Active surveillance for small renal tumors: Have clinical concerns been addressed so far?

The incidence of small renal masses is increasing, as a result of the wide adoption of imaging exams. Their management, however, is complicated, especially in patients with decreased life expectancy or comorbidities. Approximately 20% of small renal masses are benign and, even if malignant, just 10% show aggressive pathological features. Furthermore, competing cause mortality seems to exceed the cancer‐specific mortality in patients aged over 70 years. The role of percutaneous tumor biopsy is still not well defined. All these observations raise the concern as to whether surgery might represent an overtreatment for some cases of small renal masses, calling into question the role of active surveillance. The aim of this review was to evaluate the current evidence pertaining to several hot questions that need to be addressed when contemplating active surveillance for small renal masses. The most relevant publications on this subject available in the literature were selected. Five representative series of active surveillance along with the main related variables were identified. Some relevant items surrounding the field of active surveillance were identified and submitted to an evidence‐based discussion. According to the recent evidence, small renal masses under active surveillance tend to show an indolent course with a low probability of disease progression, the latter being triggered most of the time by a tendency to grow faster. Unfortunately, we are currently unable to predict those few cases with aggressive behavior. According to the current evidence, active surveillance is feasible and safe in elderly and comorbid patients.     

Occupational allergic contact dermatitis from mercury

Occupational allergic contact dermatitis from metallic mercury is rare. Here we present the only 2 patients with relevant occupational mercury allergy detected at our clinic since 1974. The first patient was a dental nurse who became sensitized to metallic mercury from amalgam when handling uncured amalgam without protective gloves. The second patient had previously been sensitized to mercury from topical medicaments and developed work-related dermatitis when a mercury thermometer was broken at her place of work. Both patients had a positive patch test reaction to metallic mercury.     

Behavior of printable formulations of loperamide and caffeine on different substrates—Effect of print density in inkjet printing

The primary goal of the current work was to study the applicability of precision inkjet printing in fabrication of personalized doses of active pharmaceutical ingredients (APIs). Loperamide hydrochloride (LOP) and caffeine (CAF) were used as model compounds. Different doses of the drugs in a single dosage unit were produced, using a drop-on-demand inkjet printer by varying printing parameters such as the distance between jetted droplets (drop spacing) and the physical dimensions of the printed dosage forms. The behavior of the formulated printable inks for both APIs was investigated on the model substrates, using different analytical tools. The obtained results showed that printed LOP did not recrystallize on any substrates studied, whereas at least partial recrystallization of printed CAF was observed on all carrier surfaces. Flexible doses of both APIs were easily obtained by adjusting the drop spacing of the depositing inks, and the results were relevant with regards to the theoretical content. Adapting the dose by varying physical dimensions of single dosage units was less successful than the approach in which drop spacing was altered. In conclusion, controlled printing technology, by means of adjusting the distance between jetted droplets, offers a means to fabricate dosage forms with individualized doses.     

Long‐term effects of an education programme on the optimal use of clinical chemistry testing in primary health care

Objective: The aim of this study was to investigate whether continuing education on the optimal use of clinical chemistry testing in primary health care has had any long‐term effects on the test‐ordering behaviour of the participating physicians. Methods: The effects were monitored using 12 laboratory test ratios. Twenty‐three general practitioners at 16 primary health‐care centres in the county of Uppsala, Sweden, participated. A sign test was used to evaluate how individual physicians' test‐ordering patterns have changed during the 8 years since implementation of the educational programme. Maintained or improved ratios were interpreted as a sustained effect on the primary health‐care physician's test‐ordering habits. Results: Eleven out of 12 of the investigated ratios were the same or improved since the time of the short‐term follow‐up 6 months after the education. Conclusion: A short continuation course on optimal use of clinical chemistry assays can achieve permanent changes in the test‐ordering patterns of primary health‐care physicians. These findings highlight education as one possible means towards achieving cost‐efficiency and quality in test‐ordering.     

DNA damage recognition via activated ATM and p53 pathway in nonproliferating human prostate tissue

DNA damage response (DDR) pathways have been extensively studied in cancer cell lines and mouse models, but little is known about how DNA damage is recognized by different cell types in nonmalignant, slowly replicating human tissues. Here, we assess, using ex vivo cultures of human prostate tissue, DDR caused by cytotoxic drugs (camptothecin, doxorubicin, etoposide, and cisplatin) and ionizing radiation (IR) in the context of normal tissue architecture. Using specific markers for basal and luminal epithelial cells, we determine and quantify cell compartment-specific damage recognition. IR, doxorubicin, and etoposide induced the phosphorylation of H2A.X on Ser(139) (γH2AX) and DNA damage foci formation. Surprisingly, luminal epithelial cells lack the prominent γH2AX response after IR when compared with basal cells, although ATM phosphorylation on Ser(1981) and 53BP1 foci were clearly detectable in both cell types. The attenuated γH2AX response seems to result from low levels of total H2A.X in the luminal cells. Marked increase in p53, a downstream target of the activated ATM pathway, was detected only in response to camptothecin and doxorubicin. These findings emphasize the diversity of pathways activated by DNA damage in slowly replicating tissues and reveal an unexpected deviation in the prostate luminal compartment that may be relevant in prostate tumorigenesis. Detailed mapping of tissue and cell type differences in DDR will provide an outlook of relevant responses to therapeutic strategies.