Current Roles of Ramucirumab in the Sequential Treatment of Unresectable Hepatocellular Carcinoma.

BACKGROUND/AIM: The treatment algorithm for systemic therapies for advanced hepatocellular carcinoma (HCC) has changed dramatically; however, the therapeutic landscape for sequential second-line or later-line treatments, including ramucirumab, remains controversial. This study aimed to investigate the role of ramucirumab for treating HCC. PATIENTS AND METHODS: We retrospectively analyzed data from 17 patients with advanced HCC who received ramucirumab, and 8 of them who received lenvatinib re-administration after ramucirumab treatment failure. RESULTS: The median overall survival of 17 patients treated with ramucirumab was 11.5 months. The median ratios of the 1-month post-treatment α-fetoprotein (AFP) levels and albumin-bilirubin (ALBI) scores to the pre-treatment AFP levels and ALBI scores following ramucirumab treatment were 0.880 and 0.965, respectively. The median ratios of the 1-month post-treatment AFP and ALBI levels to the pre-treatment levels were 1.587 and 0.970 for mALBI grade 1/2a, and 1.313 and 0.936 for mALBI grade 2b/3, respectively. Six of the eight patients who received lenvatinib rechallenge treatment exhibited a decrease in AFP levels one month post-lenvatinib treatment. Deterioration of liver function 3 months post-lenvatinib treatment was noted in five of the eight patients who received lenvatinib rechallenge treatment after ramucirumab. CONCLUSION: Ramucirumab may be equally useful in patients with unresectable HCC who have poor liver function or whose liver function is aggravated by other therapies. Rechallenge treatment with lenvatinib after ramucirumab may be a valid treatment option for HCC.

Optimal cutoff values of drain amylase for predicting pancreatic fistula are different between open and laparoscopic distal pancreatectomy.

BACKGROUND: Drainage fluid amylase (DFA) is useful for predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after distal pancreatectomy (DP). However, difference in optimal cutoff value of DFA for predicting CR-POPF between open DP (ODP) and laparoscopic DP (LDP) has not been investigated. This study aimed to identify the optimal cutoff values of DFA for predicting CR-POPF after ODP and LDP. METHODS: Data for 294 patients (ODP, n = 127; LDP, n = 167) undergoing DP at Kobe University Hospital between 2010 and 2021 were reviewed. Propensity score matching was performed to minimize treatment selection bias. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff values of DFA for predicting CR-POPF for ODP and LDP. Logistic regression analysis for CR-POPF was performed to investigate the diagnostic value of DFA on postoperative day (POD) three with identified cutoff value. RESULTS: In the matched cohort, CR-POPF rates were 24.7% and 7.9% after ODP and LDP, respectively. DFA on POD one was significantly lower after ODP than after LDP (2263 U/L vs 4243 U/L, p < 0.001), while the difference was not significant on POD three (543 U/L vs 1221 U/L, p = 0.171). ROC analysis revealed that the optimal cutoff value of DFA on POD one and three for predicting CR-POPF were different between ODP and LDP (ODP, 3697 U/L on POD one, 1114 U/L on POD three; LDP, 10564 U/L on POD one, 6020 U/L on POD three). Multivariate analysis showed that DFA on POD three with identified cutoff value was the independent predictor for CR-POPF both for ODP and LDP. CONCLUSIONS: DFA on POD three is an independent predictor for CR-POPF after both ODP and LDP. However, the optimal cutoff value for it is significantly higher after LDP than after ODP. Optimal threshold of DFA for drain removal may be different between ODP and LDP.

Utility of plasma D-dimer for diagnosis of venous thromboembolism after hepatectomy.

BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal complication of hepatectomy. The use of postoperative prophylactic anticoagulation in patients who have undergone hepatectomy is controversial because of the risk of postoperative bleeding. Therefore, we hypothesized that monitoring plasma D-dimer could be useful in the early diagnosis of VTE after hepatectomy. AIM: To evaluate the utility of monitoring plasma D-dimer levels in the early diagnosis of VTE after hepatectomy. METHODS: The medical records of patients who underwent hepatectomy at our institution between January 2017 and December 2020 were retrospectively analyzed. Patients were divided into two groups according to whether or not they developed VTE after hepatectomy, as diagnosed by contrast-enhanced computed tomography and/or ultrasonography of the lower extremities. Clinicopathological factors, including demographic data and perioperative D-dimer values, were compared between the two groups. Receiver operating characteristic curve analysis was performed to determine the D-dimer cutoff value. Univariate and multivariate analyses were performed using logistic regression analysis to identify significant predictors. RESULTS: In total, 234 patients who underwent hepatectomy were, of whom (5.6%) were diagnosed with VTE following hepatectomy. A comparison between the two groups showed significant differences in operative time (529 vs 403 min, P = 0.0274) and blood loss (530 vs 138 mL, P = 0.0067). The D-dimer levels on postoperative days (POD) 1, 3, 5, 7 were significantly higher in the VTE group than in the non-VTE group. In the multivariate analysis, intraoperative blood loss of > 275 mL [odds ratio (OR) = 5.32, 95% confidence interval (CI): 1.05-27.0, P = 0.044] and plasma D-dimer levels on POD 5 ≥ 21 µg/mL (OR = 10.1, 95%CI: 2.04-50.1, P = 0.0046) were independent risk factors for VTE after hepatectomy. CONCLUSION: Monitoring of plasma D-dimer levels after hepatectomy is useful for early diagnosis of VTE and may avoid routine prophylactic anticoagulation in the postoperative period.

Histological diagnosis of polyploidy discriminates an aggressive subset of hepatocellular carcinomas with poor prognosis.

BACKGROUND: Although genome duplication, or polyploidization, is believed to drive cancer evolution and affect tumor features, its significance in hepatocellular carcinoma (HCC) is unclear. We aimed to determine the characteristics of polyploid HCCs by evaluating chromosome duplication and to discover surrogate markers to discriminate polyploid HCCs. METHODS: The ploidy in human HCC was assessed by fluorescence in situ hybridization for multiple chromosomes. Clinicopathological and expression features were compared between polyploid and near-diploid HCCs. Markers indicating polyploid HCC were explored by transcriptome analysis of cultured HCC cells. RESULTS: Polyploidy was detected in 36% (20/56) of HCCs and discriminated an aggressive subset of HCC that typically showed high serum alpha-fetoprotein, poor differentiation, and poor prognosis compared to near-diploid HCCs. Molecular subtyping revealed that polyploid HCCs highly expressed alpha-fetoprotein but did not necessarily show progenitor features. Histological examination revealed abundant polyploid giant cancer cells (PGCCs) with a distinct appearance and frequent macrotrabecular-massive architecture in polyploid HCCs. Notably, the abundance of PGCCs and overexpression of ubiquitin-conjugating enzymes 2C indicated polyploidy in HCC and efficiently predicted poor prognosis in combination. CONCLUSIONS: Histological diagnosis of polyploidy using surrogate markers discriminates an aggressive subset of HCC, apart from known HCC subgroups, and predict poor prognosis in HCC.

The Usefulness of Total Tumor Volume as a Prognostic Factor and in Selecting the Optimal Treatment Strategy of Chemotherapeutic Intervention in Patients with Colorectal Liver Metastases.

BACKGROUND: Few reports have discussed the association between total tumor volume (TTV) and prognosis in patients with colorectal liver metastases (CRLM). The present study aimed to evaluate the usefulness of TTV for predicting recurrence-free survival and overall survival (OS) in patients receiving initial hepatic resection or chemotherapy, and to investigate the value of TTV as an indicator for optimal treatment selection for patients with CRLM. PATIENTS AND METHODS: This retrospective cohort study included patients with CRLM who underwent hepatic resection (n = 93) or chemotherapy (n = 78) at the Kobe University Hospital. TTV was measured using 3D construction software and computed tomography images. RESULTS: A TTV of 100 cm3 has been previously reported as a significant cut-off value for predicting OS of CRLM patients receiving initial hepatic resection. For patients receiving hepatic resection, the OS for those with a TTV ≥ 100 cm3 was significantly reduced compared with those with a TTV < 100 cm3. For patients receiving initial chemotherapy, there were no significant differences between the groups divided according to TTV cut-offs. Regarding OS of patients with TTV ≥ 100 cm3, there was no significant difference between hepatic resection and chemotherapy (p = 0.160). CONCLUSIONS: TTV can be a predictive factor of OS for hepatic resection, unlike for initial chemotherapy treatment. The lack of significant difference in OS for CRLM patients with TTV ≥ 100 cm3, regardless of initial treatment, suggests that chemotherapeutic intervention preceding hepatic resection may be indicated for such patients.

Advantages of the Laparoscopic Approach for the Initial Operation in Patients who Underwent Repeat Hepatectomy.

BACKGROUND: Less intra-abdominal adhesions are expected following laparoscopic surgery. Although an initial laparoscopic approach for primary liver tumors may have advantages in patients who require repeat hepatectomies for recurrent liver tumors, this has not been sufficiently investigated. METHODS: Patients who underwent repeat hepatectomies for recurrent liver tumors at our hospital between 2010 and 2022 were retrospectively analyzed. Of 127 patients, 76 underwent laparoscopic repeat hepatectomy (LRH), of whom 34 patients initially underwent laparoscopic hepatectomy (L-LRH) and 42, open hepatectomy (O-LRH). Fifty-one patients underwent open hepatectomy as both the initial and second operation (O-ORH). We analyzed surgical outcomes between L-LRH and O-LRH groups and between L-LRH and O-ORH groups using propensity-matching analysis for each pattern. RESULTS: Twenty-one patients each were included in L-LRH and O-LRH propensity-matched cohorts. The L-LRH group had a lower rate of postoperative complications than the O-LRH group (0 vs 19%, P = 0.036). When we compared surgical outcomes between L-LRH and O-ORH groups in another matched cohort with 18 patients in each group, in addition to the lower rate of postoperative complications, the L-LRH group had additional favorable surgical outcomes including shorter operation time and lower blood loss volume than the O-ORH group (291 vs 368 min, P = 0.037 and 10 vs 485 mL, P < 0.0001). CONCLUSIONS: An initial laparoscopic approach would be favorable for patients undergoing repeat hepatectomies, as it leads to lower risk of postoperative complications. Compared with O-ORH, the advantage of the laparoscopic approach may be enhanced when it is repeatedly adopted.

Factors Predicting Over-Time Weight Increase After Liver Transplantation: A Retrospective Study.

BACKGROUND: Post-transplantation weight control is important for long-term outcomes; however, few reports have examined postoperative weight change. This study aimed to identify perioperative factors contributing to post-transplantation weight change. METHODS: Twenty-nine patients who underwent liver transplantation between 2015 and 2019 with an overall survival of >3 years were analyzed. RESULTS: The median age, model for end-stage liver disease score, and preoperative body mass index (BMI) of the recipients were 57, 25, and 23.7, respectively. Although all but one recipient lost weight, the percentage of recipients who gained weight increased to 55% (1 month), 72% (6 months), and 83% (12 months). Among perioperative factors, recipient age ≤50 years and BMI ≤25 were identified as risk factors for weight gain within 12 months (P < .05), and patients with age ≤50 years or BMI ≤25 recipients gained weight more rapidly (P < .05). The recovery time of serum albumin level ≥4.0 mg/dL was not statistically different between the 2 groups. The weight change during the first 3 years after discharge was represented by an approximately straight line, with 18 and 11 recipients showing a positive and negative slope, respectively. Body mass index ≤23 was identified as a risk factor for a positive slope of weight gain (P <.05). CONCLUSIONS: Although postoperative weight gain implies recovery after transplantation, recipients with a lower preoperative BMI should strictly manage body weight as they may be at higher risk of rapid weight increase.

Assessment of serum and drain fluid bilirubin concentrations in liver transplantation patients.

BACKGROUND: Bile leakage is a major complication after liver transplantation and remains as a significant source of morbidity and mortality. In 2011, the International Study Group of Liver Surgery (ISGLS) defined bile leakage as a drain/serum bilirubin ratio ≥3. However, to our knowledge there is no literature assessing serum and drain bilirubin concentrations after liver transplantation. The aim of this study was to describe the natural postoperative changes in serum and drain fluid bilirubin concentrations in patients after liver transplantation. METHODS: We included 32 patients who underwent liver transplantation at Kobe University Hospital from January 2007 to December 2020. We enrolled 34 living donors who had no complications as the control group. RESULTS: The recipient serum total/direct bilirubin concentration were higher compared with the donors from postoperative day (POD) 1 to 5 with a statistical difference (P < .05). The recipient drain/serum total bilirubin ratio was lower than donors on POD 3 (0.89 ± 0.07 vs 1.53 ± 0.07: P < .0001), which was also confirmed by the recipient drain/serum direct bilirubin ratio (0.64 ± 0.10 vs 1.18 ± 0.09: P < .0001). On POD 3, the drain fluid volume (647.38 ± 89.47 vs 113.43 ± 86.8 mL: P < .001) and serum total bilirubin concentration (6.73 ± 0.61 vs 1.23 ± 0.60 mg/dL: P < .001) was higher in the recipients than in donors. Categorized in 2 groups, the higher drain fluid volume and bilirubin concentration recipients showed lower drain/serum total bilirubin ratio compared with the other group (P = .03) CONCLUSION: The drain/serum bilirubin ratio in the transplanted patients could be calculated lower compared with the hepatectomy patients because of high drain fluid volume and hyperbilirubinemia. Great care should be taken when assessing the bile leakage in liver transplant recipients using the ISGLS definition.

[A Case of Ampullary Carcinoma with Celiac Axis Stenosis That Underwent Pancreaticoduodenectomy and Arterial Reconstruction].

A 72-year-old male patient presented with obstructive jaundice and was diagnosed with ampullary carcinoma. Contrast- enhanced computed tomography(CT)showed stenosis of the common hepatic artery and dilatation of the pancreaticoduodenal arcade(PDA)due to celiac axis stenosis(CAS)at the origin, suggesting that hepatic artery blood flow was supplied from the superior mesenteric artery via the PDA. Since calcification of the arterial wall was observed at the origin of the celiac artery(CA), the cause of the CAS was diagnosed as atherosclerotic. An intraoperative gastroduodenal artery(GDA) clamp test showed no obvious decrease in hepatic arterial blood flow. However, because of concerns about the postoperative patency of the CA, an inferior pancreaticoduodenal artery-GDA bypass using the left great saphenous vein and subtotal stomach-preserving pancreaticoduodenectomy were performed. The postoperative course was uneventful. When pancreaticoduodenectomy is performed in patients with atherosclerotic CAS, this arterial reconstruction method can be considered as an option.

Rechallenge With Lenvatinib After Atezolizumab Plus Bevacizumab Treatment for Hepatocellular Carcinoma.

BACKGROUND/AIM: Atezolizumab plus bevacizumab and lenvatinib are the key drugs in the current systemic chemotherapeutic regimen for hepatocellular carcinoma (HCC). Studies have reported the potential effectiveness of lenvatinib introduction after an atezolizumab plus bevacizumab treatment; however, the therapeutic effectiveness of a lenvatinib rechallenge after an atezolizumab plus bevacizumab treatment remains unclear. PATIENTS AND METHODS: Thirteen consecutive patients who were rechallenged with lenvatinib after clinical failure following treatments with lenvatinib and atezolizumab plus bevacizumab were included. A comparative study was conducted on the duration and treatment efficacy of the first and second lenvatinib treatments and on the pre- and post-treatment liver function. RESULTS: The median ratios of the 1-month post-treatment alpha-fetoprotein (AFP) levels to the pretreatment AFP levels were 0.750 and 0.667 for the first and second lenvatinib treatments, respectively, without significant difference (p=0.9327). Meanwhile, the median ratios of the 1-month post-treatment albumin-bilirubin (ALBI) scores to the pretreatment ALBI scores were 1.063 and 0.827 for the first and second lenvatinib treatments, respectively, with significant difference (p=0.015). The median duration of the second lenvatinib treatment was significantly shorter than that of the first lenvatinib treatment [2.8 months (range=0.9-4.7 months) vs. 8.7 months (range=3.1-29.7 months)]. CONCLUSION: Lenvatinib re-administration after atezolizumab plus bevacizumab treatment can act as a double-edged sword, as it exerts an anti-tumor effect while being associated with potential liver function deterioration. However, this treatment sequence can be useful, and requires careful monitoring of the transitions in the liver function and the patient's performance status.

Standardization of laparoscopic anatomic liver resection of segment 2 by the Glissonean approach.

BACKGROUND: Anatomic liver resection (ALR) has been established to eliminate the tumor-bearing hepatic region with preservation of the remnant liver volume for liver malignancies. Recently, laparoscopic ALR has been widely applied; however, there are few reports on laparoscopic segmentectomy 2. This study aimed to present the standardization of laparoscopic segmentectomy 2 with surgical outcomes. METHODS: This study included seven patients who underwent pure laparoscopic segmentectomy 2 by the Glissonean approach from January 2020 to December 2021. Four of them had hepatocellular carcinoma, two had colorectal liver metastasis, and one had hepatic angiomyolipoma, which was preoperatively diagnosed with hepatocellular carcinoma. In all patients, preoperative three-dimensional (3D) simulation images from dynamic CT were reconstructed using a 3D workstation. The layer between the hepatic parenchyma and the Glissonean pedicle of segment 2 (G2) was dissected to encircle the root of G2. After clamping or ligation of the G2, 2.5 mg of indocyanine green was injected intravenously to identify the boundaries between segments 2 and 3 with a negative staining method under near-infrared light. Parenchymal transection was performed from the caudal side to the cranial side according to the demarcation on the liver surface, and the left hepatic vein was exposed on the cut surface if possible. RESULTS: The mean operative time for all patients was 281 min. The mean blood loss was 37 mL, and no transfusion was necessary. Estimated liver resection volumes significantly correlated with actual liver resection volumes (r = 0.61, P = 0.035). After the operation, one patient presented with asymptomatic deep venous and pulmonary thrombosis, which was treated with anticoagulant therapy. The mean length of hospital stay was 8.9 days. CONCLUSION: Laparoscopic segmentectomy 2 by the Glissonean approach is a feasible and safe procedure with the preservation of the nontumor-bearing segment 3 for liver tumors in segment 2.

Suitability of Laparoscopic Liver Resection of Segment VII: a Retrospective Two-Center Study.

BACKGROUND: Resecting liver tumors located in Couinaud's segment VII is challenging; the efficacy and safety of laparoscopic liver resection for segment VII lesions compared to open liver resection remain unclear. METHODS: Medical records of 84 patients who underwent liver resection of segment VII at Kobe University Hospital and Hyogo Cancer Center between 2010 and 2021 were retrospectively analyzed. Surgical outcomes were compared between laparoscopic liver resection and open liver resection groups using propensity matching analysis. RESULTS: Thirty-one and 53 patients underwent laparoscopic liver resection and open liver resection, respectively. After propensity matching, 29 patients were included in each group. The laparoscopic liver resection group had a significantly longer operation time (407 vs. 305 min, P = 0.002), lower blood loss (100 vs. 230 mL, P = 0.004), and higher postoperative alanine aminotransferase levels (436 vs. 252 IU/L, P = 0.008) than the open liver resection group. In patients with liver cirrhosis, the proportion of patients with postoperative liver-specific complications was higher in the laparoscopic liver resection group than in the open liver resection group (57% vs 11%, P = 0.049), although there was no significant difference in postoperative liver-specific complication rates between the groups in patients without liver cirrhosis. CONCLUSIONS: For liver resection of segment VII, laparoscopic liver resection led to higher postoperative liver damage than open liver resection. Open liver resection may be better for patients with liver cirrhosis to avoid postoperative liver-specific complications. Laparoscopic liver resection could be an acceptable procedure for patients without liver cirrhosis, with some merits such as less blood loss.

Successful recanalization of completely obstructed portal vein thrombosis after right hepatectomy for perihilar cholangiocarcinoma by aspiration thrombectomy via the ileocolic mesenteric vein and subsequent systemic anticoagulation with edoxaban.

Portal vein thrombosis (PVT) is a lethal complication of hepatectomy if not properly treated. An 81-year-old woman diagnosed with postoperative PVT after right hepatectomy and caudate lobectomy for perihilar cholangiocarcinoma. Elevation of serum total bilirubin levels, D-dimer levels, and glossy ascites appeared on postoperative day 5 (POD5), and a contrast-enhanced CT confirmed PVT. Thrombi were found from the umbilical portion of the portal vein to the superior mesenteric vein. There were signs of acute liver failure due to thrombi obstructing the portal vein. Therefore, emergent catheter thrombus aspiration was performed under laparotomy. An aspiration catheter was inserted into the superior mesenteric vein from the ileocolic vein. We performed direct aspiration thrombectomy, followed by anticoagulant administration using urokinase via the catheter. Partial recanalization of the portal vein and superior mesenteric vein was observed. To dissolve residual thrombi, edoxaban administration was started on POD6. Contrast-enhanced CT 16 days after her additional operation showed the thrombi had completely disappeared. The patient was discharged on POD76. She had no recurrence of PVT over the next 6 months. Combination therapy of early intervention using aspiration catheter and systemic anticoagulant medication was useful for severe postoperative PVT accompanied with liver failure.

Prognostic Impact of Inflammation-Based Scores for Extrahepatic Cholangiocarcinoma.

INTRODUCTION: Although the relationship between systemic inflammatory responses and prognosis has been known in various cancers, it remains unclear which scores are most valuable for determining the prognosis of extrahepatic cholangiocarcinoma. We aimed to verify the usefulness of various inflammation-based scores as prognostic factors in patients with resected extrahepatic cholangiocarcinoma. METHODS: We analyzed consecutive patients undergoing surgical resection for extrahepatic cholangiocarcinoma at our institution between January 2000 and December 2019. The usefulness of the following inflammation-based scores as prognostic factor was investigated: glasgow prognostic score (GPS), modified GPS, neutrophil-to-lymphocyte ratio, platelet to lymphocyte ratio, lymphocyte-to-monocyte ratio, prognostic nutrition index, C-reactive protein to albumin ratio (CAR), controlling nutritional status (CONUT), and prognostic index. RESULTS: A total of 169 patients were enrolled in this study. Of the nine scores, CAR and CONUT indicated prognostic value. Furthermore, multivariate analysis for overall survival revealed that high CAR (>0.23) was an independent prognostic factor (hazard ratio: 1.816, 95% confidence interval: 1.135-2.906, p = 0.0129), along with lymph node metastasis and curability. There was no difference in tumor staging and short-term outcomes between the low CAR (≤0.23) and high CAR groups. CONCLUSIONS: CAR was the most valuable prognostic score in patients with resected extrahepatic cholangiocarcinoma.

Standardization of the Side-to-Side Cavo-Caval Anastomosis in Orthotopic Liver Transplantation Based on the Causal Analysis of Outflow Obstruction.

BACKGROUND: Although liver transplantation is widely accepted as the therapeutic strategy for end-stage liver failure, complication of hepatic venous outflow obstruction remains lethal. Currently, ensuring a single wide orifice in both the graft and recipient inferior vena cava has been proposed to avoid hepatic venous outflow obstruction with no theoretical concept. METHODS: We herein report a standardization technique for the reconstruction of the hepatic vein based on the causal analysis. RESULTS: During the put-in process, the graft must be positioned in contact with the recipient diaphragm and slightly pushed to the cranial direction to simulate the state after abdominal closure. Because there is no extra space between the graft and diaphragm, the graft could not rotate about the anastomotic site of the inferior vena cava toward the diaphragm after abdominal closure as the intestinal pressure increases, and accordingly hepatic venous outflow obstruction does not develop. CONCLUSIONS: With this concept, all transplant surgeons can successfully and easily perform hepatic vein reconstruction without total clamping of the inferior vena cava and without outflow block.

Impact of Sarcopenia as a Prognostic Factor on Reductive Hepatectomy for Advanced Hepatocellular Carcinoma.

BACKGROUND/AIM: Sarcopenia has been reported to be a significant prognostic factor in patients with hepatocellular carcinoma in recent years. This study aimed to clarify the prognostic significance of sarcopenia in advanced hepatocellular carcinoma treated with reductive hepatectomy. PATIENTS AND METHODS: We retrospectively analyzed 93 patients who underwent reductive hepatectomy for advanced hepatocellular carcinoma. RESULTS: Median survival time of the sarcopenia group (16.4 months) was significantly shorter than that of the non-sarcopenia group (20.4 months). The overall survival rates at 1, 3, and 5 years of the sarcopenia group were significantly lower than those of the non-sarcopenia group (57.9%, 8.6%, and 2.9% vs. 67.3%, 29.2%, and 15.7%, respectively; p=0.035). On multivariate analysis, sarcopenia was a significant risk factor of overall survival (hazard ratio=1.60, 95% confidence interval=1.00-2.56, p=0.049). CONCLUSION: Sarcopenia was a significant prognostic factor of survival after reductive hepatectomy in advanced hepatocellular carcinoma.

Lenvatinib Rechallenge After Ramucirumab Treatment Failure for Hepatocellular Carcinoma.

BACKGROUND/AIM: While there is increasing evidence supporting the role of several first- and second-line treatment regimens for advanced hepatocellular carcinomas (HCC), the clinical relevance of rechallenge treatment with previously administered drugs, however, remains to be explored. PATIENTS AND METHODS: Five consecutive patients with advanced HCC who received lenvatinib rechallenge treatment after ramucirumab were assessed. RESULTS: All patients were clinically diagnosed with failure after ramucirumab treatment, and the frequencies of ramucirumab administration before lenvatinib re-administration ranged from 3 to 11. The alfa-fetoprotein level in four of five patients decreased 1 month after the lenvatinib rechallenge. Radiological findings via the modified Response Evaluation Criteria in Solid Tumors showed stable diseases in four patients and a partial response in one. CONCLUSION: Rechallenge treatment with lenvatinib after ramucirumab can be effective, and may be a treatment option for HCC in cases wherein the disease progressed after an initial response to lenvatinib treatment.

Indication of Surgical Hepatectomy for the Patients of Hepatocellular Carcinoma with Inferior Vena Cava Tumor Thrombosis.

The prognosis of hepatocellular carcinoma (HCC) presenting with inferior vena cava tumor thrombus (IVCTT) is extremely poor. The aim of this study was to reveal the postoperative course and to identify patients who have survived surgical hepatectomy among HCC patients with IVCTT. Between January 2006 and December 2018, 643 patients underwent surgical hepatectomy for HCC at Kobe University Hospital. Among them, 20 patients were categorized as Vv3 according to the Japanese staging system. We retrospectively collected detailed data on these patients. The statistical, clinical, and pathological data were recorded prospectively and analyzed retrospectively. The median survival time was 9.8 months. Among all patients, 11 (55%) achieved R0 resection, and only two survivors were from this group. The number of tumors (solitary vs. multiple; p=0.050) and pathological Vp (pVp0 vs. other; p=0.009) were identified as risk factors for overall survival in the univariate analysis. In the multivariate analysis, pathological Vp (pVp0 vs. other; p=0.037) was identified as a significant prognostic factor for survival. Pathological Vp affected overall survival among IVCTT patients; the median survival time was 53.7 months with pVp0, 10.2 months with pVp1, and 8.8 months with pVp2-4 (p=0.035). For patients with IVCTT, surgical hepatectomy should be indicated only for those who do not have portal vein invasion and could achieve R0 resection.

Laparoscopic repeat hepatectomy is a more favorable treatment than open repeat hepatectomy for contralateral recurrent hepatocellular carcinoma cases.

BACKGROUND: We compared surgical outcomes, with a focus on tumor characteristics, of laparoscopic repeat hepatectomy (LRH) and open repeat hepatectomy (ORH) to identify recurrent hepatocellular carcinoma (HCC) cases where the LRH procedure would be more favorable than ORH. METHODS: Eighty-one HCC patients who underwent repeat hepatectomy in our hospital from 2008 to 2019 were retrospectively analyzed in this study. Of these patients, 30 and 51 patients underwent LRH and ORH, respectively. We analyzed surgical outcomes of LRH and ORH, focusing on tumor characteristics such as tumor size, location, distance from major vessels, and contralateral or ipsilateral tumor recurrence to determine what factors could affect surgical outcomes. Subsequently, using a propensity-matched cohort, we compared the impact of those factors on LRH and ORH outcomes. RESULTS: In the entire cohort, the LRH operation time was significantly shorter in contralateral recurrent HCC cases than in ipsilateral recurrent HCC cases (252 vs. 398 min, P = 0.008); however, such a difference was not observed in the ORH operation time. We subsequently compared the surgical outcomes, in terms of the location of tumor recurrence, between the LRH and ORH groups in a propensity-matched cohort. In total, 23 patients were included in each of these groups. We found that the LRH procedure had significantly shorter operative time than the ORH procedure in the contralateral recurrent HCC cases (253 vs. 391 min, P = 0.018); however, we did not observe such a difference in the ipsilateral recurrent HCC cases (372 vs. 333 min, P = 0.669). LRH had lower blood loss, similar postoperative complications and shorter hospital stay than ORH in both contralateral and ipsilateral recurrent HCC cases. CONCLUSIONS: LRH is likely considered a more favorable approach than ORH in treating patients with contralateral recurrent HCC.