Noninvasive Visualization of Tumor Blood Vessels within Hepatocellular Carcinoma by Application of Superb Microvascular Imaging to Contrast-Enhanced Ultrasonography.

The combination or sequential use of systemic therapies, such as lenvatinib and locoregional therapies, can improve the curability rate of hepatocellular carcinoma. This is based on the notion that lenvatinib remodels abnormal tumor vessels into normal vessels, potentially enhancing the efficacy of locoregional therapies. In this case report, we achieved noninvasive visualization of tumor blood vessels by applying superb microvascular imaging (SMI) to contrast-enhanced ultrasonography (CEUS). A man in his 80s with a borderline resectable hepatocellular carcinoma received preoperative therapy using lenvatinib. The patient achieved a complete response after lenvatinib therapy, underwent hepatectomy, and maintained a cancer-free status. CEUS and SMI revealed a decrease in tumor blood vessels at 1 week after lenvatinib administration and a decrease in tumor perfusion at 2 weeks. Although CEUS alone is adequate for noninvasive real-time evaluation of tumor perfusion, it is not sufficient to achieve accurate assessments of tumor blood vessels. We performed a noninvasive time-course evaluation of vascular normalization after lenvatinib administration by applying SMI. The evaluation of vascular normalization with lenvatinib therapy using CEUS and SMI can support the decision to proceed to conversion therapies.

Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone: NCC-GCTB8-C1 and NCC-GCTB9-C1.

Giant cell tumor of bone (GCTB) is a rare osteolytic bone tumor consisting of mononuclear stromal cells, macrophages, and osteoclast-like giant cells. Although GCTB predominantly exhibits benign behavior, the tumor carries a significant risk of high local recurrence. Furthermore, GCTB can occasionally undergo malignant transformation and distal metastasis, making it potentially fatal. The standard treatment is complete surgical resection; nonetheless, an optimal treatment strategy for advanced GCTB remains unestablished, necessitating expanded preclinical research to identify appropriate therapeutic options. However, only one GCTB cell line is publicly available from a cell bank for research use worldwide. The present study reports the establishment of two novel cell lines, NCC-GCTB8-C1 and NCC-GCTB9-C1, derived from the primary tumor tissues of two patients with GCTB. Both cell lines maintained the hallmark mutation in the H3-3A gene, which is associated with tumor formation and development in GCTB. Characterization of these cell lines revealed their steady growth, spheroid-formation capability, and invasive traits. Potential therapeutic agents were identified via extensive drug screening of the two cell lines and seven previously established GCTB cell lines. Among the 214 antitumor agents tested, romidepsin, a histone deacetylase inhibitor, and mitoxantrone, a topoisomerase inhibitor, were identified as potential therapeutic agents against GCTB. Conclusively, the establishment of NCC-GCTB8-C1 and NCC-GCTB9-C1 provides novel and crucial resources that are expected to advance GCTB research and potentially revolutionize treatment strategies.

Hyaline-vascular type unicentric Castleman disease with dysplastic follicular dendritic cell proliferative lesions: a case report.

Castleman disease (CD) is a rare lymphoproliferative disease. Hyaline-vascular type unicentric CD has a good prognosis if completely resected during surgery. However, follicular dendritic cell proliferative lesions have the potential for recurrence and metastasis. A 22-year-old man was referred to our hospital with the chief complaint of nausea and vomiting. These symptoms were caused by a right mesocolonic tumor pushing the duodenum. The patient underwent laparoscopic tumorectomy and complete surgical excision. The postoperative course was uneventful, with no complications. Pathological examination confirmed that the tumor was an enlarged lymph node, typical of hyaline vascular-type CD; however, follicular dendritic cell proliferative lesions were noted. We report a rare case of hyaline-vascular-type CD with follicular dendritic cell proliferative lesions associated with malignancy, as limited case reports exist on this particular disease.

Beneficial Effects of Combined Use of Extracorporeal Membrane Oxygenation and Hypothermic Machine Perfusion in Porcine Donors after Cardiac Death for Liver Transplantation.

Grafts from donors after cardiac death (DCD) have greatly contributed to expanding the donor organ pool. This study aimed to determine the benefits of subnormothermic extracorporeal membrane oxygenation (ECMO) and hypothermic machine perfusion (HMP) in a porcine model of DCD liver. Female domestic crossbred Large Yorkshire and Landrace pigs weighing approximately 20 kg were used. The abdominal aorta and inferior vena cava were cannulated and connected to an ECMO circuit for in situ perfusion of the abdominal organs at 22 °C for 60 min, 45 min after cardiac death. The pigs were divided into the cold storage (CS) group (n = 3), where liver grafts were preserved at 4 °C, and the HMP group (n = 3), where liver grafts were preserved by HMP at 8-10 °C. After 4 h of preservation, liver function was evaluated using an isolated liver reperfusion model for 2 h. Although the difference was insignificant, the liver effluent enzyme levels in the HMP group were lower than those in the CS group. Furthermore, morphological findings showed fewer injured hepatocytes in the HMP group than in the CS group. The combined use of in situ subnormothermic ECMO and HMP was beneficial for the functional improvement of DCD liver grafts.

Laparoscopic Extended Left Lateral Sectionectomy for Hepatocellular Carcinoma in a Patient with Right-Sided Ligamentum Teres: A Case Report and Literature Review.

Right-sided ligamentum teres (RSLT) is a rare anatomic variant in which the fetal umbilical vein connects to the right portal vein. Patients with RSLT frequently have hepatic vasculature and bile duct anomalies, which increase the risk of complications with hepatectomy. Most patients with RSLT undergo open hepatectomy. Herein, we describe a patient with RSLT and hepatocellular carcinoma who underwent laparoscopic hepatectomy. The patient was a 69-year-old man with hepatocellular carcinoma located in the left liver based on computed tomography (CT) and magnetic resonance imaging. Imaging also demonstrated RSLT. Three-dimensional CT analysis revealed independent right lateral type anomalies of the portal vein and bile duct. A laparoscopic extended left lateral sectionectomy was performed after careful surgical planning. Ultrasonography was used frequently during surgery to avoid damaging the right hepatic vasculature. The left lateral and partial left median sections were removed as planned. The patient's postoperative recovery was uneventful. Avoiding injury to the right hepatic vasculature is essential when performing left lobectomy, including left lateral sectionectomy, in patients with RSLT. Laparoscopic hepatectomy can be performed safely in patients with RSLT, provided that careful surgical planning is conducted using preoperative three-dimensional CT analysis and intraoperative ultrasonography.

Applicability of the histidine-tryptophan-ketoglutarate solution as a machine perfusion solution for marginal liver grafts.

BACKGROUND AND AIM: There are very few reports comparing the use of the University of Wisconsin solution and histidine-tryptophan-ketoglutarate solution as machine perfusion solutions for marginal liver grafts. We aimed to clarify whether the use of the histidine-tryptophan-ketoglutarate solution in hypothermic machine perfusion improves the split-liver graft function in a large animal model. METHODS: Porcine split-liver grafts were created by 75% liver resection. Hypothermic machine perfusion experimental groups were divided as follows: Group 1, perfusate, University of Wisconsin gluconate solution (UW group; n = 5), and Group 2, perfusate, histidine-tryptophan-ketoglutarate solution (HTK group; n = 4). After 4 h of preservation, the liver function was evaluated using an isolated liver reperfusion model for 2 h. RESULTS: In the HTK group, the portal vein and hepatic artery resistance during hypothermic machine perfusion and the portal vein resistance during isolated liver reperfusion were lower than those in the UW group. In addition, the total Suzuki score for hepatic ischemia-reperfusion injury in the HTK group was significantly better than that in the UW group. The number of anti-ETS-related genes staining-positive sinusoid epithelial cell nuclei in the HTK group was higher than that in the UW group (not significant). CONCLUSIONS: The histidine-tryptophan-ketoglutarate solution can be perfused with lower vascular resistance than the University of Wisconsin solution, reducing shear stress and preventing sinusoid epithelial cell injury in marginal grafts used as split-liver grafts.

The experience of 100 cases of 8K/two-dimensional laparoscopic colorectal surgery - The evaluation of 8K/two-dimensional laparoscopy and how to use it.

Background: The resolution of 8K ultra-high-definition imaging technology (7680 × 4320 pixels) is 16-fold higher than the current high-definition technology (1920 × 1080 pixels). 8K/two-dimensional (2D) laparoscopy was clinically available in 2014, but few reports concerning its application have been published. The aim of this study was to evaluate the appropriate methods of usage and problems learned from clinical use of 8K/2D laparoscopy. Subjects and Methods: The patients were 100 colorectal surgery patients who underwent 8K/2D laparoscopy at Asahikawa Medical University Hospital between November 2018 and March 2021. We evaluated the effectiveness, operating conditions, methods and issues of 8K/2D laparoscopy. Results: The median age was 68.5 years. The primary disease was malignancy of the left side of the colon and rectum in 92 patients. The right-sided colectomy was performed in five cases, total proctocolectomy of ulcerative colitis was performed in 3 cases. The proper application of 8K/2D laparoscopy can be achieved by adhering to certain tips, such as darkening the operation room and keeping an appropriate distance from the monitor. Regarding intraoperative complications caused by the 8K/2D laparoscope, skin burns due to heat from the tip of the laparoscope were observed in one patient. There were no cases of complications due to the 8K/2D laparoscopy. Conclusion: 8K/2D laparoscopy can be used safely in colorectal surgery. There are still some tips for proper use, such as keeping an appropriate distance to the monitor and darkening the room. However, 8K/2D laparoscopy can provide delicate images and can be used without any operational problems.

Contrast-enhanced ultrasonography for the diagnosis of spontaneous necrosis of hepatocellular carcinoma: A report of 2 cases.

Spontaneous necrosis of hepatocellular carcinoma (HCC) is rare and difficult to diagnose preoperatively if it occurs before the definitive diagnosis of HCC; this is because spontaneous necrosis of HCC exhibits various patterns in imaging studies. We compared imaging and pathological findings, and examined the possibility of diagnosing spontaneous necrosis of HCC using contrast-enhanced ultrasonography (CEUS). We experienced 2 cases of spontaneous necrosis of HCC. In case 1, spontaneous necrosis occurred after HCC diagnosis, while in case 2 it occurred before the first admission. The tumor in case 2 contained internal nodules and outer fibrous tissue. CEUS revealed a vascular spot in the hypovascular area during the vascular phase and a complete defect during the Kupffer phase. These findings accorded with the pathological findings and may be important for diagnosing spontaneous necrosis of HCC.

Successful Multidisciplinary Treatment with Laparoscopic Hepatectomy and Adjuvant Therapy for Metachronous Solitary Hepatic Metastasis after Excision of a Primary Anorectal Malignant Melanoma: A Case Report.

Anorectal malignant melanoma (ARMM) is extremely rare and generally lethal, irrespective of the treatment administered. The disease is often diagnosed late, metastases being present in approximately two-thirds of patients at the time of initial diagnosis. Solitary metastasis of ARMM to a distant organ is exceedingly rare. A 76-year-old woman with a history of laparoscopic abdominoperineal resection of an ARMM 13 months previously, was found to have a solitary liver metastasis in the follow-up computed tomography. A preoperative work-up showed no other distant metastases nor contraindication to surgery. It was therefore considered that resection was indicated. The metachronous solitary liver metastasis from an ARMM was treated by laparoscopic wedge hepatectomy of the eighth segment 18 months after excision of her primary ARMM. Adjuvant therapy with pembrolizumab was initiated and continued at 6-week intervals. The patient has not exhibited any immune related Adverse Effects (irAE) during or subsequent to treatment with pembrolizmab and has now completed 12 months of adjuvant pembrolizumab therapy, having survived 33 months from the initial operation for primary ARMM, and remaining recurrence-free 14 months after hepatectomy. ARMM is extremely rare and resection of a metachronous solitary metastasis followed by adjuvant therapy has not previously been reported. We hope this case will be useful for clinicians who might treat similar patients.

Lymphoepithelioma-like cholangiocarcinoma not associated with Epstein-Barr virus or hepatitis virus: case report and literature review of 100 reported cases.

Lymphoepithelioma-like cholangiocarcinoma (LEL-CC) is a type of lymphoepithelioma-like carcinoma (LELC) and a rare variant of primary liver tumor. Although it is uncommon and only 100 cases have been reported thus far, the number of reports has increased in recent years. LEL-CC reportedly occurs more frequently in Asian women; Epstein-Barr virus (EBV) and hepatitis viruses are both strongly associated with tumor development. Here, we describe a 76-year-old woman who exhibited LEL-CC not associated with EBV or hepatitis virus. She was referred to our department with a 3.0-cm × 2.8-cm tumor in the left lobe of the liver. Based on computed tomography and magnetic resonance imaging findings, the tumor was preoperatively diagnosed as hepatocellular carcinoma. Thus, we performed extended left hepatectomy with caudal lobectomy. Histopathological examinations revealed columnar tumor cells with atypical nuclei that proliferated in a cord-like or glandular tubular pattern with dense lymphocytic infiltration. Immunohistochemical analysis showed negative HepPar-1 and arginase findings, indicating non-hepatocyte origin; however, the biliary-type cytokeratins CK7 and CK19 were detected. Based on these findings, the tumor was identified as LEL-CC. EBV-encoded RNA in situ hybridization findings were negative; the patient's clinical characteristics were not suggestive of hepatitis virus infection. In conclusion, we suggest that clinicians consider LEL-CC as a differential diagnosis for liver tumors in Asian women, including patients without EBV or hepatitis virus.

Identification of CT Values That Could Be Predictive of Necrosis (N-CTav) in Hepatocellular Carcinoma after Lenvatinib Treatment.

Purpose: To assess the utility of measurement of the computed tomography (CT) attenuation value (CTav) in predicting tumor necrosis in hepatocellular carcinoma (HCC) patients who achieve a complete response (CR), defined using modified Response Evaluation Criteria in Solid Tumors (mRECIST), after lenvatinib treatment. Method: We compared CTav in arterial phase CT images with postoperative histopathology in four patients who underwent HCC resection after lenvatinib treatment, to determine CTav thresholds indicative of histological necrosis (N-CTav). Next, we confirmed the accuracy of the determined N-CTav in 15 cases with histopathologically proven necrosis in surgical specimens. Furthermore, the percentage of the tumor with N-CTav, i.e., the N-CTav occupancy rate, assessed using Image J software in 30 tumors in 12 patients with CR out of 571 HCC patients treated with lenvatinib, and its correlation with local recurrence following CR were examined. Results: Receiver operating characteristic (ROC) curve analysis revealed an optimal cut-off value of CTav of 30.2 HU, with 90.0% specificity and 65.0% sensitivity in discriminating between pathologically identified necrosis and degeneration, with a CTav of less than 30.2 HU indicating necrosis after lenvatinib treatment (N30-CTav). Furthermore, the optimal cut-off value of 30.6% for the N30-CTav occupancy rate by ROC analysis was a significant indicator of local recurrence following CR with 76.9% specificity and sensitivity (area under the ROC curve; 0.939), with the CR group with high N30-CTav occupancy (≥30.6%) after lenvatinib treatment showing significantly lower local recurrence (8.3% at 1 year) compared with the low (<30.6%) N30-CTav group (p < 0.001, 61.5% at 1 year). Conclusion: The cut-off value of 30.2 HU for CTav (N30-CTav) might be appropriate for identifying post-lenvatinib necrosis in HCC, and an N30-CTav occupancy rate of >30.6% might be a predictor of maintenance of CR. Use of these indicators have the potential to impact systemic chemotherapy for HCC.

Beneficial effects of end-ischemic oxygenated machine perfusion preservation for split-liver transplantation in recovering graft function and reducing ischemia-reperfusion injury.

This study examined the efficacy of end-ischemic hypothermic oxygenated machine perfusion preservation (HOPE) using an originally developed machine perfusion system for split-liver transplantation. Porcine split-liver grafts were created via 75% liver resection after 10 min of warm ischemia. In Group 1, grafts were preserved by simple cold storage (CS) for 8 h (CS group; n = 4). In Group 2, grafts were preserved by simple CS for 6 h and end-ischemic HOPE for 2 h (HOPE group; n = 5). All grafts were evaluated using an isolated ex vivo reperfusion model with autologous blood for 2 h. Biochemical markers (aspartate aminotransferase and lactate dehydrogenase levels) were significantly better immediately after reperfusion in the HOPE group than in the CS group. Furthermore, the HOPE group had a better histological score. The levels of inflammatory cytokines (tumor necrosis factor-α, interferon-γ, interleukin-1ß, and interleukin-10) were significantly lower after reperfusion in the HOPE group. Therefore, we concluded that end-ischemic HOPE for split-liver transplantation can aid in recovering the graft function and reducing ischemia-reperfusion injury. HOPE, using our originally developed machine perfusion system, is safe and can improve graft function while attenuating liver injury due to preservation.

Severe liver injury with traumatic cardiac arrest successfully treated by damage control surgery and transcatheter arterial embolization in the hybrid operating room: a case report.

BACKGROUND: The damage control approach is known to reduce the mortality rate in severely injured patients and has now become a common practice. Transcatheter arterial embolization (TAE) has been shown to be useful with combining with damage control laparotomy in identifying and controlling active arterial hemorrhage. Hybrid operating room (OR) allows both damaged control surgery and TAE in the same location in minimal time. We report a case of a patient with three cardiac arrests who was saved by early intervention using damage control surgery (DCS) with interventional radiology (IVR) in the hybrid OR. CASE PRESENTATION: A 46-year-old woman was injured in a collision with a tree while snowboarding. She was eventually transported to hybrid operating room in our hospital with the diagnosis of significant liver laceration and hemorrhagic shock. Damage control surgery was performed with perihepatic packing (PHP) and TAE was conducted to stop active bleeding from right hepatic artery. She experienced 3 times of cardiopulmonary arrest, which was successfully resuscitated on each occasion. Although she had total of 3 times of laparotomy but tolerated well. She was discharged on day 82 of hospitalization and showed no neurological sequelae. CONCLUSION: Saving the life of a patient with severe trauma requires a multidisciplinary approach with cooperation and early information sharing among trauma team members. Sharing treatment strategy with the trauma team and early intervention using DCS with IVR in the hybrid operating room could save the patient's life.

Serum fatty acid-binding protein 5 is a significant factor in hepatocellular carcinoma progression independent of tissue expression level.

Fatty acid-binding protein 5 (FABP5) is highly expressed in hepatocellular carcinoma (HCC) tissues and is related to HCC progression. In this study, we analyzed the potential of serum FABP5 (sFABP5) as a tumor marker in HCC and its clinical significance in HCC progression. We compared the sFABP5 concentration in patients with HCC (HCC group) with that of patients with hepatitis without HCC (hepatitis group). Moreover, we measured the FABP5 expression levels in resected HCC tissues (tFABP5) and analyzed their relationship with sFABP5. We also performed cell-based assays using FABP5 knockout and overexpressing HCC cell lines to analyze the effect of extrinsic FABP5 (exFABP5) on HCC cells. We showed that sFABP5 was not a useful tumor marker for HCC, as HCC and sFABP5 were not correlated. However, sFABP5 and tFABP5 significantly correlated with survival after surgery for HCC, while sFABP5 and tFABP5 were independent of each other. In cell-based assays, exFABP5 was taken up by HCC cell lines and positively affected cell survival under glucose-depleted conditions by complementing the endogenous FABP5 function. In conclusion, sFABP5 had a significant impact on HCC progression irrespective of tFABP5 by augmenting cell viability under glucose-depleted conditions. As tFABP5 and sFABP5 are important factors that are independent of each other in HCC progression, both of them should be considered independently in improving the prognosis of patients with HCC.

Analysis of the correlation between alterations in N­glycans and invasiveness in liver cancer cell lines.

The N­glycoforms of glycoproteins modify protein function and control a number of biological pathways. The aim of the present study was to investigate the correlation between alterations in N­glycans and cancer aggressiveness in terms of cancer cell invasion ability. The expression of urokinase­type plasminogen activator (uPA) and N­acetylglucosaminyltransferase V (GnT­V) in liver cancer cell lines was analyzed by western blotting. Cell invasiveness was analyzed by Matrigel invasion assays. uPA and GnT­V expression in liver cancer cell lines was knocked down by RNA interference. Furthermore, uPA was overexpressed in liver cancer cells using lentiviral vectors, and a mutant strain of HepG2 cells overexpressing uPA deficient in N­glycans was established. A glycoblotting­assisted matrix­assisted laser desorption/ionization­time­of­flight/mass spectrometry­based quantitative analysis of liver cancer cell lines was performed, in which invasiveness was altered by modifying the expression of uPA and GnT­V. N­glycan profiles were found to differ between the highly invasive liver cancer cell line HLE and the less invasive cell line HepG2. The expression of several N­glycans, including a form with m/z=1892, was changed according to invasiveness controlled by knockdown and overexpression of uPA. The invasiveness of HepG2 cells with mutant uPA did not increase regardless of the level of expression of uPA. Following GnT­V knockdown and N­glycan alteration, uPA expression did not change, whereas cell invasiveness decreased. One N­glycan (m/z=1892) was common among N­glycans in the comparative analysis between HLE and HepG2, HLE and uPA knockdown HLE, HepG2 and uPA­overexpressing HepG2, and HLE and GnT­V knockdown HLE cells and among N­glycan profiles in human uPA. Therefore, N­glycosylation is an important factor controlling invasiveness of liver cancer cells, and a specific N­glycan (m/z=1892) associated with the invasion of liver cancer cells via uPA was identified in the present study.

Role of Wnt5a in suppressing invasiveness of hepatocellular carcinoma via epithelial-mesenchymal transition.

Inappropriate activation of the canonical Wnt signaling pathway is associated with progression of hepatocellular carcinoma (HCC). However, the association between the non-canonical pathway activated by Wnt5a and HCC is not well known. The present study investigated the significance of Wnt5a expression in HCC. Immunohistochemical staining of Wnt5a was performed on specimens from 243 patients who underwent hepatic resection for HCC. The present study investigated whether Wnt5a expression was associated with clinical and pathological factors and prognosis. Wnt5a expression in human HCC cell lines was investigated using western blotting. The effects of overexpression or knockdown of Wnt5a were evaluated using proliferation and invasion assays. Changes in epithelial-mesenchymal transition (EMT)-related molecules were investigated using western blotting. Wnt5a negativity was significantly associated with poor tumor differentiation and positive vascular invasion. In univariate analysis, Wnt5a negativity was identified as a significant prognostic factor for overall survival (OS). Multivariate analysis of OS demonstrated that Wnt5a negativity was an independent prognostic factor. Wnt5a expression was lower in HLE and HLF cells than in HepG2 and Huh7 cells. Knockdown of Wnt5a by short hairpin RNA transfection increased the proliferation and invasiveness of Huh7 cells, and decreased the expression levels of E-cadherin. In HLF cells, overexpression of Wnt5a inhibited invasiveness and decreased the expression levels of vimentin. Wnt5a negativity was associated with poor tumor differentiation and positive vascular invasion, and was an independent poor prognostic factor in patients with HCC. Wnt5a may be a tumor suppressor involved in EMT-mediated changes in invasiveness.

Adenomatous polyposis coli-binding protein end-binding 1 promotes hepatocellular carcinoma growth and metastasis.

This study was performed to determine the clinical significance of adenomatous polyposis coli (APC)-binding protein end-binding 1 (EB1) in hepatocellular carcinoma (HCC) and to characterize its biochemical role in comparison with previous reports. We performed immunohistochemical staining to detect EB1 expression in tissues from 235 patients with HCC and investigated its correlations with clinicopathological features and prognosis. We also investigated the roles of EB1 in cell proliferation, migration, and tumorigenesis in vitro and in vivo by siRNA- and CRISPR/Cas9-mediated modulation of EB1 expression in human HCC cell lines. The results showed that EB1 expression was significantly correlated with several important factors associated with tumor malignancy, including histological differentiation, portal vein invasion status, and intrahepatic metastasis. Patients with high EB1 expression in HCC tissue had poorer overall survival and higher recurrence rates than patients with low EB1 expression. EB1 knockdown and knockout in HCC cells reduced cell proliferation, migration, and invasion in vitro and inhibited tumor growth in vivo. Further, genes encoding Dlk1, HAMP, and SLCO1B3 that were differentially expressed in association with EB1 were identified using RNA microarray analysis. In conclusion, elevated expression of EB1 promotes tumor growth and metastasis of HCC. EB1 may serve as a new biomarker for HCC, and genes coexpressed with EB1 may represent potential targets for therapy.

Preoperative chemotherapy in colorectal cancer patients with synchronous liver metastasis.

The response to preoperative chemotherapy is useful for predicting prognosis in unresectable and resectable disease. However, the prognostic benefit of chemotherapy prior to hepatectomy in patients with colorectal carcinoma and resectable or marginally resectable liver metastases remains unclear. The present study investigated the effect of preoperative chemotherapy on the prognosis of patients with colorectal cancer and resectable or marginally resectable synchronous liver metastasis. A total of 106 patients were retrospectively reviewed, who underwent hepatectomy for colorectal metastasis. The prognosis of 64 patients who received neoadjuvant chemotherapy (NAC) were compared with the 42 patients who did not (non-NAC). Furthermore, a total of 43 patients who responded to chemotherapy were compared with the 21 who did not. Preoperative chemotherapy was administered for 5.7 months, wherein 50 patients (78%) received a single regimen, and 54 (84%) received oxaliplatin. There were more patients with <3 metastases and maximum diameters <5 cm in the non-NAC group. The median survival time was 86.0 and 71.6 months in the NAC and non-NAC groups, respectively (P=0.33). Subgroup analysis on the basis of tumor size and number showed no prognostic differences between the two groups. The median survival time was longer in responders than in non-responders (85 vs. 56 months; P=0.01). However, the median relapse-free survival was equivalent in both groups (16.4 and 10.7 months). Preoperative chemotherapy did not prolong survival. Furthermore, it did not prevent recurrence, even in clinical responders. Therefore, it should not be routinely offered to patients with resectable liver metastasis before their hepatectomy.

Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real-world setting.

BACKGROUND AND AIM: Lenvatinib has been recently approved as a first-line systematic therapy for patients with advanced hepatocellular carcinoma (HCC) based on the results of the phase 3 clinical trial REFLECT. This trial excluded patients with a history of systemic chemotherapy, bile duct invasion, and Child-Pugh grade B. We aimed to investigate the efficacy and safety of lenvatinib for these patients and in the real-world setting. METHODS: Among patients who were administered lenvatinib for advanced HCC between April and October 2018 in Hokkaido University Hospital and related hospitals, we evaluated those who were followed for more than 2 months and whose treatment response was evaluated via dynamic computed tomography at baseline and 2 months after treatment initiation. Meanwhile, patients were excluded if they had decompensated liver cirrhosis, were followed up less than 2 months, or were not evaluated at 2 months. Patients were also stratified according to compliance with the REFLECT inclusion criteria for further analysis. RESULTS: A total of 41 patients were included; more than 50% did not meet the REFLECT inclusion criteria. In total, 5 (12.2%), 20 (48.8%), 12 (29.3%), and 4 (9.3%) showed complete response, partial response, stable disease, and progressive disease, respectively. The objective response rate was 61.2%. The objective response rate and disease control rate were similar between patients who did and did not meet the REFLECT inclusion criteria. Moreover, the safety profile was also similar between the two patient groups. CONCLUSION: Lenvatinib showed high early response rate and tolerability in patients with advanced HCC. Favorable outcomes were similarly observed in patients who did not meet the REFLECT inclusion criteria.

Successful hepatic resection for recurrent hepatocellular carcinoma after lenvatinib treatment: A case report.

BACKGROUND: Lenvatinib has been shown to be noninferior to sorafenib regarding prognosis and recurrence rate in patients with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic chemotherapy. In patients treated with lenvatinib, 40% of cases achieved sufficient tumor reduction to make potential surgery possible. However, the outcomes of such surgery are unknown. We report a successful case of hepatic resection for recurrent HCC after lenvatinib treatment. CASE SUMMARY: A 69-year-old man underwent right anterior sectionectomy for HCC in segment 8 of the liver. Ten months later, he was found to have an intrahepatic HCC recurrence that grew rapidly to 10 cm in diameter with sternal bone metastases. After confirming partial response to lenvatinib administration for 2 mo, a second hepatectomy was performed. Pathological examination showed that 80% of the tumor was necrotic. The patient did not develop any adverse effects under lenvatinib treatment. He was discharged at 25 d after surgery. Radiation therapy for bone metastases continued to be given under lenvatinib, and the patient has remained alive for 1 year after the second hepatectomy. CONCLUSION: The prognosis of patients with recurrent HCC may be improved by liver resection combined with prior lenvatinib therapy.