Association between tumor morphology and efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma.

AIM: The IMbrave150 trial revealed that atezolizumab plus bevacizumab (AtezoBv) showed a higher objective response rate (ORR) in patients with advanced hepatocellular carcinoma (HCC). Although conversion therapy after AtezoBv has been recently reported, markers predictive of its efficacy, particularly radiological imaging markers, have not yet been identified. The present study focused on tumor morphological appearance on radiological imaging and evaluated whether it could be associated with AtezoBv efficacy. METHODS: Ninety-five intrahepatic lesions in 74 patients who were given AtezoBv for advanced HCC were recruited for evaluation. The lesions were divided into two groups, simple nodular (SN group) and non-simple nodular (non-SN group), based on the gross morphology on pretreatment imaging, and retrospectively evaluated for treatment response and other relevant clinical outcomes. RESULTS: Assessing the size of individual tumors after treatment, waterfall plots showed that tumor shrinkage in the non-SN group including 56 lesions was higher than that in the SN group comprising 39 lesions. The ORR was significantly higher in the non-SN group (39.3% vs. 15.4%, p = 0.012). Additionally, the median time to nodular progression was longer in the non-SN group (21.0 months vs. 8.1 months, p = 0.119) compared to the SN group. Six patients with non-SN lesions underwent sequential local therapy. CONCLUSIONS: Atezolizumab plus bevacizumab may show increased therapeutic efficacy in patients with tumors with a higher potential for aggressive oncological behavior, such as non-SN lesions. Treatment strategies focusing on conversion therapy may be crucial in patients with non-SN lesions.

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.

A Novel Method Using Gadolinium-Ethoxybenzyl Diethylenetriamine Pentaacetate Acid-Enhanced Magnetic Resonance Imaging for Predicting Post-Hepatectomy Liver Failure in Hepatocellular Carcinoma Patients with a Major Portal Vein Tumor Thrombus.

INTRODUCTION: The usefulness of gadolinium-ethoxybenzyl diethylenetriamine pentaacetate acid-enhanced magnetic resonance imaging (EOB-MRI) in assessing the functional future remnant liver volume (fFRLV) to predict post-hepatectomy liver failure (PHLF) has been previously reported. Herein, we evaluated the efficacy of this technique in patients with hepatocellular carcinoma (HCC) with a major portal vein tumor thrombus (PVTT). METHODS: This study included 21 patients with PVTT in the ipsilateral first-order branch (Vp3) and 30 patients with PVTT in the main trunk/contralateral branch (Vp4). To evaluate fFRLV, the signal intensity (SI) of the remnant liver was determined on T1-weighted images, using both conventional and newly developed methods. The fFRLV was calculated using the SI of the remnant liver and muscle, remnant liver volume, and body surface area. Preoperative factors predicting PHLF (≥grade B) in HCC patients with Vp3/4 PVTT were evaluated. RESULTS: In the Vp3 group, we found fFRLV area under the receiver-operating characteristic curves (AUCs) above 0.70 (AUC = 0.875, 0.750) using EOB-MRI results calculated using either the plot or whole method. None of the parameters in the Vp4 group had an AUC greater than 0.70. CONCLUSION: The fFRLV calculated by EOB-MRI using the whole method can be as useful as the conventional method in predicting PHLF (≥grade B) for HCC patients with Vp3 PVTT.

DKK1-CKAP4 signal axis promotes hepatocellular carcinoma aggressiveness.

Hepatocellular carcinoma (HCC) is the most prevalent malignant liver neoplasm. Despite the advances in diagnosis and treatment, the prognosis of HCC patients remains poor. Cytoskeleton-associated membrane protein 4 (CKAP4) is a receptor of the glycosylated secretory protein Dickkopf-1 (DKK1), and the DKK1-CKAP4 axis is activated in pancreatic, lung, and esophageal cancer cells. Expression of DKK1 and CKAP4 has been examined in HCC in independent studies that yielded contradictory results. In this study, the relationship between the DKK1-CKAP4 axis and HCC was comprehensively examined. In 412 HCC cases, patients whose tumors were positive for both DKK1 and CKAP4 had a poor prognosis compared to those who were positive for only one of these markers or negative for both. Deletion of either DKK1 or CKAP4 inhibited HCC cell growth. In contrast to WT DKK1, DKK1 lacking the CKAP4 binding region did not rescue the phenotypes caused by DKK1 depletion, suggesting that binding of DKK1 to CKAP4 is required for HCC cell proliferation. Anti-CKAP4 Ab inhibited HCC growth, and its antitumor effect was clearly enhanced when combined with lenvatinib, a multikinase inhibitor. These results indicate that simultaneous expression of DKK1 and CKAP4 is involved in the aggressiveness of HCC, and that the combination of anti-CKAP4 Ab and other therapeutics including lenvatinib could represent a promising strategy for treating advanced HCC.

Laparoscopic Medial-to-Lateral Approach for the Resection of Hepatocellular Carcinoma Located at the Spiegel Lobe of the Liver.

BACKGROUND: Laparoscopic caudate lobe resection is a challenging procedure. Several researchers have reported the safety of laparoscopic liver resections;1.Transl Gastroenterol Hepatol. 1:56;2.Asian J Endosc Surg. 12:232-236;3.Ann Surg Oncol. 26:2980; however, a standardized procedure has not yet been established. Herein, we present a video showing laparoscopic Spiegel lobectomy in a patient with 6-cm hepatocellular carcinoma (HCC) using a novel approach. PATIENT AND METHODS: A 63-year-old man with a caudate lobe HCC was referred to our hospital. Computed tomography showed a 5 × 6 cm2 HCC located in the Spiegel lobe, which profoundly displaced the inferior vena cava (IVC) to the lower right side, and mobilization of the Spiegel lobe was considered difficult. To perform the dissection between the Siegel lobe and IVC safely, we performed parenchymal transection along the ventral side of the IVC initially. The Spiegel lobe was then dislocated to the left side of the IVC. We dissected the left lateral side of the IVC, including the proper hepatic vein draining the caudate lobe and the left IVC ligament with a safe operative field, and successfully removed the Spiegel lobe with large HCC. RESULTS: The operation time was 383 min. The blood loss was 10 mL. The patient was discharged on the seventh postoperative day without any complications. Histopathological examination revealed well-differentiated HCC with a negative surgical margin. CONCLUSIONS: Laparoscopic medial-to-lateral approach with initial parenchymal transection at the medial side of the Spiegel lobe followed by dissection of the left lateral side of the IVC is considered as a safe and effective procedure for large tumors in the Spiegel lobe.

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.

Efficacy and safety of laparoscopic liver resection for hepatocellular carcinoma in segment 8: a propensity score-matched two-center study.

BACKGROUND: The safety and efficacy of laparoscopic liver resection (LLR) have been reported worldwide. However, those of LLR for tumors located in Couinaud's segment 8 are not sufficiently investigated. METHODS: We retrospectively analyzed 108 patients who underwent liver resection for hepatocellular carcinoma (HCC) in segment 8 at Kobe University Hospital and Hyogo Cancer Center between January 2010 and December 2021. The patients were categorized in LLR and open liver resection (OLR) groups, and 1:1 propensity score matching (PSM) was performed to compare surgical outcomes between the groups. RESULTS: Forty-seven and 61 patients underwent LLR and OLR, respectively. After PSM, each group contained 34 patients. There was no significant difference in operation time between the groups (331 min vs. 330 min, P = 0.844). Patients in the LLR group had significantly less blood loss (30 mL vs. 468 mL, P < 0.001) and shorter length of postoperative hospital stay (10 days vs. 12 days, P = 0.015) than those in the OLR group. There was no significant difference in the occurrence of postoperative complications between the groups (12% vs. 9%, P = 0.690). Further, the 1-year cumulative incidence of recurrence was not significantly different between the groups (16% vs. 19%, P = 0.734). CONCLUSIONS: The surgical outcomes and short-term prognosis of LLR were similar or better than those of OLR. LLR could be an effective and safe procedure, even for lesions located in segment 8, which is considered a difficult anatomical location for LLR.

Risk Factors for Recurrence of Cholangitis After Pancreaticoduodenectomy and Comparison of Stents in Hepaticojejunostomy.

BACKGROUND: Postoperative cholangitis is a common complication of pancreaticoduodenectomy. Frequent cholangitis impairs patients' quality of life after pancreaticoduodenectomy. However, the risk factors for recurrence of cholangitis remain unclear. Hence, this retrospective study aimed to identify risk factors for recurrence of cholangitis after pancreaticoduodenectomy. METHODS: The medical records of patients who underwent pancreaticoduodenectomy between 2015 and 2019 in our institution were retrospectively reviewed. At least two episodes of cholangitis a year after pancreaticoduodenectomy were defined as 'recurrence of cholangitis' in the present study. Univariate and multivariate analyses were performed. RESULTS: The recurrence of cholangitis occurred in 40 of 207 patients (19.3%). Multivariate analysis revealed that internal stent (external, RR: 2.16, P = 0.026; none, RR: 4.76, P = 0.011), firm pancreas (RR: 2.61, P = 0.021), constipation (RR: 3.49, P = 0.008), and postoperative total bilirubin>1.7 mg/dL (RR: 2.94, P = 0.006) were risk factors of recurrence of cholangitis. Among patients with internal stents (n = 54), those with remnant stents beyond 5 months had more frequent recurrence of cholangitis (≥5 months, 75%; <5 months, 30%). CONCLUSIONS: Internal stents, firm pancreas, constipation, and postoperative high bilirubin levels are risk factors for cholangitis recurrence after pancreaticoduodenectomy. In addition, the long-term implantation of internal stents may trigger cholangitis recurrence.

Transarterial chemoembolization for liver metastases of a pancreatic neuroendocrine neoplasm: a single-center experience.

Transarterial chemoembolization (TACE) is performed for pancreatic neuroendocrine tumor (PanNEN) liver metastases; however, the safety and efficacy of TACE procedures, especially for patients who have undergone previous pancreatic surgery, have not been established. We reviewed 48 TACE procedures (1-6 procedures/patient) performed on 11 patients with PanNEN liver metastases, including 16 TACE procedures (4-6 procedures/patient) for 3 patients with a history of biliary-enteric anastomosis. The overall tumor objective response rate was 94%. The incidence of Clavien‒Dindo grade ≥ 2 complications was 1/16 (6%) and 1/32 (3%), and the median time to untreatable progression was 31 (14-41) and 27 (2-60) months among patients with and without a history of biliary-enteric anastomosis, respectively. Although validation is needed in future studies, our experiences have shown that TACE treatment is a viable treatment option for PanNEN liver metastases, even after biliary-enteric anastomosis with experienced teams and careful patient follow-up.

[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.

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.

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.

[Laparoscopic Distal Pancreatectomy for Pancreatic Metastasis of Undifferentiated Pleomorphic Sarcoma-A Case Report].

Undifferentiated pleomorphic sarcoma(UPS)is a non-epithelial malignant tumor with a high rate of recurrence and metastasis. The frequent metastasis site is lung, lymph node, liver and bone. Pancreatic metastasis is rare. 71-year-old woman whose course after right foot UPS resection had been followed up at our hospital. But multiple bone and muscle metastasis occurred 1 year after operation. She had resection or radiation for the recurrence. 3 years after the first operation, PET-CT and EUS-FNA revealed pancreatic tail metastasis. The tumor grew up in 6 months, so we performed laparoscopic distal pancreatectomy. The patient recovered uneventfully and was discharged on post-operative day 14. Currently 5 years and 6 months have passed since the first surgery and she is alive. Function-preserving and minimally invasive surgery for UPS pancreatic metastasis is considered to be essential.

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.

Pineal gland differentiation in mature teratoma: An under-recognized condition and potential pitfalls for overdiagnosis.

We herein report three cases of mature teratomas with pineal gland differentiation, which is a less recognized phenomenon. Case 1 was a 6-year-old male with a neck mass, Case 2 was a 23-year-old female with a retroperitoneal mass, and Case 3 was a 45-year-old female with a retroperitoneal mass. Each case showed the typical macroscopic and histological findings of mature teratoma, such as solid and cystic lesions mainly lined with a mature squamous epithelium. All cases also showed glial differentiation. Small foci of lobulated cell nests were detected in the center of or adjacent to mature glial tissue. Cells had a clear to pale eosinophilic cytoplasm with small round nuclei. Immunohistochemically, cells were positive for synaptophysin, neurofilament protein with a perivascular "club-shaped swelling" pattern, and cone-rod homeobox protein. To the best of our knowledge, this is the first report of pineal gland differentiation arising in mature teratoma, which may be easily overlooked or misdiagnosed as somatic-type tumors, particularly neuroendocrine tumors. To avoid overtreatment, pathologists need to be aware that pineal gland differentiation may occur in mature teratomas.

[A Case of Pancreatic Cancer with Gastric Wall Recurrence after Laparoscopic Distal Pancreatectomy Due to Needle Tract Seeding following EUS-FNA].

A woman in her 80s was diagnosed with pancreatic tail cancer by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). We performed laparoscopic distal pancreatectomy followed by adjuvant chemotherapy with S-1 for 6 months. One year after surgery, contrast-enhanced computed tomography revealed a 15 mm mass in the posterior wall of the gastric body. EUS showed a hypoechoic mass in the muscular layer in the gastric wall, which was diagnosed as adenocarcinoma by FNA. We diagnosed gastric wall recurrence due to needle tract seeding(NTS)following EUS-FNA and performed partial gastrectomy. Histopathological diagnosis was gastric wall recurrence of pancreatic cancer. Since NTS following EUS-FNA can be proven only by the presence of gastric wall recurrence after surgery for pancreatic body or tail cancer, the actual risk of NTS including peritoneal dissemination is not clear and may have been underestimated. In case of resectable pancreatic body or tail cancer, indication for EUS-FNA should be carefully considered.

Clinical Significance of Hepatectomy for Hepatocellular Carcinoma Associated with Extrahepatic Metastases.

BACKGROUND: This study evaluated the prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastases who can undergo hepatectomy. METHODS: A total of 32 patients who underwent hepatectomy for HCC with extrahepatic metastases, including lymph node and/or distant metastases were recruited for this study. RESULTS: Fourteen patients had lymph node metastasis only, 16 had distant metastasis only, and 2 had both metastasis types during preoperative diagnosis. The 3-year overall survival (OS) rate of all patients was 17.9%, and the median survival time (MST) was 11.8 months. Univariate analysis revealed that intrahepatic maximal tumor size, intrahepatic tumor number, and intrahepatic tumor control after hepatectomy were significant factors influencing OS (p < 0.05). Multivariate analysis revealed that independent risk factors for OS were intrahepatic maximal tumor size and intrahepatic tumor number (p < 0.05). The MST and 3-year OS rate of patients with maximal tumor size <100 mm and intrahepatic tumor number ≤2 were 39.0 months and 51.9%, respectively. CONCLUSIONS: Hepatectomy is not recommended for HCC patients with extrahepatic metastasis with ≥3 intrahepatic tumors, even when all intrahepatic tumors can be eliminated via hepatectomy. Aggressive surgery may be justified for HCC patients with ≤2 intrahepatic tumors and maximal tumor size <100 mm, irrespective of vascular invasion.

Assessment of lenvatinib treatment for unresectable hepatocellular carcinoma with liver cirrhosis.

BACKGROUND: The present study aimed to assess the clinical features of patients who received lenvatinib treatment for unresectable hepatocellular carcinoma (HCC). METHODS: The clinical characteristics, adverse events, and radiological responses were evaluated for 51 consecutive patients. RESULTS: Of the study subjects, 37 patients had Child-Pugh class A (CPA) liver function, and 14 patients had Child-Pugh class B (CPB) liver function. The overall response rates in the CPA and CPB groups were 42.9% and 25.0%, respectively, and disease control rates were 82.9% and 83.3%, respectively, without significant difference (p = 0.2621 and 0.9697). There was no significant difference between CPA and CPB groups regarding the incidence of adverse events, except for hepatic coma. No significant difference was observed in the relative dose intensity between the CPA and CPB groups, for the first month, 1-2 months, or 2-3 months (p = 0.2368, 0.9368, and 0.9293). CONCLUSION: The comparable outcomes between the CPA and CPB groups suggest the acceptability of lenvatinib treatment in patients with impaired liver function, at least in the acute phase. With careful follow-up, the dose can be relatively intensified, even in patients with impaired liver function and this may contribute to offering comparable treatment.

Clinical Relevance of Reductive Hepatectomy for Barcelona Clinic Liver Cancer Stages B and C Advanced Hepatocellular Carcinoma: A Single-Center Experience of 102 Patients.

BACKGROUND: This study aimed to evaluate the clinical relevance of hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stages B and C advanced hepatocellular carcinoma (HCC). METHODS: A total of 314 patients (149 and 165 BCLC stages B and C, respectively) who underwent hepatectomy were included. Complete hepatectomy (without residual tumors after hepatectomy) and reductive hepatectomy (apparent residual tumors after hepatectomy) were performed for 212 and 102 patients, respectively. Short-term operative and postoperative outcomes, as well as long-term outcomes, were evaluated. RESULTS: The median survival times of patients with stage B disease undergoing complete hepatectomy and reductive hepatectomy were 48.9 and 20.1 months, respectively (p = 0.0075), whereas those of patients with stage C disease were 19.5 and 17.6 months, respectively (p = 0.0140). The 3-year overall survival rates of patients with stage B disease undergoing reductive hepatectomy with and without subsequent local treatments after surgery were 47.5% and 0%, respectively, whereas those of patients with stage C diseases were 18.6% and 0%, respectively. CONCLUSIONS: Survival benefits are obvious for both BCLC stages B and C HCC when complete hepatectomy can be performed safely. Reductive hepatectomy is also acceptable for BCLC stages B and C when subsequent local treatment for remnant liver tumors can be performed safely after reductive hepatectomy. Without subsequent local treatment, reductive hepatectomy has little clinical relevance. Thus, a cautious approach to patient selection is required for this aggressive strategy.

[Analysis of Hepatectomy for Extreme Elderly Patients with Hepatocellular Carcinoma].

Although the first-line treatment for hepatocellular carcinoma(HCC)is hepatectomy, extreme elderly(80 years or older) patients often tend to have a variety of underlying diseases and decreased cardiopulmonary function, which means that surgery involves a high risk. In this case, we examined the safety and efficacy of hepatectomy performed in an extreme elderly patient with HCC. Of the patients with HCC that underwent initial hepatectomy at Kobe University Hospital(n=348)between 2009 and 2015, 23 patients aged 80 years or older at the time of surgery(Group 1, n=23)and those younger than 80 years at the time(Group 2, n=325)were compared, based on parameters related to safety and prognosis. We did not identify differences between the 2 groups with respect to blood loss and operating time. Intraoperative blood transfusion was more common in Group 1. There was no significant difference between the 2 groups with respect to complications of Grade Ⅲ or higher. The median survival of Group 2 patients following hepatectomy(42 months)was better than that of Group 1 patients(34 months), but there was no significant difference between the 2 groups(p=0.429). Furthermore, when the same parameters were compared after adjusting for and matching propensity scores, there were no significant differences in complications, hospitalization periods, and prognosis between the 2 groups. Through proper assessment of oncologic factors and patient risk factors, hepatectomy can be performed safely and effectively even for extreme elderly patients with HCC. If there is no other disease regulating the prognosis, we can expect to achieve similar prognosis in non-extreme elderly patients. Hence, treatments should not be limited solely based on a patient being extremely elderly; rather, proactive treatments should be considered.