The impact of surging transplantation of alcohol-associated liver disease on transplantation for HCC and other indications.

BACKGROUND: Liver transplantation (LT) for alcohol-associated liver disease (ALD) is increasing and may impact LT outcomes for patients listed for HCC and other indications. METHODS: Using US adults listed for primary LT (grouped as ALD, HCC, and other) from October 8, 2015, to December 31, 2021, we examined the impact of center-level ALD LT volume (ATxV) on waitlist outcomes in 2 eras: Era 1 (6-month wait for HCC) and Era 2 (MMaT-3). The tertile distribution of ATxV (low to high) was derived from the listed candidates as Tertile 1 (T1): <28.4%, Tertile 2 (T2): 28.4%-37.6%, and Tertile 3 (T3): >37.6% ALD LTs per year. Cumulative incidence of waitlist death and LT within 18 months from listing by LT indication were compared using the Gray test, stratified on eras and ATxV tertiles. Multivariable competing risk regression estimated the adjusted subhazard ratios (sHRs) for the risk of waitlist mortality and LT with interaction effects of ATxV by LT indication (interaction p). RESULTS: Of 56,596 candidates listed, the cumulative waitlist mortality for those with HCC and other was higher and their LT probability was lower in high (T3) ATxV centers, compared to low (T1) ATxV centers in Era 2. However, compared to ALD (sHR: 0.92 [0.66-1.26]), the adjusted waitlist mortality for HCC (sHR: 1.15 [0.96-1.38], interaction p = 0.22) and other (sHR: 1.13 [0.87-1.46], interaction p = 0.16) were no different suggesting no differential impact of ATxV on the waitlist mortality. The adjusted LT probability for HCC (sHR: 0.89 [0.72-1.11], interaction p = 0.08) did not differ by AtxV while it was lower for other (sHR: 0.82 [0.67-1.01], interaction p = 0.02) compared to ALD (sHR: 1.04 [0.80-1.34]) suggesting a differential impact of ATxV on LT probability. CONCLUSIONS: The high volume of LT for ALD does not impact waitlist mortality for HCC and others but affects LT probability for other in the MMAT-3 era warranting continued monitoring.

Myxoinflammatory fibroblastic sarcoma of the liver: Case report and literature review.

RATIONALE: Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare low-grade malignant soft tissue sarcoma that primarily affects the distal extremities in adults, with the highest incidence in patients in their 40s and 50s. It has a high local recurrence rate and a low metastasis rate. Although MIFSs have been documented in other sites, an MIFS in the liver is highly unusual. Herein, we present a case of a patient with hepatic MIFS. PATIENT CONCERNS: The patient was a 58-year-old Chinese man with abdominal pain as the primary symptom. Abdominal computed tomography and magnetic resonance imaging revealed a mass in the right posterior lobe of the liver. The patient underwent surgical excision, and the excised specimen was identified as MIFS. Three years later, the patient returned to our hospital for abdominal pain. Computed tomography and magnetic resonance imaging revealed a mass in liver segments 2/3/4. DIAGNOSIS: Postoperative pathological examination of the tumor revealed the recurrence of MIFS. INTERVENTIONS: The patient underwent surgical resection of the MIFS. OUTCOMES: The patient received multiple pirarubicin-based chemotherapy treatments and an ALK inhibitor (anlotinib) within 6 months after surgery, but the tumor recurred. LESSONS: MIFS can not only occur in the proximal limbs, trunk, head, and neck but can also affect the abdominal organs. Surgical resection remains the primary treatment option for MIFS in the absence of any contraindications. Because the recurrence rate of MIFS is high, meticulous long-term monitoring is required.

Prediction power of radiomics in early recurrence of hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: Raiomics is an emerging auxiliary diagnostic tool, but there are still differences in whether it can be applied to predict early recurrence of hepatocellular carcinoma (HCC). The purpose of this meta-analysis was to systematically evaluate the predictive power of radiomics in the early recurrence (ER) of HCC. METHODS: Comprehensive studies on the application of radiomics to predict ER in HCC patients after hepatectomy or curative ablation were systematically screened in Embase, PubMed, and Web of Science. RESULTS: Ten studies which is involving a total of 1929 patients were reviewed. The overall estimates of radiomic models for sensitivity and specificity in predicting the ER of HCC were 0.79 (95% confidence interval [CI]: 0.68-0.87) and 0.83 (95% CI: 0.73-0.90), respectively. The area under the summary receiver operating characteristic curve (SROC) was 0.88 (95% CI: 0.85-0.91). CONCLUSIONS: The imaging method is a reliable method for diagnosing HCC. Radiomics, which is based on medical imaging, has excellent power in predicting the ER of HCC. With the help of radiomics, we can predict the recurrence of HCC after surgery more effectively and provide a useful reference for clinical practice.

A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC).

BACKGROUND: Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking. METHODS: Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses. DISCUSSION: The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research. TRIAL REGISTRATION: anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

Heparin is an effective treatment for preventing liver failure after hepatectomy.

BACKGROUND: Posthepatectomy liver failure (PHLF) is one of the most important causes of death following liver resection. Heparin, an established anticoagulant, can protect liver function through a number of mechanisms, and thus, prevent liver failure. AIM: To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy. METHODS: The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) v1. 4 pinpointed patients who had undergone hepatectomy for liver cancer, subdividing them into two cohorts: Those who were injected with heparin and those who were not. The statistical evaluations used were unpaired t-tests, Mann-Whitney U tests, chi-square tests, and Fisher's exact tests to assess the effect of heparin administration on PHLF, duration of intensive care unit (ICU) stay, need for mechanical ventilation, use of continuous renal replacement therapy (CRRT), incidence of hypoxemia, development of acute kidney injury, and ICU mortality. Logistic regression was utilized to analyze the factors related to PHLF, with propensity score matching (PSM) aiming to balance the preoperative disparities between the two groups. RESULTS: In this study, 1388 patients who underwent liver cancer hepatectomy were analyzed. PSM yielded 213 matched pairs from the heparin-treated and control groups. Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples. Further analysis in the matched cohorts confirmed a significant association, with heparin reducing the risk of PHLF (odds ratio: 0.518; 95% confidence interval: 0.295-0.910; P = 0.022). Additionally, heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations, diminished requirements for respiratory support and CRRT, and lower incidences of hypoxemia and ICU mortality. CONCLUSION: Liver failure is an important hazard following hepatic surgery. During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure. This indicates that heparin may provide a hopeful option for controlling PHLF.

Feasibility, safety, and efficacy of intraoperative magnetic resonance imaging-guided hepatectomy for small hepatocellular carcinoma: A retrospective study.

Advancements in diagnostic modalities, such as enhanced magnetic resonance imaging, provide increased opportunities for identifying small hepatocellular carcinoma that is undetectable on preoperative ultrasonography. Whether it is acceptable to leave these lesions untreated is uncertain. This study aimed to evaluate the safety and efficacy of intraoperative magnetic resonance imaging-guided hepatectomy using new navigation systems. This study was conducted between July 2019 and January 2023. We retrospectively studied the clinicopathological features and prognoses of patients with small hepatocellular carcinoma who underwent curative intraoperative magnetic resonance imaging-guided hepatectomy. We evaluated 23 patients (median age, 75 years), among whom 20 (87.0%) were males. Seven (30.4%) and 15 (65.2%) patients had liver cirrhosis and a history of hepatectomy, respectively. The median size of the target lesions was 9 mm, with a median distance of 6 mm from the liver surface. Despite being undetectable preoperatively on contrast-enhanced ultrasonography, all lesions were identified using intraoperative magnetic resonance imaging. Based on pathological findings, 76.0% of the lesions were malignant. The complete resection rate was 100%, and tumor-free margins were confirmed in 96.0% of the patients. Intraoperative magnetic resonance imaging-guided hepatectomy is safe and effective in identifying and resecting small hepatocellular carcinoma lesions that are undetectable on preoperative ultrasonography.

Safety and feasibility of liver resection including major hepatectomy for geriatric patients with hepatocellular carcinoma: a retrospective observational study.

BACKGROUND: It is unclear whether hepatectomy, which ranges in invasiveness from partial to major hepatectomy, is safe and feasible for older adult patients. Therefore, we compared its postoperative complications and long-term outcomes between younger and older adult patients. METHODS: Patients who underwent hepatectomies for hepatocellular carcinoma (N = 883) were evaluated. Patients were divided into two groups: aged < 75 years (N = 593) and ≥ 75 years (N = 290). Short-term outcomes and prognoses were compared between the groups in the entire cohort. The same analyses were performed for the major hepatectomy cohort. RESULTS: In the entire cohort, no significant differences were found in complications between patients aged < 75 and ≥ 75 years, and the multivariate analysis did not reveal age as a prognostic factor for postoperative complications. However, overall survival was significantly worse in older patients, although no significant differences were noted in time to recurrence or cancer-specific survival. In the multivariate analyses of time to recurrence, overall survival, and cancer-specific survival, although older age was an independent poor prognostic factor for overall survival, it was not a prognostic factor for time to recurrence and cancer-specific survival. In the major hepatectomy subgroup, short- and long-term outcomes, including time to recurrence, overall survival, and cancer-specific survival, did not differ significantly between the age groups. In the multivariate analysis, age was not a significant prognostic factor for complications, time to recurrence, overall survival, or cancer-specific survival. CONCLUSION: Hepatectomy, including minor and major hepatectomy, may be safe and oncologically feasible options for selected older adult patients with hepatocellular carcinoma.

A novel surgical scheme for hepatectomy in hepatocellular carcinoma patients with clinically significant portal hypertension.

OBJECTIVE: Clinically significant portal hypertension (CSPH) seriously affects the feasibility and safety of surgical treatment for hepatocellular carcinoma (HCC) patients. The aim of this study was to establish a new surgical scheme defining risk classification of post-hepatectomy liver failure (PHLF) to facilitate the surgical decision-making and identify suitable candidates for individual hepatectomy among HCC patients with CSPH. BACKGROUNDS: Hepatectomy is the preferred treatment for HCC. Surgeons must maintain a balance between the expected oncological outcomes of HCC removal and short-term risks of severe PHLF and morbidity. CSPH aggravates liver decompensation and increases the risk of severe PHLF thus complicating hepatectomy for HCC. METHODS: Multivariate logistic regression and stochastic forest algorithm were performed, then the independent risk factors of severe PHLF were included in a nomogram to determine the risk of severe PHLF. Further, a conditional inference tree (CTREE) through recursive partitioning analysis validated supplement the misdiagnostic threshold of the nomogram. RESULTS: This study included 924 patients, of whom 137 patients (14.8%) suffered from mild-CSPH and 66 patients suffered from (7.1%) with severe-CSPH confirmed preoperatively. Our data showed that preoperative prolonged prothrombin time, total bilirubin, indocyanine green retention rate at 15 min, CSPH grade, and standard future liver remnant volume were independent predictors of severe PHLF. By incorporating these factors, the nomogram achieved good prediction performance in assessing severe PHLF risk, and its concordance statistic was 0.891, 0.850 and 0.872 in the training cohort, internal validation cohort and external validation cohort, respectively, and good calibration curves were obtained. Moreover, the calculations of total points of diagnostic errors with 95% CI were concentrated in 110.5 (range 76.9-178.5). It showed a low risk of severe PHLF (2.3%), indicating hepatectomy is feasible when the points fall below 76.9, while the risk of severe PHLF is extremely high (93.8%) and hepatectomy should be rigorously restricted at scores over 178.5. Patients with points within the misdiagnosis threshold were further examined using CTREE according to a hierarchic order of factors represented by the presence of CSPH grade, ICG-R15, and sFLR. CONCLUSION: This new surgical scheme established in our study is practical to stratify risk classification in assessing severe PHLF, thereby facilitating surgical decision-making and identifying suitable candidates for individual hepatectomy.

Oncologic Outcomes of Interventions to Decrease Allograft Ischemia-Reperfusion Injury within Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma: A Systematic Review.

Ischemia-reperfusion injury (IRI) during liver transplantation has been implicated in the recurrence of hepatocellular carcinoma (HCC). This systematic review aimed to evaluate interventions to reduce IRI during liver transplantation for HCC and their impact on oncologic outcomes. A comprehensive literature search retrieved four retrospective studies involving 938 HCC patients, utilising interventions such as post-operative prostaglandin administration, hypothermic machine perfusion, and normothermic machine perfusion. Overall, treated patients exhibited reduced post-operative hepatocellular injury and inflammation and significantly enhanced recurrence-free survival. Despite these promising results, the impact of these interventions on overall survival remains unclear. This underscores the imperative for further prospective research to comprehensively understand the efficacy of these interventions in HCC patients undergoing transplantation. The findings highlight the potential benefits of these strategies while emphasising the need for continued investigation into their overall impact.

Comparison of genomic profiling of patient-matched primary colorectal and surgical resected distant metastatic (stage IV) colorectal carcinoma for drug actionability.

It is often difficult to obtain adequate tissue for genomic study from distant metastases for assessment of targeted therapy in colorectal carcinomas. The study aims to explore the genomic differences between matched distant metastatic colorectal carcinomas (mCRC) and primary carcinoma using surgical specimens of both with adequate tissue. Thirty-four paired primary and distant metastatic colorectal carcinoma samples (liver, ovary, and lung) were obtained from surgical excisions (not small biopsies) and are microsatellite stable. They were subjected to DNA sequencing using comprehensive next-generation sequencing. This included mutation concordance analysis and mutational signature analysis. The mutation concordance analysis showed 49.6% shared mutations between primary and metastatic tumours, with 23.0% mutations exclusive to primary tumours and 27.4% mutations exclusive to distant metastases. While many patients with KRAS/BRAF mutations had shared mutations, two cases had unique KRAS mutations in the primary tumours only. Additionally, TMB (tumour mutational burden) analysis revealed that half of the TMB-high (≥7.5 mutations/Mb) metastatic colorectal carcinomas had a low TMB (<7.5 mutations/Mb) in the primary tumours. The mutational signature analysis identified de novo signatures consistent with known single base substitution patterns such as SBS11 (alkylation agents) and SBS30 (base excision repair deficiency) post-chemotherapy. To conclude, this study demonstrates significant genomic variations in resected distant metastasis when compared to primary colorectal carcinomas when adequate tissue is available. This finding underscores the importance of considering these differences and selecting tissue for mutation analysis in planning targeted and effective treatment strategies for mCRC.

Outcomes after laparoscopic or open liver resection for nonalcoholic fatty liver disease-associated hepatocellular carcinoma: a propensity score-matching study.

BACKGROUND: Laparoscopic liver resection (LLR) is rapidly gaining popularity; however, its efficacy for nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) (NAFLD-HCC) has been not evaluated. The purpose of this study was to compare short- and long-term outcomes between LLR and open liver resection (OLR) among patients with NAFLD-HCC. METHODS: We used a single-institution database to analyze data for patients who underwent LLR or OLR for NAFLD-HCC from January 2007 to December 2022. We performed propensity score-matching analyses to compare overall postoperative complications, major morbidities, duration of surgery, blood loss, transfusion, length of stay, recurrence, and survival between the two groups. RESULTS: Among 210 eligible patients, 46 pairs were created by propensity score matching. Complication rates were 28% for OLR and 11% for LLR (p = 0.036). There were no significant differences in major morbidities (15% vs. 8.7%, p = 0.522) or duration of surgery (199 min vs. 189 min, p = 0.785). LLR was associated with a lower incidence of blood transfusion (22% vs. 4.4%, p = 0.013), less blood loss (415 vs. 54 mL, p < 0.001), and shorter postoperative hospital stay (9 vs. 6 days, p < 0.001). Differences in recurrence-free survival and overall survival between the two groups were not statistically significant (p = 0.222 and 0.301, respectively). CONCLUSIONS: LLR was superior to OLR for NAFLD-HCC in terms of overall postoperative complications, blood loss, blood transfusion, and postoperative length of stay. Moreover, recurrence-free survival and overall survival were comparable between LLR and OLR. Although there is a need for careful LLR candidate selection according to tumor size and location, LLR can be regarded as a preferred treatment for NAFLD-HCC over OLR.

Clinical impact and role of major vessels involvement in laparoscopic resection for hepatic hemangioma.

BACKGROUND: Severe bleeding remains a significant concern in laparoscopic resection for hepatic hemangioma. It is rarely reported that how the degree of major vessels involvement impacts on severe bleeding. The present study primarily aimed to analyze the impacts of the number of involved major vessels (NIMV) during laparoscopic surgery for hepatic hemangioma and evaluate the risk factors associated with increased bleeding. METHODS: A database search was carried out for consecutive patients who underwent laparoscopic resection for liver hemangiomas at our department from January 2018 to December 2023. The collected data included demographics, characteristics of the hemangiomas, laboratory data, operation method, surgical and postoperative variables. RESULTS: A total of 72 patients were enrolled in the study. 42 patients were categorized into the group with NIMV < 2, while 30 patients were divided into the group with NIMV ≥ 2. The group with NIMV ≥ 2 demonstrated a significant correlation with special segments, involved multiple segments and diameter of the hemangiomas (P < 0.01). And the perioperative variables including the extent of resection, operative time, blood loss, Pringle maneuver times, postoperative stay, drainage tube duration, and postoperative liver function (ALT, AST) also showed significant differences between the two groups (P < 0.05). Notably, NIMV ≥ 2 was identified as the most important independent risk factor for intraoperative blood loss ≥ 500 ml in laparoscopic surgery for hepatic hemangioma (P = 0.011). For NIMV ≥ 2, the independent risk factor was special segments in multivariate analysis (P = 0.000). CONCLUSION: The involvement of multiple major vessels (NIMV ≥ 2) was significantly associated with special segments, resulting in increased intraoperative blood loss, operation difficulty, and delayed postoperative recovery. Moreover, it was identified as the single independent risk factor with a considerable risk for increased blood loss during laparoscopic resection for hepatic hemangioma.

Surgical margin status outcome of intraoperative indocyanine green fluorescence-guided laparoscopic hepatectomy in liver malignancy: a systematic review and meta-analysis.

BACKGROUND: Hepatectomy stands as a curative management for liver cancer. The critical factor for minimizing recurrence rate and enhancing overall survival of liver malignancy is to attain a negative margin hepatic resection. Recently, Indocyanine green (ICG) fluorescence imaging has been proven implemental in aiding laparoscopic liver resection, enabling real-time tumor identification and precise liver segmentation. The purpose of this study is to conduct a systematic review and meta-analysis to ascertain whether ICG-guided laparoscopic hepatectomy yields a higher incidence of complete tumor eradication (R0) resections. METHODS: The search encompassed databases such as PubMed, Cochrane Library database, Scopus, ScienceDirect, and Ovid in April 2024, in strict adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies involving patients with malignant liver lesions who underwent ICG-guided laparoscopic hepatectomy and reported R0 resection outcomes were eligible for inclusion in this review. RESULTS: In a total of seven studies, involving 598 patients, were included in the meta-analysis. The ICG demonstrated a significantly elevated R0 resection rate compared to the non-ICG group [98.6% (359/364) vs. 93.1% (339/364), odds ratio (OR) = 3.76, 95% confidence intervals (CI) 1.45-9.51, P = 0.005]. Notably, no heterogeneity was observed (I2 = 0%, P = 0.5). However, the subtype analysis focusing on hepatocellular carcinoma [98.2% (165/168) vs. 93.6% (161/172), OR = 3.34, 95% CI 0.94-11.91, P = 0.06) and the evaluation of margin distance (4.96 ± 2.41 vs. 2.79 ± 1.92 millimeters, weighted mean difference = 1.26, 95% CI -1.8-4.32, P = 0.42) revealed no apparent differences. Additionally, the incidence of overall postoperative complications was comparable between both groups, 27.6% (66/239) in the ICG group and 25.4% (75/295) in the non-ICG group (OR = 0.96, 95% CI 0.53-1.76, P = 0.9). No disparities were identified in operative time, intraoperative blood loss, postoperative blood transfusion, and length of hospital stay after the surgery. CONCLUSIONS: The implementation of ICG-guided laparoscopic hepatectomy can be undertaken with confidence, as it does not compromise either intraoperative or postoperative events. Furthermore, the ICG-guided approach is beneficial to achieving a complete eradication of the tumor during hepatic resection. TRIAL REGISTRATION: PROSPERO registration number CRD42023446440.

Stereotactic Body Radiotherapy and Liver Transplant for Liver Cancer: A Nonrandomized Controlled Trial.

Importance: Whether stereotactic body radiotherapy (SBRT) as a bridge to liver transplant for hepatocellular carcinoma (HCC) is effective and safe is still unknown. Objective: To investigate the feasibility of SBRT before deceased donor liver transplant (DDLT) for previously untreated unresectable HCC. Design, Setting, and Participants: In this phase 2 nonrandomized controlled trial conducted between June 1, 2015, and October 18, 2019, 32 eligible patients within UCSF (University of California, San Francisco) criteria underwent dual-tracer (18F-fluorodeoxyglucose and 11C-acetate [ACC]) positron emission tomography with computed tomography (PET-CT) and magnetic resonance imaging (MRI) with gadoxetate followed by SBRT of 35 to 50 Gy in 5 fractions, and the same imaging afterward while awaiting DDLT. Statistical analysis was performed on an intention-to-treat basis between October 1 and 31, 2023. Intervention: Patients received SBRT followed by DDLT when matched deceased donor grafts were available. Main Outcomes and Measures: Coprimary end points were progression-free survival (PFS) and objective response rates (ORRs) by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), modified RECIST (mRECIST), and PET Response Criteria in Solid Tumors (PERCIST). Secondary end points were local control rate, overall survival (OS), and safety. Results: A total of 32 patients (median age, 59 years [IQR, 54-63 years]; 22 men [68.8%]) with 56 lesions received SBRT. After a median follow-up of 74.6 months (IQR, 40.1-102.9 months), the median PFS was 17.6 months (95% CI, 6.6-28.6 months), and the median OS was 60.5 months (95% CI, 29.7-91.2 months). The 5-year PFS was 39.9% (95% CI, 19.9%-59.9%), and the 5-year OS was 51.3% (95% CI, 31.7%-70.9%). In terms of number of patients, ORRs were 62.5% ([n = 20] 95% CI, 54.2%-68.7%) by RECIST 1.1, 71.9% ([n = 23] 95% CI, 63.7%-79.0%) by mRECIST, and 78.1% ([n = 25] 95% CI, 73.2%-86.7%) by PERCIST. In terms of number of lesions, ORRs were 75.0% ([n = 42] 95% CI, 61.6%-80.8%) by RECIST 1.1, 83.9% ([n = 47] 95% CI, 74.7%-90.6%) by mRECIST, and 87.5% ([n = 49] 95% CI, 81.3%-98.6%) by PERCIST. Twenty patients with 36 lesions received DDLT, of whom 15 patients (75.0%) with 21 lesions (58.3%) exhibited pathologic complete response. Multivariable analyses revealed that pretreatment metabolic tumor volume (MTV) based on ACC (hazard ratio [HR], 1.06 [95% CI, 1.01-1.10]; P = .01) and complete metabolic response (CMR) by PERCIST (HR, 0.31 [95% CI, 0.10-0.96]; P = .04) were associated with PFS, while pretreatment MTV based on ACC (HR, 1.07 [95% CI, 1.03-1.16]; P = .01), total lesion activity based on ACC (HR, 1.01 [95% CI, 1.00-1.02]; P = .02), and CMR by PERCIST (HR, 0.21 [95% CI, 0.07-0.73]; P = .01) were associated with OS. Toxic effects associated with SBRT were reported for 9 patients (28.1%), with 1 grade 3 event. Conclusions and Relevance: This phase 2 nonrandomized controlled trial demonstrated promising survival and safety outcomes of SBRT before DDLT for unresectable HCC. Future randomized clinical trials are warranted.

New horizons in liver transplantation for hepatocellular carcinoma.

Primary liver cancer was the third most common cause of death due to cancer worldwide in 2020. As the predominant type, hepatocellular carcinoma (HCC) represents the overwhelming majority of newly diagnosed primary liver tumours. Liver transplantation remains the treatment of choice for a cure in otherwise unresectable HCC. For nearly thirty years, the Milan and Barcelona Clinic Liver Cancer (BCLC) criteria have guided physicians' clinical decision-making for selection of liver transplant candidates in the treatment of HCC. More recently, studies have demonstrated survival benefit for patients transplanted beyond Milan criteria. This remains an area of active research and includes advancements in local-regional therapies and their role in downstaging tumours to within transplant criteria as a bridge to transplant. Other advancements on the horizon include the identification of tumour biomarkers that may lead to earlier diagnosis and more accurate prediction of prognosis and risk of recurrence, as well as new neoadjuvant therapies and post-transplant immunosuppression regimens that may allow for further expansion of transplant eligibility criteria. Additionally, several recent studies have investigated the potential survival benefit of combination therapy using local-regional intervention with systemic immunotherapy to downstage otherwise unresectable disease that is beyond Milan criteria. Liver transplantation will continue to play an important role in the treatment of HCC for the foreseeable future and based on currently available evidence, both local-regional therapies and immunomodulation in combination are poised to change the landscape of liver transplantation for HCC as we currently know it.

Inflammatory myofibroblastic tumours of the liver - a systematic review.

BACKGROUND: Hepatic inflammatory myofibroblastic tumours (HIMTs) are rare and poorly described in the literature. Most publications are single patient case reports and lack detailed reporting on characteristics, management, and outcomes. This systematic review aimed to assess the demography, clinical presentation, typical imaging features, histopathology, treatment, and outcomes of patients presenting with HIMTs. METHODS: A systematic literature search was performed in MEDLINE (PubMed), EMBASE (Scopus), JSTOR, Cochrane CENTRAL (Cochrane Library), and the databases included in the Web of Science for studies published between 1940 and 2023 on HIMTs, including its reported synonyms. Case series or cohort studies that reported on the management and outcomes of at least four patients with histologically confirmed HIMTs were included in the analysis. RESULTS: After screening 4553 publications, 22 articles including a total of 440 patients with confirmed HIMTs were eligible for inclusion. The average age was 53.4 years (range 42.0-65.0) with a male to female ratio of 1.7:1. Abdominal pain, discomfort, fever, and loss of weight were the most common presenting symptoms. Surgical resection is the standard of care for HIMTs and is associated with low mortality of 3.4% and low disease recurrence. CONCLUSION: HIMT is a disease more often affecting middle-aged males. The lesions are typically solitary with low recurrence after treatment. The relative roles of surgical versus medical treatment remain unclear. Differences in clinical presentation, histopathology, and treatment of HIMTs compared to inflammatory myofibroblastic tumour (IMT) at extrahepatic sites could challenge the current view of IMT as a single pathological entity.

Deep learning-based pathway-centric approach to characterize recurrent hepatocellular carcinoma after liver transplantation.

BACKGROUND: Liver transplantation (LT) is offered as a cure for Hepatocellular carcinoma (HCC), however 15-20% develop recurrence post-transplant which tends to be aggressive. In this study, we examined the transcriptome profiles of patients with recurrent HCC to identify differentially expressed genes (DEGs), the involved pathways, biological functions, and potential gene signatures of recurrent HCC post-transplant using deep machine learning (ML) methodology. MATERIALS AND METHODS: We analyzed the transcriptomic profiles of primary and recurrent tumor samples from 7 pairs of patients who underwent LT. Following differential gene expression analysis, we performed pathway enrichment, gene ontology (GO) analyses and protein-protein interactions (PPIs) with top 10 hub gene networks. We also predicted the landscape of infiltrating immune cells using Cibersortx. We next develop pathway and GO term-based deep learning models leveraging primary tissue gene expression data from The Cancer Genome Atlas (TCGA) to identify gene signatures in recurrent HCC. RESULTS: The PI3K/Akt signaling pathway and cytokine-mediated signaling pathway were particularly activated in HCC recurrence. The recurrent tumors exhibited upregulation of an immune-escape related gene, CD274, in the top 10 hub gene analysis. Significantly higher infiltration of monocytes and lower M1 macrophages were found in recurrent HCC tumors. Our deep learning approach identified a 20-gene signature in recurrent HCC. Amongst the 20 genes, through multiple analysis, IL6 was found to be significantly associated with HCC recurrence. CONCLUSION: Our deep learning approach identified PI3K/Akt signaling as potentially regulating cytokine-mediated functions and the expression of immune escape genes, leading to alterations in the pattern of immune cell infiltration. In conclusion, IL6 was identified to play an important role in HCC recurrence.