The rising incidence of parotid metastases: our experience from four decades of parotid gland surgery.

Secondary neoplasia in the parotid gland is increasingly frequent. We examined outcomes from 40 years of parotid surgery to analyse patterns for metastasis, review the staging procedure and discuss management. We retrospectively examined 772 consecutive cases of parotid surgery in a university hospital between 1975 and 2015 and assessed changes in incidence and management over four decades. In all, 71% percent of patients were male and 29% were female, with a mean age of 68 years, aged between 23 and 93 years. We diagnosed 683 parotid tumours of which 15.8% (n = 108) were malignant; 44% (n = 48) of all malignant lesions were metastases. The incidence of malignant tumours rose from 8% in the first decade, 14% in the second, 17% in the third to 21% in the fourth. The incidence increased even further from 10% in the first to 57% in the final decade. Most frequent tumours were metastases of squamous cell carcinoma (79%), and the majority of these lesions (87%) arose from above the clavicle, with 30 primary tumours in the skin. In most cases, the skin tumour had been excised between 6 and 24 months prior to parotid metastasis. Management consisted of surgery with neck dissection. 48 patients (67%) received adjuvant therapy, but despite aggressive multimodal treatment, disease progressed in the majority of cases, in 57% squamous cell carcinoma of the skin primaries, 67% of mucosal primaries above the clavicle and 83% of infraclavicular primaries. Parotid malignant tumours are increasing in incidence, mostly due to a rise in metastatic malignant tumours within the parotid gland, most of which are metastases of skin tumours, commonly squamous cell carcinoma. Despite multimodal therapy, their recurrence and progression rate remains high. We propose inclusion in head and neck follow-up in all cases of head and neck skin cancers.

[Significance of Secondary Mucosal Primaries in Patients with a Cervical CUP-Syndrome]. / Bedeutung des sekundär auftretenden Primärtumors bei einem zervikalen CUP-Syndrom.

BACKGROUND: We discuss the significance of an occult primary in the prognosis of cervical carcinoma with unknown primary (CUP) after completion of diagnostic and treatment. PATIENTS/METHODS: A series of 36 patients diagnosed between 2001 and 2009 underwent staging including panendoscopy, mapping and tonsillectomy, ultrasound and CT/MRI of the neck, thorax and abdomen. The patients recieved neck surgery followed by adjuvant radio-(chemo-)therapy of cervical fields as well as limited mucosal irradiation (IMRT, GHD 50 Gy). The results of tumor control and therapy-related toxicity were ascertained. RESULTS: A secondary primary of the cervical metastases was not detected during follow-up. 6 patients died from distant metastases and 1 from chemotherapy; 4 patients died from a different secondary tumour, 2 patients died intercurrently. We did not observe late toxicity but 8% of patients had Grade 3 dysphagia. DISCUSSION: Efficacy of diagnostic procedure and therapy are important in treating occult primary tumours in CUP. Our results show that omitting PET-CT, which was not available in diagnostic workup of the study-patients, did not impact negatively on the manifestation rate of mucosal primaries and/or was compensated for by intensive therapy. Distant metastases and infraclavicular secondary primaries had a negative impact for the survival. Elective therapy of a presumed occult primary tumour in CUP should be included into the therapeutic discussion considering its efficacy and toxicity.

Self concept, action control and ADHD symptoms under methylphenidate treatment in adults with ADHD.

INTRODUCTION: Self-efficacy of adults with ADHD might be changed unfavourably under methylphenidate treatment. Therefore, we sought to investigate the initial situation and changes under this medication, regarding features related to self-efficacy (self concept, locus of control and action control). METHODS: 3 self-rating scales (FSKN, IPC, and HAKEMP-90/ACS-90) were applied to 24 adults with ADHD combined type, before and after 5 months of methylphenidate treatment. RESULTS: No negative changes with respect to ADHD symptoms or any questionnaire were found under medication. In fact, both ADHD symptom domains, 5 out of 10 self concept subscale scores, and all 3 action control subscale scores changed favourably. Regression analysis revealed that only facets of self concept, but not of locus of control or of action control, predicted the patients' response to stimulant medication (i.e., a reduction of ADHD symptoms). DISCUSSION: Positive changes of self-concept and action control features under methylphenidate treatment in this study may encourage therapists to treat adults with ADHD with stimulants, thus not being at risk to decrease their patients' self-efficacy. In combined pharmacological/psychotherapeutic approaches, self-concept scales could be used to predict treatment outcome, and in order to monitor interactions between ADHD symptom reduction and self concept.

Determination of CYP activity in precision-cut liver slices: whether to use intact slices or slice homogenate.

Despite CYP induction in vitro in precision-cut liver slices (LS) is well documented, there are no standardised assays for determining CYP activity as a major end-point. In this paper, short-term assays with intact and homogenised LS from male and female rats were directly compared. We obtained similar results for 7-ethoxycoumarine O-deethylation (ECOD) with LS from both sexes: higher basal activities were measured in LS homogenate, whereas slightly stronger induction by BNF was found with intact LS. CYP3A-dependent basal and dexamethasone (Dex)-induced 2beta-, 15beta- and 6beta-testosterone hydroxylation (TH) rates were higher in both intact and homogenised LS from male compared to female rats. CYP3A induction in vitro could likewise be detected in intact and homogenised LS preferentially by determining 2beta- and 15beta-TH, with higher induction factors observed in LS from females. 6beta-TH seems to be less inducible in intact LS of males. In vivo pretreatment of liver donors with BNF and Dex did not substantially disturb the subsequent in vitro induction of ECOD and TH, respectively.

Safety and efficacy of endoscopic pharyngeal pouch stapling in a large UK study.

Endoscopic stapling of pharyngeal pouch is minimally invasive surgery, ensuing fast recovery and shorter hospitalisation, but previous small case series may have biased outcome. Perioperative and long-term outcome of endoscopic stapling of pharyngeal pouch were examined retrospectively in the largest (n = 62) UK case series. Stapling was not possible in seven patients because of small size of the pouch. Most patients made a full recovery immediately post-operatively. Two patients developed a leak at the stapling site, but critical complications or direct mortality were not observed. Persistence or recurrence of symptoms were observed in 18% of patients and successfully treated by revision endoscopic stapling or open procedure. We recommend endoscopic stapling for all patients with moderate or large pharyngeal pouches.

Fluid shear of low magnitude increases growth and expression of TGFbeta1 and adhesion molecules in human bone cells in vitro.

Deformation of the bone matrix by mechanical strain causes fluid shifts within the osteocytic canaliculi which affect osteocytic cell metabolism. We applied low fluid shear (1 - 63 micro Pa for 10 - 48 h) to human osteoblastic cells (HOB) in vitro to study its impact on cell proliferation and differentiated functions. Proteins involved in translating the physical force into a cellular response were characterised. Low fluid shear stress stimulated proliferation of HOB 1.2-fold when stress was applied intermittently for 24 h. Shear stress also increased differentiated cellular properties such as alkaline phosphatase (ALP) activity (121 % of control), fibronectin (FN) and fibronectin receptor (FNR) expression (290 % and 200 %, respectively). Prostaglandin E (2) (PGE (2)) and TGFbeta1 release into the medium were significantly stimulated when shear stress was applied for 6 - 12 h and 24 - 48 h, respectively. TGFbeta1 + 2 neutralising antibodies or the presence of indomethacine inhibited the mitogenic effect of fluid shear and reduced ALP activity to its control level. Furthermore, TGFbeta treatment induced a dose-dependent increase in FN and FNR expression. Therefore, fluid shear stress of low magnitude (a) suffices to affect HOB metabolism and (b) regulates anchorage of HOB via FN and FNR by stimulating osteoblastic PGE (2) and TGFbeta secretion.