Third, diagnosis of HCC and cirrhosis of patients in RFA group were not based on histopahologic evidence but on radiologic and clinical findings.
In conclusion, when hepatectomy was conducted to treat small HCC, a more significant extension of DFS could be ex- pected than RFA. Thus, HCC with three or fewer nodules 3 cm or less in diameter or a single nodule of 5 cm or less should be performed hepatectomy as the primary treatment if the patient's liver function and general conditions are good enough to undergo surgical operation. Despite a higher recurrence rate, RFA was revealed to have similar OS as HR for the treatmentof HCC within the Milan criteria. And in terms of less invasiveness, RFA has advantages over HR. So, RFA can be an alternative therapy for patients who are eligible for surgical resection.
Conclusions: Our results failed to show any significant survival differences between two center-related TACE strategies but showed a significantly smaller proportion of grade ≥ 3 adverse events and shorter hospitalisation for the overall treatment when the “on-demand”
strategy was used.
pISSN: 2508-5778ㆍeISSN: 2508-5859
Annals of Hepato-Biliary-Pancreatic Surgery ∙ pISSN: 2508-5778ㆍeISSN: 2508-5859
With the advance in imaging technologies and im- proved HCC surveillance, the incidence of early stage tu- mor has been improved gradually and effective treatmentof early stage HCC has become increasingly important. 1 Although HCC surveillance and advance in treatment technologies have led to improved patient survival, the rate of recurrence is still high. Hepatic resection (HR) andradiofrequencyablation (RFA) are now widely used to treat patients with early stage HCC. Although it remains debatable which treatment has superiority over other, HR has been regarded as the first-line treatmentfor patients with early stage HCC and preserved hepatic function due to its acceptable mortality, morbidity and long-term
Exposure was initial treatment modality which was either resection, RFA, or TACE. Liver resection included single or multiple segmentectomies aiming to remove all macroscopic tumors. Minor resection, defined as the resection of 2 or fewer liver segment. Resection of 3 or more segments was considered a major hepatic resection. For possible confounders or mediators, the following variables were used: age, sex, etiology of liver disease, Child-Pugh score, platelet count, ALBI grade, tumor size, tumor number, and serum AFP and PIVKA level at the time of HCC diagnosis. ALBI grade was calculated using albumin and bilirubin levels as described in a previous study . We also reviewed treatment response after initial treatment. Complete response (CR) was defined when complete resection was done for resection, complete ablation at immediate follow-up CT after RFA, and CR by modified response evaluation criteria in solid tumors (mRECIST) criteria after TACE (either by 1 or after 2 sessions of TACE). Recurrence was also collected for those who had CR after initial treatment.
Depending on the nature of the tumor, including size, number, growth pattern, and anatomical location, the treatment response is not always easy to obtain from a single session, showing differ- ences in outcomes between reports. 5,6 Thus, repeated TACEs are often performed to achieve a sufficient outcome. However, the method for predicting “TACE refractoriness” that does not show a therapeutic response even after repeated TACE treatments is still unclear. Enhanced criteria of TACE refractoriness were pro- posed by Japanese experts, which considered insufficient treat- ment response, increase in tumor number, new structural invasion or metastasis, and change in tumor markers. 7 In the recent Korean guideline, 8-10 sorafenib treatment was recommended if the stage progressed despite more than three repeated TACE treatments within 6 months.
Liver resection has been accepted as the best treatment modality to achieve curative goals ofhepatocellularcarcinoma (HCC), particularly in patients with a single tumor, although nonsurgical treatments such as transarterialchemoembolization (TACE), radiofrequencyablation (RFA), percutaneous ethanol injection (PEIT), and radiation treatment have been performed widely fortreatmentof HCC in cases of small tumors, multiple bilateral tumors, and anatomically or functionally unresectable tumors. Single HCC has generally manifested good prognosis after resection and accepted as a good candidate. However, tumor size has been considered as an important prognostic factor and adopted in the recent staging system, the 7th edition
Intraoperatively, compression of the tumor mass with gauze made hemostasis easy using RFA when the tumor size was less than 7 cm. However, if the tumor diameter was more than 10 cm, hemostasis was not possible even with several times ofablationfor every 10 minutes. In addition, tumor spillage was further increased by several ablations. We have used a straight single type RFA electrode. If we used another electrode later, for example, multitined radiofrequency electrode, it might be possible to ablate larger diameter HCC. The 5year survival rate of the RFA group was 83.3%. It was similar to that of nonruptured HCC. Because all our patients with srHCC were nodular type HCC, presumably their survival rate was not worse. In addition, since srHCC usually occurs in nodule type HCC, the prognosis is not worse than that of the same size HCC when the treatment method is well selected. All patients in the hepatectomy only group had a worse prognosis. They all died within 13 months. This result was similar to those of other studies [1,18]. Therefore, until the development of an electrode capable ofablationof a larger diameter srHCC, we think that a staged hepatectomy after emergent TAE is reasonable for a srHCC of larger than 10 cm.
In the HAIC group, patients with intractable, advanced HCC including major portal vein invasion or bilobar involvement were enrolled in a multicenter, prospective study from January 2006 to January 2008, with the intent of evaluating efficacy and safety. 13 In the TACE group, data were retrospectively collected from patients in a single center meeting the same inclusion criteria between January 2003 and December 2007. The diagnosis of HCC was made either histologically or by typical radiologic findings of HCC on two dynamic imaging examinations, or based upon one dynamic technique with an elevated serum alpha-fetoprotein (AFP) levels (> 400 ng/mL). Intractable, advanced HCC was defined as HCC with main portal invasion, diffuse bilobar involvement and/or refractory to surgical resection or nonsurgical intervention [TACE, radiofrequency (RF) ablation, or percutaneous ethanol injection (PEI)]. 11
According to the BCLC staging system, chemotherapy with a molecular-targeted agent is the only treatment option for patients with advanced HCC. In 2008, a large randomized, controlled study showed that patients with advanced HCC who received sorafenib treatment had a median survival benefit of approxi- mately 3 months, as compared with the placebo group. 10 Other studies have shown that TACE is more effective than best sup- portive care, even though the outcomes of TACE remain poor. 12-15 However, the treatmentof locally advanced HCC remains contro- versial. In Asian countries, various treatment methods have been attempted. The Asian Pacific Association for the Study of the Liver and the Japan Society of Hepatology recommended TACE, HAIC, ablation, or surgical treatmentfor locally advanced HCC. 16,17 Peng et al., 18 who conducted a retrospective study of patients with HCC with PVTT comparing HR and TACE, concluded that HR provided a survival benefit for patients with resectable HCC with PVTT. Shi et al. also suggested that HR was associated with better clinical results than TACE for the treatmentof HCC with PVTT. 11
Tumor recurrence post-RFA differed from post-liver re- section that makes sufficient safety margin. In immediate postoperative state, RFA area could be confirmed via a comparisonof before and after CT scan, but this imaging may not be sufficient for defining tumor necrosis and suf- ficient margin 27 because of mobilization during intra- operative manipulation. As such, some RFA results could cause misinterpretation of complete ablation. Tumor pop-up is another key problem. Superficially located tu- mors that are directly punctured can pop-up though the needle hole. This complication could be a source of peri- toneal drop metastasis but can be easily prevented by puncturing though normal tissue and capping the tumor with surgical gauze. These tumor pop-ups could also cause tumor spreading to small intrahepatic vessels and bile ducts because of high pressure gradients that occur during ablation. 28 These could be the main cause of high rate of recurrence in the initial first year post treatment. In our study, the cumulative rate of tumor recurrence in the first year was much higher than that following NAHR.
Nevertheless, RFA is known to provide better local control of disease than TACE and can achieve complete necrosis for small HCCs. However, the effectiveness of RFA in patients with intermediate or large HCC is unsatisfactory, with a relatively low complete necrosis rate that ranges from 29% to 70%, even if an overlapping technique or repeated procedures are used. However, Tanaka et al  investigated the long- term effects of combination therapy for intermediate HCC. A total of 58 patients with BCLC stage B (single nodule > 5 cm or measuring more than 30 mm in diameter or two to three nodules, each measuring more than 30 mm in diameter, or more than three nodules, no vascular invasion, and no extrahepatic group than in the TACE group (65% vs 17%, p <
Regarding HR, the complication rate including surgical mortality rate is higher than RFA. However, it has been persistently de- creased, down to less than 1% mortality, even close to zero mor- tality in high volume liver surgery centers. 21,22 Furthermore, mini- mal invasive laparoscopic HR was dramatically established for last 10 years. For another issue of HR, benefit of anatomical resection in comparison to non-anatomical resection has been controversy for long time. According to the three papers based on a case con- trol study with propensity score matching have shown no survival benefit. 23-25 If it is true, hepatic surgeon may not insist to do ana- tomical resection better obtainable by open surgery. In apart, ac- cording to the improvement of advanced laparoscopic technique, laparoscopic anatomical resection has been well established par- ticularly for resection more than sectionectomy, even for segmen- tectomy. 26-28 Through gradual introduction of laparoscopic ana- tomical HR, the perioperative and oncological outcomes are comparable to those with open anatomical resection by experi- enced laparoscopic surgeon. 29 For the tumors located on the sur- face of the liver, even though the tumor size is less than 3 cm, lo- cal recurrence rate is high with RFA. However it is privileged indication for laparoscopic resection with enough tumor free mar- gin. 30
Laparoscopic RFA procedure
All patients underwent scheduled surgery under general anesthesia. A 12-mm laparoscopy trocar was placed in a subumbilical incision and two 5-mm trocars were inserted in the subcostal area bilaterally to handle the liver. After the dissection of ligaments around the liver and adhesive tissue, another 12-mm trocar was placed in the upper middle quadrant of the abdomen for the US probe (Aloka Inc., Tokyo, Japan). Once the target tumor was considered to be exposed, intraoperative US was performed so the lesion could be confirmed by the surgeon and radiologist. The tumor size and the distance between the abdominal wall and index tumor were then measured to determine the puncture site. A radiologist inserted the electrode percutaneously to the correct position in the index tumor. RFA was conducted using internally cooled electrode systems with generators (Cool-tip RF System, Covidien, Mansfield, MA, USA; or VIVA RFA System, STARmed, Goyang, Korea) by 1 of 2 radiologists with sufficient experience in RFA. The 15-G or 17-G electrode and the single- (Proteus RF Electrode, STARmed) or multiple-separable-electrode (Octopus electrode, STARmed) were deployed by a radiologist. It was difficult to achieve a sufficient ablation margin when there was a poor sonic window due to echogenic bubbles after initial ablation with a single electrode. The multiple separable electrodes were applied using overlapping ablation techniques to overcome such shortcomings. Ablative treatment consisted of one or more cycles on the tumor lesion to accomplish complete ablation. The RFA energy was transmitted for 6–12 min per ablation. On completion of the procedure, we cauterized the tract during electrode removal to prevent postoperative bleeding.
There is still no consensus on the optimal treatments of BBF. Generally, there are two treatment options for BBF, such as operative procedures and nonsurgical inter- ventions. Surgical treatments have traditionally been per- formed with two-fold principles: first, to relieve any bili- ary obstructions and permit continuous free drainage of bile into the digestive tract usually through the creation of Roux-en-Y hepaticojejunostomy; and second, to drain all abscesses and to excise the fistula tract together with the diseased lung segment or to completely obliterate the fistula tract. 3,6 In this case, liver resection was performed due to disruptions of the bile duct wall and liver abscess, and thus, the abscess drainage of the lung was performed without resections of lung parenchyma. However, surgery for BBF in a patient, who has undergone liver resections and who is in a state of sepsis, could add to the negative sentiments for retrieval. 3,7 Nonsurgical treatments such as radiological and endoscopic interventions, which are less riskier than surgery, have been recently highlighted. In the previous cases, patients with BBF following RFA which are complicated by biloma or liver abscess successfully underwent external drainages with or without endoscopic
여러 간세포암 치료 가이드라인에서도 고주파열치료의 효 용성은 인정받고 있어 3 cm 이하 3개 이하의 조기 간세포암 에 대해서는 근치적 치료법 중 하나로 적용이 가능한 것으로 제시되고 있다. 특히 2012년 BCLC 가이드라인의 개정안에 는 간이식을 고려하지 않는 very early HCC (stage 0, 즉, 2 cm 이하 단일결절)의 경우 수술적 치료에 앞서 국소 소작 술을 우선 고려할 수 있다고 전향적 제안을 제시한바 있다 . 그러나 간세포암을 지닌 환자는 간세포암이라는 악성 종양과 잔여 간기능 보존이라는 두 가지 목표를 동시에 만족 해야 하는 다른 종양에서는 찾기 어려운 특성이 있음을 깊이 인지하고, 단순히 어느 치료가 우선이어야 한다는 식의 단순 한 경쟁이 아닌 진정한 협력이라는 새로운 패러다임으로의 전향이 필요한 시점이라 생각한다.
Departments of 1 Internal Medicine and 2 Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea Transarterial chemoembolization (TACE) is a widely accepted nonsurgical modality used for the treatmentof multinodular hepatocellularcarcinoma (HCC). The careful selection of the candidate is important due to the risk of developing various side effects. Fever, nausea, abdominal pain, and liver enzyme elevation are commonly known side effects of TACE. Hepatic failure, ischemic cholecystitis, and cerebral embolism are also reported, although their incidence might be low. Pulmonary complication after TACE is rare, and the reported cases of lipiodol pneumonitis are even rarer. A 53-year-old man was treated with TACE for rup- tured HCC associated with hepatitis B virus infection. On day 19 after the procedure, the patient complained of dyspnea and dry cough. Chest computed tomography showed diffuse ground glass opacities in the whole- lung fields, suggesting lipiodol-induced pneumonitis. After 2 weeks of conservative management, the clinical symptoms and radiologic abnormalities improved. Reported herein is the aforementioned case of lipiodol-in- duced pnemonitis after TACE, with literature review.
PIVKA-II, proteins induced by vitamin K absence or antagonist-II; S1, caudate lobe; PET, positron emission tomography
Since this study was focused on the role of ALP and its potential correlation with early intrahepatic metastasis, we set the eligibility criteria as follows: resection of HCC lesions larger than 10 cm in the longest diameter; no peri- operative mortality; no evidence of bile duct tumor thrombus; and the performance of the protocol TACI at 1 month. The reason why the 1-month protocol TACI was included was that it is the most sensitive test to de- tect intrahepatic metastasis and it can be concurrently used as an effective treatment modality for recurrent lesions.