Radiological Diagnosis of Ovarian Cancer - Coursework Example

RADIOLOGICAL DIAGNOSIS OF OVARIAN CANCER JOHN DOE SOME AUGUST 4, INTRODUCTION There is nothing worse to a patient than being told they have cancer. Early detection and diagnosis of said disease is essential to early treatment and curative procedures. In women, ovarian cancer is the 5th leading cause of all types of cancer in both the UK and USA. In the UK, we find that it is the second most common cause of cancer overall second only to lung cancer, which is linked closely to smoking. In diagnosing the disease, we must be certain of what we believe to be true regarding the patients health and what is found diagnostically. Radiological techniques have improved diagnoses many-fold and therefore are used much more frequently and effectively versus exploratory surgeries, which were the gold standard of diagnosing cancer only a few decades ago. Today, we find cancerous lesions without so much as scratching a patient with Magnetic Resonance Imaging (MRI), Computerized Tomography (CT), and UltraSound imaging (US). We will look at the techniques used, how effective they are at finding many types of the cancer and what the treatments to be determined are once a full diagnoses is given. A brief examination of the pathophysiology and the epidemiology will enhance our understanding and give a full picture of the process of Ovarian Cancer. Pathophysiology and Epidemiology of those affected by Ovarian Cancer Ovarian cancer is unique only to women, but the strata of women affected by the several types of ovarian cancer is also fairly unique as well. In the UK, Table 1 taken from the UK Office for National Statistics (Cancer Statistics: Registrations Series MB1), we find that the rate of ovarian cancer incidence by an Age-Standardised rate is 16.2 per 100,000 women in the UK. Comparatively the US has a dramatically higher rate of 33 per 100,000 while Asian and African rates are well below 5 per 100,000. Only if they move to western Europe or the USA does the risk of ovarian cancer increase among this population. The major link to this variant seems to be related to dietary considerations among other things, however it should be noted that genetics of this disease are very strong which will be why the European and US populations remain statistically more likely to develop this cancer. Further, it should be noted, that if a family member has ovarian cancer or has survived it, the risk for it occurring later in the family is 10% compared with 1.6% in the general population.(Bankhead et al, 2008) Ironically, men who have women in the family with ovarian cancer have increased risk of prostate cancer and should be screened properly by their physician. The cancer itself has a predominant affect on women who are post-menopausal. Table 2 shows the ages affected by ovarian cancer and that the increase in incidence occurs at or around the age of 45-49 when the rate jumps 60% from 11.4 for those 40-44 to over 19. This jump occurs at or around the age of menopause, which suggests that a genetic insult may occur due to a decrease in the amount of hormones being produced by a formerly fertile female. Further similar increases are found as the female population ages. Table 1 Table 2 The pathophysiology of the disease was mentioned earlier concerning BRCA-1. This particular gene is responsible for an increased risk causing 50% of hereditary breast cancers and 80% of hereditary ovarian cancers. It is autosomal dominant in nature and is not located on the X chromosome. BRCA1, located on chromosome 17q12-21, and BRCA2, on 13q12-13 are identified as the loci with associations to further processes which affect genomic integrity and cause a single cell to become cancerous given the proper stimuli. (Green 2011) Genetically, BRCA-1 gene product is involved in DNA repair and transcription regulation. It is said to act as a "caretaker gene" preventing DNA damage from leading to cancer. It complexes with RAD51, a protein involved in the repair of dsDNA breaks. When functioning properly, of course, there are many times a DNA strand becomes damaged, for instance an error such as a missense or deletion error occurs, the BRCA-1 gene is able to produce a protein that repairs it. When the gene itself is damaged, then the protein that is ultimately produced is either never made or is truncated. This truncation leads to improper folding of the protein and causes signaling within the cell to cease which can lead to run away mitosis and the first formation of cancer. (Cheng 2008) When presenting for analysis, 70% of all patients with ovarian cancer have metastasis outside the true pelvis. (Kasper et al 2008) This is presumptive because unlike endometrial and uterine cancer there is no bleeding and chronic pain associated with the disease. Acute symptoms like pain and hemorrhage are indicative mainly of torsion of the ovaries and requires immediate surgical intervention. Differing studies and texts indicate that some diffuse symptoms may exist but that they are incorrectly diagnosed as GI symptoms or some other generalized abdominal pain not associated with ovarian disease. (Goff 2004) The presentation of bloating, nausea, diarrhea, and dull abdominal pain are so vague as to lead to a lack of diagnostic discovery unless there is a clear history of familial cancer syndromes. The most common types of ovarian cancer are epithelial in origin and are subdivided into 3 groups. Benign tumors comprise 50% of all epithelial tumors, malignant are approximately 33%, and so-called tumors of Low Malignant Potential cover ~15%. (Kasper et al. 2008) The diagnosing of these patients follows a routine course with a little variation, but in general we find that most patients will have a simple US, either abdominal or trans-vaginal is effective for comparative studies along with a CT scan or MRI depending on physician preference. A blood serum CA-125 establishes a protein marker for the tumor type and is diagnostically accurate for ovarian cancer involvement in post-menopausal women. (Woodward 2010) It is not effective in pre-menopausal females however. After non-invasive procedures have been exhausted, the gold standard still remains surgical and the method of choice is the laparotomy. It is this method which gives accurate staging of the cancer and a first hand look at any potential sites of metastasis and invasion. It also allows extraction of the ovary or ovaries in question and to determine if the epithelial capsule of the organ has been breached and contacted other organs. Diagnostics and Radiological Findings In ovarian cancer, the MRI is largely ineffective because of its methodology of looking at tissues. MRI scans magnets instead of x-rays. The energy from radio waves is absorbed and discharged in a pattern formed by the type of tissue. A computer translates the pattern into a detailed image. This produces cross sectional slices of the body like a CT scanner horizontally and vertically. MRI scans are not used often to look for ovarian cancer. (Ryerson 2004) The main drawback to MRI scans is the confining nature of the traditional “donut” and for patients with claustrophobia, it can be prohibitive unless some generalized anxiety medication is used. Open MRI versions lack the detail and can lack the sensitivity and specificity of the closed type. MRIs and CT scans are both used to do initial diagnosing studies in the formative stages of patient care for suspected ovarian cancer. However, the use of CT and MRI are not predictive for staging. That remains solely the perview of laproscopic domains as seeding of peritoneal deposits cannot be accurately seen on MRI/CT or US due to the density of tissues in that area of the body. Decreased sensitivity and specificity are seen as well in recurrent disease, when small deposits are best visualised directly, instead of with scanning techniques. (Jafru and Liddicoat 2010) The MRI is, however, very good in giving visualised access without surgical intervention to identifying malignant ovarian tumors. Identifying markers when looking at MRI scans include irregular or solid components to a cystic mass, thick septations, as well as evidence of peritoneal, lymphatic, or hematogenous spread. Local invasion is identified via both CT and MRI resources. (Graphic 2 and 3 shows a pelvic mass in one female with both a T1 Axial view and a T2 sagittal view.) As the author of Imaging Techniques for the Diagnosis of Ovarian Cancers: Magnetic Resonance Imaging states at the end of his article “it is used for problem solving in the assessment of pelvic masses.“ A T1 Axial view of a pelvic mass A T2 Sagittal view of same patient Current thought is that CT scans and MRIs are roughly equivalent when doing pre-surgical assessment of a patient with clinically suspected ovarian masses.(Semelka, 1993) Further the presentation of advanced cancer is usually accompanied by a CT scan of the pelvic region followed by the chest as well to rule out distant metastasis. In very advanced cases, as stated previously laproscopic sampling of the tissues and area are the only efficacious methods currently in practice. However, CT maintains many advantages in non-invasive diagnosing of ovarian cancers. CT holds a unique ability to detect metastasis in localised lymph nodes and involvement of the omentum, whether or not the patient has ascites, and if there is subsequent involvement of the liver. (Jafru and Liddicoat , 2011) A major negative is the amount of radiation that the patient is exposed to during the procedure. While CT accounts for 4% of all radiological investigations, it accounts for approximately 40% of all radiation in medical diagnostics. (Jafru and Liddicoat , 2011) CT scans can assist in pre-operative diagnosing as its clarity and specificity can give an amount of surgical cyto-reduction required for the surgeon to undertake. This effort will aid both the surgeon and the operating room staff in determining the level of care needed pre-opeartively, operatively, and post-operatively. This is critical in limiting the possibility of recurrence and post-operative infections as well. Further, in cases where the patient is advised and does in fact undergo chemotherapy prior to surgery, the CT scan can detect a reduction in the size of the primary tumor where advanced ovarian cancer is detected. It is widely available at most NHS hospitals and while the radiological factors play a role, in advanced cancers such as this, the risk-benefit of exposure is irrelevant. Graphic 4 at left, shows a CT scan of a patient with advanced ovarian disease. There is metastatic ovarian cancer at presentation, with pelvic mass and omental cake and liver metastases. The area taken in this scan is marked by areas of dark and light density. The area to the right of the screen image is a large ovarian mass. The advantage in the UK is that the CT is readily available, is inexpensive to use, and is proven as a diagnostic resource with high sensitivity. Ultrasound (US), on the other hand, contains no radiation and is also inexpensive to use. US has a high diagnostic accuracy at around 90%. (Yazbek, 2008) It is also able to differentiate in some cases, according to Jafru and Liddicoat (2010), between benign and malignant ovarian masses or cysts. In some cases, US is very sensitive for the detection of ascites but because of the image projected to the screen and radiologist it is not considered very sensitive for the detection of omental or peritoneal metastases. (Yazbek et al, 2008) One major advantage of US is that it can be performed both abdominally and trans-vaginally. The ability to use Real-time transvaginal ultrasound scan (TVS) enables the clinician to use higher frequencies and visualise the organ region closely without invasive procedures. TVS has better spatial resolution as well because it eliminates imaging through the abdominal wall and places the transducer closer to the target organ (ovaries). It reduces the problem of acoustic shadowing from bowel gas encountered during TAS. However, the field of view is more limited. Most often, the initial scan will use both TAS and TVS during the same procedure. This aids in ruling out the possibility of missing a large ovarian mass, which may lie external to the field of view of the TVS transducer.(Yazbek et al, 2008) Unlike TAS, TVS does not require a full bladder which most female patients would find uncomfortable while having their abdomen pressed down upon during the scan. A complete US can evaluate the size, architecture, and contour of the ovaries and paint a clear picture of the possibility of a cancerous lesion. (Green, 2010) These managements, all 3, equate to a unified system of diagnostic assistance to which the clinician and supporting staff rely upon to accurately begin to paint a picture or tell the story of what is happening in this patients life at the current time. All 3 are effective in giving a baseline from which to work and to assist in ruling in or out, the framework of a diagnosis. All 3 have various strengths as has been mentioned and all have weaknesses. However, the part that non-invasive scans play is still secondary to the role of the surgeon and laproscopic evaluations. Only in taking samples and removing the cancerous ovary(s) can we see firsthand what is truly going on. Until then, we are assured that we know something is happening, but not confident of quite what that is until post-op assessments are completed. Treatments for Ovarian Cancer Treatments for Ovarian Ca depend almost entirely on the extent of invasion or metastases outside the ovary itself. Patients whose disease has metastases into the liver and above the diaphragm (Stage IV) should have cyto-reductive laproscopic surgery combined with standard chemotherapy regimens of cisplatin and paclitaxel.(Green 2010) The key issue surgically is the extent of invasion and metastases even within the peritoneal cavity. The generalized rules for surgeons is to take the ovary intact and to also remove lymph nodes found within the region of the ovary. Second, the inferior omentum might also be removed if visual inspection reveals potential seeding sites not seen on the scans prior to surgery. Lastly, the protocols for chemotherapy are as varied as they are numerous. A patients clinical oncologist will determine the scope, frequency, and types of chemotherapeutics to be used depending on the staging of the cancer itself. Patients with Stage 1 and 2 cancer may only have a 3 course order for therapy with one or two platinum-based drugs, while patients with Stage 3 might have a more extensive course with 3 or more platinum-based drugs and others used to combat their cancer.(Harrison, 2008) Patients with recurrent cancer are likely candidates for investigational drug regimens which are not available under normal primary tumor investigations. (Green, 2010) CONCLUSION Ovarian cancer kills thousands worldwide every year. Familial and environmental factors increase the risk depending on many factors we have covered here. Certainly, the efforts to accurately diagnose this disease pre-operatively are a vital component to getting a patient back to full health. However, as was mentioned, most patients present when the disease itself has advanced to a stage beyond the course we might see in other cancers like uterine and endometrial due to a lack of clinical diagnostic aptitude or even a misdiagnosis of the disease for a simple GI related illness. It is there that the initial investigations should have taken place and should always be included in females above 40 years of age, who present with simple GI symptoms which do not resolve in short periods with standard treatments. Early detection, as we see in the charts above, can prevent an increased rate of prevalence and death from the disease. 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Available: http://emedicine.medscape.com/article/255771-overview. Last accessed 4th August 2011. · Goff BA, Mandel LS, Melancon CH, Muntz HG. (2004 ) Frequency of Symptoms of Ovarian Cancer in Women Presenting to Primary Care Clinics. JAMA;291(22):2705-12. · Kasper, DL; Braunwald, E; Fauci, AS; Hauser, SL; Longo, DL; Jameson, JL; Loscalzo, J. (2008). Harrisons Principles of Internal Medicine. 17th ed. New York: McGraw-Hill Medical Publishing . 1009-1012. · Staff Writers. (2010). Tests and diagnosis of Ovarian Cancer,.Available: http://www.mayoclinic.com/health/ovarian-cancer/DS00293/DSECTION=tests-and-diagnosis. Last accessed 4th August, 2011. · Ryerson AB, Eheman C, Burton J, McCall N, Blackman D, Subramanian S, et al. (2007) Symptoms, diagnoses, and time to key diagnostic procedures among older U.S. women with ovarian cancer. Obstet Gynecol. ;109(5):1053-61. · Semelka, R. C., Lawrence, P. H., Patrick Shoenut, J., Heywood, M., Kroeker, M. A. and Lotocki, R.. (2005). Primary ovarian cancer: Prospective comparison of contrast-enhanced CT and pre-and postcontrast, fat- suppressed MR imaging, with histologic correlation. Journal of Magnetic Resonance Imaging. 3 (10), 99-106. · Woodward ER, Sleightholme HV, Considine AM, Williamson S, McHugo JM, Cruger DG.(2007) Annual surveillance by CA125 and transvaginal ultrasound for ovarian cancer in both high-risk and population risk women is ineffective. BJOG.An International Journal of Obstetrics & Gynaecology ;114(12):1500-9 · Yazbek J, Raju SK, Ben-Nagi J, Holland TK, Hillaby K, Jurkovic D. (2008) Effect of quality of gynaecological ultrasonography on management of patients with suspected ovarian cancer: a randomised controlled trial. Lancet Oncol. ;9(2):124-31. Read More