Microsatellite instability is highly prevalent in older patients with colorectal cancer.

Background: Clinical guidelines suggest screening of colorectal cancer (CRC) for microsatellite instability (MSI). However, microsatellite instability-high (MSI-H) CRC is not rare in older patients. This study aimed to investigate the prevalence of MSI-H CRC in an unselected population in an age-based manner. Material and methods: A retrospective analysis of data from patients undergoing radical surgery for CRC was performed. Only cases with results from MSI testing using immunochemistry (IHC) were analyzed. Age-based analyses were performed using two cut-off ages: 50 years. as stated in Amsterdam II guidelines, and 60 years. as outlined in the revised Bethesda criteria. Results: The study population included 343 (146 female and 197 male) patients with a median age of 70 years (range 21-90 years). The prevalence of MSI-H tumors in the entire cohort was 18.7%. The prevalence of MSI-H CRC was 22.5% in the group ≤50 years vs. 18.2% in the group >50 years using the age limit in the Amsterdam II guidelines. MSI-H CRC was present in 12.6% of the group aged ≤60 years compared to 20.6% in the control group >60 years. Conclusion: MSI screening of CRC based on age alone is associated with negative selection of a relevant number of cases. MSI-H CRC is also common in elderly patients, who may be negatively selected secondary to an age-based screening algorithm. Following the results of this study, screening based on clinical criteria should be omitted in favor of systematic screening as is already internationally practiced.

Family history as a major prerequisite for microsatellite instability screening in colorectal cancer is a poor selection tool.

Background: Deficient mismatch repair (MMR) leading to microsatellite instability (MSI) in tumors is thought to be present in over 15% of colorectal cancer (CRC) cases. Testing CRC for MSI has traditionally been recommended following the fulfillment of clinical criteria. However, the performance of clinical criteria, especially the family history, as a selection tool for MSI screening in CRC is questionable. Methods: We retrospectively investigated the incidence of high degree MSI (MSI-H) tumors in an unselected population of CRC patients and compared its prevalence between individuals with and without family history of cancers within the spectrum of MSI-H tumors as defined in the revised Bethesda criteria. Results: The study population included 274 patients, 70 with positive and 204 without family history of MSI-H tumors with complete data including findings from MSI analysis. The overall incidence of MSI-H CRC was 18.98%. There was no statistically significant difference in the incidence of MSI-H CRC amongst both groups. The sensitivity and specificity of family history with regard to the presence of an MSI-H tumor in this collective was 36.5% and 77.5%, respectively. Conclusions: A relevant number of cases with high MSI-H CRC may be missed secondary to screening based on clinical criteria like family history alone. Thus, systematic screening independent of clinical characteristics, especially family history of cancer should be recommended in all cases with CRC.

Changes of individual retinal layer thickness post-uneventful cataract surgery determined by spectral-domain optical coherence tomography over a 3-months period.

Purpose: To evaluate retinal thickness changes of individual retinal layers using spectral-domain optical coherence tomography (SD-OCT) after uneventful cataract surgery over a 3-months period. Design: Prospective cohort study. Methods: 41 patients who underwent uneventful cataract surgery were included. Retinal SD-OCT images of both eyes were acquired preoperatively, 1 day after surgery as well as 1 month and 3 months postoperatively. Changes of retinal layer thickness were estimated after semi-automated segmentation for the following individual layers in the central subfield (CS, 1 mm) and inner ring (IR, 1-3 mm) of the early treatment diabetic retinopathy study (ETDRS) grid: retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), RNFL-GCL-IPL complex, inner nuclear layer (INL), outer plexiform layer (OPL), INL-OPL complex, outer nuclear layer (ONL), inner retina layer (IRL) and the total retina (TR). Furthermore, a sub-analysis with exclusion of patients devoid CME and an analysis in regard of patient age, lens status of the fellow eye, best corrected visual acuity and duration of surgery was conducted. Results: This study found significant alterations in all analysed retinal layers except for the RNFL (p = 0.33) and the GCL (p = 0.06) in the central subfield and the INL-OPL complex (p = 0.07) in the inner ring over the 3-months period (all p < 0.05). Retinal thickness decreases on the first postoperative day, followed by a significant increase 1 month after surgery and subsequent reduction at 3 months following uneventful cataract surgery could be observed. Conclusion: These results assume the hypothesis that the apex of inflammatory response, characterized by an augmentation in the thickness of individual retinal layers, occurs around 1 month after uneventful cataract surgery, and subsequently experience a reduction in activity. Therefore, we suggest that additional therapy for cystoid macular edema does not have to be initiated as early as the first month in mild cases.

Management of adverse events related to checkpoint inhibition therapy.

IO treatments (immuno-oncology treatments) have become reality and are now daily practice or, in some cases, a daily challenge. New recommendations are being made with the prime purpose of increasing alertness and awareness as well as emphasizing standard operating strategies to deal with immune-related adverse events (ir-AEs) in patients treated with immune checkpoint inhibitors (ICI). This brief review refers to systemic reviews, guidelines and meta-analyses, randomized controlled trials and case series published from 2000 to the present. Existing recommendations for optimal management of toxicities vary according to organ systems affected and grading. Grade 1 toxicities (exception to the rule: neurologic, hematologic, cardiac manifestation) require close monitoring. Grade 2 toxicities prompt immediate treatment interruption combined with corticosteroid administration (prednisone or methylprednisolone 0.5-1 mg/kg/day) until the symptoms revert to grade 1 or less. ir-AEs up to grade 3 or 4 justify suspension of treatment together with increased dosage of prednisone or methylprednisolone (1-2 mg/kg/day) combined with close monitoring to continuously adapt the current immunosuppressive strategy. In some cases, a different additional immunosuppressive agent has to be evaluated. Only when all symptoms have disappeared and immunosuppressive treatment produces a response can all immunosuppressive agents be tapered. Endocrinopathies are the exception to the rule and are mostly controllable by hormone replacement, at least in low-grade manifestation. This short review focuses on the main aspects that help manage immune-related side-effects and elucidates all the additional aspects surrounding and contributing to successful treatment and management of cancer patients.