Assessing value of contrast-enhanced ultrasound vs. conventional transthoracic ultrasound in improving diagnostic yield of percutaneous needle biopsy of peripheral lung lesions.

OBJECTIVE: The aim of the present study was to systematically assess the value of contrast-enhanced ultrasound (CEUS) vs. conventional transthoracic ultrasound (TUS) in improving diagnostic accuracy of percutaneous needle biopsy (PTNB) for subpleural lung lesions. PATIENTS AND METHODS: 232 patients with subpleural lesions were 1:1 randomly assigned to a group were CEUS was performed (n=116, mean age=65.5±5.6, M=69) or not (n=116, mean age=66.0±5.3, M=70). For CEUS study was used an injection of 4.8 mL of SonoVue (Bracco, Italy). For PTNB was employed a Menghini-modified technique with a semi-automatic 18-gauge needle. RESULTS: The mean diameter of subpleural lesions was 2.85±0.7 cm in the CEUS+ group and 2.95±0.6cm in the CEUS- group. Only 3 lesions, 1 in the CEUS+ group and 2 in the CEUS- group measured >5 cm. CEUS showed no superiority in terms of diagnostic accuracy compared to conventional TUS (p=0.34). Similar results were obtained in the sub-analysis of lesions sized between 1-2 cm (p=1.00) and 2-5 cm (p=0.08). As the lesion size increased, the detection rate of necrosis in lesions increased by CEUS (from 8% to 31%). CEUS showed no superiority in terms of diagnostic accuracy in the sub-analysis of necrotic lesions at CECT (p=0.38). AUC values for both the groups assessed an excellent diagnostic yield for TUS-PTNB (≥0.80). CONCLUSIONS: CEUS study does not improve the diagnostic accuracy of TUS-guided PTNB for peripheral lung lesions <5 cm of diameter. Further studies evaluating CEUS guidance for larger (>5 cm) and necrotic lesions are needed prior that its potential can be clarified.

Ultrasound-guided fine needle aspiration biopsy (FNAB) demonstrating upper distal extremity metastasis of lung adenocarcinoma: a case report and review of the literature.

Due to early metastasis and delayed diagnosis, lung cancer is the leading cause of cancer-related deaths. Although the most common metastasis sites are brain, bone, lung, adrenal glands, liver, and extra-thoracic lymph node, soft tissues, such as skeletal muscles, skin, and subcutaneous tissues, can also be undermined. This article aims to report the first case of an asymptomatic radial extensor muscle metastasis generating from a lung adenocarcinoma that was diagnosed by ultrasound-guided fine-needle aspiration biopsy (FNAB).

Real-world outcomes according to treatment strategies in ALK-rearranged non-small-cell lung cancer (NSCLC) patients: an Italian retrospective study.

PURPOSE: Anaplastic lymphoma kinase (ALK) rearrangement confers sensitivity to ALK inhibitors (ALKis) in non-small-cell lung cancer (NSCLC). Although several drugs provided an impressive outcome benefit, the most effective sequential strategy is still unknown. We describe outcomes of real-life patients according to the treatment strategy received. PATIENTS: We retrospectively collected 290 ALK rearranged advanced NSCLC diagnosed between 2011 and 2017 in 23 Italian institutions. RESULTS: After a median follow-up of 26 months, PFS for crizotinib and a new generation ALKis were 9.4 [CI 95% 7.9-11.2] and 11.1 months [CI 95% 9.2-13.8], respectively, while TTF were 10.2 [CI 95% 8.5-12.6] and 11.9 months [CI 95% 9.7-17.4], respectively, being consistent across the different settings. The composed outcomes (the sum of PFS or TTF) in patients treated with crizotinib followed by a new generation ALKis were 27.8 months [CI 95% 24.3-33.7] in PFS and 30.4 months [CI 95% 24.7-34.9] in TTF. The median OS from the diagnosis of advanced disease was 39 months [CI 95% 31.8-54.5]. Patients receiving crizotinib followed by a new generation ALKis showed a higher median OS [57 months (CI 95% 42.0-73.8)] compared to those that did not receive crizotinib [38 months (CI 95% 18.6-NR)] and those who performed only crizotinib as target agent [15 months (CI 95% 11.3-34.0)] (P < 0.0001). CONCLUSION: The sequential administration of crizotinib and a new generation ALKis provided a remarkable clinical benefit in this real-life population, being an interesting option to consider in selected patients.

Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids.

The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms.

The 2015 World Health Organization Classification of lung tumors: new entities since the 2004 Classification.

In the last few years different new pulmonary neoplastic lesions have been recognised and some of them, namely NUT carcinoma, PEComatous tumors, pneumocytic adenomyoepithelioma, pulmonary myxoid sarcoma, myoepithelial tumors/carcinomas entered in the last 2015-WHO classification of lung tumors. In addition angiomatoid fibrous histiocytoma and ciliated muconodular papillary tumor have been morphologically and genetically characterized albeit not yet included in the 2015-WHO classification.In the present paper we summarised the clinical, morphological, immunohistochemical and molecular features of these new entities. The knowledge of key histologic and molecular characteristics may help pathologists in achieving a correct diagnosis thus leading to an adequate therapeutic approach.

EZH2 and ZFX oncogenes in malignant behaviour of parathyroid neoplasms.

Several studies reported somatic mutations of many genes (MEN1, CTNNB1, CDKIs and others) in parathyroid adenoma, although with different prevalence. Recently, activating mutations of the EZH2 and ZFX oncogenes were identified in benign parathyroid adenoma by whole exome sequencing. The same mutations had been found in blood and ovary malignant tumours. On one hand, this result raised the hypothesis that these oncogenes may play a role in the onset of parathyroid tumour, but it would also suggest they may be involved in malignant, rather benign, parathyroid neoplasm. Our aim was to verify the occurrence of selected mutations of the EZH2 and ZFX genes in an Italian cohort of 23 sporadic parathyroid carcinomas, 12 atypical and 45 typical adenomas. DNA was extracted from paraffin-embedded tissues, PCR amplified and directly sequenced. No mutations were detected in the coding sequence and boundaries of both genes in any of the samples. Two polymorphisms of the EZH2 gene were identified with different prevalence: the rs2072407 variant was present in the 30 % of the samples, in keeping with the overall frequency in larger populations, while the rs78589034 variant, located close to the 5' end of the exon 16, was detected in only one proband with familial isolated hyperparathyroidism; we investigated the possible outcome on the splicing process. EZH2 and ZFX genes do not seem to have an impact on the onset of most parathyroid tumours, both benign and malignant, though further studies on larger cohorts of different ethnicity are needed.

Bilateral hypertrophy of masseteric and temporalis muscles, our fifteen patients and review of literature.

OBJECTIVE: The association of bilateral hypertrophy of temporalis and masseteric muscles is a rare clinical entity. The origin of the condition is unclear, causing cosmetic problems, pain, and functional impairment. PATIENTS AND METHODS: In this paper we analyzed 15 patients treated at the Department of Maxillo-Facial Surgery of the University of Naples Federico II, from 2000 to 2013, for temporalis and/or masseteric muscle hypertrophy, and in particular, a rare case of a patient with a marked bilateral swelling of the temporalis and masseteric region, in conjunction with a review of the literature. RESULTS: Fourteen patients have not any kind of postoperatively problems. The last patient had been aware of the swelling for many years and complained of recurrent headaches. We adopted a new protocol fort this patients and the patient was very pleased with the treatment results, and reported a reduction in headaches and a continuation of his well-being, in addition to greater self-confidence. The last follow-up was performed three years after the first treatment, and the patient showed a complete resolution of his symptoms, and just a small increase of the swelling. CONCLUSIONS: The treatment of temporalis and masseteric hypertrophy with Botulin toxin could be an effective option compared to conservative treatment or surgical intervention, although the review of the literature shows that this is only a temporary treatment. In fact, surgery still remains the best option. The treatment must be repeated every 4/6 months for 2-3 consecutive years before having stable benefits. To overcome this problem, an association with a bite treatment allowed us to achieve more lasting and more stable results over time without a recurrence of symptoms between the treatments. Furthermore, this association has enabled us to obtain a more rapid reduction of the hypertrophy.

Endoscopic treatment of primary benign central airway tumors: Results from a large consecutive case series and decision making flow chart to address bronchoscopic excision.

BACKGROUND: Benign tracheo-bronchial neoplasms are rare, but potentially dangerous conditions with life threatening consequences. Tumor removal should be pursued by methods minimizing the procedural stress. The role of endoscopic treatment, as an alternative to open surgery, remains controversial. OBJECTIVES: report the twelve-years endoscopic experience in Rome, Italy. Fifty-seven benign tracheo-bronchial tumors were diagnosed and 130 tracheo-bronchial resections by rigid bronchoscopy performed. METHODS: we identified histotypes associated with higher recurrence rate and assessed their relationship with gender, age and tracheo-bronchial location. We provided data on safety and complications and suggested a decision making flow chart to address the patients to endoscopic resection. RESULTS: complete eradication after a single procedure without recurrence at 2 years was obtained in 63.1% of cases (36/57). Need of a second intervention within few months but no further recurrence at follow up was seen in a further 8.8% (5/57). Histotypes associated with recurrence were papillomas and inflammatory polyp. Seven patients (12.3%) were addressed to surgery because of multiple recurrence. Ten patients (17.5%) were lost at follow up. In case of recurrence, the bronchial biopsy was always repeated and no malignant transformation was observed. No major complications, pneumothorax or pneumomediastinum occurred. CONCLUSIONS: endoscopic treatment of benign tracheo bronchial tumors is safe and effective, provided that the procedure is carefully and systematically planned. The rate of eradication is satisfactory and the incidence of complications negligible. This will encourage this approach as first line treatment especially in patients, frequently elderly people, having increased surgical risk due to concomitant respiratory failure or major comorbidities.

Prevention of postnatal growth restriction by the implementation of an evidence-based premature infant feeding bundle.

OBJECTIVE: To develop an evidence-based feeding bundle to safely decrease the rate of PNGR in VLBW infants. STUDY DESIGN: The bundle was developed and implemented in January 2010, followed by 3 years of monitoring bundle compliance and infant outcomes (days to first feed (FD), days to reach full feeds (FF), and birth-discharge growth trajectories (delta z-score)). RESULTS: Data were collected on 482 infants (119 pre-bundle). PNGR decreased from 35% to 19% (P<0.01) and weight delta z-score improved from -0.82 to -0.45 (P<0.001). Percentage of infants with head circumference (HC) below 10th percentile at discharge decreased from 21% to 9% (P<0.01) and HC delta z-score improved from -0.65 to -0.17 (P<0.001). FD and FF also decreased significantly. Rates of necrotizing enterocolitis, peak alkaline phosphatase and peak direct bilirubin levels all trended downward. CONCLUSIONS: An evidence-based, standardized feeding bundle was safe and effective in reducing the rate of PNGR and in improving head growth in VLBW infants.

Castleman's disease mimicking a parotid gland tumor: report of a case and review of the literature.

Castleman's disease (giant lymph node hyperplasia, angiofollicular hyperplasia, lymphoid hamartoma, benign giant lymphoma), is a quite rare and complex disease of lymphoid tissue that causes progressive lymph node enlargement, typically presenting as a solitary mediastinal mass. It was first described by Castleman et al in 1956. The head and neck regions are the second, less common site for this lesion. The preoperative diagnosis is very often extremely difficult and the routine investigations are often inconclusive. A multicentric extension of this disease shows poorer prognosis compared to the unifocal Histologically, three types do exist: the hyaline-vascular type, the plasma cell type and the mixed type. The etiology and pathogenesis is still unclear. In the literature, to our knowledge, only 112 cases have been reported involving head and neck, and only 22, including our own, interesting the parotid gland. In this report we describe a rare singular of Castleman's disease presenting as a tumor of the inferior pole of the parotid gland extending in the submandibular region, in a 35-year-old woman. The patient undergone a surgical treatment and, therefore, the mass was successfully totally removed.

Large cell carcinoma of the lung: clinically oriented classification integrating immunohistochemistry and molecular biology.

This study aimed at challenging pulmonary large cell carcinoma (LLC) as tumor entity and defining different subgroups according to immunohistochemical and molecular features. Expression of markers specific for glandular (TTF-1, napsin A, cytokeratin 7), squamous cell (p40, p63, cytokeratins 5/6, desmocollin-3), and neuroendocrine (chromogranin, synaptophysin, CD56) differentiation was studied in 121 LCC across their entire histological spectrum also using direct sequencing for epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and FISH analysis for ALK gene translocation. Survival was not investigated. All 47 large cell neuroendocrine carcinomas demonstrated a true neuroendocrine cell lineage, whereas all 24 basaloid and both 2 lymphoepithelioma-like carcinomas showed squamous cell markers. Eighteen out of 22 clear cell carcinomas had glandular differentiation, with KRAS mutations being present in 39 % of cases, whereas squamous cell differentiation was present in four cases. Eighteen out of 20 large cell carcinomas, not otherwise specified, had glandular differentiation upon immunohistochemistry, with an exon 21 L858R EGFR mutation in one (5 %) tumor, an exon 2 KRAS mutation in eight (40 %) tumors, and an ALK translocation in one (5 %) tumor, whereas two tumors positive for CK7 and CK5/6 and negative for all other markers were considered adenocarcinoma. All six LCC of rhabdoid type expressed TTF-1 and/or CK7, three of which also harbored KRAS mutations. When positive and negative immunohistochemical staining for these markers was combined, three subsets of LCC emerged exhibiting glandular, squamous, and neuroendocrine differentiation. Molecular alterations were restricted to tumors classified as adenocarcinoma. Stratifying LCC into specific categories using immunohistochemistry and molecular analysis may significantly impact on the choice of therapy.

Predicting weight outcomes in preadolescence: the role of toddlers' self-regulation skills and the temperament dimension of pleasure.

OBJECTIVES: To investigate the role of toddlers' self-regulation skills and temperament in predicting weight outcomes in preadolescence. METHODS: Participants for this study included 195 children (114 girls) obtained from three different cohorts participating in a larger ongoing longitudinal study. At 2 years of age, participants participated in several laboratory tasks designed to assess their self-regulation abilities, including emotion regulation, sustained attention and delay of gratification, whereas parents filled out a temperament questionnaire to assess toddlers' pleasure expression. Height and weight measures were collected when children were 4, 5, 7 and 10 years of age. Children also filled out a body image and eating questionnaire at the 10-year visit. RESULTS: Self-regulation skills in toddlers were associated with body mass index (BMI) development and pediatric obesity as well as body image/eating concerns. The temperament dimension of pleasure was also associated with BMI development and pediatric obesity but not body image/eating concerns. CONCLUSIONS: Self-regulation difficulties across domains as well as temperament-based pleasure in toddlers represented significant individual risk factors for the development of pediatric obesity 8 years later. Early self-regulation difficulties also contributed to body image and eating concerns that typically accompanied overweight children. The mechanisms by which early self-regulation skills and temperament-based pleasure may contribute to the development of pediatric obesity and associated weight concerns are discussed.

Intra-articular loose osteochondroma of the temporomandibular joint.

Osteochondroma or osteocartilaginous exostosis is one of the most common benign bone tumours. It usually develops in the metaphyses of long flat bones, but rarely occurs in the oral and maxillofacial area, where it is generally associated with the coronoid process or the condyle. Loose osteochondromas inside the joint are generally a rare pathology usually described in large joints. The authors present a case of an intra-articular loose osteochondroma of the temporomandibular joint (TMJ), which represents the first case of such a pathological entity in the literature. The authors suggest that it should be considered in any differential diagnosis of loose bodies described in the TMJ.

Co-occurring weight problems among children with attention deficit/hyperactivity disorder: the role of executive functioning.

OBJECTIVE: To explore the link between pediatric obesity and attention deficit/hyperactivity disorder (ADHD) by examining whether executive functioning (EF) and medication status are associated with body mass index (BMI) and weight status in children with ADHD. METHOD: Participants for this study included 80 children (mean age=10 years, 9 months) with a DSM-IV diagnosis of ADHD, confirmed by a comprehensive clinical diagnostic assessment. Children's EF was measured using three neuropsychological tests, and severity of ADHD symptoms and medication status were obtained from parent report. Children's height and weight were also measured during the visit using a wall-mounted stadiometer and a balance beam scale. RESULTS: Children with ADHD who performed poorly on the neuropsychological battery had greater BMI z-scores, and were more likely to be classified as overweight/obese compared with children with ADHD who performed better on the neuropsychological battery. In addition, children with ADHD who were taking a stimulant medication had significantly lower BMI z-scores compared with children with ADHD who were not taking medication or who were taking a non-stimulant medication. CONCLUSION: EF is more impaired among children with ADHD and co-occurring weight problems, highlighting the importance of self-regulation as a link between pediatric obesity and ADHD.

Immunodetection of occult eosinophils in lung tissue biopsies may help predict survival in acute lung injury.

BACKGROUND: Acute lung injury (ALI) is a serious respiratory disorder for which therapy is primarily supportive once infection is excluded. Surgical lung biopsy may rule out other diagnoses, but has not been generally useful for therapy decisions or prognosis in this setting. Importantly, tissue and peripheral blood eosinophilia, the hallmarks of steroid-responsive acute eosinophilic pneumonia, are not commonly linked with ALI. We hypothesized that occult eosinophilic pneumonia may explain better outcomes for some patients with ALI. METHODS: Immunohistochemistry using a novel monoclonal antibody recognizing eosinophil peroxidase (EPX-mAb) was used to assess intrapulmonary eosinophil accumulation/degranulation. Lung biopsies from ALI patients (n = 20) were identified following review of a pathology database; 45% of which (i.e., 9/20) displayed classical diffuse alveolar damage (ALI-DAD). Controls were obtained from uninvolved tissue in patients undergoing lobectomy for lung cancer (n = 10). Serial biopsy sections were stained with hematoxylin and eosin (H&E) and subjected to EPX-mAb immunohistochemistry. RESULTS: EPX-mAb immunohistochemistry provided a >40-fold increased sensitivity to detect eosinophils in the lung relative to H&E stained sections. This increased sensitivity led to the identification of higher numbers of eosinophils in ALI patients compared with controls; differences using H&E staining alone were not significant. Clinical assessments showed that lung infiltrating eosinophil numbers were higher in ALI patients that survived hospitalization compared with non-survivors. A similar conclusion was reached quantifying eosinophil degranulation in each biopsy. CONCLUSION: The enhanced sensitivity of EPX-mAb immunohistochemistry uniquely identified eosinophil accumulation/degranulation in patients with ALI relative to controls. More importantly, this method was a prognostic indicator of patient survival. These observations suggest that EPX-mAb immunohistochemistry may represent a diagnostic biomarker identifying a subset of ALI patients with improved clinical outcomes.

[Occult mediastinal node involvement in non-small cell lung cancer after negative uptake on PET/CT: ripples through staging and therapy. Case report and critical review]. / Linfonodi mediastinici "occulti" nel NCCLC: ripercussioni della falsa negatività PET/TC sulla stadiazione e sulla terapia. Caso clinico e rassegna critica.

A 78-years old man, heavy smoker, with a persistent and hacking cough, was diagnosed with an adenocarcinoma of upper lobe of left lung. Clinical stage was defined as cT2N0M0 also on the basis of a negative (18)FDG-PET/TC. After lobectomy, pathological stage resulted, on the contrary, pT2N2M0. Because the considerable incidence of preoperative false negative uptakes of PET/TC for involvement of mediastinal lymph nodes, this case report is highlighted as emblematic, particularly in relation to post-operative treatment of early stage NSCLC.

Toddler self-regulation skills predict risk for pediatric obesity.

OBJECTIVE: To investigate the role of early self-regulation skills, including emotion regulation, sustained attention and inhibitory control/reward sensitivity, in predicting pediatric obesity in early childhood. METHOD: Participants for this study included 57 children (25 girls) obtained from three different cohorts participating in a larger ongoing longitudinal study. At 2 years of age, participants participated in several laboratory tasks designed to assess their self-regulation skills. Height and weight measures were collected when children were 2 and 5.5 years of age. RESULTS: Self-regulation skills in toddlerhood were predictive of both normal variations in body mass index (BMI) development and pediatric obesity. Specifically, emotion regulation was the primary self-regulation skill involved in predicting normative changes in BMI as no effects were found for sustained attention or inhibitory control/reward sensitivity. However, both emotion regulation and inhibitory control/reward sensitivity predicted more extreme weight problems (that is, pediatric obesity), even after controlling for 2-year BMI. Thus, toddlers with poor emotion regulation skills and lower inhibitory control skills/higher reward sensitivity were more likely to be classified as overweight/at risk at 5.5 years of age. CONCLUSION: Early self-regulation difficulties across domains (that is, behavioral and emotional) represent significant individual risk factors for the development of pediatric obesity. Mechanisms by which early self-regulation skills may contribute to the development of pediatric obesity are discussed.

Maternal Behavior and Children's Early Emotion Regulation Skills Differentially Predict Development of Children's Reactive Control and Later Effortful Control.

The role of maternal behavior and children's early emotion regulation skills in the development of children's reactive control, specifically behavioral impulsivity, and later effortful control was examined in a sample of 435 children. HLM analyses indicated significant growth in reactive control across the toddlerhood to early childhood period. Emotion regulation at age-2 positively predicted initial levels of children's reactive control abilities while maternal overcontrol/intrusiveness predicted lower levels of reactive control growth. Maternal behaviors at age-2 predicted children's effortful control abilities at age-5.5. Emotion regulation did not predict effortful control abilities. Maternal behavior and children's early emotion regulation skills may differentially facilitate the development of reactive and effortful control abilities.