Transarterial Chemoembolization Combined with Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis.

Purpose: This study aimed to explore the clinical efficacy of transarterial chemoembolization (TACE) in combination with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (triple therapy) compared to TACE alone (monotherapy) for advanced hepatocellular carcinoma (HCC). Material and Methods: Data of consecutive advanced HCC patients receiving triple therapy or monotherapy at our center between January 2019 and December 2022 were collected and retrospectively analyzed. Propensity score matching (PSM) and subgroup analyses were performed to reduce the bias between the two groups. The primary outcomes of the study were the overall survival (OS) and progression-free survival (PFS). The secondary outcomes were the objective response rate (ORR) and disease control rate (DCR). Results: A total of 104 patients were enrolled in this study: 41 in the triple therapy group and 63 in the monotherapy group. After PSM analysis, each group included 37 patients. The median OS and PFS were significantly longer in the triple therapy group than in the monotherapy group in the whole cohort (median OS, 18.8 vs 11.7 months, P = 0.022; median PFS, 10.5 vs 6.4 months, P = 0.012) and after PSM (median OS, 19.6 vs 12.5 months, P = 0.030; median PFS, 10.5 vs 6.7 months, P = 0.008). Furthermore, the treatment modality was an independent prognostic factor for OS (hazard ratio [HR]: 0.449, 95% confidence interval [CI]: 0.240-0.840, P = 0.012) and PFS (HR: 0.406, 95% CI: 0.231-0.713, P = 0.002) according to the multivariate cox regression analysis. A greater ORR was also observed in the triple therapy group (ORR: 56.7% vs 32.4%, P = 0.035). No significant difference was observed in DCR between the two groups (83.7% vs 72.9%, P = 0.259). Conclusion: The triple therapy was superior to the monotherapy regarding OS, PFS, and ORR of advanced HCC patients.

ICG-mediated fluorescence-assisted debridement to promote wound healing.

The purpose of this study was to examine the efficacy of ICG-mediated fluorescence molecular imaging (FMI) in debridement of necrotic tissue. 96 wound-infected rats were randomly divided into control group, ICG group, excitation light (EL)group and FMI group for debridement of necrotic tissue (n = 24). (I) Control group: only debridement; (II) ICG group: ICG injection before debridement; (III) EL group: Debridement under EL; (IV) FMI group: Debridement guided by ICG-mediated FMI. On the 3rd, 6th, and 9th days, the wound tissues of the rats in each group were collected for histological examination, and the levels of serum interleukin-4 (IL-4) and interferon-γ (INF-γ) were analyzed. The wound healing rate, wound score and body weight of the rats in each group were followed up until the wound healed. The results showed that the infected wounds of the rats in the FMI group had significant fluorescence development. The level of serum IL-4 in the FMI group was higher than that in the other three groups on the 6th day (p<0.01), while the level of INF-γ was lower than that in the other three groups on the 6th and 9th day (p<0.05). The results of dynamic wound tissue H&E staining indicated that the wound healing in the FMI group was better than the other three groups. The in vivo follow-up results showed that the wound healing rate and wound score of the FMI group were better than the other three groups, and the growth of rats had no difference with the other groups. ICG-mediated FMI can achieve accurate imaging of necrotic tissue for debridement, and so can accelerate wound healing, which has good clinical application prospects.

Efficacy and safety of enhanced recovery after surgery protocol on minimally invasive bariatric surgery: a meta-analysis.

BACKGROUND: Enhanced recovery after surgery (ERAS), a multidisciplinary and multimodal perioperative care protocol, has been widely used in several surgical fields. However, the effect of this care protocol on patients receiving minimally invasive bariatric surgery remains unclear. This meta-analysis compared the clinical outcomes of the ERAS protocol and standard care (SC) in patients who underwent minimally invasive bariatric surgery. MATERIAL AND METHODS: PubMed, Web of Science, Cochrane Library, and Embase databases were systematically searched to identify literature reporting the effects of the ERAS protocol on clinical outcomes in patients undergoing minimally invasive bariatric surgery. All the articles published until 01 October 2022, were searched, followed by data extraction of the included literature and independent quality assessment. Then, pooled mean difference (MD) and odds ratio with a 95% CI were calculated by either a random-effects or fixed-effects model. RESULTS: Overall, 21 studies involving 10 764 patients were included in the final analysis. With the ERAS protocol, the length of hospitalization (MD: -1.02, 95% CI: -1.41 to -0.64, P <0.00001), hospitalization costs (MD: -678.50, 95% CI: -1196.39 to -160.60, P =0.01), and the incidence of 30-day readmission (odds ratio =0.78, 95% CI: 0.63-0.97, P =0.02) were significantly reduced. The incidences of overall complications, major complications (Clavien-Dindo grade ≥3), postoperative nausea and vomiting, intra-abdominal bleeding, anastomotic leak, incisional infection, reoperation, and mortality did not differ significantly between the ERAS and SC groups. CONCLUSIONS: The current meta-analysis indicated that the ERAS protocol could be safely and feasibly implemented in the perioperative management of patients receiving minimally invasive bariatric surgery. Compared with SC, this protocol leads to significantly shorter hospitalization lengths, lower 30-day readmission rate, and hospitalization costs. However, no differences were observed in postoperative complications and mortality.

Efficacy of lenvatinib combined with sequential transarterial chemoembolization for primary hepatocellular carcinoma and the effects on serum basic fibroblast growth factor and vascular endothelial growth factor.

Objective: The aim of this research was to investigate the therapeutic efficacy of lenvatinib combined with sequential transarterial chemoembolization (TACE) on primary hepatocellular carcinoma (HCC) and the effects on serum basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Method: A total of 104 patients with primary HCC, admitted to People's Hospital of Leshan from April 2018 to January 2021, were selected as the study subjects and were divided into the TACE-LEN group (n = 53) who were treated with lenvatinib combined with sequential TACE and the TACE group (n = 51) who were treated with TACE alone, according to the appropriate treatment modalities. The clinical efficacy 8 weeks after treatment; the serum levels of total bilirubin, conjugated bilirubin, and alanine aminotransferase (ALT); the prothrombin time (PT); the indocyanine green retention rate at 15 min (ICGR15); and the serum bFGF and VEGF levels before treatment and at 8 weeks after treatment were compared between the two groups. The incidence of adverse events and the survival rates at 18 months were also recorded for both groups. COX regression analysis was used to analyze the risk factors affecting the survival of patients. Results: Eight weeks after treatment, the objective response rate was higher in the TACE-LEN group than in the TACE group (77.36% vs. 56.36%, p < 0.05), but there were no statistically significant differences in the bilirubin and ALT levels, the PT, and the ICGR15 between the two groups (p > 0.05). The serum bFGF and VEGF levels post-therapeutic were lower in the TACE-LEN group than in the TACE group (p < 0.05). The differences in the incidence of postoperative adverse events and the survival rate within 6 months were not statistically significant between the two groups (p > 0.05). In addition, the survival rates within 12 and 18 months after treatment were higher in the TACE-LEN group than in the TACE group than in the TACE group (81.1% vs. 64.7%, 69.8% vs. 49.1%, p < 0.05). ICG-R15 and treatment regimen are risk factors for survival. Conclusion: The worse the liver reserve is, the worse the prognosis is. The combination of TACE and lenvatinib showed better efficacy and longer survival than TACE monotherapy for HCC patients and reduced the levels of bFGF and VEGF.

Risk of Adverse Events in Cancer Patients Receiving Nivolumab With Ipilimumab: A Meta-Analysis.

Background: Combining two immune checkpoint inhibitors (ICIs) instead of using one can effectively improve the prognosis of advanced malignant tumors. At present, ipilimumab alongside nivolumab is the most widely used combinatorial regimen of ICIs. However, the risk of treatment-related adverse events is higher in combinatorial regimens than in single-drug regimens. Thus, this study aimed to evaluate the risks of common adverse events associated with the combinatorial regimen of ipilimumab and nivolumab by using meta-analysis. Methods: We searched Pubmed, Medline, EMBASE, and Cochrane Library for reports published by 30 September 2021. A randomized controlled study was developed and analyzed using the statistical software R to determine the efficacy of the combinatorial treatment. Risk estimates (hazard ratios, RR) and 95% confidence intervals for various common serious adverse events were used. Results: A total of 23 randomized control trials (n = 3970 patients) were included. Our meta-analysis indicated the risks of adverse events of any grade and grade ≥ 3 as 90.42% (95%CI: 85.91% ~ 94.18%) and 46.46% (95%CI: 39.37% ~ 53.69%), respectively; the risks of treatment-related death and adverse events leading to discontinuation were estimated at 0.42% (95% CI, 0.18% ~ 0.72%) and 19.11% (95% CI, 14.99% ~ 24.38%), respectively. Classification of 19 common adverse events. The top 5 grade 1-2 adverse events were found to be fatigue (30.92%, 95% CI: 24.59% ~ 37.62%), pruritus (26.05%, 95%CI: 22.29%~29.99%), diarrhea (23.58%, 95% CI: 20.62% ~ 26.96%), rash (19.90%, 95%CI: 15.75% ~ 25.15%), and nausea (17.19%, 95% CI:13.7% ~ 21.57%). The top 5 grade ≥ 3 adverse events were identified as increased alanine aminotransferase(8.12%, 95% CI: 5.90%~10.65%), increased lipase(7.62%, 95% CI: 4.88% ~ 10.89%), and colitis (6.39%, 95%CI: 3.98% ~ 10.25%), increased aspartate aminotransferase (6.30%, 95% CI: 4.61% ~ 8.22%), and diarrhea(5.72%, 95%CI: 3.50% ~ 8.44%). Subgroup analysis revealed some differences in the adverse events between the N1-I3 and N3-I1 subgroups and between subgroups of different cancer types. Conclusion: This study summarized the risks of common adverse events in the co-treatment of malignant-tumor patients with ipilimumab and nivolumab and identified the impacts of various initial administration schemes on the risks of such events, thereby providing an important reference for the toxicity of co-treatment with ipilimumab and nivolumab. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42020181350.

Efficacy and safety of lenvatinib versus sorafenib in first-line treatment of advanced hepatocellular carcinoma: A meta-analysis.

Objective: Lenvatinib and sorafenib are first-line oral multikinase inhibitors approved for the treatment of advanced hepatocellular carcinoma (HCC). However, the choice of the primary therapeutic agent among these two remains controversial. This meta-analysis aimed to estimate the efficacy and safety of lenvatinib and sorafenib in patients with advanced HCC. Methods: PubMed, Cochrane Library, Web of Science, and Embase databases were searched for relevant research published up to June 30, 2022. After quality assessment and data extraction of the included studies, RevMan 5.3 software was used for analysis. Odds ratio (OR) and hazard ratio (HR) with a 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. Results: Fifteen studies containing 3908 patients were included after final scrutiny. Our meta-analysis showed that there was no significant difference in overall survival (OS) between the lenvatinib and sorafenib groups (HR = 0.86; 95% CI: 0.72-1.02; p = 0.09); however, the progression-free survival (PFS) (HR = 0.63; 95% CI: 0.53-0.74; p < 0.00001), complete response (CR) (OR = 5.61; 95% CI: 2.71-11.64; p < 0.00001), partial response (PR) (OR = 4.62; 95% CI: 3.06-6.98; p < 0.00001), objective response rate (ORR) (OR = 5.61; 95% CI: 3.90-8.09; p < 0.00001), and disease control rate (DCR) (OR = 2.42; 95% CI: 1.79-3.28; p < 0.00001) in the lenvatinib group were significantly better than those in the sorafenib group. In terms of treatment safety, lenvatinib had similar incidences of any grade adverse events (AEs) (OR = 0.99; 95% CI: 0.47-2.09; p = 0.98) and grade ≥ 3 AEs (OR = 1.17, 95% CI; 1.00-1.37; p = 0.05) compared to sorafenib. Besides, lenvatinib was significantly associated with a higher incidence of hypertension, proteinuria, fatigue, decreased appetite, and weight loss, whereas sorafenib was associated with a higher incidence of diarrhea and hand-foot skin reaction (p < 0.05). Conclusion: Given its potential survival benefit and good tolerability, lenvatinib is an appropriate and promising alternative to sorafenib as first-line systemic therapy in patients with advanced HCC. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD 42022327398.

Intratumoral Administration of Thermosensitive Hydrogel Co-Loaded with Norcantharidin Nanoparticles and Doxorubicin for the Treatment of Hepatocellular Carcinoma.

BACKGROUND: The efficacy of systemic chemotherapy for hepatocellular carcinoma (HCC) is predominantly hampered by low accumulation in tumor tissue and the high systemic toxicity of anticancer drugs. In this study, we designed an in situ drug-loaded injectable thermosensitive hydrogel system for the simultaneous delivery of norcantharidin-loaded nanoparticles (NCTD-NPs) and doxorubicin (Dox) via intratumoral administration to HCC tumors. METHODS: NCTD-NPs were prepared by the thin film dispersion method using PCEC polymers as the carrier. Then, NCTD-NPs and Dox were co-encapsulated in a thermosensitive hydrogel based on Pluronic F127 (PF127) to construct a dual drug-loaded hydrogel system. The rheological properties of the drug-loaded hydrogel were studied using a rheometer. Drug release of the drug-loaded hydrogel and cytotoxicity in HepG2 cells were evaluated in vitro. An H22 tumor-bearing mice model was used to assess the in vivo antitumor activity of the drug-loaded hydrogel via intratumoral administration. RESULTS: The prepared drug-loaded hydrogel exhibited good thermal-sensitive properties, which remained liquid at room temperature and rapidly transformed into a non-flowing gel at body temperature, and released the drugs in a sustained manner. In vitro studies revealed that the drug-loaded hydrogel exhibited remarkable antiproliferative activity in HepG2 cells compared to free drugs. In vivo antitumor efficacy experiments showed that the drug-loaded hydrogel significantly suppressed tumor growth, alleviated side effects, and prolonged the survival time of mice bearing H22 tumors compared to the other groups. Moreover, immunohistochemical staining revealed that the expression of Ki-67 and CD31 in the drug-loaded hydrogel group was significantly lower than that in the other groups (P < 0.05), indicating that the drug-loaded hydrogel effectively inhibited tumor proliferation and angiogenesis. CONCLUSION: The formulated hybrid thermosensitive hydrogel system with sustained drug release and enhanced therapeutic efficacy was demonstrated to be a promising strategy for the local-regional treatment of HCC via intratumoral administration.

Application of Near-Infrared Fluorescence Imaging Technology in Liver Cancer Surgery.

Background. Hepatocellular carcinoma, among the most common malignant digestive system tumorsworldwide, is most effectively treated with precise surgical resection. Near-infrared fluorescence imaging technology is being increasingly used clinically and has achieved great initial results in the navigation of liver cancer surgery. Methods. This review describes the application of indocyanine green fluorescence (ICG) imaging technology with near-infrared window I in the navigation of liver cancer surgery, explores novel fluorescent probes and near-infrared window II fluorescence imaging technology, and discusses the development status of the 2 emerging tools. Results. ICG fluorescence imaging technology can precisely localize the tumor, reveal the boundary of liver cancer or liver segment, and identify the bile leakage. The novel fluorescent probe is more targeted than ICG, which makes the detection of cancer more accurate. Near-infrared window II fluorescence imaging technology can lead to outstanding gains in deeper detection, higher resolution, and fidelity. But, due to the shortcomings of machine and probe, it is not widely used in clinical. Conclusion. Near-infrared fluorescence imaging has great development potential. With the advent of precision medicine and the progress of various biotechnology studies, fluorescence imaging technology will be better developed and applied in the diagnosis, surgical navigation, and treatment of liver cancer.

Clinical Efficacy of Perioperative Immunonutrition Containing Omega-3-Fatty Acids in Patients Undergoing Hepatectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The effect of immunonutrition in patients undergoing hepatectomy remains unclear. This meta-analysis aimed to assess the impact of immunonutrition on postoperative clinical outcomes in patients undergoing hepatectomy. METHODS: A literature search of PubMed, Cochrane Library, Web of Science, and Embase databases was performed to identify all randomized controlled trials (RCTs) exploring the effect of perioperative immunonutrition in patients undergoing hepatectomy until the end of March 10, 2020. Quality assessment and data extraction of RCTs were conducted independently by 3 reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software. RESULTS: Nine RCTs involving a total of 966 patients were finally included. This meta-analysis showed that immunonutrition significantly reduced the incidences of overall postoperative complications (OR = 0.57, 95% CI: 0.34-0.95; p = 0.03), overall postoperative infectious complications (OR = 0.53, 95% CI: 0.37-0.75; p = 0.0003), and incision infection (OR = 0.50, 95% CI: 0.28-0.89; p = 0.02), and it shortened the length of hospital stay (MD = -3.80, 95% CI: -6.59 to -1.02; p = 0.007). There were no significant differences in the incidences of pulmonary infection (OR = 0.60, 95% CI: 0.32-1.12; p = 0.11), urinary tract infection (OR = 1.30, 95% CI: 0.55-3.08; p = 0.55), liver failure (OR = 0.54, 95% CI: 0.23-1.24; p = 0.15), and postoperative mortality (OR = 0.69, 95% CI: 0.26-1.83; p = 0.46). CONCLUSION: Given its positive impact on postoperative complications and the tendency to shorten the length of hospital stay, perioperative immunonutrition should be encouraged in patients undergoing hepatectomy.

Solid pseudopapillary neoplasm (SPN) of the pancreas presenting with ascites misdiagnosed as pancreatic tuberculosis: a case report and literature review.

INTRODUCTION: Solid pseudopapillary neoplasm (SPN) is a rare pancreatic tumor that mainly affects young women. It is a low-grade malignant neoplasm, with an excellent prognosis after surgical treatment. We report herein a case of SPN presenting with ascites that was misdiagnosed as pancreatic tuberculosis (TB). CASE REPORT: A 16-year-old female initially presented with a large volume of ascites. Contrast-enhanced ultrasound and computed tomography found a heterogeneous lesion in the pancreatic body, which had slight contrast enhancement on the arterial phase. Analysis of ascites showed it was exudative. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the mass only revealed a few blood clots. The diagnosis was highly suggestive of a pancreatic TB. However, after 6 months of anti-TB therapy, the pancreatic lesion remained essentially unchanged. Subsequently, magnetic resonance imaging indicated a mixed solid and cystic lesion with a well-defined margin in the pancreatic body. Further EUS-FNA showed monomorphic neoplastic cells with papillary architecture and immunohistochemical analysis revealed that the tumor cells were positive for ß-catenin, CD10, vimentin, cytokeratin, and synaptophysin. These findings were consistent with SPN. After distal pancreatectomy with splenectomy, postoperative pathology and immunohistochemical staining confirmed the diagnosis of SPN. CONCLUSION: Clinicians should consider the possibility of SPN for pancreatic heterogeneous masses. Multiple diagnostic imaging modalities and EUS-FNA may contribute to the preoperative diagnosis of this disease.