Gynecologic Oncology 97 (2005) 296 – 300 www.elsevier.com/locate/ygyno
Case Report
Pediatric radical abdominal trachelectomy for cervical clear cell carcinoma: A novel surgical approach Nadeem R. Abu-Rustuma,T, Wendy Sub, Douglas A. Levinea, Jeff Boyda, Yukio Sonodaa, Michael P. LaQuagliab b
a Gynecology Service, Memorial Sloan-Kettering Cancer Center, USA Pediatric Surgery Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Room C-1096, New York, NY 10021, USA
Received 19 October 2004
Abstract Introduction. Clear cell carcinoma of the cervix and vagina is rare in the pediatric population. Many of these tumors are associated with prior intrauterine diethylstilbestrol (DES) exposure. All DES-associated tumors are believed to contain microsatellite instability (MI). Historically, the recommended treatment is radical hysterectomy and pelvic lymphadenectomy, which result in infertility in all cases. Radical abdominal or vaginal trachelectomy and pelvic lymph node dissection is a new technique utilized in adult women with early cervical cancer who wish to retain fertility. This novel approach is also pertinent to the pediatric patient and is described in this report. A molecular analysis is also performed to determine if these are DES-associated tumors. Methods. Due to the narrow vaginal anatomy in pediatric patients, a vaginal approach is not possible, and an abdominal approach is performed. The resection includes the cervix, upper vagina, parametrium, and paracolpos. Pelvic lymphadenectomy is performed in a similar manner to the adult patient. Matched pairs of normal and tumor DNA from both cases were examined for evidence of MI using a consensus panel of microsatellite markers. Results. Two girls aged 6 and 8 years and without history of DES exposure presented with vaginal bleeding. Vaginoscopy revealed cervical polyp in both cases. Biopsies demonstrated clear cell cancer stage IB1 in both patients. They underwent radical abdominal trachelectomy and bilateral pelvic lymph node dissection along with anastomosis of uterine isthmus to upper vagina. Intraoperative frozensection analysis confirmed negative uterine and vaginal margins. No adjuvant treatment was given and both girls remain disease free. Neither tumor showed evidence for MI, confirming that these are not DES-associated tumors. Conclusion. To our knowledge, this is the first report of radical abdominal trachelectomy in the pediatric age group and it is likely to include the youngest patient with clear cell carcinoma of the uterine cervix not associated with DES exposure. This novel approach is feasible and appears safe in the pediatric age group. D 2004 Elsevier Inc. All rights reserved. Keywords: Trachelectomy; Cervical cancer; Clear cell cancer; Fertility sparing surgery
Introduction Clear cell carcinoma of the cervix and vagina is rare in the pediatric population. Many of these tumors are associated with prior intrauterine diethylstilbestrol (DES)
T Corresponding author. Fax: +1 631 864 4618. E-mail address:
[email protected] (N.R. Abu-Rustum). 0090-8258/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2004.12.050
exposure. All DES-associated tumors are believed to contain microsatellite instability (MI). Historically, the recommended treatment is radical hysterectomy and pelvic lymphadenectomy, which result in infertility in all cases. Radical abdominal or vaginal trachelectomy and pelvic lymph node dissection are new techniques utilized in adult women with early cervical cancer who wish to retain fertility. This novel approach is also pertinent to the pediatric patient and is described in this report.
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Case report Two young girls aged 6 and 8 years and without history of DES exposure presented with vaginal bleeding. Vaginoscopy revealed a cervical polyp in both cases. Polypectomy demonstrated clear cell cancer, International Federation of Gynecology and Obstetrics (FIGO) stage IB1 in both patients. There was no history of human papillomavirus infection or sexual abuse in either case. After extensive counseling, both patients underwent radical abdominal trachelectomy, bilateral pelvic lymph node dissection, and anastomosis of uterine isthmus to upper vagina. The first patient underwent these procedures in February of 2004. The second patient underwent these procedures in April 2004. Intraoperative frozen-section analysis confirmed negative uterine and vaginal margins and negative lymph nodes. Final pathologic review of the first case revealed a poorly differentiated clear cell carcinoma in a 1.4 cm polyp with no residual carcinoma in the trachelectomy specimen and 38 negative pelvic lymph nodes. Final pathologic review of the second case also revealed clear cell carcinoma in a 2 cm polyp with no residual carcinoma in the trachelectomy specimen and 38 negative lymph nodes as well. No adjuvant treatment was given. Follow-up consisted of exam under anesthesia, Papanicolaou smears, and vaginoscopy every 3 months as well as repeat pelvic imaging studies every 6 months. Both girls remained prepubertal and disease free at the time of this report. A molecular analysis was also performed to determine if the tumors were associated with DES. Using a consensus panel of microsatellite markers, matched pairs of normal and tumor DNA from both cases were examined for evidence of MI. Neither tumor showed evidence of MI, confirming that they were not DES-associated tumors. Technique of pediatric radical abdominal trachelectomy Due to the very narrow vaginal anatomy in pediatric patients, a vaginal trachelectomy approach, similar to that used in adult patients, was not possible, and an abdominal approach was performed. The resection included the cervix, upper vagina, parametrium, and paracolpos (Fig. 1). The uterus is extremely small in pediatric patients and measures approximately 1.5 cm 1.5 cm; the ovaries are larger than the uterus at this early age and measure approximately 2.5 cm in length. A vaginoscopy using a 308 cystoscope to inspect the vaginal fornices and the cervix was performed at the beginning of the operation. Digital examination was not feasible because of the patients’ very narrow vaginal anatomy. Following vaginoscopy, laparotomy and a bilateral complete pelvic lymphadenectomy were performed in a similar manner to the adult patients who undergo radical hysterectomy. The limits of nodal dissection were the deep circumflex iliac vein caudally and the proximal common
Fig. 1. Pediatric radical abdominal trachelectomy: resection (area in rectangle) includes the cervix, upper vagina, parametrium, and paracolpos.
iliac artery cephalad. Any suspicious lymph nodes were sent for frozen-section analysis. It was our intent to abandon a fertility-sparing approach if positive lymph nodes were identified. The paravesical and pararectal spaces were developed and the bladder was dissected caudal to the mid vagina. The round ligaments were preserved and the infundibulopelvic ligaments with ovarian blood supply were kept intact. Care was taken not to injure the fallopian tubes or disrupt the uteroovarian ligament. The uterine vessels were then ligated and divided at their origin from the hypogastric vessels. The parametria and paracolpos with uterine vessels were pulled medially with the specimen, and a complete ureterolysis was performed similar to a type III radical abdominal hysterectomy. The lower uterine segment was then estimated, and, using a knife, the fundus was separated from the upper endocervix. The uterine fundus with preserved attachments to the round ligaments and uteroovarian ligaments were placed in the superior part of the pelvis, and the specimen consisting of cervix and parametrial was placed on traction cephalad. After completely freeing the parametria and paracolpos, the anterior vaginal wall was identified again and approximately 1 cm of upper vagina was resected with the specimen. An anterior colpotomy was performed with the knife, the vaginal wall was tagged with sutures, and the vaginal incision carried circumferentially to completely resect the specimen (Figs. 2, 3). The uterine fundus was inspected and the distal lower uterine segment was biopsied and sent for frozen-section analysis. Frozen section is also obtained on the distal vaginal margin. Once all frozen sections tested benign, the uterus was reconstructed to the upper vaginal with several 3-0 delayed absorbable sutures (Fig. 4). No cerclage was placed due to the small nature of the uterus and its expected growth with time (Fig. 5). No drains were placed. Standard
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Fig. 2. Reconstruction of uterus to upper vagina with absorbable sutures, no cerclage is placed. Resected specimen showing parametria and vaginal margins, suture marks 12 o’clock position (insert).
antibiotic prophylaxis and routine postoperative care were prescribed.
Discussion In adult women, radical trachelectomy with pelvic lymphadenectomy is a reasonable fertility-sparing approach for the treatment of selected stage I cervical cancers. This operation is considered a major innovation in the surgical therapy of early cervical cancer [1]. Although the concept of a radical abdominal trachelectomy was described and performed on women with cervical cancer by Aburel [2,3] in Romania in the last century, the
Fig. 3. Radical abdominal trachelectomy specimen, suture marks 12 o’clock in vaginal margin. Parametria and paracolpos are demonstrated.
abdominal procedure did not become popular. Fertilitysparing surgery in cervical cancer remained limited to cervical conization for women with very early lesions and a strong desire to retain reproductive function. The radical abdominal hysterectomy with pelvic lymphadenectomy formed the mainstay of treatment for earlystage cervical carcinoma. More recently, the technique of
Fig. 4. Completed reconstruction of fundus to upper vagina. The round ligaments, infundibulopelvic ligaments, and uteroovarian ligaments are preserved. The uterine arteries are divided at the origin from the hypogastric artery.
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Fig. 5. Completed reconstruction fundus is reattached to vagina with no evidence of ischemia, both adnexa remain viable and in their normal positions.
radical abdominal trachelectomy in adult patients was revived and modified. Smith et al. [4] in 1997 reported their technique where the ovarian vessels were not ligated, and, following lymphadenectomy and skeletonization of the uterine arteries, the cervix, parametrium, and vaginal cuff were excised. The remaining cervix was then sutured to the vagina and the uterine arteries reanastomosed [4]. Moreover, the abdominal approach was reported in 3 more cases; two of these patients underwent bilateral ligation of the uterine artery. All 3 patients’ normal menstrual function returned, and 1 patient had a successful pregnancy delivered at 39 weeks by cesarean section [5]. These data confirmed that preservation of uterine function is possible following bilateral abdominal uterine artery ligation as long as collateral circulation is maintained. Radical abdominal trachelectomy is clearly a technically feasible operation in adults and may result in wider parametrial resections than radical vaginal trachelectomy, particularly if the uterine artery is transected at the hypogastric artery and not reanastomosed. In our pediatric patients, we relied on the preservation of collaterals from the round ligaments and uteroovarian ligaments to maintain uterine viability and hopefully normal menstrual function in the future. In addition, it is expected that the pediatric uterus will continue to grow and possibly develop more collaterals. The radical vaginal approach to trachelectomy was developed and popularized by Professor Daniel Dargent in 1987 in France [1]. It is a modification of the radical vaginal hysterectomy (Schauta) to treat early cervical cancer and preserve uterine morphology and reproductive function. This is by far the more popular and preferred approach, and to date several series are available in the English literature to document the feasibility and safety of this operation (Table 1). In addition, many healthy births have been documented in women treated for early cervical cancer with this approach including a case of pregnancy after radical trachelectomy and pelvic irradiation [6]. Unfortunately, the vaginal approach is not technically
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feasible in pediatric patients, and only the abdominal approach is possible. The general eligibility criteria for radical vaginal trachelectomy include: women aged less than 40 years who have a strong desire to preserve fertility, no clinical evidence of impaired fertility, lesion size less than 2 cm, FIGO stage IA–IB1 lesions, no involvement of the upper endocervical canal, and negative regional lymph nodes [7]. These general guidelines may also be adapted for pediatric patients; considerations should include age, limited physical exam, and the long waiting period needed to determine the reproductive outcome for each patient. As to the etiology and risk factors in our patients, clear cell carcinoma of the cervix and upper vagina remains a rare tumor, which is histologically similar to clear cell carcinoma of the ovary and endometrium and is well known for its association with in utero exposure to the synthetic estrogen DES in young patients. Genomic instability as manifested by somatic mutation of microsatellite repeats is commonly seen in these tumors along with evidence of MI in all DES-associated tumors and in 50% of those tumors not associated with DES exposure. Therefore, it has been suggested that the induction of genomic instability may be an important mechanism of DES-induced carcinogenesis [8]; however, in our 2 cases, we could not document a DES exposure in parents or grandparents and this mechanism could not be confirmed. The etiology of carcinogenesis in these 2 cases remains undetermined. We hope that his new procedure will offer pediatric patients with similar presentations and possibly patients with other types of pediatric cervicovaginal tumors amenable to resection an opportunity for cancer therapy with hope for preservation of future reproduction. This procedure represents an attempt towards a less radical fertility-sparing operation that targets the primary tumor and regional lymph Table 1 Summary of laparoscopic pelvic and/or aortic lymph node dissection with radical vaginal trachelectomy Author
Na
Dargent ’94 [1]
28
3
Roy ’98 [7] Shepherd ’98 [9] Renaud ’00 [10]
30 10 34
4 3 –
Dargent ’00 [11]
47
13
Shepherd ’01 [12] Dargent ’02 [13] Covens ’03 [14]
30 96 81
9 – 18
Schlaerth ’03 [15] Burnett ’03 [16] Plante ’04 [17]
12 21 72
2 3 –
a
Patients who gave birth
Some patients may be reported more than once.
Recurrence 1 aortic lymph node 1 local – 1 local 1 distant 1 local 1 distant – 4 2 pelvic 3 none pelvic None None Recurrence free survival = 95%
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nodes. The fact that no residual disease was noted and all lymph nodes were negative is encouraging and supportive of a more precise approach to treat these tumors. With improvements in preoperative imaging modalities, we hope that one day we can identify patients who may even be candidates for a more conservative approach. The role of neoadjuvant chemotherapy in pediatric clear cell cervicovaginal carcinoma remains to be determined. Clearly, a longer follow-up in the pediatric population is needed to determine the oncologic and reproductive outcome of this approach.
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