Eight patients who underwent vaginal RT with pelvic lymphadenectomy during pregnancy in our institute between 2010 and 2020 (Group A), and ten pregnant patients who underwent vaginal RT with pelvic lymphadenectomy before pregnancy during the same period (Group B) were reviewed in this study. Patients who underwent transabdominal cerclage (TAC) and patients before 2010 were excluded from the study. The study protocol was approved by the review board and the ethics committee in our institute (approval number 05–26). Written informed consent was also obtained from each patient.
Clinical characteristics of the patients are summarized in Table 1. Various obstetrical parameters such as fetal growth, changes of uterine cervical length, infectious markers, and oncological parameters such as the results for uterine cervical cytology and tumor markers were obtained from medical records.
Table 1
Clinical characteristics of Group A and Group B.
Patient
|
age
|
parity G(P)
|
clinical stage
|
Histology2
|
diagnostic conization3
|
Group A
|
1
|
32
|
1(0)
|
1B1
|
SCC
|
―
|
2
|
30
|
1(0)
|
1B1
|
SCC
|
―
|
3
|
34
|
2(0)
|
1B1
|
Adeno
|
―
|
4
|
32
|
2(0)
|
1B1
|
Adeno
|
―
|
5
|
41
|
1(0)
|
1B1
|
SCC
|
―
|
6
|
23
|
2(0)
|
IIA
|
SCC
|
―
|
7
|
31
|
2(0)
|
1B1
|
SCC
|
+
|
8
|
29
|
2(0)
|
1B1
|
Adeno
|
―
|
Group B
|
9
|
34
|
1(0)
|
1B1
|
SCC
|
་
|
10
|
29
|
2(0)
|
1A2
|
Adeno
|
་
|
11
|
36
|
1(0)
|
1B1
|
SCC
|
་
|
12
|
37
|
2(1)
|
1B1
|
SCC
|
་
|
13
|
31
|
1(0)
|
1B1
|
SCC
|
―
|
14
|
29
|
2(0)
|
IB1
|
Adeno
|
―
|
15
|
37
|
0(0)
|
1B1
|
SCC
|
―
|
16
|
31
|
0(1)
|
1B1
|
Adeno
|
―
|
17
|
31
|
0(0)
|
1A2
|
SCC
|
་
|
18
|
36
|
0(1)
|
1B1
|
Adeno
|
―
|
Difference1
|
n.s
|
n.s
|
n.s
|
n.s
|
n.s
|
1. “n.s” means statistically “not significant” between Group A and Group B. |
Differences between Group A and Group B were estimated for age, the first |
delivery or not, clinical stage 1B1 or others, SCC or adenocarcinoma, and the |
diagnostic conization was performed or not, respectively |
2. “SCC” means squamous cell carcinoma. “Adeno” means adenocarcinoma. |
3. ”+” means diagnostic conzation was done. “―” means diagnostic conization was not done. |
The clinical indications for vaginal RT in our institute, including those for pregnant patients, are as follows: (1) age ≦ 45 years with a strong desire to preserve fertility, (2) International Federation of Gynecology and Obstetrics (FIGO) stage 1A1 with vascular space involvement, stage 1A2 or stage 1B1, (3) lesion size ≦ 2cm, (4) squamous histology or adenocarcinoma (including adenosquamous carcinoma), and (5) no involvement of the upper endocervical canal as determined by colposcopy or magnetic resonance imaging (MRI), and no evidence of lymph node metastasis.
All of the patients except one had FIGO 2009 stages 1A2–1B1 uterine cervical cancer in this study. Vaginal RT was performed for one patient with stage IIA who strongly desired the preservation of fertility after repeated explanations to her and her family. Adjuvant chemotherapy using paclitaxel and carboplatin was used for her both during the pregnancy and after cesarean section. Assessment of pelvic lymph node metastasis was performed by laparotomy or laparoscopy at the time of vaginal RT. For pregnant patients, it was performed by magnetic resonance imaging (MRI) before the operation and lymph node sampling at the time of the operation.
Vaginal RT was performed based on a modification of the procedure of Dargent et al. Amputation height was preoperatively determined by transvaginal ultrasonography and a careful search of the lesion area by colposcopy for each patient. There were no differences of operative procedures between vaginal RT for pregnant patients and vaginal RT for non-pregnant patients.
Pelvic lymphadenectomy or lymph node sampling by laparotomy or laparoscopy was performed first, followed by vaginal RT. Briefly, a rim of vaginal mucosa was delineated circumferentially and excised so that the anterior and posterior mucosae could cover the cervix. The vesicovaginal space was defined laterally on each side. Then the descending branches of the uterine arteries and the cardinal ligaments were cut at the level of Type II hysterectomy. After this procedure, we usually amputated the uterine cervix 10mm below the internal os of the uterus. A nylon suture was placed around the residual cervix to support cervical strength, and Strumdorf sutures were placed to cover the surface of the cervix. For pregnant patients, we confirmed the fetal status by ultrasonography soon after the operation, and carefully checked the amount of bleeding from the vaginal wound, and the existence of leakage of amniotic fluid. For pregnant patients, continuous prophylactic intravenous administration of tocolytic agents was performed for at least one week after RT.
Follow-up of the cancer was performed by periodical examination of cytology, tumor markers, CT scans, and/or MR imaging. Tumor marker examination and CT scans were not usually performed for pregnant patients.
For the management of pregnant patients after vaginal RT, there are as yet no international guidelines. Of course, there were no differences of the management methods between patients who underwent RT during pregnancy and those who underwent RT before pregnancy. Follow-up of pregnant patients after vaginal RT was performed according to a protocol described previously [6]. We recommend that patients enter hospitalization early in the second trimester of the pregnancy even if there are no signs of threatened abortion. Under hospitalization, patients undergo: (1) bed rest, (2) daily vaginal disinfection with 0.3% chlorhexidine, (3) prophylactic administration of an ulinastatin vaginal suppository, (4) routine examinations for bacterial vaginosis and maintenance of normal vaginal flora, (5) examination of the Nugent score, granulocyte elastase level and oncofetal fibronectin in vaginal secretion, serum CRP, general blood examination, and the administration of metronidazole in cases with a Nugent score > 5, and/or that are cervical elastase or fibronectin positive, (6) routine examination of uterine cervical length using transvaginal ultrasonography, (7) long-term tocolysis using ritodrine hydrochloride, magnesium sulfate, and nifedipine for patients with abdominal pain/tension, or for those with the uterine cervical length shortened to < 2cm, and (8) weekly administration of a hydroxyprogesterone caproate depot.
Considering the maternal physical and psychological conditions from the long-term bed rest and tocolysis, and to avoid the sudden occurrence of preterm premature rupture of membranes (pPROM), cesarean section was usually scheduled at around 35 weeks of pregnancy except for patients who required emergent cesarean section.
Standard statistical tests, including Welch t-test, were used to analyze the clinicopathological data using Microsoft EXCEL 2016. A p-value of less than 0.05 was considered statistically significant.