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9.3 Abdominal Pregnancy
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Fig. 9.25 (a) The gestational sac is in direct contact with the anterior wall; (b) placental implantation site; (c) the gestational sac; (d) fundal uterine wedge resection; (e) elimination of the placental villi; (f) the excised fundal myometrium before applying sutures; (g) mattress sutures of the excised fundal myometrium; (h) the excised placenta and the fetus. (Reproduced with permission from [186] under the CC Attribution License)
a
c
b
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9 Ruptured Ectopic Pregnancy
9.4 Primary Hepatic Pregnancy
9.4.1 Historical Perspective
Cornell and Lash, in 1933, collected records of 236 pregnancies involving placental attachment to 641 sites, the great majority being in the pel­vis. In eight cases, one attachment site was the liver, but the note was not made whether this was the sole area [192], probably meaning abdominal and not primary hepatic pregnancy. Chester M Echols in 1934 [193] and ME Barrett in 1952 [194] mentioned patients with the placental site on several organs, one of which was the liver, but these cannot be termed primary hepatic pregnan­cies. Billington and Goodchild in 1948 [195], Serebryakova and Kanshin in 1952 [196], Van de Loo in 1952, AHG Murley in 1956 [197], and Norman G. Kirby in 1969 [198] described the liver as the only placental site. Mear et al., in 1965, described a full-term living infant deliv­ered at laparotomy (died after 45 min), but the mother died after further severe bleeding from the liver [199]. Luwiliza-Kirunda reported a lith­opedion from a hepatic pregnancy in 1978 [200].
9.4.2 Incidence
Primary hepatic pregnancy is extremely rare. Since 1956, there have been approximately 60 cases published [201203]. The median age of onset was 29.2years (18–46years) [202].
and hepatic pregnancy. Most splenic pregnancies become symptomatic, commonly as bleeding up to 8weeks of pregnancy (see Sect. 24.2). On the con­trary, hepatic pregnancy can be detected in more advanced pregnancy, and the incidence of hemor­rhagic shock or peritonism is present in 1/3 of patients [202]. Live preterm fetuses can be deliv­ered from hepatic pregnancy [207]. Most (93.5%) hepatic pregnancies involve the right lobe, mostly on its inferior surface [202]. Two mechanisms explain such a high incidence of this location of implantation: (1) peritoneal uid circulation from the right paracolic gutter to the diaphragm due to intestinal and diaphragmatic movements and (2) effect of gravity—with the supine position, the lower surface of the right lobe of the liver is the lowest position of the abdominal cavity.
9.4.4 Clinical Presentation
Abdominal pain was the most common symp­tom, mainly in the right upper quadrant. Shoulder pain is rare, more commonly on the right side. Approximately 50% have amenorrhea or a his­tory of vaginal bleeding with dark blood after menstruation [203]. Hemorrhagic shock or peri­tonism is present in 1/3 of patients. Gastrointestinal symptoms include vomiting, nausea, and abdominal distension, while gyne­cological symptoms are vaginal bleeding and discharge [202].
9.4.3 Risk Factors
andPathophysiology
Risk factors for any location EP are similar and listed in Table9.1 [203]. An additional risk factor is perihepatic adhesions from ascending pelvic inam­matory disease entrapping fertilized eggs [204].
The liver and the spleen are favorable for implantation because they are at organs, rich in blood ow, and easily reached by the fertilized ovum [205]. However, both cannot allow placental attachment, resulting in rupture with massive hemoperitoneum [206]. Still, there is a signicant difference in bleeding incidence between splenic
9.4.5 Dierential Diagnosis
The leading symptom of upper right abdominal pain, primarily without (awareness of) amenor­rhea, may mislead to digestive and hepatobiliary pathologies. Another misleading symptom is dyspepsia due to the close relation of the gall­bladder and the duodenum [198].
9.4.6 Diagnosis
9.4.6.1 Laboratory Findings
A complete blood count is mandatory for patients with abdominal pain and signs of hypovolemic/
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9.4 Primary Hepatic Pregnancy
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hemorrhagic shock, including BUN, creatinine, liver, and pancreatic enzymes. Amenorrhea man­dates βHCG testing. Without rupture and intra­peritoneal bleeding, complete blood count can be normal [203].
9.4.6.2 Transvaginal Ultrasound
With elevated βHCG levels, transvaginal US denes the adnexa, the uterus, and gestational status. A normal-sized uterus with a thickened endometrium without an individual gestational sac is suspicious of EP.
9.4.6.3 Transabdominal Ultrasound
Potential locations of EP should be checked, especially when Fallopian tube EP is excluded. Most hepatic gestations are subcapsular with an irregular mass that exceeds the contour of the liver, although some are located within the liver (Fig.9.26). All conrmed cases included hemodynamically stable patients. Doppler can estimate the vascularity of the lesion (Fig.9.27a).
9.4.6.4 Abdominal CT
Contrast-enhanced abdominal CT is indicated when the transabdominal US is unequivocal in hemodynamically stable patients. While abdominal CT has been used in 32% of patients with an accuracy of 100% for splenic pregnancy [210], there are no data for hepatic pregnancy
[202]. Except for the size and location of the ges­tational sac, the extent of the hemoperitoneum, primarily around the liver, can be dened (Fig.
15.27b–d). In more advanced pregnancy, fetal
parts and placenta in the liver are visualized on CT [211] or MRI (Fig.9.28).
9.4.6.5 Abdominal MRI
For suspected pregnancy, MRI should be per­formed after the inconclusive US.It reveals the location and size of the gestational sac (Fig.9.29). Noncontrast MRI, using T2-weighted imaging, is sensitive, specic, and accurate for hepatic EP.It usually showed a round-like, high-signal mass, mainly homogeneous, with unclear margins. At T1-weighted imaging, MRI displayed a hepatic round-like, low-signal mass with undened mar­gins. With contrast enhancement in the arterial phase, the hepatic pregnancy appears as a round­like, low-signal mass with no intensication in the central or peripheral portions. Noncontinuous ring-like intensication is displayed during the venous phase, with lower irregular intensication in the center [213].
9.4.6.6 PET-CT
In one case report, PET-CT discovered unex­pected hepatic pregnancy. The display indicated a lesion with glucose metabolism increased in the peripheral but not in the central portion (Fig.9.30).
Fig. 9.26 (a) Transabdominal US shows uneven fatty liver and a cystic echo mass (arrow) measuring 30×19×25mm, (b) with a hypoechoic nucleus attached
to the inferior surface of the right hepatic lobe. (Reproduced with permission from [208])
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9 Ruptured Ectopic Pregnancy
Fig. 9.27 (a) Transabdominal US (no gestational sac in the uterine cavity) shows a 5.4×4.6cm hyperechoic mass (arrow) in the right hepatic lobe and a uid sonolucent area of 2.7×2.1cm within the mass. The cystic sonolu­cent area within the uid sonolucent area suggests an ectopic pregnancy. (b) CT reveals a mass in the right hepatic lobe (arrow) with a slightly low-density periph­eral portion and an oval lower-density central portion in
the plain scan. (c) CT in the arterial phase shows a periph­eral portion with a signicantly increased density, a peripheral portion with a slightly increased density (arrow) compared with that of the liver parenchyma in the (d) venous phase shows a non-enhanced lower-density central portion in the enhanced scan (arrow). (Reproduced with permission from [209])
9.4.7 Treatment
Management primarily depends on the hemody­namic stability and location of the lesion.
9.4.7.1 Medical Treatment
The gestational sac of >3.5cm is a relative con­traindication for MTX treatment [212]. Medical treatment with IM MTX (1mg/kg) can be admin­istered when blood pressure, pulse, and body temperature are normal, in addition to a normal Fernandez score. Guarding or rebound tender-
Fig. 9.28 Abdominal MRI shows an intrahepatic lesion with fetal parts (arrow). A crescent-shaped area laterally represents placental tissue. (Reproduced with permission from [212])
ness should be absent. Laboratory ndings should exclude acute bleeding; leukocyte count, platelet count, liver transaminases, and renal function
9.4 Primary Hepatic Pregnancy
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Fig. 9.29 MRI characteristics of primary hepatic preg­nancy. (a) T1 reveals a round low-signal focus (3×4.5cm) between the inferior margin of the left hepatic lobe and the lesser curvature of the stomach. Most edges of the focus are clear. (b) T2 reveals the focus appears to be obvious high signals, most of which are homogeneous. (c) The focus appears to be low elliptical signals with enhanced MRI during the arterial phase, and there is no
a b
Fig. 9.30 Positron emission tomography-CT. (a) A max- imum intensity PET-CT shows hepatic pregnancy (blue arrow) (the same patient from Fig. 9.27). (b) Orange
sign of intensication inside the focus and on the edge. (d) Slight intensication is displayed in focus during the venous phase; a bit of ring-shaped intensication may be seen on the edge of the right frontal. (e) Coronal scan reveals that the disease takes on a round-like low signal with a slight noncontinuous ring-like intensication and slight irregular intensication inside [213]
arrow points to the location of the hepatic pregnancy. (Reproduced with permission from [209])
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9 Ruptured Ectopic Pregnancy
Fig. 9.31 Hepatic angiography of primary hepatic preg­nancy. (a) before transcatheter arterial chemoemboliza­tion (TACE), hepatic angiography shows a hypervascular lesion of residual trophoblast tissue in the right hepatic
should be normal. βHCG should be checked once a week for several weeks [214].
lobe and its supply branch from the right hepatic artery; (b) after TACE, Lipiodol on X-ray is densely deposited in the lesion. (Reproduced with permission from [215])
slowly. After embolization, an X-ray conrms the deposition of Lipiodol inside the lesion (Fig.9.31b).
9.4.7.2 Radiological Intervention
Techniques
With bleeding hepatic pregnancy, selective embo­lization can stop the bleeding and stop the preg-
Another option is US-guided MTX or KCL intragestational sac injection transhepatically [212]. Both procedures eliminate surgical complications.
nancy by ischemia (Fig. 9.31). Other methods include US-guided fetal intracardiac potassium chloride and MTX alone or combined, united with maternal IM injection of MTX [212, 216]. Selective embolization is also indicated when (1) hepatic nodule cannot be removed completely because of deep implantation into the hepatic parenchyma and hilum [215], primarily when a hepatobiliary surgeon is unavailable; and (2) postoperative βHCG is rising [215].
A common femoral artery approach is com­mon. A mixture of 6mL of Lipiodol (iodized oil; Guerbet, Roissy, France) and 50mg (1mg/ kg) of MTX is infused via the microcatheter as close as possible to the feeding branch, fol­lowed by embolization of the feeding artery with gelatin sponge particles (0.5–1.0mm). An MTX–Lipiodol emulsion is used to localize the MTX inside the hepatic lesion and release it
9.4.7.3 Surgical Treatment
Signicant bleeding or hemorrhagic shock should be treated with surgical hemostasis. Until 2018, 84% were treated by laparotomy [202]. Intraoperatively, clot-like bulging is found on the surface of the liver, with bleeding from that site (Fig. 9.32). Different surgical procedures are used, including omental transplantation, hepatic artery ligation, liver packing, lobectomy with fetus, and laparotomy combined with intraopera­tive intragestational injection of 20–25mg. MTX (for gestational sac <35mm) or potassium chlo­ride, laparotomy with a maternal postoperative injection of MTX, and postoperative hepatic artery embolization [202, 217].
The intragestational sac injections producing fetal death by cardiac arrest eliminate the need to extirpate a gestational sac in the liver. This mini-
9.4 Primary Hepatic Pregnancy
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Fig. 9.32 Bleeding from hepatic segment 6: a 3-cm bulg­ing mass was detected. This area presented with a smooth surface covered by Glisson’s capsule. Trophoblastic-like material and active bleeding emerged from a break in the continuity of 1cm (arrow). (Reproduced with permission from [201])
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mizes the possibility of hepatic bleeding or bili­ary tract injury. In more advanced pregnancies, maternal MTX involutes the placenta and fetal tissue and reduces the risk of bleeding. The tim­ing of MTX administration related to surgical procedures is not dened. It can be administered preoperatively via IM injection, intraoperatively into the location of implantation, or postopera­tively via IM injection. Postoperative IM admin­istration is routine or selective if postoperative βHCG values rise [218].
Laparoscopy is increasingly used for surgi­cal hemostasis and EP removal in hemodynam­ically stable patients [201, 209, 218]. The trocar position depends on the location of the gesta­tional sac in specic liver segments (Fig.9.33). The suction of blood clots and EP is followed by hemostasis of the bleeding spot with topical hemostats (Fig. 9.34). Pathophysiology of evacuated contents conrms blood clots with clusters of cytotrophoblasts and syncytiotro­phoblasts, consistent with EP.The pathohisto­logical analysis of resected gestational sac reveals hepatic tissue and products of concep­tion (Fig.9.35).
Fig. 9.33 The liver segment 6 gestational sac location necessitates the left lateral decubitus position. The rst trocar inserted by open technique is in the subcostal right region at the midaxillary line (1). Another two trocars are placed under direct visualization in the right ank (2) and the epigastric region (3). ER epigastric region, MAL midaxillar line, PAL posterior axillar line
9.4.7.4 Continuation ofPregnancy andDelivery
Expectant management is possible in centers with immediate recourse to emergency interven­tions and neonatal care. The transabdominal US should detect a viable pregnancy with adequate amnion and an absence of congenital abnormali­ties. The oligohydramnios on US and abdominal pain warrant intervention [207].
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Fig. 9.34 Primary hepatic pregnancy (arrow) implanted on the liver hilum and removed (a) piecemeal and (b) with the aid of suction. (Reproduced with permission from [218])
9 Ruptured Ectopic Pregnancy
through an avascular area to deliver a live new­born. No attempt is made to remove the placenta. Bleeding from the membrane edges is controlled by interlocking sutures and gauze packs. For inadequate bleeding control, gauze packs were removed after 48h [207].
9.4.7.5 Anesthetic andPerioperative Management
See Chap. 2. The operative specimen should be sent to the pathohistological examination, which reveals gestational villi in the hepatic mass. With retained placenta and gestational
Fig. 9.35 Histologic examination of the resected speci­men shows chorionic villi inltrating into the liver tissue (H&E, ×40). (Reproduced with permission from [208])
parts, serial serum βHCG and the transabdomi­nal US during the rst several weeks detect the continuation of hepatic pregnancy (Fig.9.36). Maternal renal and liver function tests should
With fetal viability, operative delivery is indi­cated by median laparotomy or (extended) sub­costal incision. Following the dissection of the surrounding organs (mostly bowel) off the pla­cental membranes, the amniotic cavity is entered
be checked before and after MTX administra­tion. With the remaining gestational sac, suc­cessful intragestational injections result in the disappearance of βHCG levels within 4weeks [212, 217].
9.5 Primary Ovarian Pregnancy
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Intracardiac injection of MTX
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80000
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70000
60000
50000
40000
30000
hCG (milli-international units/mL)
20000
10000
0
0123
Fig. 9.36 βHCG trend after fetal intracardiac injection of MTX (unsuccessful) and KCl (successful) after a week. MTX methotrexate, KCl potassium chloride. (Reproduced with permission from [212])
9.5 Primary Ovarian Pregnancy
9.5.1 Historical Perspective
Intracardiac injection of KCI
456789
Weeks
9.5.2 Incidence
Paul Moulonguet-Doleris, in 1924, reported 77
cases [222], and CR Strother-Stewart, in 1953, De Saint Maurice of Périgord (former province of France, which corresponds roughly to the cur­rent Dordogne) was the rst to observe a case of ovarian pregnancy in 1682. It was a letter in a French journal composed by the Abbe de la Rocque. It was translated to the Latin, in the
Bibliotèque Anatomique de Manget, tome pre­mier, page 623. The fetus was lying in the
abdominal cavity after being torn from the ovary, surrounded by blood. The laceration was visible on the ovary. The patient died of intraperitoneal hemorrhage, and the diagnosis was made post­mortem [219]. Without exacting laboratory examination, ovarian apoplexy [220] may often be misconstrued as an idiopathic event when early abortion of an ovarian pregnancy has occurred. Another misdiagnosis was bleeding corpus luteum [221].
reported at least 125 cases in the English litera-
ture [223]. The incidence of primary ovarian
EP is increasing. In the 1950s, it was estimated
from 1:25,000 to 1:40,000 [224]; in the 1980s
from 1/5000 to 1/8000 [225] and even 1:2850
[226]. Of all ovarian pregnancies, 75–90% are
primary [225, 227]. In the rst half of the
twentieth century, 75.5% were terminated dur-
ing the rst trimester, 12.2% during the second
trimester, and 12.2% lasted to the third trimes-
ter or beyond [224]. HP with ovarian EP is
exceedingly rare, comprising <2% of cases
[227]. The incidence of ovarian EP is still
likely underestimated due to the possibility
that certain cases were successfully treated
with MTX, but were denoted as tubal pregnan-
cies or pregnancies of unknown location [24,
227, 228].
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Both ovaries are equally affected [225,
227, 229], except in women with IUCDs,
where the right side is almost exclusively affected [230232], although left-sided cases exist [221].
9.5.3 Risk Factors
andPathophysiology
Risk factors for EP that include ovarian preg­nancy [224, 225] are presented in Table 9.1. The most common are previous abdominal sur­gery, endometriosis, and IVF [233]. The IUCD is present in 4–68% of ovarian pregnancies [225, 227, 229, 234]. The association between ovarian pregnancy and IUCD use was recog­nized in 1930 [235]. The Lippes’ loop’s free end pointed towards the affected side in each case [236]. Most cases occurred with the Lippes Loop* in place and a single one with a Dalkon Shield [230]. From 1966 to 1983, 27% of ovar­ian pregnancy cases were associated with the IUD in the USA and involved the Cu-7 IUD [237], while in others, copper-based IUCS was present in 88% [229]. It has been suggested that Cu-7 does not increase or decrease the risk of ovarian pregnancy relative to inert plastic IUCDs [237]. During the 1960s and 1970s, the ratio of ovarian pregnancies to EP in IUCD users ranged between 1:7 and 1:13 [226, 229,
238, 239]; its prevalence in the general popula-
tion is smaller but still increasing—from 1:332 [232], over 1:150 to 1:200 [225, 234], over 1:117 [224] to 1:40–1:63 [227]. Approximately 25% do not have known risk factors for (ovar­ian) EP [227].
Prostaglandin-mediated hypercontractility of the tubes in IUCD users may impair the pickup of the ovum [221, 240]. An IUCD causes alterations in the level of prostaglandins in the different seg­ments of the Fallopian tube with inverse peristal­sis and reversed suction [236]. Changes in tissue levels and the ratio between the concentration of prostaglandin E and prostaglandin F are essential for tubal peristalsis [241]. Also, a signicantly larger number of mast cells is present in the tubal
9 Ruptured Ectopic Pregnancy
stroma of IUCD users than in controls [242]. Prostaglandins are mast cell mediators [23]. The mast cells are situated nearer to the smooth mus­cle cells in the tube than to the small vessels due to their role in tubal peristalsis [22]. Different types (including composition, hormones, and concentrations) of IUCDs could have different inuences on ovarian pregnancy rates [229].
In 1876, Ferdinand Hueppe, in an inaugural dissertation, established the conditions to con­sider an ovarian pregnancy: (1) fecundation on the ovary, the ruptured follicle closing itself after­wards, and the fetus developing in the interior of the ovary as a cyst; (2) the ruptured follicle does not close itself, but the placenta retains its implan­tation in the ovary [243].
Spiegelberg criteria from 1878 differenti-
ate an ovarian pregnancy from a tubal preg-
nancy [244]:
• gestational sac is in the region of the ovary,
• EP is attached to the uterus by the ovar­ian ligament,
• histologically proven ovarian tissue in the wall of the gestational sac,
• Fallopian tube of the involved side is intact.
Norris, in 1909, further amplied the rst pos­tulate by stating that the tube must show no microscopic evidence of pregnancy [245]. Stander enlarged the fourth postulate by requir­ing ovarian tissue to be found in several places at some distance from each other in the sac wall [246]. Further modication of Stander’s modi­cation is that ovarian tissue must be demonstrated in the sac walls in several places at some distance from each other and intervening between fetal tissues and any adherent extraneous tissue [224].
Baden and Heins suggested functional classi­cation of “primary ovarian pregnancy” based on the implantation site and later development of the fertilized ovum. Ovarian tissue forms an intact layer around the embryonic tissues. It is subdi-