Thursday, January 25, 2024

IMAGE GUIDED UTERINE FIBROID TREATMENT

By Dr. Robert L. Bard

Historically, the detection of pelvic tumors is linked to the current state of diagnostic technology.  Critical is the differentiation of benign pathology of the uterine/ovarian complex from malignancies. [1]

According to the Society for Women's Health Research, Over 20,000 women will be diagnosed with ovarian cancer this year in the United States and women have a 92% chance of surviving for five years post-diagnosis. However, more than three-fourths of women are not diagnosed until later stages." [2] Abnormal ovaries are often benign simple cysts, however the complex cysts are classifiable with the new ultrasound scoring system as to how suspicious they may be. The same way we detect prostate tumors by routine yearly ultrasound screening in high risk patients, we could save many lives because sometimes the first sign of ovarian cancer is a gland in the neck that pops up, a mass under the arm or jaundice because the liver is filled with metastatic tumor.

EVOLUTION IN DIAGNOSTICS
In 1980, I gave a talk for the American College of Obstetricians at Memorial Sloan Kettering Cancer Center where we presented the use of real-time imaging for the instantaneous documentation of the fetal heart beat by intrauterine cardiac sonogram to detect fetal demise instead of waiting 2 weeks to see if the fetus was growing. We asserted a similar use of ultrasound technology to monitor abnormal ovarian cysts as small as two centimeters (2-3 cm is about the size of a normal ovary). Early cancers could not be felt, but are imaged with ultrasound as the technology advanced. With today's high resolution and 3D imaging, (including endo probes with elastography for the uterus and ovaries) recent upgrades offer even better capabilities to conduct regular screening in real time called a noninvasive “virtual biopsy”. Ultrasound technology is now able to see three millimeter cancers in the glands and Doppler with Elastography shows activity and fibrosis.

Thanks to modern endo probes that can scan deeper organs, we study micrometastatic nodules throughout the body in superficial areas like lymph nodes and in deeper areas like the ovary. The endo probe resolution is 5x greater than the MRI or the CT scanner.  It is able to see not only the size, location and irregularity in the fibroid mass  it quantitively measures the blood flow, which gives you a number of the abnormal vessels supporting tissue growth.  This same group of imaging devices validates treatment effect since fewer feeding blood vessels implies less aggression. Important distinction between size and activity is that sometimes masses outgrow their blood supply and fill with fluid as they die-cystic internal necrosis of fibroids is common and fortunately diagnosed non invasively.

TREATMENT OPTIONS
While most fibroids involute with patient aging, a small nodule blocking the ureter produces kidney damage. Standard ultrasound testing routinely checks for hydronephrosis of the renal organs as a dilated kidney is a call for surgery.   From our early work with prostate embolization we have adapted uterine artery embolization so that it is acceptable as minimally invasive treatment for women. [3]  Recent adoption of PEMF and NIR Laser (red light treatment) has non invasively provided pain relief and diminished feeding blood vessels with fibroid size and symptom reduction. [4]

(1)-Hassani/Bard Gynecologic Ultrasound   SpringerHeidelberg 1978  (2)-"Ovarian Cancer: Outdated Diagnostics for a Deadly Disease" Society for Women's Health Research 2020. https://swhr.org/ovarian-cancer-outdated-diagnostics-for-a-deadly-disease/ (3)-Awad M etal PEMF in Primary Dysmenorrhea  2020 MJCU 88;2165-2175 (4)-Thabet A etal High intensity Laser vs PEMF in Dysmenorrhea  J Phys Ther Sci 2017 10:1742-1748




Uterine Fibroids: New Approaches to an Underdiagnosed Health Issue

Written and produced by: Dr. Roberta Kline for the Women's Health Digest / Balance & Longevity educational seminar series.


FIBROIDS are the most common tumor of the female pelvis and are the number one reason for hysterectomy. While prevalence estimates vary widely, in part due to systemic underdiagnosis, they range worldwide from 4-70%. Globally, Black women have the highest rate, often 3x that of White women. In addition, Black women are more likely to have more severe symptoms and undergo hysterectomy at an earlier age, adding the burden of lost fertility for these women.  The economic burden is also enormous. It is estimated that fibroids contribute to up to $34 billion in direct and indirect healthcare costs every year. [1] 


NEED MORE ATTENTION TO THIS COMMON WOMEN'S DISORDER
For many decades, the understanding of causes and effective treatments has progressed slowly. With the acceleration of technology enabling molecular and genetic expression research and advanced non-invasive treatment, that is starting to change.


WHAT ARE FIBROIDS?

Fibroids are classified based on where they occur in the uterus. 

Uterine fibroids, also known as uterine leiomyomas, are benign growths within the uterine wall that are made up of the same smooth muscle tissue as normal myometrium. But for reasons that are still not fully understood, they form into 3-dimensional spheres rather than the linear, elongated pattern of normal tissue. 

Up to half of all women with fibroids are symptomatic. Although fibroids are typically benign, they can cause significant health effects. The most common symptoms are painful periods and heavy menstrual bleeding. Pelvic pressure and pain during intercourse are not uncommon. Depending on their size and location, fibroids can press on nerves and cause pain; obstruct nearby organs including ureters, bladder, and intestines. Fibroids can also cause reproductive problems including infertility, recurrent pregnancy loss, and other complications of pregnancy.

WHAT CAUSES FIBROIDS?
Fibroids occur after the onset of menses, and typically shrink after menopause, so clearly estrogen plays a role. Other standard risk factors for fibroids include ethnicity, age, family history, time since last birth, hypertension and diet. Vitamin D deficiency in particular, has been consistently linked with fibroids. [2] 

Genetics clearly plays a role. Having a family member with fibroids increases the risk – and if it’s your mother, you are 3x more likely to develop them too. A hereditary mutation in the FH gene (fumarate hydratase) that causes renal cell carcinoma (HRCC) is now being linked to the development of fibroids, especially at younger ages. [3]

GENETIC EXPRESSION PROVIDES NEW CLUES
Emerging research is revealing the role of underlying molecular pathways and the genes and epigenetics that regulate them in fibroid development and growth. These include estrogen metabolism, inflammation, oxidative stress, insulin and glucose regulation, nutrient processing, telomere length and DNA repair. [4] Interestingly, but perhaps not surprisingly, there is significant overlap with other health conditions including endometriosis, as well as many chronic diseases of aging. 

One of the surprising findings of gene expression research is that almost half of all fibroids have chromosomal abnormalities. [5] Despite this, progression to the cancerous form (leiomyosarcoma) is rare – less than 1%. As researchers look deeper, it appears that it is not the genetic changes within the fibroid that have the most influence on the development of fibroids and the progression to cancer. Rather, it is the microenvironment, or the cellular health around the fibroid, that has this role. [6] 

Therefore, it may be that improving the microenvironment in which these fibroids develop could be effective early intervention strategies. Noninvasive therapies that can reduce inflammation and oxidative stress including diet, medication, PEMF, and photobiomodulation may be new opportunities for early intervention for fibroids as well. [7] 

While genetic expression research on fibroids is shedding light on some of the genomic and genetic alterations that contribute to discrepancies between women of different ethnicities, it is clear that these aren’t the only drivers. [8] As with many other health conditions, where a woman lives and works plays an outsized role.

Environmental toxins including endocrine disruptors and air pollution, stress, and socioeconomic status all have been shown to be connected with higher rates of fibroids. These are likely related to bidirectional effects of epigenetic alterations, access to care and bias within the healthcare system, as well as other factors still to be identified. [9] 

DIAGNOSIS
Ultrasound, and preferably transvaginal ultrasound, is the best initial diagnostic imaging procedure for detection of fibroids. 3D ultrasound can provide even more information than the standard 2D. With the addition of hysterosonography, or introduction of fluid into the uterine cavity under ultrasound guidance, impingement on the uterine cavity can be clearly demonstrated.

 


Image source: Freytag, D., Günther, V., Maass, N., & Alkatout, I. (2021). Uterine Fibroids and Infertility. Diagnostics, 11(8). https://doi.org/10.3390/diagnostics11081455 [OPEN ACCESS}


TREATMENT OPTIONS
Despite many women already having symptoms by age 25, most aren’t diagnosed until their 30’s or 40’s. By that time, the fibroids are typically larger and more problematic. 

Current treatment options include medication to address symptoms – accounting for up to 70% of women at some point. Surgery to remove the fibroids (myomectomy) or the entire uterus along with the fibroids (hysterectomy) is the oldest and most invasive option. Newer techniques such as laparoscopy have improved these surgical approaches. Within the past couple of decades uterine artery embolization (UAE) has offered a less invasive option, and newer noninvasive approaches are now emerging that utilize radiofrequency ablation (RFA), and high intensity focused ultrasound (HIFU). [2] 

Here, too, treatment options are impacted by ethnicity and socioeconomic factors. "Despite minimally invasive options, Black women continue to dominate the percentages of women having hysterectomies for benign disease," Marsh says. "We need to understand why." [1]

One of the main limitations for these newer techniques is that they are more effective on smaller fibroids. Since fibroids tend to grow over time, it would seem a benefit to have earlier diagnosis so that women have better treatment options. In fact, a recent study in Ghana showed that routine ultrasounds at yearly clinic visits increased the rate of diagnosis, and at younger ages. [10] 

THE FUTURE OF FIBROIDS
While more definitive research specific to fibroids is needed, we already have noninvasive tools and strategies to address some of the most common underlying contributors. Let’s advance the science with research as we simultaneously give women more options to proactively improve their health.


REFERENCES

(1) Marsh, E. E., Al-Hendy, A., Kappus, D., et al. (2018). Burden, Prevalence, and Treatment of Uterine Fibroids: A Survey of U.S. Women. Journal of Women's Health, 27(11), 1359-1367. https://doi.org/10.1089/jwh.2018.7076  (2) Freytag, D., Günther, V., Maass, N., & Alkatout, I. (2021). Uterine Fibroids and Infertility. Diagnostics, 11(8). https://doi.org/10.3390/diagnostics11081455  (3) Lu, E., Hatchell, K. E., Nielsen, S. M., et al. (2022). Fumarate hydratase variant prevalence and manifestations among individuals receiving germline testing. Cancer, 128(4), 675-684. https://doi.org/10.1002/cncr.33997  (4) Välimäki N, Kuisma H, Oskari AP et al. (2018) Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability eLife 7:e37110.  (5) Kubínová K, Mára M, Horák P, et al. Genetic factors in etiology of uterine fibroids. Ceska Gynekol. 2012 Feb;77(1):58-60. Czech. PMID: 22536642.  (6) Bharambe, B. M., Deshpande, K. A., Surase, S. G., & Ajmera, A. P. (2014). Malignant Transformation of Leiomyoma of Uterus to Leiomyosarcoma with Metastasis to Ovary. Journal of Obstetrics and Gynaecology of India, 64(1), 68-69. https://doi.org/10.1007/s13224-012-0202-4  (7) Tinelli, A., Vinciguerra, M., Malvasi, A., et al. (2021). Uterine Fibroids and Diet. International Journal of Environmental Research and Public Health, 18(3), 1066. https://doi.org/10.3390/ijerph18031066 (8) Edwards, T. L., Giri, A., Hellwege, J. N., et al. (2019). A Trans-Ethnic Genome-Wide Association Study of Uterine Fibroids. Frontiers in Genetics, 10. https://doi.org/10.3389/fgene.2019.00511  (9) Cheng, L., Li, H., Gong, Q., et al. (2022). Global, regional, and national burden of uterine fibroids in the last 30 years: Estimates from the 1990 to 2019 Global Burden of Disease Study. Frontiers in Medicine, 9, 1003605. https://doi.org/10.3389/fmed.2022.1003605  (10) Mesi Edzie, E. K., Dzefi-Tettey, K., Brakohiapa, E. K., et al. (2023). Age of first diagnosis and incidence rate of uterine fibroids in Ghana. A retrospective cohort study. PLOS ONE, 18(3), e0283201. https://doi.org/10.1371/journal.pone.0283201


ABOUT THE AUTHOR

ROBERTA KLINE, MD (Educational Dir. /Women's Diagnostic Group) is a board-certified ObGyn physician, Integrative Personalized Medicine expert, consultant, author, and educator whose mission is to change how we approach health and deliver healthcare. She helped to create the Integrative & Functional Medicine program for a family practice residency, has consulted with Sodexo to implement the first personalized nutrition menu for healthcare facilities, and serves as Education Director for several organizations including the Women’s Diagnostic Health Network, Mommies on a Mission. Learn more at https://robertaklinemd.com/




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LINKING DENSE BREAST WITH BREAST CANCER
We have known for a very long time that there is an increased risk of breast cancer for women who have dense breasts. Until recently, the research has been lagging in terms of what's the molecular mechanism, why do dense breasts present an increased risk of breast cancer? Without this knowledge, we can’t address the root causes, and are left with a lot of trial and error based on incomplete understanding. It's very encouraging to know that currently there are 124 clinical trials ongoing looking at dense breasts and the relationship with breast cancer, anywhere from improved diagnostics, to treatment, to prevention, and, what’s close to my heart, to understanding the molecular mechanisms - what's happening at the cell level, at the genetic level that is causing different women to have an elevated risk of breast cancer. (see feature)



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