Chronic lymphocytic thyroiditis (CLT) has a positive prognostic value in papillary thyroid cancer (PTC) patients: the potential key role of Foxp3+ T lymphocytes.

BACKGROUND: An impact of chronic lymphocytic thyroiditis (CLT) on papillary thyroid cancer (PTC) outcome has long been advocated but it is still controversial. PURPOSE: The aim of this study was to evaluate the prognostic value of CLT in a retrospective cohort of PTC patients and to characterize the lymphocytic subpopulations and infiltrate (LI). MATERIALS AND METHODS: We assessed 375 PTC patients, aged 45.2 ± 16.4 years, and treated with thyroidectomy and radioiodine remnant ablation, with a mean follow-up of 6.28 ± 3.86 years. In a subgroup of patients (n = 81) tissue sections were reviewed for the presence of CLT or lymphocytes associated with tumor in absence of background thyroiditis (TAL); cytotoxic CD8+/regulatory Foxp3+ T lymphocyte (CD8+/Foxp3+) ratio was characterized by immunohistochemistry: a low ratio is suggestive of a less effective anti tumor immune response. RESULTS: Seventy-five/375 patients (20%) had a histological diagnosis of CLT and showed at the last follow-up a significantly better outcome compared to those with no CLT (cure rate: 91.8 versus 76.3%, p = 0.003). LI was characterized in 81 PTC patients (24 with CLT and 57 with TAL): the peri-tumoral CD8+/Foxp3+ ratio was lower in patients not cured at the final evaluation. CONCLUSIONS: Our data suggest that concurrent CLT has a protective effect on PTC outcome and that the imbalance between cytotoxic and regulatory T lymphocytes in the peri-tumoral TAL may affect the tumor-specific immune response favoring a more aggressive behavior of cancer.

The efficacy of 0.12% chlorhexidine versus 0.12% chlorhexidine plus hyaluronic acid mouthwash on healing of submerged single implant insertion areas: a short-term randomized controlled clinical trial.

OBJECTIVES: The study was performed to evaluate the incidence of post-surgical adverse events at submerged implant sites as well as the antiplaque, antigingivitis and antistaining effects in the entire dentition of patients treated with two mouthwashes. METHODS: The present randomized controlled clinical study considered 40 patients subjected to dental implant treatment. Two 0.12% chlorhexidine mouthwashes were compared for 15 days: one with 0.1% hyaluronic acid (CHX⊗HYL group) and one without it (CHX group). Surgical outcome variables, and plaque, gingival, and staining indexes were recorded. RESULTS: Significant differences were found between the two rinses regarding the presence of oedema within 2 days after surgery (20% for the CHX⊗HYL group and 78% for the CHX group). No other significant differences were recorded between the two mouthwashes. No intergroup differences in plaque, staining and gingivitis indexes were registered. The intragroup analysis revealed that for the plaque and gingival indexes, the differences between the baseline values (before surgery) and those at 15 days were all found to be significant just for CHX⊗HYL rinse, with final values ranging from 0.18 to 0.23 for the plaque index and from 0.06 to 0.07 for the gingival index. The staining index increased for both mouthwash types with significant results (with final value of 0.19 and 0.31 for CHX⊗HYL and CHX groups, respectively). CONCLUSIONS: In the sites of patients subjected to dental implant placement, an additional anti-oedematigenous effect in early healing seemed to be disclosed for 0.12% CHX⊗HYL mouthwash. Regarding antiplaque and antigingivitis activities, HYL seemed to be ineffective.

Detection of calcifications in retinoblastoma using gradient-echo MR imaging sequences: comparative study between in vivo MR imaging and ex vivo high-resolution CT.

BACKGROUND AND PURPOSE: Intratumoral calcifications are very important in the diagnosis of retinoblastoma. Although CT is considered superior in detecting calcification, its ionizing radiation, especially in patients with hereditary retinoblastoma, should be avoided. The purpose of our study was to validate T2*WI for the detection of calcification in retinoblastoma with ex vivo CT as the criterion standard. MATERIALS AND METHODS: Twenty-two consecutive patients with retinoblastoma (mean age, 21 months; range, 1-71 months) with enucleation as primary treatment were imaged at 1.5T by using a dedicated surface coil. Signal-intensity voids indicating calcification on T2*WI were compared with ex vivo high-resolution CT, and correlation was scored by 2 independent observers as poor, good, or excellent. Other parameters included the shape and location of the signal-intensity voids. In 5 tumors, susceptibility-weighted images were evaluated. RESULTS: All calcifications visible on high-resolution CT could be matched with signal-intensity voids on T2*WI, and correlation was scored as excellent in 17 (77%) and good in 5 (23%) eyes. In total, 93% (25/27) of the signal-intensity voids inside the tumor correlated with calcifications compared with none (0/8) of the signal-intensity voids outside the tumor. Areas of nodular signal-intensity voids correlated with calcifications in 92% (24/26), and linear signal-intensity voids correlated with hemorrhage in 67% (6/9) of cases. The correlation of signal-intensity voids on SWI was better in 4 of 5 tumors compared with T2*WI. CONCLUSIONS: Signal-intensity voids on in vivo T2*WI correlate well with calcifications on ex vivo high-resolution CT in retinoblastoma. Gradient-echo sequences may be helpful in the differential diagnosis of retinoblastoma. The combination of funduscopy, sonography, and high-resolution MR imaging with gradient-echo sequences should become the standard diagnostic approach for retinoblastoma.

Five-year outcome of bone remodelling around implants in the maxillary sinus: assessment of differences between implants placed in autogenous inlay bone blocks and in ungrafted maxilla.

The placement of implants in the posterior maxillary area is considered a reliable procedure, offering recognized rehabilitative advantages. The aim of this study was to evaluate the performance of dental implants placed in the sinus floor augmented with a block autograft by comparing the outcomes over 5 years with those of dental implants positioned in non-augmented bone. This retrospective cohort study included 16 patients who had undergone prosthetic rehabilitation supported by dental implants between 2000 and 2006. One implant per patient was included and assigned to one of two predictor groups: grafted versus ungrafted maxillary sinus. Changes in marginal bone level (MBL) and apical bone level (ABL) over time, at 1, 3, and 5 years, were the primary outcome variables. Appropriate pair-wise comparison tests were performed. No significant differences were seen with regard to ABLs and among times between the grafted group (nine implants) and the ungrafted group (seven implants). Significant marginal bone resorption was found over time, primarily at the buccal aspect, in both study groups. The bone surrounding the apex of dental implants appeared stable after sinus augmentation in the grafted area. The behaviour of the two groups with regard to loss of MBLs over time was very similar.

IL-1ß and TGF-ß weaken the placental barrier through destruction of tight junctions: an in vivo and in vitro study.

INTRODUCTION: Chorioamnionitis is a gestational pathological condition characterized by acute inflammation of the amniochorionic membranes and placentas leading to high concentrations of IL-1ß, Il-6, Il-8 and TGF-ß in the amniotic fluid. In normal conditions, the permeability of foeto-maternal barrier is due to the assembly and maintenance of different cellular junctional domains. METHODS: In the present study, first we aimed to evaluate the protein expression (by immunohistochemistry and western blotting) and mRNA (by real time PCR) levels of the molecular components of tight junctions (Zonula occludens-1 and occludin), and of adherent junctions (VE-cadherin and ß-catenin) in placentas from chorioamnionitis compared to that in normal pregnancies. RESULTS: Western blotting results showed a significant down-regulation of occludin in placentas affected with chorioamnionitis. No differences were detected for the other proteins analysed. We evaluated whether occludin expression was regulated by IL-1ß, IL-6, IL-8 and TGF-ß by means of in vitro studies using HUVEC cultures and demonstrated a key role of IL-1ß and TGF-ß in the disappearance of occludin at cellular border. CONCLUSIONS: We conclude by suggesting a pivotal role of these two cytokines in facilitating intra-placental infection via para-cellular way due to the disassembly of tight junctions at trophoblastic and endothelial cells in placental tissues.

Is CT still useful in the study protocol of retinoblastoma?

BACKGROUND AND PURPOSE: Intralesional calcium deposition is considered a key element for differentiating retinoblastoma from simulating lesions. Our aim was to assess whether MR imaging associated with ophthalmologic investigations (ophthalmoscopy and ultrasonography) could replace CT in the detection of diagnostic intralesional calcifications in retinoblastoma. MATERIALS AND METHODS: Ophthalmoscopic findings, MR images, CT scans, and histologic examination of 28 retinoblastomas from 23 consecutive children (11 males, 12 females; age range at admission, 1-35 months; mean age, 11 months; median age, 9 months) were retrospectively evaluated. Ultrasonography was performed in 18 patients with 21 retinoblastomas. MR imaging included T2-weighted spin-echo and gradient-echo images, fluid-attenuated inversion recovery images, and T1-weighted spin-echo images with and without contrast enhancement. Clinical data were integrated with MR imaging data to evaluate the utility of both approaches to discover calcifications; particularly, a correlation between intralesional signal-intensity void spots on MR imaging and hyperattenuating areas on CT scans was performed. RESULTS: Ophthalmoscopy detected calcifications in 12 of 28 eyes (42.85%). Ultrasonography detected calcifications in 20 of 21 eyes (95.23%). CT showed hyperattenuating intralesional areas consistent with calcifications in 27 of 28 eyes (96.42%). MR imaging showed intralesional signal-intensity void spots in 25 of 28 eyes (89.28%). All spots detected with MR imaging matched the presence of calcifications on CT scans. Gradient-echo T2*-weighted and fast spin-echo T2-weighted images showed the highest degree of correlation with CT. When we put together ophthalmoscopy, ultrasonography, and MR imaging data, no calcifications detected on CT were missed, and the differential diagnosis was thorough. CONCLUSIONS: A combination of clinical data and MR images may remove potentially harmful ionizing radiation from the study protocol of retinoblastoma.

Volume changes of autogenous bone grafts after alveolar ridge augmentation of atrophic maxillae and mandibles.

The aim of the present retrospective chart review was to determine the relationship between nonvascularized osseous graft remodeling and the three-dimensional (3D) features of grafts and recipient sites, the anatomical recipient regions and different graft sources. 32 iliac crest or chin grafts were onlay-positioned in the mandible or maxilla of 14 patients. CT scans, taken before implant positioning and after 1 year, revealed a mean volume resorption of 35-51%. For iliac crest grafts, the average resorption was 42% when the onlay was positioned in the anterior maxilla and 59% when it was positioned in the posterior mandible. Spearman correlation and 3D interpolation analysis revealed, for both iliac crest groups, a moderate or advanced remodeling pattern depending on 3D features, namely graft thickness and shape, basal bone volume of recipient site, and the basal bone/graft volume ratio of the recipient site. No statistically significant differences were found between the recipient and donor site groups. Retrospective analysis of the data indicates that iliac crest grafts, onlay-positioned on adequate basal bone volume, may register a reduced volume remodeling when shaped thick in the anterior maxilla or rounded and convex, on the external surface, in the posterior mandible.

Clinical survey of neurosensory side-effects of mandibular parasymphyseal bone harvesting.

The aim of the present survey was to assess neurosensory disturbances and/or tooth-pulp sensitivity losses after mandibular parasymphyseal bone-harvesting procedures. Twenty-eight harvesting areas in 16 patients were surveyed. Mucosal and skin sensitivity of the chin/lower lip, divided into four regions, were determined via Pointed-Blunt and Two-Point-Discrimination Tests. Pulp sensitivity of the mandibular teeth from the left second bicuspid to the right second bicuspid was tested by cold vitality preoperatively and 12 months postoperatively. Teeth were grouped according to sensitivity alterations and distance from the harvesting defects, as measured on CT scans, and statistically significant differences sought. At 12 months, 29% of preoperatively vital cuspids overlying the harvesting defects revealed pulp-sensitivity losses; no patient reported anaesthesia or analgesia; hypoaesthesia was present in 4% (8 sites; 2 patients), hypoalgesia was present in 3% (5 sites; 2 patients) and Two-Point-Discrimination Tests yielded pathologic responses in 5% of tested areas (10 sites; 4 patients). Teeth with and without pulp sensitivity changes were statistically indistinguishable regarding distances between root apices or mental foramen and the harvesting defect. The loss of pulp sensitivity in any tooth cannot be predicted simply on the basis of the distance between its apex and the harvesting osteotomy line.

Familial non-medullary thyroid carcinoma displays the features of clinical anticipation suggestive of a distinct biological entity.

Non-medullary thyroid carcinoma (NMTC) is mostly sporadic, but familial clustering is described. We aimed to compare the features of patients with sporadic and familial NMTC (FNMTC) patients and to assess whether FNMTC patients with parent-child relationship exhibit the 'anticipation' phenomenon (earlier age at disease onset and increased severity in successive generations). Among 300 NMTCs followed in the Section of Endocrinology (University of Siena, Italy), 34 (11.3%) patients, all with the papillary histotype, (16 kindred), met the criteria of FNMTC. Twenty-seven of them (79.4%) exhibited a parent-child relationship and seven (20.6%) a sibling relationship. These patients were compared with 235 patients with sporadic papillary thyroid cancer (PTCs). To analyze the features of FNMTC of the first and second generations, we cumulated the series of Siena with 32 additional FNMTC patients (15 kindred) from the Department of Endocrinology-Endocrine Oncology, Thessaloniki, Greece. Significant difference between sporadic PTC and FNMTC patients included more frequent tumor multifocality (P=0.001) and worse final outcome in FNMTC patients (P=0.001). Among 47 FNMTC with parent-child relationship, we found an earlier age at disease presentation (P<0.0001), diagnosis (P<0.0001), and disease onset (P=0.04) in the second generation when compared with the first generation. Patients in the second generation were more frequently males (P=0.02); their tumors were more frequently multifocal (P=0.003) and bilateral (P=0.01), had higher rate of lymph node metastases at surgery (P=0.02) and worse outcome (P=0.04) when compared with the first generation. In conclusion, FNMTC displays the features of clinical 'anticipation' with the second generation acquiring the disease at an earlier age and having more advanced disease at presentation.

Mortality from second tumour among long-term survivors of retinoblastoma: a retrospective analysis of the Italian retinoblastoma registry.

Survivors of retinoblastoma (Rb) are at high risk of dying from second malignant tumour. The occurrence of second malignant neoplasm (SMN) and related mortality in a cohort of 1111 cases from the Italian Retinoblastoma Registry was analysed, considering the possible role of both genetic and iatrogenic causes. Rb patients had a greater than 10-fold excess in overall mortality compared with the general population (standardized mortality ratio (SMR) 10.73, 95% CI 9.00-12.80). Their excess risk attributable to cancers other than Rb was 14.93 95% CI 10.38-21.49). Survivors of hereditary Rb had an SMR for all causes of 16.25 (95% CI 13.20-20.00), whereas their SMR for all cancers was 25.72 (95% CI 17.38-38.07). Survivors of unilateral sporadic Rb had an SMR of 4.12 from all cancers (95% CI 1.55-10.98) and a much higher excess for overall mortality (SMR 13.34, 95% CI 10.74-16.56). As expected, survivors of hereditary Rb had higher mortality from cancers of the bone (SMR 391.90, 95% CI 203.90-753.20) and soft tissue (SMR 453.00, 95% CI 203.50-1008.40), small intestine (SMR 1375.50, 95% CI 344.00-5499.70), nasal cavity (SMR 13.71, 95% CI 1.93-97.35) and cancers of the brain and central nervous system (SMR 41.14, 95% CI 13.2-127.55).

Phthisis bulbi and buphthalmos as presenting signs of retinoblastoma: a report of two cases and literature review.

PURPOSE: To report two cases of bilateral retinoblastoma (RB) with unusual presentations. METHODS: The medical records of 321 patients from the Retinoblastoma Referral Center in Siena were reviewed. A total of 111 patients had bilateral RB, 2 of them presenting with phthisis bulbi and buphthalmos. Both patients underwent bilateral enucleation. Clinical features, imaging studies, and histopathology were reviewed. RESULTS: These 2 cases represent 0.62% (2/321) in our series. Histopathology did not reveal viable tumor cells in the phthisical eyes; in both buphthalmic eyes the tumor was active, infiltrating the choroid and optic nerve. CONCLUSIONS: Phthisis bulbi and buphthalmos are unusual presenting signs of RB. This very rare combination of these two signs in different eyes of the same patient is probably due to a delay in diagnosis.

Pleomorphic adenoma of the lacrimal gland in an 18-year-old girl irradiated for bilateral retinoblastoma.

PURPOSE: To report a case of pleomorphic adenoma of the lacrimal gland following irradiation for bilateral retinoblastoma. MATERIALS AND METHODS: Case report. A 4-month-old girl, with bilateral retinoblastoma, underwent enucleation of the right eye, systemic chemotherapy and bilateral external beam irradiation with a lateral field. The right anophthalmic socket (because of infiltration of the optic nerve) and the left eye (for relapse) were irradiated;. 17 years later, she developed a mass in the superotemporal quadrant of the left orbit. The mass was completely excised. RESULTS: Pleomorphic adenoma is rare in children and teenagers; it usually presents as a painless, slow growing mass in healthy adults. In this case, it developed as a second primary tumor after irradiation for retinoblastoma.

Nestin expression in normal adrenal gland and adrenocortical tumors.

Human adrenocortical cells have been shown to express cytokeratins and vimentin. Nestin is an intermediate filament protein that is mainly expressed in the developing nervous system and that has been recently reported in rat adrenal gland as well. Using immunohistochemical and biochemical approaches, the present study demonstrates that nestin is constantly expressed in situ in the cortex of normal human adrenal glands. Nestin expressing cells were prevalently located in the zona reticularis but some positive cells could be spotted in the zona fasciculata as well. Moreover, patches of nestin-positive cells have been constantly detected on sections of cortical adenomas. In contrast, adrenal carcinomas displayed a variable number of nestin-immunoreactive cells that in some cases were virtually absent. Samples of renal clear cell carcinoma metastasis in the adrenals were also examined which did not show nestin-immunoreactivity. We propose that a positive nestin-immunoreaction could be useful in differential diagnosis of clear cell tumors in adrenal glands.

Early neonatal brain injury in histologic chorioamnionitis.

The relation between clinical or histologic chorioamnionitis and early neonatal adverse neurologic outcome was investigated (n = 483). Histologic, but not clinical, evidence of chorioamnionitis was found to be a significant predictor of periventricular echodensity (odds ratio, 2.4; 95% CI, 1.8-3.2), echolucency (3.3; 1.9-5.6), ventriculomegaly (2.7; 1.8-4.2), intraventricular hemorrhage > or =3 (3.5; 2.4-5.2), and seizures (2.3; 1.4-3.7).

Hepatitis C virus infection and myositis: a polymerase chain reaction study.

Muscle biopsy tissue from a patient with chronic hepatitis, who was hepatitis C virus (HCV) positive and showed slight weakness of the right arm and leg associated with increased serum creatine kinase levels, was studied using immunocytochemical and polymerase chain reaction (PCR) techniques. Muscle biopsy showed changes compatible with an inflammatory myopathy. Immunohistochemical studies included the use of monoclonal antibodies against human T lymphocytes, macrophages, immunoglobulins, major histocompatibility complex class I molecules (MHC-I), and the neoantigens of the terminal C5b-9 complement membrane attack complex (MAC). In addition to confirming the potential importance of cytotoxic T cells and MHC-I antigen expression in inducing muscle pathology, we demonstrated MAC deposition and the presence of HCV-RNA in the muscle of our patient, suggesting that direct involvement of the virus leading to complement activation might be important in inducing muscle damage.

Scarring in papillary carcinoma of the thyroid: report of two new cases with exuberant nodular fasciitis-like stroma.

AIMS: To describe two new cases of papillary carcinoma of the thyroid with exuberant nodular fasciitis-like stroma, one of which was characterized by previously unreported transformation into a poorly differentiated lesion. Moreover, we explore the presence of TGF-beta to help to clarify the pathogenesis of the collagen formation. METHODS AND RESULTS: The case characterized by an aggressive behaviour exhibited areas of transformation into a poorly differentiated (insular) carcinoma of the thyroid. In both cases, as revealed by immunohistochemistry, neoplastic cells produced and secreted high amounts of TGF-beta. On the contrary, TGF-beta immunoreaction was never present in the normal thyroid or in papillary carcinomas without collagen bundles, while a weak, exclusively intracellular reaction was present in a patchy manner in cases showing intratumoral fibrous bundles. CONCLUSIONS: The rare variant of papillary thyroid carcinoma characterized by exuberant stroma may give rise to more aggressive lesions, as do other histotypes of differentiated thyroid carcinomas. TGF-beta, the fundamental cytokine which mediates scarring and activation of myofibroblasts, most probably induces the exuberant stroma.

Congenital cystic adenomatoid malformation of the lung associated with esophageal atresia and tracheoesophageal fistula.

Bronchopulmonary malformations associated with esophageal atresia (EA) and tracheoesophageal fistula (TEF) are extremely rare. The authors describe a case of type II congenital cystic adenomatoid malformation (CCAM) of the right lower lobe associated with EA and TEF (Vogt-Gross type C) in a full-term female infant. The CCAM presented as an incidental radiologic finding, and a contralateral tension pneumothorax developed shortly after surgical repair of the EA. Early recognition of this rare association is essential for correct operative management.

Cell composition and immunohistochemical detection of VEGF, TGF-beta, and TNF-alpha in proliferative vitreoretinopathy.

Formation of vascularized membranes inside the vitreous leads to retinal detachment and blindness. In this paper it is shown that vitreal membranes are composed of newly formed vessels and myofibroblasts, immersed in a loose stroma with sparse histocytes. Vascular endothelial growth factor (VEGF) is clearly present in cellular constituents of the membranes and, therefore, represents a fundamental cytokine in their formation, while transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) are not. Considering that the composition of vitreal membranes clearly resembles scar tissue, the absence of TGF-beta in the membranes could explain their peculiar histological appearance.

World Health Organization (WHO) and the World Heart Federation (WHF) Pathobiological Determinants of Atherosclerosis in Youth (PBDAY) Study. Histomorphometric investigation of the aorta and coronary arteries in young people from different geographical locations.

BACKGROUND AND AIM: At the Morphometric Reference Center of the World Health Organization (WHO) and the World Heart Federation (WHF) for the Pathobiological Determinants of Atherosclerosis in Youth (PBDAY) Project, histomorphometric studies were carried out on aortic and coronary artery walls of 590 people ranging from 5 to 34 yr of age, who were of European, American, Asian and African origin (6 countries) and died of trauma. The aim was to evaluate the mean intimal and medial thickness of arterial tissues. METHODS AND RESULTS: Computerized operator-assisted morphometry with a semiautomatic image analyzer was carried out on 2,893 histological slides (prepared at the WHO Reference Center in Malmö, Sweden). Our data show that age-dependent trends for prevalence of fatty streaks and atherosclerotic plaques in arteries are different: prevalence of fatty streaks increases until a plateau is reached, while exponential growth characterizes atherosclerotic plaque prevalence. Age is statistically associated with an increase in mean intimal and medial thickness in all specimens. CONCLUSIONS: Mean intimal and medial thickness differs in arterial wall specimens of individuals from various geographic locations: persons from countries with high mortality rates from cardiovascular disease tend to have greater mean intimal thickness in youth. Men with hypertension and those who smoke have significantly greater combined means of intimal thickness than normotensives and non-smokers respectively. The also have significantly greater combined means of medial thickness than normotensive men. Histomorphometric data provide evidence of the development of atherosclerotic lesions at an early age and relate their progression to ethnic and lifestyle factors and to major coronary heart disease risk factors.