The importance of adjuvant treatment and primary anatomical site in head and neck basaloid squamous cell carcinoma survival: an analysis of the National Cancer Database.

PURPOSE: Basaloid squamous cell carcinoma (BSCC) of the head and neck is an aggressive and highly malignant variant of squamous cell carcinoma that accounts for 2% of head and neck cancers. Previous studies have not analyzed the significance of adjuvant chemoradiation and anatomical site within BSCC subtype and its impact on survival. METHODS: A cohort of 1999 patients with BSCC of the head and neck was formed from the National Cancer Database and analyzed with descriptive studies, median survival and 5- and 10-year survival. A multivariable Cox hazard regression was performed to determine the prognostic significance of anatomical site and adjuvant therapy. RESULTS: The most common primary anatomical site was the oropharynx (71.9%) followed by oral cavity (11.5%), larynx (10.1%), hypopharynx (3.5%), esophagus (1.9%), and nasopharynx (1.1%). The presence of metastasis increased the risk of mortality (HR = 2.14; 95% CI 1.40-3.26). Tumors localized to the oropharynx demonstrated better survival compared to all sites except nasopharynx, including the oral cavity (HR = 2.45; 95% CI 1.83-3.29), hypopharynx (HR = 2.58; 95% CI:1.64-4.05), and larynx (HR = 2.89; 95% CI:2.25-3.73). Adjuvant chemoradiation (HR = 0.36; 95% CI 0.23-0.58) and adjuvant radiation (HR = 0.38; 95% CI 0.23-0.64) had better survival outcomes compared to adjuvant chemotherapy. Patients with microscopic margins had better survival outcomes when compared to no surgery (HR = 0.38, 98% Cl 0.23-0.64) while there were no better survival outcomes of patients with macroscopic margins compared to no surgery. CONCLUSION: This study illustrated that tumors in the oropharynx, lower age, adjuvant chemoradiation and radiation, and microscopic margins were associated with greater survival.

Important prognostic factors in leiomyosarcoma survival: a National Cancer Database (NCDB) analysis.

BACKGROUND: Leiomyosarcoma (LMS) is an aggressive, malignant mesenchymal tumor with characteristic smooth muscle lineage accounting for 10-20% of all soft tissue tumors. The goal of this study is to determine the impact of prognostic factors on leiomyosarcoma survival irrespective of primary anatomical site. METHODS: There were a total of 7154 patients with primary leiomyosarcoma identified and analyzed from the National Cancer Database. Descriptive statistics, median survival, and 5- and 10-year survival probabilities were calculated along with a Cox proportional hazard model to determine independent prognostic factors. RESULTS: In this study, females comprised 68.3% of the cohort with a median age of 58 years. The most common primary anatomical sites were the extremities followed by female reproductive organs, abdomen, pelvis, thorax or lung, and head or neck. Tumors localized in the female reproductive organs had the worst survival (5-year survival probability: 45.3%), while tumors localized in the extremities had the best survival outcomes (5-year survival probability: 73.4%). Surgery with adjuvant radiation yielded better outcomes compared to surgery alone (HR 0.82, 95% CI 0.74-0.91). Microscopic and macroscopic margins resulted in a 32% and a 134% increased risk in mortality, respectively, when compared to negative surgical margins (p < 0.0001). CONCLUSION: This study showed a significantly higher risk of mortality associated with older patients, tumors localized to the female reproductive organs, African American patients, higher tumor stage, increased Charlson/Deyo scores, tumors treated with surgery alone without adjuvant radiation, and tumors with positive microscopic, macroscopic, or indeterminate surgical margins.

Trends in the use of radiation therapy for stage IIA prostate cancer from 2004 to 2013: a retrospective analysis using the National Cancer Database.

BACKGROUND: Recent studies have shown a decrease in the overall use of radiation therapy in the treatment of prostate cancer over the past several decades, as well as a more conservative overall treatment approach. We aim to determine whether this trend continued from 2004 to 2013, and to determine whether there were changes in utilization for various types of radiation. METHODS: We conducted this retrospective study using the National Cancer Database. We identified 706 877 patients with sufficient treatment information diagnosed with stage IIA prostate cancer between 2004 and 2013. Logistic regression models were used to evaluate the yearly trend in radiation therapy utilization. RESULTS: There was a significant decline in the use of radiation therapy from 2004 to 2013, from 54.4% in 2004 to 34.5% in 2013 compared with all the other treatments. The use of external beam radiation therapy (EBRT) declined from 27.1% in 2004 to 25.0% in 2013, brachytherapy declined from 19.7% in 2004 to 6.1% in 2013, and combination therapy declined from 6.8% in 2004 to 2.6% in 2013. However, when considering only patients receiving radiation treatments, the use of EBRT steadily increased from 50.6% in 2004 to 74.0% in 2013, whereas the use of brachytherapy declined from 36.7% in 2004 to 18.2% in 2013. Finally, although the proportion of patients receiving combination radiation therapy initially declined from 2004 to 2009 (from 12.7 to 8.3%), there was little change in utilization from 2009 to 2013 (8.3 to 8.5%). CONCLUSIONS: There has been a significant decline in the use of overall radiation therapy, as well as for each radiotherapy modality, for the treatment of prostate cancer since 2004. For patients that are receiving radiation, the use of EBRT has increased while brachytherapy use has decreased. These data serve to encourage further analysis as to the causes of these trends and how they affect patient care.

Denileukin diftitox in combination with rituximab for previously untreated follicular B-cell non-Hodgkin's lymphoma.

Follicular lymphoma exhibits intratumoral infiltration by non-malignant T lymphocytes, including CD4+CD25+ regulatory T (T(reg)) cells. We combined denileukin diftitox with rituximab in previously untreated, advanced-stage follicular lymphoma patients anticipating that denileukin diftitox would deplete CD25+ T(reg) cells while rituximab would deplete malignant B cells. Patients received rituximab 375 mg/m(2) weekly for 4 weeks and denileukin diftitox 18 mcg/kg/day for 5 days every 3 weeks for 4 cycles; neither agent was given as maintenance therapy. Between August 2008 and March 2010, 24 patients were enrolled. One patient died before treatment was given and was not included in the analysis. Eleven of 23 patients (48%; 95% confidence interval (CI): 27-69%) responded; 2 (9%) had complete responses and 9 (39%) had partial responses. The progression-free rate at 2 years was 55% (95%CI: 37-82%). Thirteen patients (57%) experienced grade ≥3 adverse events and one patient (4%) died. In correlative studies, soluble CD25 and the number of CD25+ T cells decreased after treatment; however, there was a compensatory increase in IL-15 and IP-10. We conclude that although the addition of denileukin diftitox to rituximab decreased the number of CD25+ T cells, denileukin diftitox contributed to the toxicity of the combination without an improvement in response rate or time to progression.

Rapid subthalamic nucleus deep brain stimulation lead placement utilising CT/MRI fusion, microelectrode recording and test stimulation.

Subthalamic nucleus (STN) deep brain stimulation (DBS) has become an established treatment strategy for patients with medically refractory Parkinson's disease (PD). There are however numerous strategies employed for STN lead placement. Variations include method of STN localisation, use of microelectrode recording, number of microelectrode recording passes and time taken for the procedure. We describe a relatively simple and rapid technique of STN lead placement utilising CT/ MRI image fusion, microelectrode recording and test stimulation. The first 58 consecutive patients undergoing STN DBS were assessed pre- and post-operatively. UPDRS scores, medication use and any surgical complication were assessed. Bilateral STN DBS was an efficacious treatment option for medically refractory PD. We have described a technique which can be performed with effect and low morbidity, and in a time which is well tolerated by patients.

Activation of the subthalamic region during emotional processing in Parkinson disease.

OBJECTIVE: To elucidate the involvement of the human subthalamic nucleus (STN) region in the processing or transmission of emotional information. METHODS: Local field potentials (LFPs) were recorded from this region in 10 patients with Parkinson disease (PD) undergoing bilateral implantation of the STN for high-frequency stimulation. LFP recordings were made while patients viewed pleasant and unpleasant emotionally arousing and neutral pictures. RESULTS: A significant decrease (event-related desynchronization [ERD]) in the local alpha power (8 to 12 Hz) was found for all stimulus categories starting at about 0.5 seconds after stimulus presentation. However, 1 to 2 seconds poststimulus, the ERD was larger in trials of pleasant (mean ERD: 21.6 +/- 2.8%; p < 0.009) and unpleasant (mean ERD: 15.0 +/- 4.2%; p = 0.018) stimuli compared with neutral stimuli (mean ERD: 4.4 +/- 4.2%). CONCLUSION: The delayed modulation of alpha activity recorded from the area of the subthalamic nucleus in PD may reflect the processing or transmission of information related to emotional stimuli. "Limbic" activation in the region of the subthalamic nucleus may explain why high-frequency stimulation of the subthalamic nucleus alters affect in some patients with PD.

Dural arteriovenous fistulae causing pseudotumour cerebri syndrome in an elderly man.

The clinical presentation of dural arteriovenous fistulae (DAVF) is dependent on their location and the nature of their venous drainage. The latter plays a critical part in determining whether or not the fistula gives rise to intracranial hypertension, which is present in only a minority of cases. We present a case of the pseudotumour cerebri syndrome in an elderly man with bilateral intracranial DAVF supplied by the occipital arteries. Cerebral angiography was required for definitive diagnosis, and to characterise the abnormal venous drainage. The pathophysiology of intracranial hypertension in DAVF is discussed.

A case of neurosyphilis with a florid Jarisch-Herxheimer reaction.

A 37 year old man with a 2 year history of progressive cognitive decline, unilateral tinnitus and deafness presented with complex partial seizures and a fever. On examination there was a sluggish right pupillary response but no other abnormal findings. Serum and CSF syphilis serology were both strongly positive. High dose intravenous penicillin therapy was complicated by a severe Jarisch-Herxheimer reaction (JHR) characterised by fever, obtundation, fluctuating upper motor neuron signs and complex visual and auditory hallucinations. These symptoms resolved over three days and the course of penicillin was completed. At discharge the patient's cognitive functioning was unchanged from the pretreatment state. He made gradual improvement over the following months but remains unable to live alone or work. Clinical, pathologic and radiologic findings of neurosyphilis are reviewed, as is the JHR, a self-limiting, systemic febrile response related to massive cytokine release that can occur in response to treatment of a number of bacterial infections. The similarities in pathophysiology of the JHR and the Septic Shock Syndrome are discussed, with particular reference to use of the JHR as a potential model for therapeutic agents in the treatment of septic shock.

Controlled-release oxycodone compared with controlled-release morphine in the treatment of cancer pain: a randomized, double-blind, parallel-group study.

Controlled-release oral formulations of oxycodone and morphine are both suitable analgesics for moderate to severe pain. They were compared in cancer-pain patients randomized to double-blind treatment with controlled-release oxycodone (n = 48) or controlled-release morphine (n = 52) every 12 h for up to 12 days. Stable analgesia was achieved by 83% of controlled-release oxycodone and 81% of controlled-release morphine patients in 2 days (median). Following titration to stable analgesia, pain intensity (0=none to 3=severe) decreased from baseline within each group (p

Congenital spigelian hernia with cryptorchidism.

Congenital spigelian hernia (SH) is a rarity. The authors present two cases of congenital SH with undescended testis, and examine the significance of the concurrence of these events.

Autosomal recessive congenital intrauterine infection-like syndrome of microcephaly, intracranial calcification, and CNS disease.

We present data on 10 patients from 5 families with a condition of microcephaly, intracranial calcification, and a clinical course resembling congenital TORCH infection. Repeatedly, negative TORCH investigations are a prerequisite for the identification of this disorder and the value of disturbed liver function and thrombocytopenia as aids to diagnosis is emphasised. Several similar families with recurrence of the disease in sibships are identified in the literature and the genetic implications of our observations are considered.

Angelman's syndrome: a neuropathological study.

We report the neuropathological findings of a 3-year-old boy with Angelman's syndrome. The main abnormalities were macroscopic consisting of small temporal and frontal lobes which also showed disorganised and irregular gyri. The occipital lobes appeared flattened but were otherwise normal as were the parietal lobes. The brain stem and cerebellum appeared normal externally. Microscopically there was irregular distribution of neurons in layer 3 and in the cerebral white matter a few subcortical ectopic neurons were present in the temporal and frontal lobes. A single "Purkinje" cell heterotopia was seen but otherwise the cerebellum appeared normal.

Steroids decrease granulocyte membrane fluidity, while phorbol ester increases membrane fluidity. Studies using electron paramagnetic resonance.

High concentrations of corticosteroids inhibit granulocyte responses and disrupt agonist receptor function. Dose-response and time-course considerations make it unlikely that these effects are mediated via the glucocorticoid receptor, a concept further supported by the ability of sex steroids to work similar effects. We postulated that steroids nonspecifically altered granulocyte membrane fluidity, which we measured directly by electron paramagnetic resonance. As predicted, methylprednisolone caused a dose-dependent increase in order parameter (decrease in fluidity) calculated on the basis of EPR spectra, using 5-doxylstearic acid (5-DS) as a probe of resting PMN membranes. This trend was highly significant (P less than 0.001; P at 0.5 mg/ml less than 0.01). Qualitatively similar results (but with different dose-response features) were obtained with conjugated estrogen. Granulocyte agonists (such as PMA) showed an opposite effect, which was not oxidatively mediated and which was steroid-inhibitable. 16-DS showed less prominent effects, suggesting that the membrane leaflets were more strongly affected than was the deep region of the membrane. Ibuprofen, which has similar effects to those of methylprednisolone on PMN aggregation and receptor function, caused a fluidizing rather than a stiffening of the membrane; this surprising result may indicate that there is a critical range of membrane fluidity for normal function, outside of which--in either direction--agonist receptor dysfunction occurs. We conclude that the immediate effects of very high doses of steroids are probably not mediated by corticoid receptors; instead, they may be due to changes in membrane fluidity.

Inhibition of granulocyte function by steroids is not limited to corticoids. Studies with sex steroids.

Noting that corticosteroid doses required for protection in shock models exceeded those required to saturate glucocorticoid receptors in mammalian cells, we postulated a nonspecific physicochemical effect of steroids upon the cell membrane, and therefore tested three noncorticoid steroids for their effects on granulocyte function. All three (conjugated equine estrogen, a synthetic progestogen, and a synthetic androgen) behaved in manner analogous to corticoids at similar concentrations, inhibiting granulocyte aggregation, chemotaxis, and chemiluminescence, as well as binding to the granulocytes of the synthetic oligopeptide agonist f-Met-Leu-Phe. Estrogen was further shown to reduce granulocyte membrane fluidity, assessed by electron paramagnetic resonance. We propose that the unique effects of extremely high-dose corticosteroids are not mediated via the glucocorticoid receptor, but result rather from physicochemical effects of the drugs upon the membranes of effector cells.

Pelizaeus-Merzbacher disease in a brother and sister.

A brother and sister developed a slowly progressive neurological disorder with cerebellar and pyramidal signs and mild dementia. The brother developed symptoms at 6 months and died aged 11 years; the sister developed symptoms at 3 years and died aged 18 years. At post-mortem both had severe widespread central nervous system demyelination with islands of preserved myelin, and small amounts of sudanophilic lipid products. Metachromatic material, globoid cells, and adrenal abnormalities were not seen. The features were those of Pelizaeus-Merzbacher disease (PMD). It has been proposed, on the basis of only a few family studies, that PMD is an X-linked recessive disorder. These cases suggest that autosomal recessive inheritance may occur.

Hemophilic arthropathy complicated by polyarticular septic arthritis.

A case of multiple pyarthroses due to Staphylococcus aureus occurring in a severe classical hemophiliac is presented. Successful management depended on drainage of the infected joints and a prolonged course of antibiotics. Several criteria are suggested for recognition of hemophiliacs who might benefit from joint aspiration as a diagnostic tool for the presence of septic arthritis.