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Damaged DNA and Cellular Apoptosis: The Story on Bladder Cancer in the Elderly

Damaged DNA and Cellular Apoptosis: The Story on Bladder Cancer in the Elderly

Teaser: 

D'Arcy Little, MD, CCFP
Director of Medical Education,
York Community Services,
Toronto, ON

Munir A. Jamal, MD, FRCSC
Staff Urologist,
Credit Valley Hospital,
Mississauga, ON

Introduction

Epidemiology:
Cancer of the urinary bladder is essentially a disease of the elderly. The median age at diagnosis is 69 years for males and 71 years for females, and more than one-third of cases occur in patients over the age of 75 years of age.1,2 The incidence of transitional cell carcinoma (TCC) of the bladder, the most common subtype of bladder cancer, accounting for over 90% of cases, is rising and currently ranks as the fourth highest new cancer diagnosis in men.3 However, the mortality rate of this disease has fallen over the last two decades.1 The following review article will address the epidemiology, natural history, clinical presentation, and treatment of this disease, with an emphasis on issues pertaining to elderly patients. (See Figure 1)

Bladder cancer is unique among human neoplasms in that it has been associated with several distinct etiological factors.4 Risk factors related to the development of TCC, in addition to age, include tobacco smoking and occupational exposures in the dye, rubber, textile, and leather industries.

CABG in the Elderly: Is it Economically Feasible

CABG in the Elderly: Is it Economically Feasible

Teaser: 

D'Arcy Little, MD, CCFP
Director of Medical Education,
York Community Services, Toronto, ON

Background
Coronary artery bypass grafting (CABG) is an accepted therapeutic intervention for the treatment of coronary artery disease (CAD). Depending on the clinical situation, CABG can improve the symptoms of angina, patient survival (triple vessel or left main disease), and quality of life. Over the last two decades, there has been a substantial growth in the use of CABG in Canada and it is now one of the most common surgical procedures performed in North America. Most of the overall increase in the frequency with which this procedure is performed has been seen in the elderly population.1,2 However, this increase has not taken place without controversy. While some health critics have argued that the procedure is overused, patients often express concern about waiting lists.3 This article will discuss the costs of CABG in the elderly and potential avenues to reduce these costs and improve patient outcomes.

In Ontario, the overall rate of CABG grew 31% during the years 1981 to 1989, and in 1989-90 this surgery was performed at a rate of 66 procedures per 100,000 members of the population. Notably, during this period, the highest annual increase was in those patients aged 65 to 74 years. Thirty-seven percent of cases were performed in patients over 65 years of age.

Baycrest’s Unit-based Ethics Rounds: A Prototype for Long-term Care Facilities

Baycrest’s Unit-based Ethics Rounds: A Prototype for Long-term Care Facilities

Teaser: 

 

Michael Gordon, MD, FRCPC
Vice President Medical Services
and Head Geriatric and Internal Medicine,
Baycrest Centre for Geriatric Care,
Head, Division of Geriatrics,
Mt. Sinai Hospital,
Professor of Medicine,
University of Toronto,
Toronto, ON

Leigh Turner, Ph.D|
Baycrest Centre for Geriatric Care

Ethics Education in the Geriatric and Long-Term Care Setting
Baycrest Centre for Geriatric Care now has an innovative program in ethics education. Developing a well-rounded educational program in bioethics, intended to benefit all levels of staff within the geriatric and long-term health care setting, was a considerable challenge. With few models to emulate, this program was undertaken to provide the staff with the knowledge and means to respond to important ethical challenges in an appropriate manner. The system of unit-based ethics rounds, which has been implemented over the last several years, has been very successful and may serve as a prototype for other long-term care and geriatric facilities.

The Unit-based Model
The standard hospital model for providing assistance in resolving ethical issues includes an ethics committee that offers a consultation service. This structure, which exists at Baycrest, has been in existence for about a decade in the long-term care system, following its introduction to the acute care system years before.

Response to Therapy in Acute Myeloblastic Leukemia Dependent on Genetic Make-up of Leukemic Cells

Response to Therapy in Acute Myeloblastic Leukemia Dependent on Genetic Make-up of Leukemic Cells

Teaser: 

M.D. Minden, M.D., Ph.D., FRCPC
Princess Margaret Hospital
University Health Network
Toronto, ON

Introduction
Leukemias are malignancies of the blood and bone marrow and are classified as either acute or chronic malignancies of the myeloid--red blood cell, granulocyte, platelet lineage--or lymphoid--T or B lymphocyte. In this article we will focus on acute myeloblastic leukemias (AML) and recent advances in their classification and therapy.

In the United States, approximately 10,100 cases of AML are diagnosed each year and the yearly mortality rate from this disease is approximately 6,900 individuals. The incidence of AML is low in children (<1/100,000) and increases with age, such that by the time a person reaches the age of 80 the incidence is approximately 15/100,000 (Figure 1).1 Over 60% of patients are 55 years of age or older, making this a significant problem in the aging population.

AML develops as the result of genetic changes in hematopoietic stem cells of the bone marrow.2 These changes block the ability of the cell to undergo normal differentiation resulting in a blast-like morphology. In some cases, the patient may have large numbers of circulating leukemic blast cells compromising blood flow to vital organs.

Radiation Therapy for the Treatment of Esophageal and Gastric Cancers in the Elderly

Radiation Therapy for the Treatment of Esophageal and Gastric Cancers in the Elderly

Teaser: 

Jolie Ringash, MD, MSc
Department of Radiation Oncology,
Princess Margaret Hospital
University Health Network,
Toronto, ON

Background
Esophageal and gastric carcinomas are primarily diseases of older persons. Of 498 new cases of esophageal cancer in Ontario in 1997, 237 (48%) occurred in individuals aged 65 to 79, and 101 (20%) in those over the age of 80. The corresponding numbers for gastric cancer are (of a total of 1,032 cases) 492 (48%) for those aged 65 to 79, and 200 (19%) for those over 80.1 For all age groups, gastric cancer is decreasing in incidence, with only 2, 800 cases in Canada in the year 2000. In contrast, the incidence of esophageal cancers is gradually increasing (1,350 cases in 2000).2,3 Adenocarcinoma, primarily of the distal esophagus, has replaced squamous cell carcinoma as the most frequent histology. Tumours of the gastroesophageal junction pose a particular challenge, since management may differ depending on whether the tumour is felt to originate in esophagus or stomach.

Canadian oncologists frequently face difficult treatment decisions in the elderly. Unfortunately, since older patients are usually excluded from clinical trials, evidence for their tolerance of, and response to, therapeutic radiation is limited. Existing reports are limited to retrospective reviews and subgroup analyses, many of which originate in Japan.

Cancer and Aging: Two Sides of the RecQ-Like Helicase Coin

Cancer and Aging: Two Sides of the RecQ-Like Helicase Coin

Teaser: 

Haim Cohen, Ph.D
Department of Pathology,
Harvard Medical School,
Boston, MA

The incidence of cancer increases as we age: during the last decade of life, the risk of developing cancer is a startling 50% for men and 33% for women.1 What is the underlying link between aging and cancer? This link may be found by investigating diseases that are associated with both a high frequency of cancer and premature signs of aging. Such diseases, known collectively as RecQ syndromes, are caused by mutations in genes encoding RecQ-like proteins.2 The RecQ family of proteins has a high degree of homology to the helicase domain of the RecQ helicase of E. coli. The helicase region is required for all RecQ helicases to unwind duplex DNA from 3' to 5' direction in vitro; however, the in vivo function of the eukaryotic RecQ is unknown.

At least three inherited human diseases are caused by mutations in RecQ-like genes: Werner syndrome (WS), Bloom syndrome (BS), and Rothmund-Thomson syndrome (RTS).3 These diseases share two main features: premature aging and a high level of genomic instability that manifests itself as a high incidence of cancer.

The hallmark of Bloom syndrome is an increased level of sister chromatid exchange, and patients present with sun-sensitive skin pigmentation and a predisposition to certain malignancies.

Multiple Myeloma: The Debilitating Disease that ‘Punches Out’ the Elderly

Multiple Myeloma: The Debilitating Disease that ‘Punches Out’ the Elderly

Teaser: 

Dr. Christine I. Chen, MD, FRCPC
Princess Margaret Hospital,
University Health Network,
Toronto, ON

Introduction
Multiple myeloma arises from a malignancy of plasma cells in the bone marrow which typically produce an immunoglobulin, also referred to as a monoclonal protein (M-protein), that is detectable in the patient's blood and/or urine. Myeloma is not a common disease (incidence of 1400/year in Canada), typically affecting older individuals (median age 65 years). It is more common in blacks and slightly more prevalent in males. Since myeloma is a relatively slow-growing malignancy, many patients will have the disease for months or even years before a diagnosis is made and may continue to follow an indolent course. The pathogenesis of the disease is poorly understood.

Clinical Features
Characteristic clinical features of multiple myeloma are anemia, renal failure, bony lesions with pathologic fractures and associated pain, hypercalcemia, and recurrent infections (See Table 1). Many patients, however, will present with asymptomatic anemia or a monoclonal gammopathy, which is usually discovered during incidental lab testing.

Elderly Patients Excluded from Clinical Trials

Elderly Patients Excluded from Clinical Trials

Teaser: 

Tawfic Nessim Abu-Zahra, BSc, MSc

Elderly people (i.e. those over 65 years of age) tend to be excluded from clinical research trials in areas such as cancer and heart disease.1-4 Physicians wishing to make evidence-based treatment decisions for elderly patients may have to extrapolate clinical data from studies that have been conducted in a younger population. However, given that there are age-related changes that occur even in healthy elderly people, any such extrapolation may not be scientifically sound.1-3 Changes in physiological parameters that occur with increasing age, such as decreases in renal and cardiovascular function, blood flow and hepatic volume, make the disposition of drugs more variable in the elderly and predispose them to drug toxicities and adverse drug reactions.3 The result is that geriatric patients may not receive the newest therapies or may receive a treatment whose efficacy and safety in the elderly is not known.1-3

In a study published in the New England Journal of Medicine, Hutchins and colleagues5 determined the enrollment rate of cancer patients aged 65 years or older in clinical trials, and compared this with the corresponding rate of elderly cancer patients in the general population. Overall, the authors reported that the elderly were significantly underrepresented in all cancer trials and in 14 of the 15 types of cancer that were individually investigated.

Diet and Education in the Control of Diabetes in the Elderly

Diet and Education in the Control of Diabetes in the Elderly

Teaser: 

Tess Montada-Atin, RN, CDE
Care Leader

Marilyn Mori, RD
Lina Medeiros, MSW
Diabetes Education Centre,
Toronto Western Hospital
University Health Network
Toronto, ON

Diabetes is a chronic illness with significant short and long term complications.1 The Diabetes Education Centre (DEC) at the Toronto Western Hospital, University Health Network, supports people with diabetes, their family and friends to better understand and manage diabetes. The 1998 Clinical Practice Guidelines (CPG) for the management of diabetes in Canada, recommends initial and ongoing education for the person with diabetes as part of diabetes care and not just as an adjunct to treatment. Diabetes Education should be recognized as a life long commitment.2 Comprehensive management of diabetes should be planned around an interdisciplinary diabetes health care team,1-3 which can be through a DEC. To learn and use the varied complex skills required, people with diabetes need the support of such a team of expert professionals.1 Interdisciplinary interventions have been shown to improve glycemic control in the elderly. Studies have suggested that a team approach toward older people with diabetes improves blood glucose control, quality of life and adherence to therapy.3

Factors that affect glycemic control are diet, diabetes medications and exercise.

Vintage Advice

Vintage Advice

Teaser: 

Both the British Medical Journal and the Journal of the American Medical Association (JAMA) participate in the charming and instructive activity of reprinting short sections from their pages of 100 years ago. These pieces are often quaint, always entertaining and frequently outdated--but not always.

Many a time, and oft, in fact, they still speak to the heart of our clinical practice, even from over a century in which both the practice and face of medicine have changed so dramatically. For example, published in a recent issue of JAMA (Volume 182(17):1606i), and penned over a century ago by Dr. J.W. Bell in his prime as Professor of Physical Diagnosis and Clinical Medicine at the University of Minnesota, was an impassioned "Plea for the Aged".

It should be pointed out that, in 1899, geriatrics did not yet formally exist as a specialty and that Ignatz Naccher's seminal work, "Geriatrics: The Diseases of Old Age and their Treatment" would not come out in print for another 14 years. Marjorie Warren, considered the founder of modern hospital geriatrics in the UK for work in the 1940's, was then barely three years old.

Bell acknowledged that, despite the paucity of current American literature on the subject of the elderly, the French (Charcot, Pine) and British (Day, McLachlan) authorities had helped "to furnish the nucleus of our present knowledge of senile pathology". However, despite the interest of these eminent authorities, Dr. Bell offered a criticism that unfortunately is still quite relevant today: "The want of interest, as indicated by the scanty and fragmentary character of the literature on the subject, is largely responsible for the apathy existing today in our medical schools".

As we enter the new millenium, it must be acknowledged that there has been a modest improvement in the number of Canadian medical schools offering a course in geriatrics. Still, the growth is not at all proportional to the increase in the numbers of elderly. In 1899, less than 5% of the continent's population was over the age of 65. Today, that percentage has almost tripled and life expectancy has increased significantly throughout the developed world.

Despite his critique of the system, Bell understood the circular wars of the medical schools that still rage today. He offers that "It would seem criminal to even suggest that addition of another distinct course to the already overcrowded college [medical] cirriculum (sic)…." But he does offer two suggestions, the first of which still makes sense: "That the chairs of anatomy and physiology impart to the student the necessary primary instruction…". To the contemporary reader, his second suggestion may seem a bit quaint but it was obviously born out of desperation and the faint hope that colleagues might heed his plea. Here, Bell suggests that the "The chair of practice [Internal Medicine], or if deemed best, in order to contrast disease, the chair of pediatrics enlarge its scope and furnish the necessary…instruction…"

Were Dr. Bell to survey the situation today, he would also still have much room and justification for complaint. Despite improvements in our field, his words from one hundred years ago ring true today: "[the medical student] scarcely recalls reference by one of his teachers to old age, unless suggested in mitigation of the failure of some brilliantly planned but misjudged operation or equally ill-timed drug treatment".

JAMA's recent '100 Years Ago' column has helped us to realize that despite some improvement, at least in the field of treating the elderly, 'plus ça change; plus c'est le meme chose".

Dr. A. Mark Clarfield is the Chief of Academic Affairs at the Herzog Hospital in Jerusalem and on staff in the Division of Geriatric Medicine, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal.