CD73 expression in lymph node metastases in patients with head and neck cancer

Introduction: CD73 is an enzyme crucial in the metabolism of immunosuppressive adenosine. In cancer, it has various functions including tumor growth and metastases. Squamous cell carcinoma of the head and neck has an overall poor prognosis, also due to early spread of metastatic cells.

Materials and methods: Tumor and lymph node specimens of 65 patients with HNSCC were subjected to immunohistochemical and H-score analysis of CD73 expression. Demographics, diagnoses, histopathology and subsequent outcome were analyzed.

Results: The primary cancer was squamous cell carcinoma in all patients (male/female 55:10) with the following locations: oral cavity n:16, oropharynx n:28, hypopharynx n:11 and larynx n:10. H-score for CD73 expression in the primary lesion and metastatic lymph nodes was significantly higher in advanced compared to early stages with no significant differences among tumor locations. High CD73 expression was associated with reduced overall survival rates at a mean follow-up of 83.4 months (6–204 months).

Conclusions: CD73 expression in HNSCC correlated positively with tumor stage and was associated with poor prognosis. Therefore, CD73 expression in primary lesions and regional metastases appears to predict HNSCC patients at high risk of all tumor sites. Therapeutic approaches targeting CD73 might seem promising for this patient population.     

Effect of sertindole on QTc interval in patients with schizophrenia

Sertindole has been marketed and offered daily clinical practice only for 9 months in our country, so no data has been its QTc prolongation potential. In the present study, we performed a clinical trial to investigate the effects of sertindole on QTc in patients with schizophrenia. The study comprised 21 patients with schizophrenia. Sertindole was administered in the following dosing regime: treatment was initiated with 4 mg/day sertindole. From day 3 to day 6, the dose was increased to 8 mg/day, and up to day 9, it was raised to 12 mg/day. The protocol allowed up to dose of 20 mg/day according to effectiveness and tolerability. QTc values were determined at beginning, months 3 and 6. In addition, Positive and Negative Syndrome Scale (PANSS) were scored concomitantly. At the beginning of 6-month period, the mean QTc interval of patients was 391.7 ± 19.2 ms. At the end of this period, it was 402.8 ± 23.8 ms. Although the mean QTc interval changing was significant throughout 6-month period, of the patients, at any evaluation point, only 1 female (451 ms) and 1 male (433 ms) had borderline prolongation at month 3 for both, without any exceeding the dangerous limits. In summary, our results suggest that sertindole is tolerable and despite dose-related QT prolongation, sertindole had not the proarrhythmic profile. Future studies with larger sample evaluating the effects of treatment are required.     

Thyrotoxic hypokalaemic periodic paralysis in a Turkish population: three new case reports and analysis of the case series

Objective Thyrotoxic hypokalaemic periodic paralysis (THPP) is an uncommon condition with intermittent episodes of muscle weakness and occasionally severe paralysis. THPP is a common complication of hyperthyroidism in Asian populations, and has also been reported in other ethnic groups including Caucasians. This study aimed to conduct an analysis of THPP in a Turkish population, and is to our knowledge the first analysis of a homogeneous Caucasian group. Subjects Forty cases with THPP were identified in the Turkish population. Three out of the 40 were new cases and were assigned as index cases. Two cases were not included in the analysis because of lack of data. Results THPP was diagnosed in 10 cases during the first attack and was observed to have a significant shorter complete recovery time statistically in this group (P < 0·01). The majority of cases were hypokalaemic, while there were two normokalaemic cases. Classification of the cases according to their potassium (K) levels revealed that the group with K levels < 2·5 mEq/l had a statistically longer amelioration time than the group with K levels ≥ 2·5 mEq/l. When the cases were classified according to intravenous or oral application of K, the mean amelioration time was 6·8 ± 3·6 h for the intravenous group and 13·1 ± 7·6 for the oral group. Mean complete recovery times of the groups were 29·4 ± 16·2 h and 52·8 ± 18·0 h, respectively. The intravenous group had a shorter amelioration time and complete recovery time, and both were statistically significant (P < 0·05 for each). Conclusions THPP may be seen among Caucasians. Diagnosing THPP during the first attack might decrease the recovery time. The level of hypokalaemia seems to affect the recovery time and initial low K levels may lead to more deterioration in a patient's health compared with mild or near‐normal levels. Intravenous, rather than oral, application of K may be advantageous for shortening both the amelioration and complete recovery times.     

An axillary arch

An axillary (axillopectoral) muscle (arch) was observed extending between the upper border of the latissimus dorsi and the lower border of the pectoralis major muscles in a 48-year-old male cadaver during our dissections. In the same cadaver, the pectoralis major muscle has entirely inserted into the most distal part of the tendon of deltoideus. © 1996 Wiley-Liss, Inc.     

PGT for aneuploidy does not affect three-cycle cumulative IVF discontinuation rate in women of advanced maternal age

Research questionDoes preimplantation genetic testing for aneuploidy (PGT-A) influence the discontinuation rate in women with advanced maternal age (AMA) undergoing IVF?DesignRetrospective longitudinal cohort study carried out at a single IVF clinic in Turkey. In total, 401 consecutive AMA cases were included. Discontinuation rates of pre-intervention (conventional IVF; June 2013 to October 2014; 203 couples; 270 cycles) and post-intervention (PGT-A; April 2015 to June 2016; 198 couples; 285 cycles) periods were compared. To delineate the reason for discontinuation, a telephone survey was conducted. Primary outcome measure was cumulative discontinuation rate before completing three cycles of IVF treatment without achieving an ongoing pregnancy.ResultsThe discontinuation rates after the first and second failed cycles were comparable between the two arms as were the cumulative discontinuation rates before completing three cycles. The cumulative ongoing pregnancy rate per embryo transfer was significantly higher in the PGT-A arm (43.2% versus 16.8%; P < 0.001). The cumulative ongoing pregnancy rate per patient was comparable between the two arms (20.7% versus 16.3%, respectively). Female age was the only significant contributor to treatment discontinuation (hazard ratio [HR] 1.07; 95% CI 1.09 to 1.13). Of the 296 couples discontinuing treatment in both arms, 179 (179/296 [60.5%]) participated in the survey; overall, psychological burden was the main reason for treatment discontinuation (37/179 [20.7%]).ConclusionsAbout 90% of AMA cases not achieving an ongoing pregnancy discontinue IVF treatment before completing three cycles. Discontinuation rate is not reduced by carrying out PGT-A. Female ageing is the only significant contributor, with a hazard of discontinuing further IVF treatment of 7% with female ageing of 1-year.     

The molecular pathogenesis and management of bronchial carcinoids

INTRODUCTION: In terms of well-differentiated neuroendocrine tumors (NETs), the lung is the second most common site of occurrence, after the gastro-entero-pancreatic axis, and comprises ～ 25% of all NETs which may occur in various parts of the body. Pulmonary NETs are classified into four groups including typical carcinoid tumors, atypical carcinoid tumors, small cell lung carcinoma and large cell neuroendocrine carcinomas. Among pulmonary NETs, typical and atypical carcinoid tumors of the lung are generally indolent, but do have a (albeit low) potential to metastasize. AREAS COVERED: The molecular biology and novel molecular pathways and drug targets in bronchial carcinoids are reviewed in this paper. A full data search is performed through PubMed over the years 2000 - 2010 with key words 'neuroendocrine tumors of the lung, bronchial carcinoid, lung carcinoid, foregut carcinoid, pulmonary carcinoid, pulmonary NETs, lung NETs, molecular biology, autoradiography, nuclear medicine, treatment'; all relevant publications are included, together with selected publications prior to that date. EXPERT OPINION: Although lying at the benign end of the spectrum of pulmonary NETs, bronchial carcinoids can metastasize, and the pathogenesis of these tumors is poorly understood. Several intracellular signaling pathways are under investigation to define new targets for the successful treatment of these tumors. In terms of treatment, further research should additionally focus on the already known but promising drug options.