Prognostic Value of Pathological Response for Patients with Unresectable Hepatocellular Carcinoma Undergoing Conversion Surgery.

Introduction: Transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor (triple therapy) has displayed encouraging clinical outcomes for unresectable hepatocellular carcinoma (uHCC). We aimed to explore the prognostic value of pathological response (PR) in patients with initially uHCC who underwent conversion surgery following triple therapy and identify predictors of major pathological response (MPR). Methods: A total of 76 patients with initially uHCC who underwent conversion surgery following triple therapy were retrospectively analyzed. PR was calculated as the proportion of nonviable tumor cell surface area of the whole tumor bed surface area. MPR was identified when PR was ≥90%. Pathological complete response (pCR) was defined as the absence of viable tumor cells. Results: MPR and pCR were identified in 53 (69.7%) and 25 (32.9%) patients, respectively. The 1- and 2-year overall survival in patients with MPR were significantly higher than in those without MPR (100.0% and 91.3% vs. 67.7% and 19.4%; p < 0.001). The corresponding recurrence-free survival was also improved in patients with MPR compared to those without (75.9% and 50.8% vs. 22.3% and 11.2%; p < 0.001). Similar results were observed among patients with pCR and those without. Patients who achieved MPR without pCR exhibited survival rates comparable to those of patients who achieved pCR. Baseline neutrophil-to-lymphocyte ratio ≥2.6 (p = 0.016) and preoperative alpha-fetoprotein level ≥400 ng/mL (p = 0.015) were independent predictors of MPR. Conclusion: The presence of MPR or pCR could improve prognosis in patients with initially uHCC who underwent conversion surgery following triple therapy. The PR may become a surrogate marker for predicting the prognosis of these patients.

The combination of transarterial chemoembolization, lenvatinib, and PD-1 inhibitor is an efficacious conversion therapy for uHCC. In this multicenter retrospective study, we discovered that PR was associated with the prognosis of patients who underwent conversion surgery. Predictors of MPR included neutrophil-to-lymphocyte ratio and alpha-fetoprotein levels.

Impact of Duration of Adjuvant Therapy on Patients with Initially Unresectable Hepatocellular Carcinoma After Conversion Surgery: A Propensity Score Matching Study.

Background: This study aimed to assess the effect of adjuvant therapy with different durations in patients with initially unresectable hepatocellular carcinoma (uHCC) after conversion surgery. Methods: This study included 85 patients with initially uHCC who received conversion surgery between May 2019 and November 2022. They were divided into the long duration group (n = 57) and short duration group (n = 28) based on postoperative medication duration. Recurrence-free survival (RFS) and overall survival (OS) were analyzed and compared between the cohorts. Results: No significant difference in RFS or OS was found between the two groups [RFS: hazard ratio (HR) = 0.486; 95% confidence interval (CI), 0.229-1.034, P = 0.061; OS: HR = 0.377; 95% CI, 0.119-1.196, P = 0.098]. Patients without major pathologic response (MPR) in the long duration group had better RFS and OS results compared to those in the short duration group (RFS: HR = 0.242; 95% CI, 0.092-0.634, P = 0.004; OS: HR = 0.264; 95% CI, 0.079-0.882, P = 0.031). No significant difference was detected in RFS or OS between the two groups in patients with MPR (RFS: HR = 1.250; 95% CI, 0.373-4.183, P = 0.718; OS: HR = 7.389; 95% CI, 0.147-372.4, P = 0.317). After propensity score matching, 25 pairs of patients were selected and the results remained consistent. Conclusion: At least 6 months of adjuvant therapy may be beneficial for patients without MPR after conversion surgery. However, in patients with MPR, the effect of adjuvant therapy remains unclear. Further studies are needed to confirm the optimal duration of adjuvant therapy.

Combination Therapy Consisting of Transarterial Chemoembolization, Lenvatinib, and Programmed Cell Death Protein 1 Blockade for Hepatocellular Carcinoma with Inferior Vena Cava Tumor Thrombus: A Case Series Study and Literature Review.

INTRODUCTION: Patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT) have poor prognosis. Combination therapy involving the blockade of programmed cell death protein 1 (PD-1) and tyrosine kinase inhibitors is an efficient treatment strategy for advanced HCC. However, surgical treatment after a combination of systemic therapy and transarterial chemoembolization (TACE) for HCC with IVCTT has not been widely reported, and the efficacy and safety of this treatment have not been studied. METHODS: In the 21 cases reported herein, the patients were treated with TACE, lenvatinib, and PD-1 blockade. The treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated, and the related literature was reviewed. RESULTS: The overall response and disease control rates were 66.7% and 85.7%, respectively. The median PFS time was 16.0 months, with a 1-year PFS rate of 55.60%. The median OS was not reached, with a 1-year OS rate of 66.70%. Four patients underwent hepatectomy without serious complications and survived for 29.1, 24.7, 14.2, and 13.8 months. Three patients survived tumor-free, and 1 patient experienced intrahepatic recurrence. Pathological complete response and major pathological responses were observed in 1 and 3 patients, respectively. Treatment-related adverse events of any grade occurred in 8/9 patients (88.9%), and grade 3 treatment-related adverse events occurred in 1 patient. CONCLUSION: The combination of TACE, lenvatinib, and PD-1 is effective for HCC with IVCTT and has acceptable adverse effects.

Case report: Emerging BRCA mutation confers benefit from olaparib after chemotherapy intolerance in advanced triple-negative breast cancer.

Key Clinical Message: In a patient with metastatic breast cancer, an acquired BRCA mutation in the BRCA gene was detected, resulting in benefits from olaparib treatment. This underscores the importance of ongoing genetic phenotype testing after paclitaxel chemotherapy. Abstract: Triple-negative breast cancer (TNBC) is associated with a poor prognosis and elevated mortality risk. BRCA mutations are commonly regarded as prevalent mutations in TNBC patients, strongly associated with congenital familial heredity. Dynamic changes in mutation sites, however, are rarely reported. In this case report, we report a 59-year-old TNBC patient who developed pulmonary metastases post-chemoradiotherapy. No BRCA mutations were detected through NGS. After 7.6 months of nab-paclitaxel treatment, the patient experienced progression of lung metastases, and BRCA mutations were detected through NGS testing. Subsequent administration of olaparib resulted in a reduction in lung metastasis, demonstrating significant therapeutic efficacy. This case underscores the infrequent occurrence of treatment-induced BRCA mutations and emphasizes the significance of dynamic NGS genetic testing for real-time assessment of a patient's mutational status.

Long-term surgical outcomes of bile duct tumor thrombus versus portal vein tumor thrombus for hepatocellular carcinoma: a propensity score matching analysis.

Background: Portal vein tumor thrombus (PVTT) seriously affects the prognosis of hepatocellular carcinoma (HCC). However, whether bile duct tumor thrombus (BDTT) significantly affects the prognosis of HCC as much as PVTT remains unclear. We aimed to compare the long-term surgical outcomes of HCC with macroscopic PVTT (macro-PVTT) and macroscopic BDTT (macro-BDTT). Methods: The data of HCC patients with macro-BDTT or macro-PVTT who underwent hemihepatectomy were retrospectively reviewed. A propensity score matching (PSM) analysis was performed to reduce the baseline imbalance. The recurrence-free survival (RFS) and overall survival (OS) rates were compared between the cohorts. Results: Before PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.043 and P = 0.008, respectively). Multivariate analyses identified PVTT (hazard ratio [HR] = 1.835, P = 0.016) and large HCC (HR = 1.553, P = 0.039) as independent risk factors for poor OS and RFS, respectively. After PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.037 and P = 0.004, respectively). The 3- and 5-year OS rates were significantly higher in the BDTT group (59.5% and 52.1%, respectively) than in the PVTT group (33.3% and 20.2%, respectively). Conclusion: Aggressive hemihepatectomy provides an acceptable prognosis for HCC patients with macro-BDTT. Furthermore, the long-term surgical outcomes of HCC patients with macro-BDTT were significantly better than those of HCC patients with macro-PVTT.

A new scoring system for predicting the outcome of hepatocellular carcinoma patients without microvascular invasion-a large-scale multicentre study.

BACKGROUND: The prognosis of HCC patients without MVI (so called M0) is highly heterogeneous and the need for adjuvant therapy is still controversial. METHODS: Patients with HCC with M0 who underwent liver resection (LR) or liver transplantation (LT) as an initial therapy were included. The Eastern Hepatobiliary Surgery Hospital (EHBH)-M0 score was developed from a retrospective cohort to form the training cohort. The classification which was developed using multivariate cox regression analysis was externally validated. RESULTS: The score was developed using the following factors: α-fetoprotein level, tumour diameter, liver cirrhosis, total bilirubin, albumin and aspartate aminotransferase. The score differentiated two groups of M0 patients (≤3, >3 points) with distinct long-term prognoses outcomes (median overall survival (OS), 98.0 vs. 46.0 months; p < 0.001). The predictive accuracy of the score was greater than the other commonly used staging systems for HCC. And for M0 patients with a higher score underwent LR. Adjuvant transcatheter arterial chemoembolization (TACE) was effective to prolong OS. CONCLUSIONS: The EHBH M0 scoring system was more accurate in predicting the prognosis of HCC patients with M0 after LR or LT. Adjuvant therapy is recommended for HCC patients who have a higher score.

Adult type I Gaucher disease with splenectomy caused by a compound heterozygous GBA1 mutation in a Chinese patient: a case report.

Gaucher disease (GD) is an autosomal recessive ailment resulting from glucocerebrosidase deficiency caused by a mutation in the GBA1 gene, leading to multi-organ problems in the liver, spleen, and bone marrow. In China, GD is extremely uncommon and has a lower incidence rate than worldwide. In this study, we report the case of an adult male with an enlarged spleen for 13 years who presented with abdominal distension, severe loss of appetite and weight, reduction of the three-line due to hypersplenism, frequent nosebleeds, and bloody stools. Regrettably, the unexpected discovery of splenic pathology suggestive of splenic Gaucher disease was only made after a splenectomy due to a lack of knowledge about rare disorders. Our patient's delayed diagnosis may have been due to the department where he was originally treated, but it highlights the need for multidisciplinary consultation in splenomegaly of unknown etiology. We then investigated the patient's clinical phenotypes and gene mutation features using genetically phenotypical analysis. The analysis of the GBA1 gene sequence indicated that the patient carried a compound heterozygous mutation consisting of two potentially disease-causing mutations: c.907C > A (p. Leu303Ile) and c.1448 T > C (p. Leu483Pro). While previous research has linked the p. Leu483Pro mutation site to neurologic GD phenotypes (GD2 and GD3), the patients in this investigation were identified as having non-neuronopathic GD1. The other mutation, p. Leu303Ile, is a new GD-related mutation not indexed in PubMed that enriches the GBA1 gene mutation spectrum. Biosignature analysis has shown that both mutations alter the protein's three-dimensional structure, which may be a pathogenic mechanism for GD1 in this patient.

Salvage Surgery for Initially Unresectable HCC With PVTT Converted by Locoregional Treatment Plus Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody.

BACKGROUND: This study aimed to compare the survival outcomes of patients with initially unresectable hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) who underwent or did not undergo salvage surgery followed by a triple combination conversion treatment consisted of locoregional treatment (LRT), tyrosine kinase inhibitors (TKIs), and anti-PD-1 antibodies. METHODS: The data from 93 consecutive patients with initially unresectable HCC and PVTT across 4 medical centers were retrospectively reviewed. They were converted successfully by the triple combination treatment and underwent or did not undergo salvage resection. The baseline characteristics, conversion schemes, conversion treatment-related adverse events (CTRAEs), overall survival (OS), and progression-free survival (PFS) of the salvage surgery and non-surgery groups were compared. Multivariate Cox regression analysis was performed to identify independent risk factors for OS and PFS. Additionally, subgroup survival analysis was conducted by stratification of degree of tumor response and type of PVTT. RESULTS: Of the 93 patients, 44 underwent salvage surgery, and 49 did not undergo salvage surgery. The OS and PFS of the salvage surgery and non-surgery groups were not significantly different (P = .370 and .334, respectively). The incidence and severity of CTRAEs of the 2 groups were also comparable. Subgroup analyses revealed that for patients with complete response (CR) or types III-IV PVTT, there was a trend toward better survival in patients who did not undergo salvage surgery. Multivariate analysis showed that baseline α-fetoprotein and best tumor response per mRECIST criteria were independent prognostic factors for OS and PFS. CONCLUSIONS: For patients with initially unresectable HCC and PVTT who were successfully converted by the triple combination therapy, salvage liver resection may not be necessary, especially for the patients with CR or types III-IV PVTT.

Outcomes of Salvage Surgery Versus Non-Salvage Surgery for Initially Unresectable Hepatocellular Carcinoma After Conversion Therapy with Transcatheter Arterial Chemoembolization Combined with Lenvatinib Plus Anti-PD-1 Antibody: A Multicenter Retrospective Study.

BACKGROUND: Combination treatment with transcatheter arterial chemoembolization (TACE), lenvatinib, and anti-programmed death-1 (anti-PD-1) antibodies (triple therapy) has a high rate of tumor response and converted resection for initially unresectable hepatocellular carcinoma (uHCC) patients. This study aimed to assess the outcomes of salvage surgery in uHCC patients after conversion therapy with triple therapy. METHODS: uHCC patients who met the criteria for hepatectomy after receiving triple therapy as first-line treatment were eligible for inclusion in this study. The overall survival (OS) and progression-free survival (PFS) rates in patients who received salvage surgery (SR group) and those who did not (non-SR group) were compared. RESULTS: Of the 144 patients assessed, 91 patients underwent salvage surgery and 53 did not. The OS rates in the SR group were significantly better than those in the non-SR group. The 1- and 2-year OS rates in the SR group were 92.0% and 79.9%, respectively, whereas those in the non-SR group were 85.5% and 39.6 %, respectively (p = 0.007); however, there was no significant difference in the PFS rates. Upon further stratification, OS and PFS were significantly better in the SR group than in the non-SR group in patients who were assessed as partial responses (PR), while there was no significant difference in patients who were assessed as complete response (CR). CONCLUSIONS: Salvage surgery is recommended and is associated with a favorable prognosis for uHCC patients who were assessed as PR after conversion therapy, however it may not be necessary for uHCC if CR was achieved.

Decreased NSD2 impairs stromal cell proliferation in human endometrium via reprogramming H3K36me2.

In brief: The proliferation of the endometrium is regulated by histone methylation. This study shows that decreased NSD2 impairs proliferative-phase endometrial stromal cell proliferation in patients with recurrent implantation failure via epigenetic reprogramming of H3K36me2 methylation on the promoter region of MCM7. Abstract: Recurrent implantation failure (RIF) is a formidable challenge in assisted reproductive technology because of its unclear molecular mechanism. Impaired human endometrial stromal cell (HESC) proliferation disrupts the rhythm of the menstrual cycle, resulting in devastating disorders between the embryo and the endometrium. The molecular function of histone methylation enzymes in modulating HESC proliferation remains largely uncharacterized. Herein, we found that the levels of histone methyltransferase nuclear receptor binding SET domain protein 2 (NSD2) and the dimethylation of lysine 36 on histone H3 are decreased significantly in the proliferative-phase endometrium of patients with RIF. Knockdown of NSD2 in an HESC cell line markedly impaired cell proliferation and globally reduced H3K36me2 binding to chromatin, leading to altered expression of many genes. Transcriptomic analyses revealed that cell cycle-related gene sets were downregulated in the endometrium of patients with RIF and in NSD2­knockdown HESCs. Furthermore, RNA-sequencing and CUT&Tag sequencing analysis suggested that NSD2 knockdown reduced the binding of H3K36me2 to the promoter region of cell cycle marker gene MCM7 (encoding minichromosome maintenance complex component 7) and downregulated its expression. The interaction of H3K36me2 with the MCM7 promoter was verified using chromatin immunoprecipitation-quantitative real-time PCR. Our results demonstrated a unifying epigenome-scale mechanism by which decreased NSD2 impairs endometrial stromal cell proliferation in the proliferative-phase endometrium of patients with RIF.

Matrix metalloproteinases as attractive therapeutic targets for chronic pain: A narrative review.

Chronic pain constitutes an abnormal pain state that detrimentally affects the quality of life, daily activities, occupational performance, and stability of mood. Despite the prevalence of chronic pain, effective drugs with potent abirritation and minimal side effects remain elusive. Substantial studies have revealed aberrant activation of the matrix metalloproteinases (MMPs) in multiple chronic pain models. Additionally, emerging evidence has demonstrated that the downregulation of MMPs can alleviate chronic pain in diverse animal models, underscoring the unique and crucial role of MMPs in different stages and types of chronic pain. This review delves into the mechanistic insights and roles of MMPs in modulating chronic pain. The aberrant activation of MMPs has been linked to neuropathic pain through mechanisms involving myelin abnormalities in peripheral nerve and spinal dorsal horn (SDH), hyperexcitability of dorsal root ganglion (DRG) neurons, activation of N-methyl-d-aspartate receptors (NMDAR) and Ca2+-dependent signals, glial cell activation, and proinflammatory cytokines release. Different MMPs also contribute significantly to inflammatory pain and cancer pain. Furthermore, we summarized the substantial therapeutic potential of MMP pharmacological inhibitors across different types of chronic pain. Overall, our findings underscore the promising therapeutic prospects of MMPs targeting for managing chronic pain.

Interleukin-17: A Putative Novel Pharmacological Target for Pathological Pain.

Pathological pain imposes a huge burden on the economy and the lives of patients. At present, drugs used for the treatment of pathological pain have only modest efficacy and are also plagued by adverse effects and risk for misuse and abuse. Therefore, understanding the mechanisms of pathological pain is essential for the development of novel analgesics. Several lines of evidence indicate that interleukin-17 (IL-17) is upregulated in rodent models of pathological pain in the periphery and central nervous system. Besides, the administration of IL-17 antibody alleviated pathological pain. Moreover, IL-17 administration led to mechanical allodynia which was alleviated by the IL-17 antibody. In this review, we summarized and discussed the therapeutic potential of targeting IL-17 for pathological pain. The upregulation of IL-17 promoted the development of pathological pain by promoting neuroinflammation, enhancing the excitability of dorsal root ganglion neurons, and promoting the communication of glial cells and neurons in the spinal cord. In general, the existing research shows that IL-17 is an attractive therapeutic target for pathologic pain, but the underlying mechanisms still need to be investigated.

The TAE score predicts prognosis of unresectable HCC patients treated with TACE plus lenvatinib with PD-1 inhibitors.

BACKGROUND AND AIMS: Transcatheter arterial chemoembolization combined with lenvatinib and PD-1 inhibitors (triple therapy) exhibits promising efficacy for unresectable hepatocellular carcinoma (uHCC). We aimed to evaluate the prognosis of patients with uHCC who received triple therapy and develop a prognostic scoring model to identify patients who benefit the most from triple therapy. METHODS: A total of 246 patients with uHCC who received triple therapy at eight centers were included and assigned to the training and validation cohorts. Prognosis was evaluated by the Kaplan-Meier curves. The prognostic model was developed by utilizing predictors of overall survival (OS), which were identified through the Cox proportional hazards model. RESULTS: In the training cohort, the 3-year OS was 52.0%, with a corresponding progression-free survival (PFS) of 30.6%. The median PFS was 13.2 months [95% confidence interval, 9.7-16.7]. Three variables (total bilirubin ≥ 17 µmol/L, alpha-fetoprotein ≥ 400 ng/mL, and extrahepatic metastasis) were predictors of poor survival and were used for developing a prognostic model (TAE score). The 2-year OS rates in the favorable (0 points), intermediate (1 point), and dismal groups (2-3 points) were 96.9%, 61.4%, and 11.4%, respectively (p < 0.001). The PFS was also stratified according to the TAE score. These findings were confirmed in an external validation cohort. CONCLUSIONS: Triple therapy showed encouraging clinical outcomes, and the TAE score aids in identifying patients who would benefit the most from triple therapy.

Clinical Complete Response After Conversion Therapy for Unresectable Hepatocellular Carcinoma: Is Salvage Hepatectomy Necessary?

Background: This study aimed to determine whether salvage hepatectomy offers prognostic advantages for unresectable hepatocellular carcinoma (uHCC) patients with clinical complete response (cCR) after conversion therapy. Methods: A total of 74 consecutive uHCC patients with cCR after conversion therapy at seven major cancer centers in China between October 2018 and December 2021 were included. One-to-one propensity score matching (PSM) was performed to minimize the influence of potential confounders. Disease-free survival (DFS) and overall survival (OS) rates were compared between the surgical group and the non-surgical group. Results: Before PSM, 45 patients received salvage hepatectomy, and 29 patients received nonsurgical treatment. The 1-, 2-, and 3-year DFS rates were 77.8%, 61.5%, and 61.5% in the surgical group and 81.2%, 60.9%, and 60.9% in the non-surgical group, respectively. The 1-, 2-, and 3-year OS rates were 92.9%, 92.9%, and 69.7% in the surgical group and 100%, 70%, and 70% in the non-surgical group, respectively. There were no statistical differences in DFS and OS between groups [hazard ratio (HR)=0.715, 95% confidence interval (CI): 0.250-2.043, p=0.531; HR=0.980, 95% CI: 0.177-5.418, p=0.982, respectively]. After PSM, 26 pairs of patents were selected; there remained no significant differences in DFS and OS between these two groups (HR=1.547, 95% CI: 0.512-4.669, p=0.439; HR=1.024, 95% CI: 0.168-6.242, p=0.979, respectively). Conclusion: Through the study, it tend to show that salvage hepatectomy may be not essential for uHCC patients with cCR, especially for patients with a high risk of surgical complications. Prospective trials with long term follow-up are warranted to evaluate this treatment option.

Surgical outcomes of hepatocellular carcinoma with extrahepatic bile duct tumor thrombus: a multicenter study.

Background: The long-term prognosis after surgery of patients with hepatocellular carcinoma (HCC) and extrahepatic bile duct tumor thrombus (Ex-BDTT) remains unknown. We aimed to identify the surgical outcomes of patients with HCC and Ex-BDTT. Methods: A total of 138 patients with Ex-BDTT who underwent hepatectomy with preservation of the extrahepatic bile duct from five large hospitals in China between January 2009 and December 2017 were included. The Cox proportional hazards model was used to analyze overall survival (OS) and recurrence-free survival (RFS). Results: With a median follow-up of 60 months (range, 1-127.8 months), the median OS and RFS of the patients were 28.6 and 8.9 months, respectively. The 1-, 3-, and 5-year OS rates of HCC patients with Ex-BDTT were 71.7%, 41.2%, and 33.5%, respectively, and the corresponding RFS rates were 43.5%, 21.7%, and 20.0%, respectively. Multivariate analysis identified that major hepatectomy, R0 resection, and major vascular invasion were independent prognostic factors for OS and RFS. In addition, preoperative serum total bilirubin ≥ 4.2 mg/dL was an independent prognostic factor for RFS. Conclusion: Major hepatectomy with preservation of the extrahepatic bile duct can provide favorable long-term survival for HCC patients with Ex-BDTT.

Transarterial Chemoembolization Plus Lenvatinib and PD-1 Inhibitors for Hepatocellular Carcinoma with Main Trunk Portal Vein Tumor Thrombus: A Multicenter Retrospective Study.

Purpose: In recent years, immune checkpoint inhibitors have been used in combination with tyrosine kinase inhibitors and local therapies, creating a new era in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, the benefits of this triple therapy remain unclear. Thus, this study evaluated whether the combination of transarterial chemoembolization (TACE), lenvatinib, and programmed death-1 (PD-1) inhibitors (triple therapy) was effective and safe for unresectable HCC with main trunk portal vein tumor thrombus (Vp4). Patients and Methods: This study enrolled patients receiving triple therapy at four institutions between August 2018 and April 2022. Patient characteristics and course of treatment were extracted from patient records. Tumors and tumor thrombus response were evaluated using an HCC-specific modified RECIST. Kaplan-Meier curve analysis demonstrated overall survival (OS) and progression-free survival (PFS). Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Results: Median follow-up duration was 18 (4.0-26.3) months. Overall, 41 patients with HCC and Vp4 receiving first-line triple therapy were enrolled. The intrahepatic tumor objective response rate was 68.3%. The median OS was 21.7 (range, 2.8-30.5) months, whereas the median PFS was 14.5 (range, 1.3-27.6) months. Twelve patients received sequential resections. Resection was independently associated with favorable OS and PFS. Fever (31.7%), hypertension (26.8%), fatigue (24.4%), abnormal liver function (63.4%) and decreased appetite (21.9%) were the AEs frequently associated with treatment. No treatment-related mortality occurred. Conclusion: TACE plus lenvatinib and PD-1 inhibition was effective and tolerable for treating unresectable HCC with Vp4, with a high tumor response rate and favorable prognosis.

Early Tumor Marker Response Predicts Treatment Outcomes in Patients with Unresectable Hepatocellular Carcinoma Receiving Combined Lenvatinib, Immune Checkpoint Inhibitors, and Transcatheter Arterial Chemoembolization Therapy.

Purpose: Few reliable biomarkers for predicting the efficacy of triple therapy (lenvatinib + immune checkpoint inhibitors + transarterial chemoembolization) exist for patients with unresectable hepatocellular carcinoma (uHCC). This study explored the prognostic role of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) levels in patients with uHCC receiving triple therapy. Patients and Methods: This retrospective study included 93 patients with uHCC who received triple therapy at Fujian Provincial Hospital between August 2020 and November 2022. Depending on the respective baseline levels, the patients were divided into high-AFP and high-DCP groups. An early response was defined as an AFP or DCP concentration >50% less than the baseline concentration after 6 weeks of triple therapy. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results: After 6 weeks of triple therapy, 75.3% (58/77) and 78.9% (60/76) of patients in the high-AFP and high-DCP groups achieved an objective response. Early AFP and DCP responses were positively associated with ORR (high-AFP group: odds ratio [OR]: 13.542; 95% confidence interval [CI]: 3.991-45.950, p<0.001; high-DCP group: OR: 17.853; 95% CI: 4.478-71.179, p<0.001). In the high-AFP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the AFP responders than those in the non-responders (PFS: 66.4%, 59.6%, 48.2% vs 42.3%, 19.3%, 0%, p<0.001; OS: 94.5%, 90.4%, 77.3% vs 75.6%, 66.2%, 49.6%, p=0.006). In the high-DCP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the DCP responders than those in the non-responders (PFS: 67.4%, 57.7%, 39.0% vs 38.9%, 8.1%, 0%, p<0.001; OS: 94.7%, 94.7%, 83.3% vs 77.0%, 53.9%, 36.0%, p<0.001). Conclusion: After 6 weeks of triple therapy, an AFP or DCP reduction of >50% predicts better treatment outcomes in uHCC patients.

Efficacy of cecal retroflexion observed on adenoma missing of ascending colon during colonoscopy: A prospective, randomized, pilot trial.

BACKGROUND: Although colonoscopic retroflexion has been proved effective in reducing missed adenomas, there is still a lack of comprehensive and in-depth research focused on the ascending colon. We aimed to conduct a randomized controlled trial and tandem colonoscopy to investigate whether cecal retroflexion observed during colonoscopy can reduce missed adenomas in the ascending colon. METHODS: Men and women required to be between 45 and 80 years of age were screened for enrollment in the trial. Patients were randomly assigned according to a 1:1 ratio to either the trial group or control group. Patients in the trial group underwent 2 forward examination and a cecal retroflexion observed in the ascending colon, while patients in the control group underwent only 2 forward examinations in the ascending colon. The primary outcome was adenoma miss rate. The secondary outcomes contained adenoma detection rate, polyp miss rate, polyp detection rate, insertion time and withdrawal time. Differences between groups in the primary outcome and in the other categorical indicators were tested using chi-squared test and Fisher exact test. For the comparison of continuous outcomes, the Student t test was applied. RESULTS: A total of 60 subjects were eligible for the study between April to June 2020, of which 55 were randomized and eligible for analysis (26 to the control group and 29 to the trial group). The characteristics of patients were no significant differences statistically between the trial group and the control group. Similarly, the characteristics of the colonoscopy procedures included cecal insertion distance, the length of cecum and ascending colon, insertion time, withdrawal time, quality of bowel preparation, numerical rating scale for pain, polyps detected, and adenomas detected, and there were no significant differences statistically between the 2 groups (P = .864, P = .754, P = .700, P = .974, P = .585, P = .835, P = .373, P = .489). The characteristics of the polyps were also no significant differences statistically between the 2 groups. CONCLUSION: This pilot trial failed to show benefit of cecal retroflexion observed on adenoma missing of ascending colon during colonoscopy; however, further conclusions require a prospective study with a higher level of evidence. (NCT03355443).