ABSTRACT
PURPOSE: Elderly women diagnosed with metastatic breast cancer (MBC) are living longer, however their primary care management may be sub-optimal. Influenza results in preventable hospitalizations and deaths. Guidelines recommend the influenza vaccine for those > 65 years and those with cancer but use is unknown. METHODS: A retrospective analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data. Patients were included if they were diagnosed with MBC from 1/1/2008-12/31/2017 and were ≥ 65 years of age. The primary outcome was influenza vaccine use among patients surviving ≥ 3-years. We conducted multivariable analyses using demographic and clinical factors to identify associations with vaccine use. We compared utilization to cancer-free controls. RESULTS: We identified 1,970 patients with MBC that survived for ≥ 3 years. The median age at diagnosis was 73 years. Furthermore, 1,742 (88%) patients were White, and 153 (8%) patients were Black. Only 1,264 (64%) received an influenza vaccine at least one time and 51% received the vaccine at least two times. A multivariable model found lower odds of vaccine receipt for Black patients (OR = 0.48; 95%Ā CI 0.34-0.68, p < 0.001) and higher odds for patients that saw primary care in the year prior to diagnosis (OR = 1.91, 95%Ā CI 1.57-2.33, p < 0.001). Patients with MBC had lower odds of vaccine use compared to cancer free controls (OR = 0.85, 95%Ā CI 0.74-0.97, p < 0.001). CONCLUSION: Over 1/3 of long-term MBC survivors in our cohort did not receive the influenza vaccine. Black patients are about half as likely to be vaccinated. Given the known benefit of the vaccine, improving uptake could be an important strategy to improve outcomes.
Subject(s)
Breast Neoplasms , Influenza Vaccines , Humans , Female , Aged , United States/epidemiology , Breast Neoplasms/pathology , Retrospective Studies , Medicare , SurvivorsABSTRACT
BACKGROUND: While use of neoadjuvant chemotherapy (NAC) in pancreatic adenocarcinoma (PDAC) downstages cancers to be eligible for resection, weight loss during the neoadjuvant period due to cancer progression, gastric outlet obstruction, or neoadjuvant therapy itself is an area of concern. The goal of this study is to determine the effect of weight loss during NAC on perioperative outcomes of pancreatectomies. METHODS: The NSQIP database 2014-2019 was utilized to study patients who received NAC for PDAC and underwent significant weight loss, defined as at least 10Ā % body weight loss in the six months prior to surgery. Univariate and multivariate analyses were conducted using Fisher's Exact Test, Pearson's Chi-squared Test, and logistic regression. RESULTS: Of the 5590 PDAC patients who received NAC, 913 (16%) experienced significant weight loss. Patients who experienced significant weight loss were more likely to experience at least one complication compared to those who did not undergo weight loss (42.2% vs. 38.7%, pĀ =Ā 0.023). Those who had significant weight loss were more likely to undergo unplanned intubation postoperatively (3.8% vs 2.2Ā %, pĀ =Ā 0.004), have postoperative ventilator need >48Ā h (3.7% vs 1.8%, pĀ <Ā 0.001), have postoperative septic shock (3.9% vs 1.8Ā %, pĀ <Ā 0.001), and undergo reoperation (6.0% vs 4.3%, pĀ =Ā 0.027). However, there were no differences for pancreatic fistula (7.7% vs 9.3Ā %, pĀ =Ā 0.15), readmission rates (15% vs 15Ā %, pĀ =Ā 0.7), or 30-day mortality (1.5% vs 1.2%, pĀ =Ā 0.5). Utilizing logistic regression, BMI (OR: 1.05, pĀ =Ā 0.032), significant weight loss (ORĀ =Ā 1.18, pĀ =Ā 0.025), sex (ORĀ =Ā 1.26 with female baseline, pĀ <Ā 0.001), history of COPD (ORĀ =Ā 1.39, pĀ =Ā 0.012), hypertensive medication use (ORĀ =Ā 1.18, pĀ =Ā 0.004), and pancreatic radiotherapy (ORĀ =Ā 1.16, pĀ =Ā 0.010) were independent preoperative predictors of a post-operative complication. CONCLUSIONS: Nutritional measures to stabilize weight during NAC should be considered to decrease post-pancreatectomy complications.
Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Humans , Female , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Neoadjuvant Therapy , Adenocarcinoma/drug therapy , Adenocarcinoma/surgery , Adenocarcinoma/pathology , Chemotherapy, Adjuvant , Pancreas/pathology , Pancreatectomy , Retrospective StudiesABSTRACT
Alcoholic hepatitis is a major cause of morbidity and mortality. However, there are limited population-based data on its incidence, demographics, and temporal trends. We performed a retrospective cohort study using the State Inpatient Databases from Florida, Massachusetts, New York, and Washington from 2010 to 2014. We included patients aged 20-79Ā years admitted with alcoholic hepatitis and calculated incidence using population denominators obtained from the Centers for Disease Control and Prevention WONDER database. We fit multivariable Poisson regression models to explore interactions between alcoholic hepatitis incidence rates and several predictors including state, calendar year, age, race/ethnicity, and gender. Among 56,973 unique individuals with alcoholic hepatitis, the majority were male (39,702; 69.7%) and white non-Hispanic (40,934; 72.0%). In multivariable Poisson models, there was a significant interaction between calendar year and age group (p < 0.001), with the highest incidence rates in those ages 40-49 and 50-59 across all years. The absolute increase in incidence rate across calendar years was highest in the 20-29 and 30-39 age groups in every state. Female gender was associated with a lower rate (incidence rate ratio (IRR) 0.42, 95% confidence interval (CI) 0.41-0.42, p < 0.001). Compared to white non-Hispanics, black non-Hispanics (IRR 0.79, CI 0.77-0.81, p < 0.001) and Hispanics (0.66, CI 0.65-0.68, p < 0.001) had lower incidence rates. The incidence of alcoholic hepatitis in the USA varies by age, gender, race/ethnicity, and state of residence. The group with the fastest rising incidence is those aged 20-39. More work is needed to evaluate the reasons for the temporal trends for admissions for alcoholic hepatitis.
Subject(s)
Hepatitis, Alcoholic/ethnology , Adult , Age Distribution , Age Factors , Aged , Databases, Factual , Female , Hepatitis, Alcoholic/diagnosis , Hepatitis, Alcoholic/mortality , Hepatitis, Alcoholic/therapy , Humans , Incidence , Inpatients , Male , Middle Aged , Race Factors , Retrospective Studies , Risk Assessment , Risk Factors , Sex Distribution , Sex Factors , Time Factors , United States/epidemiology , Young AdultABSTRACT
ABSTRACT: Telemedicine holds the potential to transform cancer care delivery and optimize value, access, and quality of care. A transformed regulatory environment coupled with the need to continue medical care despite operational limitations led to the rapid expansion of telemedicine in cancer care during the COVID-19 pandemic. Its utilization has since varied, and it has faced significant challenges. In this review, we will explore the state of telemedicine in cancer care delivery, the challenges it faces, and strategies to enhance its successful implementation.
Subject(s)
COVID-19 , Neoplasms , Telemedicine , Humans , Pandemics , Neoplasms/diagnosis , Neoplasms/therapyABSTRACT
PURPOSE: Oral anticancer drugs (OACDs) have become increasingly prevalent over the past decade. OACD prescriptions require coordination between payers and providers, which can delay drug receipt. We examined the association between insurance type, pursuit of copayment assistance, pursuit of prior authorization (PA), and time to receipt (TTR) for new OACD prescriptions. METHODS: We prospectively collected data on new OACD prescriptions for adult oncology patients from January 1, 2018, to December 31, 2019, including demographic and clinical characteristics, insurance type, and pursuit of PA and copayment assistance. TTR was defined as the number of days from prescription to OACD receipt. We summarized TTR using cumulative incidence and compared TTR by insurance type, pursuit of copayment assistance, and PA activity using the log-rank test. RESULTS: Our cohort of 1,024 patients was 53% male, and 40% were younger than 65. Twenty-six percent had commercial insurance only, 16% had Medicaid only, and 59% had Medicare with or without additional insurance. Eighty-six percent of prescriptions were successfully received. Across all prescriptions, 69% involved PA activity, and 21% involved the copayment assistance process. In unadjusted analyses, prescriptions involving the copayment assistance process had longer TTR compared with those not involving assistance (log-rank P value = .005) and OACDs covered by Medicare/commercial insurance had a longer TTR compared with Medicaid (log-rank P value = .006). The PA process was not associated with TTR (log-rank P value = .124). CONCLUSION: The process for obtaining OACDs is complex. The copayment assistance process and Medicare/commercial insurance are associated with delayed TTR. New policies are needed to reduce time to OACD receipt.
Subject(s)
Antineoplastic Agents , Neoplasms , Aged , Adult , Humans , Male , United States , Female , Medicare , Prior Authorization , Antineoplastic Agents/therapeutic use , Medicaid , Neoplasms/drug therapy , Neoplasms/epidemiologyABSTRACT
Modern cancer care is costly and logistically burdensome for patients and their families despite an expansion of technology and medical advances that create the opportunity for novel approaches to care. Therefore, there is a growing appreciation for the need to leverage these innovations to make cancer care more patient centered and convenient. The Memorial Sloan Kettering Making Telehealth Delivery of Cancer Care at Home Efficient and Safe Telehealth Research Center is a National Cancer Institute-designated and funded Telehealth Research Center of Excellence poised to generate the evidence necessary to inform the appropriate use of telehealth as a strategy to improve access to cancer services that are convenient for patients. The center will evaluate telehealth as a strategy to personalize cancer care delivery to ensure that it is not only safe and effective but also convenient and efficient. In this article, we outline this new center's research strategy, as well as highlight challenges that exist in further integrating telehealth into standard oncology practice based on early experiences.
Subject(s)
Neoplasms , Patient-Centered Care , Telemedicine , Humans , Neoplasms/therapy , United States , Medical Oncology/methods , Health Services Accessibility , National Cancer Institute (U.S.)ABSTRACT
BACKGROUND: Molecular profiles of renal cell carcinoma (RCC) brain metastases (BMs) are not well characterized. Effective management with locoregional therapies, including stereotactic radiosurgery (SRS), is critical as systemic therapy advancements have improved overall survival (OS). OBJECTIVE: To identify clinicogenomic features of RCC BMs treated with SRS in a large patient cohort. DESIGN, SETTING, AND PARTICIPANTS: A single-institution retrospective analysis was conducted of all RCC BM patients treated with SRS from January 1, 2010 to March 31, 2021. INTERVENTION: SRS for RCC BMs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Next-generation sequencing was performed to identify gene alterations more prevalent in BM patients. Clinical factors and genes altered in ≥10% of samples were assessed per patient using Cox proportional hazards models and per individual BM using clustered competing risks regression with competing risk of death. RESULTS AND LIMITATIONS: Ninety-one RCC BM patients underwent SRS to 212 BMs, with a median follow-up of 38.8 mo for patients who survived. The median intracranial progression-free survival and OS were 7.8 (interquartile range [IQR] 5.7-11) and 21 (IQR 16-32) mo, respectively. Durable local control of 83% was achieved at 12 mo after SRS, and 59% of lesions initially meeting the radiographic criteria for progression at 3-mo evaluation would be considered to represent pseudoprogression at 6-mo evaluation. A comparison of genomic alterations at both the gene and the pathway level for BM+ patients compared with BM- patients revealed phosphoinositide 3-kinase (PI3K) pathway alterations to be more prevalent in BM+ patients (43% vs 16%, pĀ =Ā 0.001, qĀ =Ā 0.01), with the majority being PTEN alterations (17% vs 2.7%, pĀ =Ā 0.003, qĀ =Ā 0.041). CONCLUSIONS: To our knowledge, this is the largest study investigating genomic profiles of RCC BMs and the only such study with annotated intracranial outcomes. SRS provides durable in-field local control of BMs. Recognizing post-SRS pseudoprogression is crucial to ensure appropriate management. The incidence of PI3K pathway alterations is more prevalent in BM+ patients than in BM- patients and warrants further investigation in a prospective setting. PATIENT SUMMARY: We examined the outcomes of radiotherapy for the treatment of brain metastases in kidney cancer patients at a single large referral center. We found that radiation provides good control of brain tumors, and certain genetic mutations may be found more commonly in patients with brain metastasis.
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Cannabis is among the most used recreational and medicinal drugs in the United States. The effects of chronic use on hypertension remain poorly understood. Our study retrospectively evaluated data collected by the National Health and Nutrition Examination Survey from 2017 to 2018. Cannabis use was measured with five metrics: (1) sustained use at any point in the past, (2) sustained use within the past year, (3) frequency of use, (4) age of first cannabis use, and (5) current use. Hypertension status was determined by individuals reporting having been diagnosed in the past. Multivariable logistic regressions were performed, controlling for age, race, and gender. A total of 4565 respondents were identified, of which 867 (19.0%) reported sustained cannabis use in the past. Participants who reported past sustained cannabis use did not have statistically different odds of having hypertension (OR: 1.12; 95% CI: .66-1.91; pĀ =Ā .6). Moderate (OR: 1.08; 95% CI: .36-3.25; pĀ =Ā .8) and highly-frequent users (OR: 1.30; 95% CI: .56-3.03; pĀ =Ā .4) did not have different odds of having hypertension than infrequent users. No relationship between the age of first cannabis use and hypertension was observed. The recency of sustained cannabis use was not associated with hypertension status. Current cannabis users had similar odds of hypertension as past users (OR: 1.03; 95% CI: .59-1.79; pĀ =Ā .9). The findings of this study indicate that neither past nor current cannabis use is associated with clinical hypertension.
Subject(s)
Cannabis , Hypertension , Marijuana Smoking , Humans , United States/epidemiology , Nutrition Surveys , Retrospective Studies , Hypertension/epidemiologyABSTRACT
INTRODUCTION: Depression and anxiety are common leading causes of disability and are associated with systemic effects including cardiovascular comorbidities. Low-income populations may experience higher frequencies of depressive or anxiety-related symptoms, and be at greater risk for developing hypertension. AIM: We performed a cross-sectional study of low-income participants who completed hypertension and disability questionnaires as part of the 2017-2018 cycle of the National Health and Nutrition Examination Survey (NHANES) to identify associations between depressive/anxiety-related symptoms and hypertension status. METHODS: Multivariable logistic regressions were performed to identify whether (1) frequency of depressive symptoms, (2) frequency of anxiety-related symptoms, (3) self-reported depression medication use, or (4) self-reported anxiety medication use predicted previous hypertension diagnosis. RESULTS: A total of 74,285,160 individuals were represented in our cohort. Participants that reported taking depression (OR 2.72; 95% CI 1.41-5.24; P = 0.009) and anxiety (OR 2.50; 95% CI 1.42-4.41; P = 0.006) medications had greater odds of hypertension. Individuals with depressive feelings daily, monthly, and few times per year were more likely to have hypertension. Respondents with daily (OR 2.28; 95% CI 1.22-4.24; P = 0.021) and weekly (OR 1.88; 95% CI 1.05-3.38; P = 0.040) anxiety symptoms were more likely to have hypertension. CONCLUSIONS: Low-income adults in the United States with symptoms of anxiety or depression have higher likelihood of hypertension than those with no symptoms. Respondents who indicated taking medication for anxiety disorders or depression were more likely to have been diagnosed with hypertension.
Subject(s)
Depression , Hypertension , Adult , Humans , United States/epidemiology , Depression/diagnosis , Depression/drug therapy , Depression/epidemiology , Nutrition Surveys , Cross-Sectional Studies , Anxiety/diagnosis , Anxiety/epidemiology , Anxiety/drug therapy , Anxiety Disorders/diagnosis , Anxiety Disorders/epidemiology , Poverty , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/epidemiologyABSTRACT
PURPOSE: To evaluate sitravatinib, an inhibitor of multiple receptor tyrosine kinases (RTK), for the treatment of well-differentiated/dedifferentiated liposarcoma (WD/DD LPS). PATIENTS AND METHODS: This multicenter, open-label, Phase II trial enrolled patients with advanced WD/DD LPS who had received at least one prior systemic regimen and had progression within 12 weeks of enrollment. Patients received sitravatinib 150 mg (later amended to 120 mg) orally daily. A Simon two-stage design was used to evaluate for an improvement in the primary endpoint, progression-free rate at 12 weeks (PFR12), from 20% to 40%. Secondary endpoints included antitumor activity and safety. A subset of patients underwent paired biopsies analyzed using reverse-phase protein array. RESULTS: Twenty-nine patients enrolled. Median age was 62 years and 31% had received 3 or more prior lines. Most patients (93%) had DDLPS or mixed WD/DD LPS. Overall, 12 of 29 patients (41%) were alive and progression-free at 12 weeks and the study met the primary endpoint. There were no confirmed responses. Median progression-free survival was 11.7 weeks [95% confidence interval (CI): 5.9-35.9] and median overall survival was 31.7 weeks (95% CI: 18.1-90.1). The most common treatment-related adverse events were diarrhea (59%), hypertension (52%), hoarseness (41%), mucositis (31%), and nausea (31%). Baseline expression of phospho-RTKs was not significantly different between patients with and without clinical benefit from sitravatinib, but the number of samples was small. CONCLUSIONS: Sitravatinib provided a PFR12 of 41% and meaningful disease control in a subset of patients with advanced, progressive WD/DD LPS.
Subject(s)
Lipopolysaccharides , Liposarcoma , Humans , Middle Aged , Lipopolysaccharides/therapeutic use , Pyridines/therapeutic use , Anilides/therapeutic use , Liposarcoma/drug therapy , Liposarcoma/pathologyABSTRACT
PURPOSE: Oral anticancer drug (OACD) prescriptions require extensive coordination between providers and payers, which can delay drug receipt. Specialty pharmacies facilitate communication between multiple entities. In 2018, our cancer center partnered with a freestanding organization to implement a hospital-based specialty pharmacy (HB-SP). We evaluated the time to drug receipt (TTR) before and after HB-SP implementation. METHODS: Data were prospectively collected on all new OACD prescriptions for adult oncology patients from January 1, 2018, to December 31, 2019. In fall 2018, a HB-SP was initiated. We collected patient sociodemographic, clinical, and prescription data. TTR was the number of days from OACD prescription to drug receipt. We used multivariable logistic regression to examine factors associated with TTR ≤ 7 days before and after HB-SP implementation. RESULTS: In total, 954 patients were included, representing 1,102 new OACDs. The majority of prescribed drugs were targeted OACDs (56%, n = 617), and 71% (n = 779) required prior authorization. Of all prescriptions, 84% (n = 960) were successfully received with an overall median TTR of 7 days. In unadjusted analysis, HB-SP implementation, drug class, race and ethnicity, and prior authorization requirement were significantly associated with TTR. Adjusted analyses found that patients were more likely to receive their drugs ≤ 7 days after HB-SP implementation (53% v 47%; adjusted odds ratio [aOR], 1.29; 95% CI, 1.00 to 1.68; P = .05). CONCLUSION: The implementation of a HB-SP in partnership with a collaborative care model contributed to a decrease in TTR for OACDs. This difference is in part attributable to improved care coordination and communication. A centralized approach may improve overall efficiency due to fewer practice disruptions.
Subject(s)
Antineoplastic Agents , Neoplasms , Pharmacy , Adult , Humans , Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , HospitalsABSTRACT
BACKGROUND: Although different kidney cancers represent a heterogeneous group of malignancies, multiple subtypes including Von Hippel-Lindau (VHL)-altered clear cell renal cell carcinoma (ccRCC), fumarate hydratase (FH)- and succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC), and renal medullary carcinoma (RMC) are affected by genomic instability. Synthetic lethality with poly ADP-ribose polymerase inhibitors (PARPis) has been suggested in preclinical models of these subtypes, and paired PARPis with immune checkpoint blockade (ICB) may achieve additive and/or synergistic effects in patients with previously treated advanced kidney cancers. OBJECTIVE: To evaluate combined PARPiĀ +Ā ICB in treatment-refractory metastatic kidney cancer. DESIGN, SETTING, AND PARTICIPANTS: We conducted a single-center, investigator-initiated phase 2 trial in two genomically selected advanced kidney cancer cohorts: (1) VHL-altered RCC with at least one prior ICB agent and one vascular endothelial growth factor (VEGF) inhibitor, and (2) FH- or SDH-deficient RCC with at least one prior ICB agent or VEGF inhibitor and RMC with at least one prior line of chemotherapy. INTERVENTION: Patients received talazoparib 1 mg daily plus avelumab 800 mg intravenously every 14 d in 28-d cycles. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was objective response rate (ORR) by Immune Response Evaluation Criteria in Solid Tumors at 4 mo, and the secondary endpoints included progression-free survival (PFS), overall survival, and safety. RESULTS AND LIMITATIONS: Cohort 1 consisted of ten patients with VHL-altered ccRCC. All patients had previously received ICB. The ORR was 0/9 patients; one patient was not evaluable due to missed doses. In this cohort, seven patients achieved stable disease (SD) as the best response. The median PFS was 3.5 mo (95% confidence interval [CI] 1.0, 3.9 mo). Cohort 2 consisted of eight patients; four had FH-deficient RCC, one had SDH-deficient RCC, and three had RMC. In this cohort, six patients had previously received ICB. The ORR was 0/8 patients; two patients achieved SD as the best response and the median PFS was 1.2 mo (95% CI 0.4, 2.9 mo). The most common treatment-related adverse events of all grades were fatigue (61%), anemia (28%), nausea (22%), and headache (22%). There were seven grade 3-4 and no grade 5 events. CONCLUSIONS: The first clinical study of combination PARPi and ICB therapy in advanced kidney cancer did not show clinical benefit in multiple genomically defined metastatic RCC cohorts or RMC. PATIENT SUMMARY: We conducted a study to look at the effect of two medications, talazoparib and avelumab, in patients with metastatic kidney cancer who had disease progression on standard treatment. Talazoparib blocks the normal activity of molecules called poly ADP-ribose polymerase, which then prevents tumor cells from repairing themselves and growing, while avelumab helps the immune system recognize and kill cancer cells. We found that the combination of these agents was safe but not effective in specific types of kidney cancer.
ABSTRACT
Importance: Oral anticancer drugs (OACDs) are increasingly prescribed for cancer treatment and require significant coordination of care. Retrospective studies suggest that 10% to 20% of OACD prescriptions are never received by the patients, but the reasons behind this are poorly understood. Objectives: To estimate the rate of failure to receive OACD prescriptions among patients with cancer and to examine the underlying reasons for this failure. Design, Setting, and Participants: A prospective cohort study was conducted among patients with cancer who were prescribed a new OACD from January 1, 2018, to December 31, 2019, at an urban academic medical center. Data analysis was conducted between 2021 and 2022. Main Outcomes and Measures: Patient demographic, clinical, and insurance data and OACD delivery dates were collected. The reasons for a failure to receive a prescribed OACD within 3 months were confirmed by manual review of medical records and were classified into 7 categories: clinical deterioration, financial access, clinician-directed change in decision-making, patient-directed change in decision-making, transfer of care, loss to follow-up, and unknown or other. A multivariable random-effects model was developed to identify factors associated with failure to receive a prescribed OACD. Results: The cohort included 1024 patients (538 men [53%]; mean [SD] age, 66.2 [13.9] years; 463 non-Hispanic White patients [45%], 140 non-Hispanic Black patients [14%], and 300 Hispanic patients [29%]), representing 1197 new OACD prescriptions. Of the 1197 prescriptions, 158 (13%) were categorized as having not been received by the patient. The most common reason for the failure to receive a prescribed OACD was due to patient and clinician decision-making (73 of 158 [46%]), and 20 cases (13%) in which prescriptions were not received were associated with financial access issues. In multivariable analysis, patients with a nonmetastatic solid malignant neoplasm were significantly less likely to not receive their OACDs than those with a hematologic malignant neoplasm (odds ratio, 0.57 [95% CI, 0.33-1.00]; P = .048). Conclusions and Relevance: This cohort study of patients prescribed a new OACD found that 13% of prescriptions were not received. The failure to receive a prescribed OACD was most frequently due to a change in clinical decision-making or patient choice. Ultimately, the reasons for the failure to receive a prescribed OACD were multifactorial and may have been appropriate in some cases.
Subject(s)
Antineoplastic Agents , Neoplasms , Aged , Antineoplastic Agents/therapeutic use , Cohort Studies , Humans , Male , Neoplasms/drug therapy , Prospective Studies , Retrospective StudiesABSTRACT
Sarcoma is a rare cancer arising from soft tissue and bone and consists of more than 50 distinct subtypes. There is an increasing emphasis on understanding the cancer biology of individual sarcoma subtypes to inform the development of targeted and immunotherapy-based treatment approaches. While some advances have recently been made in this respect, most sarcomas are still treated with chemotherapy. The homologous recombination DNA repair pathway plays an important role in repairing highly cytotoxic double-stranded DNA breaks and restarting stalled replication forks. A subset of human cancers, notably ovarian, breast, prostate, and pancreatic cancers, harbor defects in components of the homologous recombination repair pathway, such as mutation or loss of BRCA1/2, and are sensitive to treatments which induce double stranded DNA breaks or replication fork arrest, including oral small molecule poly-ADP-ribose polymerase (PARP) inhibitors. Our understanding of DNA repair defects in sarcoma remains at an early stage. Recently, uterine leiomyosarcoma was identified as a sarcoma subtype with characteristic defects in the homologous recombination repair pathway and frequent BRCA2 loss. Preclinical data, presented here, demonstrates marked activity for the PARP inhibitor olaparib in combination with the alkylating agent temozolomide in leiomyosarcoma models. Ongoing research promises to identify other sarcomas with DNA repair defects and may offer a new opportunity for the targeted treatment of this rare, aggressive cancer.
Subject(s)
Antineoplastic Agents/pharmacology , DNA Repair-Deficiency Disorders/drug therapy , Recombinational DNA Repair/drug effects , Sarcoma/drug therapy , Animals , Humans , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Sarcoma/geneticsABSTRACT
We report a case of acute pancreatitis after an elective screening colonoscopy. A 51-year-old male with a left ventricular assist device for end-stage nonischemic cardiomyopathy and a family history of colorectal cancer was admitted for an expedited heart transplant evaluation. He underwent screening colonoscopy during this admission which was technically uncomplicated apart from requiring slight maneuvering at the splenic flexure. The following day, the patient developed acute epigastric pain and one episode of emesis. Subsequent laboratory evaluation revealed a significantly elevated lipase level and cross-sectional imaging consistent with acute pancreatitis. With no evidence of gallstones, alcohol use, and hypertriglyceridemia, the acute pancreatitis was deemed to be a complication of colonoscopy. The presumed mechanism of the pancreatitis was due to mechanical trauma from insufflation and abdominal pressure, applied to at the splenic flexure, which is in close proximity to the pancreatic tail. The patient was treated with supportive care (intravenous fluid, analgesia, and pancreatic rest) and improved significantly over a three-day period.
ABSTRACT
AIM OF THE STUDY: Autoimmune hepatitis (AIH) may result in liver fibrosis and cirrhosis. While the gold standard for staging fibrosis is biopsy, transient elastography (TE) represents a non-invasive alternative. TE has been validated in several chronic liver diseases, but no data exist to establish an association between histologic fibrosis on biopsy and TE liver stiffness measurements among a United States cohort of AIH patients. MATERIAL AND METHODS: We conducted a retrospective cohort study of 53 AIH patients who received TE assessment and liver biopsy. Histologic fibrosis was classified as advanced (F3-F4) or mild/moderate (F0-F2). Liver stiffness by TE was measured in kilopascals (kPa). We performed a score test for trend to test the association between histologic fibrosis stage and increasing TE kPa categories. Analyses incorporated probe type (medium or extra-large) and body mass index (BMI). Linear regression was used to generate predicted associations between median kPa and histologic fibrosis score with the medium probe. RESULTS: The cohort was primarily female (83%) with median age 56.3 years. Increasing kPa category was associated with worsening fibrosis stage when using the medium probe (p = 0.04), but not the extra-large probe (p = 0.40). BMI, however, differed between these groups (median 25.8 vs. 33.1, respectively, p < 0.001). In adjusted linear regression, increasing median kPa corresponded well to worsening fibrosis stage (p = 0.003). CONCLUSIONS: In a United States AIH cohort, increasing TE kPa measurements are associated with worsening histologic fibrosis staging. While medium probe performance was superior to the extra-large probe, significant variation in BMI between groups may explain this difference.
ABSTRACT
BACKGROUND: Patients heterozygous for an abnormal α-1 antitrypsin (A1AT) mutation may have an increased risk of liver disease in the setting of a secondary contributing factor. METHODS: This single-center retrospective cohort study compared donor and recipient outcomes of A1AT heterozygous versus normal phenotype adult living-donor liver transplants (LDLTs). RESULTS: Between 2010 and 2016, 11 A1AT heterozygous donors and 10 recipients were compared to 57 normal donors and 41 recipients. There were no significant differences in sex, age, or race/ethnicity by A1AT phenotype. Heterozygous donors had significantly lower serum A1AT (median 100 mg/dL versus 131 mg/dL; P < 0.001). Median liver volume at 3 months post-LDLT was not different among donors or their recipients (1164 mm in heterozygous versus 1257 mm in normal [P = 0.449] for donors; 1563 mm versus 1606 mm [P = 0.387], respectively, for recipients). Recipient serum alkaline phosphatase at 1 month and 1 year post-LDLT was significantly higher in recipients of A1AT heterozygous grafts (160 U/L versus 99.5 U/L; P = 0.025 at 1 mo) but did not persist at 2 years. In addition, there was no association between A1AT level and liver volume at 3 months posttransplant in donors or recipients. CONCLUSIONS: Patients with a heterozygous A1AT mutation should be considered for living-liver donation.
Subject(s)
Donor Selection , Heterozygote , Liver Transplantation , Living Donors , Mutation , alpha 1-Antitrypsin Deficiency/genetics , alpha 1-Antitrypsin/genetics , Adult , Clinical Decision-Making , Female , Humans , Liver Transplantation/adverse effects , Male , Phenotype , Postoperative Complications/etiology , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , alpha 1-Antitrypsin Deficiency/blood , alpha 1-Antitrypsin Deficiency/diagnosisABSTRACT
Background. Numerous barriers to outpatient colonoscopy completion exist, causing undue procedure cancellations and poor bowel preparation. We piloted a text message navigation program to improve colonoscopy adherence. Method. We conducted a prospective study of patients aged 18 to 75 years scheduled for outpatient colonoscopy at an urban endoscopy center in April 2018. An intervention arm consisting of bidirectional, automated text messages prior to the procedure was compared with a usual care arm. We enrolled 21 intervention patients by phone and randomly selected 50 controls. Outcomes included colonoscopy appointment adherence, bowel preparation quality, and colonoscopy completion. Results. The arms had similar demographics and comorbidities. Intervention patients had higher colonoscopy appointment adherence (90% vs. 62%, p = 0.049). There were no significant differences in preparation quality or procedure completeness. Poststudy surveys indicated high patient satisfaction and perceived usefulness of the program. Conclusion. A bidirectional, automated texting navigation program improved colonoscopy adherence rates as compared with usual care.