Department of Hepatobiliary and Pancreatic Surgery, Moscow Clinical Scientific Center, Russia
Introduction: The aim ofthe study was to compare the short- and long-term outcomes of laparoscopic liver resection (LLR) and open liver resection (OLR) for hepatocellularcarcinoma (HCC) andto identify patients who might gain more benefits from LLR depending on tumorsize.
Results: During the study period, 153 patients, 112 (73.2%) men and 41 (26.8%) women with a mean age of 56.4 ± 10.8 years, under- went R0 resection for cHCC-CCA. Mean tumor diameter was 4.2 ± 2.6 cm, and 147 (96.1%) patients had solitary tumors. According to 2019 World Health Organization (WHO) classification, 111 (72.5%) patients had cHCC-CCA alone, and 29 of them (26.1%) showed stem cell features. cHCC-CCA-intermediate cell carcinomaand cHCC-CCA-cholangiolocellular carcinoma were identified in 27 (17.6%) and 15 (9.8%), respectively. The 1-, 3-, and 5-year tumor recurrence and patient survival rates were 31.8% and 92.1%, 49.8% and 70.9%, and 59.0% and 61.7%, respectively. Univariate analyses revealed that significant prognostic factors were tumorsize > 5 cm, mi- croscopic and macroscopic vascular invasion, lymph node metastasis, 8th American Joint Committee on Cancer (AJCC) tumor stage, and status of stem cell feature. Multivariate analysis revealed 8th AJCC tumor stage and status of stem cell features as independent prognostic factors. The 2019 WHO classification was not associated with post-resection prognosis.
Patients were positioned in supine or left lateral decu bitus
position accordingtothetumor location. The pneumo- peritoneum with carbon dioxide was introduced, and then intraabdominal pressure was monitored and maintained below 14 mmHg. Four or five trocars were used, depending on the surgical requirements. The trocar insertion sites were determined by thetumor locations. A flexible laparoscopic ultrasound probe was used to localize thetumorand determine the transection line before parenchymal dissection. If anatomical resection was planned such as segmentectomy, hepatic vein for resection margin was firstly recognized with intraoperative ultrasound, then portal pedicle was divided intraparenchymally, then liver parenchyma is dissected along the areas of demarcation ofthe liver surface. One to 2 cm depth of liver parenchyma was transected using a Harmonic Scalpel (Ethicon Endo-Surgery Inc., Cincinnati, OH, USA). An ultrasonic dissector (CUSA Excel, Integra Lifesciences Co., Plainsboro, NJ, USA) was used to dissect deep portions ofthe liver to skeletonize the portal and hepatic vein. An endoclip was used to control larger structures. We did not routinely apply the Pringle maneuver to control blood flow tothe liver, but in selected cases, we used selective extraglissonian pedicle clamping with laparoscopic bulldog clamp for bleeding control or anatomical resection. The specimen was extracted using a vinyl bag. An argon beam coagulator was used on the cut liver surface to control bleeding with ventilation due tothe risk of air embolism. Finally, fibrin glue was applied tothe cut surface.
Methods: We analyzed RNA expression and DNA variant data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TC- GA-LIHC) to examine their associations with serum biomarker levels andclinical data. From 371 TCGA-LIHC patients, we selected 91 seen at 3 institutions in Korea andthe United States and measured AFP, AFP-L3, and DCP from preoperatively obtained serum. We conducted an integrative clinicaland molecular analysis, focusing on biomarkers, and validated the findings with the remaining 280 patients in the TCGA-LIHC cohort.
Although surgery start time may not measurably affect the postoperative morbidity of patients due to self-regulation and wellness control by surgeons, it remains unclear whether the progressive fatigue of surgeons during a normal working day can significantly weaken their judgment and performance in surgery. The present study is important, as it is the first to investigate the long-term prognosis of HCC following morning versus afternoon HR. The patient characteristics, tumor feature, and surgical procedures were not significantly different between morning and afternoon surgery groups. Of note, the long-term prognosis was equivalent regardless of surgery start times.
Between December 2000 and August 2012, 165 patients with gallbladder cancer underwent complete resection at a tertiary hospital in Daegu, Korea. Of these, 78 patients (47.2%) had pT2 gallbladder cancer. R1 resection was performed in 4 patients and R0 resection in 74 patients. The following preoperative demographic andclinicalcharacteristics were retrospectively obtained from the patients’ medical records: age, sex, types of operative procedure, tumor markers, operation time, need for transfusion, postoperative complications, hospital stay, and mode of recurrence. The location ofthetumor was defined based on preoperative radiologic images, mostly CT scan.
In addition, blood transfusion had borderline significance as a prognostic factor for OS. Furthermore, in our subgroup analyses accordingto a tumor diameter of 5 cm, blood transfusion had an adverse effect on DFS and OS, mainly in patients with tumor diameters > 5 cm. Thus, the primary aim ofthe surgeon during hepatectomy should be to achieve the least bleeding and blood transfusion, particularly for patients with large tumors through hepatic inflow control (Pringle maneuver). However, if using the Pringle maneuver, there might be ischemia-reperfusion injury. There has been long debated for the potential of liver remnant ischemia-reperfusion injury and its resultant impact on tumor progression [27-30]. Most of studies arguing that ischemia-reperfusion injury may promote progression of HCC were experimental for microenvironmental condition such as disrupting hepatic microvasculature, antiapoptosis induced by proinflammatory cytokine. As a clinical surgeon, it is more reasonable to practice as clinical studies rather than to follow experimental studies on condition that the hypothesis would not be proven.
HCC is often only diagnosed at an advanced stage . The incidence of HCC and performance of cura- tive treatments such as hepatic resection in Japan and Korea appear to be among the highest worldwide [26, 27]. We believe that the present multicenter-based col- laboration study of both Japan and Korea is of great clinical signi ﬁcance for HCC treatment. The main problem that sur- geons face while operating on patients with cirrhosis is the balance between achieving a radical intervention while simultaneously preventing the development of postopera- tive liver failure that could ensue from removal of too much liver parenchyma. This problem is the basis ofthe dispute between which technique is more effective: AR, which should theoretically be a more radical procedure from an oncologic point of view, or NAR, which should reduce the risk of postoperative hepatic failure. In the present study, the patient eligibility criteria included tumor number, tumorsize, and preoperative liver function. PSM analysis was applied to minimize selection bias between the groups.
The results of our study are limited by the non-random- ized design, small number of cases, andthe selection bias related tothe choice of approach based merely on tumorcharacteristics. Although the potential historical bias was reduced by the study design, resulting in an open re- section group that was well matched with a laparoscopic resection group for age, gender, ASA class, tumor location andsize, type of liver resection, and degree of liver cir- rhosis, our disease-free survival results after laparoscopic liver resection for HCC are short-term results. Thus, a larg- er group of patients and further examinations (longer- term follow-up) are necessary to analyze the role of lapa- roscopic liver resection.
We performed subgroup analyses of patients without ascites and patients belonging to CTP class A. In both of these subgroups, HR was associated with significantly better survival than TACE or
sorafenib. Accordingly, we believe that the differences in baseline laboratory characteristicsand liver cirrhosis did not influence our assessment of effectiveness. In addition, the presence of cirrhosis has not been included as a meaningful factor in any guideline’s treatment algorithm for patients with HCC. Because sorafenib was approved in South Korea partway through the study period, we divided our enrollment period into two periods: A and B. We found that HR was associated with superior survival in both peri- od A and period B. However, in the HR group, the median survival time was 15.4 months in period A and 24.6 months in period B, and in the TACE group, the median survival time was and 6.1 months in period A and 9.5 months in period B. These results may be explained by advancements in TACE, operative techniques, and bedside care. Recently, there have been further developments in the treatment methods and techniques for HCC. Therefore, it is debatable whether sorafenib alone is the best choice for patients with advanced-stage HCC, accordingtothe BCLC. 7 There are some limitations tothe current study. First, it is a retrospective design. Second, there may be selection bias because patients with relatively good hepatic function and easy-to-resection HCC might be included in the HR group. Third, the sample size was small and limited to South Korea. Because of differences in underlying liver diseases, our results may not be applicable to patients with HCC with PVTT in other countries. Fourth, portal hypertension andthe indocyanine green clearance level were not assessed in all ofthe enrolled patients, although these factors are strongly associated with prognosis. Fifth, TACE, RFA, HAIC, operations, molecular- targeted agents, and other treatment modalities were applied for recurrent or remnant tumor after initial treatment.
Surveillance after surgical resection
The procedures used for surveillance after liver resection have been described previously . All patients were followed postoperatively one month. After then, all patients were followed every 2 or 3 months. Follow-up parameters were physical examination, serum α-FP, liver function tests, and chest x-rays. Abdominal CT was performed every 3 months or when recurrence was suspected. MRI and/or PET scans were performed if CT did not show definitive evidence of recurrence andtumor markers elevated. Disseminated HCC recurrence was defined as tumor number > 10 in both lobes and total tumorsize >10 cm. Patients with intrahepatic recurrences were treated with RFA, TACE, liver resection, liver transplantation, or radiation accordingto functional liver reserve andthe pattern of recurrence. Follow-up time was the length of time from surgery tothe final follow-up or death.
AR in patients with HCC has a theoretical benefit in terms of improving recurrence-free survival, and this is partly observed in clinical practice. However, three recently published, well-designed, case-controlled studies using the propensity score matching method did not show an improvement in recurrence-free survival following AR. Studies examining the benefits of AR displayed considerable bias, including liver function, surgical techniques, anatomical variability, tumorsize, tumor location, pathologic heterogeneity and chronology. Because prospective randomized studies are not possible for ethical reasons, it is difficult to reach a conclusion on the benefit of AR in HCC. However, the results of previous studies suggest that AR is associated with favorable perioperative and long-term outcomes in some conditions, including in patients with a tumorof 2-5 cm in size that is located in a deep region ofthe parenchyma.
Two studies 22,27 was excluded from the meta-analysis be- cause the reconstruction of survival data from original KM graph was not possible because no KM survival graph was reported or there were inadequate data ofthe numbers of patients at risk andthe total numbers of events (death). The remaining 5 studies including 1422 patients were finally included in this meta-analysis. The groups were classified as follows: 559 patients in the SR group and 863 patients in the TACE group. Patients enrolled in the systematic review were within Child-Pugh class A or B in all the studies. No study reported statistically sig- nificant differences in the baseline demographic or clinicalandtumorcharacteristicsofthe two groups. The NOS scores ofthe included studies ranged from 5-7 and were considered of high quality: 5 studies 12,23-25,27
or vascular invasion. The medical records of these patients were reviewed retrospectively andthefollowing data were collected for each patient: demographics; laboratory data including tumor marker and hepatitis serologic test; tumor pathology; operative outcomes; date of last followup, recurrence, and death. Hepatic reserve was assessed using ChildPugh classification and preoperative Indocyanine green retention at 15 minutes (ICG R15) was routinely performed to assess liver function. Tumor size was defined as the largest diameter ofthetumor in the specimen. Anatomical resection was defined as the systematic resectionof hepatic segment accordingtothe segmental and sectional anatomy described at the International Hepato
≥ 3.5 cm, venous/lymphatic invasion, presence of satellite lesions, and poor tumor differentiation; however, grade 2 patients showed no associations with ER. It can be as- sumed that ER is mainly affected by histological factors in ALBI grade 1 patients, which means liver function is favorable. However in ALBI grade 2 patients, no risk fac- tors were associated with ER. According to these results, liver function impairment is mainly associated with ER when liver function is not favorable. Lise et al. 3 reported that CP class was an independent prognostic factor for disease-free survival and overall survival in multivariate analysis, while liver function impairment may be asso- ciated with recurrence of HCC. Hirokawa et al. 19 reported that ER after curative hepatectomy in HCC patients was associated with ICGR15 ＞16%, and that recurrence pat- terns and risk factors vary by liver function status. These results suggest that liver function may be associated with ER.
vention. The patients who had an available liver donor underwent LT.
Eradicating all ofthe multifocal tumors required a multimodality approach using not only en-bloc resection but also separate multi-site resection or resection com- bined with RFA. All ofthe patients who underwent sur- gical resection were routinely assessed by intra-operative US. The effectiveness and safety of combined hepa- tectomy with RFA for multi-site HCCs were reported by Choi et al  , and our previous work has also shown comparable results between en-bloc resectionand multi- site resection or combination hepatectomy with RFA  . Separate multi-site resection or resection plus RFA was performed for the multifocal tumors ineligible for en- bloc resection because of bilobar involvement or when there was not enough hepatic function reserve after en- bloc resection. Wedge resection was considered for super- ficial tumors, and RFA was performed for tumors less than 3 cm in diameter that were located deep in the liver.
Boffano et al. reported that if sufficient bone remained to buttress the fracture, traditional open reduction and in- ternal fixation were performed, in association with cyst enucleation or marsupialization, in almost all reported cases. When remaining healthy bone is insufficient or sepa- rated by a large defect, resectionofthe involved mandibular region, eventually followed by immediate or secondary re- construction, may be necessary. Abir et al. suggest that in cases where there is no potential for normal union, the bone must be resected until normal, bleeding bone is reached. When sufficient normal bone remains, traditional reduction is performed using rigid fixation. Coletti and Orb also reported that in the few cases in which sufficient bone was left to buttress the fracture, traditional fracture reduc- tion with rigid fixation was employed. As a result, if the po- tential for bone healing exists, traditional rigid fixation rather than bone resection is recommended [1, 11, 12].
Copyright Ⓒ 2012 by The Korean Association of Hepato-Biliary-Pancreatic Surgery Korean Journal of Hepato-Biliary-Pancreatic Surgery ∙ pISSN: 1738-6349
The five-year survival rate for hepatocellular carncino- ma patients following hepatectomy is approximately 50%. 1-3 One ofthe main causes of such poor prognosis is tumor recurrence. 1,4 The 5-year tumor recurrence rate is up to 80%. 1,4 HCC recurrence after curative hepatectomy often occurs in the liver (64-86.5%), and extrahepatic recur- rences are relatively infrequent. 5-7 Extrahepatic recurrences have a worse prognosis, mostly likely from their pre- sentation at multiple sites with aggressive features. Many patients with extrahepatic recurrences are poor candidates for surgical resections. Chemotherapy might be considered the only treatment for systemically advanced HCC, but it is ineffective and requires further investigation. 5,8,9 The ob- jective of our study is to evaluate the patterns and clin- icopathologic features ofthe extrahepatic recurrence of HCC after curative resection, based on data from HCC