Stephen A. Hoption Cann

Hypothesis : Dietary iodine intake in the etiology of cardiovascular disease

This paper reviews evidence suggesting that iodine deficiency can have deleterious effects on the cardiovascular system, and correspondingly, that a higher iodine intake may benefit cardiovascular function. In recent years, public health bodies have aggressively promoted sodium restriction as a means of reducing hypertension and the risk of cardiovascular disease. These inducements have led to a general decline in iodine intake in many developed countries. For example, a United States national health survey conducted in the early 1970s observed that 1 in 40 individuals had urinary iodine levels suggestive of moderate or greater iodine deficiency; twenty years later, moderate to severe iodine deficiency was observed in 1 in 9 participants. Regional iodine intake has been shown to be associated with the prevalence of hypothyroidism and hyperthyroidism, where autoimmune hypothyroidism is the more common of the two in regions with moderate to high iodine intake. Both of these thyroid abnormalities have been shown to negatively affect cardiovascular function. Selenium, an important antioxidant in the thyroid and involved in the metabolism of iodine-containing thyroid hormones, may play an interactive role in the development of these thyroid irregularities, and in turn, cardiovascular disease. Iodine and iodine-rich foods have long been used as a treatment for hypertension and cardiovascular disease; yet, modern randomized studies examining the effects of iodine on cardiovascular disease have not been carried out. The time has come for investigations of sodium, hypertension, and cardiovascular disease to also consider the adverse effects that may result from mild or greater iodine deficiency.

A Prospective Study of Iodine Status, Thyroid Function, and Prostate Cancer Risk: Follow-up of the First National Health and Nutrition Examination Survey

Abstract: Few studies have investigated the association between iodine status, thyroid disease, and cancer risk despite evidence that thyroid function impacts many organs, including the prostate. We investigated iodine status and prostate cancer risk prospectively using data from the NHANES I Epidemiologic Follow-up Study. Participants were stratified into tertiles according to the urinary iodine/creatinine ratio, as a marker of iodine exposure. As iodine is an integral constituent of thyroid hormones, we also examined the relationship between thyroid disease and prostate cancer risk. Relative to the group with low urinary iodine, the age-adjusted hazard ratio was higher (although marginally insignificant) in the moderate group, hazard ratio 1.33 (95% confidence interval 1.00–1.78), and significantly lower in the high group, 0.71 (0.51–0.99). Thyroid disease was associated with an increased prostate cancer risk, 2.34 (1.24–4.43). Similarly, > 10 yr since thyroid disease diagnosis was associated with an elevated risk, 3.38 (1.66–6.87). After adjusting for other confounding factors, only a history of thyroid disease, 2.16 (1.13–4.14), and > 10 yr since diagnosis of thyroid disease, 3.17 (1.54–6.51) remained significant. Although the role of dietary iodine remains speculative, a role for thyroid disease and/or factors contributing to thyroid disease as a risk factor for prostate carcinogenesis warrants additional investigation.

Cancer cluster among police detachment personnel.

An apparent cancer cluster at a police detachment in a coastal British Columbia community was investigated. Police personnel suspected that the detachment building may have been a factor. Police personnel (20 current and 154 previous employees) associated with the detachment since 1963, the date of occupancy, were traced. After all 174 cases were contacted directly, or next of kin in case of death, a total of 16 cases of cancer or suspected cancers were reported. Of these 16, eight cases of cancer were confirmed through a cancer registry. Cancers included testicular, cervical, colon, skin (including melanoma), leukemias and lymphomas with an age range of diagnosis between 22 and 44 years. There was no evidence for an underlying event, factor or condition in the police building that could be attributed to the observed cancer cases. A possible association between these cancers and the use of police traffic radar is discussed.

A pinch of salt for convulsive status epilepticus

www.thelancet.com Vol 370 December 8, 2007 1905 5 Goldberg RM, Kohne CH, Seymour MT, et al. A pooled safety and effi cay analysis examinig the eff ect of performance status on outcomes in fi rst-line treatment trials of 6286 patients with metastatic colorectal cancer. J Clin Oncol 2007; 25 (suppl 18S): 166s. under-represented in clinical trials. In the meta-analysis of patients with performance status 2 (which included the FOCUS trial), initial combination chemotherapy showed a signifi cant advantage in overall survival compared with initial monotherapy. As we seek to further improve outcomes of patients with this still terminal disease, we feel that initial combination chemotherapy is the preferred platform from which to embark, a strategy which is also followed in the more recent CAIRO trials.

Anti-angiogenic treatment for breast cancer?

http://dx.doi.org/10.1016/j.ctrv.2017.02.008 0305-7372/ 2017 Elsevier Ltd. All rights reserved. The article by Aalders et al. [1] in this journal addresses some very important aspects for the treatment of women with breast cancer such as successes, failure and future perspectives. How can it be improved? The opening sentence of the article states: ‘‘The importance of angiogenesis in the development of tumors and metastases is well established”. It cites the work of Folkman [1]. This work was done with breast cancer cells growing in animal systems. Such systems may not reflect the growth of spontaneous breast cancer growing in humans. For example, we have reported [2,3] on the relative absence of blood vasculature in IDC (Infiltrating Ductal Carcinoma) compared to lymphatic vasculature. This is in contrast to human breast cancer cells growing in mice producing red tumors that are very sensitive to anti-angiogenic treatment [4]. Also, when we analyzed a series of 268 fresh human IDC biopsies for color, we found 86% were reported as white, yellow or gray. In contrast, no red or reddish tumors were reported, while only 14% were described as pinkish during ‘rapid section’ analysis. Although this is subjective analysis, it does indicate to us that in general the blood vascular system is not well developed in spontaneous IDCs. It would appear that anti-lymphatic rather than anti-angiogenic treatment may be more useful for patients with IDC, although it is by no means certain.

Spontaneous remission of Crohn's disease following a febrile infection: case report and literature review

Crohns disease is a chronic illness that may often follow a relapsing-remitting course. Many of the factors that may be associated with the spontaneous remission of this disease (i.e. not related to specific treatment) remain to be determined. In the present report, we review the medical history of a patient with a long history of moderate to severe Crohns whose complete remission immediately followed the development of a febrile infection.Crohns disease is a chronic illness that may often follow a relapsing-remitting course. Many of the factors that may be associated with the spontaneous remission of this disease (i.e. not related to specific treatment) remain to be determined. In the present report, we review the medical history of a patient with a long history of moderate to severe Crohns whose complete remission immediately followed the development of a febrile infection.The patient first developed symptoms of Crohns in her late adolescent years. At the time of diagnosis at age 23, she was placed on mesalamine - without effective control her disease symptoms. Due to progressive deterioration, the patient underwent a bowel resection at age 25. Soon afterwards symptoms recurred, gradually increasing in severity. In February 2005, at age 36, the patient developed a painful abscess associated with a rectal fistula. Other symptoms at the time included chronic bone and stomach pain, swollen joints, and debilitating fatigue. Surgical correction was scheduled in mid-March. In late February, the patient developed a respiratory infection associated with fevers of 103-104°F. After the onset of fever, the abscess pain disappeared and this was soon followed by a disappearance of all other disease symptoms. By the time the corrective surgery occurred, she had no Crohns symptoms. Her remission lasted 10 weeks when the previous symptoms then reappeared. The patient has subsequently used a variety of conventional therapies, but still suffers from severe symptoms of her disease.In recent years, a growing body of literature has emphasized the important role that innate immunity plays in the etiology of Crohns disease; however, a key component of innate immunity, the febrile response, has been overlooked. Other cases of spontaneous remission following febrile infection in inflammatory bowel disease have been reported. Moreover, induction of a febrile response was in the past used as a treatment for inflammatory bowel disease, but was later replaced by surgery and corticosteroids. Further exploration of this arm of the innate immune response may provide new opportunities for patients where conventional therapies fail to secure relief.

The lymphatics in infiltrating ductal carcinoma (IDC) of the breast

https://doi.org/10.1016/j.ctrv.2017.10.015 0305-7372/ 2017 Elsevier Ltd. All rights reserved. ⇑ Corresponding author at: 4080 O’Toole Place, Victoria, B.C. V9C 3Z6, Canada. E-mail addresses: jpvannetten@shaw.ca (J.P. van Netten), hoptioncann@ubc.ca (S.H. Cann), carolian@shaw.ca (I.G. Thornton), finrory@hotmail.com (R.P. Finegan). Johannes P. van Netten a,⇑, Stephen Hoption Cann , Ian G. Thornton , Rory P. Finegan a

Growing concern following compression mammography

A patient without clinical symptoms had a mammogram in October 2008. The procedure caused intense persistent pain, swelling and development of a haematoma following mediolateral left breast compression. Three months later, a 9×11 cm mass developed within the same region. Core biopsies showed a necrotizing high-grade ductal carcinoma, with a high mitotic index. Owing to its extensive size, the patient began chemotherapy followed by trastuzumab and later radiotherapy to obtain clear margins for a subsequent mastectomy. The mastectomy in October 2009 revealed an inflammatory carcinoma, with 2 of 3 nodes infiltrated by the tumour. The stage IIIC tumour, oestrogen and progesterone receptor negative, was highly HER2 positive. A recurrence led to further chemotherapy in February 2011. In July 2011, another recurrence was removed from the mastectomy scar. She died of progressive disease in 2012. In this article, we discuss the potential influence of compression on the natural history of the tumour.

Days of giants: remembering Albert Schweitzer

Paul Webster’s World Report, “Can Canada reckon with its health costs?” (Sept 8, p 875) suggests that our ageing population is putting the main fi nancial strain on the Canadian health-care system. The story states that caring for “increasing numbers of elderly patients with expensiveto-treat chronic health conditions” will infl ict “stinging new costs” and represents a “coming chronic care crisis”. In other words, the diagnosis is demographics. Unfortunately, the evidence suggests that the diagnosis is somewhat more complex than this. Yes, an ageing population does lead to more health-care spending, as the reputable experts in your report highlight—but that’s only part of the story. As research shows, ageing constitutes only a small and predictable portion of the rising costs of health care in this country: a manageable 1% per year increase. Of greater fi nancial concern is an increasing intensity of care for all age groups, and rising costs for medical screening and diagnostic tests, prescription drugs, and doctors’ fees. All patients are also using signifi cantly more publicly funded health services than a decade ago. Whether they’re 50 or 85, Canadians are seeing more specialists and undergoing more tests. They’re also taking more drugs and often more expensive drugs than before. Boomers aren’t to blame. It isn’t the ageing population per se that threatens the sustainability of our health-care system, but the interaction of that growing population segment with current shortfalls in health-care delivery, including poor coordination of services, and, in many cases, unnecessary use of some health products and services. Instead of creating a generational divide by pointing the fi nger at our seniors, now is the time to have a deeper discussion about how best to reform our health system to ensure our seniors—and everyone else— receive quality care, when and where they need it.

Stromal regulation of cancer growth: a balancing act in surgery.

There are examples in the literature of dormant cancer cells being stimulated after tissue injury. On the other hand, there are also reports of cancer regression following injury.6–8 What explanation can be offered for this discrepancy? The answer may involve the stroma or connective tissue bed of solid tumour. Traditionally this stroma has been regarded mainly as a physical support for the growing cancer cells. More recently, however, there is evidence that stromal cells, many of which are immune cells, may exude active growth control of cancer. For example, macrophages have been reported to produce many growth factors. These cells can also produce collagen,10 can differentiate into fibroblastlike cells, and it has also been suggested that macrophages can also transform into endothelial-like cells.13 The truly multifunctional capacity of macrophages gives them the potential to play a major role in tumour growth. In addition, other immune cells such as T-cells and B-cells have been reported to produce growth factors.14,15 Thus, stromal cell populations present in cancer tissue can be engaged in opposing functions such as paracrine growth regulation as well as the more traditional role of defense. A more comprehensive name may be needed to reflect the dual role of these stromal ‘immune’ cells. In fact, the reticulo-endothelial system (RES) described by Aschoff over 80 years ago comes close. Cancer develops with abnormal local growth of cells as well as stroma in the parent organ. The next step is metastatic spread. It is interesting to note that we found evidence that this metastatic spread may involve macrophage/cancer cell units17 migrating through the vascular system and establishing new growth at distant sites. Formation of such units suggests that paracrine growth regulation may occur at a very early stage of the metastatic process. At the metastatic site, cancer cells are still dependent on the presence of stroma for support and growth. End stage cancer, on the other hand, can be composed of cells that are completely independent of stromal regulation and can grow in the peritoneal or pleural cavity as isolated cells.18 Using such cells for the study of solid cancer growth regulation may not reflect the natural process. In the stromal dependent phase of tumour growth there is a window of opportunity to control cancer by interfering with this support. Examples are anti-angiogenic and anti-lymphagenic treatment, reducing of growth factor output, disrupting physical support, and increasing classical immunological activity, etc. Ultimately, the goal of such treatments is stromal collapse. An analogy may be drawn between this process and the shedding of the endometrium during the menstrual cycle where collagen producing cells (fibroblast-like) during the follicular phase can transform into phagocytic cells (macrophage-like) during the menstrual phase.19 This process is hormonally controlled. Likewise,