Cumulative Recurrence-free Survival Rates Research Articles

Influence of intraoperative blood salvage and autotransfusion on tumor recurrence after deceased donor liver transplantation: a large nationwide cohort study.

The practice of intraoperative blood salvage and autotransfusion (IBSA) during deceased donor liver transplantation for hepatocellular carcinoma (HCC) can potentially reduce the need for allogeneic blood transfusion. However, implementing IBSA remains debatable due to concerns about its possible detrimental effects on oncologic recurrence. This study retrospectively enrolled nationwide recipients of deceased donor liver transplantation for HCC between 2015 and 2020. The focus was on comparing the cumulative recurrence rate and the recurrence-free survival rate. Propensity score matching was conducted repeatedly for further subgroup comparison. Recipients were categorized based on the Milan criteria, macrovascular invasion, and pretransplant α-Fetoprotein (AFP) level to identify subgroups at risk of HCC recurrence. A total of 6196 and 329 patients were enrolled in the non-IBSA and IBSA groups in this study. Multivariable competing risk regression analysis identified IBSA as independent risk factors for HCC recurrence ( P <0.05). Postmatching, the cumulative recurrence rate and recurrence-free survival rate revealed no significant difference in the IBSA group and non-IBSA group (22.4 vs. 16.5%, P =0.12; 60.3 vs. 60.9%, P =0.74). Recipients beyond Milan criteria had higher, albeit not significant, risk of HCC recurrence if receiving IBSA (33.4 vs. 22.5%, P =0.14). For recipients with macrovascular invasion, the risk of HCC recurrence has no significant difference between the two groups (32.2 vs. 21.3%, P =0.231). For recipients with an AFP level <20ng/ml, the risk of HCC recurrence was comparable in the IBSA group and the non-IBSA group (12.8 vs. 18.7%, P =0.99). Recipients with an AFP level ≥20ng/ml, the risk of HCC recurrence was significantly higher in the IBSA group. For those with an AFP level ≥400ng/ml, the impact of IBSA on the cumulative recurrence rate was even more pronounced (49.8 vs. 21.9%, P =0.011). IBSA does not appear to be associated with worse outcomes for recipients with HCC exceeding the Milan criteria or with macrovascular invasion. IBSA could be confidently applied for recipients with a pretransplant AFP level <20ng/ml. For recipients with AFP levels ≥20ng/ml, undertaking IBSA would increase the risk of HCC recurrence.

Long-Term Follow-Up of Ultrasound-Guided Glossopharyngeal Nerve Block Treatment for Glossopharyngeal Neuralgia: A Retrospective Clinical Study of 43 Cases.

Glossopharyngeal neuralgia (GPN) is a rare chronic neuropathic pain disorder that significantly impacts quality of life. Ultrasound-guided glossopharyngeal nerve blocks (UGPNB) have gained popularity due to their various advantages. However, there have been no studies reporting the long-term outcomes of UGPNB in a larger cohort of GPN patients. This study aims to evaluate the efficacy and safety of UGPNB in patients with GPN. We reviewed the electronic medical records of patients with GPN who received UGPNB at the Department of Pain Medicine of the First Medical Center, PLA General Hospital between June 1, 2011, and June 1, 2022. The effect of UGPNB was evaluated using the Barrow Neurological Institute (BNI) scale. Improvement was defined as a reduction in pain category by comparing pain categories before and after therapy. Recovery was defined as achieving BNI I after treatment. Patients who responded to treatment but then regressed to the category before therapy were considered to have experienced pain relapse. A total of 43 patients with GPN who received UGPNB were included in the analysis. At discharge, 35 (81.4%) patients experienced pain improvement after treatment, and among them, 13 (30.2%) patients achieved recovery. After discharge, 13 patients (37.1%) out of the 35 effective patients experienced pain relapse at different time intervals: 0.5, 0.7, 1, 1, 3, 3, 4, 12, 15, 36, 45, 63, and 96 months. The cumulative recurrence-free survival rates were 88.85% at month 1, 82.83% at month 3, 77.04% at month 12, 70.31% at month 36, and 54.66% at month 120. Among the 13 patients who experienced relapse, four patients received a second UGPNB treatment, and pain improved in two patients (50%). No severe adverse reactions were documented. UGPNB is an effective, repeatable, safe, and minimally invasive treatment for patients with GPN. It may be preferable to consider UGPNB before undergoing invasive intracranial surgery or neurodestructive methods.

Management of type 1 gastric neuroendocrine tumors: an 11-year retrospective single-center study

BackgroundType 1 gastric neuroendocrine tumors (NETs) are relatively rare to the extent that some physicians have little experience in diagnosing and treating them. The purpose of this study was to increase the understanding of the disease by analyzing and summarizing the management and prognoses of patients with type 1 gastric NETs at our center.MethodsThe data of 229 patients (59.4% female) with type 1 gastric NETs who were treated at our center during 2011–2022 were retrospectively analyzed.ResultsThe average patient age was 50.5 ± 10.8 years. Multiple tumors affected 72.5% of the patients; 66.4% of the tumors were < 1 cm, 69.4% were NET G1, and 2.2% were stage III-IV. A total of 76.9% of the patients had received endoscopic management, 60.7% had received traditional Chinese medicine treatment, 10.5% received somatostatin analogues treatment, and 6.6% underwent surgical resection. Seventy patients (41.2%) experienced the first recurrence after a median follow-up of 31 months (range: 2-122 months), and the median recurrence-free time was 43 months. The 1-, 2-, and 3-year cumulative recurrence-free survival rates were 71.8%, 56.8%, and 50.3%, respectively. During a median follow-up of 39 months (range: 2-132 months), one patient had bilateral pulmonary metastasis, and no disease-related deaths were observed.ConclusionType 1 gastric NETs have a high recurrence rate and a long disease course, underscoring the importance of long-term and comprehensive management.

Prognostic implications of alpha-fetoprotein and C-reactive protein elevation in hepatocellular carcinoma following resection (PACE): a large cohort study of 2770 patients

BackgroundRoutine clinical staging for hepatocellular carcinoma (HCC) incorporates liver function, general health, and tumor morphology. Further refinement of prognostic assessments and treatment decisions may benefit from the inclusion of tumor biological marker alpha-fetoprotein (AFP) and systemic inflammation indicator C-reactive protein (CRP).MethodsData from a multicenter cohort of 2770 HCC patients undergoing hepatectomy were analyzed. We developed the PACE risk score (Prognostic implications of AFP and CRP Elevation) after initially assessing preoperative AFP and CRP’s prognostic value. Subgroup analyzes were performed in BCLC cohorts A and B using multivariable Cox analysis to evaluate the prognostic stratification ability of the PACE risk score and its complementary utility for BCLC staging.ResultsPreoperative AFP ≥ 400ng/mL and CRP ≥ 10 mg/L emerged as independent predictors of poorer prognosis in HCC patients who underwent hepatectomy, leading to the creation of the PACE risk score. PACE risk score stratified patients into low, intermediate, and high-risk groups with cumulative 5-year overall (OS) and recurrence-free survival (RFS) rates of 59.6%/44.9%, 43.9%/38.4%, and 20.6%/18.0% respectively (all P < 0.001). Increased PACE risk scores correlated significantly with early recurrence and extrahepatic metastases frequency (all P < 0.001). The multivariable analysis identified intermediate and high-risk PACE scores as independently correlating with poor postoperative OS and RFS. Furthermore, the PACE risk score proficiently stratified the prognosis of BCLC stages A and B patients, with multivariable analyses demonstrating it as an independent prognostic determinant for both stages.ConclusionThe PACE risk score serves as an effective tool for postoperative risk stratification, potentially supplementing the BCLC staging system.

Decision to perform additional surgery after non-curative endoscopic submucosal dissection for gastric cancer based on the risk of lymph node metastasis: a long-term follow-up study.

Radical surgery after non-curative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) may be excessive, since only 5-10% of patients have lymph node metastasis (LNM). This study investigated the suitability of the eCura system for determining the need for radical surgery after non-curative ESD. We retrospectively investigated 343 patients who underwent non-curative ESD for EGC from 2006 to 2021 at a tertiary hospital in Korea. These patients were divided into surgery (n = 191) and observation (n = 152) groups based on whether they underwent additional surgery post-ESD. Each group was further classified into low-risk (eCura score 0-1), intermediate-risk (eCura score 2-4) and high-risk (eCura score 5-7). All patients were regularly followed-up at least annually after the initial treatment. The cumulative overall and recurrence-free survival rates were calculated for each category and compared between the surgery and observation groups. No significant differences in overall survival were found between the surgery and observation groups in low-risk (p = 0.168) and intermediate-risk patients (p = 0.306); however, high-risk patients had better 5-year overall survival rate in the surgery group than in the follow-up group (95.2% vs. 71.4%, p < 0.001). The 5-year recurrence-free survival rate was higher in the surgery group than in the observation group for low-risk (100% vs. 84.3%; p = 0.034), intermediate-risk (96.1% vs. 88.4%; p = 0.081) and high-risk patients (100% vs. 83.3%; p = 0.023). Follow-up without additional surgery after non-curative ESD can be a reasonable option for low-risk and even intermediate-risk patients according to the eCura system. However, surgery is warranted for eCura high-risk patients.

Pancreatic ductal adenocarcinomas concomitant with intraductal papillary mucinous neoplasms of the pancreas: A investigation of those clinicopathological features by analyzing 48 patients who underwent surgery for those lesions

BackgroundDifferences between pancreatic ductal adenocarcinomas (PDACs) concomitant with intraductal papillary mucinous neoplasm (IPMN) (C-PDACs), those without IPMN (NC-PDACs) and invasive cancers derived from IPMN (IC-Ds) have not been fully clarified. MethodsForty-eight patients with C-PDAC were included to investigate the differences in 1) clinicopathological features and 2) post-operative courses among the three invasive cancer groups. Results1) Characteristics of C-PDACs were mostly similar to those of NC-PDACs; whereas, between C-PDACs and IC-Ds, the rate of mucinous carcinoma (2%/25%, p = 0.003) and pathological stage (IA, 15%/36%, p = 0.033; III, 31%/4%, p = 0.015) significantly differed. Most C-PDACs coexisted with small, multifocal IPMNs without mural nodules. 2) Cumulative 5-year recurrence-free survival (RFS) rate related to extra-pancreatic recurrence was significantly worse in C-PDACs than in IC-Ds (35%/69%, p = 0.008) and was not significantly different between C-PDACs and NC-PDACs (35%/18%). This related to intra-pancreatic recurrence tended to be poor in the order of IC-Ds, C-PDACs, and NC-PDACs (69%/82%/93%). ConclusionsBecause characteristics of IPMNs remarkably differed between C-PDACs and IC-Ds, another algorithm specific to the early detection of C-PDACs is necessary. Appropriate post-operative managements according to the two types of recurrences may contribute to the improvement in the prognoses of C-PDACs/IC-Ds.

The safety and efficacy of donafenib combined with anti-PD-1 antibody as adjuvant therapy for patients (pts) with hepatocellular carcinoma (HCC): Updated results of a phase 2 study.

e16202 Background: Adjuvant therapy may have an important role in decreasing recurrence rates and improve survival in selected pts with HCC following surgical resection. However, there is no standard treatment options or strategies. This study aimed to investigate the safety and efficacy of donafenib combined with anti-PD-1 antibody as adjuvant therapy for HCC pts with high risks of recurrence. Methods: This prospective, open-label, single-arm study planned to enroll 30 pts who had undergone radical surgery and were diagnosed as HCC confirmed by histology or cytology with any of the following risk factors: a) Microvascular invasion (MVI); b) Satellite nodules in specimens; c) &gt;3 tumor nodules; d) Portal vein tumor thrombosis (excluded main portal vein invasion). Donafenib combined with anti-PD-1 antibody was initiated at 4 to 8 weeks after surgical resection and continued for up to six months. The primary endpoint was the cumulative 1-year recurrence-free survival rate (RFSR). The secondary endpoints were recurrence-free survival (RFS), overall survival, and safety. Results: As of December 31st, 2022, a total of 23 pts received donafenib plus anti-PD-1 antibody (toripalimab) with a mean follow-up of 7.6 months (safety set). The most common risk factor was MVI (91%). 20 pts were included in efficacy set (three pts were excluded due to ineligibility), of whom 16 pts had one risk factor and four had two. Intrahepatic recurrence occurred in 3 pts (15%) and no extrahepatic metastasis or death was reported. The RFSR at one year was 83.0% (90%CI, 61.6%-93.1%) in all the pts from efficacy set, 81.9% (90%CI, 59.6%-92.6%) and 92.3% (90%CI, 66.0%-98.5%) in pts with MVI and MVI-low risk, and 85.1% (90%CI, 59.6%-95.1%) in pts with only one risk factor. The median RFS was not reached. The incidence of grade 3 adverse events related to donafenib and/or toripalimab was 52.2% (12/23). No pts had grade 4/5 adverse events. Adverse events leading to withdrawal of any and both treatments occurred in six (26.1%) and one (4.3%) pts, respectively. The most common grade 3 treatment-related adverse events (occurred in more than one patient) were palmar-plantar erythrodysesthesia syndrome (17.4%), rash (17.4%), alanine aminotransferase increased (13.0%), and aspartate aminotransferase increased (8.7%). Conclusions: These results were consistent with earlier reports. The combination of donafenib and toripalimab may be a promising adjuvant therapy for pts with MVI, satellite nodules or multiple tumor after hepatectomy. No safety issues were noted. Clinical trial information: NCT04418401 . [Table: see text]

Lipid metabolism for predicting the recurrence of hypertriglyceridemic acute pancreatitis

Rationale and objectivesTo investigate the predictive value of lipid metabolism in predicting the recurrence of hypertriglyceridemic acute pancreatitis (HTG-AP). Materials and methodsA total of 892 patients were admitted to our hospital for acute pancreatitis (AP) from January 2017 to December 2020, of whom 198 diagnosed with HTG-AP were enrolled in this retrospective study. Demographic information, length of stay, smoking index, alcohol abuse, necrosis, severity, baseline lipid metabolism and other blood biochemical indicators were recorded. The risk factors of recurrence were evaluated using univariate and multivariate Cox proportional risk analyses, and the cumulative recurrence-free survival rate of patients were calculated using Kaplan Meier method and the differences between groups were compared using the log-rank test. ResultsUnivariate and multivariate analysis showed that triglyceride (hazard ratio, 2.421; 95% CI, 1.152–5.076; P = 0.020), non high-density lipoprotein (hazard ratio, 4.630; 95% CI, 1.692–12.658; P = 0.003) and apolipoprotein A1 (hazard ratio, 1.735; 95% CI, 1.093–2.754; P = 0.019) were important predictors for recurrence of HTG-AP. Subsequently, patients were divided into four groups according to the cut off values of triglyceride, non high-density lipoprotein and apolipoprotein A1. It was found that the cumulative recurrence-free survival rate of patients in highest-risk group or high-risk group was significantly lower than that of medium-risk group (P < 0.001, P = 0.003) or low risk group (P < 0.001). ConclusionSerum triglycerides, non high-density lipoprotein and apolipoprotein A1 are independent predictors of recurrence in HTG-AP patients, which can provide reference for individualized treatment and prevention of recurrence in HTG-AP patients.

The efficacy and safety of donafenib-containing regimens as postoperative adjuvant therapy for hepatocellular carcinoma (HCC): A multicenter retrospective study.

e16213 Background: Hepatectomy is a key treatment for long-term survival in patients (pts) with HCC, but a high recurrence rate seriously affects the prognosis. Currently, there is no standard treatment for adjuvant therapy, transarterial chemoembolization (TACE), anti-angiogenic therapy, immune checkpoint inhibitor (ICI) therapy, or combination strategies being evaluated. Donafenib as first-line systemic therapy is recommended in advanced HCC, but this as adjuvant therapy is still explored. This study evaluated the efficacy and safety of donafenib-containing regimens as postoperative adjuvant therapies in HCC. Methods: We retrospectively reviewed the data of pts who had received donafenib monotherapy (D) or a combined regimen (D+TACE, D+ICI, or D+TACE+ICI) as adjuvant therapy in 5 Chinese centers from June 2021 to December 2022. Recurrence was assessed using imaging. A high-risk (HR) subpopulation was defined as pts with any of the following conditions: [i] single lesion &gt;5 cm or multiple lesions of any size; [ii] lesion(s) complicated by tumor thrombus (TT); and [iii] microvascular invasion (MVI) grade ≥1. We analyzed the median relapse-free survival (mRFS) and one-year cumulative recurrence-free survival rate (1y-RFS) of the overall population and HR subpopulation, and safety (CTCAE5.0) of the overall population. Results: This study included 102 pts. At the data cut-off, mRFS had not yet been achieved, with a 1y-RFS rate of 78.2%; 12 pts (11.8%) experienced recurrence. In the HR subpopulation (N=80), the 1y-RFS rate was 79.4%, based on different treatment regimens, the 1y-RFS rates of the D (n=20), D+TACE (n=26), D+ICI (n=23), and D+TACE+ICI (n=11) groups were 87.5%, 87.7%, 72.4%, and 74.1%, respectively, and mRFS had not yet been reached; based on different clinical stages, the 1y-RFS rates of pts with China liver cancer staging stage Ib (n=35) and IIa (n=15) were 93.3% and 71.6%, respectively, with stage Ⅰa (n=12) and Ⅱb (n=7) were not reached, mRFS with IIIa (n=11) was 8.9 months (95% CI: 2.9–15.0 months). Among the overall population, 68 pts (66.7%) had treatment-related adverse events (TRAE) of any grade, and the incidence of grade 3 TRAE was 8.8% (9/102). None of the pts experienced grade 4 or 5 TRAE. Conclusions: These results preliminarily showed that donafenib-containing regimens as postoperative adjuvant therapies were safe and effective for HCC. [Table: see text]

Risk factors for the postoperative recurrence of ulcerative colitis-associated colorectal cancer.

Although ulcerative colitis-associated colorectal cancer (UC-CRC) has been described, there are few reports regarding recurrent cases of UC-CRC. In this study, we investigated the risk factors for UC-CRC recurrence. Recurrence-free survival (RFS) was determined for 144 stage I to III cancer patients among 210 UC-CRC patients from August 2002 to August 2019. The Kaplan‒Meier method was used to obtain the cumulative RFS rate, and the Cox proportional hazard model was used to extract recurrence risk factors. The interaction term between cancer stage and prognostic factors specific to UC-CRC was evaluated using the Cox model. The Kaplan‒Meier method was applied by cancer stage to the UC-CRC-specific prognostic factors for which interaction effects were indicated. There were 18 cases of recurrence involving patients with stage I to III cancer, and the recurrence rate was 12.5%. The cumulative 5-year RFS rate was 87.5%. Multivariable analysis showed that age at surgery (hazard ratio (HR): 0.95, 95% CI: 0.91-0.99, p = 0.02), undifferentiated carcinoma (HR: 4.42, 95% CI: 1.13-17.24, p = 0.03), lymph node metastasis (HR: 4.11, 95% CI: 1.08-15.69, p = 0.03), and vascular invasion (HR: 8.01, 95% CI: 1.54-41.65, p = 0.01) were significant risk factors for recurrence. Patients with stage III CRC in the young adult (age < 50years) group had a significantly worse prognosis than those in the adult (age ≥ 50years) group (p < 0.01). Age at surgery was identified as a risk factor for UC-CRC recurrence. Young adult patients with stage III cancer may have a poor prognosis.

The role of prophylactic central compartment neck dissection in patients with T1-T2 cN0 papillary thyroid carcinoma.

It remains controversial whether prophylactic central compartment neck dissection (pCCND) is necessary in cases of stage T1-T2 cN0 papillary thyroid carcinoma (PTC). Some studies have demonstrated the benefits of pCCND on oncologic outcomes, whereas others reported that any advantages were insignificant. The purpose of this study was to investigate the effects of pCCND on cancer recurrence and its pattern in patients with T1-T2 cN0 PTC. We retrospectively reviewed 2,902 patients with PTC who had undergone thyroidectomy between 2006 and 2012 at Seoul St. Mary's Hospital: 2,099 patients had undergone pCCND and thyroidectomy (pCCND group), whereas 803 did not undergo pCCND (non-pCCND group). We investigated the effects of pCCND on cancer recurrence by comparing these two groups. Recurrence was classified according to the location of the recurrence. The mean follow-up period was 112 months. The mean patient age was significantly younger in the pCCND group than in the non-pCCND group. There were no statistically significant differences in the distribution of sex, tumor size, or thyroidectomy extension between the groups. In the pCCND group, 883 (42%) patients showed evidence of N1a disease, and the mean number of metastatic lymph nodes was 1.26±2.2. Recurrence occurred in 67 (2.3%) patients in the total cohort. Recurrence was observed in 20 (2.5%) and 47 (2.2%) patients in the non-pCCND and pCCND groups, respectively, but there were no significant differences between the groups (P=0.687). When analyzed by the site of recurrence, 50% and 4.3% of recurrent disease in the non-pCCND and pCCND groups, respectively, occurred in the central compartment (P<0.001). There were no differences between the two groups in recurrent disease at other sites. The 15-year cumulative central compartment recurrence-free survival (RFS) rates of patients in the non-pCCND and pCCND groups were 99% and 100%, respectively (P<0.001). In the multivariate analysis, not performing pCCND was the only independent risk factor related to central compartment RFS, and the hazard ratio was 13.362 [95% confidence interval (CI): 2.928-60.986; P<0.001]. The omission of pCCND was found to be an independent risk factor for recurrence in the central compartment in patients with T1-T2 cN0 PTC.

Extending surgical resection for hepatocellular carcinoma beyond Barcelona Clinic for Liver Cancer (BCLC) stage A: A novel application of the modified BCLC staging system.

503 Background: Intermediate hepatocellular carcinoma is a heterogenous group of disease. 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 based on the Milan Criteria (MC), the “Up-to-7” criteria, and location of lesions: 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). The respective primary and secondary time-to-event outcomes were overall survival (OS) and recurrence-free survival (RFS). Results: 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). Conclusions: We adopted a novel approach combining the modified BCLC B sub-classification and dispersion of tumour to show that surgical resection may be curative in a select subgroup of patients with intermediate HCC that fall outside BCLC Stage A, specifically those with unilobar lesions and are within the “up-to-7” criteria. Furthermore, We found that size prognosticates resection outcomes in solitary tumours.

Percutaneous thermal ablation combined with transcatheter arterial chemoembolization for hepatitis C virus-related hepatocellular carcinoma: Efficacy and survival.

ObjectiveThe aim of this study was to investigate the efficacy and survival of Hepatitis C virus (HCV) -related hepatocellular carcinoma (HCC) undergoing percutaneous thermal ablation combined with transcatheter arterial chemoembolization (TACE).MethodsA total of 83 HCV-related HCC patients who were treated with percutaneous thermal ablation combined with TACE were retrospectively analyzed. The demographic and clinical data were collected. The overall survival (OS) and recurrence free survival (RFS) rates were assessed by the Kaplan-Meier method. Univariate and multivariate Cox regression analysis was used to assess independent risk factors of OS and RFS.Results92.8% patients (77/83) and 96.6% (170/176) tumor lesions achieved complete response (CR) 1 month after all treatment, and 10.8% (9/83) patients had minor complications. The median OS was 60 months (95% confidence interval (CI)= 48.0-72.0), and the 1-, 2-, 3-, 5- and 10-year cumulative OS rates were 94%, 78.3%, 72.3%, 43.4% and 27.5%, respectively. The cumulative RFS rates at 1-, 2-, 3- and 5-year were 74.7%, 49.3%, 30.7% and 25.3%, respectively. Sex (HR =0.529, P=0.048), ablation result (HR=5.824, P=0.000) and Albumin-bilirubin (ALBI) score (HR=2.725, P=0.011) were independent prognostic factors for OS. Alpha-fetoprotein (AFP) (HR =2.360, P = 0.005) and tumor number(HR=2.786, P=0.000) were independent prognostic factors for RFS.ConclusionsPercutaneous thermal ablation combined with TACE is a safe and effective treatment for HCV-related HCC. Sex, ablation result and ALBI are significant prognostic factors for OS. AFP and tumor number are significant prognostic factors for RFS.

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

ObjectiveWe 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.MethodsThis 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).ResultsA 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).ConclusionWe 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.

Expression characteristics and diagnostic value of angiogenic molecules in intravenous leiomyomatosis

Objective: This study aims to analyze the clinicopathological characteristics of patients with intravenous leiomyoma (IVL), and to explore the expression characteristics and diagnostic value of angiogenesis related molecules in IVL. Methods: The clinicopathological data of 40 patients with IVL at Women's Hospital, School of Medicine, Zhejiang University from January 2013 to April 2021 were reviewed. Log-rank test was performed to compare the difference in recurrence-free survival (RFS) rates among patients with different clinicopathological characteristics. Immunohistochemistry (IHC) staining was performed on 10 angiogenesis related molecules to analyze their expression characteristics in IVL. The sensitivity and specificity of molecules with high expression rates in the diagnosis of IVL were calculated, the receiver operating characteristic curve (ROC) was plotted and the area under ROC (AUC) was calculated to evaluate the diagnostic value. Results: Median age of the 40 patients was 47 (43, 50) years. The clinical manifestations of IVL were atypical with the diagnostic accuracy of preoperative ultrasound was 12.5% (5/40), CT and/or MRI was 26.7% (8/30), and intraoperative frozen section was 30.0% (12/40). The overall recurrence rate of IVL was 10.0% (4/40). The Log-rank test showed that the cumulative recurrence-free survival rate of IVL patients with previous cesarean section (40.9%) was lower than that of those without cesarean section (96.4%) (P<0.05); and their median RFS time was shorter than those without cesarean section (16.4 months vs 22.2 months). The overall positive rates of adrenomedullin (ADM), fibroblast growth factor receptor 1 (FGFR1), vascular endothelial growth factor receptor 3 (VEGFR3) and angiogenin receptor tyrosine kinase receptor 1 (TIE1) were 65.0% (26/40), 75.0% (30/40), 57.5% (23/40) and 50.0% (20/40), respectively. FGFR1 expression intensity and positive rate were higher in tumors with a maximum diameter greater than 5 cm than in tumors with a maximum diameter smaller than 5 cm (P<0.05). The AUC of FGFR1 combined with ADM, VEGFR3, and TIE1 was 0.876 (95%CI: 0.788-0.964, P<0.001). Conclusions: There was no typical clinical manifestation of IVL. A history of the previous cesarean section indicated a lower cumulative recurrence-free survival rate and shorter recurrence interval. It was hard to diagnose IVL by sonography, radiography, or frozen section pathology. FGFR1, ADM, VEGFR3, and TIE1 were all highly expressed in IVL, and the efficacy of the combination of the four molecules in diagnosing IVL was higher than that of imaging and classical vascular endothelial markers, which are expected to be promising molecular diagnostic markers.

Preliminary data of a prospective study on the safety and efficacy of donafinib combined with anti-PD-1 antibody as adjuvant therapy for patients with hepatocellular carcinoma (HCC).

e16131 Background: Surgical resection is one of the most effective treatments for HCC. However, the recurrence rate after hepatectomy is still very high with the 5-year recurrence rate of 60̃70%, which is even higher in patients with high-risk recurrence factors (the cumulative 1-year recurrence rate was about 50% without intervention). Here investigators intended to explore the safety and efficacy of donafenib combined with anti-PD-1 antibody as adjuvant therapy for HCC patients with high risks of recurrence. Methods: In this single-center study, eligible HCC patients with high-risk recurrence factors after radical surgery were recruited to receive donafenib combined with anti-PD-1 antibody for six months. The starting dose of donafenib was 100 mg PO BID in the first six patients and then reduced to 100 mg PO QD at the investigator’s discretion on tolerability in the adjuvant setting. For patients who started with donafenib 100 mg QD, the dose could be escalated to 100 mg BID from the second 21-day cycle if there were no experience grade ≥2 major adverse reactions (i.e. hand-foot syndrome, abnormal liver or kidney function, and blood cell decreased) reported in cycle 1. The primary endpoint was the cumulative 1-year recurrence-free survival rate. The secondary endpoints were recurrence-free survival (RFS), overall survival, quality of life (QoL) measured with FACT- Hepatobiliary questionnaire, and adverse events (AEs). Results: Between June 2020 and December 2021, thirteen patients with BCLC stage A-B HCC were enrolled. 11/13 (84.6%) patients had microvascular invasion (8 w/ M1 and 3 w/ M2). 11/13 (84.6%) patients had one tumor. 4/13 (30.8%) patients had tumor size ≥5 cm and 4/13 (30.8%) had satellite nodules. The median tumor size was 3.00 cm (IQR 2.60 to 6.00) and 3.29 cm (IQR 2.20 to 6.50) based on pathological findings and image, respectively. Eleven patients were included in efficacy analysis (two were excluded due to ineligibility). The median duration of follow-up was 8.30 months (IQR 2.90-14.40). Two patients experienced recurrence. The cumulative 1-year recurrence-free survival rate was 80% (90%CI, 49% to 93%). The median RFS was not reached. QoL showed a trend of improvement after 9 weeks of treatment. Among all the patients who received donafenib plus anti-PD-1 antibody, grade 3 treatment-related AEs (TRAEs) occurred in 7/13 (53.8%) patients (no grades 4 or 5 were reported). Common TRAEs included alanine aminotransferase increased (53.8%), aspartate aminotransferase increased (53.8%), blood bilirubin increased (38.5%), white blood cell decreased (38.5%), platelet count decreased (38.5%), rash (38.5%). No deaths were reported. Conclusions: The combination of donafinib and anti-PD-1 antibody as adjuvant therapy was well tolerated and demonstrated promising efficacy in HCC patients with high risks of recurrence. Clinical trial information: NCT04418401.

Aspartate aminotransferase-to-platelet ratio index for predicting late recurrence of hepatocellular carcinoma after radiofrequency ablation

Background Our study aimed to explore the prognostic value of the aspartate aminotransferase–platelet ratio index (APRI) and to develop a new nomogram for patients with hepatocellular carcinoma (HCC) who experience late recurrence after radiofrequency ablation (RFA). To date, no study has explored the value of APRI for assessing the late recurrence of HCC after RFA. Materials and Methods The prognostic value of APRI was evaluated and validated in our multicenter retrospective analysis. A total of 466 HCC patients undergoing RFA were reviewed as a training cohort, and 234 HCC patients were included in the external validation cohort. The nomogram was built based on significant prognostic factors in a multivariate analysis and validated in the external validation cohort. Results The cutoff APRI score was 0.78, and it appropriately discriminated between low- and high-risk groups for late recurrence in HCC patients. The cumulative recurrence-free survival rates of the low-risk group were significantly higher than those of the high-risk group (p < 0.001), according to the Kaplan–Meier curves. Late recurrence in HCC patients after RFA was associated with APRI, sex and multiple tumors. The nomogram based on potential risk factors (APRI score, sex and multiple tumors) as indicated by multivariate Cox regression analysis showed good discrimination and calibration in the training and external verification groups. Conclusions The APRI score is a feasible independent prognostic factor for the late recurrence of HCC after RFA. The proposed nomogram could aid clinicians in following disease progression and providing tailored therapy for patients.

The monocyte to lymphocyte ratio not only at baseline but also at relapse predicts poor outcomes in patients with hepatocellular carcinoma receiving locoregional therapy

BackgroundMonocyte to lymphocyte ratio (MLR) represents a pro-inflammatory immune microenvironment. The aim of this study was to elucidate the effect of MLR and subsequent MLR when relapse occurred (R-MLR) on prognosis for hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) combined with ablation.MethodsA prospective analysis was conducted on 606 patients with HCC who were treated with TACE combined with local ablation in Beijing You’an Hospital affiliated to Capital Medical University from January 1, 2012 to December 31, 2016. MLR or R-MLR were stratified according to the optimal cut-off values. The cumulative recurrence-free survival (RFS), overall survival (OS) , and recurrence-death survival (RDS) rates were calculated by Kaplan–Meier method. The Cox proportion hazard model and logistic regression analysis was conducted to screen for independent predictive factors for indicating early relapse and long-term prognosis.ResultsHigh MLR was significantly associated with relapse, early recurrence, and overall survival. After a median follow-up of 59.4 months, The cumulative 1-, 3-, 5-year RFS rates of low MLR were 74.6%, 43.8%, and 34.0%; while 66.1%, 32.2%, and 22.6% for high group (P < 0.001). There were also significant differences in corresponding OS rates of the two groups (P = 0.003). The cumulative 1-, 3-, 5-year OS rates of low R-MLR were 99.5%, 87.2%, 75.5%; while 98.3%, 78.3%, 61.7% for high group (P < 0.001). There were also significant differences in corresponding RDS rates in the two groups (P = 0.008). 436 patients were divided into four groups on the base of cut-off values of MLR and R-MLR (low-low, low–high, high-low, and high-high). The low-low group has shown better outcomes including the cumulative 1-, 3-, 5-year OS, and RDS rates(P < 0.001).ConclusionsHigh MLR was related to unfavorable outcome. Subsequent change of MLR between baseline and HCC relapse could indicate poor long-term survival after relapse.

Hepatectomy with Perioperative Chemotherapy for Multiple Colorectal Liver Metastases is the Available Option for Prolonged Survival.

Hepatic resection combined with perioperative chemotherapy is the standard of care for patients with multiple colorectal liver metastases (CLMs). However, the optimal surgical strategy for treating advanced CLMs remains unclear. The role of the two-stage hepatectomy (TSH) strategy in the management of multiple CLMs remains challenging. This study aimed to compare the outcomes of one-step hepatectomy (OSH)-treated and TSH-treated patients with multiple CLMs. This single-institution study included 742 consecutive patients who underwent initial liver resection for histologically confirmed CLMs. The study enrolled patients with 10 or more tumors (n = 106). Clinicopathologic characteristics and long-term outcomes were compared between patients who underwent OSH and those who underwent TSH for 10 or more CLMs. The study planned OSH for 67 patients (63%) and TSH for 39 patients (37%). One of the OSH-planned patients and two of the TSH-planned patients underwent a trial laparotomy because of non-curative factors. Five patients (13%) did not progress to the second stage of TSH. In the entire cohort, the cumulative 3-year overall survival rate was 58.4% for the patients who had 10 or more CLMs treated with OSH compared with 61.1% for the patients treated with TSH (P = 0.746). In the curative resection cohort, the cumulative 1-year recurrence-free survival rate was 18.2% for the patients treated with OSH and 17.9% for the patients treated with TSH (P = 0.640). Hepatectomy with perioperative chemotherapy for advanced CLMs with 10 or more tumors is feasible and effective. To prolong survival, TSH is a promising option when curative resection with OSH is impossible.

Long-term clinical outcomes of patients diagnosed with pT1a-muscularis mucosae with lymphovascular invasion or pT1b after endoscopic resection for cT1N0M0 esophageal squamous cell carcinoma.

Endoscopic resection (ER) is performed for early esophageal squamous cell carcinoma (ESCC) cases. Additional esophagectomy or chemoradiotherapy is recommended for non-curative resection (NCR) even with pathologically negative vertical margins (pVM0); however, their clinical outcomes remain unknown. We examined the long-term clinical outcomes of NCR for ESCCs according to additional treatments. We retrospectively analyzed the data of patients who underwent ER for cT1N0M0 ESCC between 2009 and 2017 judged to have NCR, which defined when pathologically diagnosed as invading the submucosa (SM) or muscularis mucosae (MM) involving lymphovascular invasion (LVI), pVM0, and endoscopically judged as negative horizontal margin. Additional esophagectomy (involving three-field lymphadenectomy), chemoradiotherapy [mainly cisplatin and 5-fluorouracil with concurrent radiotherapy (41.4Gy)], or observation was undertaken. Thereafter, computed tomography was performed every 6-12months. The cumulative recurrence (CRR) and recurrence-free survival (RFS) rates were evaluated. Eighty-nine patients were included. Among them, 14 had pathologically diagnosed pMM with LVI; 9 and 6, and 32 and 28 patients had pSM1 and pSM2 without and with LVI. Twenty-one patients underwent observation, whereas 18 and 50 underwent esophagectomy and chemoradiotherapy. During the 60.6-month median follow-up period, nine patients had recurrence; among them, six patients had occurrence at > 4years after ER. The 5-year CRR/RFS rates were 35.7%/48.1%, 13.4%/80.4%, and 0.0%/98.0% in the observation, esophagectomy, and chemoradiotherapy groups, respectively (observation vs. chemoradiotherapy; P < 0.001). Additional treatments showed better long-term outcomes than observation for patients with NCR. As recurrence may occur at > 4years after ER, careful long-term follow-up examinations are needed.