Journal of Long-Term Eﬀ ects of Medical Implants, 14(5)341–346 (2004)
Joseph K. McLaughlin, PhD A World Leader in Implant Research William J. Blot, PhD¹ & Joseph F. Fraumeni, Jr., MD²
¹International Epidemiology Institute, Rockville, Maryland, USA, and Vanderbilt University
Medical Center, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA; ²Division of
Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
Address all correspondence to William Blot, International Epidemiology Institute, 1455 Research Blvd, Suite 550, Rockville, MD 20850; firstname.lastname@example.org
1050-6934/04 $20.00 2004 by Begell House, Inc.
341 342 W. J. BLOT & J. F. FRAUMENI, JR. ABSTRACT: Objective. To describe the key contributions of Dr. Joseph K. McLaughlin, Outstanding Scientist of 2004. Methods. We review the scientiﬁ c literature and indicate how epidemiologic research conducted by Dr. McLaughlin has clariﬁ ed long-term health eﬀ ects among persons with breast and other medical implants. Results. Dr. Joseph K. McLaughlin has conducted and directed more research into the long-term eﬀ ects of human implants than any other scientist worldwide. His insights greatly elucidated the long-term health consequences associated with a variety of implanted devices, including silicone and saline breast implants, hip and knee replacements, temporomandibular and ﬁ nger joint devices, and pacemakers. By initiating and bringing to fruition a series of innovative epidemiologic investigations, Dr. McLaughlin and his colleagues have provided the scientiﬁ c basis for making judgments about alleged adverse health eﬀ ects following cosmetic, reconstructive, and reparative implant surgery. Conclusions. Dr. McLaughlin’s seminal investigations have provided reassurance that breast and other implants have not demonstrably increased the risk of cancer or other systemic diseases. Th e comprehensive and rigorous nature of this research merits his selection as Outstanding Scientist of 2004. KEY WORDS: breast implants, medical devices, epidemiology, surveillance, cancer, connective tissue disease, neurologic disease, birth defects, confounding Dr. joseph k. mclaughlin is President of of renal cell carcinoma, and that the risk of kidney
the International Epidemiology Institute cancer rose progressively with increasing body mass (IEI), headquartered in Rockville, Mary- and with use of the analgesic phenacetin.¹-² Th e latter
land, and Professor in the Department of Medicine ﬁ nding led to follow-on studies by Dr. McLaughlin of the Vanderbilt University Medical School and and by others assessing acetaminophen, the primary Vanderbilt-Ingram Cancer Center in Nashville, metabolite of phenacetin, as a potential risk factor. Tennessee. He also holds an appointment as adjunct While these studies revealed no substantial adverse Professor of Epidemiology at the Johns Hopkins eﬀ ect, the jury is still out on whether acetaminophen, Bloomberg School of Public Health in Baltimore, aspirin, or other non-narcotic analgesics may impart Maryland. Prior to cofounding IEI in 1994, he a small increase in the risk of renal cancer or chronic served as Epidemiologist and then Deputy Chief in renal failure.³-⁴the Epidemiology and Biostatistics Program of the
Dr. McLaughlin also conducted research into
National Cancer Institute. He spent two years as As- the causes of oral, esophageal, stomach, colorectal, sistant Professor at Johns Hopkins after receiving his lung, bladder, and other cancers. He showed, for in-doctoral degree in epidemiology from the University stance, that smoking and drinking account for about of Minnesota in 1981.
three-fourths of all oral cancers, while low intake
Dr. McLaughlin has had an exceptionally pro- of fruits and vegetables also contribute to elevated
ductive career in epidemiologic research. His initial risk.⁵-⁶ He has also helped track the epidemic rise studies focused on the etiology of cancer, including in esophageal adenocarcinoma in the United States research on renal cancer that clariﬁ ed the roles of and showed a causal relation to obesity and to gas-tobacco smoking, diet, obesity, medical conditions, troesophageal reﬂ ux disease rather than (as previously pharmaceutical agents, and occupational exposures. reported) acid-inhibiting drugs used as treatment.⁷ He was one of the ﬁ rst to show, for example, that Furthermore, in a series of exploratory studies using cigarette smoking increased the risk of cancer of the linked employment–cancer registries in Sweden, Dr. renal pelvis up to 10-fold while doubling the risk McLaughlin uncovered and conﬁ rmed a number of
Journal of Long-Term Effects of Medical Implants OUTSTANDING SCIENTIST OF 2003 343
occupation–cancer associations. While certain occu- from impaired survival after breast cancer diagnosis. pational exposures appeared causally linked to cancer, For example, in a review by the International Agency he found that many reported associations were more for Research on Cancer (IARC), it was concluded that likely to be false-positives resulting from random ﬂ uc- there was suﬃ cient evidence that silicone implants tuations from multilayered and multi-subset analyses. are not carcinogenic to the breast.¹⁷Th is experience prompted Dr. McLaughlin to publish
However, concerns were also voiced that women
several methodologic papers on the conduct and in- with silicone gel-ﬁ lled breast implants may be at terpretation of epidemiologic studies and how bias increased risk of developing other cancers, such as and confounding can aﬀ ect study ﬁ ndings.⁸-¹¹
leukemia and multiple myeloma. Th e subsequent
Perhaps the speciﬁ c area of research for which Dr. work of Dr. McLaughlin was central to the conclu-
McLaughlin has devoted most attention is the eﬀ ect sion reached by scientiﬁ c review bodies that there is of implanted devices on human health. Dr. McLaugh- no demonstrable excess of any form of cancer among lin has launched a series of epidemiologic studies to women with silicone breast implants.¹⁷-²² evaluate whether implants increase the risk of cancer,
In recent years, concerns began to center on a pos-
connective tissue diseases, and various other condi- sible link between connective tissue disease (CTD) tions. In a bibliography of more than 360 publications, and silicone breast implants. In the 1980s and early over 50 original papers in the peer-reviewed scientiﬁ c 1990s, anecdotal case reports suggesting a possible literature have described risks of disease among indi- excess of autoimmune disorders among women viduals receiving surgical implants. Th
e most extensive with breast implants came to the attention of the
series of publications involved breast implants.
US Food and Drug Administration (FDA). While
Th e initial concerns about the adverse eﬀ ects of the initial publications focused on systemic sclerosis
breast implants involved cancer, especially breast (scleroderma), clinical reports also appeared on the cancer. It was suggested that foreign materials such occurrence of other autoimmune diseases, including as silicone might lead to scarring, inﬂ ammation, or Graves’ disease, Hashimoto’s thyroiditis, systemic other changes with malignant potential, and that and discoid lupus erythematosus, mixed connective the ability to detect early breast cancer would be tissue disease, morphea, polymyositis, dermatomyo-limited in women with breast implants, because the sitis, Raynaud’s syndrome, rheumatoid arthritis, and opaque implants might interfere with physical breast Sjogren’s syndrome. In large-scale, long-term cohort examination or mammographic visualization of breast studies by Dr. McLaughlin, no evidence was found tumors, leading to delays in breast cancer diagnosis linking silicone breast implants to any individual and thus to higher fatality rates. In cohort studies CTD or all CTDs combined.²³-²⁵ Th ese results were in Denmark, Sweden, and Fınland involving a total conﬁ rmed by other investigators, leading to an In-of about 12,000 women with breast implants, Dr. stitute of Medicine consensus report indicating “no McLaughlin and his colleagues found that the risks elevated relative risk or odds ratio for an association were actually decreased rather than increased among of implants with disease.”¹⁸women with breast implants.¹²-¹⁵ In addition, they
More diﬃ cult to evaluate has been the concern
showed that women with breast implants were on that breast implants may lead to subtle or atypical average diagnosed with breast cancer at the same manifestations of CTD. However, in nationwide stage as controls, with no statistically signiﬁ cant dif- cohort studies with virtually 100% follow-up in ference in overall survival between the two groups.¹⁶ Sweden and Denmark, Dr. McLaughlin and his Th is research was instrumental to consensus reports colleagues found no excess of ﬁ bromyalgia among indicating that women with cosmetic breast implants women with implants.²⁶-²⁸ Furthermore, validation of are not at increased risk for breast cancer or for de- the diagnosis “unspeciﬁ ed rheumatism” did not reveal layed detection of breast cancer, nor do they suﬀ er a pattern of symptoms suggestive of atypical CTD
Volume 14, Number 5, 2004 344 W. J. BLOT & J. F. FRAUMENI, JR.
in women with silicone implants.²⁹ With regard to confounding is addressed. Based on this experience their musculoskeletal pain proﬁ le or the prevalence with implant studies, Dr. McLaughlin has reported of ﬁ bromyalgia, the group exposed to silicone did not on the insidious eﬀ ects of “confounding by indica-diﬀ er from women with breast reduction surgery or tion” in epidemiologic research of implants.¹¹ In this from an additional comparison group with no breast situation, an association reported between a device surgery. Moreover, by examining rheumatic diagnoses or medication and disease may actually be due to the and symptoms among groups of women with breast underlying condition for which the device or medi-implants, breast reduction, or no breast surgery,³⁰ sig- cation is prescribed. Identifying and correcting for niﬁ cant diﬀ erences were not seen in the occurrence such confounding is often very diﬃ cult, prompting of ﬁ bromyalgia or related complaints. However, in Dr. McLaughlin to alert the epidemiologic as well as all groups the frequency of symptoms was strongly clinical communities to its distorting eﬀ ects. associated with preimplant rheumatic conditions,
In addition, Dr. McLaughlin has evaluated the
underscoring the importance of taking antecedent long-term eﬀ ects of other implanted devices, includ-conditions into account when evaluating the risk of ing artiﬁ cial hips, knees, ﬁ nger joints, temporoman-CTDs among women with breast implants. In ad- dibular joints, and pacemakers.³⁶-⁴¹ He has used the dition, Dr. McLaughlin and colleagues performed a same scientiﬁ c model—namely, population cohort series of studies of neurologic disease among women studies that take advantage of the unique data systems with breast implants and found no excess of these in Scandinavian countries. Th ese investigations have conditions when compared with controls.³¹-³³ Finally, been reassuring in ﬁ nding no evidence of increased Dr. McLaughlin has taken the lead in evaluating the risk of cancer or other systemic illness among indi-association between breast implants and suicide risk, viduals with other implant types. which was previously reported in epidemiologic stud-ies.³⁴ In a recent review, he set forth the methodologic framework necessary for research to evaluate whether CONCLUSIONthis association is causal or a result of preimplant patient characteristics.³⁵
In summary, Dr. McLaughlin has been a pioneer
Th e studies of women with breast implants in and leader in the initiation and conduct of a sys-
Scandinavian populations illustrate the rigorous, tematic series of epidemiologic investigations that methodologic approach taken by Dr. McLaughlin in have comprehensively evaluated the health eﬀ ects evaluating potential disease risks. He has taken care of medical implants. His seminal contributions to to ensure that followup is complete, that appropriate the ﬁ eld clearly merit his selection as Outstanding control or comparison groups are employed, and that Scientist of 2004.
Jr. Renal Cancer. In: Schottenfeld D, Fraumeni JF Jr (Eds): Cancer Epidemiology and Prevention. New
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Mehl ES, Fraumeni JF Jr. A population-based case-
Acetaminophen, aspirin, and chronic renal failure.
control study of renal cell carcinoma. J Natl Cancer
5. McLaughlin JK, Gridley G, Block G, Winn DM,
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S, Fraumeni JF Jr, Adami HO. Cancer risk among 25. Nyren O, Josefsson S, McLaughlin JK, Blot WJ, women with cosmetic breast implants: a population-
Engqvist M, Hakelius L, Boice JD Jr, Adami H-O.
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Risk of connective tissue disease and related disor-
ders among women with breast implants: A nation-
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Pakkanen M, Teppo L. Incidence of breast and 26. Lipworth L, Tarone RE, McLaughlin JK. Breast other cancers among Finnish women with cosmetic
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conditions following cosmetic breast implantation in
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review of the epidemiologic evidence. J Long Term
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after hip replacement with metal implants: a popula-
Samsoe B, Bliddal H, Blot WJ, Olsen JH. Muscular
tion-based cohort study in Sweden. J Natl Cancer
rheumatism following breast surgery in Denmark.
37. Olsen JH, McLaughlin JK, Nyren O, Mellemkjaer
30. Jensen B, Bliddal H, Kjoller K, Wittrup IH, Friis
L, Lipworth L, Blot WJ, Fraumeni JF Jr. Hip and
S, Hoier-Madsen M, Rogind H, McLaughlin JK,
knee implantations among patients with osteoar-
Lipworth L, Danneskiold-Samsoe B, Olsen JH.
thritis and risk of cancer: a record-linkage study
Rheumatic manifestations in Danish women with
from Denmark. Int J Cancer 1999; 81:719–722.
silicone breast implants. Clin Rheumatol 2001; 20:
38. Fryzek JP, Mellemkjaer L, McLaughlin JK, Blot
WJ, Olsen JH. Cancer risk among patients with
31. Winther JF, Bach FW, Friis S, Blot WJ, Mellemkjaer
ﬁ nger and hand joint and temporo-mandibular
L, Kjøller K, Høgsted C, McLaughlin JK, Olsen
joint prostheses in Denmark. Int J Cancer 1999;
JH. Neurologic disease among women with breast
implants. Neurology 1998; 50:951–955.
39. Fryzek JP, Mellemkjaer L, Friis S, McLaughlin JK,
32. Winther JF, Friis S, Baach FW, Mellemkjaer L,
Rosenthal AK, Blot WJ, Olsen JH. Connective tis-
Kjøller K, McLaughlin JK, Lipworth L, Blot WJ,
sue disease and other related rheumatic conditions
Olsen JH. Neurological disease among women with
among patients with ﬁ nger and hand joints and
silicone breast implants in Denmark. Acta Neurol
temporomandibular joint prostheses in Denmark.
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Engqvist M, Hakelius L, Blot WJ, Adami HO.
BL, Kjøller K, Høgsted C, Winther JF, Blot WJ,
Breast implants and risk of neurologic disease: a
Olsen JK. Connective tissue disease after hip and
population-based cohort study in Sweden. Neurol-
knee implant surgery. Scand J Rheumatol 2001; 30:
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Journal of Long-Term Effects of Medical Implants
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Journal of Hospital Infection (2005) 59, 159–162High frequency of Candida parapsilosis on thehands of healthy hostsL.A. Bonassolia, M. Bertolia, T.I.E. Svidzinskib,*aUniversidade Estadual de Maringa´, Hospital Universita´rio Regional de Maringa´, Parana´, BrazilbUniversidade Estadual de Maringa´, Departamento de Ana´lises Clı´nicas, Laborato´rio de Micologia Clı´nica,Avenida Colomb