KRAS Sequence Variation as Prognostic Marker in Patients With Young- vs Late-Onset Colorectal Cancer.

Importance: The understanding of the association between KRAS sequence variation status and clinical outcomes in colorectal cancer (CRC) has evolved over time. Objective: To characterize the association of age at onset, tumor sidedness, and KRAS sequence variation with survival among patients diagnosed with CRC. Design, Setting, and Participants: This cross-sectional study used data extracted from the Surveillance, Epidemiology, and End Results database. Patients diagnosed with adenocarcinoma of the colon or rectum from 2010 through 2015 were included and were classified as having young-onset (YO) cancer if diagnosed between ages 20 to 49 years and late-onset (LO) cancer if diagnosed at age 50 years or older. Data were analyzed from April 2021 through August 2023. Main Outcomes and Measures: CRC cause-specific survival (CSS) was summarized using Fine and Gray cumulative incidence and Kaplan-Meier curves. Estimation of subdistribution hazard ratios (sHRs) for the association of KRAS status, age at onset, and tumor location with CRC CSS was conducted using the Fine and Gray competing risk model. Cox proportional hazards regression was used to estimate and compare HRs. Results: Among 21 661 patients with KRAS sequence variation status (mean [SD] age at diagnosis, 62.50 [13.78] years; 9784 females [45.2%]), 3842 patients had YO CRC, including 1546 patients with KRAS variants, and 17 819 patients had LO CRC, including 7311 patients with KRAS variants. There was a significant difference in median CSS time between patients with variant vs wild-type KRAS (YO: 3.0 years [95% CI, 2.8-3.3 years] vs 3.5 years [95% CI, 3.3-3.9 years]; P = .02; LO: 2.5 years [95% CI, 2.4-2.7 years] vs 3.4 years [95% CI, 3.3-3.6 years]; P < .001). Tumors with variant compared with wild-type KRAS were associated with higher risk of CRC-related death (YO: sHR, 1.09 [95% CI, 1.01-1.18]; P = .03; LO: sHR, 1.06 [95% CI, 1.02-1.09]; P = .002). Among patients with YO cancer, mortality hazards increased by location, from right (sHR, 1.02 [95% CI, 0.88-1.17) to left (sHR, 1.15 [95% CI, 1.02-1.29) and rectum (sHR, 1.16 [95% CI, 0.99-1.36), but no trend by tumor location was seen for LO cancer. Conclusions and Relevance: In this study of patients diagnosed with CRC, KRAS sequence variation was associated with increased mortality among patients with YO and LO tumors. In YO cancer, variant KRAS-associated mortality risk was higher in distal tumors than proximal tumors.

Trends in Epidemiology of Esophageal Cancer in the US, 1975-2018.

Importance: Esophageal cancer (EC) is the 7th most common cancer worldwide and 14th in the US. More data are needed to study the changing incidence patterns of its 2 primary histologic subtypes, squamous cell carcinoma of the esophagus (SCE) and adenocarcinoma of the esophagus (ACE). Objective: To examine temporal trends in incidence rates of EC, ACE, and SCE from 1975 through 2018. Design, Setting, and Participants: In this population-based cross-sectional study, data were derived from 9 Surveillance, Epidemiology, and End Results (SEER) registries from January 1975 through December 2018 and from all 21 registries for January 2000 through December 2018 for patients with a diagnosis of EC from 1975 through 2018 (International Classification of Disease-Oncology, Third Edition codes). Age-adjusted incidence rates (AAIRs) of EC, ACE, and SCE were calculated. The timing and magnitude of the annual percentage change (APC) in incidence were examined using Joinpoint regression analyses. Data analysis was started in 2021 and updated and completed in 2023. Main Outcome and Measures: The APC for age-adjusted EC incidence rates as stratified by histology, anatomical location, stage, sex, age, race and ethnicity, and geographic region. Results: A total of 47 648 patients with a diagnosis of EC were retained for analysis. These included 22 419 (47.1%) with a diagnosis of SCE, 22 217 (46.6%) with ACE, and 3012 (6.3%) with other subtypes. The AAIR for EC changed from 4.14 per 100 000 population in 1975 to 4.18 in 2018, AAIRs of SCE declined from 3.06 in 1975 to 1.15 in 2018 as well as for ACE, and AAIRs increased from 0.42 in 1975 to 2.78 in 2018. From 1975 through 2004, EC incidence significantly increased (APC, 0.53; 95% CI, 0.4 to 0.7) but significantly decreased (APC, -1.03; 95% CI, -1.3 to -0.7) from then until 2018. The APC of SCE significantly continued to decline (-2.80, 95% CI, -3.0 to -2.6), and ACE increased from 2000 to 2006 (APC, 2.51; 95% CI, 1.0 to 4.0) but has since stabilized from 2006 to 2018. Conclusions and Relevance: The results of this cross-sectional study suggest that the incidence of EC modestly declined since 2004 and that the incidence of SCE continued to decline while the incidence rate of ACE plateaued for more than a decade. Understanding factors associated with plateaued rates of ACE may help inform public health interventions.

Adverse Events in the Pediatric Cardiac Catheterization Suite: Does Having Pediatric Cardiac Anesthesiologists Make a Difference?

INTRODUCTION: It has been suggested that anesthesiologists with subspecialty expertise in pediatric cardiac anesthesia are best qualified to care for patients with complex congenital cardiac anomalies and manage the complex physiology frequently encountered in the pediatric cardiac catheterization lab. We evaluated the incidence of adverse events in our pediatric cardiac catheterization lab, comparing care provided by cardiac and noncardiac pediatric attending anesthesiologists. METHODS: Data were collected on each anesthetic in the pediatric cardiac catheterization lab from January 1, 2016 to December 31, 2019. A generalized linear mixed effect model was used to identify associations between pediatric cardiac and noncardiac anesthesiologists and the presence of adverse events adjusting for age, American Society of Anesthesiologists physical status, emergency status, and interventional versus diagnostic procedures. RESULTS: A total of 3,761 procedures involving 1,729 patients were included in the study. There was no significant difference between noncardiac and cardiac anesthesia attendings for overall adverse events (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.82 to 1.75 P=0.349). Specific respiratory adverse events (OR, 1.22; 95%, CI 0.73 to 2.03 P=0.443) or cardiac adverse events (OR, 1.26; 95% CI, 0.64 to 2.48 P=0.502) were also not significantly different with respect to noncardiac compared with cardiac attending anesthesiologists. CONCLUSIONS: In our analysis, the incidence of adverse events in the pediatric cardiac catheterization lab during the study period was not statistically different, whether anesthesia care was provided by a cardiac or a noncardiac anesthesiologist.

Association of COVID-19 Vaccination With SARS-CoV-2 Infection in Patients With Cancer: A US Nationwide Veterans Affairs Study.

Importance: Patients with cancer are at increased risk for severe COVID-19, but it is unknown whether SARS-CoV-2 vaccination is effective for them. Objective: To determine the association between SARS-CoV-2 vaccination and SARS-CoV-2 infections among a population of Veterans Affairs (VA) patients with cancer. Design, Setting, and Participants: Retrospective, multicenter, nationwide cohort study of SARS-CoV-2 vaccination and infection among patients in the VA health care system from December 15, 2020, to May 4, 2021. All adults with solid tumors or hematologic cancer who received systemic cancer-directed therapy from August 15, 2010, to May 4, 2021, and were alive and without a documented SARS-CoV-2 positive result as of December 15, 2020, were eligible for inclusion. Each day between December 15, 2020, and May 4, 2021, newly vaccinated patients were matched 1:1 with unvaccinated or not yet vaccinated controls based on age, race and ethnicity, VA facility, rurality of home address, cancer type, and treatment type/timing. Exposures: Receipt of a SARS-CoV-2 vaccine. Main Outcomes and Measures: The primary outcome was documented SARS-CoV-2 infection. A proxy for vaccine effectiveness was defined as 1 minus the risk ratio of SARS-CoV-2 infection for vaccinated individuals compared with unvaccinated controls. Results: A total of 184 485 patients met eligibility criteria, and 113 796 were vaccinated. Of these, 29 152 vaccinated patients (median [IQR] age, 74.1 [70.2-79.3] years; 95% were men; 71% were non-Hispanic White individuals) were matched 1:1 to unvaccinated or not yet vaccinated controls. As of a median 47 days of follow-up, 436 SARS-CoV-2 infections were detected in the matched cohort (161 infections in vaccinated patients vs 275 in unvaccinated patients). There were 17 COVID-19-related deaths in the vaccinated group vs 27 COVID-19-related deaths in the unvaccinated group. Overall vaccine effectiveness in the matched cohort was 58% (95% CI, 39% to 72%) starting 14 days after the second dose. Patients who received chemotherapy within 3 months prior to the first vaccination dose were estimated to have a vaccine effectiveness of 57% (95% CI, -23% to 90%) starting 14 days after the second dose vs 76% (95% CI, 50% to 91%) for those receiving endocrine therapy and 85% (95% CI, 29% to 100%) for those who had not received systemic therapy for at least 6 months prior. Conclusions and Relevance: In this cohort study, COVID-19 vaccination was associated with lower SARS-CoV-2 infection rates in patients with cancer. Some immunosuppressed subgroups may remain at early risk for COVID-19 despite vaccination, and consideration should be given to additional risk reduction strategies, such as serologic testing for vaccine response and a third vaccine dose to optimize outcomes.

Digital healthcare technologies: Modern tools to transform prosthetic care.

INTRODUCTION: Digital healthcare technologies are transforming the face of prosthetic care. Millions of people with limb loss around the world do not have access to any form of rehabilitative healthcare. However, digital technologies provide a promising solution to augment the range and efficiency of prosthetists. AREAS COVERED: The goal of this review is to introduce the digital technologies that have the potential to change clinical methods in prosthetic healthcare. Our target audience are researchers who are unfamiliar with the field of prostheses in general, especially with the newest technological developments. This review addresses technologies for: scanning of amputated limbs, limb-to-socket rectification, additive manufacturing of prosthetic sockets, and quantifying patient response to wearing sockets. This review does not address biomechatronic prostheses or biomechanical design practices. EXPERT OPINION: Digital technologies will enable affordable prostheses to be built on a scale larger than with today's clinical practices. Large technological gaps need to be overcome to enable the mass production and distribution of prostheses digitally. However, recent advances in computational methods and CAD/CAM technologies are bridging this gap faster than ever before. We foresee that these technologies will return mobility and economic opportunity to amputees on a global scale in the near future.

Treatment of Stage IV Colon Cancer in the United States: A Patterns-of-Care Analysis.

BACKGROUND: National guidelines recommend chemotherapy as the mainstay of treatment for stage IV colon cancer, with primary tumor resection (PTR) reserved for patients with symptomatic primary or curable disease. The aims of this study were to characterize the treatment modalities received by patients with stage IV colon cancer and to determine the patient-, tumor-, and hospital-level factors associated with those treatments. METHODS: Patients diagnosed with stage IV colon cancer in 2014 were extracted from the SEER Patterns of Care initiative. Treatments were categorized into chemotherapy only, PTR only, PTR + chemotherapy, and none/unknown. RESULTS: The total weighted number of cases was 3,336; 17% of patients received PTR only, 23% received chemotherapy only, 41% received PTR + chemotherapy, and 17% received no treatment. In multivariable analyses, compared with chemotherapy only, PTR + chemotherapy was associated with being married (odds ratio [OR], 1.9), having bowel obstruction (OR, 2.55), and having perforation (OR, 2.29), whereas older age (OR, 5.95), Medicaid coverage (OR, 2.46), higher T stage (OR, 3.51), and higher N stage (OR, 6.77) were associated with PTR only. Patients who received no treatment did not have more comorbidities or more severe disease burden but were more likely to be older (OR, 3.91) and non-Hispanic African American (OR, 2.92; all P<.05). Treatment at smaller, nonacademic hospitals was associated with PTR (± chemotherapy). CONCLUSIONS: PTR was included in the treatment regimen for most patients with stage IV colon cancer and was associated with smaller, nonacademic hospitals. Efforts to improve guideline implementation may be beneficial in these hospitals and also in non-Hispanic African American and older populations.

Microsatellite Instability and Adjuvant Chemotherapy in Stage II Colon Cancer.

BACKGROUND: Randomized control trials and population-based studies do not demonstrate a definitive benefit for adjuvant chemotherapy (ACT) in stage II colon cancer (CC). Tumor sidedness and microsatellite instability (MSI) status may predict response to ACT, but previous studies have limited microsatellite data. We assessed the efficacy of ACT and possible interaction with MSI status and tumor sidedness in patients with resected stage II CC diagnosed between 2010 and 2013 using the National Cancer Database. MATERIALS AND METHODS: Overall survival was evaluated with the Kaplan-Meier method and multivariate and propensity score matched Cox proportional hazards models. The interaction between receipt of ACT, MSI status, and tumor sidedness was evaluated. The efficacy of ACT was assessed in patient subgroups by MSI status and tumor sidedness. RESULTS: Among 6964 stage II CC patients with known MSI status, 1497 (21.5%) received ACT, 843 had MSI tumors, and 6121 had microsatellite stable (MSS) tumors. In multivariate and propensity score matched analyses, ACT was associated with improved survival after adjusting for factors including high-risk features, MSI status, and tumor sidedness (multivariate hazard ratio, 0.52; P<0.001). There was no interaction between receipt of ACT and MSI status (P=0.25). Patients with MSS tumors benefitted from ACT (multivariate hazard ratio, 0.47; P<0.001), even without other high-risk features. Patients with MSI tumors did not (P=0.671). ACT was associated with improved survival regardless of tumor sidedness. CONCLUSIONS: MSS alone may warrant ACT in stage II CC while patients with MSI tumors may not derive significant benefit from ACT.

Small cell carcinoma of the kidney: a case report and analysis of data from the Surveillance, Epidemiology, and End Results registry.

BACKGROUND: Primary small cell carcinoma of the kidney is an extremely rare neoplasm. The clinical features of small cell carcinoma of the kidney are not well established due to its rarity and scarcity of case reports. We present an unusual case of small cell carcinoma of the kidney complicated by syndrome of inappropriate antidiuretic hormone secretion. We identify cases using a population-based dataset from the Surveillance, Epidemiology, and End Results registry and compare small cell carcinoma of the kidney with small cell carcinoma of the lung. CASE PRESENTATION: A 69-year-old Filipino man presented with hematuria for 1 month. A computed tomography scan demonstrated a large left kidney mass with biopsy demonstrating small cell carcinoma. Within 2 months he developed dizziness and was found to have a metastatic lesion to his brain. He was hyponatremic due to syndrome of inappropriate antidiuretic hormone secretion. He did not receive chemotherapy due to his poor functional status. He died within 8 months of presentation. RESULTS: From 1973 to 2013, 60 cases with small cell carcinoma of the kidney were identified in the Surveillance, Epidemiology, and End Results registry. Most (62%) presented with extensive stage, which occurred predominantly in white men in their seventh decade. The median overall survival with extensive stage small cell carcinoma of the kidney was 3 months versus 11 months with limited stage of small cell carcinoma of the kidney; this was worse than small cell carcinoma of the lung with a median survival of 5 and 13 months, respectively. CONCLUSION: We present a rare case of small cell carcinoma of the kidney complicated by syndrome of inappropriate antidiuretic hormone secretion. This adds to our understanding of the clinical features of small cell carcinoma of the kidney. Furthermore, this is the first population-based study of small cell carcinoma of the kidney using the Surveillance, Epidemiology, and End Results database. Analysis shows that overall survival is worse in small cell carcinoma of the kidney relative to that of small cell carcinoma of the lung. Small cell carcinoma of the kidney presents very aggressively, and further studies are needed to develop a standard of care.

Tumor Molecular Testing Guides Anti-PD-1 Therapy and Provides Evidence for Pathogenicity of Mismatch Repair Variants.

Lynch syndrome is characterized by germline abnormalities in mismatch repair (MMR) genes, leading to predisposition to multiple cancers [1]. A second hit to the unaffected allele is required for tumorigenesis. MMR proteins repair incorrectly paired nucleotides and prevent generation of insertions and deletions at microsatellites [2]. Aberrancies in these MMR proteins can be a result of germline mutations or somatic alterations. Defective MMR results in microsatellite instability (MSI) and a high mutational burden [3].The clinical implications of MSI are becoming readily apparent, as presence of MSI leads to the generation of neoantigens, stimulating tumor-associated lymphocytes [4], [5]. This has led to the use of programmed cell death protein 1 blockade for MMR-deficient tumors [6]. The U.S. Food and Drug Administration recently approved pembrolizumab for any advanced solid tumor demonstrating MSI and nivolumab for metastatic MSI colorectal cancer. However, the clinical significance of numerous MMR gene variants remains uncertain. The International Society for Gastrointestinal Hereditary Tumors classification system categorizes 2,360 MMR variants, which can be used to gauge pathogenicity [7]. There are many variants of uncertain significance (VUS; or class 3) for which clinicians are unable to provide recommendations. In this study, we employed the combination of germline testing and tumor mutational assessment to help discern the clinical relevance of VUS and guide immunotherapeutic decisions. KEY POINTS: A clinical dilemma arises when genomic testing yields variants of uncertain significance (VUS).Germline VUS were identified in two patients with gastrointestinal malignancies, but only one patient had a second-hit mutation in a mismatch repair gene leading to mismatch repair deficiency that conferred response to immunotherapy.The combination of germline testing along with tumor mutational assessment can help discern the clinical relevance of VUS and can help guide therapeutic decision-making toward individualized patient care.

Identification of perioperative pulmonary aspiration in children using quality assurance and hospital administrative billing data.

BACKGROUND: Perioperative aspiration is a rare but potentially devastating complication, occurring in 1-10 per 10 000 anesthetics based on studies of quality assurance databases. Quality assurance reporting is known to underestimate the incidence of adverse outcomes, but few large studies use supplementary data sources. This study aims to identify the incidence of and risk factors for perioperative aspiration in children using quality assurance data supplemented by administrative billing records, and to examine the utility of billing data as a supplementary data source. METHODS: Aspiration events for children receiving anesthesia at a tertiary care pediatric hospital between 2008 and 2014 were identified using (i) a perioperative quality assurance database and (ii) hospital administrative billing records with International Classification of Diseases, Ninth Revision Clinical Modification coded diagnoses of aspiration. Records were subject to review by pediatric anesthesiologists. Following identification of all aspiration events, the incidence of perioperative aspiration was calculated and risk factors were assessed. RESULTS: 47 272 anesthetic cases were evaluated over 7 years. The quality assurance database identified 20 cases of perioperative aspiration occurring in surgical inpatients, same-day admissions, and outpatients. Using hospital administrative data (which excludes outpatients with shorter than a 24-hour stay), 9 cases of perioperative aspiration were identified of which 6 had not been found through quality assurance data. Overall, International Classification of Diseases, Ninth Revision coding demonstrated a positive predictive value of 94.5% for any aspiration event; however, positive predictive value was <4% for perioperative aspiration. A total incidence of 5.5 perioperative aspirations per 10 000 (95% CI: 3.7-8.0 per 10 000) anesthetics was found. CONCLUSION: Quality assurance data offer an efficient way to measure the incidence of rare events, but may underestimate perioperative complications. International Classification of Diseases, Ninth Revision codes for aspiration used as a secondary data source were nonspecific for perioperative aspiration, but when combined with record review yielded a 30% increase in identified cases of aspiration over quality assurance data alone. The use of administrative data therefore holds potential for supplementing quality assurance studies of rare complications.

Acute Kidney Injury Secondary to Cell Saver in Posterior Spinal Fusion.

BACKGROUND: Autologous blood transfusion, commonly referred to as cell saver, is frequently used in spinal fusion to salvage red blood cells because of the risk of significant intraoperative blood loss. This case report describes a case of acute kidney injury (AKI) secondary to cell saver use. Our objective is to increase the knowledge about the process of red blood cell salvage and this exceedingly rare complication. METHODS: Chart and renal biopsy results for a single case were reviewed and reported in this retrospective study. RESULTS: A healthy 18-year-old male patient underwent posterior spinal instrumentation and fusion for adolescent idiopathic scoliosis with utilization of intraoperative autologous blood transfusion. The patient subsequently developed hematuria and AKI with a peak creatinine of 13.9 mg/dL. An extensive clinical workup, including autoimmune serology, excluded any identifying causes. A renal biopsy showed pigment-induced acute tubular necrosis. CONCLUSIONS: This case, to our knowledge, is the first and only case report of AKI secondary to cell saver demonstrated by renal biopsy. The literature has shown both the benefit of cell saver by decreasing the need for allogeneic transfusion and the risk of transient hematuria. However, this case demonstrates the importance of monitoring patients for potential complications.