Clinical, pathological, and adjuvant chemotherapy use differences among microsatellite unstable and microsatellite stable colon cancers.

Background: Colon cancers are categorized into mismatch repair deficient/microsatellite unstable (MSI-H) and mismatch repair proficient/microsatellite stable (MSS) cancers. This study aims to compare the disease characteristics and trends in the utilization of cancer therapies across different age groups and stages in these two groups. Methods: MSI-H and MSS colon adenocarcinomas from 2010 to 2016 were identified using the National Cancer Database. We compared patient and disease characteristics between the two groups and evaluated the use of adjuvant chemotherapy across age groups and cancer stages. Within MSI-H and MSS groups, we conducted a landmark analysis after propensity score matching for adjuvant chemotherapy versus no chemotherapy to determine its effect on survival. Results: Of the 542,368 patients that met inclusion criteria, 120,751 (22%) had mismatch repair results available-out of these 96,928 (80%) had MSS colon cancers while 23,823 (19.7%) had MSI-H cancers. MSI-H disease had a bimodal age distribution (<40 years = 22%; ≥75 years = 26%) and was frequent among females (22%) and non-Hispanic Whites (20%). Among those < 65 years, 15% of low-risk stage 2 MSI-H patients and 40% of high-risk stage 2 MSI-H patients received adjuvant chemotherapy. More than two-thirds of stage 3 patients <65 years received adjuvant chemotherapy in both groups. After conducting propensity-score matching for age, gender, and co-morbidities, we found that adjuvant chemotherapy use had a trend towards lower overall survival (OS) in low-risk stage 2 MSI-H (HR = 1.8 [95% CI, 0.8-4.02]) and high-risk stage 2 MSI-H (HR = 1.42 [95% CI, 0.96-2.12]) groups. Adjuvant chemotherapy significantly improved OS in stage 3 colon cancer patients irrespective of microsatellite status or risk category of disease. Conclusions: MSI-H colon cancer had bimodal age distribution. Among stage 2 MSI-H patients <65 years, a notable proportion received adjuvant chemotherapy. Among MSI-H stage 2 patients, adjuvant chemotherapy use was associated with lower survival while it significantly improved survival for stage 3 patients, irrespective of MSI status.

Immune Checkpoint Inhibitors in pMMR/MSS Colorectal Cancer.

BACKGROUND: Immune checkpoint inhibitors have recently replaced over chemotherapy as the first-line treatment for microsatellite instability-high or mismatch repair deficient (dMMR/MSI-H) stage 4 colorectal cancers. Considering this success, many studies have tried to replicate the use of immune checkpoint inhibitors, either as a single agent or in combination with other therapeutic agents, in the treatment of proficient mismatch repair (pMMR/MSS) stage 4 colorectal cancers. This review summarizes the seminal clinical data about the immune checkpoint inhibitors used in pMMR/MSS colorectal cancers and some future directions. RESULTS: Studies concerning the use of immune checkpoint inhibitors as a single agent or in combination with other immune checkpoint inhibitors, targeted therapy, chemotherapy, or radiotherapy have proven inefficient in the treatment of pMMR/MSS colorectal cancer. However, a small subset of patients with pMMR/MSS colorectal cancer who has a mutation in POLE and POLD1 enzymes may respond to immunotherapy. Moreover, patients without liver metastasis appear to have a better chance of response. New immune checkpoint targets are being identified, such as VISTA, TIGIT, LAG3, STING signal pathway, and BTLA, and studies are ongoing to determine their efficiency in this disease type. CONCLUSION: Immune checkpoint inhibitor-based regimens have not yet shown any meaningful positive outcomes for most pMMR/MSS colorectal cancers. A beneficial effect among a minority of these patients has been observed, but concrete biomarkers of response are lacking. Understanding the underlying mechanisms of immune resistance should guide further research for overcoming these obstacles.

Management of type 3 Kienbock's disease in manual workers by scaphocapitate fusion with minimum 7-year follow-up.

Background: Kienbock's disease results in altered wrist biomechanics producing debilitating pain at the wrist. The disease is staged according to radiological and clinical findings and the stage guides the treatment. Various treatment options have been described for stage 3, however, there is a lack of consensus over these treatment methods. Scaphocapitate fusion is the preferred surgical option for advanced Kienbock's disease. Previous studies had heterogeneous cohorts with a short duration of follow-up and a lack of uniform surgical technique. The purpose of the study was to show the long-term functional and radiological outcome of scaphocapitate arthrodesis (SCA) by using Herbert screw for the treatment of Kienbock's disease in manual workers. Methods: For this single-centre, retrospective study, all consecutive patients who were manual workers and managed by SCA between January 2010 and Jan 2014 for Lichtman stage IIIA and IIIB with at least 7 years of follow-up were included. Patients were assessed using clinical and radiological parameters preoperatively and in the follow-up period. Disabilities of the Arm, Shoulder, and Hand (DASH), Patient-Related Wrist Evaluation (PRWE), and VAS for pain were assessed. Results: Out of 27 patients, 4 lost to follow-up, therefore, 23 patients (14 women and 9 men) with 30 years of median age at the time of the surgery were included. DASH scores, PRWE scores, and VAS for pain significantly improved (p < 0.5) after surgery. Wrist range of motion and grip strength also improved significantly (p < 0.5). Postoperative radiological parameters were found to be within a normal range. Conclusion: Scaphocapitate fusion by Herbert screws gives good functional, clinical, and radiological outcomes, in stage 3 of Kienbock's disease with excellent rates of fusion with low complications. Even, in manual workers, scaphocapitate fusion can reliably provide good outcomes and this is maintained in the mid to long-term follow-up. Therefore, it should be considered as one of the procedures of choice. Level of evidence: Retrospective, Level 4.

First-dose idarubicin cardiomyopathy: a case of new heart failure after induction chemotherapy for acute myeloid leukaemia.

Anthracyclines are an effective chemotherapy agent. However, very few cases of idarubicin-induced cardiomyopathy exist. Herein, we describe a case of first-dose idarubicin-related acute heart failure in a woman with a history of myelodysplastic syndrome converted to acute myeloid leukaemia.