral lobe PTC was detected in 2.9% (7/242) of patients from the UN group and 3.9% (5/128) of patients from the CN group (p = 0.601). The 5-year contralateral lobe recurrence-free survival (RFS) rates were 96.8% in the UN group and 97.4% in the CN group (p = 0.396). The 5-year loco-regional RFS rates were 98.4% in the UN group and 97.8% in the CN group (p = 0.690). The 5-year disease-specific survival rates were both 100%. Conclusion: PTC patients with benign or nonsuspicious CNs have similar recurrence and survival rates after lobectomy compared to those without CNs. CNs alone should not be an indication for total or completion thyroidectomy.

Ectopic Thyroid Papillary Carcinoma with Cervical Lymph Node Metastasis as the Initial Presentation, Accompanied by Benign Thyroid Gland.

BACKGROUND: Ectopic thyroid papillary carcinoma presenting as bilateral neck lymph nodes metastasis is very rare. Ectopic thyroid tissue may appear in any location along the trajectory of the thyroglossal duct from the foramen cecum to the mediastinum. It is subject to malignant transformation and is classically accompanied by a similar transformation of the native thyroid gland. Similar to that of the native thyroid gland, the most common malignancy found is Papillary thyroid carcinoma. Unusual cases in which ectopic thyroid carcinoma presents with normal native tissue support an alternative hypothesis that ectopic thyroid tissue may develop malignancies independently from the native thyroid gland. OBJECTIVE: We present an extremely rare case of a 30-year-old woman previously diagnosed with Hashimoto's thyroiditis, presenting with a palpable mass in the lateral neck suspicious for malignancy. RESULTS: After several examinations and surgical removal of the mass, histopathologic evaluation of the continuous sections of the thyroid, demonstrated metastatic disease from papillary carcinoma of the thyroid. Total thyroidectomy and biopsy revealed benign thyroid tissue without any foci of microcarcinoma. A hypothesis of ectopic thyroid tissue and its malignant transformation was made. CONCLUSION: By presenting this case, our goal is to highlight and make the physicians aware of the possibility of developing primary carcinoma of the ectopic thyroid tissue, without an active tumor of the thyroid gland.

The prognostic roles of the prognostic nutritional index in patients with intraductal papillary mucinous neoplasm.

The preoperative accurate diagnosis is difficult in the patients with intraductal papillary mucinous neoplasm (IPMN). The aim of the present study was to elucidate the roles of systemic inflammation responses and nutritional status indexes in IPMN. High-grade dysplasia was classified as a malignant neoplasm in the study. We retrospectively reviewed 155 patients who underwent pancreatectomy. The correlation between the clinical factors and several indexes of a systemic inflammation response and nutritional status was analyzed. Among the biomarkers, prognostic nutritional index (PNI) value of malignant IPMN patients was significantly lower than that of benign IPMN patients (P = 0.023), whereas PNI was not significant predictor for malignant IPMN. The multivariate analysis showed that a PNI < 43.5 (odds ratio [OR] 16.1, 95% CI 1.88-138.5, P = 0.011) and a carbohydrate antigen (CA) 19-9 level > 22.5 U/mL (OR 6.64, 95% CI 1.73-25.6, P = 0.006) were significant independent predictors of the presence of lymph node metastasis (LNM). Our scoring system developed based on these two factors. Patients with a score of 0 had no LNM and zero disease-related death. The present study suggested the roles of PNI on the IPMN patients who undergo curative pancreatectomy.

Familial non-medullary thyroid cancer: a critical review.

BACKGROUND: Familial non-medullary thyroid carcinoma (FNMTC), mainly of papillary histotype (FPTC), is defined by the presence of the disease in two or more first-degree relatives in the absence of other known familial syndromes. With the increasing incidence of PTC in the recent years, the familial form of the disease has also become more common than previously reported and constitutes nearly 10% of all thyroid cancers. Many aspects of FNMTC are debated, concerning both clinical and genetic aspects. Several studies reported that, in comparison with sporadic PTCs, FPTCs are more aggressive at disease presentation, while other authors reported no differences in the clinical behavior of sporadic and familial PTCs. For this reason, recent guidelines do not recommend screening of family members of patients with diagnosis of differentiated thyroid cancer (DTC). FNMTC is described as a polygenic disorder associated with multiple low- to moderate-penetrance susceptibility genes and incomplete penetrance. At the moment, the genetic factors contributing to the development of FNMTC remain poorly understood, though many putative genes have been proposed in the recent years. PURPOSE: Based on current literature and our experience with FNMTC, in this review, we critically discussed the most relevant controversies, including its definition, the genetic background and some clinical aspects as screening and treatment.

Papillary Thyroid Cancer-Aggressive Variants and Impact on Management: A Narrative Review.

INTRODUCTION: Aggressive variants of papillary thyroid cancer (PTC) have been described with increasing frequency. These variants include diffuse sclerosing variant, tall cell variant, columnar cell variant, solid variant, and hobnail variant. METHODS: We have performed a review of the more aggressive variants of PTC with respect to main characteristics, histological and molecular features, and the consequences that the knowledge of these variants should have in the treatment of the patients. RESULTS: At the present time, we do not know the prognostic value of these aggressive PTC variants. The extent of the surgical treatment and adjuvant therapy necessary should be decided on the basis of the extent of the tumor at presentation and the opinion of experienced clinicians. CONCLUSION: These aggressive variants should be known by clinicians, to avoid underdiagnosis, and treated according to the latest recommendations in the literature.

Quality of Life in Patients with Papillary Thyroid Microcarcinoma According to Treatment: Total Thyroidectomy with or without Radioactive Iodine Ablation.

BACKGROUND: Recently, there has been some controversy regarding the role of radioactive iodine (RAI) ablation in the treatment of low-risk differentiated thyroid carcinoma (DTC), especially papillary thyroid microcarcinoma (PTMC). This study aimed to compare quality of life (QoL) parameters between patients with PTMC who underwent total thyroidectomy (TT) alone and those who underwent TT with RAI ablation. METHODS: In this cross-sectional study, patients with PTMC who underwent TT with/without RAI remnant ablation were prospectively enrolled between June 2016 and October 2017. All patients completed three questionnaires: the 12-item short-form health survey (SF-12), thyroid cancer-specific quality of life (THYCA-QoL) questionnaire, and fear of progression (FoP) questionnaire. RESULTS: The TT and TT with RAI groups comprised 107 and 182 patients, respectively. The TT with RAI group had significantly lower serum thyrotropin (TSH) levels than the TT group. However, after matching for TSH levels between the groups (n=100 in both groups), there were no significant differences in baseline characteristics. According to the SF-12, the score for general health was significantly lower in the TT with RAI group than in the TT group (P=0.047). The THYCA-QoL also showed a significant difference in the "felt chilly" score between groups (P=0.023). No significant differences in FoP scores were observed between the groups. CONCLUSION: Patients with PTMC who underwent TT with RAI ablation experienced more health-related problems than those managed with TT alone. These findings support the idea that RAI ablation should be carefully considered in patients with low-risk DTCs.

Localization and characterization of thyroid microcalcifications: A histopathological study.

Thyroid calcification is frequent in thyroid nodules. The aim of our study was to evaluate the prevalence of calcifications in thyroid tissue samples of patients with various thyroid diseases, and to identify their composition according to their localization. Among 50 thyroid samples included, 56% were malignant (papillary carcinoma) and 44% were benign (adenoma, multinodular goiter, Graves' disease, sarcoidosis). Calcifications were found in 95% of samples using polarised light microscopy, whereas only 12% were described in initial pathological reports. Three types were individualised and analyzed by infrared spectrometry (µFTIR): colloid calcifications composed of calcium oxalate, capsular calcifications and psammoma bodies, both composed of calcium phosphate. Of notice, psammoma bodies characterized by FE-SEM were composed of concentric structure suggesting a slow process for crystal deposition. Calcium phosphates were found only in malignant samples whereas calcium oxalate was not associated with a define pathology. Proliferation assessed by KI67 staining was high (33% of positive follicles), and RUNX2, OPN, and CD44 positive staining were detected in thyrocytes with a broad variation between samples. However, thyrocyte proliferation and differentiation markers were not associated with the number of crystals. TRPV5 and CaSR expression was also detected in thyrocytes. mRNA transcripts expression was confirmed in a subgroup of 10 patients, altogether with other calcium transporters such as PMCA1 or Cav1.3. Interestingly, TRPV5 mRNA expression was significantly associated with number of colloid calcifications (rho = -0.72; p = 0.02). The high prevalence of calcium oxalate crystals within colloid gel raises intriguing issues upon follicle physiology for calcium and oxalate transport.

Longitudinal Assessment of Quality of Life According to Treatment Options in Low-Risk Papillary Thyroid Microcarcinoma Patients: Active Surveillance or Immediate Surgery (Interim Analysis of MAeSTro).

Background: In this ongoing multicenter prospective cohort study on active surveillance (AS) in low-risk papillary thyroid microcarcinoma (PTMC), we aimed to compare the quality of life (QoL) of participants based on their choice of treatment, that is, AS or immediate surgery (OP). Methods: QoL of 203 participants who chose AS and 192 participants who underwent OP was evaluated using a thyroid-specific QoL questionnaire at diagnosis and during follow-up (median 8 months). Results: The mean ages of the participants in the AS and OP groups were 47.3 ± 11.7 and 45.6 ± 10.5 years (p = 0.138), respectively, and the mean tumor sizes were 5.7 ± 1.6 and 6.5 ± 2.1 mm (p = 0.065), respectively. At baseline, significantly better psychological health (7.1 ± 1.3 vs. 6.8 ± 1.6, p = 0.023) and overall health (6.8 ± 1.2 vs. 6.5 ± 1.3, p = 0.018) were observed in the AS group than in the OP group. During follow-up, significantly better physical (7.9 ± 1.1 vs. 7.4 ± 1.2, p < 0.001), psychological (7.4 ± 1.3 vs. 6.9 ± 1.6, p = 0.004), and overall health (6.9 ± 1.0 vs. 6.5 ± 1.1, p = 0.002) were observed in the AS group than in the OP group, whereas spiritual health was comparable between the two groups. Compared with the AS group, the OP group experienced more fatigue, changes in voice and appearance, less satisfaction, and low fear of recurrence. The self-assessed financial burden was similar at baseline and follow-up in both groups. Conclusion: The QoL of PTMC patients is different according to the type of treatment. Better psychological health at baseline and physical and psychological health at follow-up were observed in the AS group than in the OP group. However, studies with longer follow-up periods are needed.

Quality of Life in Patients with Papillary Thyroid Microcarcinoma Managed by Active Surveillance or Lobectomy: A Cross-Sectional Study.

Background: Active surveillance (AS) is recommended as an alternative to immediate surgery in patients with papillary thyroid microcarcinoma (PTMC), but the impact of AS on quality of life has not been reported. The aim of this study was to compare quality-of-life parameters in patients with PTMC under AS versus those who underwent lobectomy (LB). Methods: In this cross-sectional study, patients with PTMC were prospectively enrolled between June 2016 and October 2017. All patients completed three questionnaires: the 12-item short-form health survey, thyroid cancer-specific quality of life, and fear of progression. The results were compared after adjusting for age, sex, and serum thyrotropin levels. Results: The AS group comprised 43 patients, and the LB group comprised 148 patients. According to the 12-item short-form health survey questionnaire, the score for role limitations due to emotional problems showed a significant negative association between the groups (coefficient [coef]: -7.71 [confidence interval (CI) -15.26 to -0.16], p = 0.045). The thyroid cancer-specific quality of life questionnaire also showed statistically significant differences between the groups with respect to three scores: neuromuscular problems (coef: 4.99 [CI 0.63-10.62], p = 0.020), throat/mouth problems (coef: 5.28 [CI 0.18-10.38], p = 0.043), and scar problems (coef: 9.34 [CI 4.38-14.29], p < 0.001), suggesting a higher level of complaint in the LB group than in the AS group. No significant differences in fear of progression scores were seen between the two groups. Conclusions: Patients with PTMC underwent LB experienced more health-related problems than those managed by AS. These findings support the role of AS as a reasonable management option for patients with PTMC.

Low-Grade Papillary Schneiderian Carcinoma of the Sinonasal Cavity and Temporal Bone.

OBJECTIVES:: The aim of this study was to further characterize a newly described neoplasm, low-grade papillary Schneiderian carcinoma, occurring simultaneously in the sinonasal cavity and mastoid. Additionally, the authors review the only 2 similar cases within the literature and describe the common clinical features, radiographic findings, and pathologic characteristics of this exceptionally rare disease process. METHODS:: Chart review for single patient, review of literature. RESULTS:: The patient presented with bilateral nasal obstruction. Computed tomography revealed a left sinonasal mass with skull base hyperostosis, and follow-up magnetic resonance imaging showed a concomitant olfactory groove meningioma. Examination showed a bilateral, completely obstructing sinonasal mass with skip areas, and biopsy confirmed inverted papilloma (human papilloma virus strains 16 and 18 indeterminate). The patient underwent bilateral endoscopic sinus surgery, left medial maxillectomy, and left partial nasopharyngectomy. Given her multifocal disease, she was advised that she would require additional excision, but was lost to follow up. One year later she developed acute left facial paralysis. Magnetic resonance imaging demonstrated an enhancing mass in the left mastoid with enhancement along the Eustachian tube in addition to her known recurrent sinonasal disease. Simultaneous endoscopic sinus surgery and mastoidectomy were performed. Polypoid tissue was removed from the nasopharynx, mesotympanum, epitympanum, and retrofacial air cells. Immunohistochemistry showed that cells stained positive for p63 and dermCK and negative for synaptophysin. Morphologically, cells were bland, without classic stromal invasion, retaining their smooth, cystic, and papillary features, despite their increased depth within the tissue. Upon further review and consultation with an outside pathologist, a diagnosis of low-grade papillary Schneiderian carcinoma was made. The patient was referred for radiation therapy and is disease free at 3-month follow-up, with return of her facial function. CONCLUSIONS:: This case represents the first report of concurrent low-grade papillary Schneiderian carcinoma of both the nasal cavity and mastoid. It emphasizes the importance of recognizing this new entity through pathologic analysis and suspecting it when the clinical course does not follow an expected pattern.

Lymph Node Metastases Papillary Thyroid Carcinoma and their Importance in Recurrence of Disease.

BACKGROUND: The purpose of this study is to establish whether the lymph node metastases of the papillary thyroid carcinoma are a significant factor in recurrence of the disease by analyzing the time until recurrence of the disease and frequency of recurrence of the disease. METHODS: From 1 January 1995 until 30 June 2017, 102 patients were treated at the Public Health Institute Hospital "Sveti Vracevi" in Bijeljina for PTC. In all patients, surgery of the thyroid gland and/or lymph nodes of the neck was performed. Total thyroidectomy (TT) was performed in 20 patients and near-total thyroidectomy leaving <1 g thyroid tissue adjacent to the recurrent laryngeal nerve in 7 patients. TT and lymph nodes dissection were performed in 71 patients. Palliative surgery and biopsy due to locally advanced disease were performed in 3 patients. RESULTS: In our study, 102 patients with PTC were analyzed. 82 patients experienced pure PTC (80.4%), the other 20 patients (19.6%) experienced other variants of PTC. 24 patients (23.5%) experienced multi centric or bilateral tumors. 71 patients (69.6%) experienced histologically verified metastases in the lymph nodes of the neck. 7 patients (6.8%) experienced distant metastases. 20 patients underwent total thyroidectomy (TT), and 7 near-total thyroidectomy. Total thyroidectomy + dissection of central and lower jugular lymph nodes with frozen section histopathology verification was performed in 71 patients (69.6%). Out of these 71 patients, in 50 patients (70.4%) metastases were verified in the lower jugular lymph nodes. A modified lymph node dissection (MRND) was also performed in these patients. CONCLUSION: Lymph node metastases of the papillary thyroid carcinoma are a plausible prognostic factor. They are important for recurrence of the disease, but not for survival.

Resection of benign side-branch intraductal papillary mucinous neoplasm of the pancreas-is long term follow-up indicated?: A case report and review of the literature.

RATIONALE: Intraductal papillary mucinous neoplasms of the pancreas (IPMNs) are benign cystic tumors with a relevant risk of malignant transformation over time. Currently, follow-up after surgical resection of benign IPMNs remains controversial. PATIENT CONCERNS: This is a case report of a 68-year-old male who underwent pancreatic head resection for a multicystic side-branch IPMN with low-grade epithelial dysplasia in March 2009 at the Katharinenhospital Stuttgart, Germany. DIAGNOSES: During postoperative follow-up, a new solid, slightly hypodense lesion in the tail of the pancreas measuring 2.4 cm in diameter was diagnosed in July 2016. Preoperative staging revealed no signs of distant metastasis. INTERVENTION: Subsequently, the patient underwent pancreatic tail resection including splenectomy. Histology revealed IPMN-associated adenocarcinoma of the pancreas pT3, pN1 (2/24), M0, R0. OUTCOMES: Patients with IPMN bare a relatively high overall risk of developing pancreatic cancer. The 5-year incidence has been described to be as high as 6.9%. The current Consensus-Guidelines therefore recommend a structural life-time follow-up. In contrast, in 2015 the American Gastroenterological Association (AGA) explicitly states that follow-up is not recommended for resected benign IPMN. Currently, a general and international consensus is lacking. LESSONS: The presented case demonstrates that even more than 5 years following resection of benign IPMN, pancreatic cancer can occur in a separate location of the pancreatic gland. We believe that IPMNs can be considered as indicator lesions for pancreatic cancer. Patients with resected side-branch IPMN should therefore undergo long term follow-up.

Effects of different extracts of curcumin on TPC1 papillary thyroid cancer cell line.

BACKGROUND: The thyroid gland is one of the largest endocrine glands in the body. The vast majority of TCs (> 90%) originate from follicular cells and are defined as differentiated thyroid cancers (DTC) and the two histological subtypes are the papillary TC with its variants and the follicular TC. Curcumin possesses a wide variety of biological functions, and thanks to its properties, it has gained considerable attention due to its profound medicinal values (Prasad, Gupta, Tyagi, and Aggarwal, Biotechnol Adv 32:1053-1064, 2014). We have undertaken the present work in order to define the possible role of curcumin in modulating the genetic expression of cell markers and to understand the effectiveness of this nutraceutical in modulating the regression of cancer phenotype. METHODS: As a template we used the TPC-1 cells treated with the different extracts of turmeric, and examined the levels of expression of different markers (proliferative, inflammatory, antioxidant, apoptotic). RESULTS: Treatment with the three different curcumin extracts displays anti-inflammatory, antioxidant properties and it is able to influence cell cycle with slightly different effects upon the extracts. Furthermore curcumin is able to influence cell metabolic activity vitality. CONCLUSIONS: In conclusion curcumin has the potential to be developed as a safe therapeutic but further studies are needed to verify its antitumor ability in vivo.

Capsaicin inhibits the metastasis of human papillary thyroid carcinoma BCPAP cells through the modulation of the TRPV1 channel.

Capsaicin (CAP), a potent transient receptor potential vanilloid type 1 (TRPV1) agonist, is a major ingredient of red pepper. Recently, capsaicin has attracted increasing attention owing to its multiple biological activities. However, the anticancer effects of capsaicin against various types of cancers, especially on thyroid carcinoma, have not been completely elucidated. TRPV1, which can be activated by capsaicin, plays a key role in many biological and physiological processes. In the present study, the anticancer properties of capsaicin against papillary thyroid cancer BCPAP cells were investigated. Our results indicated that TRPV1 and TRPV6 were universally expressed in different types of thyroid cell lines. Capsaicin could inhibit multiple steps of metastasis without affecting the viability of BCPAP cells. The activation of TRPV1 by capsaicin (25-100 µM) significantly suppressed the migration and invasion of BCPAP cells as well as their adhesion. The protein levels of Snail1 and Twist1, two critical EMT transcription factors (EMT-TFs), dramatically decreased in a dose-dependent manner after capsaicin treatment, accompanied by the up-regulation of downstream protein E-cadherin. Subsequently, the activation of TRPV1 by capsaicin also caused significant inhibition of the expression of MMP-2 and MMP-9. Moreover, the inhibitory effects of capsaicin on the metastasis of BCPAP cells were abrogated by the pre-treatment of a specific TRPV1 antagonist (capsazepin). Our results suggest that the activation of TRPV1 by capsaicin is associated with the metastatic inhibition of papillary thyroid cancer BCPAP cells, indicating that targeting of TRPV1 functions remains a feasible strategy for cancer treatment.

Identification of topological features in renal tumor microenvironment associated with patient survival.

Motivation: As a highly heterogeneous disease, the progression of tumor is not only achieved by unlimited growth of the tumor cells, but also supported, stimulated, and nurtured by the microenvironment around it. However, traditional qualitative and/or semi-quantitative parameters obtained by pathologist's visual examination have very limited capability to capture this interaction between tumor and its microenvironment. With the advent of digital pathology, computerized image analysis may provide a better tumor characterization and give new insights into this problem. Results: We propose a novel bioimage informatics pipeline for automatically characterizing the topological organization of different cell patterns in the tumor microenvironment. We apply this pipeline to the only publicly available large histopathology image dataset for a cohort of 190 patients with papillary renal cell carcinoma obtained from The Cancer Genome Atlas project. Experimental results show that the proposed topological features can successfully stratify early- and middle-stage patients with distinct survival, and show superior performance to traditional clinical features and cellular morphological and intensity features. The proposed features not only provide new insights into the topological organizations of cancers, but also can be integrated with genomic data in future studies to develop new integrative biomarkers. Availability and implementation: https://github.com/chengjun583/KIRP-topological-features. Contact: 1271992826@qq.com or kunhuang@iu.edu. Supplementary information: Supplementary data are available at Bioinformatics online.

Eosinophil Cationic Protein in Patients with Differentiated Thyroid Cancer Treated with Radioactive Iodine 131.

Published data indicate the involvement of eosinophil granulocytes and eosinophil cationic protein (ECP) in tumor defense. The aim of this study was to analyze serum ECP concentrations in patients with differentiated thyroid cancer (DTC) before, 3 days and 7 days after radioactive iodine (131-I) therapy. Association of ECP concentrations with histological type of tumor, stage of disease and/or levels of selected T-helper 2 (Th2) cytokines was examined. The study population included 17 DTC patients and 10 control subjects. ECP was measured by fluoroimmunoassay (FIA). Th2 (cytokines interleukin 4 (IL-4), interleukin 5 (IL-5), and interleukin 13 (IL-13)) were determined by enzyme-linked immunosorbent assays (ELISA). We found that ECP values in DTC patients before radioactive iodine therapy were approximately two-fold higher than in the controls, but the difference was statistically significant only if the patients with DTC and associated Hashimoto thyroiditis (HT) were included. There was no correlation between the serum concentrations of IL-5 and ECP. Radioactive iodine therapy led to a decrease in serum ECP level which did not follow the decline in serum protein levels. Additional studies are needed to determine the significance of these findings.

The Influence of Inverted Growth Pattern on Recurrence for Patients with Non-Invasive Low Grade Papillary Urothelial Carcinoma of Bladder.

AIMS: To evaluate the impact of a histologically inverted pattern on recurrence in patients with newly diagnosed non-invasive, low-grade papillary urothelial carcinoma of the urinary bladder. METHODS: A total of 81 patients with primary bladder non-invasive, low-grade papillary urothelial carcinoma diagnosed in a single tertiary-care centre who had at least 1-year follow-up after an initial resection were included. All slides from each case were reviewed to determine the growth pattern (exophytic versus endophytic, i.e. inverted) and other histological parameters. Clinical data were retrieved from hospital records. RESULTS: Disease recurrence occurred in 41 (50.6%) patients. Cases with an inverted pattern showed a lower recurrence rate than those with pure exophytic tumours (37.5% versus 52.1%), a longer time to first recurrence (mean 34 versus 21.5 months) and fewer recurrence episodes (p=0.482, 0.564 and 0.051, respectively). All recurring inverted cases recurred only once during follow-up. No tumour with >80% inverted architecture recurred. CONCLUSION: Our results suggest that non-invasive, low-grade papillary urothelial carcinoma of the bladder tends to have a better outcome in terms of disease recurrence if it shows an inverted growth pattern. To indicate the presence and percentage of the inverted pattern in low-grade urothelial carcinomas in the pathology report might be considered as an adjunct to help long-term patient management.

Measurement and Variation in Estimation of Quality of Life Effects of Patients Undergoing Treatment for Papillary Thyroid Carcinoma.

BACKGROUND: Thyroid cancer incidence is increasing. The effect of diagnosis and treatment on health-related quality of life (HRQoL) is an essential variable in the absence of a change in life span for the majority of patients. HRQoL instruments, with data useful for between-disease comparisons, are being increasingly used for health policy and outcomes evaluation. Variation exits among the instruments based on the impact of a specific disease. We assessed which of four well-validated, preference-based surveys detect changes in health and clinical intervention in patients diagnosed with papillary thyroid cancer (PTC). METHODS: Four commonly used HRQoL questionnaires (Short Form-12v2® [SF6D], EuroQol-5D [EQ5D], and Health Utilities Index Mark 2 and 3 [HUI2, HUI3]) were administered to patients with the diagnosis of PTC at three perioperative time points during the first year of treatment. Clinicopathological and treatment course data were assessed for HRQoL impact including complications from surgery, re-operation for persistence/early recurrence, and adjuvant radioactive iodine treatment. We compared standard metrics, including ceiling effect, intraclass correlation coefficient, effect sizes, and quality-adjusted life-years between the four instruments. RESULTS: Of 117 patients, 27% had a preoperative diagnosis of anxiety or depression, 41% had regional lymph node metastases, three had distant metastases and 49% underwent adjuvant radioactive iodine treatment. The ceiling effect (i.e., proportion with a perfect score) was greatest with EQ5D and least with SF6D. Index scores ranged from 0.77 (SF6D) to 0.90 (EQ5D). All scores declined at two weeks postoperatively and returned to pretreatment levels at six months. The SF6D was the only instrument to exceed the conventional minimally important difference between all three time points. Quality-adjusted life-years were as follows: SF6D, 0.79; EQ5D, 0.90; HUI2, 0.88; and HUI3, 0.86. CONCLUSIONS: Our results reflect the general good health of PTC patients. The effect on quality of life is primarily related to emotional and social impacts of treatment. The results support the measurement of a similar underlying construct, although variation in detecting changes in health exists between the instruments. Of the instruments assessed, the SF6D is the most responsive to treatment effects and should be utilized in future economic analyses in this patient population.