Pancreatic ductal adenocarcinoma: exploring clinicopathological trends and racial disparities in a comprehensive U.S. population-based study.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy about 50% of PDAC are metastatic at presentation. In this study, we evaluated PDAC demographics, annual trend analysis, racial disparities, survival rate, and the role of different treatment modalities in localized and metastatic disease. METHODS: A total of 144,824 cases of PDAC were obtained from the SEER database from 2000 to 2018. RESULTS: The median age was 69 years, with a slightly higher incidence in males (52%) and 80% of all cases were white. Among cases with available data, 43% were grade III tumors and 57% were metastatic. The most common site of metastasis was the liver (15.7%). The annual incidence has increased steadily from 2000 to 2018. The overall observed (OS) 5-year survival rate was 4.4% (95% CI 4.3-4.6%), and 5 years cause-specific survival (CSS) was 5% (95% CI 5.1-5.4%). The 5-year survival with multimodal therapy (chemotherapy, surgery, and radiation) was 22% (95% CI 20.5-22.8%). 5-year CSS for the blacks was lower at 4.7% (95% CI 4.2-5.1%) compared to the whites at 5.3% (95% CI 5.1-5.4%). Multivariate analysis found male gender and black race associated with worse prognosis. Kaplan-Meier survival analysis found multimodal therapy to have the best outcomes in all three stages. CONCLUSION: PDAC is an aggressive malignancy with male gender and black race are associated with a poor prognosis. Surgery with chemoradiation was associated with the best overall survival. With steadily increasing rates of PDAC, improved treatment modalities are paramount to improving survival in these patients.

Utility of amyloid PET Imaging in a Memory Clinic.

There is greater interest in amyloid biomarker for the diagnosis of Alzheimer disease (AD) with the recent Food and Drug Administration approval of amyloid-targeted therapy. The goal of this study was to assess the clinical utility of amyloid positron emission tomography (PET) in clinically ambiguous cases of cognitive impairment by examining outcomes of patients enrolled in the Imaging Dementia-Evidence of Amyloid Scanning study at 2 academic institutions. Of the 112 patients in the study, 66.1% (n=74) of patients had a positive amyloid PET scan, and 33.96% (n=38) had a negative amyloid PET scan. Lower cognitive test scores were predictive of positive amyloid PET scan ( P =0.001). Eighty-two percent (92/112) of the patients were seen for follow-up. Of the 30 patients with negative amyloid PET scan results, 90% had a diagnosis of non-AD etiology after receiving the negative results, suggesting a negative amyloid scan can be used to rule out AD diagnosis.

Papillary Renal Cell Carcinoma: Demographics, Survival Analysis, Racial Disparities, and Genomic Landscape.

Papillary renal cell carcinoma (PRCC) is the second most common histological subtype of renal cell cancer. This research aims to present a large database study highlighting the demographic, clinical, and pathological factors, racial disparities, prognosis, and survival of PRCC. The clinical and demographic data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, and molecular data was cured from the Catalogue Of Somatic Mutations in Cancer (COSMIC) database. PRCC had a median age of diagnosis at 64 years, with a higher incidence in men (77%), and Whites (68%). 70.3% of cases were Grades I-IV (13, 53, 31, and 3%, respectively). In patients with known data, 85% were localized to the kidney, and 84% of cases were 7 cm in size. No metastasis occurred in 97% of the known data. The most common treatment offered was surgical resection (9%). The 5-year overall survival was 79%, with patients undergoing surgery having a 90.6% 5-year survival. Multivariable analysis revealed age > 60 years, Black race, poor histologic differentiation, distant metastases, and tumor size > 10 cm as independent risk factors for mortality. The most common mutations identified from the COSMIC database were MET, KMT2D, KMT2C, ARID1A, and SPEN. PRCC affects male individuals in the sixth decade of life. Increased age, Black race, distant metastases, and tumors > 10 cm are associated with a worse prognosis. Surgical resection offers a favorable survival outcome. Next-generation sequencing (NGS) could identify potentially targetable alterations and future personalized therapeutic approaches.

PD-L1 Over-Expression Varies in Different Subtypes of Lung Cancer: Will This Affect Future Therapies?

Programmed death-ligand (PD-L) 1 and 2 are ligands of programmed cell death 1 (PD-1) receptor. They are members of the B7/CD28 ligand-receptor family and the most investigated inhibitory immune checkpoints at present. PD-L1 is the main effector in PD-1-reliant immunosuppression, as the PD-1/PD-L pathway is a key regulator for T-cell activation. Activation of T-cells warrants the upregulation of PD-1 and production of cytokines which also upregulate PD-L1 expression, creating a positive feedback mechanism that has an important role in the prevention of tissue destruction and development of autoimmunity. In the context of inadequate immune response, the prolonged antigen stimulation leads to chronic PD-1 upregulation and T-cell exhaustion. In lung cancer patients, PD-L1 expression levels have been of special interest since patients with non-small cell lung cancer (NSCLC) demonstrate higher levels of expression and tend to respond more favorably to the evolving PD-1 and PD-L1 inhibitors. The Food and Drug Administration (FDA) has approved the PD-1 inhibitor, pembrolizumab, alone as front-line single-agent therapy instead of chemotherapy in patients with NSCLC and PD-L1 ≥1% expression and chemoimmunotherapy regimens are available for lower stage disease. The National Comprehensive Cancer Network (NCCN) guidelines also delineate treatment by low and high expression of PD-L1 in NSCLC. Thus, studying PD-L1 overexpression levels in the different histological subtypes of lung cancer can affect our approach to treating these patients. There is an evolving role of immunotherapy in the other sub-types of lung cancer, especially small cell lung cancer (SCLC). In addition, within the NSCLC category, squamous cell carcinomas and non-G12C KRAS mutant NSCLC have no specific targetable therapies to date. Therefore, assessment of the PD-L1 expression level among these subtypes of lung cancer is required, since lung cancer is one of the few malignances wherein PD-L1 expression levels is so crucial in determining the role of immunotherapy. In this study, we compared PD-L1 expression in lung cancer according to the histological subtype of the tumor.

Neurobiologic Rationale for Treatment of Apathy in Alzheimer's Disease With Methylphenidate.

The public health burden of Alzheimer's disease (AD) is related not only to cognitive symptoms, but also to neuropsychiatric symptoms, including apathy. Apathy is defined as a quantitative reduction of goal-directed activity in comparison to a previous level of functioning and affects 30%-70% of persons with AD. Previous attempts to treat apathy in AD-both nonpharmacologically and pharmacologically-have been wanting. Catecholaminergic treatment with methylphenidate has shown encouraging results in initial trials of apathy in AD. Understanding the neuronal circuits underlying motivated behavior and their reliance on catecholamine actions helps provide a rationale for methylphenidate actions in the treatment of apathy in patients with AD. Anatomical, physiological, and behavioral studies have identified parallel, cortical-basal ganglia circuits that govern action, cognition, and emotion and play key roles in motivated behavior. Understanding the distinct contributions to motivated behavior of subregions of the prefrontal cortex-dorsolateral, orbital-ventromedial, and dorsomedial-helps to explain why degeneration of these areas in AD results in apathetic behaviors. We propose that the degeneration of the prefrontal cortex in AD produces symptoms of apathy. We further propose that methylphenidate treatment may ameliorate those symptoms by boosting norepinephrine and dopamine actions in prefrontal-striatal-thalamocortical circuits.

Depression, cognitive, and functional outcomes of Problem Adaptation Therapy (PATH) in older adults with major depression and mild cognitive deficits.

OBJECTIVES: Antidepressants have limited efficacy in older adults with depression and cognitive impairment, and psychosocial interventions for this population have been inadequately investigated. Problem Adaptation Therapy (PATH) is a psychosocial intervention for older adults with major depression, cognitive impairment, and disability. DESIGN: This study tests the efficacy of PATH versus Supportive Therapy for Cognitively Impaired Older Adults (ST-CI) in reducing depression (Montgamery Asberg Depression Rating Scale [MADRS]) and disability (World Health Organization Disability Assessments Schedule-II [WHODAS-II]) and improving cognitive outcomes (Mini Mental State Examination [MMSE]) over 24 weeks (12 weeks of treatment and 12-week post-treatment follow-up). SETTING: Participants were recruited through collaborating community agencies of Weill Cornell Institute of Geriatric Psychiatry. Both interventions and all research assessments were conducted at home. PARTICIPANTS: Thirty-five older adults (age ≥ 65 years) with major depression and cognitive impairment no dementia (CIND). INTERVENTIONS: PATH aims to increase emotion regulation by incorporating a problem-solving approach, teaching compensatory strategies, and inviting caregiver participation. Supportive Therapy aims to facilitate the expression of affect, as well as promote empathy. MEASUREMENTS: Depression was measured using the MADRS, disability using the WHODAS-II, and cognition using the MMSE. RESULTS: PATH participants showed significantly greater reduction in MADRS total score (7.04 points at 24 weeks, treatment group by time interaction: F[1,24.4] = 7.61, p = 0.0108), greater improvement in MMSE total score (2.30 points at 24 weeks, treatment group by time interaction: F[1,39.8] = 13.31, p = 0.0008), and greater improvement in WHODAS-II total score (2.95 points at 24 weeks, treatment group by time interaction: F[1,89] = 4.93, p = 0.0290) than ST-CI participants over the 24-week period. CONCLUSIONS: PATH participants had better depression, cognitive, and disability outcomes than ST-CI participants over 6 months. PATH may provide relief to depressed older adults with CIND who currently have limited treatment options.