Calcinosis cutis dermatologic toxicity associated with fibroblast growth factor receptor inhibitor for the treatment of Wilms tumor

Small‐molecule inhibitors (nibs) have revolutionized cancer therapy with the emergence of clinically efficacious treatment for advanced‐stage malignancies. Fibroblast growth factor receptor (FGFR) inhibitors have shown therapeutic efficacy in malignancies with molecular‐genetic alterations in the FGFR/fibroblast growth factor pathway. In a phase 1 clinical trial, erdafitinib, a pan FGFR inhibitor, was well tolerated with a manageable toxicity profile. Hyperphosphatemia was a frequent adverse event in patients treated with erdafitinib; however, no serious complications were observed with this therapy. Here, we report the development of calcinosis cutis dermatologic toxicity in a patient with hyperphosphatemia while treated with a novel selective FGFR inhibitor, INCB 54828‐101. Awareness of this form of dermatologic toxicity from an FGFR inhibitor will be important for close monitoring of serum levels of phosphate, FGF23, vitamin D, and calcitriol, the management of adverse serum chemistry with chelators, and treatment decisions to either reduce dose or withhold FGFR inhibitor.     

Comparing clinician knowledge and online information regarding Alli (Orlistat)

Background

Many consumers join online communities focused on health. Online forums are a popular medium for the exchange of health information between consumers, so it is important to determine the accuracy and completeness of information posted to online forums.

Objective

We compared the accuracy and completeness of information regarding the FDA-approved over-the counter weight-loss drug Alli (Orlistat) from forums and from clinicians.

Methods

We identified Alli-related questions posted on online forums and then posed the questions to 11 primary care providers. We then compared the clinicians’ answers to the answers given on the forums. A panel of blinded experts evaluated the accuracy and completeness of the answers on a scale of 0-4. Another panel of blinded experts categorized questions as being best answered based on clinical experience versus review of the literature.

Results

The accuracy and completeness of clinician responses was slightly better than forum responses, but there was no significant difference (2.3 vs. 2.1, p = 0.5). Only one forum answer contained information that could potentially cause harm if the advice was followed.

Conclusions

Forum answers were comparable to clinicians’ answers with respect to accuracy and completeness, but answers from both sources were unsatisfactory.     

What is biomedical informatics?

Biomedical informatics lacks a clear and theoretically-grounded definition. Many proposed definitions focus on data, information, and knowledge, but do not provide an adequate definition of these terms. Leveraging insights from the philosophy of information, we define informatics as the science of information, where information is data plus meaning. Biomedical informatics is the science of information as applied to or studied in the context of biomedicine. Defining the object of study of informatics as data plus meaning clearly distinguishes the field from related fields, such as computer science, statistics and biomedicine, which have different objects of study. The emphasis on data plus meaning also suggests that biomedical informatics problems tend to be difficult when they deal with concepts that are hard to capture using formal, computational definitions. In other words, problems where meaning must be considered are more difficult than problems where manipulating data without regard for meaning is sufficient. Furthermore, the definition implies that informatics research, teaching, and service should focus on biomedical information as data plus meaning rather than only computer applications in biomedicine.     

Histologic changes associated with false‐negative sentinel lymph nodes after preoperative chemotherapy in patients with confirmed lymph node‐positive breast cancer before treatment

BACKGROUND:

A wide range of false‐negative rates has been reported for sentinel lymph node (SLN) biopsy after preoperative chemotherapy. The purpose of this study was to determine whether histologic findings in negative SLNs after preoperative chemotherapy are helpful in assessing the accuracy of SLN biopsy in patients with confirmed lymph node‐positive disease before treatment.

METHODS:

Eighty‐six patients with confirmed lymph node‐positive disease at presentation underwent successful SLN biopsy and axillary dissection after preoperative chemotherapy at a single institution between 1994 and 2007. Available hematoxylin and eosin‐stained sections from patients with negative SLNs were reviewed, and associations between histologic findings in the negative SLNs and SLN status (true negative vs false negative) were evaluated.

RESULTS:

Forty‐seven (55%) patients had at least 1 positive SLN, and 39 (45%) patients had negative SLNs. The false‐negative rate was 22%, and the negative predictive value was 67%. The negative SLNs from 17 of 34 patients with available slides had focal areas of fibrosis, some with associated foamy parenchymal histiocytes, fat necrosis, or calcification. These histologic findings occurred in 15 (65%) of 23 patients with true‐negative SLNs and in only 2 (18%) of 11 patients with false‐negative SLNs (P = .03, Fisher exact test, 2‐tailed). The lack of these histologic changes had a sensitivity and specificity for identifying a false‐negative SLN of 82% and 65%, respectively.

CONCLUSIONS:

Absence of treatment effect in SLNs after chemotherapy in patients with lymph node‐positive disease at initial presentation has good sensitivity but low specificity for identifying a false‐negative SLN. Cancer 2010. © 2010 American Cancer Society.     

Improving the detection of patients with inherited predispositions to hematologic malignancies using next‐generation sequencing‐based leukemia prognostication panels

Recognizing and referring patients with possible inherited cancer predisposition syndromes for appropriate genetic evaluation and testing provides insights into optimal patient treatment approaches and also can provide education and testing opportunities for family members. Next‐generation sequencing (NGS)‐based, targeted genotyping for somatic mutations is increasingly used in the diagnosis, prognostication, and treatment selection for patients with hematologic malignancies. However, certain mutations that may be somatically acquired can also be present as germline mutations in some individuals and families. Whether the results of NGS‐based leukemia panels can be used to inform decisions and subsequent evaluation of patients with possible inherited cancer predispositions has not been described previously. Because a normal control often is not available when using NGS panels in patients with hematologic malignancies, NGS panel results offer both an opportunity and a challenge to determine the origin and pathogenicity of identified mutations. In the absence of a matched germline control, variant allele frequency (VAF) estimation and data from publically available data sets provide important clues to the possible germline origin of a variant. Careful annotation and review of NGS panels in patients with hematologic malignancies can provide a useful screening tool to systematically improve upon the detection of potentially pathogenic germline variants. Cancer 2018;124:2704‐2713 . © 2018 American Cancer Society     

Epidemiology of Primary Liver Cancer in Serbia and Possible Connection With Cyanobacterial Blooms

Today, the occurrence of harmful cyanobacterial blooms is a common phenomenon and a potential global health problem. Cyanobacteria can produce metabolites highly toxic to humans. More than 80% of reservoirs used for water supply in Central Serbia have bloomed over the past 80 years. A 10-year epidemiological study showed a significant increase in the incidence of primary liver cancer (PLC) in the regions where water from the blooming reservoirs was used for human consumption. At the same time, no correlation was found between the incidence of PLC and other risk factors, such as cirrhosis and hepatitis viruses. Given the strong association with PLC induction and various known possible mechanisms of carcinogenic action, it is highly possible that, cyanotoxins—acting as initiator and promoter—may be the major risk factor that acts synergistically with other risk factors to cause increased incidence of PLC. However, at present, it is still not certain whether cyanotoxins alone were sufficient to induce PLC. Therefore, additional assessment of the health risks that may arise from human exposure to cyanotoxins is advisable.