Emergence of KRAS-mutation in liver metastases after an anti-EGFR treatment in patient with colorectal cancer: Are we aware of the therapeutic impact of intratumor heterogeneity?

Tumors represent a dynamic system where the genomic plasticity permits to adapt to the perturbation induced by environmental pressures, supporting the importance of longitudinal tumor sampling strategies to deciphering the temporal acquisition of driver event that could impact treatment outcome. We describe the case of a metastatic colorectal cancer (mCRC) patient, RAS wild-type, who responded to anti-EGFR therapy and underwent liver surgery, revealing a KRAS mutations in the metastatic lesion, not detectable prior to initiation of therapy in the colonic biopsy. After liver surgery, the patient received chemotherapy alone, then underwent left colectomy and the final pathological report confirmed the KRAS wild-type status. We can speculate the existence of two distinct populations of KRAS wild-type and mutant CRC cells sharing the same genetic origin. The anti-EGFR treatment represented a selective pressure which allowed the selection of KRAS mutant subclones. The prognostic and /or predictive role of intratumor heterogeneity has not been assessed prospectively. Our case report is of clinical relevance because patients with mCRC who respond to anti-EGFR antibodies often develop resistance within several months of initiating therapy, thus outlining the importance to better ascertain the molecular landscape of tumors to design better therapeutic strategies.     

Mrs. Doubtfire Mentoring Program: Helping Children in Residential Care Transition to Bedtime

An exploratory qualitative study was conducted for the Mrs. Doubtfire mentoring program designed to connect volunteers with young children (6–11 years) in residential care to help with the bedtime transition and develop positive relationships with caring adults. Details of the program are provided. Positive effects on the agency, staff, volunteers, and children are discussed. Mrs. Doubtfire provides an innovative approach to meeting needs of children in residential care while also building strong community relationships and dedicated volunteers.     

The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice.     

Ruolo delle epatopatie nella fase acuta del lichen planus orale

ObjectivesOral lichen planus (OLP) is considered an extrahepatic manifestation of chronic liver disease (CLD). To survey the incidence of OLP clinical exacerbations (OLPCE) in atrophic-erosive lesions, we assessed functional status of their liver in OLP patients by serological assays.Material and methodsWe selected 96 patients with CLD-related OLP-CLD (mean age 62.28 years ± 7.42, range 48-78 years; female:male ratio 2.3:1) from a cohort of 476 OLP patients. As intervention group, forty-eight out of 96 patients OLP patients had chronic HCV infection. As controls, forty-eight of 96 OLP-CLD patients had a chronic drug-induced hepatitis. The other 48 had a chronic drug-induced hepatitis (control group). Clinical signs were scored according to the criteria reported by Thongprasom et al. Serum samples from each patient were analyzed to determine the following: serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (γ-GT), pseudo-cholinesterase (PCHE), albumin/globulin ratio (AGR), alkaline phosphatase (AP), and blood glucose (BG) levels. Statistical analysis was based on the unpaired Student t-test. Differences were considered significant when p was < 0.05 (two-tailed).ResultsSGOT, SGPT, γ-GT, PCHE and BG were resulted significantly altered in 33/48 and 9/48 patients in the intervention group as well as control group, respectively. In both groups, the clinical score of OLP lesions was higher in patients with alterations of blood tests, mainly liver enzymes. The incidence of OLPCE was also significantly higher among OLP-CLD patients with alterations of the laboratory data. The atrophic-erosive form was the one most frequently observed.ConclusionsThe status of HCV infections and of toxic hepatitis alone does not seem to be the cause of OLPCE. Altered liver function parameters may trigger OLPCE with both types of CLD. Interdiscilinary cooperation between oral pathologists and hepatologists is vital whenever elevated transaminases levels are observed in OLP patients, to improve the clinical course of disease.