It also causes multiple noncancerous, tumor-like growths that resemble skin tags, goosebumps or razor burn on various parts of the body. People with Cowden syndrome inherit the condition in an autosomal dominant pattern. Last reviewed by a Cleveland Clinic medical professional on 12/16/2022. [3] Other conditions have been reported to be associated, but may not be caused by the mutation in FLCN or may not be related at all. Heterozygotes have renal abnormalities seen very early in life that develop into clear-cell and hybrid tumors, significantly shortening the animals' lifespans; they also are prone to endometrial and salivary gland clear-cell hyperplasia as well as rhabdomyolysis. Log in to our secure, personalized website to manage your care (formerly myMDAnderson). No. Cowden syndrome - About the Disease - Genetic and Causes NSML is inherited as an autosomal dominant A person can also receive a diagnosis of CS if they have one major and three minor criteria. But after confirming Jon had thyroid cancer, the doctor became convinced that thyroid cancer had spread to Jons left lung, resulting in the troublesome X-ray. Early onset means people develop disease at relatively young ages. As part of our mission to eliminate cancer, MD Anderson researchers conduct hundreds of clinical trials to test new treatments for both common and rare cancers. You dont know if theyre cancerous or not, so my motto is better safe than sorry. I tell Dr. Thomas anytime I see a new growth.. A hamartoma (pronounced HA-mar-TOH-muh) is a benign, or noncancerous, tumor-like growth. Yehia L, Eng C. PTEN Hamartoma Tumor Syndrome. Like the protein produced from the PTEN gene, killin probably acts as a tumor suppressor. Ask your healthcare provider if you should watch for specific signs and symptoms that may be cancer. If you have Cowden syndrome, youre at greater risk than the general population for certain cancers. The only known risk factor for Cowden syndrome is a family history of the condition. 2012 Jan described as "gain-of-function" because they appear to enhance the activity of the WWP1 protein. Pain on your right side is common, with many minor to serious causes. The information on this site should not be used as a substitute for professional medical care or advice. Theyll consider whether you have a family member with a history of tumors or PTEN mutations. About 40% of people or families with the disease have papules in their mouths, which can be located on the cheeks (buccal mucosa), tongue, gums, or lips. I told them, No, Ive come this far, Im going to push through.. [3], A homolog of FLCN called DBHD has been discovered in the common fruit fly, Drosophila melanogaster. [28] Further, DBHD regulates GSC maintenance downstream or in parallel of the JAK/STAT and Dpp signal-transduction pathways, which suggest that BHD regulates tumorigenesis by controlling stem cells in human {[29] Singh et al. The Hidden Risks of Sepsis: What You Need to Know. Disease Overview Summary Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare genetic disorder that is present at birth and is characterized by a large head size (macrocephaly), pigmented spots (maculae) on the penis and benign tumors and tumor-like growths in the intestine called hamartomas. Experts estimate that the condition affects fewer than 5,000 people in the United States. Another seven years would pass before Jon confronted another new cancer diagnosis: skin cancer. A biopsied trichilemmoma, meaning tissue samples studied under a microscope show signs of trichilemmoma. Talk with your doctor about ways to manage CS. [2][5] Dermatologic examination every 6-12 months due to risk of melanoma . Routine screening for patients diagnosed with Cowden syndrome should start immediately. People with a known family history of Cowden syndrome might consider surveillance as early as 10 years younger than the age of the relative's cancer diagnosis. BirtHoggDub syndrome can manifest similarly to other diseases, which must be ruled out when making a diagnosis. While intestinal polyps are common among Cowden patients who undergo Prenatal Before Birth Newborn Birth-4 weeks Infant 1-23 months Child 2-11 years Adolescent 12-18 years Adult 19-65 years Last reviewed by a Cleveland Clinic medical professional on 03/14/2023. You may develop cancer at an early age and you may have more than one kind of cancer at different times in your life. While hamartomas can be relatively common, the presence of different hamartomas in multiple locations is rare. Cowden syndrome is not very common. Knowing when symptoms began to appear can help medical providers find the correct diagnosis. It is not a substitute for professional medical advice, diagnosis or treatment. 2018 Aug;25(8):T121-T140. Though its function is not fully understood, it appears to be a tumor suppressor gene that restricts cell growth and division. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, In some cases, the genetic cause of CS is unknown. Your healthcare provider will diagnose you with PHTS if they find a mutation in the PTEN gene. Dermatologic examinations, neck ultrasounds and colonoscopies should be considered as well [1]. Coming to a Cleveland Clinic location?Hillcrest Cancer Center check-in changesCole Eye entrance closingVisitation and COVID-19 information, Notice of Intelligent Business Solutions data eventLearn more. Men, especially those with Cowden syndrome, can develop breast cancer, Jon explains. Many wart-like growths in your mouth (oral mucosal papillomatosis). Men and women with CS have about a three to 10 percent lifetime risk for developing thyroid cancer (compared to one percent for an average risk person). [5], People over 20 years of age with BHD have an increased risk of developing slow-growing kidney tumors (chromophobe renal carcinoma and renal oncocytoma, respectively), kidney cysts, and possibly tumors in other organs and tissues. People with Cowden syndrome often have many noncancerous, tumor-like growths. risks in individuals with germline PTEN mutations. According to experts, at least 40% of people with CS will experience at least one type of cancer. Many wart-like growths on your face (cutaneous facial papules). This includes early and frequent screenings for certain cancers. Its important to consult with a genetics professional so they can order PTEN gene testing. The goal is to catch it early, then force it to back down.. Theyll need frequent cancer screening tests that may detect cancer before it causes symptoms. It is considered to be under-diagnosed[3][6] because of the variability in its expression. Three of the major conditions, excluding macrocephaly. Lynch syndrome is a condition that increases the risk of many kinds of cancer. Cowden syndrome is a rare genetic (inherited) condition. People with Cowden syndrome often have many noncancerous, tumor-like growths. They may also have an increased risk of developing certain cancers. Is it common? No. Cowden syndrome is rare. Experts estimate it affects 1 in 200,000 people. Your genetic counselor can help you understand next steps. People with this condition may develop both benign (noncancerous) and malignant (cancerous) tumors. My collection is up to about 150,000 cards, but whos counting?, During the last dozen years, Jon has been diagnosed with thyroid, lung, skin and kidney cancers. But the Cowden mutation prevents PTEN from making this protein. I wasnt willing to give up.. With PHTS, a mutation of your PTEN gene causes uncontrolled cell growth. Rarely, Cowden syndrome and Cowden-like syndrome result from a change involving the KLLN gene. Genetic basis of Cowden syndrome and its implications for clinical practice and risk management. And every year, Jon undergoes full-body PET and CT scans to detect abnormal growths that may signal cancer. Thats an understandably frightening thought, even if you know there are screening tests that may find cancer even before you have symptoms. [17] Folliculin interacts with FNIP1 and FNIP2 (FLCN-interacting protein) to form a complex with AMP-activated protein kinase. Coming to a Cleveland Clinic location?Hillcrest Cancer Center check-in changesCole Eye entrance closingVisitation and COVID-19 information, Notice of Intelligent Business Solutions data eventLearn more. Syndrome Colonoscopies should be considered. The cysts can be detected by chest CT scan. Jon underwent a four-hour surgery to remove the invasive tumor, along with his entire thyroid gland. What are the odds of having two, unrelated, back-to-back cancers? Jon recalls thinking. I have one kind of cancer because of this condition. Annu It can cause susceptibility to kidney cancer, renal and pulmonary cysts, and noncancerous tumors of the hair follicles, called fibrofolliculomas. Cowden syndrome | University of Iowa Hospitals & Clinics Find out what helps constipation at home and when it's time to see a gastroenterologist. Kidney failure is slow and progressive and results in a reduced life expectancy of approximately 30-40 years. Mutations in a few other genes are each responsible for a very small percentage of cases of Cowden syndrome and Cowden-like syndrome. 2011 Jan 7;88(1):42-56. doi: Predisposition. The PTEN hamartoma tumor syndrome (PHTS) is a spectrum of disorders caused by mutations of the PTEN tumor suppressor gene in egg or sperm cells [19][6] Though nephrectomy is sometimes indicated, kidney tumors in cases of BHD are often removed without taking the whole kidney, in a partial nephrectomy. Seattle (WA): University No significant difference has been found in the symptoms experienced by families with an insertion at that location compared to those who have a deletion, but mutations in FLCN associated with BHD syndrome are heterogeneous, and are often nonsense mutations or frameshift mutations that cause early truncation of the protein product at the carboxy terminus. PTEN germline mutation? Kim Taylor is an editor with Healthgrades working to positively impact the lives of others through empathetic and meaningful content. This is done by placing a thin, needle-like probe through the skin in the back and into the tumor. The renal and pulmonary symptoms are managed preventatively: CT scans, ultrasounds, or MRIs of the kidneys are recommended regularly, and family members are advised not to smoke. Multiple Advertising on our site helps support our mission. The disease was discovered in 1977, but the connection with FLCN was not elucidated until 2002, after kidney cancer, collapsed lungs, and pulmonary cysts were all definitively connected to BHD. WebPeople with PTEN hamartoma tumor syndrome are at high risk for certain cancers. Your privacy is important to us. [6], Other tumors can include trichodiscomas (tumors of the hair disc, which may be identical to fibrofolliculomas), angiofibromas, and perifollicular fibromas. Excessive binding impairs PTEN's tumor suppressor activity, allowing cells to proliferate unchecked and, leading to the formation of tumors. Here are a few other common questions about CS. The process involves comparing your situation with major and minor criteria. [4] People with BHD were once thought to be at higher risk for colorectal polyps and neoplasms, but this has been disproven. A large number of tumors on the face can be associated with hyperseborrhea (abnormally elevated sebum production). [11], Thyroid nodules[2] have been associated with the BirtHoggDub phenotype, present in 65% of individuals and 90% of families with the syndrome. [7], Renal cystogenesis and tumorigenesis in BHD have been shown to be driven by the constitutive activation of TFEB. Facebook - National Cancer Institute Amemiya A, editors. PTEN Hamartoma Tumor Syndrome - Children's Hospital If you are ready to make an appointment, select a button on the right. These include those affecting the thyroid, breast, and endometrium. [2][8] Rarely, it is associated with clear cell renal cell carcinoma and papillary renal cell carcinoma. By day, hes an accountant at a property management company. WebNCI's Dictionary of Cancer Terms provides easy-to-understand definitions for words and phrases related to cancer and medicine. Mutations in the FLCN gene may interfere with the ability of folliculin to restrain cell growth and division, leading to the formation of noncancerous and cancerous tumors. Genetic tests show I carry a mutated gene that causes Cowden syndrome. In general, healthcare providers may suspect Cowden syndrome if you have a combination of specific symptoms. Any of these conditions that occurs in a family can indicate a diagnosis of BirtHoggDub syndrome, though it is only confirmed by a genetic test for a mutation in the FLCN gene, which codes for the protein folliculin. [14] FLCN is highly conserved in vertebratesit is very similar between many vertebrate species. Hereditary bilateral, multifocal kidney tumors similar to those seen in BHD can occur with von HippelLindau disease (clear cell renal cell carcinoma), hereditary papillary renal cancer (papillary renal cell carcinoma), and hereditary leiomyomatosis and renal cell cancer syndrome. It sometimes has tentacles that can grow into surrounding fat, muscle and even bone. Unlike benign growths that stay in one place, cancerous tumors can spread throughout your body (metastasize). Change the lives of cancer patients by giving your time and talent. 2019 Feb 1;129(2):452-464. doi: A PTEN mutation can cause cells to grow out of control and form tumors. Submission of this form is subject to Healthgrades, Help Millions of people find the right doctor and care they need, Get immediate care and visit with providers from the comfort of your home, or anywhere, Urgent care centers can be faster and cheaper for situations that are not life threatening, Doctors and patients discuss the latest medical treatments and health tips, Search prescription drugs for why theyre used, side effects and more, Back and Neck Surgery (Except Spinal Fusion), View All Symptoms and Conditions Articles, https://medlineplus.gov/genetics/condition/cowden-syndrome/, https://rarediseases.info.nih.gov/diseases/6202/cowden-syndrome, https://www.ncbi.nlm.nih.gov/books/NBK525984/, https://dermnetnz.org/topics/cowden-disease, https://www.frontiersin.org/articles/10.3389/fmed.2021.658842/full, macrocephaly, or a larger-than-usual head, irregularities in the blood or lymphatic vessels. The lifetime risk of cancer in individuals with LFS is =70% for men and =90% for women. This is a privacy-protected site that provides up-to-date information for individuals interested in the latest scientific news, trials, and treatments related to rare lung diseases. There isnt a cure for PHTS. Rev Med. People with Bannayan-Riley-Ruvalcaba syndrome also develop hamartomas and other noncancerous tumors. Need a Telehealth Visit? Endometrial, thyroid, and breast cancers occur more often in people with CS. Although you have one working copy, the mutated PTEN gene causes problems associated with PHTS. Genetic testing can be useful to confirm the clinical diagnosis and to provide a means of determining other at-risk individuals in a family even if they have not yet developed BHD symptoms. Around 24% of people with the disease have at least one spontaneous pneumothorax, 30 times the occurrence in unaffected people. 2008 Aug;83(2):261-8. [2] The BHD Foundation supports research into the syndrome and holds regular symposia in BHD and related disorders for researchers, clinicians, and family members. metabolic syndromes: PTEN-opathies and precision medicine. While PHTS is most commonly associated with benign tumors called hamartomas, out-of-control cell growth can also cause malignant tumors to form. For the next eight months, his life revolved around the clinical trial. Because chronic constipation can cause pain and bloating, it's understandable to seek quick constipation relief. Cowden syndrome is rare. Learn more about pain on the left side. http://www.ncbi.nlm.nih.gov/books/NBK1488/. Individual with BirtHoggDub syndrome, showing the characteristic facial fibrofolliculomas. If you have the mutation, your family members should also receive testing. Cleveland Clinic Cancer Center provides world-class care to patients with cancer and is at the forefront of new and emerging clinical, translational and basic cancer research. Get useful, helpful and relevant health + wellness information. These tumors are usually benign, but they can become cancerous. These lesions are usually found in the armpit, on the eyelids, and in folds of skin. Cowden syndrome is a genetic disorder characterized by multiple noncancerous, tumor-like growths called hamartomas and an increased risk of developing certain cancers. Ask your healthcare provider about any symptoms that you should be on the lookout for. Your doctor can begin or change your treatment to help you manage depression. Youll need to receive genetic testing to see if you have a mutation, which will involve a blood test. [5] Men and women are equally affected, and there is It can cause susceptibility to kidney cancer, renal and pulmonary cysts, and Homozygotes die in utero. Now all the pieces fit together. No. If Id known the extent of your disease, the doctor told Jon, I would have sent you to MD Anderson the minute you walked through my door. For example, if you have early-onset breast cancer thats diagnosed after the cancer spreads, your life expectancy may be shorter than someone whose cancer was diagnosed and treated early on. People with Cowden syndrome are also more likely to develop more than one cancer during their lifetimes compared to the general population. Id been trying to remain positive until then, Jon says. [5], Birt, Hogg, and Dub examined a family with a hereditary thyroid cancer, and discovered that many of the members had fibrofolliculomas, trichodiscomas, and acrochordons, which became defined as the classical symptoms of the eponymous disease. Catching and treating cancer early is one of the best ways to improve your prognosis. Youll need lifelong cancer screening to manage the risk. With PHTS, the PTEN gene doesnt work correctly. Instead, treatment will address your symptoms. This means that some people with the clinical diagnosis have mutations that are not detectable by current technology, or that mutations in another currently unknown gene could be responsible for a minority of cases. Peutz-Jeghers syndrome (PJS) is an inherited condition that is associated with an increased risk of growths along the lining of the gastrointestinal tract (called hamartomatous polyps) and certain types of cancer. Copyright 2023 Healthgrades Marketplace, LLC, Patent US Nos. The symptoms seen in each family are unique, and can include any combination of the three symptoms. Your gift will help support our mission to end cancer and make a difference in the lives of our patients. Cowden Syndrome | Cancer.Net [3] When a wild-type FLCN gene was added, the phenotype was rescued. The major criteria include: To receive a diagnosis of Cowden syndrome, a person must have two of the major criteria. One of these criteria must be either Lhermitte-Duclos disease or macrocephaly. A person can also receive a diagnosis of CS if they have one major and three minor criteria. Genetic testing confirmed their hunch. This is why cancer screenings are so important. These genes have different functions in the body: These genetic mutations may be passed down from a parent or occur spontaneously during a persons life. Although there arent standard guidelines for monitoring people with BRRS, your healthcare provider may recommend similar screening as with Cowden syndrome. The results came back as inconclusive. [3] Hornstein-Knickenberg syndrome is a now-deprecated name for the inherited fibrofolliculomas inherent to BHD. Li-Fraumeni syndrome 1 Clin Cancer Res. [2][5] Kidney cancer associated with BHD have been diagnosed in people at ages as young as 20. They had a similar pattern of tumorigenesis to human BHD in that the skin lesions were heterozygous for the FLCN mutation, and the renal tumors were likely caused by loss of heterozygosity. 9500 Euclid Avenue, Cleveland, Ohio 44195 |, Important Updates + Notice of Vendor Data Event. Staying one step ahead of cancer and Cowden syndrome. Most individuals with Rotor syndrome are born to consanguineous couples, and its diagnosis may coincidently identify consanguinity. Cowden syndrome causes lots of lumps and bumps, Jon says. While these growths are benign, people with the condition are at increased risk for certain types of cancer. [9] Though the types of tumors typically associated with BHD are considered less aggressive, cases of advanced or metastatic kidney cancer have been observed in people with the syndrome. WebThe lifetime risk for developing specific cancers related to PHTS includes: Breast cancer (females only) up to 85 percent, with an average age of diagnosis between 35 and 45 2019 Aug 21. Some people do not meet the strict criteria for a clinical diagnosis of Cowden syndrome, but they have some of the characteristic features of the condition, particularly the cancers. Therefore, people with CS will also need regular screenings to monitor for the development of additional malignancies. Language links are at the top of the page across from the title. BirtHoggDub syndrome (BHD), also HornsteinBirtHoggDub syndrome, HornsteinKnickenberg syndrome, and fibrofolliculomas with trichodiscomas and acrochordons[1] is a human, adult onset, autosomal dominant genetic disorder caused by the FLCN gene. This page was last edited on 18 April 2023, at 07:35. Blumenthal GM, Dennis PA. PTEN hamartoma tumor syndromes. Other cancers may include melanoma, colorectal cancer, and kidney cancer. of Washington, Seattle; 1993-2023. Syndrome It turns out thyroid cancer had not spread to his lung, after all. The support I get at MD Anderson is phenomenal.. Cells can grow out of control when theres a mutation, causing hamartomas. When overgrowth bumps into cancer: the PTEN-opathies. Singh SR, Zhen W, Zheng Z, Wang H, Oh SW, Liu W, Zbar B, Schmidt LS, Hou SX. Versions of FLCN have been found in other animals, including fruit flies, German Shepherds, rats, and mice. Cowden syndrome (CS), due to germline mutations of the PTEN tumor-suppressor gene, is an often overlooked cancer predisposition syndrome associated with an increased risk of breast, thyroid, and endometrial cancers, as well as benign manifestations. BHD-associated tumorigenesis differs between the kidney, where loss of FLCN heterozygosity is responsible for cancers, and the skin, where FLCN is strongly expressed in heterozygotes. Its a condition that requires close monitoring news that most people find frustrating. With nothing to lose, Jon opted for the clinical trial. If you have PHTS, youre at increased risk of developing hamartomas and other benign growths. [2] These tumors often occur in both kidneys and in multiple locations in each kidney. The National Comprehensive Cancer Network and Cleveland Clinic have established genetic testing guidelines for Cowden syndrome that are updated frequently based on new research. [5][8] People over 40 years old and men are more likely to develop kidney tumors, which are diagnosed at a median age of 48. probands. That means they inherit one copy of the gene from each biological parent and have a 50% chance of inheriting the mutated gene. [6] FLCN has been found to be overexpressed in fibrofolliculoma tissue, and to have very low levels of expression in affected kidneys. doi: 10.1016/j.ajhg.2008.07.011. Eventually, the cells form growths like hamartomas or noncancerous tumors. People with Cowden syndrome often have many noncancerous, tumor-like growths and skin issues. Advertising on our site helps support our mission. Recent studies suggest that folliculin accomplishes this function through its involvement with cellular metabolism, possibly through modulation of the mTOR (mammalian target of rapamycin) pathway and/or oxidative phosphorylation in mitochondria. During this process, the WWP1 protein attaches (binds) to the PTEN protein, which impairs PTEN's function. Mutations in the PTEN gene prevent the PTEN protein from regulating cell proliferation effectively, leading to uncontrolled cell division and the formation of hamartomas and cancerous tumors. This is a benign growth of blood vessels underneath the skin where blood vessels are normally found. WebNCCN Clinical Practice Guidelines in Oncology Cowden syndrome treatment options survival rates, surgery success factors, Cowden syndrome cancer life expectancy treating metastatic Cowden syndrome cancer death rates natural remedies for Cowden syndrome chemotherapy radiotherapy success rates Cowden syndrome ancer best hospitals and If you have Cowden syndrome, ask your genetic counselor if your family members should have genetic testing. Use of this website and any information contained herein is governed by the Healthgrades User Agreement. Other names for CS include Cowden disease and multiple hamartoma syndrome. These cancers generally occur in adults, not children, with the condition. Thomas removed the lump and diagnosed it as a dermatofibrosarcomaprotuberans, a rare cancer that develops in the deep layers of skin. mtDNA tRNA mutation. WebSymptoms of the disease most commonly manifest in the third and fourth decades of life, although it may onset at any age. WebNoonan syndrome with multiple lentigines (NSML) is a very rare inherited disorder. The resulting image revealed a curious shadow on his lower left lung. Recent 2020 Oct 20;29(R2):R150-R157. [14], People with BHD are born with one mutated copy of the FLCN gene in each cell. Many hamartomas in your gastrointestinal (GI) tract. They are differentiated with examination of the tumors' histology. Hum Mol Genet. 7,752,060 and 8,719,052. After consulting Jons medical team, urologist Christopher Wood, M.D., used radiofrequency ablation to destroy the tumor with heat. However, following cancer screening guidelines helps prevent cancer or at least catch cancer at the earliest possible treatable stage. Cowden syndrome (CS) is an inherited condition that causes multiple hamartomas, or noncancerous growths. [5], The cutaneous manifestations of BHD were originally described as fibrofolliculomas (abnormal growths of a hair follicle), trichodiscomas (hamartomatous lesions with a hair follicle at the periphery, often found on the face), and acrochordons (skin tags). syndrome They may also have an increased risk of developing certain cancers. Cleveland Clinic is a non-profit academic medical center. I needed another option, and I needed it fast, he says. Based on these similarities, researchers have proposed that Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome represent a spectrum of overlapping features known as PTEN hamartoma tumor syndrome (named for the genetic cause of the conditions) instead of two distinct conditions. Birt-Hogg-Dub Syndrome patients, families, and caregivers are encouraged to join the NIH Rare Lung Diseases Consortium Contact Registry. Differentiated thyroid cancer, with over-representation of. We want them to see us, he says, not just read about us in a book.. Cowden syndrome is a rare genetic (inherited) condition. This enzyme also tells a cell when its time to die (apoptosis) to make space for new, healthy cells. [2][5] The most common mutation in this region is the insertion or deletion of a cytosine residue, found in 53% of BHD-affected families. It had grown beyond the thyroid and travelled down my neck and into my right shoulder.. Still, careful screening can potentially save or prolong your life if you develop cancer. These answers were reviewed by William C. Lloyd III, M.D. Cowden syndrome, especially those found to have a germline PTEN mutation or PTEN hamartoma tumor syndrome (PHTS), is linked to many kinds of cancer. 2023 The University of Texas MD Anderson [8][4] Folliculin's participation in the mTOR pathway may explain the similarity in phenotype between BHD syndrome, Cowden syndrome, tuberous sclerosis, and PeutzJeghers syndrome. Almost everyone with Cowden syndrome develops hamartomas. [6] Smokers with BirtHoggDub have more severe pulmonary symptoms than non-smokers. In a small set of people with Cowden syndrome, researchers found other mutated genes, including PIK3CA/AKT1, SDHB-D, KLLN and SEC23B. Policy. Your outlook depends on many factors, including your symptoms and overall health. To diagnose Cowden syndrome, doctors will look for symptoms that match a specific set of criteria. Third Party materials included herein protected under copyright law. Pigmented macule (darker spot) on the glans penis (head). Doctors once viewed Cowden syndrome and BRRS as separate conditions. 2010 Dec 22;304(24):2724-31. doi: Anesthesiologist Vivian Porche, M.D., was by Jons side, as always.
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