HCC during pregnancy, which is believed to have a worse prognosis than that among non-pregnant woman, is extremely rare, with only 62 cases having been reported worldwide to date [1,2,3,4,5,6,7,8,9,10,11,12,13,14]. Accordingly, studies have shown an overall 6-month and 1-, 2-, and 3-year survival rates of 50%, 29.5%, 18.2%, and 13.6%, respectively, with a median survival of 18 months in pregnant patients with HCC [2]. Moreover, the previous reports have revealed that 20% of the pregnant patients with HCC developed distant metastasis upon presentation [3]. Although hepatic resection has been the best potentially curative therapy for HCC [1,2,3,4,5], Choi et al. [2] reported that only 16 of 48 pregnant mothers with HCC underwent liver resection. Currently, repeat hepatectomy seems to be a better choice for recurrent HCC. However, no long-term survival after HCC recurrence during pregnancy has been reported in the literature [5]. Nonetheless, the present case survived without recurrence for approximately 2 years after the second hepatectomy for recurrent HCC and 5 years after the first hepatectomy.
Several studies have shown that pregnancy clearly has an adverse effect on the prognosis of HCC [3, 6,7,8], with only 3 of 29 patients surviving 12 months or more after diagnosis [6, 9]. HCC becomes aggressive during pregnancy, primarily due to two main etiologies: (1) estrogen elevation, which accelerates HCC evolution, and (2) immune suppression during pregnancy [3]. Accordingly, estrogen has been shown to increase hepatocyte mitosis, hypervascularity, and free radicals; reactivate the hepatitis B virus; and decrease humoral immunity [3]. During pregnancy, large amounts of human chorionic gonadotropin, estrogen, and placental lactogen secreted from the placenta are believed to promote the growth and reproduction of cancer cells, thus aggravating the aggressiveness of the underlying HCC [4]. Moreover, gestational immune suppression may be an enabling factor for tumor progression [6, 8].
Previous studies have reported that pregnancy itself could promote rapid HCC growth and increase the risk of tumor rupture [6] and hemorrhage—both of which are life-threatening complications. Indeed, approximately 10% of HCCs during pregnancies are complicated by tumor rupture, perhaps, partly due to tumor liquefaction necrosis, which, together with the increased intra-abdominal pressure secondary to the pregnancy, predisposes patients to rupture and hemorrhage [4, 6,7,8]. Therefore, delaying treatment until delivery after 32 weeks of gestation could threaten both maternal and fetal survival [1]. Despite our patient being 20 weeks pregnant, we determined that surgery could not be delayed any longer given that the tumor was protruding from the liver surface and had a high risk of rupture.
Treatment strategies for malignant neoplasms detected during pregnancy remain controversial given the need to consider both the mother and the fetus. Accordingly, majority of the reported cases had resulted in termination of pregnancy upon diagnosis of cancer [4, 7, 9, 10]. For pregnancies in the first trimester, maternal survival usually takes precedence. Delaying resection until the 28th week would be futile considering that neither the mother nor the baby will have survived [4, 6, 11]. Therefore, therapeutic abortion should be offered, so that the mother can received treatment as soon as possible [7]. For patients in the second or third trimesters, a thorough discussion with the patient on the management plan should be adopted [7]. Thorough discussions with a multidisciplinary team of surgeons, oncologists, and obstetricians would be necessary to decide the appropriate timing of surgery while considering the potential viability of the fetus. For smaller neoplasms, a delay in resection to allow more fetal maturity may be a reasonable approach [4]. During the third trimester, surgery should not be delayed given that the fetus can be delivered through Cesarean section simultaneously with hepatectomy [4]. The 28th gestational week is the critical point of fetal maturation. Premature birth has been defined as that before the 28th week of gestation, before which survival of the baby is much less probable. Therefore, the gestational age of the baby plays a major role in decision-making [4]. In addition, delivery before 32 weeks of gestation should be avoided because of fetus immaturity [1].
Recently, various surgeries, including hepatectomy, have been safely performed during the second and third trimesters, suggesting that patients do not always need to terminate their pregnancy [1]. We think that the important points to note in hepatectomy of pregnant women when performing hepatectomy while continuing pregnancy are to avoid pressure on the uterus, shorten the operation time, and reduce blood loss. Preoperative simulation of hepatectomy and monitoring fetal heartbeat are essential. Complications of anesthesia should also be considered. In this case, after discussions with a cancer board consisting of experts from the departments of gastroenterology, obstetrics and gynecology, and surgery, as well as obtaining appropriate informed consent from the patient and her family, we decided to perform a hepatic resection after therapeutic abortion. Considering that the patient was still 20 week pregnant, delivery was not viable. However, surgery could not be delayed any longer given the rapid tumor growth, such that rupture was imminent, which was likely associated with pregnancy. Moreover, given that the tumor was in contact with the IVC and RHV, massive bleeding during surgery could cause a sudden drop in blood pressure, endangering both maternal and fetal life. Despite other opinions regarding the treatment choice, hepatic resection had been performed after abortion, prioritizing the rapidly growing HCC and maternal safety.
