Real-world efficacy and safety of TACE-HAIC combined with TKIs and PD-1 inhibitors in initially unresectable hepatocellular carcinoma.

BACKGROUND: Local treatment may function synergistically with immunotherapy and targeted agents. This study aimed to assess the effectiveness and safety of transcatheter arterial chemoembolization (TACE) and hepatic artery infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and programmed death-1 (PD-1) inhibitors in patients with initially unresectable hepatocellular carcinoma (uHCC). METHODS: A retrospective study was conducted on patients diagnosed with initially uHCC who received combined treatment of TACE-HAIC combined with TKIs and PD-1 inhibitors from July 2020 to February 2023. The primary endpoints were overall survival (OS) and progression free survival (PFS) and adverse events (AEs). Objective response rate (ORR), disease control rate (DCR) and conversion surgery rate (CSR), whereas the secondary endpoints. RESULTS: After screening, a total of 62 patients were selected for this study. The overall median OS was 18.2 (95% CI 16.24-20.16) months and median PFS was 9.2 (95% CI 7.24-11.16) months. Based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria and RECIST v1.1 criteria, ORR was 67.7% (42/62), and the DCR was 90.3% (56/62), the CSR was 27.4% (17/62). The most common treatment-emergent adverse events (TEAEs) were transaminitis (56.4%, 35/62), nausea and vomiting (43.5%, 27/62), thrombocytopenia (37.1%, 23/62), abdominal pain (33.9%, 21/62), and fever (33.9%, 21/62). CONCLUSIONS: TKIs combined with PD-1 inhibitors plus TACE-HAIC therapy represents an effective and tolerable treatment option in patients with uHCC. Patients undergoing surgery after combination therapy may have survival benefits.

Prognostic significance of postoperative serological incomplete conversion of AFP and PIVKA-II after hepatic resection for hepatocellular carcinoma: a multicenter analysis of 1755 patients.

BACKGROUND: The value of serum biomarkers, particularly alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), gains increasing attention in prognostic evaluation and recurrence monitoring for patients with hepatocellular carcinoma (HCC). This study investigated the implications of serological incomplete conversion (SIC) of these 2 biomarkers as prognostic indicators for long-term outcomes after HCC resection. METHODS: A multicenter observational study was conducted on a cohort of HCC patients presenting with AFP (>20 ng/mL) or PIVKA-II (>40 mAU/mL) positivity who underwent curative-intent resection. Based on their postoperative AFP and PIVKA-II levels at first postoperative follow-up (4~8 weeks after surgery), these patients were stratified into the serological incomplete conversion (SIC) and serological complete conversion (SCC) groups. The study endpoints were recurrence and overall survival (OS). RESULTS: Among 1755 patients, 379 and 1376 were categorized as having SIC and SCC, respectively. The SIC group exhibited 1- and 5-year OS rates of 67.5% and 26.3%, with the corresponding recurrence rates of 53.2% and 79.0%, respectively; while the SCC group displayed 1- and 5-year OS rates of 95.8% and 62.5%, with the corresponding recurrence rates of 16.8% and 48.8%, respectively (both P < .001). Multivariate Cox regression analysis demonstrated that postoperative SIC was an independent risk factor for both increased recurrence (HR: 2.40, 95% CI, 2.04-2.81, P < .001) and decreased OS (HR: 2.69, 95% CI, 2.24-3.24, P < .001). CONCLUSION: The results emphasize that postoperative incomplete conversion of either AFP or PIVKA-II is a significant prognostic marker, indicating a higher risk for adverse oncologic outcomes following HCC resection. This revelation has crucial implications for refining postoperative adjuvant therapy and surveillance strategies for HCC patients.

Cardiorespiratory fitness and morbidity and mortality in patients with non-small cell lung cancer: a prospective study with propensity score weighting.

INTRODUCTION: This study aimed to investigate the association between cardiorespiratory fitness (CRF) and perioperative morbidity and long-term mortality in operable patients with early-stage non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: This prospective study included consecutive patients with early-stage NSCLC who underwent presurgical cardiopulmonary exercise testing between November 2014 and December 2019 (registration number: ChiCTR2100048120). Logistic and Cox proportional hazards regression were applied to evaluate the correlation between CRF and perioperative complications and long-term mortality, respectively. Propensity score overlap weighting was used to adjust for the covariates. We performed sensitivity analyses to determine the stability of our results. RESULTS: A total of 895 patients were followed for a median of 40 months [interquartile range 25]. The median age of the patients was 59 years [range 26-83], and 62.5% were male. During the study period, 156 perioperative complications and 146 deaths were observed. Low CRF was associated with a higher risk of death (62.9 versus 33.6 per 1000 person-years; weighted incidence rate difference, 29.34 [95% CI, 0.32 to 58.36] per 1000 person-years) and perioperative morbidity (241.6 versus 141.9 per 1000 surgeries; weighted incidence rate difference, 99.72 [95% CI, 34.75 to 164.70] per 1000 surgeries). A CRF of ≤ 20 ml/kg/min was significantly associated with a high risk of long-term mortality (weighted hazard ratio, 1.98 [95% CI, 1.31 to 2.98], p < 0.001) and perioperative morbidity (weighted odds ratio, 1.93 [1.28 to 2.90], p = 0.002) compared to higher CRF. CONCLUSION: The study found that low CRF is significantly associated with increased perioperative morbidity and long-term mortality in operable patients with early-stage NSCLC.

Low cardiorespiratory fitness is significantly associated with increased perioperative morbidity and long-term mortality in operable patients with early-stage non-small cell lung cancer.Future research is recommended to investigate the potential prognostic role of integrating cardiorespiratory fitness into the currently used prognosis algorithm for patients with non-small cell lung cancer.

An Eastern Hepatobiliary Surgery Hospital/Portal Vein Tumor Thrombus Scoring System as an Aid to Decision Making on Hepatectomy for Hepatocellular Carcinoma Patients With Portal Vein Tumor Thrombus: A Multicenter Study.

Portal vein tumor thrombus (PVTT) is a significant poor prognostic factor for hepatocellular carcinoma (HCC). Patients with PVTT limited to a first-order branch of the main portal vein (MPV) or above could benefit from negative margin (R0) liver resection (LR). An Eastern Hepatobiliary Surgery Hospital (EHBH)/PVTT scoring system was established to predict the prognosis of HCC patients with PVTT after R0 LR and guide selection of subgroups of patients that could benefit from LR. HCC patients with PVTT limited to a first-order branch of the MPV or above who underwent R0 LR as an initial therapy were included. The EHBH-PVTT score was developed from a retrospective cohort in the training cohort using a Cox regression model and validated in a prospective internal validation cohort and three external validation cohorts. There were 432 patients in the training cohort, 285 in the prospective internal validation cohort, and 286, 189, and 135 in three external validation cohorts, respectively. The score was calculated using total bilirubin, α-fetoprotein (AFP), tumor diameter, and satellite lesions. The EHBH-PVTT score differentiated two groups of patients (≤/>3 points) with distinct long-term prognoses (median overall survival [OS], 17.0 vs. 7.9 months; P < 0.001). Predictive accuracy, as determined by the area under the time-dependent receiver operating characteristic curves (AUCs; 0.680-0.721), was greater than that of the other commonly used staging systems for HCC and PVTT. Conclusion: The EHBH-PVTT scoring system was more accurate in predicting the prognosis of HCC patients with PVTT than other staging systems after LR. It selected appropriate HCC patients with PVTT limited to a first-order branch of the MPV or above for LR. It can be used to supplement the other HCC staging systems.

Short- and mid-term outcomes of robotic versus laparoscopic distal pancreatosplenectomy for pancreatic ductal adenocarcinoma: A retrospective propensity score-matched study.

BACKGROUND: Robotic distal pancreatectomy exhibits short-term benefits over laparoscopic distal pancreatectomy. The use of minimal invasive techniques to carry out distal pancreatosplenectomy (DPS) for pancreatic ductal adenocarcinoma (PDAC) remains controversial and has not gained popular acceptance. A comparative study was designed to analyze the short- and mid-term outcomes of robotic DPS (RDPS) versus laparoscopic DPS (LDPS) on patients with PDAC. METHODS: The baseline characteristics, perioperative outcomes and survival data among patients who underwent RDPS (n = 35) versus LDPS (n = 35) for PDAC between December 2011 and December 2015 were compared after a 1:1 propensity score matching. RESULTS: There were no significant differences in the operative time, blood loss, blood transfusion rate, and morbidity and pancreatic fistula rates between the RDPS and LDPS groups. RDPS significantly reduced the rate of conversion to laparotomy (5.7% vs. 22.9% when compared with LDPS, p = 0.04). There were no significant differences in R0 resection rates, number of harvested lymph nodes, positive to harvested lymph node ratios, and disease-free survival and overall survival rates between the two groups. A Cox proportional hazards analysis showed N1 stage to be significantly associated with worse survival and suggested that chemotherapy might prolong overall survival in these PDAC patients. CONCLUSIONS: This single-center study demonstrated that RDPS was safe and efficacious in treatment of PDAC. When compared with LDPS, RDPS was associated with a reduced rate of conversion to open surgery. There were no significantly differences in oncological outcomes and mid-term survival rates between the groups of patients who underwent RDPS or LDPS.

Causes of peripheral cytopenia in hepatitic cirrhosis and portal hypertensive splenomegaly.

The clinical data of 183 patients with hepatitic cirrhosis and portal hypertensive splenomegaly complicated by peripheral cytopenia were retrospectively analyzed to investigate the causes of peripheral cytopenia, as well as the proportion of the causes in these patients. All patients underwent splenectomy. Before operation, these patients had one or more types of peripheral cytopenia (cumulative cytopenia: 390 patient-times). After splenectomy, blood counts in 79.2% (309/390) returned to normal, while in 15.9% (62/390) they increased but failed to reach to normal levels, and in 4.9% (19/390) they became lower than before the operations. For the last group of patients ( n = 19), long-term follow-up showed that blood counts returned to normal in five patients. In other words, in 80.5% [(309 + 5)/390 or 314/390] of patient-times, the peripheral cytopenia was due to hypersplenism, in 15.9% it was due to a combination of factors, and in 3.6% [14/390] it had nothing to do with the hypersplenism. Thus, hypersplenism is a major cause, but not the only cause, of peripheral cytopenia in patients with hepatic cirrhosis and portal hypertensive splenomegaly, and splenectormy is an effective treatment for these patients. Impact statement For a long time, the development of peripheral cytopenias as a complication to cirrhotic portal hypertension has been attributed to hypersplenism; however, this has never been fully demonstrated. Dameshek summarized that hypersplenism should be diagnosed by the presence of four conditions: (a) mono- or multi-lineage peripheral cytopenias; (b) compensatory hyperplasia of bone marrow; (c) splenomegaly; and (d) correction of cytopenias after splenectomy. We retrospectively analyzed the clinical data from 183 surgical patients, and found that 80.5% of peripheral cytopenias was caused by hypersplenism, 16% by a combination of factors, and 3.5% by other factors unrelated to hypersplenism. As the first quantitative findings in this field, our results verify that hypersplenism is a major, but not exclusive, cause of peripheral cytopenias, and provides important clinical evidence for investigating the cause of peripheral cytopenias.

Pringle manoeuvre versus selective hepatic vascular exclusion in partial hepatectomy for tumours adjacent to the hepatocaval junction: a randomized comparative study.

OBJECTIVE: To compare the efficacy of selective hepatic vascular exclusion versus Pringle manoeuvre in partial hepatectomy for tumours adjacent to the hepatocaval junction. METHODS: A randomized comparative trial was carried out. The primary endpoint was intraoperative blood loss. The secondary endpoints were operation time, blood transfusion, postoperative liver function recovery, procedure-related morbidity and in-hospital mortality. RESULTS: 160 patients were randomized into 2 groups: the Pringle manoeuvre group (n = 80) and the selective hepatic vascular exclusion (SHVE) group (n = 80). Intraoperative blood loss and transfusion requirements were significantly less in the SHVE group. In the SHVE group, laceration of hepatic veins happened in 18 patients. Profuse intraoperative blood loss of over 2 L happened in 2 patients but no patient suffered from air embolism because the hepatic veins were controlled. In the Pringle group, the hepatic veins were lacerated in 20 patients, with profuse blood loss of over 2 L in 7 patients and air embolism in 3 patients. The rates of postoperative bleeding, reoperation, liver failure and mortality were significantly higher and the ICU stay and hospital stay were significantly longer in the Pringle group. CONCLUSIONS: SHVE was more efficacious than Pringle manoeuvre for partial hepatectomy in patients with tumours adjacent to the hepatocaval junction.

A prospective randomized controlled trial to compare Pringle maneuver, hemihepatic vascular inflow occlusion, and main portal vein inflow occlusion in partial hepatectomy.

BACKGROUND: blood loss during liver resection and the need for perioperative blood transfusions have negative impact on perioperative morbidity, mortality, and long-term outcomes. METHODS: a randomized controlled trial was performed on patients undergoing liver resection comparing hemihepatic vascular inflow occlusion, main portal vein inflow occlusion, and Pringle maneuver. The primary endpoints were intraoperative blood loss and postoperative liver injury. The secondary outcomes were operating time, morbidity, and mortality. RESULTS: a total of 180 patients were randomized into 3 groups according to the technique used for inflow occlusion during hepatectomy: the hemihepatic vascular inflow occlusion group (n = 60), the main portal vein inflow occlusion group (n = 60), and the Pringle maneuver group (n = 60). Only 1 patient in the hemihepatic vascular occlusion group required conversion to the Pringle maneuver because of technical difficulty. The Pringle maneuver group showed a significantly shorter operating time. There were no significant differences between the 3 groups in intraoperative blood loss and perioperative mortality. The degree of postoperative liver injury and complication rates were significantly higher in the Pringle maneuver group, resulting in a significantly longer hospital stay. CONCLUSIONS: all 3 vascular inflow occlusion techniques were safe and efficacious in reducing blood loss. Patients subjected to hemihepatic vascular inflow occlusion, or main portal vein inflow occlusion responded better than those with Pringle maneuver in terms of earlier recovery of postoperative liver function. As hemihepatic vascular inflow occlusion was technically easier than main portal vein inflow occlusion, it is recommended.