Liver Resection Criteria for Patients with Hepatocellular Carcinoma and Multiple Tumors Based on Total Tumor Volume.

BACKGROUND: In many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits. METHODS: We reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan-Meier method. RESULTS: In all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria. CONCLUSION: Patients with TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria.

Optimal treatment strategy and prognostic analysis of salvage liver transplantation for patients with early hepatocellular carcinoma recurrence after hepatectomy.

AIM: We aimed to investigate the prognostic factors for salvage liver transplant in patients with early hepatocellular carcinoma recurrence after hepatectomy. METHODS: This retrospective analysis included 53 patients who underwent salvage living-donor liver transplantation between January 2007 and January 2018. There were 24 and 29 patients in the early (recurrence ≤24 months after primary liver resection) and the late recurrence groups, respectively. RESULTS: In the multivariate Cox regression model, pre-liver transplant downstaging therapy, early recurrence (ER) after primary liver resection , and recurrence-to-liver-transplant ≥12 months were independent risks to predict recurrent hepatocellular carcinoma recurrence after salvage living-donor liver transplantation. Compared with the late recurrence group, the ER group showed lower disease-free survival rates (p < 0.001); however, the overall survival rates did not differ between the two groups (p = 0.355). The 1-, 3-, and 5-year disease-free survival rates were 83.3%, 70.6%, and 66.2%, and 96.0%, 91.6%, and 91.6% in the early and late recurrence groups, respectively. When stratified by recurrence-to-liver transplant time and pre-liver transplant downstaging therapy in the ER group, disease-free survival and overall survival rates were significantly different. CONCLUSION: ER after primary liver resection with advanced tumor status and a longer period of recurrence-to-liver-transplant (≥12 months) have a negative impact on salvage liver transplant. Our findings provide novel recommendations for treatment strategies and eligibility for salvage liver transplant candidates.

Concurrent Atezolizumab Plus Bevacizumab and High-Dose External Beam Radiotherapy for Highly Advanced Hepatocellular Carcinoma.

BACKGROUND: Atezolizumab plus bevacizumab (atezo-bev) has been recommended for advanced hepatocellular carcinoma (HCC). High-dose external beam radiotherapy (RT) is recognized for its excellent local tumor control. The efficacy and safety of concurrent atezo-bev with RT for highly advanced HCC has been minimally explored. METHODS: In this preliminary retrospective study, we assessed patients with highly advanced HCC, characterized by Vp4 portal vein thrombosis or tumors exceeding 50% of liver volume, who received concurrent atezo-bev and RT (group A). Group A included 13 patients who received proton radiation at a dose of 72.6 GyE in 22 fractions, and one patient who received photon radiation at a dose of 54 Gy in 18 fractions. This group was compared with 34 similar patients treated atezo-bev alone as a control (group B). The primary objectives were to evaluate the objective response rate (ORR), overall survival (OS), and safety. RESULTS: Baseline characteristics were similar between groups, except for a higher incidence of Vp4 portal vein thrombosis in group A (78.6% vs. 21.4%, P = .05). Group A achieved a higher ORR (50.0% vs. 11.8%, P < .01) and a longer OS (not reached vs. 5.5 months, P = .01) after a median follow-up of 5.2 months. Multivariate analysis indicated that concurrent RT independently favored longer OS (hazard ratio: 0.18; 95% CI, 0.05-0.63, P < .01). Group A did not increase any grade adverse events (78.6% vs. 58.8%, P = .19) or severe adverse events of grade ≥ 3 (14.3% vs. 14.7%, P = .97) compared to group B. CONCLUSIONS: The concurrent high-dose external beam radiotherapy appears to safely enhance the effectiveness of atezolizumab plus bevacizumab for highly advanced patients with HCC. Further studies are warranted to confirm these findings.

Recurrence Pattern Is an Independent Surgical Prognostic Factor for Long-Term Oncological Outcomes in Patients with Hepatocellular Carcinoma.

BACKGROUND: The perioperative outcomes of a partial hepatectomy for hepatocellular carcinoma (HCC) have improved. However, high recurrence rates after a curative hepatectomy for HCC is still an issue. This study aimed to analyze the difference between various recurrence patterns. METHODS: We retrospectively reviewed 754 patients with HCC who underwent a curative hepatectomy between January 2012 and March 2021. Patients with recurrent events were categorized into three types: regional recurrence (type I), multiple intrahepatic recurrence (type II), or presence of any distant metastasis (type III). RESULTS: The median follow-up period was 51.2 months. Regarding recurrence, 375 (49.7%) patients developed recurrence, with 244 (32.4%), 51 (6.8%), and 80 (10.6%) patients having type I, II, and III recurrence, respectively. Type III recurrence appeared to be more common in male patients and those with major liver resection, vascular invasion, a large tumor size (>5 cm), a higher tumor grade, and higher levels of AST and AFP (p < 0.05). Patients who had distant metastasis at recurrence had the shortest recurrence time and the worst overall survival (p < 0.001 and p < 0.001). CONCLUSIONS: our study demonstrated that recurrence with distant metastasis occurred earliest and had the worst outcome compared to regional or multiple intrahepatic recurrences.

The effect of a helmet type, home-use low-level light therapy device for chemotherapy-induced alopecia: study protocol for a randomized controlled trial.

BACKGROUND: Alopecia is one of the most common adverse effects of chemotherapy. It reduces the patient's self-esteem and quality of life and the effect of therapy. Scalp cooling is the only verified current method for prevention but success is not guaranteed, particularly after receiving anthracycline-based combinations. Low-level light therapy has been clinically proven to inhibit the progress of androgenic alopecia. A previous study using human subjects shows limited benefits for low-level light therapy for patients who suffer chemotherapy-induced alopecia but an increase in the number of probes and the optimization of light sources may improve the efficacy. This study determines the efficacy of low-level light therapy for the prevention of chemotherapy-induced hair loss for patients with breast cancer using a randomized controlled trial. METHODS: One hundred six eligible breast cancer patients were randomly distributed into a low-level light therapy group and a control group, after receiving chemotherapy. Subjects in the low-level light therapy group received 12 courses of intervention within 4 weeks. Subjects in the control group received no intervention but were closely monitored. The primary outcome is measured as the difference in the hair count in a target area between the baseline and at the end of week 4, as measured using a phototrichogram (Sentra scalp analyzer). The secondary outcomes include the change in hair count at the end of week 1, week 2, and week 3 and hair width at the end of week 1, week 2, week 3, and week 4, as measured using a phototrichogram, and the change in distress, the quality of life, and self-esteem due to chemotherapy-induced alopecia, at the end of week 4, as measured using a questionnaire. DISCUSSION: This study improves cancer patients' quality of life and provides clinical evidence. TRIAL REGISTRATION: Registered at ClinicalTrials.gov- NCT05397457 on 1 June 2022.

A combination of locoregional treatment with systemic therapy after atezolizumab plus bevacizumab failure for unresectable hepatocellular carcinoma provides survival benefit.

Atezolizumab plus bevacizumab (A+B) is used to treat unresectable hepatocellular carcinoma (HCC), but the optimal rescue therapy after A+B remains unclear. Combining locoregional therapy (LRT) with systemic treatment has been shown to improve tumor control, but the role in patients who fail A+B is unknown. We retrospectively enrolled patients who experienced radiological progression after A+B. Objective response rate (ORR), disease control rate (DCR), post progression survival (PPS), and secondary progression-free survival (PFS) were evaluated by modified RECIST. Inverse probability weighting (IPW) was used to balance baseline clinical features. A total of 61 patients were enrolled with a median age of 60.7 years, 83.6% male, 88.5% viral hepatitis-related, and 60.7% without prior systemic treatment before A+B. Patients receiving sequential therapies had significantly longer PPS than supportive care (10.5 vs. 2.3 months, P<0.0001). Among 37 patients received sequential systemic treatment, 18 received combined LRT. The median follow-up after post A+B failure was 6.6 months. The combined LRT group had higher ORR (27.8 vs. 0%, P=0.0197) and DCR (72.2 vs. 26.3%, P=0.0052) than systemic alone group. The median PPS and secondary PFS were significantly longer in combined LRT group (PPS: 12.2 vs. 5.8 months, P=0.0070; PFS: 5.0 vs. 2.6 months, P=0.0134) than systemic alone group. After IPW analysis, patients with combined LRT had superior PPS and secondary PFS. The incidence rates of AEs were higher in LRT combination compared to systemic alone (any grade AEs: 94.4 vs. 63.2%, P=0.0422; severe AEs: 33.3 vs. 5.3%, P=0.0422). No significant albumin-bilirubin index changed in the first 3 months in combined LRT group (0.966 [0.647-1.443], P=0.867) though a trend of deterioration in systemic alone group. In conclusion, sequential systemic therapy provides survival benefits after A+B failure. Furthermore, combining LRT with systemic treatment could provide better tumor responses and survival benefits with acceptable toxicity than systemic therapy alone.

Adding nutritional status to the original BCLC stage improves mortality prediction for hepatocellular carcinoma patients in HBV-endemic regions.

Hepatocellular carcinoma (HCC) is associated with high mortality, especially in Asian populations where chronic HBV infection is a major cause. Accurate prediction of mortality can assist clinical decision-making. We aim to (i) compare the predicting ability of Barcelona Clinic Liver Cancer classification (BCLC) stage, neutrophil-to-lymphocyte ratio (NLR), and Albumin-Bilirubin (ALBI) score in predicting short-term mortality (one- and two-year) and (ii) develop a novel model with improved accuracy compared to the conventional models. This study enrolled 298 consecutive HCC patients from our hepatology department. The prognostic values for mortality were assessed by area under the receiver operating characteristic curve (AUROC) analysis. A novel model was established and internally validated using 5-fold cross-validation, followed by external validation in a cohort of 100 patients. The primary etiology of cirrhosis was hepatitis B virus (HBV), with 81.2% of HCC patients having preserved liver function. Significant differences were observed in hemoglobin (Hb) and serum albumin levels, which reflect patients' nutrition status, between patients who survived for one year and those who died. BCLC exhibited superior predictive accuracy compared to NLR but had borderline superiority to the ALBI score. Therefore, a novel model incorporating BCLC, Hb, and serum albumin was developed, internally and externally validated, as well as subgroup sensitivity analysis. The model exhibited significantly higher predictive accuracy for one- and two-year mortality than conventional prognostic predictors, with AUROC values of 0.841 and 0.805, respectively. The novel "BCLC-Nutrition Model", which incorporates BCLC, Hb, and serum albumin, may provide improved predictive accuracy for short-term mortality in HCC patients compared to commonly used prognostic scores. This emphasizes the importance of nutrition in the management of HCC patients.

Bioinspired, Non-Enzymatic, Aqueous Synthesis of Size-Tunable CdS Quantum Dots for Sustainable Optoelectronic Applications.

The enzymatic production of hydrogen sulfide (H2S) from cysteine in various metabolic processes has been exploited as an intrinsically "green" and sustainable mode for the aqueous biomineralization of functional metal sulfide quantum dots (QDs). Yet, the reliance on proteinaceous enzymes tends to limit the efficacy of the synthesis to physiological temperature and pH, with implications for QD functionality, stability, and tunability (i.e., particle size and composition). Inspired by a secondary non-enzymatic biochemical cycle that is responsible for basal H2S production in mammalian systems, we establish how iron(III)- and vitamin B6 (pyridoxal phosphate, PLP)-catalyzed decomposition of cysteine can be harnessed for the aqueous synthesis of size-tunable QDs, demonstrated here for CdS, within an expanded temperature, pH, and compositional space. Rates of H2S production by this non-enzymatic biochemical process are sufficient for the nucleation and growth of CdS QDs within buffered solutions of cadmium acetate. Ultimately, the simplicity, demonstrated robustness, and tunability of the previously unexploited H2S-producing biochemical cycle help establish its promise as a versatile platform for the benign, sustainable synthesis of an even wider range of functional metal sulfide nanomaterials for optoelectronic applications.

Daily Aspirin Reduced the Incidence of Hepatocellular Carcinoma and Overall Mortality in Patients with Cirrhosis.

BACKGROUND: Cirrhosis is the primary risk factor for hepatocellular carcinoma (HCC) and gastrointestinal bleeding (GI). We aimed to assess the efficacy and safety of daily aspirin on HCC occurrence, overall survival, and GI bleeding in cirrhotic patients. METHODS: A total of 35,898 eligible cases were enrolled for analyses from an initial 40,603 cirrhotic patients without tumor history. Patients continuously treated with aspirin for at least 84 days were in the therapy group, whereas those without treatment were controls. A 1:2 propensity score matching by age, sex, comorbidities, drugs, and significant clinical laboratory tests with covariate assessment was used. RESULTS: Multivariable regression analyses revealed that daily aspirin use was independently associated with a reduced risk of HCC (three-year HR 0.57; 95% CI 0.37-0.87; p = 0.0091; five-year HR 0.63, 95% CI 0.45-0.88; p = 0.0072) inversely correlated with the treatment duration [3-12 months: HR 0.88 (95% CI 0.58-1.34); 12-36 months: HR 0.56 (0.31-0.99); and ≥ 36 months: HR 0.37 (0.18-0.76)]. Overall mortality rates were significantly lower among aspirin users compared with untreated controls [three-year HR 0.43 (0.33-0.57); five-year HR 0.51 (0.42-0.63)]. Consistent results were obtained when the laboratory data were included in the propensity score for matching. CONCLUSIONS: Long-term aspirin use significantly reduced the incidence of HCC and overall mortality without increasing gastrointestinal bleeding in cirrhotic patients.

Significance of Physical Status and Liver Function Reserve for Outcome of Patients with Advanced Hepatocellular Carcinoma Receiving Lenvatinib Treatment.

Background: Tyrosine kinase inhibitors (TKIs) remain the primary therapeutic option for patients with advanced-stage hepatocellular carcinoma (HCC). However, the selection of a suitable TKI is an issue in real-world clinical practice. Thus, this study aimed to identify patients most likely to benefit from lenvatinib treatment. Methods: A retrospective review of 143 patients with unresectable advanced-stage HCC treated with lenvatinib between January 2020 and December 2021 was performed. Outcomes related to lenvatinib treatment were measured, and the clinical parameters affecting prognosis were analyzed. Results: Overall, the median time of progression-free survival (PFS) and overall survival (OS) were 7.1 months and 17.7 months, respectively. Prognostic analyses found that Child-Pugh score > 5 (hazard ratio [HR] = 2.43, 95% confidence interval [CI] = 1.55-3.80, p = 0.001) was a significant factor affecting the PFS of HCC after lenvatinib treatment. Child-Pugh score > 5 (HR = 2.12, 95% CI = 1.20-3.74, p = 0.009), body weight ≥ 60 kg (HR = 0.54, 95% CI = 0.32-0.90, p = 0.020), and additional trans-arterial chemoembolization (TACE) treatment (HR = 0.38, 95% CI = 0.21-0.70, p = 0.003) were significant prognostic factors for OS. However, early α-fetoprotein reduction was not significantly correlated with patient outcomes. Additionally, patients with pre-treatment neutrophil-lymphocyte ratio > 4.07 showed a significant worse PFS and OS than other patients. Conclusion: The outcome of patients with advanced-stage HCC remains poor. However, the host condition, including good physical status and better functional liver preservation, largely affected the outcome of patients receiving lenvatinib treatment. Moreover, additional locoregional therapy for intrahepatic HCC, other than TKI treatment, can be considered in certain patients to achieve a favorable outcome.

Modified preoperative score to predict disease-free survival for hepatocellular carcinoma patients with surgical resections.

BACKGROUND: No prognostic models specific to hepatocellular carcinoma patients receiving surgical resection have been considered strong and convincing enough for survival prediction thus far, and there are no models including only preoperative predictors. We derived a nomogram to predict disease-free survival in a previous study. AIM: To simplify our score and compare research outcomes among other scoring systems. METHODS: We retrospectively reviewed data from 1106 patients with hepatocellular carcinoma who underwent liver resection at the Linkou Chang Gung Memorial Hospital between April 2003 and December 2012. Multivariate analyses were conducted to identify the significant survival predictors. Homogeneity, Harrell's C-index, and Akaike information criterion were compared between our score, AJCC 8th edition, Tokyo score, and Taipei Integrated Scoring System (TTV-CTP-AFP model). RESULTS: Among the 1106 patients, 731 (66.1%) had tumor recurrence at a median follow-up of 83.9 mo. Five risk factors were identified: platelet count, albumin level, indocyanine green retention rate, multiplicity, and radiologic total tumor volume. Patients were divided into three risk groups, and the 5-year survival rates were 61.7%, 39%, and 25.7%, respectively. The C-index was 0.617, which was higher than the Tokyo score (0.613) and the Taipei Integrated Scoring System (0.562) and equal to the value of the AJCC 8th edition (0.617). CONCLUSION: The modified score provides an easier method to predict survival. Appropriate treatment can be planned preoperatively by dividing patients into risk groups.

Differential Response to Sorafenib Administration for Advanced Hepatocellular Carcinoma.

Sorafenib has been used to treat advanced hepatocellular carcinoma (aHCC). However, there is no evidence for a response of different target lesions to sorafenib administration. Therefore, we aimed to evaluate the effect of sorafenib on various aHCC target lesions. The outcomes of sorafenib treatment on aHCC, i.e., treatment response for all Child A status patients receiving the drug, were analyzed. Of 377 aHCC patients, 73 (19.3%) had complete/partial response to sorafenib, while 134 (35.4%) and 171 (45.2) had a stable or progressive disease, respectively, in the first six months. Of the evaluated metastatic lesions, 149 (39.4%), 48 (12.7%), 123 (32.5%), 98 (25.9%), 83 (22.0%), and 45 (11.9%) were present in liver, bone, lung, portal/hepatic vein thrombus, lymph nodes, and peritoneum, respectively. The overall survival and duration of treatment were 16.9 ± 18.3 and 8.1 ± 10.5 months (with median times of 11.4 and 4.6, respectively). Our analysis showed poor outcomes in macroscopic venous thrombus and bone, higher AFP, and multiple target lesions. ALBI grade A had a better outcome. Sorafenib administration showed good treatment outcomes in selected situations. PD patients with thrombus or multiple metastases should be considered for sorafenib second-line treatment. The ALBI liver function test should be selected as a treatment criterion.

Recurrence Patterns After Hepatectomy With Very Narrow Resection Margins for Hepatocellular Carcinoma.

Background: The extent of hepatic resection In HCC depends on the remnant liver reserve or the proximity of the tumor to major vessels. In this study, we evaluated the effects of very close resection margins on postoperative recurrence. Methods: Consecutive LR for HCC between 2003 and 2009 were studied. Patients were divided into groups with very narrow (≤1 mm) or wider (>1 mm) resection margins. Propensity score matching (PSM) was used to balance demographic, surgical, and pathological factors. Results: 983 patients were included in the study. After PSM, 173 patients were analyzed in each group. 5-year tumor recurrence and survival rates were comparable. Most recurrences were multiple intrahepatic. Section margin recurrences were similar in both groups. By multivariate analysis, tumor size >5 cm was associated with a very narrow resection margin, whereas low platelet count and tumor macrovascular invasion were significant factors related to tumor recurrence. Conclusions: Patients with very narrow surgical margins showed outcomes comparable to those with wider surgical margins. Most recurrences were multiple intrahepatic and associated with the degree of portal hypertension and adverse tumor biology. Although wide surgical margins should be aimed whenever possible, a narrow tumor-free margin resection still represents an effective therapeutic strategy.

Individualized Selection Criteria Based on Tumor Burden in Future Remnant Liver for Staged Hepatectomy of Advanced CRLM: Conventional TSH or ALPPS.

Staged hepatectomy is a promising strategy for curative resection of advanced colorectal liver metastasis (CRLM) to prevent inadequate future remnant liver (FRL). However, the selection criteria for conventional two-stage hepatectomy (cTSH) and associating liver partitioning and portal vein ligation for staged hepatectomy (ALPPS) remain unclear. This study aimed to propose a selection criterion for determining the optimal staged hepatectomy for patients with advanced CRLM. A selection criterion based on the degree of metastatic tumors within the FRL was established to determine staged hepatectomy approaches. Generally, ALPPS is recommended for patients with ≤3 metastatic nodules and whose nodules do not measure >3 cm in the FRL. cTSH is performed for patients whose tumor burden in FRL beyond the selection criteria. Data of 37 patients who underwent staged hepatectomy and curative intent of CRLM were analyzed. The clinical characteristics and outcomes of the two approaches were compared. Overall, cTSH and ALPPS were performed for 27 (73.0%) and 10 (27.0%) patients, respectively. Of those, 20 patients in the cTSH group and all patients in the ALPPS group had completed staged hepatectomy. The 1-, 3-, and 5-year survival rates were 91.6%, 62.4%, and 45.4% for all patients, respectively. The outcomes of patients who had successfully completed the staged hepatectomy were significantly better than those of other patients who failed to achieve staged hepatectomy. However, no significant difference was observed in the overall survival of patients who underwent staged hepatectomy between the two groups, but those in the ALPPS group had 100% survival at the end of this study. The individualized selection criteria based on tumor burden in the FRL that could balance the operative risk and oncologic outcome appear to be a promising strategy for achieving complete staged hepatectomy in patients with advanced CRLM.

Living-Donor Liver Transplantation for Hepatocellular Carcinoma: Impact of the MELD Score and Predictive Value of NLR on Survival.

Background: Patients with hepatocellular carcinoma (HCC) tend to be referred for liver transplantation (LT) at an early stage of cirrhosis, with lower pre-LT Model of End-Stage Liver Disease (MELD) scores. We investigated the impact of high MELD scores on post-LT outcomes in patients with HCC and validated the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR). Patients and Method: This retrospective single-center cohort study enrolled 230 patients with HCC who underwent LDLT from 2004−2019 in our institute. We defined a high MELD score as ≥20. Results: The MELD < 20 and MELD ≥ 20 groups comprised 205 and 25 cases, respectively. Although there was no significant difference in disease-free survival between the two groups (p = 0.629), the incidence of septic shock (p = 0.019) was significantly higher in the high MELD group. The one-, three-, and five-year overall survival rates were not significantly different between the two groups (p = 0.056). In univariate analysis, a high pre-LT NLR was associated with poorer survival in the high MELD group (p = 0.029, hazard ratio [HR]: 1.07, 90% confidence interval [CI]: 1.02−1.13). NLR cut-off values of ≥10.7 and <10.7 were predictive of mortality, with an AUC of 0.705 (90% CI: 0.532−0.879). The one-, three-, and five-year post-LT survival rates were significantly higher among the recipients with an NLR < 10.7 than those with an NLR ≥ 10.7 (p = 0.005). Conclusions: Pre-LT MELD score ≥ 20 was associated with a higher risk of developing post-LT septic shock and mortality. The pre-LT serum NLR is a useful predictive factor for clinical outcomes in patients with HCC with high MELD scores.

Reappraisal of the Role of Alkaline Phosphatase in Hepatocellular Carcinoma.

Background: Alkaline phosphatase (ALP) is a marker of liver function and is associated with biliary tract disease. It was reported as a prognostic factor for hepatocellular carcinoma (HCC). The genetic expression in tumor-tissue microarrays and the perioperative serologic changes in ALP have never been studied for their correlation with HCC prognosis. Methods: The genetic expression of ALP isoforms (placental (ALPP), intestinal (ALPI) and bone/kidney/liver (ALPL)) was analyzed in tumor and non-cancerous areas in 38 patients with HCC after partial hepatectomy. The perioperative change in ALP was further analyzed in a cohort containing 525 patients with HCC to correlate it with oncologic outcomes. A total of 43 HCC patients were enrolled for a volumetry study after major and minor hepatectomy. Results: The genetic expression of the bone/kidney/liver isoform was specifically and significantly higher in non-cancerous areas than in tumors. Patients with HCC with a higher ALP (>81 U/dL) had significantly more major hepatectomies, vascular invasion, and recurrence. Cox regression analysis showed that gender, major hepatectomies, the presence of satellite lesions, higher grades (III or IV) and perioperative changes in liver function tests were independent prognostic factors for recurrence-free survival, and a postoperative increase in the ALP ratio at postoperative day (POD) 7 vs. POD 0 > 1.46 should be emphasized. A liver regeneration rate more than 1.8 and correlation analysis revealed that the ALP level at POD 7 and 30 was significantly higher and correlated with remnant liver growth. Conclusions: This study demonstrated that the perioperative ALP change was an independent prognostic factor for HCC after partial hepatectomies, and the elevation of ALP represented a functional biomarker for the liver but not an HCC biomarker. The higher regeneration capacity was possibly associated with the elevation of ALP after operation.

Rare Occurrence of Aristolochic Acid Mutational Signatures in Oro-Gastrointestinal Tract Cancers.

BACKGROUND: Aristolochic acids (AAs) are potent mutagens commonly found in herbal plant-based remedies widely used throughout Asian countries. PATIENTS AND METHODS: To understand whether AA is involved in the tumorigenesis of the oro-gastrointestinal tract, we used whole-exome sequencing to profile 54 cases of four distinct types of oro-gastrointestinal tract cancer (OGITC) from Taiwan. RESULTS: A diverse landscape of mutational signatures including those from DNA mismatch repair and reactive oxygen species was observed. APOBEC mutational signatures were observed in 60% of oral squamous cell carcinomas. Only one sample harbored AA mutational signatures, contradictory to prior reports of cancers from Taiwan. The metabolism of AA in the liver and urinary tract, transient exposure time, and high cell turnover rates at OGITC sites may explain our findings. CONCLUSION: AA signatures in OGITCs are rare and unlikely to be a major contributing factor in oro-gastrointestinal tract tumorigenesis.

Preferred Treatment with Curative Intent for Left Lateral Segment Early Hepatocellular Carcinoma under the Era of Minimal Invasive Surgery.

BACKGROUND: Hepatocellular carcinoma (HCC) occurring at the left lateral segment (LLS) is relatively susceptible to treatment with curative intent in terms of tumor location. However, outcomes might vary depending on the selection of treatment modalities. This study aimed to analyze patients who had undergone curative treatment for early HCC at LLS. METHODS: A retrospective analysis of 179 patients who underwent curative treatment for early HCC at LLS was performed. Patients were grouped based on treatment modalities, including radiofrequency ablation (RFA) and liver resection (LR). The long-term outcomes of the two groups were compared. Additionally, the impact of the LR approach on patient outcomes was analyzed. RESULTS: Among these patients, 60 received RFA and 119 underwent LR as primary treatment with curative intent. During follow-up, a significantly higher incidence of HCC recurrence was observed in the RFA group (37/60, 61.7%) than in the LR group (45/119, 37.8%) (p = 0.0025). The median time of HCC recurrence was 10.8 (range: 1.1-60.9 months) and 17.6 (range: 2.4-94.8 months) months in the RFA and LR groups, respectively. In addition, multivariate analysis showed that liver cirrhosis, multiple tumors, and RFA treatment were significant risk factors for HCC recurrence. The 1-, 2-, and 5-year overall survival rates in the RFA and LR groups were 96.4%, 92.2%, and 71.5% versus 97.3%, 93.6%, and 87.7%, respectively. (p = 0.047). Moreover, outcomes related to LR were comparable between laparoscopic and conventional open methods. The 1-, 2-, and 5-year recurrence free survival rates in the laparoscopic (n = 37) and conventional open (n = 82) LR groups were 94.1%, 82.0%, and 66.9% versus 86.1%, 74.6%, and 53.1%, respectively. (p = 0.506) Conclusion: Early HCC at LLS had satisfactory outcomes after curative treatment, in which LR seems to have a superior outcome, as compared to RFA treatment. Moreover, laparoscopic LR could be considered a preferential option in the era of minimally invasive surgery.

Reconstruction of Separated Intrahepatic Ducts Using the Cystic and Common Hepatic Ducts in Right-Lobe Living-Donor Liver Transplantation: Experiences of Surgical Techniques, Biliary Complications, and Outcomes in a Single Institution.

BACKGROUND Duct-to-duct biliary reconstruction has been increasingly used in living-donor liver transplantation. Information regarding dual duct-to-duct biliary anastomoses is limited. We present the largest case series to date on the use of the cystic and common hepatic ducts as dual-ductal anastomosis, along with long-term follow-up results. MATERIAL AND METHODS In this study, 740 patients underwent right-lobe living-donor liver transplantation; 56 of them were documented as dual-ductal anastomoses. We analyzed recipient and donor characteristics, surgical procedures, appearance of biliary complications, corresponding interventions, and long-term biliary outcomes. RESULTS Cystic and common hepatic ducts were utilized in 56 cases of dual-ductal biliary reconstruction, which we categorized into 2 types: A (78.6%), in which the right anterior intrahepatic duct was anastomosed to the common hepatic duct and the right posterior intrahepatic duct to the cystic duct; and B (21.4%), which was the reverse of A. After a median follow-up period of 46.4 months, 23 patients (41.1%) experienced complications, including biliary leakage and biliary stricture. However, after aggressive intervention (patent biliary anastomosis in most of them), 50 of 56 patients (89.3%) had patent biliary anastomosis and restored normal liver function at the end of follow-up. A small graft (graft-to-recipient weight ratio <0.9%) was the only predictor of biliary complications after multivariate analysis. CONCLUSIONS Dual-ductal biliary reconstruction in adult right-lobe living-donor liver transplantation is challenging but feasible. Our findings support the use of the cystic duct for reconstruction in selected patients. Good long-term results can be achieved with adequate management of patients with biliary complications.