Therapeutic Biomarkers in Lung Neuroendocrine Neoplasia

The well-known classification of neuroendocrine neoplasms of the lung into four major subtypes (including typical and atypical carcinoids and small- and large-cell neuroendocrine carcinomas) has a proven prognostic validity but only partially helps to predict the response to specific therapies. Therapeutic biomarkers are incompletely known and include morphological, immunophenotypic, and molecular markers. Morphology alone has no specific predictive role, nor has any immunophenotypic marker been proven to bear predictive implications. Ki67 is a relevant prognostic marker and can indirectly predict response to chemotherapy, when levels are extremely high in high-grade neuroendocrine (NE) carcinomas. The expression of somatostatin receptors, especially of the type 2A, has been shown to predict response to somatostatin analog treatments, paralleling the information derived from octreotide scintigraphy. mTOR pathway is targeted by specific inhibitors, but the exact cellular molecules predicting response are still to be defined. It seems that high levels of phosphorylated forms of mTOR and of its downstream factor S6K are associated to a better response to rapalogs in experimental models. Data from gene expression profiling and mutational analyses are currently emerging, providing a more detailed map of different molecular activation pathways, potentially leading to a more accurate molecular classification of lung NE tumors as well as to the discovery of new therapeutic targets. The combination of mutational profiles with those of upregulated or downregulated genes also by gene gains or losses may ultimately provide a better characterization of NE tumor histological types in terms of response to specific chemotherapy or biotherapy.     

Interobserver reproducibility of the controlled attenuation parameter (CAP) for quantifying liver steatosis

Purpose

This study was conducted to prospectively investigate the interobserver reproducibility of controlled attenuation parameter (CAP) measurements and the relationship among the CAP and body mass index (BMI), gender and age.

Methods

Consecutive subjects were studied using the M+ probe of the FibroScan device (Echosens, Paris, France). Measurements were performed by two raters (rater1 and rater2). Interobserver agreement was assessed by using the concordance correlation coefficient (CCC). The Pearson r coefficient was used to test correlation between two study variables, and linear regression was used for the multivariate model.

Results

Three hundred fifty-one subjects (227 males and 124 females) were prospectively studied. The CCC was 0.82 (95 % CI 0.78–0.85) overall, 0.80 (95 % CI 0.75–0.85) for BMI <25 kg/m², 0.76 (95 % CI 0.69–0.84) for BMI 25–29 kg/m² and 0.65 (95 % CI 0.41–0.88) for BMI ≥30 kg/m². The CCC was 0.44 (95 % CI 0.31–0.56) for CAP values ≤240 dB/m and 0.72 (95 % CI 0.65–0.79) for CAP values >240 dB/m. In univariate analysis, age and BMI by gender were correlated with the CAP. Multiple regression analysis confirmed the relationship of the CAP with age and BMI, but not with gender.

Conclusions

The results of this study show that the interreader agreement in CAP measurement is good. In healthy volunteers, the CAP is strongly correlated with age and BMI.     

Cicatricial iatrogenic lower eyelid malposition in skin cancer surgery: results of a combined approach

PurposeMalposition of the lower lid, including rounding of the lateral canthal angle, lower eyelid retraction with inferior scleral show, and ectropion, is a relatively frequent complication in the surgical treatment of skin cancer of the cheek and zygomatic areas. The tarsal strip technique, in association with a vertical vector cheek lift, is a reliable method for correcting lower lid malposition.Materials and patientsFrom January 2008 to January 2010, we treated 19 patients with lower eyelid malposition after skin cancer surgery of the cheek and zygomatic areas. To correct lower eyelid malposition, we used the tarsal strip technique and a vertical vector cheek lift in all patients.ResultsEleven patients had scleral show and eight patients had ectropion. Sixteen patients obtained satisfactory correction of the eyelid malposition in a single surgical procedure, while three patients required a second surgical step to correct the remaining scleral show. Good esthetic and functional results were achieved in all cases.ConclusionsThe surgical treatment of skin cancer of the cheek and zygomatic areas has the potential for postoperative sequelae. The tarsal strip technique, in association with a vertical vector cheek lift, is a relatively simple technique for correcting scleral show and ectropion.     

The 9-bp deletion in region V of mtDNA: a risk factor of hearing loss and encephalomyopathy in Caucasian populations?

A deletion of one of the two copies of the 9-bp tandem repeat sequence (CCCCCTCTA), in the small non-coding/untranslated segment located between the cytochrome oxidase II and lysine tRNA genes of mitochondrial DNA (mtDNA), has previously been used as a polymorphic anthropological marker (MIC9D) for people of Africa and Asia, but it has been rarely reported in Europe. 32 Sicilian patients with syndromic hearing loss, negative for mutations in GJB2 and GJB6 genes, were tested for mtDNA known point mutations associated with syndromic or non-syndromic hearing loss by RFLP and/or direct sequencing. We identified the presence of the MIC9D in homoplasmy in lymphocytes and muscle of three subjects with sensorineural hearing loss and encephalomyopathy, two of these also presented moderate mental retardation. This deletion was absent in 300 Caucasian controls. Although further studies are warranted, our results suggest that the MIC9D polymorphism could have a susceptibility role in Caucasus, such as Sicily population.     

Clodronate and hydroxychloroquine in erosive osteoarthritis: a 24-month open randomized pilot study

We evaluated the efficacy of clodronate for treating active erosive osteoarthritis of the hand and to compare it with hydroxychloroquine. Group A consisted of 24 patients treated for 24 months with clodronate 300 mg i.v. for 7 days, followed by clodronate i.m. 100 mg for 14 days every 3 months. Group B comprised 14 patients treated with hydroxychloroquine 400 mg daily for 30 days, followed by 200 mg daily for the next 11 months. In group A, 21/24 patients completed the trial and obtained significant pain reduction (p < 0.001), Dreiser’s score (p = 0.012), and number of tender joints (p = 0.011). Strength of right (p = 0.04) and left (p = 0.016) hands, physician’s global assessment (p ≤ 0.001), and patient’s global assessment (p = 0.021) improved. In group B, 8/14 patients completed 12 months of the study, which showed the inefficacy of hydroxychloroquine and its lack of acceptance by patients (worsening pain and patient’s global assessment). Therefore, enrolment was stopped. Differences between groups showed a pain decreasing trend for group A and a slightly increasing one for group B (p = 0.018). Physician and patient global assessments showed a strong increase in group A compared with group B (p < 0.001). Clodronate is effective in erosive osteoarthritis; hydroxychloroquine seems to be ineffective.     

Primary multicentric anaplastic pleomorphic xanthoastrocytoma with atypical features

Pleomorphic xanthoastrocytoma (PXA) is a rare tumor with good prognosis after surgery. Few cases of anaplastic PXA (either de novo or secondary to transformation of a recurrent low grade PXA) have been reported. Moreover, primary anaplastic PXA with dissemination at diagnosis has been described only in two patients, to our knowledge. We report the first case of primary multicentric anaplastic PXA and discuss its atypical features and the pertinent literature.