Discussion
Bourreille et al (7) first reported an AFP-producing gastric tumor in 1970. Ishikura et al (8) proposed the term HAC of the stomach for this type of primary gastric carcinoma in 1985. The stomach is the most common site of origin of HAC (9), but HAC has been reported in other organs, including the bladder, lungs, pancreas, colon, gall bladder, ovaries and uterus. The reported incidence of HAC is 1.3–15% of all gastric carcinomas (10). As HAC is relatively rare, the pre-operative diagnostic rate is low, and the diagnosis is usually made through post-operative pathological examination.
It is difficult to differentiate HCC resulting from hepatic metastases from HAC. One previous study (11) reported that the tumors have similar enhancement on CT and magnetic resonance imaging, so it is not easy to differentiate them on the basis of imaging findings. HAC is a relatively rare disease, while liver cirrhosis and chronic hepatitis infection can usually be found among patients with HCC, therefore, the differential diagnosis should be based on the medical history, dynamic image studies and liver biopsy. The proportion of HAC with a positive CEA stain is >75%, so high levels of serum AFP and CEA together should prompt suspicion of HAC. The patient in the present study had a history of hepatitis B infection and an elevated serum AFP level pre-operatively, therefore, the mass could have been misdiagnosed as HCC. However, the patient also had a history of HAC, had undergone a previous splenic metastasis tumor resection and presented with significant increases in serum CEA level; accordingly, a diagnosis of liver metastasis from HAC was formed.
A number of studies have reported that the prognosis of HAC is extremely poor even when discovered at an early stage. Motoyama et al (4) attributed the poor prognosis of HAC to the frequent occurrence of liver or lymph node metastases. Metastasis of the liver can occur within a year post-operation, even if no metastasis is found pre-operatively. Chang et al (12) reported that the majority of patients in their series, including three who underwent radical surgery for early gastric cancer, succumbed to liver metastasis within two years. Thus, liver metastasis is the main factor affecting the prognosis of HAC, and the close observation and long-term follow-up of patients is required.
Holistic therapy based on surgery is the optimal treatment method for HAC, and surgical treatment for HAC with liver metastasis may still be valuable. the patient in the present case patient developed splenic and hepatic metastases five years after radical resection and chemotherapy for HAC. Metastases of HAC to the spleen are believed to be unusual, but a splenectomy was performed on the present patient, as there was no endoscopic evidence of recurrence of the gastric tumor (5). The hepatic metastatic carcinoma was rapidly growing, with invasion of the IVC and the second porta hepatis. The patient's response to TACE was extremely poor. The IVC was stenotic due to the tumor, so surgery was considered as the only option for a cure.
In recent years, with a better understanding of the vascular and segmental anatomy of the liver through the experience of liver transplantation, the results of liver surgery have rapidly improved. Liver tumor metastasis to the vena cava does not obviate the requirement for liver resection (2). Ex vivo liver resection is a novel surgical technique mainly used for large liver tumors located in the dorsum of the liver with involvement of the hepatic veins or the retrohepatic IVC (2). Pichlmayr et al (1) first reported the surgery in 1988 and subsequently performed 11 procedures. This approach has now become recognized and is promoted worldwide. Ex vivo liver resection has increased the resectability rate in patients with advanced tumors, provided a partial solution for bleeding and long-term blocking in certain liver tumor resections, and avoided the requirement for liver transplantation in specific patients. The technique can also be applied to cases of hilar cholangiocarcinoma and complex liver trauma. The present patient presented with liver metastases invading the hepatic vein and retrohepatic IVC, so the tumor was unresectable with conventional surgery. For achieving R0 resection, ex vivo liver resection appears to be suitable, as it provides enough time for the completion of complex resections and vascular reconstructions in a bloodless environment, thereby reducing the risk of bleeding. Complete pre-operative assessments of liver function and reserve are essential. A computer-aided pre-operative planning system for liver surgery based on CT images has been used to define the association between the tumor and blood vessels (13), and a simulation resection can be used to evaluate the resection range and residual liver volume.
Maintaining a stable hemodynamic status and avoiding ischemia-reperfusion injury are two prominent considerations for this surgery. Certain studies recommend the use of veno-venous bypass during the anhepatic period. The aim of this technique is to reduce hemodynamic instability, ensure splanchnic decompression, and minimize venous hypertension and intestinal edema (14). However, the ex situ ex vivo procedure is associated with complications, including air embolism, thromboembolic events and mechanical injury due to global capillary leak, which can lead to severe post-operative water, electrolyte and acid-base imbalances (15). Thus, the present study used a vascular prosthesis to reconstitute blood flow in the portal vein and IVC to ensure the stability of general circulation, lessen ischemia-reperfusion injury, and avoid acid-alkali and electrolyte imbalances. Wen et al (16) recommended construction of a temporary portacaval shunt to improve hemodynamic status, reduce the requirement for intraoperative blood transfusion and preserve renal function. The shunt can also permit enough time for the completion of the ex vivo liver resection. Compared with the traditional veno-venous bypass technology, this procedure has a shorter surgical duration and anhepatic phase. Zhang et al (17) reported three cases of ex-vivo hepatectomy using this procedure and found no post-operative hepatic dysfunction resulting from the delayed liver hemoperfusion; thus, it was suggested that this method is feasible and safe, with a shortened surgical duration, and less intraoperative bleeding and reperfusion injuries. Gringeri et al (18) performed a temporary portacaval shunt with a stretch of aortic graft to replace the caval vein in a porcine model; the temporary shunt ensured hemodynamic stability during the anhepatic phase and lengthened the portal vein, which facilitated construction of a good anastomosis.
The amount of time that the liver can safely tolerate warm ischemia appears to be limited, so hypothermic perfusion has been considered. The advantage of this technique is that the low temperature increases the tissue tolerance to ischemia. Hannoun et al (19) suggested that hypothermia facilitated the bloodless transection of liver parenchyma and increased the chance of resectability for advanced tumors. The histidine-tryptophan-ketoglutarate solution is better than the University of Wisconsin preservation solution, as it minimizes the risk of cardiocirculatory complications following reperfusion (20). The patient in the present study had a good recovery, without the complications of renal insufficiency and heart failure. At the hypothermic perfusion stage, CUSA and bipolar coagulation were used for transection of the liver parenchyma; thus, the small vessels and bile ducts could be separated during a bloodless condition to prevent bleeding and leakage following re-perfusion. Once all the vessels had been reconstructed, implantation of the remnant liver and anastomosis of vessels was performed exactly as in living donor transplantation. The patient presented with hepatic metastases from HAC, so lymphatic and connective tissue from the hepatoduodenal ligament were removed, which could have compromised the blood supply of the bile duct. Consequently, partial resection of the bile duct was performed and the bile flow was reconstituted with a hepatic-jejunostomy.
Ex situ ex vivo surgery should only be performed in specialized centers, where surgeons are familiar with complex hepatobiliary surgery and liver transplantation. This technique may be the last resource for otherwise unresectable malignancy (14), but the associated morbidity and mortality remain high, and tumor recurrence is a major problem. Raab et al (21) also recommended that the ex situ procedure be used only in specialized centers with extensive experience in both conventional liver surgery and transplantation.
HAC is prone to liver and lymph node metastasis, which predicts high malignancy and a poor prognosis, but this does not mean that there is no chance of treatment with a good prognosis. Ex situ liver surgery may be the only effective treatment for patients with liver tumors that cannot be resected by traditional procedures. The surgery offers a chance for hepatectomy of the primary and secondary liver tumors, even with hepatic vein and IVC infiltration within the tumor. The safety and efficacy of this technique requires verification through further clinical studies in practice.