Intrahepatic caval leiomyosarcomas are rare tumors with limited therapeutic options as patients with the disease are not eligible for liver transplantation from the deceased-donor pool. Advances in surgical techniques gained in split and domino liver transplant procedures can be applied to resection of advanced tumors involving the hepatocaval confluence. Here, we describe the case of a 58-year-old white female who presented with visible abdominal wall collaterals and a palpable right subcostal tumor. Imaging revealed a 5.7 × 5.7 × 11-cm intrahepatic caval soft tissue mass extending into the hepatic veins, right renal vein, and infrarenal caval vein. The entire inferior caval vein was resected en bloc with the liver and right kidney and replaced with a blood group-identical fresh caval vein graft from a deceased donor. The splanchnic circulation was decompressed with a temporary portocaval shunt to the caval vein graft, and caudal inflow into the caval vein graft was established with a left iliac anastomosis. Ex vivo resection of the native inferior caval vein containing the intravascular tumor together with a sleeve of liver was performed under hypothermic conditions, and hepatic outflow was reconstructed with vein from the deceased donor. The liver was autotransplanted via the classical piggyback technique with uneventful portal reperfusion following a cold ischemic time of 2 hours. Histology confirmed a grade 3 leiomyosarcoma with clear resection margins. Liver function was stable, and the patient is currently alive at 2 years after resection. Follow-up imaging at 12 months was unremarkable, but local recurrence was detected on the most recent computed tomography scan. In conclusion, ex vivo resection of an intrahepatic caval leiomyosarcoma with inferior caval vein replacement by a deceased-donor caval graft and subsequent liver autotransplantation are technically demanding but provide a chance on prolonged survival.
Key words : Hepatocaval confluence, Surgical diagnostic technique, Vascular grafting
Leiomyosarcomas of vascular origin are rare mesenchymal tumors. Approximately 400 cases have been reported, most commonly arising from the inferior vena cava (IVC).1 An aggressive surgical approach is the only possible curative therapy; margin status, tumor size, and radical resection have been recently identified as dominant predictors of survival.
Involvement of the upper IVC and hepatic veins, although uncommon, carries an increased risk of death and is traditionally considered to be unresectable by conventional surgical techniques.2 Preservation of the hepatic outflow poses the main challenge in surgical resection of these tumors and requires sophisticated reconstruction during total vascular exclusion of the liver. We report a rare case of caval leiomyosarcoma involving the orifice of the hepatic veins, which required en bloc IVC resection, hepatectomy, and right nephrectomy with subsequent IVC vein engraftment from a deceased donor and liver reimplantation after ex vivo tumor excision.
Clinical and radiologic findings
A 58-year-old white female presented with a palpable right subcostal tumor and visible abdominal collaterals that had developed over 6 months. Cross-sectional imaging by computed tomography scan and magnetic resonance imaging revealed a 5.7 × 5.7 × 11-cm intrahepatic caval soft tissue mass that extended from the hepatic veins to the infrarenal IVC and into the right renal vein (Figure 1). The left hepatic vein outflow was compromised by the extent of the intravascular sarcoma. An occlusive thrombus of the caudal IVC below the intravascular mass extending into the iliac veins caused extensive venous collater-alization, in particular via the gonadal veins. Imaging showed no evidence of metastatic disease elsewhere in the body. A transjugular biopsy obtained only non-lesional tissue, but tissue diagnosis of high-grade leiomyosarcoma was established by endoscopic ultrasonography-guided fine needle aspiration. Liver and kidney function tests were within normal ranges. A dimercaptosuccinic acid nuclear scan demon-strated homogenous renal cortical activity with a differential function of 56% in the left kidney and 44% in the right kidney.
Surgery was carried out as a joint procedure by the sarcoma service and the hepatobiliary and liver transplant unit after an interdisciplinary planning meeting involving anesthesiology and surgical group staff. The liver appeared healthy, and no metastatic spread was detected within the peritoneal cavity. Maximum length of the suprahepatic IVC was obtained by ligation of the diaphragmatic veins. The liver was mobilized, and the infrahepatic IVC was dissected in full length to the iliac bifurcation and left renal vein. The caval mass was dissected from the pancreatoduodenal complex, and the right renal artery was isolated. The structures of the hepatoduodenal ligament were individually transected (common hepatic artery cut at gastroduodenal artery level and bile duct closer to the duodenum) just before en bloc resection of the entire infradiaphragmatic IVC, liver, and right kidney, leaving an empty right hemi-abdomen (Figure 2, A and B).
The native IVC was replaced with an identical blood group, previously reconstructed fresh vein from a deceased donor composed of 2 caval grafts. The upper caval anastomosis was fashioned by continuous suture of the posterior wall, leaving the anterior half of the circumference to be closed with interrupted sutures. The splanchnic circulation was decompressed by creation of a temporary portocaval shunt to the IVC graft utilizing a fresh iliac vein interpositional graft from the same deceased donor (Figure 2C). Caudal inflow in the IVC graft was subsequently established with a running suture of the left iliac vein of the graft to the native IVC confluence after iliac thrombectomy. The left renal vein was not reinserted into the caval graft as it was adequately drained by gonadal and adrenal collat-eralization. A veno-venous bypass was not used.
The explanted liver had meanwhile been perfused via the portal route with 2 liters of cooled heparinized histidine-tryptophan-ketoglutarate by a separate surgical team on the backbench, and the bile duct was flushed. The intrahepatic caval leio-myosarcoma was resected ex vivo with a sleeve of caudate lobe after ligation of short hepatic veins. A small patch of the 3 hepatic veins was obtained free of tumor, and the hepatic vein outflow was reconstructed with a skirt-like graft venoplasty from the deceased donor (Figure 2D). Reimplantation of the liver was performed after an anhepatic time of 2 hours with the use of the classical piggyback technique.
Part of the upper caval graft anastomosis with interrupted sutures was reopened with an exact size match to the reconstructed hepatic outflow, and a longitudinal venotomy of the IVC graft was made to create a wider orifice. Complete clamping of the IVC graft was required for the 15 minutes needed for the caval anastomosis, after which flow in the caval graft was restored. The temporary portocaval shunt was disengaged. The extra length of the portal vein reconstruction was discarded as the end-to-end portal vein anastomosis could be comfortably fashioned to the native portal vein without the need for extension and portal reperfusion was uneventful. The native gastroduodenal artery patches were used for the arterial anastomosis, and the biliary system was reconstructed by end-to-end choledochocholedochos-tomy without a T tube (Figure 2E). Cholecystectomy was performed before abdominal closure as complete transection of the hepato-duodenal ligament causes gallbladder denervation, and, additionally, auto-transplantation placed the patient at risk of ischemic cholecystitis. Intra-operative Doppler ultrasonography of the liver demonstrated satisfactory flow across all vascular reconstructions. The total duration of surgery was 9 hours 35 minutes with an implantation time of 29 minutes.
The resected IVC measured 135 mm × 55 mm × 45 mm and was filled with a pale, white, whirled tumor with areas of hemorrhage and necrosis, amounting to no more than 10% of the entire tumor volume (Figure 3A). The tumor appeared to be attached to the IVC wall at multiple points. The right renal vein and a lumbar vein were filled with tumor thrombus. All longitudinal and circumferential resection margins were clear.
The spindled tumor cells contained large atypical nuclei, clumped chromatin, and prominent nucleoli (Figure 3B). Mitotic figures numbered up to 27 per 10 high-powered fields, and Ki-67 immunostaining showed positivity in at least 40% of the tumor cells. The tumor specimen strongly expressed smooth muscle actin and desmin but remained negative for CD117, CD34, and S100 antibodies (Figure 3C). Scores for tumor differentiation, mitotic count, and tumor necrosis were 2, 3, and 1, respectively, and diagnosis of a caval leiomyosarcoma grade 3 was established.
Postoperative course and follow-up
The alanine aminotransferase level peaked at 91 U/L, and liver function was stable throughout the postoperative course. The critical care stay was prolonged due to chest infection and poor renal function. Time until recovery of the single native kidney was bridged by temporary renal replacement therapy for 2 months. No immunosuppression was administered. The deceased-donor IVC graft remained patent on therapeutic anticoagulation with low molecular weight heparin, which was later switched to warfarin. The patient is currently alive at 2 years after resection. Follow-up imaging at 12 months was unremarkable, but local recurrence was detected on the most recent computed tomography scan at 18 months.
Long-term overall survival after radical resection of caval leiomyosarcomas can be achieved in half of the patients, but the reported 5-year disease-free survival rate of 6% highlights the exceedingly high risk of tumor recurrence.1,2 A tumor-free margin predicts a better outcome, which can be difficult to achieve if the tumor location involves critical central structures such as the orifice of the hepatic veins. The concept of ex situ tumor resection and liver autotransplantation facilitates a radical approach and allows for a safe complex vascular reconstruction in space-occupying hepatic lesions that cannot be treated via conven-tional liver surgery.3,4
However, liver autotransplantation remains an infrequent event at highly specialized centers, with approximately 100 reports in the literature.5,6 The main indications are benign lesions such as alveolar echinococcosis and neoplasms such as colorectal liver metastasis and cholangiocarcinoma. The latter group has no standard access to rescue therapy by deceased-donor liver transplantation, similar to leiomyosarcoma patients; therefore, liver autotrans-plantation is a valuable tool to expand surgical options for advanced tumors of these entities. Three cases of ex vivo resection of caval leiomyoma and subsequent liver autotransplantation have been published.7-9 These cases entailed concomitant IVC replacement and graft choices to substitute for the IVC that varied from prosthetic materials such as polytetrafluoroethylene and Dacron in most cases to aortic homografts and autogenous or vein grafting from deceased donors.1,10,11 In particular, the utilization of a prosthesis has been advocated, claiming that the tonicity of the material should facilitate graft patency. However, 3 factors played a role in our preference to implant a venous allograft: (1) the availability of an identical blood group, fresh deceased-donor caval vein in our local vessel bank, (2) the ability to avoid immunosuppression (as opposed to aortic grafts), and (3) the reduced incidence of infection, which is associated with prosthetic grafts.
Decompression of the splanchnic circulation by a temporary portocaval shunt during the anhepatic phase is an essential measure for successful liver autotransplantation without veno-venous bypass, by providing hemodynamic stability, reducing intra-operative blood loss, avoiding splanchnic congestion, and preserving renal function as patients lack hepatic collateralization.12 It is a simple technique and well-established in liver transplantation that can avoid the costs, complexity, and potential pitfalls of artificial veno-venous bypass, which may include wound infections and venous thromboembolism.13 Portocaval shunting has been also reported during an alternative technique of total vascular exclusion of the liver, namely, ante situm resection, where hepatic arterial inflow and the biliary tree remain undivided.11,14
Both ante situm resection and liver autotrans-plantation facilitate bloodless parenchymal transection and preservation of the future liver remnant, but only liver autotransplantation offers additionally the theoretical option of extracorporeal oncologic therapy with ex situ radiation and potential reduction in cancer spread during surgical organ manipulation for resection.15 Furthermore, an empty abdominal domain during liver autotransplantation aids in the precise and safe resection of large retroperitoneal tumors such as leiomyosarcomas, which may also require unilateral or bilateral nephrectomy. Success of the surgical procedure is dependent on careful patient selection with close collaboration between a high-volume liver transplant unit, sarcoma service, and medical specialties. With good surgical outcomes, liver autotransplantation may provide the best option of long-term progression-free disease and survival in patients with caval leiomyosarcoma without using a limited resource such as a donated liver. Recurrence-free survival has been reported, although follow-up periods have been limited to 6 and 12 months.7,9 Local recurrence was detected beyond 12 months after surgery in our patient; however, at 2 years, our patient is still alive and well. Therefore, liver autotrans-plantation may have achieved prolonged survival.
Volume : 18
Issue : 3
Pages : 396 - 401
DOI : 10.6002/ect.2018.0183
From the 1Liver Unit, the 2Department of Pathology, and the
Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, United Kingdom
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Paolo Muiesan, Liver Unit, Queen Elizabeth Hospital and Birmingham Children´s Hospital, Edgbaston, Birmingham, B15 2TH, United Kingdom
Phone: +44 121 371 4662
Figure 1. Magnetic Resonance Imaging (a) and Schematic Drawing (B)
Figure 2. Images From the Surgical Procedure
Figure 3. Histology Confirmed Grade 3 Leiomyosarcoma With a Ki-67 Activity of at Least 40%