Treatments for the intermediate stage B by Barcelona Clinic Liver Cancer classification as our present case was established by chemotherapy or TACE in the western series [10]. However, our strategy has been decided the surgical removal if possible under the well tolerated functional liver reserve even though stage B HCC as well as other groups in Japan [11]. However, postoperative cancer-relapse-free or overall survivals in the advanced stage HCC have not been improved in the cases of hepatectomy alone. The useful adjuvant chemotherapy or radiological therapy has not been fully established for a long period. In the recent developing era of novel chemotherapy for HCC, paradigm-shift of multi-modal treatments is supposed to be important [12]. As in the present case of a large size HCC located at the caudate lobe, operative risks of massive bleeding surrounding major vascular or vena cava injuries by the upfront surgery are considered as our previous experience (not published in English), which are often lethal outcomes as postoperative hepatic failure. Morphological classification pattern involving portal pedicle and hepatic veins by a large HCC were classified by the Qiu’s classification system and the present case was closed to type IV characterized by tumor close proximity to or direct invasion of both portal and hepatic venous trunks [13]. In this report, type IV showed the highest risk of increased blood loss and the lethal postoperative complications. Furthermore, the type IV showed the shortest patient survivals due to above poor surgical results. Our previous study also showed that the increased blood loss by the major venous injuries has been related to the poor patient survivals [14]. Therefore, avoiding such an operative risk was supposed to be an associated surgical factor relating to curability. In such a case, it is speculated that the preoperative novel intervention as LEN-TACE may reduce surgical outcomes and lead better patient survival by tumor shrinkage or devascularization of HCC followed by hepatectomy. Moreover, spontaneous rapture is also concerned during waiting for operation. Therefore, we surgeons nowadays expected the prior control of tumor progression or tumor shrink to improve surgical results. Lenvatinib is one of promising drug for immediate HCC necrosis and this was firstly used for cancer control in this case [5,6,7]. However, the tumor size was enlarged after Lenvatinib treatment alone although the intra-tumorous necrosis was partially observed. Prior or sequential TACE combined with Lenvatinib (LEN-TACE) is a useful regimen by the stronger anti-HCC devascularization effect although clinical evidences of this schedule of prior LEN-TACE followed by the radical hepatectomy has not been fully elucidated by the clinical trial at this stage. Adequate mechanism by addictive anti-tumor effects of LEN-TACE regimen cannot be well explain in the present case, as a tumor slightly enlarged to 7 cm during Lenvatinib administration in the first step. According to the knowable information regarding these combination treatment, we speculate that the immunological and devascularization might be complemented each other to the HCC located in the caudate lobe, which is a specific location where uniform treatment effects of drug or embolization are difficult to obtain. However, fortunately, we achieved the good result of tumor shrinkage, wide intra-tumorous necrosis, good surgical record and over 1 year cancer-free period after hepatectomy even though portal and hepatic vein trunk were compressed. However, successful case reports have frequently been reported in virtual web conferences from several high-volume institutes (not published). In this format, liver surgeons have been able to discuss the advantages and adverse effects of LEN-TACE. We expected high therapeutic efficacy to be more likely than an unresectable or borderline situation based on the novel concept of Shindoh et al. for 8.4% of surgical intervention with good prognosis [6]. Thus, the sequential TACE twice showed quite a dramatic effect of tumor shrink in the present case and the operative indication was discussed after careful follow-up for tumor relapse, appearance of new regions or general status in this elderly patient. Atezolizumab plus bevacizumab combination therapy is also an alternative option and, however, it seems difficult to decide which is the first line for the neoadjuvant or conversion regimen at this stage [15]. If the operative possibility remains, our institute choice LEN-TACE first at present. After use of these regimens, the transient impairment of liver function is really concerned. It seems to show the immediate recovery to operable liver functional reserve after drug withdrawal. By the prior LEN-TACE, the mild inflammatory findings between HCC and vena cava was observed and the liver surface seemed to be fragile during operation. While, parenchymal transection, bleeding control could be safely performed, and the curative operation could be safely achieved. The decrease in tumor size was slight, but accompanied by intra-tumoral devascularization. Compression deformation had clearly changed within a short period after starting LEN-TACE. The risk of caval injury was thus considered to have been reduced. Although compression caused by HCC can usually be relieved in cases of simple nodular (encapsulated) lesions, we have previously encountered a case with laceration of the caval wall during exfoliation of a caudal HCC with inflammation or expansion by many collateral vessels [16]. Given that experience, we considered that some preparation in terms of tumor shrinkage is preferable for treating HCCs around major vessels. In fact, inflammation after TACE was not significant in the present case.

With respect to type of hepatectomy as posterior sectionectomy with caudate lobectomy, operative selection would be unusual but adequate option for such a present case. First reason is that the remnant liver volume was larger than left side hepatectomy and the posterior portal pedicle was consistently compressively involved by the HCC. Histological finding showed no tumor involvement at the main portal pedicle but tumor infiltration to the peripheral portal branch around the main tumor was observed. The second reason is that operative view around the vena cava and hepatic veins from the right dorsal side were good by the preoperative computerized simulation using the latest workstation software. This hepatectomy option for HCC located paracaval (right side) portion of caudate lobe were reported by a few congress abstracts in Japanese but not published yet. Imamura et al. reported the similar hepatectomy for atrophic posterior section with intrahepatic cholangiocarcinoma located at the paracaval portion in Japanese [17]. In the present case, HCC mainly located the central caudate lobe including Spiegel lobe. This operative view seemed to be better in comparison with the anterior transection approach. Further, the Takayama’s highly dorsal caudate lobectomy would be difficult for such a large HCC [2]. Thus, we propose the present selection of hepatectomy for caudate HCC as a useful option. By the tumor shrink, it would be easier to dissect from the surrounding major vessels. Macroscopic and histological findings showed the high rate of tumor necrosis within the tumor capsule. LEN-TACE might provide satisfied operative feasibility and short-term patient prognosis in this case. The present incision for posterior sectionectomy was supposed to be an alternative option as described by Imamura et al. [17] and, under a right-side view from the thoracoabdominal approach, the entire vena cava was easily confirmed. Thus, the injured part seemed to be fixed with this view and we could approach Spiegel’s caudate lobe by placing spacers like large towels on the left side cavity.

In conclusion, the combined and sequential treatment of LEN-TACE is supposed to be one of preoperative useful options to control cancer progression to aim the neoadjuvant or conversion treatment strategy for a large size of HCC located in the segment 1 although our consideration of usefulness for local control by LEN-TACE option before operation would be overemphasized at this stage. The multi-modal strategy will be still developed in various situation in the locally advanced stage HCC by more accumulation of oncological evidences as a preoperative adjuvant option. In the era of such novel strategies for advanced HCC, decisions on treatment protocols should be made in collaboration among not only surgeons, but also physicians, radiologists or other liver experts similar to functioning cancer boards. By the surgical point of view, the combined posterior sectionectomy with caudate lobectomy is feasible and safe operative option for the caudate HCC under the precise computerized simulation before surgery.