Expression and clinical significance of NLRC5 in hepatocellular carcinoma.

NLRC5, the largest member of the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family, has been reported to participate in the regulation of immune function and is associated with chronic inflammatory diseases. However, the biological function of NLRC5 in hepatocellular carcinoma (HCC) has not been fully demonstrated. The aim of this study is to evaluate NLRC5 expression in the tumor tissues of HCC patients undergoing surgical treatment, assess its prognostic value, and explore its relationship with critical immune-related molecules within the tumor microenvironment. A total of 100 patients with hepatitis B virus-associated HCC receiving surgical treatment were enrolled in the study. Immunohistochemical results were obtained by scoring the intensity of cellular staining and the percentage of positive cells in the tissue sections. The association between NLRC5 expression levels and the main clinicopathological factors was analyzed by Chi-square test method. The prognostic values were analyzed by COX regression model and the Kaplan-Meier survival curve. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of NLRC5 in postoperative patients with HCC. IHC showed that high expression of NLRC5 was observed in 67% of HCC tissue samples. Chi-square test showed that NLRC5 was a risk factor associated with tumor number, satellite nodule, and envelope invasion. Kaplan-Meier survival curves and COX survival analysis showed that high expression of NLRC5 was significantly associated with decreased overall survival (OS) in HCC patients (HR = 1.79, 95% CI 1.03-3.12, p = .041). However, univariate logistic regression analysis revealed that NLRC5 showed positive relationship with GZMB and CD8α suggesting its role in immune escape of HCC. ROC curve analysis showed that the combination of tumor number, envelope invasion, and NLRC5 expression (area under the curve = 0.824, sensitivity = 77.30%, specificity = 82.4%) can more accurately evaluate the prognosis of HCC patients compared to the combination of only tumor number and envelope invasion (area under the curve = 0.690, sensitivity = 43.9%, specificity = 94.1%).NLRC5 plays a crucial role in progression of HCC and can be considered as a potential prognostic and predictive biomarker. Targeting NLRC5 may provide an attractive therapeutic approach for HCC.

CRAFITY score benefits hepatocellular carcinoma patients treated with transarterial chemoembolization and lenvatinib.

BACKGROUND: The CRAFITY score serves as a simple and effective predictive model for individuals diagnosed with hepatocellular carcinoma (HCC) and subjected to treatment with atezolizumab and bevacizumab (Atez/Bev). However, no large sample size studies have reported the application of the CRAFITY score among HCC patients undergoing transarterial chemoembolization (TACE) in conjunction with lenvatinib. This research aims to assess the prognostic role of the CRAFITY score in the context of individuals with HCC receiving TACE in combination with lenvatinib. METHODS: This retrospective analysis encompassed 314 individuals diagnosed with HCC who underwent the combination of TACE and lenvatinib at two medical facilities in China from August 2019 to August 2022 (comprising a training cohort of n = 172 and a validation cohort of n = 142). We investigated the prognostic values of overall survival (OS), progression-free survival (PFS), disease control rate, and objective response rate in the training cohort based on the CRAFITY scores. Furthermore, the predictive capacity of the model was corroborated through validation using an external cohort. RESULTS: We included 174 and 142 patients treated with TACE plus lenvatinib in the training and validation cohorts, correspondingly. PFS and OS differed across all three groups in all training and validation cohorts, based on the CRAFITY score (p < 0.001). In both cohorts, the CRAFITY score effectively predicted tumor response (p < 0.001). Moreover, among the 121 patients who received TACE, lenvatinib, and immunotherapy, the CRAFITY score showed promising predictive efficacy in PFS and OS. CONCLUSIONS: The CRAFITY score, utilizing C-reactive protein and alpha-fetoprotein values, emerges as a dependable and pragmatic instrument for forecasting the effectiveness of TACE plus lenvatinib in individuals with unresectable HCC. This scoring system holds the potential to assist oncologists in making informed clinical decisions.

HAIC Combined with lenvatinib plus PD-1 versus lenvatinib Plus PD-1 in patients with high-risk advanced HCC: a real-world study.

BACKGROUND: The treatment of hepatocellular carcinoma (HCC) patients exhibiting high-risk characteristics (Vp4, and/or bile duct invasion, and/or tumor occupancy ≥ 50%) lacks standardized approaches and yields unfavorable results. This study endeavors to evaluate the safety, efficacy, and prognostic impacts of employing hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and humanized programmed death receptor-1 (PD-1) in the treatment of high-risk HCC patients. METHODS: In this retrospective analysis, HCC patients with high-risk features were treated with either lenvatinib combined with PD-1 (LEN-PD1) or a combination of HAIC, lenvatinib, and PD-1 (HAIC-LEN-PD1). The study assessed the antitumor efficacy by calculating overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Treatment-related adverse events (TRAEs) were analyzed to assess the safety profiles. RESULTS: Between June 2019 and September 2022, a total of 61 patients were included in the LEN-PD1 group, while 103 patients were enrolled in the HAIC-LEN-PD1 group. The OS was 9.8 months in the LEN-PD1 group, whereas the HAIC-LEN-PD1 group exhibited a significantly longer median OS of 19.3 months (HR = 0.43, p < 0.001). Furthermore, PFS was notably extended in the HAIC-LEN-PD1 group compared to the LEN-PD1 group (9.6 months vs. 4.9 months, HR = 0.48, p < 0.001). Patients in the HAIC-LEN-PD1 group had a higher ORR and DCR according to the modified RECIST (76.7% vs. 23.0%, p < 0.001; 92.2% vs. 72.1%, p = 0.001). HAIC-LEN-HAIC group led to more adverse events than LEN-PD1 group, most of which were tolerable and controllable. CONCLUSION: Lenvatinib, HAIC and PD-1 showed safe and promising anti-tumor activity compared with lenvatinib alone for HCC with high-risk features.

Efficacy of TACE Combined with Lenvatinib Plus Sintilimab for Hepatocellular Carcinoma with Tumor Thrombus in the Inferior Vena Cava and/or Right Atrium.

Purpose: To validate the safety and effectiveness of transarterial chemoembolization (TACE) combination with lenvatinib and sintilimab in treating hepatocellular carcinoma (HCC) patients with inferior vena cava (IVC) and/or right atrium (RA) tumor thrombosis (TT). Methods: This study retrospectively analyzed HCC patients with IVC and/or RA TT treated with TACE combined with lenvatinib plus sintilimab. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were calculated to evaluate the anti-tumor efficacy. Treatment-related adverse events (TRAEs) were analyzed to assess the safety profiles. Results: A total of 58 patients were screened for eligibility between March 2019 and May 2022. At the time of data collection, 48.2% of patients were still receiving treatment. The median follow-up was 23.5 months. The ORR was 48.3%, the DCR was 91.4%, the median OS was 17.3 months, and the median PFS was 13.0 months. The ORR for IVC/RA TT was 62.1%, DCR was 94.9%, and the median PFS was 14.3 months. 56.9% of patients experienced ≥ grade 3 TRAEs, such as hypertension (10.3%) and elevated liver enzymes (13.8%). No new safety signals were identified. Participants with low levels of serum PCT value had satisfactory prognoses. Conclusion: TACE combination with lenvatinib plus sintilimab is effective in treating HCC with IVC and/or RA TT. The toxicities were manageable, with no unexpected safety signals. The baseline levels of serum PCT might be the predictive biomarkers for the triple combination therapy.

Hepatic Arterial Infusion Chemotherapy Combined with Lenvatinib Plus Humanized Programmed Death Receptor-1 in Patients with High-Risk Advanced Hepatocellular Carcinoma: A Real-World Study.

Purpose: The treatment of hepatocellular carcinoma (HCC) patients with high-risk features (Vp4, and/or tumor occupancy≥50%) has not been standardized and has poor outcomes. The present study aimed to assess the safety, efficacy, and prognostic impact of lenvatinib, hepatic arterial infusion chemotherapy (HAIC), and humanized programmed death receptor-1 (PD-1) in treating high-risk patients and to explore the biomarkers that may predict the efficacy. Methods: HCC patients with high-risk features treated with lenvatinib, HAIC, and PD-1 were analyzed retrospectively. Overall survival (OS), progression-free survival (PFS), duration of response (DOR), objective response rate (ORR), and disease control rate (DCR) were calculated to evaluate the antitumor efficacy. Treatment-related adverse events (TRAEs) were analyzed to assess the safety profiles. Results: Between February 2020 and July 2022, 97 patients were enrolled in this retrospective cohort study. The median follow-up time was 447 days. During analysis, 65 patients had disease progression, and 39 patients died. The median PFS and OS were 295 and 579 days, respectively. According to RECIST 1.1 and mRECIST, the ORR was 64.9% and 78.3%, respectively, and the DCR was 92.8%. The median and intrahepatic DOR was 363 and 462 days, respectively. Treatment-related grade 3 or 4 adverse events occurred in 64 (65.9%) patients, and the most common adverse events were hypertension (9.3%), thrombocytopenia (7.2%), and elevated aspartate transaminase (7.2%). Participants with low levels of serum procalcitonin (PCT) had satisfactory prognosis. Conclusion: Lenvatinib, HAIC, and PD-1 were safe and showed promising antitumor activity against HCC with high-risk features. The initial levels of procalcitonin might be the predictive biomarkers for the combined treatment.

Combined model of radiomics and clinical features for differentiating pneumonic-type mucinous adenocarcinoma from lobar pneumonia: An exploratory study.

Purpose: The purpose of this study was to distinguish pneumonic-type mucinous adenocarcinoma (PTMA) from lobar pneumonia (LP) by pre-treatment CT radiological and clinical or radiological parameters. Methods: A total of 199 patients (patients diagnosed with LP = 138, patients diagnosed with PTMA = 61) were retrospectively evaluated and assigned to either the training cohort (n = 140) or the validation cohort (n = 59). Radiomics features were extracted from chest CT plain images. Multivariate logistic regression analysis was conducted to develop a radiomics model and a nomogram model, and their clinical utility was assessed. The performance of the constructed models was assessed with the receiver operating characteristic (ROC) curve and the area under the curve (AUC). The clinical application value of the models was comprehensively evaluated using decision curve analysis (DCA). Results: The radiomics signature, consisting of 14 selected radiomics features, showed excellent performance in distinguishing between PTMA and LP, with an AUC of 0.90 (95% CI, 0.83-0.96) in the training cohort and 0.88 (95% CI, 0.79-0.97) in the validation cohort. A nomogram model was developed based on the radiomics signature and clinical features. It had a powerful discriminative ability, with the highest AUC values of 0.94 (95% CI, 0.90-0.98) and 0.91 (95% CI, 0.84-0.99) in the training cohort and validation cohort, respectively, which were significantly superior to the clinical model alone. There were no significant differences in calibration curves from Hosmer-Lemeshow tests between training and validation cohorts (p = 0.183 and p = 0.218), which indicated the good performance of the nomogram model. DCA indicated that the nomogram model exhibited better performance than the clinical model. Conclusions: The nomogram model based on radiomics signatures of CT images and clinical risk factors could help to differentiate PTMA from LP, which can provide appropriate therapy decision support for clinicians, especially in situations where differential diagnosis is difficult.

Identification of triple gene fusion ALK-LRRN2, LTBP1-ALK, and HIP1-ALK in advanced lung adenocarcinoma and response to alectinib: A case report.

RATIONALE: Anaplastic lymphoma kinase (ALK) rearrangement is the second most common targetable oncogene-dirven gene in nonsmall cell lung cancer. Owing to the advanced sequencing technologies, new partner genes of ALK have been constantly detected. PATIENT CONCERNS: A 42-year-old Chinese woman went to our hospital with the chief complaint of cough and expectoration for 1 month. The patient had no fever, chest pain, and hemoptysis. DIAGNOSES: She was diagnosed with advanced lung adenocarcinoma. The patient underwent lung biopsy guided by computed tomography and pathology showed poorly differentiated adenocarcinoma. To explore possibility of targeted therapy, the tumor samples were subjected to next-generation sequencing, and a rare 3 ALK fusion variant ALK-LRRN2, LTBP1-ALK, and HIP1-ALK was identified. INTERVENTIONS AND OUTCOMES: The patient subsequently received alectinib treatment, and achieved partial response. No significant drug related adverse reactions were found during alectinib treatment. The progression-free survival achieved 25 months. LESSONS: Together, we identified a rare triple ALK fusion variant, ALK-LRRN2, LTBP1-ALK and HIP1-ALK, in a patient with lung adenocarcinoma. The patient benefited from alectinib treatment, which could provide a certain reference for the patients with such gene alteration.

Elastic intramedullary nailing combined with methylprednisolone acetate injection for treatment of unicameral bone cysts in children: a retrospective study.

PURPOSE: The aetiology of unicameral bone cysts (UBCs) is unclear. This study aims to evaluate the feasibility of elastic intramedullary nailing (EIN) combined with injections of methylprednisolone acetate (MPA) for the treatment of UBCs in children. METHODS: We retrospectively analyzed 53 children with UBCs in our hospital between January 2010 and April 2016. A total of 24 patients (Group A) were treated by EIN and MPA, whilst 29 patients (Group B) were treated by curettage, bone grafts and EIN fixation. The radiographs of the UBCs were evaluated following the Capanna criteria. All patients were followed-up on the third, sixth, 12th, 24th and 36th months. Fixation time, hospitalization time and complications were evaluated. RESULTS: In Group A, the mean number of MPA injections was 1.8 (1 to 3). Based on radiographic evaluation, eight patients were healed (Capanna grade I), 14 were healed with residual cysts (Capanna grade II), one showed recurrence (Capanna grade III) and one showed no response to the treatment (Capanna grade IV). In Group B, 11 patients were evaluated as Capanna grade I, 12 as Capanna grade II, three as Capanna grade III and three as Capanna grade IV. There was significant difference in the early postoperative function activity (p < 0.001), hospitalization time (p = 0.028), blood loss during surgery (p < 0.001) and surgery time (p < 0.001). CONCLUSION: The combination of EIN and MPA for the treatment of UBCs in children is feasible, has little operative trauma, short surgery time, short hospitalization time, less blood loss and a low risk of incision infection. LEVEL OF EVIDENCE: III.