Laparoscopically Assisted Vaginal Hysterectomy Versus Total Abdominal Hysterectomy for Leiomyosarcoma Treatment: Analysis and Follow-Up of 20 Cases

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1 JOURNAL OF GYNECOLOGIC SURGERY Mary Ann Liebert, Inc. Laparoscopically Assisted Vaginal Hysterectomy Versus Total Abdominal Hysterectomy for Leiomyosarcoma Treatment: Analysis and Follow-Up of 20 Cases HUN-SHAN PAN, M.D., MIKE YAN-SHENG LIN, M.D., LEE-WEN HUANG, M.D., and JIANN-LOUNG HWANG, M.D. ABSTRACT This retrospective study aimed to review the prognostic factors for leiomyosarcoma (LMS) and to compare the efficacies of laparoscopically assisted vaginal hysterectomy (LAVH) and total abdominal hysterectomy (TAH) for the management of uterine LMS. The clinical records were reviewed for 20 patients who had undergone either LAVH or TAH between 1992 and 1998 at Shin-Kong Hospital, with subsequent diagnosis of uterine LMS. Mitotic index and tumor size appeared to be the factors significantly related to survival. After comparison of the two surgical procedures, it was concluded that LAVH can be as effective as the total abdominal variant for the management of LMS. (J GYNECOL SURG 17:91, 2001) INTRODUCTION LEIOMYOSARCOMA (LMS) ACCOUNTS for 35% of all sarcomas affecting the uterine corpus and is responsible for 1% to 3% of all female genital tract malignancies. 1 3 Several studies have suggested that sarcomatous change in a previously benign leiomyoma is the cause of LMS 4 A history of prior pelvic irradiation has also been proposed by some authors; however, as yet, there has been no consensus regarding the cause, with causes and pathogenesis remaining unresolved. The most important tool for LMS diagnosis is histologic examination, with malignancy dependent on the number of mitoses determined in the tumor. 1,5,6 Most investigators agree that tumors with fewer than five mitoses per 10 high-power fields (HPF) are usually more benign. By contrast, tumors with more than 10 mitoses per HPF are less predictable, with many expected to recur or metastasize. 7 Total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy has generally been considered the therapeutic hallmark for early stage LMS and all other uterine sarcomas. 1,2,7,8 Selective pelvic and aortic lymph node dissection is not necessary for LMS because it rarely involves regional lymph nodes, especially in the absence of extrauterine disease. 3 The clinical records for LMS cases at Shin-Kong Hospital (SKH) were reviewed with particular regard to patient characteristics, tumor size and mitosis, and the treatment modalities used. The object of this study was the comparison of respective survival outcomes and efficacies for laparoscopically assisted vaginal hysterectomy (LAVH) and TAH on the treatment of LMS. Department of Obstetrics and Gynecology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. 91

2 92 Pan et al. Journal of Gynecologic Surgery MATERIALS AND METHODS Signs and symptoms Between 1992 and 1998, 20 of the women who underwent either TAH or LAVH at SKH were diagnosed with LMS, with 10 of these patients reporting a history of irregular vaginal bleeding. Palpable pelvic masses were detected for 8 of these patients on examination, with 2 cases of dysmenorrhea (Table 1). All the patients underwent hysterectomy for presumed myoma of the uterus. Surgical intervention Ten of these patients underwent TAH performed through a low-midline skin incision. The surgical technique followed the procedure described by Stovall. 9 The round and cardinal ligaments, uterine vessels, and branches of the vaginal artery were clamped, divided, then ligated or sutured with nonabsorbable No. 4 silk (Sherwood Devis and Geck, USA). Vaginal cuff closure was achieved through continuous suture using absorbable Dexon 1-0 (Sherwood Devis and Geck). LAVH was performed for 10 patients. According to the classification of Munro and Parker, the LAVH procedure practiced was Type III D in the laparoscopic hysterectomy classification system. 10 After pneumoperitoneum was achieved, a 10-mm videolaparoscope was introduced into the umbilical incision. Another three 5-mm trocars were introduced into the lower abdomen (one on each side, with the third supra- TABLE 1. POPULATION CHARACTERISTICS WITH CLINICAL AND PATHOLOGIC FEATURES OF TUMOR Pathologic features Case Age* Treatment Clinical features Mitosis Size Atypia Necrosis Status 1 43 TAH Irregular vaginal bleeding.10/10 HPF 9 cm Moderate, focal (1) Alive TAH Pelvic mass.10/10 HPF 10 cm Mild, focal (1) Alive TAH Pelvic mass.10/10 HPF 8 cm Severe, focal (1) Alive TAH Irregular vaginal bleeding.10/10 HPF 7 cm Mild, focal (2) Alive TAH Pelvic mass and pressure.10/10 HPF 8 cm Moderate, focal (1) Alive TAH Pelvic mass Abundant, 24 cm Severe, focal (1) Expired 1 25/10 HPF 7 44 TAH Irregular vaginal bleeding Abundant, 10 cm Severe, focal (1) Expired 1.20/HPF 8 43 TAH Pelvic mass.10/10 HPF 9 cm Moderate, focal (1) Alive TAH Pelvic mass.10/10 HPF 18 cm Moderate, focal (1) Alive TAH Irregular vaginal bleeding.10/10 HPF 9 cm Moderate, focal (1) Alive LAVH i Irregular vaginal bleeding.10/10 HPF 9 cm Mild, focal (1) Alive LAVH Irregular vaginal bleeding.10/10 HPF 8 cm Moderate, focal (1) Alive LAVH Pelvic mass.10/10 HPF 11 cm Mild, focal (1) Alive LAVH Dysmenorrhea.10/10 HPF 7 cm Moderate, focal (2) Alive LAVH Irregular vaginal bleeding.10/10 HPF 9 cm Severe, focal (1) Alive LAVH Irregular vaginal bleeding.10/10 HPF 8 cm Severe, focal (2) Alive LAVH Pelvic mass.10/10 HPF 10 cm Moderate, focal (1) Alive LAVH Dysmenorrhea.10/10 HPF 7 cm Severe, focal (2) Alive LAVH Irregular vaginal bleeding.10/10 HPF 8 cm Severe, focal (1) Alive LAVH Irregular vaginal bleeding.10/10 HPF 7 cm Moderate, focal (1) Alive 3 *Average age of patients: years. Average size of tumors: 9.8 cm. TAH, total abdominal hysterectomy. HPF, high-power field. i LAVH, laparoscopically assisted vaginal hysterectomy. 1,2 years follow-up. 2 2 years follow-up. 3.2 years follow-up.

3 Volume 17, Number 3, 2001 Laparoscopically Assisted Vaginal Hysterectomy 93 pubic). Bilateral round ligaments, fallopian tubes, ovarian ligaments, and the ascending branch of the uterine artery were electrocauterized by use of Kleppinger forceps. Anterior and posterior culdotomy were performed by use of a monopolar cutting instrument. The cardinal ligaments were partially dissected from the uterus, with the remaining portion of the uterosacral-cardinal ligament complex then ligated vaginally. The uterus was removed through the vagina by morcellation. Vaginal cuff closure was achieved through continuous suturing, with absorbable Dexon 1-0, and the trocar-site incisions were closed with nonabsorbable Dermalon 3-0 (Sherwood Devis and Geck). Data collection and analysis Each patient had had more than 2 years ( ) of follow-up at the time of this writing. The data for this investigation were taken mainly from inpatient and outpatient records, with further details of current patient condition obtained by telephone interview. Qualitative estimation of mitotic activity is useful as a diagnostic and prognostic criterion for LMS. 5 For this study, LMS identification was based on the criteria that have been delineated by most investigators, as summarized in Luraine et al. 7 Tumors with fewer than five mitoses per HPF were considered benign. 5 Tumors with 10 or more mitoses per HPF, however, were deemed frankly malignant, and records for these cases were included in our study. For analysis in this report, survival duration was determined from the time of diagnosis (surgery) to date of last contact. Pathologic criteria Gross presentation of the tumor at the time of surgery was also taken into consideration, with size, margins, and extensions also noted during tumor measurement. Moreover, tumors were examined for the presence of coagulative tumor cell necrosis. The quantity of atypical smooth-muscle cells exhibiting pleomorphism, coarse chromatin pattern, nuclear membrane irregularities, and multiple prominent nuclei was also ascertained. Cellular atypia was classified as mild, moderate, or severe. Population characteristics RESULTS In the 7-year review period ( ), 20 patients with early-stage LMS were admitted to the SKH (population characteristics are presented in Table 1). Their ages ranged from 33 to 70 years (mean 45.85). Fourteen patients were premenopausal and were under 45 years old. Stage I LMS (sarcoma confined to the corpus uteri) was diagnosed for all of the cases. Deaths in the TAH group occurred because of early local recurrence and distant metastasis of the tumor (Table 1). Tumor size ranged from 7 to 24 cm (average 9.8). All LAVH patients were still alive after 2 years of follow-up. By contrast, two in the TAH group had expired within the same follow-up period (Table 1). Eighteen of 20 patients had tumors with mitoses per 10 HPF, with 20 mitoses per HPF determined for 2 patients who survived less than 2 years (Table 1). Cellular atypia and central necrosis were determined for 80% of patients, with necrosis revealed for all tumors.8 cm. For both the LAVH and TAH groups, most patients exhibited mild to moderate cellular atypia. Surgical modality did not influence survival for patients with severe atypia. DISCUSSION Uterine LMS is a rare tumor type, and most of the reported studies are limited by small sample size. 2 Furthermore, the dismal prognosis and uncommon occurrence present a challenge for the gynecologist. Uterine LMS occurs mostly in perimenopausal women, with ages in various studies ranging from 43 to 56 years old. 3,5,11 Furthermore, premenopausal patients have better survival rates than do their postmenopausal counterparts. 3,6 In our study, 15 (75%) patients were premenopausal, with 2 surviving less than 2 years as a consequence of local recurrence and distant metastasis. Our results confirmed the findings of

4 94 Pan et al. Journal of Gynecologic Surgery Hart and Billman, with no significant difference demonstrated for survival comparing postmenopausal and premenopausal women with the disease. 12 The presenting symptoms of LMS are usually nonspecific, resembling those of other benign conditions of the uterus. In order of frequency, the most common symptoms are vaginal bleeding, pelvic pain or pressure, and awareness of an abdominal-pelvic mass. 5,7 In our study, 50% of patients presented with irregular vaginal bleeding, with abdominal enlargement or pelvic mass reported by 40% of patients, whereas only 10% reported pelvic pain. Tumor location within the uterine corpus can be predicted on the basis of patient presentation, with pain symptoms and palpable mass frequently associated with intramural tumors. By contrast, vaginal bleeding occurs most often with submucosal lesions. 5 The diagnosis of LMS should be considered if rapid growth of the uterine mass occurs, and dilatation and curettage may establish the diagnosis if the lesion is submucosal. Because of its deep location, LMS can go unsuspected until hysterectomy is performed for a presumed benign leiomyoma. 7,13 Although hysterectomy under the impression of uterine myoma was performed for all our patients, a preoperative diagnosis was not possible because none of them had undergone curettage or endometrial biopsy. The number of tumor mitoses is a useful diagnostic and prognostic criterion for LMS. 2,5,7,14 According to Malstrom et al., the survival rate decreases from 55% to 0% for patients with,9 and.20 mitoses per 10 HPF, respectively. 15 Similarly, Gadducci et al., in a study of 24 patients with stage I/II LMS, compared the 2-year diseasefree survival rates for those with,20 mitoses and.20 mitoses per 10 HPF. 3 In our study, all patients had a mitotic count of.10 per HPF, with 18 of them still alive at the time of this writing. Two patients (10%) had a mitotic count of.20 mitoses per 10 HPF, and both expired within 2 years. Evans et al. considered tumor size the most important prognostic factor for LMS, with poor prognosis for tumors.5.0 cm in maximum diameter. 16 All of our LAVH patients were still alive 2 years after surgery; however, 2 TAH patients expired within the same follow-up period. The treatment of uterine LMS is difficult, with low radio sensitivity and chemosensitivity generally proposed. 5,7,16,17 By contrast, several studies have reported decreased pelvic recurrence rate or increased survival rate with pelvic irradiation. 13,18 In their 1992 study, Sutton et al. demonstrated the limited effectiveness of the chemotherapeutic agents ifosfamide and mesna as adjuvants for the treatment of advanced and recurrent LMS. 19 Chemotherapy did not improve survival time. Although various studies have arrived at different conclusions regarding the efficacy of adjuvant treatment for control of recurrence or metastasis, hysterectomy is still accepted as the standard therapy for LMS. 7 One study proposed that tumor excision or hysterectomy plus bilateral salpingo-oopherectomy were the treatments of choice; however, the exact surgical procedure was not specified. 5 To the best of our knowledge, this is the first study to compare the effectiveness of TAH and LAVH for LMS treatment, with no significant differences demonstrated with respect to postoperative survival rate. In our study, trocar-site metastasis or local recurrence after morcellation was not evident for LAVH patients after more than 2 years of follow-up. The two mortalities in the TAH group were a reflection of the larger tumor size and higher mitotic count (.20 mitoses per HPF). If these patients had been excluded on the basis of these anomalies, the survival rate for the TAH patients would have been equivalent. In our view, LAVH is as effective as TAH for the management of LMS on the basis of 2-year survival. Given the limited follow-up and the small sample size owing to the rarity of the disease, however, it may be premature to generalize and draw a conclusion with respect to the relative effectiveness of LAVH and TAH. In summary, patients who undergo LAVH for fibroids, with LMS confirmed histologically, may not require further surgery. For our patients, morcellation did not appear to worsen prognosis, and trocar site metastases were not observed. REFERENCES 1. Salazar OM, Bonfiglio TA, Patten SF, et al. Uterine sarcomas: natural history, treatment and prognosis. Cancer 1978;42: Wheelock JB, Krebs H-B, Schneider V, et al. Uterine sarcoma: analysis of prognostic variables in 71 cases. Am J Obstet Gynecol 1985;151:1016.

5 Volume 17, Number 3, 2001 Laparoscopically Assisted Vaginal Hysterectomy Gadducci A, Fabrini MG, Bonuccelli A, et al. Analysis of treatment failures in patients with early stage uterine leiomyosarcoma. Anticancer Res 1995;15: Silverberg SG. Leiomyosarcoma of the uterus: a clinicopathologic study. Obstet Gynecol 1971;38: Coppleson M. Gynecologic Oncology, 2nd ed., vol. 2. Edinburgh: Churchill-Livingstone, 1992: Olah KS, Dunn JA. Leiomyosarcomas have poorer prognosis than mixed mesodermal tumors when adjusting for known prognostic factors: the result of a retrospective study of 423 cases of uterine sarcoma. Br J Obstet Gynecol 1992;99: Luraine JR. Uterine cancer. In: Berek JS, Adashi EY, Hillard PA, eds. Novak s Gynecology, 12th ed. Baltimore: Williams & Wilkins, 1996: Kahanpaa KV, Wahlstrom T, Gron P, et al. Sarcomas of the uterus: a clinicopathologic study of 119 patients. Obstet Gynecol 1986;67: Stovall TG. Hysterectomy. In: Berek JS, Adashi EY, Hillard PA, eds. Novak s Gynecology, 12th edition. Baltimore: Williams & Wilkins, 1996: Munro MC, Parker WH. A classification scheme for laparoscopic hysterectomy. Obstet Gynecol 1993;82: Harlow BL, Weiss NS. The epidemiology of sarcomas of the uterus. J National Cancer Inst 1986;76: Hart WR, Billman JK. A reassessment of uterine neoplasms originally diagnosed as leiomyosarcoma. Cancer 1978;41: Hornback NB, Omura G. Observations on the use of adjuvant radiation therapy in patients with stage I and II uterine sarcoma. Int J Radiol Oncol Biol Physics 1986;12: Major FJ, Blessing JA, Silverberg SG, et al. Prognostic factors in early-stage uterine sarcoma: a gynecologic oncology group study. Cancer 1993;71: Malstrom H, Schmidt H, Persson PG, et al. Flow cytometric analysis of uterine sarcoma: ploidy and S-phase rate as prognostic indicators. Gynecol Oncol 1992;44: Evans HL, Chowla SP, Simpson C, et al. Smooth muscle neoplasm of the uterus other than ordinary leiomyoma: a study of 46 cases, with emphasis on diagnostic criteria and prognostic factors. Cancer 1988;62: Blom K. Sarcoma of the female genital tract: histopathology, DNA cytometry, p53 and mdm-2 analysis related to prognosis. Lincoping University Medical Dissertations, February 1999, Knocke TH, Kucera H, Dorfler D, et al. Results of post-operative radiotherapy in the treatment of sarcoma of the corpus uteri. Cancer 1998;83: Sutton NB, Blessing JA, Barrett RJ, et al. Phase II trial of ifosfamide and mesna in leiomyosarcoma of the uterus: a gynecologic oncology group study. Gynecol Oncol 1992;166:556. Address reprint requests to: Jiann-Loung Hwang, M.D. Department of Obstetrics and Gynecology Shin Kong Wu Ho-Su Memorial Hospital No. 95 Wen Chang Road Shih Lin District Taipei, Taiwan M004407@ms.skh.org.tw