Correlation of pathological examination with indocyanine green (ICG) intensity gradients: a prospective study in patients with liver tumor.

BACKGROUND: Intraoperative indocyanine green (ICG) fluorescence imaging has been shown to be a new and innovative way to illustrate the optimal resection margin in hepatectomy for hepatocellular carcinoma. This study investigated its accuracy in resection margin determination by looking into the correlation of ICG intensity gradients with pathological examination results of resected specimens. METHODS: This was a prospective, single-center, non-randomized controlled study. Patients who had liver tumors indicating liver resection were recruited. The hypothesis was that the use of intraoperative near-infrared/ICG fluorescence imaging would be a promising guiding tool for removing hepatocellular carcinoma with a better resection margin. Patients were given ICG (0.25 mg/kg) 1 day before operation. Resected specimens were inspected under a fluorescent imaging system. Biopsies were taken from tumors and normal tissue. Color signals obtained from ICG fluorescence imaging were compared with biopsies for analysis. RESULTS: Twenty-two patients were recruited for study. The median size of their tumors was 2.25 cm. One patient had resection margin involvement. Under ICG fluorescence, the tumors typically lighted up as yellow color, wrapped by a zone of green color. Tumors of 17 patients (77.3%) displayed yellow color and were confirmed malignancy, while tumors of 12 patients (54.5%) displayed green color and were confirmed malignancy. Receiver operating characteristic curve was used to measure the sensitivity and specificity of the green color to look for a clear resection margin. The area under the curve was 85.3% (p = 0.019, 95% confidence interval 0.696-1.000), with a sensitivity of 0.706 and specificity of 1.000. CONCLUSION: The use of ICG fluorescence can be helpful in determining resection margins. Resection of tumor should include complete resection of the green zone shown in the fluorescence image.

Stage-by-stage analysis of the effect of blood transfusion on survival after curative hepatectomy for hepatocellular carcinoma-a retrospective study.

OBJECTIVE: This study is to examine the impact of perioperative (intraoperative/postoperative) blood transfusion on the outcomes of curative hepatectomy for hepatocellular carcinoma. Hepatectomy is a well-established curative treatment for hepatocellular carcinoma, and blood transfusion cannot always be avoided in treating the disease. METHODS: A retrospective study of patients having curative hepatectomy for hepatocellular carcinoma from January 2010 to December 2019 at a single center was conducted. The patients were stratified by their disease stage. Patients with and without perioperative blood transfusion were matched by propensity-score matching and compared for each disease stage. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival for each stage. RESULTS: A total of 846 patients were studied. Among them, 125 received perioperative blood transfusion and 720 did not. Patients with blood transfusion had worse disease-free and overall survival. After stratification and matching, the ratios of transfusion to non-transfusion were 33:165 (stage 1), 28:140 (stage 2), and 45:90 (stage 3). Perioperative blood transfusion was associated with a higher incidence of postoperative complications in all three disease stages (p = 0.004/0.006/0.017), and hence longer hospitalization (p < 0.001 in all stages), but had no significant impact on hospital mortality (p = 0.119/0.118/0.723), 90-day mortality (p = 0.259/0.118/0.723), disease-free survival (p = 0.128/0.826/0.511), or overall survival (p = 0.869/0.122/0.122) in any disease stage. Prognostic factors for overall survival included tumor size, tumor number, alpha-fetoprotein level, and postoperative complication of grade ≥ 3A. CONCLUSION: Perioperative blood transfusion was associated with a higher incidence of complications but had no significant impact on survival after curative hepatectomy for hepatocellular carcinoma.

Indications of pro-inflammatory cytokines in laparoscopic and open liver resection for early-stage hepatocellular carcinoma.

BACKGROUND: Our clinical practice of laparoscopic liver resection (LLR) had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma (HCC) over open liver resection (OLR), but the underlying mechanisms are not clear. This study was to find out whether systemic inflammation plays an important role. METHODS: A total of 103 patients with early-stage HCC under liver resection were enrolled (LLR group, n = 53; OLR group, n = 50). The expression of 9 inflammatory cytokines in patients at preoperation, postoperative day 1 (POD1) and POD7 was quantified by Luminex Multiplex assay. The relationships of the cytokines and the postoperative outcomes were compared between LLR and OLR. RESULTS: Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative levels. Compared to OLR, the POD1 levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1) in the LLR group were significantly lower. Higher POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during operation. The levels of these cytokines were positively associated with postoperative liver injury, and the length of hospital stay. Importantly, a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver resection. CONCLUSIONS: Significantly lower level of GM-CSF, IL-6, IL-8, and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.

Impact of Three-Dimensional (3D) Visualization on Laparoscopic Hepatectomy for Hepatocellular Carcinoma.

BACKGROUND: The impact of three-dimensional (3D) visualization on laparoscopic hepatectomy for hepatocellular carcinoma is largely unknown. METHODS: A retrospective review with propensity-score matched analysis of 3D and two-dimensional (2D) laparoscopic hepatectomy performed in a tertiary hepatobiliary surgery center. RESULTS: Since the availability of 3D laparoscopy, the proportion of laparoscopic major hepatectomies has significantly expanded (1.7% vs. 24.0%, p < 0.0001) and the percentage of difficult resections among patients who underwent laparoscopic hepatectomy has also increased (12.6% vs. 40.0%, p = 0.0001). A total of 305 patients (92 in the 3D group and 213 in the 2D group) underwent laparoscopic hepatectomy between 2002 and 2019. The 3D group had better liver function, larger tumors at more difficult locations, more major resections, and more difficult surgeries. After propensity score matching, 144 patients were analyzed (72 in both the 3D and 2D groups). Patients were comparable in terms of liver status, tumor status, and complexity of liver surgery. Operative time (218 vs. 218 mins, p = 0.50) and blood loss (0.2 vs. 0.2L, p = 0.49) were comparable between the two groups, however overall complications were higher in the 2D group (1.4 vs. 11.1%, p = 0.03). Patients who underwent 3D laparoscopic major hepatectomy had a shorter hospital stay than their comparable counterparts operated through an open approach (7 vs. 6 days, p = 0.003). CONCLUSIONS: 3D visualization enhanced the feasibility of laparoscopic major hepatectomy and difficult laparoscopic liver resection. 3D resection was potentially associated with fewer operative morbidities and the 3D laparoscopic approach did not jeopardize the outcome of major hepatectomy.

Evaluation of Pancreatic Lesions With Endoscopic Ultrasound and Fine Needle Aspiration.

Background. Endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) are commonly used for assessing pancreatic lesions. This study aimed to evaluate the diagnostic yield and accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in a single tertiary institution. Methods. Consecutive patients who underwent EUS-FNA of the pancreas at Queen Mary Hospital, Hong Kong, from January 2015 to March 2016 were retrospectively reviewed. Endoscopic findings and FNA results were analysed. For patients who subsequently underwent surgical resection of pancreatic lesion, EUS-FNA diagnoses were compared to histopathological findings of surgical specimens to determine its diagnostic accuracy. Results. One hundred twelve EUS-FNA were performed in 99 patients within the study time period and were included for analysis. Sixty-six (66.7%) pancreatic lesions were solid in nature and 33 (33.3%) were cystic. The overall diagnostic yield of EUS-FNA was 70.5% (n = 79). On multivariate analysis, more passes of needle were associated with a higher diagnostic yield (odds ratio = 2.000, P = .049). 57.1% (n = 64) of EUS-FNA results had an impact on management. Sixteen patients with diagnostic EUS-FNA subsequently underwent surgery for resection of the pancreatic lesion. Upon correlation to the histopathological findings of surgical specimens, there were 12 true-positive, 2 true-negative, 0 false-positive, and 2 false-negative cases. Sensitivity was 85.7%, specificity was 100%, positive predictive value was 100%, and negative predictive value was 50%. The diagnostic accuracy of EUS-FNA was 87.5%. Conclusion. EUS-FNA is accurate and reliable for diagnosing pancreatic lesions.

Prognostic value of preoperative alpha-fetoprotein (AFP) level in patients receiving curative hepatectomy- an analysis of 1,182 patients in Hong Kong.

BACKGROUND: The value of alpha-fetoprotein (AFP) as a prognostic indicator in patients with hepatocellular carcinoma (HCC) has been proposed in recent studies, but the evidence so far is still contradictory. This analysis aims to evaluate the prognostic value of preoperative AFP level in patients undergoing curative resection. METHODS: This retrospective study reviewed the prospectively collected data of all patients who underwent initial liver resection for HCC at Queen Mary Hospital during the period from March 1999 to March 2013. Patients with palliative resection, positive margin after pathological examination or distant metastasis were excluded from the study. Survival of patients with AFP level of <20, 20-400 and >400 ng/mL were compared with Kaplan-Meier analysis. Subgroup analysis was performed according to tumour stage (7th edition UICC staging) and tumour size. The optimal cutoff value was determined by area under receiver operating characteristic curve. RESULTS: A total of 1,182 patients were included. Best overall (OS) and disease free survival (DFS) was observed in patients with AFP level <20 ng/mL. Progressively worse outcomes were seen for patients with increasing level of AFP. The median OS were 132.9, 77.2 and 38.4 months for patients with AFP <20, 20-400 and >400 ng/mL respectively (P<0.001). The median DFS for these three groups were 55.6, 25 and 8.4 months respectively (P<0.001). There was significant difference in both OS and DFS among all 3 groups. With subgroup analysis according to tumour stage (stage I and II versus stage III and IV) and tumour size (5 cm or less versus larger than 5 cm), such difference was still observed and remained statistically significant. Optimal cutoff value by discriminant analysis was 12,918.3 ng/mL for OS and 9,733.3 ng/mL for DFS. CONCLUSIONS: This study demonstrates that AFP is a significant prognostic indicator in HCC. Despite tumour stage and size, high level of AFP is associated with poorer OS and DFS. Whether the level of AFP should be included in current staging systems, or treatment protocols, is yet to be determined.

Left hepatectomy in a patient with a Fontan circulation.

Patients with a Fontan circulation face the long term risk of cardiac cirrhosis and the subsequent development of hepatocellular carcinoma (HCC). A hepatectomy operation imposes significant risk on such patients as the Fontan circulation can be severely compromised. Here we present a 24-year-old woman post-Fontan operation who successfully underwent a left hepatectomy, and discuss the anaesthetic and surgical management.

Blocking CDK1/PDK1/ß-Catenin signaling by CDK1 inhibitor RO3306 increased the efficacy of sorafenib treatment by targeting cancer stem cells in a preclinical model of hepatocellular carcinoma.

Rationale: Hepatocellular carcinoma (HCC) is an aggressive malignant solid tumor wherein CDK1/PDK1/ß-Catenin is activated, suggesting that inhibition of this pathway may have therapeutic potential. Methods: CDK1 overexpression and clinicopathological parameters were analyzed. HCC patient-derived xenograft (PDX) tumor models were treated with RO3306 (4 mg/kg) or sorafenib (30 mg/kg), alone or in combination. The relevant signaling of CDK1/PDK1/ß-Catenin was measured by western blot. Silencing of CDK1 with shRNA and corresponding inhibitors was performed for mechanism and functional studies. Results: We found that CDK1 was frequently augmented in up to 46% (18/39) of HCC tissues, which was significantly associated with poor overall survival (p=0.008). CDK1 inhibitor RO3306 in combination with sorafenib treatment significantly decreased tumor growth in PDX tumor models. Furthermore, the combinatorial treatment could overcome sorafenib resistance in the HCC case #10 PDX model. Western blot results demonstrated the combined administration resulted in synergistic down-regulation of CDK1, PDK1 and ß-Catenin as well as concurrent decreases of pluripotency proteins Oct4, Sox2 and Nanog. Decreased CDK1/PDK1/ß-Catenin was associated with suppression of epithelial mesenchymal transition (EMT). In addition, a low dose of RO3306 and sorafenib combination could inhibit 97H CSC growth via decreasing the S phase and promoting cells to enter into a Sub-G1 phase. Mechanistic and functional studies silencing CDK1 with shRNA and RO3306 combined with sorafenib abolished oncogenic function via downregulating CDK1, with downstream PDK1 and ß-Catenin inactivation. Conclusion: Anti-CDK1 treatment can boost sorafenib antitumor responses in PDX tumor models, providing a rational combined treatment to increase sorafenib efficacy in the clinic.

Pure laparoscopic hepatectomy with augmented reality-assisted indocyanine green fluorescence versus open hepatectomy for hepatocellular carcinoma with liver cirrhosis: A propensity analysis at a single center.

INTRODUCTION: Laparoscopic hepatectomy is considered an acceptable treatment of choice in selected patients with primary hepatocellular carcinoma (HCC). Whether indocyanine green (ICG) immunofluorescence, a new technology, may improve surgery outcomes has yet to be tested. The aim of the present study was to investigate and compare the effect of ICG fluorescence imaging on the outcomes of pure laparoscopic hepatectomy and open hepatectomy for primary HCC with background cirrhosis. METHODS: From January 2015 to June 2016, 20 patients with HCC and liver cirrhosis underwent laparoscopic hepatectomy with ICG immunofluorescence. The outcomes of pure laparoscopic hepatectomy with ICG immunofluorescence were compared with those of open hepatectomy. To avoid selection bias, patients were propensity score matched in a ratio of 1 : 6, with 20 patients in the laparoscopic group and 120 in the open group. RESULTS: The laparoscopic group had 20 patients, and the open group had 120 patients. The laparoscopic group had less blood loss (125 vs 450 mL, P < 0.001), a shorter operation time (200 vs 250 min, P = 0.003), and a shorter hospital stay (5 vs 6 days, P < 0.001). The complication rate was 0% in the laparoscopic group compared to 15.0% in the open group (P = 0.135). All patients in the laparoscopic group had negative margin involvement. Four patients (3.3%) in the open resection group had positive margin involvement. Two patients in the ICG immunofluorescence group had additional lesions identified and resected during operation. CONCLUSION: Pure laparoscopic hepatectomy with ICG immunofluorescence for primary HCC can be carried out safely with favorable short-term outcomes even in cirrhotic patients. Better identification of the bile duct structure and better assessment of the tumor resection margin and perfusion are advantages of this new technique.

Update on yttrium-90-based radio-embolization for treatment of hepatocellular carcinoma.

BACKGROUND: Catheter-based intra-arterial therapies provided effective tumour control for unresectable hepatocellular carcinoma without distant metastasis. There was a renewed interest in the advancement of yttrium-90 radio-embolization. METHOD: An extensive search on the MEDLINE databases identified seven case series and two comparative studies regarding yttrium-90 radio-embolization. RESULTS: Case series on yttrium-90 radio-embolization indicated a tumour response rate that ranged from 20% to 70%, and median survival that ranged from 7.7 to 26.6 months. Two comparative studies did not demonstrate significant difference in terms of tumour response rate and survival. One of these comparative studies demonstrated a statistically significant reduction in treatment-related neutropaenia. CONCLUSION: The current use of yttrium-90 radio-embolization was mainly based on small case series. Yttrium-90 radio-embolization seemed equivalent to conventional chemo-embolization in terms of tumour response rate and survival benefit. Emerging evidence suggested that yttrium-90 radio-embolization may have a more favourable side effects profile, in particular in reducing the chance of neutropaenia. Cost and logistics arrangement were two important considerations in generalizing the application of yttrium-90 radio-embolization.