Sonographically Guided Core Biopsy

ORIGINAL RESEARCH Sonographically Guided Core Biopsy A Minimally Invasive Procedure for Managing Adnexal Masses Tufan Oge, MD, Omer T. Yalcin, MD, S. Sinan Ozalp, MD, Mahmut Kebapci, MD, Yunus Aydin, MD, Elcin Telli, MD Received February 25, 2013, from the Departments of Gynecology and Obstetrics (T.O., O.T.Y., S.O., Y.A., E.T.) and Radiology (M.K.), Eskisehir Osmangazi University School of Medicine, Eskisehir, Turkey. Revision requested March 22, 2013. Revised manuscript accepted for publication April 6, 2013. This study was partially supported by the Eskisehir Osmangazi University Scientific Research Project Commission (project 201211021). Address correspondence to Tufan Oge, MD, Department of Obstetrics and Gynecology, Eskisehir Osmangazi University School of Medicine, 26100 Eskisehir, Turkey. E-mail: tufanoge@yahoo.com Abbreviations BMI, body mass index; CA-125, cancer antigen 125 doi:10.7863/ultra.32.11.2023 Objectives We hypothesized that sonographically guided core biopsy is an effective method for the differential diagnosis of adnexal masses and evaluated patients who underwent core biopsies in our gynecologic oncology department. Methods We reviewed the medical records of 55 patients who underwent sonographically guided core biopsies in our gynecologic oncology department between 2010 and 2013. Patients with suspected ovarian malignancies who were unsuitable for optimal debulking surgery and patients at risk for higher morbidity and mortality because of a poor performance status, suspected nongynecologic tumors, and peritoneal tuberculosis were indicated for sonographically guided biopsy. Results The indications for sonographically guided core biopsy were candidacy for suboptimal cytoreduction (n = 32 [58.2%]), a poor performance status (n = 11 [20.0%]), and suspected nongynecologic tumors (n = 12 [21.8%]). Histopathologic evaluations revealed primary ovarian tumors in 36 patients (65.5%). Tuberculosis was found to be the second most common disease (n = 8 [14.5%]) among the patients who underwent core biopsies. In 2 patients (3.6%), histologic examination revealed metastatic colorectal cancer. Conclusions Sonographically guided core biopsy may be preferred as a minimally invasive procedure for managing adnexal masses, particularly in patients with advanced ovarian cancer and high comorbidities who might benefit from neoadjuvant chemotherapy and in cases of suspected nongynecologic tumors, including pelvic tuberculosis. Key Words advanced ovarian cancer; core biopsy; neoadjuvant chemotherapy; peritoneal tuberculosis; sonographically guided biopsy Managing adnexal masses that result from primary or metastatic ovarian tumors is quite different. Moreover, abdominal peritoneal involvement by tuberculosis, which mimics an advanced malignant tumor, must also be excluded, particularly in countries where tuberculosis is common. Although age, patient history, pelvic examination, various imaging methods, and serum cancer antigen 125 (CA-125) levels may be helpful for distinguishing the origin and nature of adnexal masses, usually a definitive diagnosis requires surgical excision and histopathologic examination. 1 Frozen-section analysis is commonly used during surgical procedures to prevent unnecessary aggressive operations. 2 However, this clinical approach may not always reduce patient morbidity or mortality. 2013 by the American Institute of Ultrasound in Medicine J Ultrasound Med 2013; 32:2023 2027 0278-4297 www.aium.org

Although primary cytoreductive surgery followed by adjuvant chemotherapy remains the basic therapy for patients who have advanced-stage ovarian cancer, minimally invasive procedures may be needed for patients who are candidates for neoadjuvant chemotherapy. 3 5 Moreover, patients who have suspected metastatic ovarian cancer or pelvic tuberculosis may also need less invasive methods of evaluating histopathologic specimens to optimize the therapy. 6,7 Core biopsy is commonly used in breast and prostate cancers. 8,9 In the field of gynecologic oncology, the limited number of available studies all originated from the same center, which has investigated the importance of sonographically guided core biopsy. 10,11 From this viewpoint, we hypothesized that sonographically guided biopsy is a reliable and effective method in the differential diagnosis of adnexal masses and began testing this hypothesis. We evaluated patients who underwent core biopsies in our gynecologic oncology department. Materials and Methods For this retrospective study, we reviewed the records of 55 patients who underwent sonographically guided core biopsies in our gynecologic oncology department between 2010 and 2013. All of the patients were evaluated during weekly meetings of the gynecologic oncology department and were referred for this minimally invasive procedure. Patients were informed before the biopsies and signed informed consent forms, and the local Ethics Committee approved our study. Pelvic examination findings, transvaginal and transabdominal sonographic findings, pelvic and abdominal computed tomographic findings, serum CA-125 levels, and body mass indices (BMIs) were recorded from the patients medical records. The patients performance status was evaluated according to the Eastern Cooperative Oncology Group criteria, which grades patients on a scale ranging from 0 to 5. 12 Patients with suspected ovarian malignancies who were unsuitable for optimal debulking surgery and patients at risk for higher morbidity and mortality because of a poor performance status or suspected nongynecologic tumors and peritoneal tuberculosis were indicated for sonographically guided biopsy. Patients who were considered to be unsuitable for optimal surgery were investigated by surgeons and radiologists at the weekly joint meetings of the gynecologic oncology department. Primary optimal inoperability decisions were made after evaluating the pelvic examinations and sonographic and computed tomographic findings. Patients with suprarenal and mediastinal bulky lymph nodes, multiple metastases in the parenchyma, pulmonary and pleural area involvement, abdominal wall invasion, extensive small-bowel involvement, and diffuse peritoneal thickening were considered candidates for suboptimal cytoreduction. 13 Patients who were scheduled to undergo sonographically guided core biopsies were reevaluated with sonography. Mass localization and any interaction with nearby organs and vascular structures were all investigated with sonography, and the biopsies were performed transabdominally. Povidone iodine was used to disinfect the biopsy area skin. Lidocaine, 1%, was administered as a local anesthetic agent, and the biopsy was performed with a special 18-gauge, 25-cm-long disposable core biopsy needle (Speed Cut; Gallini Medical Devices, Mantova, Italy). During the procedure, the needle tip was visualized by sonography and guided toward the target, which was similar to amniocentesis procedures. After the procedure, the biopsy area was controlled for hemostasis, and the patients were followed in the hospital wards. No antibiotics were given before or after the procedures. Tissue was formalin fixed, paraffin embedded, and stained with hematoxylineosin. First, the samples were examined for evidence of tumors. In cases of malignancy, the origin, subtype, and grade were determined by immunohistochemical methods, and pathologic specimen adequacy was determined from the pathology reports if the samples obtained from core biopsies were sufficient to make a diagnosis. Moreover, in cases with suspected tuberculosis on histopathologic examination, the materials were both sent for a cell culture and polymerase chain reaction based assay for confirmation of tuberculosis. Results The mean patient age was 59.9 years. The most common symptoms were abdominal discomfort (n = 37 [67.3%]) and abdominal pain (n = 16 [29.1%]). Two patients (3.6%) had no symptoms, and pelvic masses were diagnosed during routine examinations. Table 1 summarizes the patients demographic characteristics, performance statuses, BMIs, serum CA-125 levels, and sonographic presence of ascites. The indications for sonographically guided core biopsy were candidacy for suboptimal cytoreduction (n = 32 [58.2%]), a poor performance status (n = 11 [20%]), and suspected nongynecologic tumors (n = 12 [21.8%]). According to the preoperative evaluations, the samples were obtained from adnexal masses (n = 23 [41.8%]), omental cakes (n = 24 [43.6%]), and the peritoneum (n = 2024 J Ultrasound Med 2013; 32:2023 2027

8 [14.5%]). After these interventions, none of the patients had complications. On average, 2 samples were taken from each patient (range, 1 4), and the biopsy materials were deemed adequate (for identifying the tumor origin and performing immunohistochemistry) by the pathologist in 53 of 55 cases (96.4%). The variation in the number of samples occurred because the simple visual inspection of the first several cores showed probable tissue inadequacy, which may have caused a delay in the diagnosis or treatment. The 2 patients whose biopsy materials were found to be inadequate by the pathologist underwent diagnostic mini laparotomies and had a diagnosis of primary ovarian tumor. These patients had BMIs higher than 35 kg/m 2. Histopathologic evaluation revealed primary ovarian tumors in 36 patients (65.5%). Tuberculosis was found to be the second most common disease (n = 8 [14.5%]) among the patients who underwent core biopsies. In 2 patients (3.6%), histologic reports revealed metastatic colorectal cancer. Table 2 summarizes the histopathologic examination findings of the materials. According to the histopathologic findings, 43 patients (78.2%) received neoadjuvant chemotherapy, 8 (14.5%) received antituberculosis therapy and were referred to a phthisiologist (specialist in tuberculosis), and 2 (3.6%) were referred to a general surgeon because of gastrointestinal tumors. Discussion Table 1. Study Group Characteristics (n = 55) Characteristic Value Age, y 59.9 ± 12.6 Parity, n 3.2 ± 1.9 BMI, kg/m 2 27.7 ± 3.4 Performance status, n (%) a 0 6 (10.9) 1 30 (54.5) 2 13 (23.6) 3 6 (10.9) Ascites on sonography, n (%) 48 (87.3) CA-125, IU/mL b 606 ± 545 Data are presented as mean ± SD where applicable. a According to Eastern Cooperative Oncology Group criteria. b Normal range, 0 to 35 IU/mL. In this study, we found that sonographically guided core biopsy was an important diagnostic method for treating patients with adnexal masses. According to our experience, patients with advanced ovarian cancer, a poor performance status, or suspected nongynecologic tumors and those who are candidates for suboptimal cytoreduction may benefit from sonographically guided core biopsy to obtain an adequate pathologic specimen for the differential diagnosis. This minimally invasive procedure may prevent unnecessary laparotomies as well as additional morbidity and mortality in patients with high comorbidity or nongynecologic tumors. As the least invasive approach, fine-needle aspiration biopsy has been used to diagnosis ovarian cancer, and cytologic evaluation is the preferred diagnostic method. 14 However, core biopsy allows more material to be obtained and permits immunohistochemical staining for the histopathologic examination. 15 The methodological design of this study was retrospective; therefore, it had some inherent biases, such as a selection bias and an information bias. For example, the physicians who performed the sonographically guided core biopsies (T.O. and O.T.Y.) were not blinded to the patients pre-evaluation procedures because they are members of the gynecologic oncology team and make decisions at weekly meetings of the gynecologic oncology department. For this reason, none of the patients were excluded from the study because of nonsafe biopsy targets. Moreover, although the material adequacy was high in our study, we did not randomize the patients with pelvic masses, which was the main limitation of the study. We prefer primary cytoreductive surgery followed by chemotherapy as a primary treatment of advanced ovarian cancer, and decisions to perform sonographically guided core biopsy were made after the complete evaluation of each patient s clinical condition, performance status, and radiologic findings. In such situations, patients with high comorbidities and suspected nongynecologic tumors are referred for core biopsy, but this referral does not decrease the importance of this minimally invasive procedure. The other limitation was the lack of transvaginal core biopsies, which are crucial for tissue sampling of the ovaries and make difficult procedures safer. However, we have recently started performing those procedures, and we will share our experiences in the near future. Last, sample track seeding is an Table 2. Histopathologic Results for the Material Obtained by Tru-Cut Biopsy Result n (%) Primary ovarian cancer 36 (65.4) Serous type 32 (58.2) Mucinous type 2 (3.6) Endometrioid type 2 (3.6) Pelvic tuberculosis 8 (14.5) Primary peritoneal cancer 7 (12.7) Nongynecologic cancer 2 (3.6) Inadequate material 2 (3.6) J Ultrasound Med 2013; 32:2023 2027 2025

important issue in this procedure. In this study, we excluded not only patients with suspected stage I and II epithelial ovarian carcinoma but also patients suspected of having advanced-stage epithelial ovarian carcinoma who may have undergone optimal cytoreduction. For this reason, sample track seeding did seem to be a major problem for this procedure. The efficacy of fine-needle aspiration biopsy and core biopsy were compared in a large-scale study group, and samples were obtained from the thorax, abdomen, retroperitoneum, and neck. The amounts of sufficient material obtained from fine-needle aspiration biopsies and core biopsies were 70% to 92% and 93% to 100%, respectively. 16 Zikan et al 11 managed to obtain adequate material for histopathologic examinations in 93.7% of cases after the core procedure, whereas our experience was nearly identical (96%) without serious complications. In gynecologic oncology, Fischerova et al 10 briefly investigated sonographically guided biopsy in managing abdominopelvic tumors and reported diagnostic accuracy as 97.7%. From the same center, Zikan et al 11 suggested that core biopsy was an effective, minimally invasive, accurate, and safe method for managing gynecologic tumors. Moreover, the authors also justified the characteristics of metastatic nongynecologic pelvic tumors in up to 26% of their cases to decide how to manage the adnexal masses. 1 We previously reported 7 cases of abdominal peritoneal tuberculosis that were diagnosed by core biopsy and concluded that minimally invasive methods may prevent unnecessary operations, particularly in cases with suspected abdominal peritoneal tuberculosis. 17 In this study, pelvic tuberculosis was the second most common disease (14.5%) after primary ovarian cancer, which confirms the importance of core biopsy in the differential diagnosis of adnexal masses. A residual tumor after surgery is one of the most important prognostic factors in patients with advanced ovarian cancer. 18 For this reason, maximal surgical efforts must be achieved to perform optimal debulking surgery, and the standard management remains primary cytoreductive surgery followed by chemotherapy in advanced ovarian cancer. 19,20 However, there is a group of women who cannot undergo optimal debulking surgery because of their comorbidities or the extent of the disease; these women are treated with neoadjuvant chemotherapy. Vergote et al 21,22 observed that neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary debulking surgery followed by chemotherapy as a treatment option for patients with bulky stage IIIC or IV ovarian carcinoma. After these studies, minimally invasive procedures became more important as first steps for treating patients with many comorbidities and candidates for suboptimal cytoreduction without changing the main goal of leaving no residual tumor after the interval debulking surgery. Moreover, patients with suspected nongynecologic tumors, including abdominal peritoneal tuberculosis, are referred for core biopsy, which is critical for avoiding unnecessary surgery, particularly in those countries in which tuberculosis is a common health problem. In future prospective studies of neoadjuvant chemo - therapy followed by interval debulking surgery versus primary debulking surgery, core biopsy may be helpful in neoadjuvant chemotherapy because it is less invasive, and the adequacy, accuracy, and safety of the procedure may be better understood without the selection bias of retrospective studies. In conclusion, sonographically guided core biopsy may be preferred as a minimally invasive procedure for managing adnexal masses. In particular, it can be performed in patients with advanced ovarian cancer and high comorbidities, patients who may benefit from neoadjuvant chemotherapy, and patients with suspected nongynecologic tumors, including pelvic tuberculosis. References 1. Zikan M, Fischerova D, Pinkavova I, Dundr P, Cibula D. Ultrasonographic appearance of metastatic non-gynecological pelvic tumors. Ultrasound Obstet Gynecol 2012; 39:215 225. 2. Heatley MK. A systematic review of papers examining the use of intraoperative frozen section in predicting the final diagnosis of ovarian lesions. Int J Gynecol Pathol 2012; 31:111 115. 3. Griffiths CT, Fuller AF. Intensive surgical and chemotherapeutic management of advanced ovarian cancer. Surg Clin North Am 1978; 58:131 142. 4. Polterauer S, Vergote I, Concin N, et al. Prognostic value of residual tumor size in patients with epithelial ovarian cancer FIGO stages IIA IV: analysis of the OVCAD data. Int J Gynecol Cancer 2012; 22:380 385. 5. Vergote I, van Gorp T, Amant F, Leunen K, Neven P, Berteloot P. Timing of debulking surgery in advanced ovarian cancer. Int J Gynecol Cancer 2008; 18:11 19. 6. Oge T, Zeck W, Tamussino K. An adenocarcinoid tumour of the appendix mimicking advanced ovarian carcinoma. J Obstet Gynaecol 2009; 29:780 781. 7. Ayhan A, Guvenal T, Salman MC, Ozyuncu O, Sakinci M, Basaran M. The role of cytoreductive surgery in nongenital cancers metastatic to the ovaries. Gynecol Oncol 2005; 98:235 241. 8. Woodcock NP, Glaves I, Morgan DR, MacFie J. Ultrasound-guided Tru-Cut biopsy of the breast. Ann R Coll Surg Engl 1998; 80:253 256. 9. Chopra S, Rowe EW, Laniado M, Patel A. A prospective study analysing 2026 J Ultrasound Med 2013; 32:2023 2027

the effect of pain on probe insertion, and the biopsy strategy, on the patients perception of pain during TRUS-guided biopsy of the prostate. NZ Med J 2008; 121:39 43. 10. Fischerova D, Cibula D, Dundr P, et al. Ultrasound-guided tru-cut biopsy in the management of advanced abdomino-pelvic tumors. Int J Gynecol Cancer 2008; 18:833 837. 11. Zikan M, Fischerova D, Pinkavova I, Dundr P, Cibula D. Ultrasoundguided tru-cut biopsy of abdominal and pelvic tumors in gynecology. Ultrasound Obstet Gynecol 2010; 36:767 772. 12. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5:649 655. 13. Kebapci M, Akca AK, Yalcin OT, Ozalp SS, Calisir C, Mutlu F. Prediction of suboptimal cytoreduction of epithelial ovarian carcinoma by preoperative computed tomography. Eur J Gynaecol Oncol 2010; 31:44 49. 14. Freedman OC, Dodge J, Shaw P, et al. Diagnosis of epithelial ovarian carcinoma prior to neoadjuvant chemotherapy. Gynecol Oncol 2010; 119:22 25. 15. Bandyopadhyay A, Chakraborty J, Chowdhury AR, Bhattacharya A, Bhattachrya P, Chowdhury M. Fine needle aspiration cytology of ovarian tumors with histological correlation. J Cytol 2012; 29:35 40. 16. Chojniak R, Isberner RK, Viana LM, Yu LS, Aita AA, Soares FA. Computed tomography guided needle biopsy: experience from 1300 procedures. Sao Paulo Med J 2006; 124:10 14. 17. Oge T, Ozalp SS, Yalcin OT, et al. Peritoneal tuberculosis mimicking ovarian cancer. Eur J Obstet Gynecol Reprod Biol 2012; 162:105 108. 18. du Bois A, Reuss A, Pujade-Lauraine E, Harter P, Ray-Coquard I, Pfisterer J. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d Investigateurs Nationaux Pour les Etudes des Cancers de l Ovaire (GINECO). Cancer 2009; 115:1234 1244. 19. Chi DS, Bristow RE, Armstrong DK, Karlan BY. Is the easier way ever the better way? J Clin Oncol 2011; 29:4073 4075. 20. Bristow RE, Eisenhauer EL, Santillan A, Chi DS. Delaying the primary surgical effort for advanced ovarian cancer: a systematic review of neoadjuvant chemotherapy and interval cytoreduction. Gynecol Oncol 2007; 104:480 490. 21. Vergote I, Tropé CG, Amant F, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 2010; 363:943 953. 22. Vergote I, Amant F, Leunen K. Neoadjuvant chemotherapy in advanced ovarian cancer: what kind of evidence is needed to convince US gynaecological oncologists? Gynecol Oncol 2010; 119:1 2. J Ultrasound Med 2013; 32:2023 2027 2027

Journal Search - IP & Science - Thomson Reuters 4/23/14 8:39 PM Site Client proxystylesheet Output Search Site Search allareas JOURNAL SEARCH Search Terms: 0278-4297 Total journals found: 1 The following title(s) matched your request: Journals 1-1 (of 1) JOURNAL OF ULTRASOUND IN MEDICINE Monthly ISSN: 0278-4297 AMER INST ULTRASOUND MEDICINE, SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, USA, MD, 20707-5906 Coverage Science Citation Index Science Citation Index Expanded Current Contents - Clinical Medicine Journals 1-1 (of 1) Search Terms: Search type: Title Word http://science.thomsonreuters.com/cgi-bin/jrnlst/jlresults.cgi?pc=master&issn=%200278-4297 Page 1 of 2