Knowledge and thresholds for palliative care and surgery among healthcare providers caring for adults with serious illness.

Introduction: Timely palliative care and surgical interventions improve symptoms, health-related quality of life (HRQoL), and reduce medical cost for seriously ill adults at end of life (EOL). However, there is still poor delivery and underutilization of these palliative services. We hypothesize that the sub-optimal delivery is due to limited understanding among healthcare providers. Methods: A nationwide cross-sectional online survey was conducted among primary and tertiary healthcare providers. The survey assessed challenges faced, palliative education, confidence in managing palliative patients, and knowledge on palliative surgery. Overall palliative care awareness and knowledge was assessed using a 6-point score. Likelihood of considering various palliative interventions at EOL was also determined using a threshold score (higher score = higher threshold). Results: There were 145 healthcare providers who completed the survey (81.9% response rate); majority reported significant challenges in providing various aspects of palliative care: 57% (n = 82) in the provision of emotional support. Sixty-nine percent (n = 97) in managing social issues, and 71% (n = 103) in managing family expectations. Most expressed inadequate palliative care training in both under-graduate and post-graduate training and lack confidence in managing EOL issues. Up to 57% had misconceptions regarding potential benefits, morbidity and mortality after palliative surgery. In general, most providers had high thresholds for Intensive Care Unit admissions and palliative surgery, and were more likely to recommend endoscopic or interventional radiology procedures at EOL. Conclusion: Healthcare providers in Singapore have poor knowledge and misconceptions about palliative care and surgery. Improving awareness and education among those caring for seriously ill adults is essential.

The distinct clinical trajectory, metastatic sites, and immunobiology of microsatellite-instability-high cancers.

Microsatellite-instability-high (MSI-H) cancers form a spectrum of solid organ tumors collectively known as Lynch Syndrome cancers, occurring not only in a subset of colorectal, endometrial, small bowel, gastric, pancreatic, and biliary tract cancers but also in prostate, breast, bladder, and thyroid cancers. Patients with Lynch Syndrome harbor germline mutations in mismatch repair genes, with a high degree of genomic instability, leading to somatic hypermutations and, therefore, oncogenesis and cancer progression. MSI-H cancers have unique clinicopathological characteristics compared to their microsatellite-stable (MSS) counterparts, marked by a higher neoantigen load, immune cell infiltration, and a marked clinical response to immune checkpoint blockade. Patients with known Lynch Syndrome may be detected early through surveillance, but some patients present with disseminated metastatic disease. The treatment landscape of MSI-H cancers, especially colorectal cancers, has undergone a paradigm shift and remains to be defined, with immune checkpoint blockade coming to the forefront of treatment strategies in the stage IV setting. We summarize in this review the clinical features of MSI-H cancers with a specific interest in the pattern of spread or recurrence, disease trajectory, and treatment strategies. We also summarize the tumor-immune landscape and genomic profile of MSI-H cancers and potential novel therapeutic strategies.

Novel prognostic score for outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer with metachronous peritoneal carcinomatosis.

BACKGROUND: This study aimed to determine pre- and peri-operative parameters with significant predictive value for post-operative outcomes in patients with recurrent colorectal cancer presenting as peritoneal carcinomatosis undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), and to develop a novel prognostic scoring system for prediction of survival outcomes. METHODS: A single-institution review of prospectively collected data from all patients who underwent CRS-HIPEC between October 2005 and October 2017 was conducted. Univariate and multivariate analyses were used to identify significant parameters for prediction of post-CRS-HIPEC disease-free survival and overall survival (OS). RESULTS: A total of 278 patients underwent CRS-HIPEC, of whom 72 were for peritoneal carcinomatosis from recurrent colorectal cancer. Disease-free interval (DFI; P = 0.006), peritoneal cancer index (PCI; P = 0.001) and left upper quadrant disease (P = 0.023) were significant independent predictors of 3-year OS. DFI (0.007), PCI (P < 0.001) and intraoperative blood loss (BL; P = 0.001) were significant independent predictors of 5-year OS. PCI and BL were significant independent predictors of both 3-year (P = 0.026, PCI; P = 0.009, BL) and 5-year (P = 0.002, PCI; P = 0.011, BL) disease-free survival. Predictive models were developed for risk stratification of OS. CONCLUSION: PCI, DFI, left upper quadrant disease and BL have significant predictive value for post-CRS-HIPEC outcomes. Risk stratification models allow for more prudent patient selection and ultimately more accurate prognostication of post-operative outcomes.