Long-term survivors of childhood,adolescent and young adult non-Hodgkin lymphoma

Progress in overall survival rates for childhood non-Hodgkin lymphoma (NHL) can be largely attributed to effective development and conduct of a number of international treatment studies. Knowledge gained from these studies has shifted the treatment paradigm from a “one-size fits all” strategy to a histologically dependent approach. More specifically, many now adhere to a risk-stratified approach, prescribing cumulative doses and intensities of chemotherapeutic exposures based upon the aggressiveness of disease. Moreover, recognition that high cure rates could be achieved without the use of radiation has eliminated the use of this modality in frontline settings for the majority of newly diagnosed children. These changes have contributed to the emergence of a heterogeneous group of NHL survivors. As the number of NHL survivors continues to increase, providers will encounter a wide spectrum of individuals whose risk for long-term complications are accordingly diverse. The following review summarizes the existing literature surrounding late effects, such as chronic health conditions, functional and neurocognitive performance outcomes, and health-related quality of life, that are unique to NHL survivors, as well as those extrapolated from the broader childhood cancer survivor population.     

Changes in dental fear and its relations to anxiety and depression in the FinnBrain Birth Cohort Study

This study aimed to: (i) evaluate short-term changes in dental fear during a 9-month period among women and men, and (ii) evaluate whether the course and magnitude of changes in dental fear were associated with changes in depression and anxiety. The longitudinal data of the FinnBrain Birth Cohort Study were used. Out of 3808 women and 2623 men, 1984 women and 1082 men filled in the Modified Dental Anxiety Scale (MDAS) at gestational weeks 14 and 34, and 3 months after childbirth. Other questionnaires used were the Edinburgh Postnatal Depression Scale and the anxiety subscale of the Symptom Checklist-90. All scales were analyzed as sum scores. The MDAS was also trichotomized to assess the stability of dental fear. Statistical significances of the changes in dental fear, depression, and general anxiety were evaluated using repeated-measures Friedman tests. Correlation coefficients were used to describe the associations between measures (Spearman) and their changes (Pearson). Dental fear more often increased than decreased, but for the majority it was stable. On average, dental fear, depression, and anxiety symptoms correlated throughout the study. The correlations tended to be stronger with depressive symptoms. However, the relationships between changes in dental fear, depression, and anxiety were not systematic.     

Encapsulated papillary carcinoma with and without frank invasion: Comparison of clinicopathologic features and role of axillary staging

To investigate clinical and pathologic features of encapsulated papillary carcinomas (EPCs) that may be associated with invasive disease and characterize the axillary staging practices for EPCs at our institution. A pathology database search for cases containing “papillary carcinoma” was performed. Slides were reviewed by two pathologists. Clinicopathological features and axillary staging practices of EPCs with and without invasion were compared. Twenty-five cases of EPCs were identified. Fifteen cases contained a frank invasive tumor (60%), which were all pT1 (0.7 ± 0.56 cm), and the majority were ER-positive, HER2-negative, low-grade IDC-NST. Seventeen patients underwent sentinel lymph node biopsies (SLNB). No nodal metastases were identified. Follow-up was available for 24 patients (mean = 39 ± 29 months); 23 had no NED. Patients that presented with a self-palpated mass (versus screening) were more likely to have an invasive component; however, no pathologic or radiologic features differentiated EPCs with and without frank invasion. Pathologic and radiologic characteristics did not differentiate EPCs with and without frank invasion. EPCs have an excellent prognosis supported by the notable disease-free survival and negative nodal status in our cohort, which supports the notion that patients with EPCs may forgo axillary staging.     

Correction to: Trends towards more active introduction of drug therapy,emphasizing methotrexate and biologic agents,for juvenile idiopathic arthritis

Clinical Rheumatology - The first and family names of the authors were interchanged and are now presented correctly. The original article has been corrected.     

Shunt-dependent hydrocephalus after subarachnoid haemorrhage and aneurysm surgery: Timing of surgery is not a risk factor

Summary Early hydrocephalus is a risk factor of shunt-dependent late hydrocephalus (SDHC). In the CT era 1980–1990 we had 835 consecutive patients operated on because of aneurysm and subarachnoid haemorrhage (SAH); 294 had an early hydrocephalus and 67 finally required a shunt. There were 14 patients with normal early CT and SDHC, in all 81 patients needed a shunt (10%). Patients with shunt did worse, they were older (53 vs 49) than the non-shunted group and there was a female preponderance.Pre-operative Grade correlated significantly with the need for a shunt operation; no one in Grade I developed SDHC, incidence in Grades III and IV was high (18% and 10%, respectively). Location was important; in vertebrobasilar area 28% and in anterior communicating area 14% but in middle cerebral area only 4% of the patients had SDHC.The amount of cisternal bleeding correlated significantly with SDHC; in 155 patients with non detectible or minimal cisternal blood only one developed SDHC, with severe cisternal bleeding the incidence was 16%. Ventricular bleeding increased the risk of SDHC, but intracerebral haematoma did not.Timing of surgery had no correlation with the risk of SDHC. Postoperative complications, haematomas and infections increased the risk of late SDHC. Delayed ischaemia correlated with the risk, but so did the treatment with nimodipine. Severe bleeding was the common predictor for the risk of SDHC. Location of the bleeding and postoperative problems are the other major causes. Outcome is, however, not so gloomy; 54% of patients with SDHC are independent one year later.     

Better visualization of a lung tumour with 99mTc-DPD than with 99mTc-glucoheptonate or 67Ga-citrate

A case of a squamous cell lung carcinoma detected with ^99mTc-DPD, ⁶⁷Ga-citrate and ^99mTc-glucoheptonate (GH) is reported. The highest uptake was seen with DPD and the lowest with ⁶⁷Ga. Emission-computed tomography was very useful in DPD imaging but gave less new information in GH and ⁶⁷Ga studies in comparison to traditional planar imaging. The patient had been given both irradiation and chemotherapy, which might be the cause of good accumulation of DPD and rather poor accumulation of GH and ⁶⁷Ga.     

HMG-CoA reductase inhibitor-induced myopathy in the rat: cyclosporine A interaction and mechanism studies

Recent clinical evidence indicates a potential for skeletal muscle toxicity after therapy with HMG-CoA reductase inhibitors (HMGRIs) in man. Although the incidence of drug-induced skeletal muscle toxicity is very low (0.1-0.2%) with monotherapy, it may increase following concomitant drug therapy with the immunosuppressant, cyclosporine A (CsA), and possibly with certain other hypolipidemic agents. In the Sprague-Dawley rat, very high, pharmacologically comparable dosages (150-1200 mg/kg/day) of structurally similar HMGRIs (lovastatin, simvastatin, pravastatin and L-647, 318) produced dose-related increases in the incidence and severity of skeletal muscle degeneration. Physical signs included inappetence, decreased activity, loss of body weight, localized alopecia and mortality. To evaluate the interaction between HMGRIs and CsA, a rat model of CsA-induced cholestasis was developed. In this 2-week model, the skeletal muscle toxicity of the HMGRIs was clearly potentiated by CsA (10 mg/kg/day). Doses of HMGRIs which did not produce skeletal muscle toxicity when given alone caused between 75 and 100% incidence of myopathy (very slight to marked skeletal muscle degeneration) when CsA was coadministered. Typical light microscopic changes included myofiber necrosis with interstitial edema and inflammatory infiltration in areas of acute injury. Histochemical characterization of the muscle lesion indicated that type 2B fibers (primarily glycolytic white fibers) were most sensitive to this toxicity but that, with prolonged administration, all fiber types were ultimately affected. Results of pharmacokinetic studies in rats treated with various HMGRIs +/- CsA indicated that coadministration of CsA alters the disposition of these compounds, resulting in increased systemic exposure (e.g., increased area under the plasma drug concentration vs. time curve-AUC) and consequent (up to 13-fold) increases in skeletal muscle drug levels. Evaluation of the potential interaction between the HMGRI, lovastatin and CsA at the level of hepatic microsomal metabolism indicated that CsA did not inhibit the metabolism of lovastatin in isolated microsomes from female rats. In light of the above findings, it appears that HMGRI-induced myopathy is a class effect in the rat, which is potentiated by CsA as the result of altered clearance and resultant increased tissue exposure. Cholestasis associated with CsA and HMGRIs may form the basis for decreased elimination and the resultant elevated systemic exposure. Furthermore, this toxicity is muscle fiber-selective and may be associated with impaired skeletal muscle energy metabolism.