First Report of a Late Lethal Pulmonary Biliary Embolism following Hepatic Microwave Ablation

Abstract

Microwave ablation (MWA) is an established tool in modern therapy of hepatic malignomas. Although it is generally a safe procedure, severe complications related to MWA have been reported in the literature. We report on the first case of a fatal pulmonary biliary embolism following hepatic MWA. The development of pulmonary biliary embolisms is possible and should be considered particularly in the case of by extensive ablation near liver veins.

Introduction

Thermal ablation is an established tool in modern therapy of primary and secondary liver tumors. It is of particular importance as a locoregional therapeutic option for patients in an inoperable condition or with unresectable disease, and it is widely accepted as a definitive therapy in well-selected patients with small tumors [1, 2]. Moreover, some specialized hepatobiliary centers worldwide provide ablation in tumors >3 cm using simultaneously multiple ablation probes or an overlapping technique [3]. The reported morbidity rate of these procedures, at 16–20%, is definitively higher than that of routine ablations (4–9%) [2, 3]. Bleeding and infectious complications followed by injury of the biliary tract and adjacent organs are commonly observed, followed by cardiopulmonary complications and, more rarely, liver failure.

Radiofrequency ablation (RFA) and microwave ablation (MWA) are the 2 clinically established thermal ablative modalities achieving tumorous tissue destruction by local heat application. RFA produces heat by means of a high-frequency alternating electrical current (300–500 kHz), that facilitates electric conductivity through tissue, and the heat conduction is mainly passive. MWA reaches a much higher operating frequency (≥900 MHz), with heat created mainly by flipping water/dipole molecules, and thereby provides a larger area of active tissue heating. Based on these different physics, last-generation MWA systems appear to have superior physical and local tissue destruction properties. They allow greater energy deposition with shorter ablation times, larger ablative zones, and less susceptibility to the “heat-sinking” effect in the proximity of large vessels. Moreover, MWA enables the simultaneous treatment of multiple tumors and there is no risk of return electrode-related burns [2, 4, 5].

In the literature, there is only one reported case of biliary pulmonary embolism (BPE) related to ablative therapy in 2003. Schmidt-Mutter observed a BPE that occurred during CT-guided drainage of an intrahepatic fluid collection with abscess characteristics following 2 courses of RFA of a hepatocellular carcinoma [6].

We report on a late lethal BPE after MWA of an unresectable colorectal liver metastasis. To our knowledge, this is the first case of a BPE after MWA reported in the literature.

Case Presentation

The 66-year-old patient had a synchronous hepatic metastatic carcinoma of the upper third of the rectum. Due to bilateral liver metastases and nonstenosing primary tumor, a “chemo-first-liver-first” concept was pursued. The patient received 4 cycles of FOL­FOX combined with cetuximab. In March 2018, a left-lateral liver resection, an atypical metastasectomy in segments 4a/8, and a right-sided portal vein ligation for hypertrophy induction were performed at another institution. One central metastasis in segment 8 remained in the liver, due to its proximity to the preserved hepatic veins. After 2 further cycles of chemotherapy, we conducted another surgical exploration in June 2018. The already-mentioned central lesion, measuring 8 cm, showed an infiltration of the remaining veins, so the procedure was aborted. After 6 more cycles of chemotherapy and radiological downsizing of the tumor, a new surgical exploration was carried out in December 2018. The tumor, measuring 5.2 cm, was still not resectable (Fig. 1), so we performed a thermal ablation with an overlapping technique (resulting in an ablation zone of 8–9 cm). Short-term restaging by liver MR showed no evidence of vital tumor tissue or newly emerged liver lesions, so the resection of the primary followed (Fig. 2).

Fig. 1.

CT scan before ablation showing the proximity of the downsized tumor to the hepatic veins.

Fig. 2.

MRI 10 weeks after ablation showing the ablation zone with a diameter of 10 × 7.5 cm, and mostly liquid portions with central hyperintense tissue and no signs of vital tumor.

A deep anterior rectal resection was performed with a protective ileostoma in February 2019. Tumor stage was ypT3, ypN0(0/25), ypM1(HEP), L0, V0, R0. The patient was transferred to our normal ward on the 2nd postoperative day (POD). On the 5th POD, standardized anastomosis monitoring was performed. This revealed an anastomotic insufficiency, which was treated with an endosponge. An empirical antibiotic therapy was started and then modified according to the antibiogram. Under this treatment and with regular changes of the endosponge system, a reduced wound cavity with clean granulation tissue was observed. The patient returned to a normal diet and mobilization was performed. On the 15th POD, the previously oligosymptomatic patient complained of slight nausea without vomiting or pain. However, the patient was only partially oriented. He was normotensive with a tachycardia of >100 bpm. A drop in oxygen saturation from 89 to 85% on room air was observed. Respiratory insufficiency was confirmed by arterial blood gas analysis. Thoracic CT scan revealed no pathological findings. The patient was transferred to the intensive care unit. Because of the clinical suspicion of a thromboembolic event, therapeutic heparinization was started.

Here, a rapid respiratory exhaustion was observed, which made emergency intubation necessary. Shortly afterwards, the patient was resuscitated. Venous congestion in the neck and impairment of the gas exchange corresponded to a pulmonary artery embolism, so that a lysis was initialized during resuscitation. A return of spontaneous circulation was achieved. Clinical and sonographic cardiological evaluation revealed a cor pulmonale. Despite the continuation of the intensive care measures, further deterioration with increasing metabolic acidosis became apparent over the next few hours. The patient died as a result of global respiratory insufficiency on the morning of the 16th POD.

On the autopsy, the site of the previous liver metastasis showed an arroded hepatic vein branch with invasion of necrotic fragments and bile into the vascular lumen (Fig. 3, 4) and subsequent disseminated biliary pulmonary embolism (Fig. 5). No vital tumor manifestations were found in the liver. The cause of death was assumed to be a consecutive right heart failure.

Fig. 3.

Autopsy specimen of liver showing the ablation zone with necrotic tissue and the adjacent hepatic vein (forceps).

Fig. 4.

Cross-section of liver parenchyma showing a large hepatic vein. Necrotic tissue and bile material can be observed (intraluminal). HE. ×100.

Fig. 5.

Cross-section of lung parenchyma showing vascular congestion. Bile material is shown in a small pulmonary artery. Normal alveoli. Microthrombosis with bile material is visible. HE. × 200.

Discussion

Bilhemia is the reverse term of hemobilia when bile passes through a fistula into the blood vessels, most commonly the portal or hepatic veins [7]. A prerequisite for it to occur is that the pressure in the bile duct or collection exceeds that in the communicating vessel [7]. This condition and its further complication, BPE, are extremely rare, and are caused mostly by hepatic trauma or iatrogenic liver injuries. After the first mention of the term bilhemia in 1974 by Clemens and Wittrin [8], the milestone publication of Sandblom et al. [7] in 2000 was the first to describe the condition; they reported 50 cases, 23 of which were due to trauma and 14 due to iatrogeny. Since then, in a period of 20 years, around 20 cases of bilhemia have been described [6, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24]. Recognized iatrogenic causes are percutaneous transhepatic cholangiography [23], transjugular interventions [12, 18, 20, 22], transhepatic central venous catheter placement [14] and liver punction or drainage [10, 11, 24] including 1 case with an abscess drainage after ablative therapy [6]. Other nontraumatic causes include local infectious processes commonly related to lithiasis [9, 13, 21]. BPE occurred in 22 of the total 70 reported cases and was always fatal (Table 1) [6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24].

Table 1.

Publications after the year 2000 describing cases of bilhemia and bile pulmonary embolism

First author [ref.]	Year	Diagnosis	Traumatic	Iatrogenic causes, n						Other causes, n
			causes, n	PTC	biopsy/drain	OP	TI	RFA	CVC
Sandblom [7]	2000	BH + BPE + review	23	8	3	3	−	−		13
Güitrón-Cantú [9]	2002	BH								1
Schmidt-Mutter [6]	2003	BH + BPE						1
Siddiqui [10]	2005	BH + BPE + review		1
Weintraub [11]	2006	BH			1
Bergmann [12]	2007	BH					1
Morentin [13]	2007	BH + BPE								1
Sierre [14]	2007	BH + BPE							1
Singh [15]	2007	BH	4
Hommes [17]	2009	BH	1
Singal [18]	2009	BH					1
Fournier [16]	2009	BH	1
Turk [19]	2010	BH	1
Kruel [20]	2013	BH					1
Lorenzo [21]	2014	BH + BPE								1
Zhang [22]	2015	BH					1
Çakır [23]	2019	BH		1
Caruso [24]	2020	BH			1
Total, n			30	10	5	3	4	1	1	16

BH, bilhemia; BPE, bile pulmonary embolism; OP, operation; PTC, percutaneous transhepatic cholangiography; RFA, radiofrequency ablation; TI, transjugular intervention; CVC, central venous catheter.

Early identification of bilhemia, which would give some room for therapeutic measures to be undertaken, is rather difficult. Suspicion should be raised when a rise in total and direct serum bilirubin, without signs of hepatic dysfunction, is observed. When BPE is its first manifestation, then it is noticed by symptoms of pulmonary distress (hypoxia or tachycardia), and then evolves rapidly, as in our case, to respiratory and hemodynamic failure. The CT scan shows no pulmonary thrombus as the bile in the lung vessels is radiolucent. The definite diagnosis is provided by the autopsy [7].

In our case, in the absence of any liver manipulation for several weeks, the plausible hypothesis was that at some point, the liquefaction and pressure in the intrahepatic collection, consisting of bile and tumor necrosis, overcame the resistance of the damaged wall of the arroded venous radical crossing the ablation zone. The rapid deterioration did not permit possible therapeutic options like biliary decompression, drainage, or venous stenting. It is noteworthy that the drainage of the collection can itself trigger the complication, as already described in the literature [6]. The autopsy showed, in the microemboli of every embolized pulmonary vessel, mainly bile material (Fig. 5). The main differential diagnosis of the “classical” pulmonary embolism, a common complication after larger-scale surgical interventions, would be a negative thoracic CT scan and the abovementioned indicative histopathological findings, not plausible in our case.

Oncological treatment protocols for patients with initially unresectable findings often require complex and staged treatment regimes. Thermal ablation, with radiofrequency or microwave technology, is claiming its distinctive role in pushing the frontiers of modern oncological liver surgery and therapy. MWA, in particular, with the advantage of less “heat-sink” effects, enables faster procedures and bigger ablation zones even near hepatic vessels [2]. In this context, clinical suspicion of rare complications such as bilhemia and its fatal complication BPE, should be high, particularly in cases of extensive ablation near the confluence of the liver veins.

Statement of Ethics

The descendants of the subject gave their written consent to publish this case (including the publication of images).

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

There was no funding.

Author Contributions

M.S.J., G.M., and K.J.O.: conception and design. M.S.J. and G.M.: acquisition of data, analysis and interpretation of data, drafting of manuscript. K.J.O. and B.F.: critical revision of manuscript.