Selected Geriatric Dermatology Case Studies

Introduction: we previously showed (Lung Cancer 80: 203; 2013) that emergency visit is a frequent event for lung cancer patients and we identified simple factors predicting hospitalisation and death. In the present report, we studied the same question in a general cancer population, taking into account the type of cancer. Methods: we retrospectively reviewed the charts of all cancer patients consulting at our emergency department from 01/2008 to 12/2010. Data included 4777 emergency consultations from 2426 cancer patients resulting in 2753 hospitalisations. Main underlying tumours (per visit) were breast (33 %), haematological (16 %), gastro-intestinal (16 %) and lung (12 %) cancers. Data were randomly divided into a derivation set (70%) to develop predictive scores for hospitalisation and death in case of admission and a validation set (30%). Results: significant independent predictive factors for admission were type and time of arrival, breast cancer, type of complaints, disease stage, number of comorbidities, abnormal vital signs, and physical signs associated with the chief complaint. For death after admission, they were arrival type, stage, poor general status, physical signs associated with the chief complaint, corticoids, abnormal vital signs and lung cancer. Other types of cancer did not appear significant at multivariate analysis. The risk to die during hospitalisation for lung cancer patients was 2.8 (95 % IC 1.57-4.98; p Conclusion: if it is not a predictive factor for admission after a visit to the emergency department, lung cancer is a significant independent predictive factor for death in case of hospitalisation.

The Center for Global Early Detection at MD Anderson has initiated two longitudinal early detection studies: LEAP (Lung Cancer Early Detection and Prevention, 2013-2019) for lung cancer screening and MERIT (Mammography Early Detection Risk Assessment and Imaging Technologies, 2017-ongoing) for breast cancer screening. Both cohorts enrolled subjects based on US standard-of-care guidelines at the time of enrollment for low-dose CT screening and mammography, respectively. The cohorts collected detailed health data from questionnaires, imaging data, and blood specimens at the time of screening. In addition to information on the screened-detected cancers, follow-up information was collected on any other types of cancers that are diagnosed after enrollment. Here, we evaluate the incidence of other cancers without available screening to assess the potential impact of multi-cancer early detection studies for these two types of screening populations. The two studies enrolled approximately 9,300 subjects (N = 2853 for LEAP; N = 6,400 for MERIT) with median follow up times of 2.99 years (IQR: 1.09-4.08) for LEAP and 2.05 years (IQR: 0.09-3.01) for MERIT. Currently, there are more than 800,000 aliquots of banked biospecimens from both cohorts. The incidence of lung cancer for the LEAP cohort undergoing low-dose CT screening was 0.91% per year. Cancers other than lung cancer were also diagnosed after enrollment including prostate, breast, bladder, head, and neck, colorectal, lymphoma, endocrine, gynecologic, and kidney cancers. Overall, the incidence of other cancers in LEAP was high for those cancers without available screening - 0.49% per year excluding breast, prostate, and colorectal cancers. The incidence of breast cancer for women in LEAP was lower than expected, 0.17% per year, likely a result of underscreening by mammography. For the MERIT cohort, the incidence of breast cancer was 0.89% per year. Cancers other than breast were diagnosed in MERIT after enrollment including gynecologic, melanoma, lung, colorectal, endocrine, bladder, and gastrointestinal cancers. The incidence of other cancers in MERIT was 0.55% per year, excluding colorectal cancer. We conclude that the incidence of cancers without a current screening modality in LEAP and MERIT is sufficiently high (0.49-0.55% per year) to justify the application of multi-cancer screening. Even for cancers with standard-of-care screening, a multi-cancer blood-based biomarker test could be useful given the possibility of underscreening, as we observed for breast cancer in the LEAP cohort. Citation Format: Jennifer Dennison, Ehsan Irajizad, Edwin Ostrin, Myrna Godoy, Olena Weaver, Jessica Leung, Samir Hanash. Application of multi-cancer early detection to lung and breast cancer screening populations. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P057.

Does a young woman living with a smoker or taking a job working in a smoky bar have a greater chance of developing breast cancer? Some scientists believe that such situations can indeed raise a woman’s risk of developing breast cancer before the age of 50. Because epidemiological and toxicological studies show that women’s breast tissue may be especially sensitive to exposure to carcinogens prior to first pregnancy, these researchers contend that public education should be directed at alerting adolescents and young women to the potential risk. However, not everyone in the international public health community agrees that the evidence to date supports a link between passive smoking and breast cancer, and some say that women are being alarmed unnecessarily. This disagreement has sparked debate that is sometimes heated. The stakes are high because breast cancer is the most common cancer in women in industrialized countries, according to the WHO. It is the leading cancer killer of nonsmoking women, and second only to lung cancer deaths among women who smoke. Among the researchers interviewed for this article who disagree that there is enough evidence to link secondhand smoke (SHS) with breast cancer, the majority call the evidence to date “suggestive but not sufficient,” as the Surgeon General’s 2006 report, The Health Consequences of Involuntary Exposure to Tobacco Smoke, put it. That characterization is based largely on the fact that the research considered when the Surgeon General’s report was being amassed did not clearly link even active smoking to breast cancer. Researchers in this camp do, however, stress that ongoing campaigns to prohibit smoking in public will protect the whole of society against the wide variety of ills proven to be caused by SHS. These include lung cancer, cardiovascular disease, and sudden infant death syndrome, among others. A smaller group contends that the question of whether or not SHS causes breast cancer is a political issue with the potential to compromise the scientific process. “A premature decision about causality could jeopardize the credibility of the entire review process and all of the other, established effects of secondhand smoke,” says Michael Thun, national vice president of epidemiology and surveillance research for the American Cancer Society. Adds Valerie Beral, director of the University of Oxford Cancer Research UK Epidemiology Unit, “To prematurely come to conclusions about the causation when there is a big division in the scientific community . . . is bad science.” Thun debated the subject in a series of public forums held in conjunction with scientific meetings. Taking the opposing view was Kenneth C. Johnson, a research scientist with the Public Health Agency of Canada, who was one of the first scientists to discern a potential link. During the debates, Johnson pointed out there are about the same number of studies linking breast cancer to passive smoking as there were linking lung cancer to SHS in 1986, when the Surgeon General concluded that passive smoking caused lung cancer. Johnson also says that more of the breast cancer studies are statistically significant, and that the estimated risk for breast cancer is higher.

Previous studies have shown that asthma is a risk factor for lung cancer, while the mechanisms involved remain unclear. We attempted to further explore the association between asthma and non-small cell lung cancer (NSCLC) via bioinformatics analysis. We obtained GSE143303 and GSE18842 from the GEO database. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) groups were downloaded from the TCGA database. Based on the results of differentially expressed genes (DEGs) between asthma and NSCLC, we determined common DEGs by constructing a Venn diagram. Enrichment analysis was used to explore the common pathways of asthma and NSCLC. A protein-protein interaction (PPI) network was constructed to screen hub genes. KM survival analysis was performed to screen prognostic genes in the LUAD and LUSC groups. A Cox model was constructed based on hub genes and validated internally and externally. Tumor Immune Estimation Resource (TIMER) was used to evaluate the association of prognostic gene models with the tumor microenvironment (TME) and immune cell infiltration. Nomogram model was constructed by combining prognostic genes and clinical features. 114 common DEGs were obtained based on asthma and NSCLC data, and enrichment analysis showed that significant enrichment pathways mainly focused on inflammatory pathways. Screening of 5 hub genes as a key prognostic gene model for asthma progression to LUAD, and internal and external validation led to consistent conclusions. In addition, the risk score of the 5 hub genes could be used as a tool to assess the TME and immune cell infiltration. The nomogram model constructed by combining the 5 hub genes with clinical features was accurate for LUAD. Five-hub genes enrich our understanding of the potential mechanisms by which asthma contributes to the increased risk of lung cancer.

Studies examining the role of signal transducer and activator of transcription 5 (STAT5) in various cancers have produced controversial results. To address this controversy, we examined the prognostic role of STAT5a in cancer patients across multiple cancers. Transcription levels of STAT5a between tumors and normal tissues, obtained from public databases, were analyzed for statistical differences using Cox regression analysis with the outcome as overall survival and covariate of interest as high STAT5a expression. Meta-analysis was then conducted to summarize the hazard ratio estimate from the Cox regression analyses. We found that STAT5a was significantly under-expressed in breast, lung, and ovarian cancers, while STAT5a was significantly overexpressed in lymphoid neoplasm diffuse large B-cell lymphoma, glioblastoma, and glioma. High STAT5a expression was significantly associated with favorable survival in bladder cancer (lnHR = -0.8689 [-1.4087, -0.3292], P-value = 0.0016), breast cancer (lnHR = -0.7805 [-1.1394, -0.4215], P-value < 0.0001) and lung cancer (lnHR = -0.3255 [-0.6427, -0.0083], P-value = 0.0443). After adjusting for clinicopathological factors, high STAT5a expression remained significantly associated with favorable survival in breast cancer (lnHR = -0.6091 [-1.0810, -0.1372], P-value = 0.0114). These results suggest that higher STAT5a expression is associated with favorable overall survival in breast cancer, and therefore might have protective effects, and that STAT5a expression could be a potential prognostic biomarker, especially in breast cancer. However, the prognostic role of STAT5a is dependent on cancer type.

Introduction: Cardiovascular disease (CVD) and cancer share a common risk factor: chronic toxic stress/allostatic load (AL). Our previous research found that a 1-point increase in AL is linked to a 25-30% higher risk of major cardiac events (MACE) in prostate cancer patients. Hypothesis: Higher AL is associated with increased MACE risk in patients with breast, lung, and colon cancer. Methods: Patients ≥18 years diagnosed for the first time with the mentioned 3 cancers of interest between 2010-2019 at a large, hybrid academic-community practice were included in this retrospective cohort study. AL was modeled as an ordinal measure (0-11; Table 1 ). Adjusted Fine-Gray Cox proportional hazard regressions estimated the impact of AL pre- and 60 days post- cancer diagnosis on 2-year MACE. Results: Demographic characteristics are summarized in Table 1. Two-year mace MACE occurred in 12.3%, 23.3%, and 9.7% of breast, lung, and colon cancer patients, respectively. Heart failure was the most common MACE, observed in 7.9%, 14.4%, and 4.8% of breast, lung, and colon cancer patients, respectively. Before cancer diagnosis, a 1-point increase in AL raised MACE risk by 11% (aHR=1.11, 95% CI 1.07-1.16) in breast cancer, 18% (aHR=1.18, 95% CI 1.11-1.25) in lung cancer, and 9% (aHR=1.09, 95% CI 1.01-1.18) in colon cancer. After cancer diagnosis, a 1-point increase in AL increased MACE risk by 10% (aHR=1.10, 95% CI 1.06-1.15) in breast cancer and 19% (aHR=1.19, 95% CI 1.12-1.25) in lung cancer, but was not statistically significant in colon cancer (aHR=1.07, 95% CI 0.99-1.16). Conclusion(s): Higher AL levels prior to breast, lung, and colon cancer diagnoses are associated with increased MACE risk. Thus, effective implementation of patient-centered communication considering stress levels, stressors, and coping mechanisms is necessary during cardiovascular screening for these cancer patients. Further prospective studies are needed.

Background: Chronic inflammation is related to carcinogenesis. Many studies reported a positive association between plasma CRP - a non-specific marker of systemic inflammation - and colorectal cancer (CRC) risk. In the ARIC study, hazard ratio (HR) for CRC was 1.97 (95% CI,1.13; 3.43) for the highest versus lowest CRP quartile, although it is unclear if the association is causal. The associations of CRP with other cancer types are inconsistent. Our goals were to prospectively 1) examine associations of plasma CRP with other cancer types and total cancer and 2) examine associations of a genetic risk score based on single nucleotide polymorphisms (SNPs), affecting CRP levels, with cancer risk. Methods: The ARIC cohort aged 45-64 y at Visit 1 in 1987-89 (55% women, 28% African-American and 72% Caucasian) was followed until 2006. Among 8,657 Caucasians, we examined the incidence of total (n=1,929), CRC (n=205), breast (n=371), lung (n=274), and prostate (n=395) cancers in relation to a weighted genetic CRP risk score (CRPRS) composed of 20 SNPs located in/near CRP, APOC1, GCKR, HNF1A, IL6R and 15 other genes. These SNPs were associated with CRP levels in a previous meta-analysis of genome-wide association studies. The CRPRS was created as a sum of risk alleles for each person by multiplying each SNP by the beta coefficient from the meta-analysis. Plasma CRP was measured at Visit 4 (1996-98). We examined associations of plasma CRP with the risk of total (n=1,481), breast (n=235), lung (n=185), and prostate (n=352) cancers among 9,857 Caucasians and African-Americans, followed from Visit 4 until 2006. Cox proportional hazards models were used to estimate HRs of cancers in relation to plasma CRP and the genetic score. Results: CRPRS was positively associated with CRC risk HR =1.18 (1.03; 1.36) per one standard deviation of the score but not with total or any other cancer in a multivariate analysis. Additional adjustment for plasma CRP only slightly attenuated the association. The HRs were similar for colon and rectal cancer. After multivariate adjustment, plasma CRP was associated positively with the risk of breast and lung cancers: 2.40 (95%CI, 1.25; 4.61) (p-trend=0.004) and 1.90 (95%CI, 1.12; 3.22)(p-trend=0.03), respectively, for the highest versus lowest quartiles. The association for breast cancer did not markedly change after excluding subjects with &amp;lt; 3 years of follow-up or CRP&amp;gt;10mg/L, whereas for lung cancer both exclusions resulted in weaker associations. Conclusions: This study provides the first evidence of a significant association of CRP polymorphisms with CRC risk suggesting a role of CRP and inflammation in colorectal carcinogenesis. CRP polymorphisms may be linked with CRC risk through plasma CRP or other mechanisms. We also found that not only colorectal but also breast and lung cancers are positively associated with plasma CRP in the ARIC study. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1028. doi:1538-7445.AM2012-1028

Introduction It is not possible to prevent the progression of degenerative disc disease of lumbar spine. Conservative treatment offered today help minimize the load coming on lumbar intervertebral disc (IVD). It has no useful effect in improving the important pathological change of degenerative lumbar disc disease that is impaired nutrition of IVD. Healthy IVD contracts during mechanical loading and expands on unloading. Nutrition of the IVD is possible only in expanded disc. Considering this pathophysiology of IVD, an exercise named lumbar spine distraction exercise was developed to distract intervertebral space with a view to make conservative treatment truly “effective” in degenerative lumbar disc disease. Materials and Methods A study was conducted to see the effect of this exercise in 100 patients presented on outdoor from June 2008 to August 2009 with low backache with sciatica of any long duration. Patients with significant motor deficit or with possibility of psychiatric component were excluded. Magnetic resonance imaging (MRI) was done before treatment. Patients having functionally disabling low back pain were put on rest for a brief period of a day or 2 before the distraction exercise was started. Back care was taught to all patients. Patients were followed up first time at 1 week and then every 3 to 4 weeks. In random 20 patients out of 80 patients who were responding to the treatment and who had significant advanced MRI changes in pretreatment MRI, repeat MRI was done at 4 weeks, 8 weeks, and 6 months. Results More than 80% (80/100) patients had significant subjective pain relief and had maintained satisfactorily improved functional capacity on average follow-up of 9 months. Objective findings on follow-up MRI such as widening of canal, increased interspinous distance, decompression of nerve root, increased whiteness of IVD, regression of Schmorl nodule, and correction of angles between vertebrae were seen in all patients followed up on MRI. Conclusion Lumbar spine distraction exercise is a very promising exercise for low backache with sciatica. Subjective improvement (in few days) is much faster than MRI changes (few weeks). It could reduce number of surgery on lower back for degenerative lumbar spine disease and could also help those operated for neuromeningeal compression in preventing recurrence. Although number of patients in whom this exercise was used effectively as treatment is 100, small number of them (20) were followed up objectively with MRI at regular interval because of financial constraint. Disclosure of Interest None declared References McCulloh J, Transfeldt E. McNab's Backache. 3rd ed. Baltimore: Williams and Wilkins; 1997:75-83, 393–413 Patel RK, Slipman CW. Lumbar degenerative disk disease. Available at: http://emedicine.medscape.com/article/309767-diagnosis. Accessed August 28, 2009 Anderson G, Singh K, Kahill P, Lee M, Tannoury C, Zmurko M. In: Fischgrund J, ed. Orthopedic Knowledge Update [OKU 9]. Chicago: American Academy of Orthopedic Surgeons; 2008:531-540, 551–564 Pandya M. Degenerative Lumbar Spine Disorder and Its Conservative Treatment. 1st ed. New Delhi, India: Jaypee Brothers Publication; 2011 Waddell G, McCulloch JA, Kummel E, Venner RM. Nonorganic physical signs in low-back pain. Spine 1980;5(2):117–125 Williams KD, Park AL. Lower back pain and disorders of intervertebral discs. In: Canale ST, ed. Campbell's Operative Orthopaedics. Vol. 2. 10th ed. Philadelphia, PA: Mosby Elsevier; 2003:1955–2002 Magee DJ. Orthopedic Physical Assessment. 5th ed. Philadelphia: Elsevier Saunders; 2008:515–621 Netter FH. Atlas of Human Anatomy. 4th ed. Philadelphia: Elsevier Saunders; 2006:263 Richards JC, Majumdar S, Lindsey DP, Beaupré GS, Yerby SA. The treatment mechanism of an interspinous process implant for lumbar neurogenic intermittent claudication. Spine 2005;30(7):744–749

We have measured the dynamic movement of the lumbar spine in 57 patients with degenerative lumbar disc disease. Each completed a questionnaire which recorded pain and subjective signs and symptoms. From plain lateral radiographs, the subjects were graded using the criteria of Kellgren and Lawrence and those of Lane et al, which are both based on the severity of degenerative changes. Measurements of the height of the disc space and the vertebral height were obtained and expressed as a ratio. We found no relationship between the characteristics of spinal movement and the overall grading of degenerative disc disease with either system. Both were influenced (p &lt; 0.01) by age, walking distance, severity of symptoms, drug intake and frequency of pain. The present systems for grading degenerative disc disease from plain lateral radiographs have limited application.

We have measured the dynamic movement of the lumbar spine in 57 patients with degenerative lumbar disc disease. Each completed a questionnaire which recorded pain and subjective signs and symptoms. From plain lateral radiographs, the subjects were graded using the criteria of Kellgren and Lawrence and those of Lane et al, which are both based on the severity of degenerative changes. Measurements of the height of the disc space and the vertebral height were obtained and expressed as a ratio. We found no relationship between the characteristics of spinal movement and the overall grading of degenerative disc disease with either system. Both were influenced (p < 0.01) by age, walking distance, severity of symptoms, drug intake and frequency of pain. The present systems for grading degenerative disc disease from plain lateral radiographs have limited application.

Background and Purpose: Total disc arthroplasty serves as the next frontier in the surgical management of intervertebral discogenic pathology. The purpose of this article was to report a patient with symptomatic degenerative disc disease treated with Charite' artificial disc (DePuy Spine, Raynham, MA) arthroplasty, and to briefly introduce and reviewe the relevant literatures of total disc arthroplasty. Methods: A 50-year-old female treated with lumbar artificial disc replacement with a SB Charite' Ⅲ prosthesis because of painful degenerative disc disease at L4/5. Results: The patient had symptomatic improvement, which was maintained over 10 months. She had greater reduction in the Oswestry Disability Index (ODI) and Visual Analog Scale (VAS). Conclusion: Total disc arthroplasty may be an attractive option for the surgical treatment of disabling mechanical low back pain secondary to lumbar disc disease. However, long-term follow-up studies is needed to assess the final role of this prosthesis.

Magnetic Resonance Imaging (MRI) is a sensitive modality to detect and characterize abnormalities of the spine. MRI can detect abnormalities of the disk and adjacent bone marrow in patients with degenerative disk disease (1). In a recent study the frequency and appearance of bone marrow changes along the end-plates in degenerative lumbar disc disease were assessed (1).

BackgroundPatient medical out-of-pocket expenses are thought to be rising worldwide yet data describing trends over time is scant. We evaluated trends of out-of-pocket expenses for patients in Australia with one of five major cancers in the first-year after diagnosis.MethodsParticipants from the QSKIN Sun and Health prospective cohort Study with a histologically confirmed breast, colorectal, lung, melanoma, or prostate cancer diagnosed between 2011 and 2015 were included (n = 1965). Medicare claims data on out-of-pocket expenses were analysed using a two-part model adjusted for year of diagnosis, health insurance status, age and education level. Fisher price and quantity indexes were also calculated to assess prices and volumes separately.ResultsOn average, patients with cancer diagnosed in 2015 spent 70% more out-of-pocket on direct medical expenses than those diagnosed in 2011. Out-of-pocket expenses increased significantly for patients with breast cancer (mean AU$2513 in 2011 to AU$6802 in 2015). Out-of-pocket expenses were higher overall for individuals with private health insurance. For prostate cancer, expenses increased for those without private health insurance over time (mean AU$1586 in 2011 to AU$4748 in 2014) and remained stable for those with private health insurance (AU$4397 in 2011 to AU$5623 in 2015). There were progressive increases in prices and quantities of medical services for patients with melanoma, breast and lung cancer. For all cancers, prices increased for medicines and doctor attendances but fluctuated for other medical services.ConclusionOut-of-pocket expenses for patients with cancer have increased substantially over time. Such increases were more pronounced for women with breast cancer and those without private health insurance. Increased out-of-pocket expenses arose from both higher prices and higher volumes of health services but differ by cancer type. Further efforts to monitor patient out-of-pocket costs and prevent health inequities are required.

A prospective, multi-center Investigational Device Exemption Study was carried out in the United States using a pedicle screw and plate system to perform a fusion in patients with degenerative disc disease or spondylolisthesis. The patients' pain function, complications, and fusion status were evaluated and compared with literature controls. To study the safety and efficacy of the ISF pedicle screw/plate system. This article focuses only on those study patients with degenerative disc disease treated with autogenous bone grafts and compares the results to those of similar patients treated without instrumentation, as reported in the literature. Twenty-eight patients were in the subgroup studied--patients with degenerative disc disease who had fusions with autogenous bone graft. This study was conducted at four clinical sites with a 2-year follow-up. Patient follow-up was greater than 95% at all time points. To be considered a patient with degenerative disc disease, radiographs had to demonstrate a collapse of the disc, the presence of bone erosion, or the compression of the vertebrae as the primary spinal abnormality. Spinal fusion must have been the recommended surgical treatment for discogenic pain. The fusion status was evaluated by the operating surgeon and an independent reviewer. After 2 years, this subset of patients (n = 28) with degenerative disc disease who had lumbar/lumbosacral fusion with autogenous bone graft was found to have a pseudarthrosis rate of 0%. Eight articles in the literature were found to be valid noninstrumented literature controls with which this subgroup could be compared. The average pseudarthrosis rate in the control group was 32%. A statistical analysis showed that patients with degenerative disc disease who underwent fusion without pedicle screw instrumentation were over 24 times more likely to have a pseudarthrosis than comparable patients implanted with a pedicle screw/plate system. Regarding the most important goal in performing a spinal fusion--fusion of the spine--the pedicle screw/plate system used in this study was shown to be a safe and efficacious method of facilitating fusion with autogenous bone graft for this patient population.

Adjuvant Chemotherapy Administration and Survival Outcomes in Lymphoma Survivors with Common Solid Tumors: A Population-Based Study