**3. Cases: The treatment of cesarean scar and ovarian pregnancies with laparoscopy-assisted local injection of etoposide**

Case I: A 37 year-old-female, gravida 5, para 2 (cesarean section twice), abortion 2, had presented with a 8-week history of gestational amenorrhea. She accidentally found herself pregnancy and asked for an elective abortion in a local clinic. Her general condition was fair. She was considered intra-uterine pregnancy at local clinic and uterine curettage had been performed 3 times since she kept suffering from vaginal bleeding after first curettage. She came to our hospital for second opinion due to persistent vaginal bleeding. trans-vaginal sonography revealed an empty uterus and suggested an ectopic sac of 1.9 × 1.7 cm in diameter between anterior wall of uterus and bladder on previous cesarean scar. β-hCG level was measured at 572.2 mIU/mL. Based on these findings, a cesarean pregnancy was suspected. A laparoscopy was then performed while an ecchymotic lesion (2cm) found bulging from the uterine wall at the previous cesarean scar area. The two fallopian tubes and two ovaries

were intact and normal. Confirmed with trans-vaginal sonography, the mass was indicated

Fig. 1. Chemotherapeutic agent was injected into the ectopic sac laparoscopically, followed by bipolar electrocoagulation (black arrow).

The Treatment of Ectopic Pregnancy with

Laparoscopy-Assisted Local Injection of Chemotherapeutic Agents 221

at laparoscopy was sent for pathologic examination, which showed scant chorionic villi and granulosa cells (GC) in support of the diagnosis of ovarian pregnancy. The patient was followed up with serial trans-vaginal sonography and checking of b-hCG levels. The b-hCG levels declined continuously to 37.34 mIU/mL 8 days after surgery and 6.01 mIU/ mL 1

The traditional treatments for ectopic pregnancies are considered more invasive procedures. Therefore, how to select one of the less invasive procedures to diagnose and treat this rare ectopic pregnancy is important. For example, in case I, a deeply implanted cesarean scar pregnancy was growing towards the abdominal cavity and bladder, thus we choose laparoscopy as a primary mean to approach the cesarean scar pregnancy (Vial, Petignat, & Hohlfeld, 2000; C. J. Wang, et al., 2006). Trans-vaginal sonography-guided local injection not only offers a precise localization of the injection site, but also offered a minimally invasive procedure for the case. Furthermore, local injection of etoposide bypasses the systemic side effects of the drug. Taken together, trans-vaginal sonography-guided laparoscopic local

**4. The comparison of etoposide and methotrexate efficacies on tubal** 

Etoposide, an antineoplastic agent, can produce cytotoxic effects by damaging DNA, thereby inhibiting or altering DNA synthesis. The drug appears to be cell-cycle dependent and cyclephase specific, inducing G2 phase arrest and killing cells in the G2 and late S phases. In 2002, Chen et al. successfully used a ultrasound-guided direct injection of etoposide to treat an interstitial pregnancy (C. L. Chen, et al., 2002). Based on the finding that etoposide was more effective and had fewer side effects in the management of low-risk gestational trophoblastic tumor, compared to methotrexate treatment (Matsui, et al., 2005), direct injection of etoposide for ectopic pregnancy is considered. Local administration of methotrexate was described in several cases (Hung, et al., 1996; Monteagudo, Minior, Stephenson, Monda, & Timor-Tritsch, 2005; Timor-Tritsch, et al., 1994). On the other aspect, the use of etoposide in ectopic pregnancy is relatively new. The standardized protocol is not yet available, although there were few cases used ultrasound-guided direct injection of etoposide to treat ectopic pregnancy (C. H. Chen, et

From 1993 through 2009, 28 patients of tubal pregnancy received local injection of methotrexate or etoposide were documented. In all cases, age, body weight, hemoglobin level and the operation time were recorded. The gestational age, cardiac activity of the conceptus, β-hCG levels before and after the treatment, and the occurrence and outcomes of subsequent pregnancies were evaluated. Among the enrolled patients, methotrexate has been administered locally to 11 patients and etoposide to 17 patients. In group (I), 50 mg of etoposide was injected into the ectopic sites by laparoscopy. In group (II), 50 mg of methotrexate was applied. All patients were followed up with serial β-hCG level monitoring. None of the patients had significant side effects of systemic treatment of the

The administration of methotrexate locally was chosen to avoid the adverse effect of systemic administration of methotrexate. Hung et al. observed that methotrexate alone or combined with procedures such as curettage or cervical tamponade is effective in ectopic pregnancies of up to 12 weeks (Hung, et al., 1996). In this survey, the median (range) of the time it took to decline to the non-pregnant β-hCG level (undetectable or below 5 mIU/mL) of methotrexate injection group was longer than the etoposide injection group, though not

agents. More than 50% of the patients had a gestational size of greater than 30 mm.

week later. The patient menstruated 25 days after the procedure.

injection of etoposide for such cases are suggested.

al., 2009; C. L. Chen, et al., 2002; Juan, et al., 2008).

significant difference is observed (Table 1).

**pregnancy treatment** 

a cesarean scar pregnancy. With the guidance of trans-vaginal sonography to precisely estimate the depth of the puncture site to the gestational sac, 100mg of etoposide was directly injected into the ectopic sac by laparoscopy (Figure 1). The puncture site was immediately sealed by bipolar electro-coagulation. The patient was followed up with serial trans-vaginal sonography and -hCG level monitoring. The trans-vaginal sonography showed a progressive shrinkage of the mass, and the -hCG levels declined continuously to 28.1 mIU/mL 9 days after the surgery, and 5.0 mIU/mL 17 days later. The patient experienced normal menstruation 45 days after the procedure.

Case II: A 33-year-old woman, gravida 1, para 0, had presented with a 7-week history of gestational amenorrhea and lower abdominal discomfort. Her general condition was fair. The serum b-hCG level was measured at 2,765 mIU/mL. The trans-vaginal sonography revealed an empty uterus and suggested an ectopic sac of 4.3 by 2.8 cm in diameter in the right ovarian region. The fluid in the Douglas pouch measured 2.0 x 1.8 cm in diameter. Based on these findings, an ovarian pregnancy was suspected. A laparoscopy was then performed. One hundred milliliters of bloody fluid was collected from the cul-de-sac. The two fallopian tubes were intact, and the uterus and left ovary were normal. A 4-cm diameter bluish and hemorrhagic mass on the right ovary indicated the possibility of an ovarian pregnancy. Punch with aspiration and direct injection of 100 mg of etoposide into the ectopic sac (Figure 2) was performed and the fluid aspirated from the hemorrhagic sac seen

Fig. 2. After local injection of the chemotherapeutic agent, bipolar electro-coagulation was used to seal the puncture site.

a cesarean scar pregnancy. With the guidance of trans-vaginal sonography to precisely estimate the depth of the puncture site to the gestational sac, 100mg of etoposide was directly injected into the ectopic sac by laparoscopy (Figure 1). The puncture site was immediately sealed by bipolar electro-coagulation. The patient was followed up with serial trans-vaginal sonography and -hCG level monitoring. The trans-vaginal sonography showed a progressive shrinkage of the mass, and the -hCG levels declined continuously to 28.1 mIU/mL 9 days after the surgery, and 5.0 mIU/mL 17 days later. The patient

Case II: A 33-year-old woman, gravida 1, para 0, had presented with a 7-week history of gestational amenorrhea and lower abdominal discomfort. Her general condition was fair. The serum b-hCG level was measured at 2,765 mIU/mL. The trans-vaginal sonography revealed an empty uterus and suggested an ectopic sac of 4.3 by 2.8 cm in diameter in the right ovarian region. The fluid in the Douglas pouch measured 2.0 x 1.8 cm in diameter. Based on these findings, an ovarian pregnancy was suspected. A laparoscopy was then performed. One hundred milliliters of bloody fluid was collected from the cul-de-sac. The two fallopian tubes were intact, and the uterus and left ovary were normal. A 4-cm diameter bluish and hemorrhagic mass on the right ovary indicated the possibility of an ovarian pregnancy. Punch with aspiration and direct injection of 100 mg of etoposide into the ectopic sac (Figure 2) was performed and the fluid aspirated from the hemorrhagic sac seen

Fig. 2. After local injection of the chemotherapeutic agent, bipolar electro-coagulation was

used to seal the puncture site.

experienced normal menstruation 45 days after the procedure.

at laparoscopy was sent for pathologic examination, which showed scant chorionic villi and granulosa cells (GC) in support of the diagnosis of ovarian pregnancy. The patient was followed up with serial trans-vaginal sonography and checking of b-hCG levels. The b-hCG levels declined continuously to 37.34 mIU/mL 8 days after surgery and 6.01 mIU/ mL 1 week later. The patient menstruated 25 days after the procedure.

The traditional treatments for ectopic pregnancies are considered more invasive procedures. Therefore, how to select one of the less invasive procedures to diagnose and treat this rare ectopic pregnancy is important. For example, in case I, a deeply implanted cesarean scar pregnancy was growing towards the abdominal cavity and bladder, thus we choose laparoscopy as a primary mean to approach the cesarean scar pregnancy (Vial, Petignat, & Hohlfeld, 2000; C. J. Wang, et al., 2006). Trans-vaginal sonography-guided local injection not only offers a precise localization of the injection site, but also offered a minimally invasive procedure for the case. Furthermore, local injection of etoposide bypasses the systemic side effects of the drug. Taken together, trans-vaginal sonography-guided laparoscopic local injection of etoposide for such cases are suggested.
