Robotic versus Laparoscopic Liver Resection in Various Settings: An International Multicenter Propensity Score Matched Study of 10.075 Patients.

OBJECTIVE: The aim of this study was to compare the perioperative outcomes of robotic liver surgery (RLS) and laparoscopic liver surgery (LLS) in various settings. SUMMARY BACKGROUND DATA: Clear advantages of RLS over LLS have rarely been demonstrated, and the associated costs of robotic surgery are generally higher than those of laparoscopic surgery. Therefore, the exact role of the robotic approach in minimally invasive liver surgery remains to be defined. METHODS: In this international retrospective cohort study, the outcomes of patients who underwent RLS and LLS for all indications between 2009 and 2021 in 34 hepatobiliary referral centers were compared. Subgroup analyses were performed to compare both approaches across several types of procedures: minor resections in the anterolateral (2, 3, 4b, 5, and 6) or posterosuperior segments (1, 4a, 7, 8), and major resections (≥3 contiguous segments). Propensity score matching (PSM) was used to mitigate the influence of selection bias. The primary outcome was textbook outcome in liver surgery (TOLS), previously defined as the absence of intraoperative incidents ≥grade 2, postoperative bile leak ≥grade B, severe morbidity, readmission, and 90-day or in-hospital mortality with the presence of an R0 resection margin in case of malignancy. The absence of a prolonged length of stay was added to define TOLS+. RESULTS: Among the 10.075 included patients, 1.507 underwent RLS and 8.568 LLS. After PSM, both groups constituted 1.505 patients. RLS was associated with higher rates of TOLS (78.3% vs. 71.8%, P<0.001) and TOLS+ (55% vs. 50.4%, P=0.026), less Pringle usage (39.1% vs. 47.1%, P<0.001), blood loss (100 vs. 200 milliliters, P<0.001), transfusions (4.9% vs. 7.9%, P=0.003), conversions (2.7% vs 8.8%, P<0.001), overall morbidity (19.3% vs. 25.7%, P<0.001) and R0 resection margins (89.8% vs. 86%, P=0.015), but longer operative times (190 vs. 210 min, P=0.015). In the subgroups, RLS tended to have higher TOLS rates, compared to LLS, for minor resections in the posterosuperior segments (n=431 per group, 75.9% vs. 71.2%, P=0.184) and major resections (n=321 per group, 72.9% vs. 67.5%, P=0.086), although these differences did not reach statistical significance. CONCLUSIONS: While both producing excellent outcomes, RLS might facilitate slightly higher TOLS rates than LLS.

Critical appraisal of surgical margins according to KRAS status in liver resection for colorectal liver metastases: Should surgical strategy be influenced by tumor biology?

BACKGROUND: KRAS mutation is a negative prognostic factor for colorectal liver metastases. Several studies have investigated the resection margins according to KRAS status, with conflicting results. The aim of the study was to assess the oncologic outcomes of R0 and R1 resections for colorectal liver metastases according to KRAS status. METHODS: All patients who underwent resection for colorectal liver metastases between 2010 and 2015 with available KRAS status were enrolled in this multicentric international cohort study. Logistic regression models were used to investigate the outcomes of R0 and R1 colorectal liver metastases resections according to KRAS status: wild type versus mutated. The primary outcomes were overall survival and disease-free survival. RESULTS: The analysis included 593 patients. KRAS mutation was associated with shorter overall survival (40 vs 60 months; P = .0012) and disease-free survival (15 vs 21 months; P = .003). In KRAS-mutated tumors, the resection margin did not influence oncologic outcomes. In multivariable analysis, the only predictor of disease-free survival and overall survival was primary tumor location (P = .03 and P = .03, respectively). In KRAS wild-type tumors, R0 resection was associated with prolonged overall survival (74 vs 45 months, P < .001) and disease-free survival (30 vs 17 months, P < .001). The multivariable model confirmed that R0 resection margin was associated with prolonged overall survival (hazard ratio = 1.43, 95% confidence interval: 1.01-2.03) and disease-free survival (hazard ratio = 1.42; 95% confidence interval: 1.06-1.91). CONCLUSIONS: KRAS-mutated colorectal liver metastases showed more aggressive tumor biology with inferior overall survival and disease-free survival after liver resection. Although R0 resection was not associated with improved oncologic outcomes in the KRAS-mutated tumors group, it seems to be of paramount importance for achieving prolonged long-term survival in KRAS wild-type tumors.

Explainable artificial intelligence prediction-based model in laparoscopic liver surgery for segments 7 and 8: an international multicenter study.

BACKGROUND: Artificial intelligence (AI) is becoming more useful as a decision-making and outcomes predictor tool. We have developed AI models to predict surgical complexity and the postoperative course in laparoscopic liver surgery for segments 7 and 8. METHODS: We included patients with lesions located in segments 7 and 8 operated by minimally invasive liver surgery from an international multi-institutional database. We have employed AI models to predict surgical complexity and postoperative outcomes. Furthermore, we have applied SHapley Additive exPlanations (SHAP) to make the AI models interpretable. Finally, we analyzed the surgeries not converted to open versus those converted to open. RESULTS: Overall, 585 patients and 22 variables were included. Multi-layer Perceptron (MLP) showed the highest performance for predicting surgery complexity and Random Forest (RF) for predicting postoperative outcomes. SHAP detected that MLP and RF gave the highest relevance to the variables "resection type" and "largest tumor size" for predicting surgery complexity and postoperative outcomes. In addition, we explored between surgeries converted to open and non-converted, finding statistically significant differences in the variables "tumor location," "blood loss," "complications," and "operation time." CONCLUSION: We have observed how the application of SHAP allows us to understand the predictions of AI models in surgical complexity and the postoperative outcomes of laparoscopic liver surgery in segments 7 and 8.

Surgery for liver metastases from primary breast cancer: A reconstructed individual patient data meta-analysis.

BACKGROUND: Currently, the outcomes of standard-of-care palliative treatment for BCLM remain poor. Recent literature has shown promising results of hepatic resection, however, not all studies concur. Given the lack of standardized international guidelines in this field, the aim of this study is to provide gold-standard evidence for breast cancer liver metastases (BCLM) through a reconstructed individual patient data meta-analysis approach. METHODS: Four databases were searched for articles comparing surgical and non-surgical treatment for BCLM. One-stage meta-analysis was performed using patient-level survival data reconstructed from Kaplan-Meier curves with plot digitizer software. Shared-frailty and stratified Cox models were fitted to compare survival endpoints. RESULTS: Four propensity-score matched (PSM) studies involving 205 surgical and 291 non-surgical patients for BCLM were included. There was a significant difference between both groups for overall survival (OS) (Hazard Ratio [HR] = 0.40, 95%CI 0.32-0.51). Sensitivity analyses for hormone receptor status of breast cancer (HR = 0.41, 95%CI 0.31-0.55) and type of resection performed (HR = 0.45, 95%CI 0.33-0.61) yielded HRs in favor of surgery. CONCLUSIONS: This meta-analysis concludes that surgery offers superior OS outcomes, compared to non-surgery, in a select group of patients. Future randomized controlled trials and PSM studies are warranted, using this study as a point of reference for similar parameters.

The impact of hospital volume on liver resection: A systematic review and Bayesian network meta-analysis.

BACKGROUND: This study aims to compare the outcomes of high-volume, medium-volume, and low-volume hospitals performing hepatic resections using a network meta-analysis. METHODS: A literature search until June 2023 was conducted across major databases to identify studies comparing outcomes in high-volume, medium-volume, and low-volume hospitals for liver resection. Bayesian network meta-analysis was conducted, and surface under cumulative ranking area values, odds ratio, and mean difference with 95% credible intervals were reported for postoperative mortality, failure-to-rescue, morbidity, length of stay, and hospital costs. RESULTS: Twenty studies comprising 248,707 patients undergoing liver resection were included. For the primary mortality outcome, overall and subgroup analyses were performed: group I: high-volume = 5 to 20 resections/year; group II: high-volume = 21 to 49 resections/year; group III: high-volume ≥50 resections/year. Results demonstrated a significant association between hospital volume and mortality (overall-high-volume versus medium-volume: odds ratio 0.66, 95% credible interval 0.49-0.87; high-volume versus low-volume: odds ratio 0.52, 95% credible interval 0.41-0.65; group I-high-volume versus low-volume: odds ratio 0.34, 95% credible interval 0.22-0.50; medium-volume versus low-volume: odds ratio 0.56, 95% credible interval 0.33-0.92; group II-high-volume versus low-volume: odds ratio 0.67, 95% credible interval 0.45-0.91), as well as length of stay (high-volume versus low-volume: mean difference -1.24, 95% credible interval -2.07 to -0.41), favoring high-volume hospitals. No significant difference was observed in failure-to-rescue, morbidity, or hospital costs across the 3 groups. CONCLUSION: This study supports a positive relationship between hospital volume and surgical outcomes in liver resection. Patients from high-volume hospitals experience superior outcomes in terms of lower postoperative mortality and shorter lengths of stay than medium-volume and low-volume hospitals.

Factors affecting overall survival and disease-free survival after surgery for hepatocellular carcinoma: a nomogram-based prognostic model-a Western European multicenter study.

Few studies have assessed the clinical implications of the combination of different prognostic indicators for overall survival (OS) and disease-free survival (DFS) of resected hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic factors in HCC patients for OS and DFS outcomes and establish a nomogram-based prognostic model to predict the DFS of HCC. A multicenter, retrospective European study was conducted through the collection of data on 413 consecutive treated patients with a first diagnosis of HCC between January 2010 and December 2020. Univariate and multivariate Cox regression analyses were performed to identify all independent risk factors for OS and DFS outcomes. A nomogram prognostic staging model was subsequently established for DFS and its precision was verified internally by the concordance index (C-Index) and externally by calibration curves. For OS, multivariate Cox regression analysis indicated Child-Pugh B7 score (HR 4.29; 95% CI 1.74-10.55; p = 0.002) as an independent prognostic factor, along with Barcelona Clinic Liver Cancer (BCLC) stage ≥ B (HR 1.95; 95% CI 1.07-3.54; p = 0.029), microvascular invasion (MVI) (HR 2.54; 95% CI 1.38-4.67; p = 0.003), R1/R2 resection margin (HR 1.57; 95% CI 0.85-2.90; p = 0.015), and Clavien-Dindo Grade 3 or more (HR 2.73; 95% CI 1.44-5.18; p = 0.002). For DFS, multivariate Cox regression analysis indicated BCLC stage ≥ B (HR 2.15; 95% CI 1.34-3.44; p = 0.002) as an independent prognostic factor, along with multiple nodules (HR 2.04; 95% CI 1.25-3.32; p = 0.004), MVI (HR 1.81; 95% CI 1.19-2.75; p = 0.005), satellite nodules (HR 1.63; 95% CI 1.09-2.45; p = 0.018), and R1/R2 resection margin (HR 3.39; 95% CI 2.19-5.25; < 0.001). The C-Index of the nomogram, tailored based on the previous significant factors, showed good accuracy (0.70). Internal and external calibration curves for the probability of DFS rate showed optimal consistency and fit well between the nomogram-based prediction and actual observations. MVI and R1/R2 resection margins should be considered as significant OS and DFS predictors, while satellite nodules should be included as a significant DFS predictor. The nomogram-based prognostic model for DFS provides a more effective prognosis assessment for resected HCC patients, allowing for individualized treatment plans.

Predictive modeling algorithms for liver metastasis in colorectal cancer: A systematic review of the current literature.

This study aims to assess the quality and performance of predictive models for colorectal cancer liver metastasis (CRCLM). A systematic review was performed to identify relevant studies from various databases. Studies that described or validated predictive models for CRCLM were included. The methodological quality of the predictive models was assessed. Model performance was evaluated by the reported area under the receiver operating characteristic curve (AUC). Of the 117 articles screened, seven studies comprising 14 predictive models were included. The distribution of included predictive models was as follows: radiomics (n = 3), logistic regression (n = 3), Cox regression (n = 2), nomogram (n = 3), support vector machine (SVM, n = 2), random forest (n = 2), and convolutional neural network (CNN, n = 2). Age, sex, carcinoembryonic antigen, and tumor staging (T and N stage) were the most frequently used clinicopathological predictors for CRCLM. The mean AUCs ranged from 0.697 to 0.870, with 86% of the models demonstrating clear discriminative ability (AUC > 0.70). A hybrid approach combining clinical and radiomic features with SVM provided the best performance, achieving an AUC of 0.870. The overall risk of bias was identified as high in 71% of the included studies. This review highlights the potential of predictive modeling to accurately predict the occurrence of CRCLM. Integrating clinicopathological and radiomic features with machine learning algorithms demonstrates superior predictive capabilities.

Impact of body mass index on perioperative outcomes of laparoscopic major hepatectomies.

BACKGROUND: Data on the effect of body mass index on laparoscopic liver resections are conflicting. We performed this study to investigate the association between body mass index and postoperative outcomes after laparoscopic major hepatectomies. METHODS: This is a retrospective review of 4,348 laparoscopic major hepatectomies at 58 centers between 2005 and 2021, of which 3,383 met the study inclusion criteria. Concomitant major operations, vascular resections, and previous liver resections were excluded. Associations between body mass index and perioperative outcomes were analyzed using restricted cubic splines. Modeled effect sizes were visually rendered and summarized. RESULTS: A total of 1,810 patients (53.5%) had normal weight, whereas 1,057 (31.2%) were overweight and 392 (11.6%) were obese. One hundred and twenty-four patients (3.6%) were underweight. Most perioperative outcomes showed a linear worsening trend with increasing body mass index. There was a statistically significant increase in open conversion rate (16.3%, 10.8%, 9.2%, and 5.6%, P < .001), longer operation time (320 vs 305 vs 300 and 266 minutes, P < .001), increasing blood loss (300 vs 300 vs 295 vs 250 mL, P = .022), and higher postoperative morbidity (33.4% vs 26.3% vs 25.0% vs 25.0%, P = .009) in obese, overweight, normal weight, and underweight patients, respectively (P < .001). However, postoperative major morbidity demonstrated a "U"-shaped association with body mass index, whereby the highest major morbidity rates were observed in underweight and obese patients. CONCLUSION: Laparoscopic major hepatectomy was associated with poorer outcomes with increasing body mass index for most perioperative outcome measures.

Early experience with pure laparoscopic donor hepatectomy: comparison with open donor hepatectomy and non-donor laparoscopic hepatectomy.

BACKGROUND: Pure laparoscopic donor hepatectomy (L-DH) has seen a rise in uptake in recent years following the popularization of minimally invasive modality for major hepatobiliary surgery. Our study aimed to determine the safety and compare the perioperative outcomes of L-DH with open donor hepatectomy (O-DH) and laparoscopic non donor hepatectomy (L-NDH) based on our single institution experience. METHODS: Eighty of 113 laparoscopic hemi-hepatectomies performed between 2015 and 2022 met study inclusion criteria. Of these, 11 were L-DH. PSM in a 1:2 ratio of L-DH versus L-NDH and 1:1 ratio of L-DH versus O-DH were performed, identifying patients with similar baseline clinicopathological characteristics. RESULTS: After 2:1 matching, the L-DH cohort were significantly younger (P < 0.001) and had lower ASA scores (P < 0.001) than the L-NDH cohort. L-DH was associated with a longer median operating time (P < 0.001) and shorter median postoperative stay (P < 0.001) than L-NDH. After 1:1 matching, there were no significant differences in baseline demographic between the L-DH and O-DH cohorts. L-DH was associated with lower median blood loss (P = 0.040) and shorter length of stay compared to O-DH (P = 0.004). There were no significant differences in recipient outcomes for both cohorts. CONCLUSION: L-DH can be adopted safely by surgeons experienced in L-NDH and ODH. It is associated with decreased blood loss and shorter length of stay compared to O-DH.

Preoperative Predictors of Early Recurrence After Liver Resection for Multifocal Hepatocellular Carcinoma.

BACKGROUND: Liver transplantation remains the optimal treatment for multifocal hepatocellular carcinoma (HCC). However, due to resource constrains, other therapeutic modalities such as liver resection (LR), are frequently utilized. LR, however, has to be balanced against potential morbidity and mortality along with the risks of early recurrence leading to futile surgery. In this study, we evaluated preoperative factors, including inflammatory indices, in predicting early (< 1 year) recurrence in patients who underwent LR for multifocal HCC. METHODS: This was a post hoc analysis of 250 consecutive patients with multifocal HCC who underwent LR. RESULTS: After exclusion of 10 patients with 30-day/in-hospital mortality, 240 were included of which 134 (55.8%) developed early recurrence. Hepatitis B/C aetiology, 3/ > more hepatic nodules and elevated alpha-fetoprotein (AFP) ≥ 200 ng/ml were significant independent preoperative predictors of early recurrence. The early recurrence rate was 72.1% when 2 out of 3 significant predictive factors were present. The conglomerate of all 3 factors predicted early recurrence of 100% with a statistically significant association between number of predictive factors and early recurrence (p < 0.001). CONCLUSION: Better patient selection via the use of preoperative predictive factors of early recurrence such as hepatitis B/C aetiology, ≥ 3 nodules and elevated AFP ≥ 200 ng/ml may assist in identifying patients in whom LR is deemed futile and improve resource allocation.

Long-term Outcomes After Laparoscopic, Robotic, and Open Pancreatoduodenectomy for Distal Cholangiocarcinoma: An International Propensity Score-matched Cohort Study.

OBJECTIVE: This study aimed to compare surgical and oncological outcomes after minimally invasive pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy (OPD) for distal cholangiocarcinoma (dCCA). BACKGROUND: A dCCA might be a good indication for MIPD, as it is often diagnosed as primary resectable disease. However, multicenter series on MIPD for dCCA are lacking. METHODS: This is an international multicenter propensity score-matched cohort study including patients after MIPD or OPD for dCCA in 8 centers from 5 countries (2010-2021). Primary outcomes included overall survival (OS) and disease-free interval (DFI). Secondary outcomes included perioperative and postoperative complications and predictors for OS or DFI. Subgroup analyses included robotic pancreatoduodenectomy (RPD) and laparoscopic pancreatoduodenectomy (LPD). RESULTS: Overall, 478 patients after pancreatoduodenectomy for dCCA were included of which 97 after MIPD (37 RPD, 60 LPD) and 381 after OPD. MIPD was associated with less blood loss (300 vs 420 mL, P =0.025), longer operation time (453 vs 340 min; P <0.001), and less surgical site infections (7.8% vs 19.3%; P =0.042) compared with OPD. The median OS (30 vs 25 mo) and DFI (29 vs 18) for MIPD did not differ significantly between MIPD and OPD. Tumor stage (Hazard ratio: 2.939, P <0.001) and administration of adjuvant chemotherapy (Hazard ratio: 0.640, P =0.033) were individual predictors for OS. RPD was associated with a higher lymph node yield (18.0 vs 13.5; P =0.008) and less major morbidity (Clavien-Dindo 3b-5; 8.1% vs 32.1%; P =0.005) compared with LPD. DISCUSSION: Both surgical and oncological outcomes of MIPD for dCCA are acceptable as compared with OPD. Surgical outcomes seem to favor RPD as compared with LPD but more data are needed. Randomized controlled trials should be performed to confirm these findings.

Prognosis after hepatic resection of patients with hepatocellular carcinoma related to non-alcoholic fatty liver disease: meta-analysis.

BACKGROUND: Whether the safety and efficacy of hepatic resection differ between patients whose hepatocellular carcinoma (HCC) is related to non-alcoholic fatty liver disease (NAFLD) or has other aetiologies is unknown. A systematic review was performed to explore potential differences between such conditions. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for relevant studies that reported hazard ratios (HRs) for overall and recurrence-free survival between patients with NAFLD-related HCC or HCC of other aetiologies. RESULTS: The meta-analysis involved 17 retrospective studies involving 2470 patients (21.5 per cent) with NAFLD-related HCC and 9007 (78.5 per cent) with HCC of other aetiologies. Patients with NAFLD-related HCC were older and had higher body mass index (BMI), but were less likely to have cirrhosis (50.4 per cent versus 64.0 per cent, P < 0.001). The two groups suffered similar rates of perioperative complications and mortality. Patients with NAFLD-related HCC had slightly higher overall survival (HR 0.87, 95 per cent c.i. 0.75 to 1.02) and recurrence-free survival (HR 0.93, 95 per cent c.i. 0.84 to 1.02) than those with HCC of other aetiologies. In the various subgroup analyses, the only significant finding was that Asian patients with NAFLD-related HCC had significantly better overall survival (HR 0.82, 95 per cent c.i. 0.71 to 0.95) and recurrence-free survival (HR 0.88, 95 per cent c.i. 0.79 to 0.98) than Asian patients with HCC of other aetiologies. CONCLUSION: The available evidence suggests that patients with NAFLD-related HCC have similar perioperative complications and mortality, but potentially longer overall and recurrence-free survival, compared with those with HCC of other aetiologies. Tailored surveillance strategies should be developed for patients with NAFLD without cirrhosis.

Association of standardized liver volume and body mass index with outcomes of minimally invasive liver resections.

INTRODUCTION: While minimally invasive liver resections (MILR) have demonstrated advantages in improved post-operative recovery, widespread adoption is hampered by inherent technical difficulties. Our study attempts to analyze the role of anthropometric measures in MILR-related outcomes. METHODS: Between 2012 and 2020, 676 consecutive patients underwent MILR at the Singapore General Hospital of which 565 met study criteria and were included. Patients were stratified based on Body Mass Index (BMI) as well as Standardized Liver Volumes (SLV). Associations between BMI and SLV to selected peri-operative outcomes were analyzed using restricted cubic splines. RESULTS: A BMI of ≥ 29 was associated with increase in blood loss [Mean difference (MD) 69 mls, 95% CI 2 to 137] as well as operative conversions [Relative Risk (RR) 1.63, 95% CI 1.02 to 2.62] among patients undergoing MILR while a SLV of 1600 cc or higher was associated with an increase in blood loss (MD 30 mls, 95% CI 10 to 49). In addition, a BMI of ≤ 20 was associated with an increased risk of major complications (RR 2.25, 95% 1.16 to 4.35). The magnitude of differences observed in these findings increased with each unit change in BMI and SLV. CONCLUSION: Both BMI and SLV were useful anthropometric measures in predicting peri-operative outcomes in MILR and may be considered for incorporation in future difficulty scoring systems for MILR.

Intraoperative blood transfusion does not impact overall and recurrence-free survival after curative hepatectomy for hepatocellular carcinoma: A propensity-score-matched and inverse probability of treatment-weighted study.

INTRODUCTION: Our primary objective was to determine if receiving intraoperative blood transfusion was a significant prognostic factor for overall and recurrence-free survival after curative resection of hepatic cellular carcinoma (HCC). METHODOLOGY: Between 2001 and 2018, 1092 patients with histologically proven primary HCC who underwent curative liver resection were retrospectively reviewed. Primary study endpoints were recurrence-free survival (RFS) and overall survival (OS). The main analysis was undertaken using propensity-score matching (PSM) to minimize confounding and selection biases in the comparison of patients with or without transfusion. RESULTS: There were 220 patients who received and 666 patients who did not receive intraoperative blood transfusion. The PSM cohort consisted of 163 pairs of patients. After PSM, the only perioperative outcome that appeared to significantly affect whether patients would receive blood transfusion was median blood loss (p = 0.001). In the PSM cohort, whether patients received blood transfusion was neither associated with OS (p = 0.759) nor RFS (p = 0.830). When the volume of blood transfusion was analyzed as a continuous variable, no significant dose-response relationship between blood transfusion volume and HR for OS and RFS was noted. CONCLUSION: Intraoperative blood transfusion had no significant impact on the survival outcomes in patients who receive curative resection in primary HCC.

Case report: Understanding the impact of persistent tissue-localization of SARS-CoV-2 on immune response activity via spatial transcriptomic analysis of two cancer patients with COVID-19 co-morbidity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected half a billion people, including vulnerable populations such as cancer patients. While increasing evidence supports the persistence of SARS-CoV-2 months after a negative nasopharyngeal swab test, the effects on long-term immune memory and cancer treatment are unclear. In this report, we examined post-COVID-19 tissue-localized immune responses in a hepatocellular carcinoma (HCC) patient and a colorectal cancer (CRC) patient. Using spatial whole-transcriptomic analysis, we demonstrated spatial profiles consistent with a lymphocyte-associated SARS-CoV-2 response (based on two public COVID-19 gene sets) in the tumors and adjacent normal tissues, despite intra-tumor heterogeneity. The use of RNAscope and multiplex immunohistochemistry revealed that the spatial localization of B cells was significantly associated with lymphocyte-associated SARS-CoV-2 responses within the spatial transcriptomic (ST) niches showing the highest levels of virus. Furthermore, single-cell RNA sequencing data obtained from previous (CRC) or new (HCC) ex vivo stimulation experiments showed that patient-specific SARS-CoV-2 memory B cells were the main contributors to this positive association. Finally, we evaluated the spatial associations between SARS-CoV-2-induced immunological effects and immunotherapy-related anti-tumor immune responses. Immuno-predictive scores (IMPRES) revealed consistent positive spatial correlations between T cells/cytotoxic lymphocytes and the predicted immune checkpoint blockade (ICB) response, particularly in the HCC tissues. However, the positive spatial correlation between B cells and IMPRES score was restricted to the high-virus ST niche. In addition, tumor immune dysfunction and exclusion (TIDE) analysis revealed marked T cell dysfunction and inflammation, alongside low T cell exclusion and M2 tumor-associated macrophage infiltration. Our results provide in situ evidence of SARS-CoV-2-generated persistent immunological memory, which could not only provide tissue protection against reinfection but may also modulate the tumor microenvironment, favoring ICB responsiveness. As the number of cancer patients with COVID-19 comorbidity continues to rise, improved understanding of the long-term immune response induced by SARS-CoV-2 and its impact on cancer treatment is much needed.

Extending Surgical Resection for Hepatocellular Carcinoma Beyond Barcelona Clinic for Liver Cancer (BCLC) Stage A: A Novel Application of the Modified BCLC Staging System.

Objective: We aimed to prognosticate survival after surgical resection of HCC stratified by stage with amalgamation of the modified Barcelona Clinic Liver Cancer (BCLC) staging system and location of tumour. Methods: This single-institutional retrospective cohort study included patients with HCC who underwent surgical resection between 1st January 2000 to 30th June 2016. Participants were divided into 6 different subgroups: A-u) Within MC with Unilobar lesions; A-b) Within MC + Bilobar lesions; B1-u) Out of MC + within Up-To-7 + Unilobar lesions; B1-b) Out of MC + within Up-to-7 + Bilobar lesions; B2-u) Out of MC + Out of Up-To-7 + Unilobar lesions; B2-b) Out of MC + Out of Up-To-7 + Bilobar lesions. A separate survival analysis was conducted for solitary HCC lesions according to three subgroups: A-S (Within MC); B1-S (Out of MC + within Up-To-7); B2-S (Out of MC + out of Up-To-7). Results: A total of 794 of 1043 patients with surgical resection for HCC were analysed. Groups A-u (64.6%), A-b (58.4%) and B1-u (56.2%) had 5-year cumulative overall survival (OS) rates above 50% after surgical resection and median OS exceeding 60 months (P = 0.0001). The 5-year cumulative recurrence-free survival rates (RFS) were 40.4% (group A-u), 38.2% (group A-b), 36.3% (group B1-u), 24.6% (group B2-u), and 7.3% (group B2-b)(P=0.0001). For solitary lesions, the 5-year OS for the subgroups were A-S (65.1%), B1-S (56.0%) and B2-S (47.1%) (P = 0.0003). Compared to A-S, there was also a significant trend towards relatively poorer OS as the lesion sizes increased in B1-S (HR 1.46, 95% CI 1.03-2.08) and B2-S (HR 1.65, 95% CI 1.25-2.18). Conclusion: We adopted a novel approach combining the modified BCLC B sub-classification and dispersion of tumour to show that surgical resection in intermediate stage HCC can be robustly prognosticated. We found that size prognosticates resection outcomes in solitary tumours.

Poor utility of current nomograms assessing the risk of intraoperative blood transfusion in patients undergoing liver resection for hepatocellular carcinoma and proposal of a new model.

BACKGROUND: The Memorial Sloan Kettering Cancer Center nomogram, the predictive scoring system of Yamamoto et al, and the 3-point transfusion risk score of Lemke et al are models used to determine the probability of receiving intraoperative blood transfusion in patients undergoing liver resection. However, the external validity of these models remains unknown. The objective of this study was to evaluate their predictive performance in an external cohort of patients with hepatocellular carcinoma. We also aimed to identify predictors of blood transfusion and develop a new predictive model for blood transfusion. METHODS: Post hoc analysis of our prospective database of 1,081 patients undergoing liver resection for hepatocellular carcinoma from 2001 to 2018. The predictive performance of current prediction models was evaluated using C statistics. Demographic and clinical variables as predictors of blood transfusion were assessed. Using logistic regression, an alternative model was created. RESULTS: The Lemke transfusion risk score performed better than the Memorial Sloan Kettering Cancer Center nomogram (0.69, 95% confidence interval 0.66-0.73 vs 0.66, 95% liver resection 0.62-0.69) (P < .001). The model from Yamamoto et al performed comparably with no statistically significant differences found through pairwise comparison. In our alternative model, hemoglobin level, albumin level, liver resection type, and tumor size were independent predictors of blood transfusion. The new HATS model obtained a C statistic of 0.74 (95% confidence interval 0.71-0.78), performing significantly better than the previous 3 models (P ≤ 0.001 for all). CONCLUSION: The existing Memorial Sloan Kettering Cancer Center, Yamamoto et al, and Lemke et al had nomograms with the suboptimal accuracy of predicting risk of intraoperative blood transfusion in patients undergoing liver resection for hepatocellular carcinoma. The proposed HATS model was more accurate at predicting patients at risk of blood transfusion.