Comparison of post-hepatectomy long-term survival outcome between non-colorectal non-neuroendocrine and colorectal liver metastases: A population-based propensity-score matching analysis.

BACKGROUND: Hepatectomy is an established treatment for colorectal liver metastasis (CLM) or neuroendocrine liver metastasis. However, its role in non-colorectal non-neuroendocrine liver metastasis (NCNNLM) is controversial. This study aims to compare long-term survival outcomes after hepatectomy between NCNNLM and CLM in a population-based cohort. METHODS: From 2009 to 2018, curative hepatectomy were performed in 964 patients with NCNNLM (n â€‹= â€‹133) or CLM (n â€‹= â€‹831). Propensity score (PS) matching was performed. Short-term and long-term outcomes were compared between PS-matched groups. Univariate and multivariate analyses were performed to identify prognostic factors affecting survival. RESULTS: There were 133 patients in the NCNNLM group and 266 patients in the CLM group. The mortality (1.5 â€‹% vs 1.5 â€‹%) and morbidity (19.5 â€‹% vs 20.3 â€‹%) rates were comparable between the two groups. There was no statistically significant difference in 5-year overall (48.9 â€‹% vs 39.8 â€‹%) and recurrence-free (25.1 â€‹% vs 23.4 â€‹%) survival rates between NCNNLM and CLM groups. A high pre-operative serum bilirubin level, severe postoperative complications and multiple tumors were independent prognostic factors for poor survival. CONCLUSION: Hepatectomy for selected patients with NCNNLM can achieve similar long-term oncological outcomes as those with CLM. High serum bilirubin, severe postoperative complication and multiple tumors are poor prognostic factors for survival.

Survival benefit of radioembolization for inoperable hepatocellular carcinoma using yttrium-90 microspheres.

BACKGROUND AND AIM: Transarterial radioembolization with yttrium-90 microspheres is one treatment option for inoperable hepatocellular carcinoma. We compared the survival in a cohort of patients receiving radioembolization or no radioembolization. METHODS: The data of 46 patients referred for radioembolization was retrospectively reviewed. The patient, tumor characteristics, and the survival were compared in the two groups. The independent predictors for survival were studied with multivariate analysis. The side-effects and the complication of radioembolization-induced liver disease was recorded. RESULTS: Thirty patients received radioembolization; 16 patients did not. The two groups did not differ in the mean age, Child-Pugh classes, Barcelona Clinic of Liver Cancer (BCLC) stages, tumor types, sum of diameter of the two biggest tumors, and extent of portal vein invasion. Those with BCLC stage C tumor, with portal vein thrombus, or with less than three nodules had significantly longer survival after radioembolization. There was a trend of longer survival in patients with Child-Pugh A liver function, or with BCLC stage B tumor after radioembolization. The median survival was more than 31.9 months, 14.5 months, and 5.2 months in patients with BCLC stage A, B, and C tumors. The independent predictors for longer survival were Child-Pugh class, tumor diameter sum, BCLC stage, and receiving radioembolization. Grade 2 irradiation-induced gastritis occurred in three patients (10%). Radioembolization-induced liver disease occurred in four patients (13%). CONCLUSIONS: Radioembolization may prolong survival for patients with inoperable hepatocellular carcinoma. Radioembolization-induced liver disease occurred and should be further studied.

Dual-tracer PET/CT in the management of hepatocellular carcinoma.

Background & Aims: Combined 18F-fluorodeoxyglucose (FDG) and 11C-acetate (dual-tracer) positron-emission tomography/computed tomography (PET/CT) is being increasingly performed for the management of hepatocellular carcinoma (HCC), although its role is not well defined. Therefore, we evaluated its effectiveness in (i) staging, (ii) characterization of indeterminate lesions on conventional imaging, and (iii) detection of HCC in patients with unexplained elevations in serum alpha-fetoprotein (AFP) levels. Methods: We retrospectively assessed 525 consecutive patients from three tertiary centers between 2014 and 2020. For staging, we recorded new lesion detection rates, changes in the Barcelona Clinic Liver Cancer (BCLC) classification, and treatment allocation due to dual-tracer PET/CT. To characterize indeterminate lesions and unexplained elevation of serum AFP levels, the sensitivity and specificity of dual-tracer PET/CT in diagnosing HCC were evaluated. A multidisciplinary external review and a cost-benefit analysis of patients for metastatic screening were also performed. Results: Dual-tracer PET/CT identified new lesions in 14.3% of 273 staging patients, resulting in BCLC upstaging in 11.7% and treatment modifications in 7.7%. It upstaged 8.1% of 260 patients undergoing metastatic screening, with estimated savings of US$495 per patient. It had a sensitivity and specificity of 80.7% (95% CI 71.2-88.6%) and 94.8% (95% CI 90.4-98.6%), respectively, for diagnosing HCC in 201 indeterminate lesions. It detected HCC in 45.1% of 51 patients with unexplained elevations in serum AFP concentrations. External review revealed substantial agreement between local and external image interpretation and patient assessment (n = 273, κ = 0.822; 95% CI 0.803-0.864). Conclusions: Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP. Impact and implications: Compared to CT or MRI, dual-tracer positron-emission tomography/computed tomography (PET/CT) led to upstaging in 12% of patients with hepatocellular carcinoma (HCC) undergoing staging, resulting in treatment modification in 8% of cases and a cost saving of US$495 per patient. It also accurately detected HCC in high-risk cases where CT or MRI were equivocal or normal. Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.

Reciprocal interactions between malignant cells and macrophages enhance cancer stemness and M2 polarization in HBV-associated hepatocellular carcinoma.

Background: The tumor microenvironment of cancers has emerged as a crucial component in regulating cancer stemness and plays a pivotal role in cell-cell communication. However, the specific mechanisms underlying these phenomena remain poorly understood. Methods: We performed the single-cell RNA sequencing (scRNA-seq) on nine HBV-associated hepatocellular carcinoma (HCC) patients. The heterogeneity of the malignant cells in pathway functions, transcription factors (TFs) regulation, overall survival, stemness, as well as ligand-receptor-based intercellular communication with macrophages were characterized. The aggressive and stemness feature for the target tumor subclone was validated by the conduction of in vitro assays including sphere formation, proliferation, Annexin V apoptosis, flow cytometry, siRNA library screening assays, and multiple in vivo preclinical mouse models including mouse hepatoma cell and human HCC cell xenograft models with subcutaneous or orthotopic injection. Results: Our analysis yielded a comprehensive atlas of 31,664 cells, revealing a diverse array of malignant cell subpopulations. Notably, we identified a stemness-related subclone of HCC cells with concurrent upregulation of CD24, CD47, and ICAM1 expression that correlated with poorer overall survival. Functional characterization both in vitro and in vivo validated S100A11 as one of the top downstream mediators for tumor initiation and stemness maintenance of this subclone. Further investigation of cell-cell communication within the tumor microenvironment revealed a propensity for bi-directional crosstalk between this stemness-related subclone and tumor-associated macrophages (TAMs). Co-culture study showed that this interaction resulted in the maintenance of the expression of cancer stem cell markers and driving M2-like TAM polarization towards a pro-tumorigenic niche. We also consolidated an inverse relationship between the proportions of TAMs and tumor-infiltrating T cells. Conclusions: Our study highlighted the critical role of stemness-related cancer cell populations in driving an immunosuppressive tumor microenvironment and identified the S100A11 gene as a key mediator for stemness maintenance in HCC. Moreover, our study provides support that the maintenance of cancer stemness is more attributed to M2 polarization than the recruitment of the TAMs.

Expanding scope of Kirkpatrick model from training effectiveness review to evidence-informed prioritization management for cricothyroidotomy simulation.

Modified Kirkpatrick model has been adopted to evaluate training effectiveness by 6 categories, including activity accounting (training objectives/success in organization change) at Level-0, reaction (satisfaction) at Level-1, learning (acquisition of surgical airway skills) at Level-2, behavior (post-training change in personal strengths) at Level-3, result (organizational or clinical outcomes) at Level-4, and Return on Investment (ROI) or Expectation (ROE) (monetary and societal values following training and other quality and safety related measures) at Level-5. The purpose of this hospital-based prospective observational study was twofold: i) To evaluate potential impacts on monetary and societal values and successful organization change following implementation of advanced Cricothyroidotomy simulator and standardized curriculum in healthcare simulation training, ii) To inform decisions of resource allocation by reviewing overall values and prioritization strategies for i) general surgeon/emergency physician ii) with seniority >5 years and iii) prior porcine training experience based on findings at Kirkpatrick Level-0, Level-4, and Level-5. Seventy doctors and 10 nurses completed Cricothyroidotomy training and follow-up questionnaires within 2021/22. All training usability scoring measured by Scales of Emergency Surgical Airway Simulator (SESAS-17) achieved over 4 out of 5 (Level-4) with effects in favor of emergency physicians or general surgeons (p < .5), regardless of seniority and prior training experience. Success in organization change (Level-0) and cost-effectiveness (Level-5) were hypothetically established using theoretical framework of Gleicher's formula and Roger's Diffusion of Innovation Theory. Overall training effectiveness, in terms of advantage in usability, cost-benefits and successful organizational changes, provided sound evidence to support continuous investment of new curriculum and innovative simulator and "Surgeon-and-emergency-physician-first" policy when it comes to resources allocation strategies for Cricothyroidotomy training. [ACGME competencies: Practice Based Learning and Improvement, Systems Based Practice.].

The Hong Kong consensus statements on unresectable hepatocellular carcinoma: narrative review and update for 2021.

Background and Objective: Hong Kong, like many parts of Asia, faces a high burden of hepatocellular carcinoma (HCC) caused by high endemic rates of hepatitis B virus infection. Hong Kong clinicians have developed a high level of expertise in HCC treatment across surgical, transarterial, ablative, radiotherapeutic and systemic modalities. This publication summarizes the latest evidence-based recommendations on how these modalities should be used. Methods: In two meetings held in 2020, a multidisciplinary panel of surgeons, oncologists and interventional radiologists performed a narrative review of evidence on the management of HCC, with an emphasis on treatment of HCC not amenable to surgical resection. Close attention was paid to new evidence published since the previous version of these statements in 2018. Key Content and Findings: The expert panel has formulated 60 consensus statements to guide the staging and treatment of unresectable HCC. Since the previous version of these statements, considerable additions have been made to the recommendations on use of targeted therapies and immunotherapies because of the large volume of new evidence. Conclusions: Our consensus statements offer guidance on how to select HCC patients for surgical or non-surgical treatment and for choosing among non-surgical modalities for patients who are not candidates for resection. In particular, there is a need for more evidence to aid physicians in the selection of second-line systemic therapies, as currently most data are limited to patients with disease progression on first-line sorafenib.

Harnessing power of simulation training effectiveness with Kirkpatrick model in emergency surgical airway procedures.

Objectives: Training effectiveness indicates how good a program has met pre-set training objectives or organizational goals for the best benefit of healthcare professionals and service users in the community. The study aimed to evaluate training effectiveness following implementation of new training curriculum of emergency surgical airway procedures (Cricothyroidotomy) organized by the Queen Elizabeth Hospital. Design: This training evaluation relied on observational descriptive study design. Timed task on Cricothyroidotomy procedures and standardized post-training questionnaire were applied to assess the first 3 levels of Kirkpatrick's model: (Level-1) Reaction by training satisfaction; (Level-2) Learning by acquisition of knowledge and skills assessment passing rate; (Level-3) Behavior by personal strengths. Setting: This program was operated in the Multi-Disciplinary Simulation and Skills Centre, a hospital-based high-fidelity simulation training center accredited by the Society for Simulation in Healthcare. Participants: The study recruited 80 trauma service providers, including 35 general surgeons, 15 emergency physicians, 10 anesthesiologists or intensivists, 6 neurosurgeons, 4 orthopedic surgeons, and 10 emergency nurses from five trauma centers under the Hospital Authority. All underwent the Advanced Trauma Life Support training in advance. Results: Compared with reference score from previous training sessions, the result of program using new training curriculum and simulator demonstrated significant training satisfaction of participants (Level-1), and high level of assertiveness, mental preparedness, self-efficacy, and internal locus of control and responsibility (p < .01, for all in Level-3). All participants (N = 80) completed entire Cricothyroidotomy procedure in 2 min without technical errors (Assessment passing rate = 100%) (Level-2). Conclusions: Under Kirkpatrick model, simulation training in Cricothyroidotomy procedure using new curriculum and simulators has been proven to be useful for healthcare professionals involved in trauma service management. The result suggests that application of a state-of-the-art training tools to advanced surgical skills training could improve training satisfaction, knowledge and skills acquisition, and personal strengths transferable to clinical practice. ACGME competencies: Practice Based Learning and Improvement.

Single-cell RNA sequencing shows the immunosuppressive landscape and tumor heterogeneity of HBV-associated hepatocellular carcinoma.

Interaction between tumor cells and immune cells in the tumor microenvironment is important in cancer development. Immune cells interact with the tumor cells to shape this process. Here, we use single-cell RNA sequencing analysis to delineate the immune landscape and tumor heterogeneity in a cohort of patients with HBV-associated human hepatocellular carcinoma (HCC). We found that tumor-associated macrophages suppress tumor T cell infiltration and TIGIT-NECTIN2 interaction regulates the immunosuppressive environment. The cell state transition of immune cells towards a more immunosuppressive and exhaustive status exemplifies the overall cancer-promoting immunocellular landscape. Furthermore, the heterogeneity of global molecular profiles reveals co-existence of intra-tumoral and inter-tumoral heterogeneity, but is more apparent in the latter. This analysis of the immunosuppressive landscape and intercellular interactions provides mechanistic information for the design of efficacious immune-oncology treatments in hepatocellular carcinoma.

Investigating effects of healthcare simulation on personal strengths and organizational impacts for healthcare workers during COVID-19 pandemic: A cross-sectional study.

INTRODUCTION: This cross-sectional study aimed at evaluating impacts of healthcare simulation training, either in-situ or lab-based, on personal strengths of healthcare workers (HCWs) and organizational outcomes during the COVID-19 pandemic. METHODS: COVID-19 Taskforce was established to formulate standardized scenario-based simulation training materials in late-January 2020. Post-training questionnaires made up of 5-point Likert scales were distributed to all participants to evaluate their personal strengths, in terms of i) assertiveness, ii) mental preparedness, iii) self-efficacy, iv) internal locus of control, and v) internal locus of responsibility. Independent sample t-tests were used to analyze between-group difference in "In-situ" and "Lab-based" group; and one-sample t-tests were used to compare change in personal strengths with reference point of 3 (Neutral). Kirkpatrick's Model served as the analytical framework for overall training effects. RESULTS: Between 05 February and 18 March 2020, 101 sessions of simulation training were conducted in "In-Situ" at either Accident & Emergency Department (20, 20%) or Intensive Care Unit (15, 14%) and "Lab-based" for Isolation (30, 30%) and General Wards (36, 36%). 1,415 hospital staff members, including 1,167 nurses (82%), 163 doctors (12%) and 85 patient care assistants (6%), were trained. All domains of personal strengths were scored 4.24 or above and statistically significantly increased when comparing with reference population (p < .001). However, no significant differences between in-situ and lab-based simulation were found (p > .05), for all domains of personal strengths. CONCLUSION: Healthcare simulation training enhanced healthcare workers' personal strengths critical to operational and clinical outcomes during the COVID-19 pandemic.

Hong Kong Consensus Statements for the Management of Unresectable Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is highly prevalent in Hong Kong due to the high prevalence of chronic hepatitis B infection. Liver cancer is the fourth most common cancer and the third most common cause of cancer death. Due to the high case load, there is a high level of local expertise in treating HCC, and the full spectrum of treatment modalities is available. This document summarizes how these modalities should be used based on the latest evidence. SUMMARY: In 2 meetings held in early 2017, a multidisciplinary group of Hong Kong clinicians, including liver surgeons, interventional radiologists, clinical oncologists, and medical oncologists, met to update local consensus statements for management of HCC. These statements are based on the latest evidence and give detailed guidance on how to deploy these modalities, in particular for cases of HCC which are not suited to surgical resection. KEY MESSAGES: These statements give detailed information on how to decide if a patient is a candidate for resection, methods to improve candidacy for resection, and guidance for use of various nonsurgical interventions to manage patients ineligible for resection.

Associating liver partition and portal vein ligation for a patient with hepatocellular carcinoma with a background of hepatitis B related fibrotic liver.

INTRODUCTION: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has recently been developed for patients with predicted insufficient future liver remnant volumes to induce more rapid hepatic hypertrophy and increase resectability. In the medical literature, the use of ALPPS in hepatocellular carcinoma (HCC) has rarely been reported. PRESENTATION OF CASE: We reported the use of ALPPS in a patient with primarily unresectable HCC arising from a background of hepatitis B related liver fibrosis. Preoperative computed tomography (CT) showed 2 large conglomerated tumors measuring 16cm×10.5cm in liver segments 5, 6, 7 and 8, and at least 3 satellite nodules with the largest one measuring 3cm around the main tumor and another 4cm tumor in segment 4. Right trisectionectomy after ALPPS was successfully performed. He was discharged from hospital on postoperative day 13 after the second operation. Follow-up CT scan at 6 weeks after the second operation showed further hypertrophy of the liver remnant and no liver recurrence. DISCUSSION: Our case showed that this novel strategy is feasible even in the context of a background of chronic hepatitis B related liver fibrosis, although the hypertrophy rate was a little bit slower and the time needed was longer. CONCLUSION: ALPPS is also feasible in liver fibrosis. It gives hope to patients with HCC who previously were considered as having unresectable diseases. More studies are needed to further evaluate the effectiveness and oncological outcomes of ALPPS from these patients.

Randomized controlled trial to compare the dose of adjuvant chemotherapy after curative resection of hepatocellular carcinoma.

BACKGROUND AND AIM: Adjuvant locoregional chemotherapy has been shown to be useful to prevent recurrence after curative resection of hepatocellular carcinoma (HCC) in some retrospective studies. Our aim was to compare the dose effect in the prevention of tumor recurrence. METHODS: A prospective randomized controlled trial was conducted in patients with curative resection of HCC; they were given either one intra-arterial dose of cisplatin/lipiodol, or received four doses, once every 3 months. The rates of recurrence, disease-free and overall survival were compared. RESULTS: During a median follow up of 818 days, 21 patients received one dose and 19 received four doses, with 10 (47.6%) and eight (42.1%) recurrences, respectively. The 1-year, 2-year and 3-year disease-free survival rates were 71%, 54% and 44% for the one-dose group and 74%, 60% and 40% for the four-dose group (P = 0.78). The respective overall survival rates were 85%, 74%, 55% and 84%, 71%, 40% (P = 0.64). The only prognostic factor was presence of vascular permeation. The side-effects were mild and tolerable. CONCLUSIONS: There is no significant difference in the survival rates between the two groups. Adjuvant chemotherapy may not be useful.