Platelet count as a predictor of vascular invasion and extrahepatic metastasis in hepatocellular carcinoma: A systematic review and meta-analysis.

Background: Vascular invasion (VI) indicates highly invasive tumor biological behavior and is a major determining factor of poor survival and high risk of metastasis in hepatocellular carcinoma (HCC). Epidemiological evidence of the association between pretherapeutic platelet count (PLT) and the risk of VI and extrahepatic metastasis in HCC remains controversial. Methods: A systematic retrieval was executed in databases of PubMed, Embase, and Web of Science until Dec 2022. Effect size and 95% confidence interval (CI) were extracted or estimated to synthetically investigate the effects of pretherapeutic PLT on VI and extrahepatic metastasis. Meta-analyses were performed by using a random or a fixed effects model. Results: Finally, the current meta-analysis included 15 studies with a total of 12,378 HCC patients. It was shown that, patients with a higher pretherapeutic level of PLT had a significantly increased risk of VI (11 studies,8,759 patients; OR = 1.44, 95%CI: 1.02-2.02) and extrahepatic metastasis (6 studies,8, 951 patients; OR = 2.51, 95% CI: 2.19-2.88) in comparison with patients with a lower PLT. Funnel plots and Begg's tests indicated that there were no significant publication biases. Conclusion: This meta-analysis shows that pretherapeutic elevated PLT is associated with an increased risk of VI and extrahepatic metastasis in HCC.

"Five steps four quadrants" modularized en bloc dissection technique for accessing hepatic hilum lymph nodes in laparoscopic pancreaticoduodenectomy.

BACKGROUND: Although en bloc dissection of hepatic hilum lymph nodes has many advantages in radical tumor treatment, the feasibility and safety of this approach for laparoscopic pancreaticoduodenectomy (LPD) require further clinical evaluation and investigation. AIM: To explore the application value of the "five steps four quadrants" modularized en bloc dissection technique for accessing hepatic hilum lymph nodes in LPD patients. METHODS: A total of 52 patients who underwent LPD via the "five steps four quadrants" modularized en bloc dissection technique for hepatic hilum lymph nodes from April 2021 to July 2023 in our department were analyzed retrospectively. The patients' body mass index (BMI), preoperative laboratory indices, intraoperative variables and postoperative complications were recorded. The relationships between preoperative data and intraoperative lymph node dissection time and blood loss were also analyzed. RESULTS: Among the 52 patients, 36 were males and 16 were females, and the average age was 62.2 ± 11.0 years. There were 26 patients with pancreatic head cancer, 16 patients with periampullary cancer, and 10 patients with distal bile duct cancer. The BMI was 22.3 ± 3.3 kg/m², and the median total bilirubin (TBIL) concentration was 57.7 (16.0-155.7) µmol/L. All patients successfully underwent the "five steps four quadrants" modularized en bloc dissection technique without lymph node clearance-related complications such as postoperative bleeding or lymphatic leakage. Correlation analysis revealed significant associations between preoperative BMI (r = 0.3581, P = 0.0091), TBIL level (r = 0.2988, P = 0.0341), prothrombin time (r = 0.3018, P = 0.0297) and lymph node dissection time. Moreover, dissection time was significantly correlated with intraoperative blood loss (r = 0.7744, P < 0.0001). Further stratified analysis demonstrated that patients with a preoperative BMI ≥ 21.9 kg/m² and a TIBL concentration ≥ 57.7 µmol/L had significantly longer lymph node dissection times (both P < 0.05). CONCLUSION: The "five steps four quadrants" modularized en bloc dissection technique for accessing the hepatic hilum lymph node is safe and feasible for LPD. This technique is expected to improve the efficiency of hepatic hilum lymph node dissection and shorten the learning curve; thus, it is worthy of further clinical promotion and application.

CDC123 promotes Hepatocellular Carcinoma malignant progression by regulating CDKAL1.

The cell proliferation protein 123 (CDC123) is involved in the synthesis of the eukaryotic initiation factor 2 (eIF2), which regulates eukaryotic translation. Although CDC123 is considered a candidate oncogene in breast cancer, its expression and role in Hepatocellular Carcinoma (HCC) remain unknown. Herein, we obtained the CDC123 RNA-seq and clinical prognostic data from the TCGA database. The mRNA level revealed that CDC123 was highly expressed in HCC patients, and Kaplan-Meier analysis implied better prognoses in HCC patients with low CDC123 expression (P < 0.001). The multivariate Cox analysis revealed that the CDC123 level was an independent prognostic factor (P < 0.001). We further confirmed a high CDC123 expression in HCC cell lines. Additionally, we found that CDC123 knockdown in HCC cell lines significantly inhibited cellular proliferation, invasion, and migration. Moreover, CDC123 was co-expressed with the CDK5 Regulatory Subunit-Associated Protein 1 Like 1 (CDKAL1), whose mRNA level was decreased after silencing CDC123. Therefore, we hypothesized that CDC123 promotes HCC progression by regulating CDKAL1.

FOXA1/MND1/TKT axis regulates gastric cancer progression and oxaliplatin sensitivity via PI3K/AKT signaling pathway.

BACKGROUND: Drug resistance is a main factor affecting the chemotherapy efficacy of gastric cancer (GC), in which meiosis plays an important role. Therefore, it is urgent to explore the effect of meiosis related genes on chemotherapy resistance. METHODS: The expression of meiotic nuclear divisions 1 (MND1) in GC was detected by using TCGA and clinical specimens. In vitro and in vivo assays were used to investigate the effects of MND1. The molecular mechanism was determined using luciferase reporter assay, CO-IP and mass spectrometry (MS). RESULTS: Through bioinformatics, we found that MND1 was highly expressed in platinum-resistant samples. In vitro experiments showed that interference of MND1 significantly inhibited the progression of GC and increased the sensitivity to oxaliplatin. MND1 was significantly higher in 159 GC tissues in comparison with the matched adjacent normal tissues. In addition, overexpression of MND1 was associated with worse survival, advanced TNM stage, and lower pathological grade in patients with GC. Further investigation revealed that forkhead box protein A1 (FOXA1) directly binds to the promoter of MND1 to inhibit its transcription. CO-IP and MS assays showed that MND1 was coexpressed with transketolase (TKT). In addition,TKT activated the PI3K/AKT signaling axis and enhanced the glucose uptake and lactate production in GC cells. CONCLUSIONS: Our results confirm that FOXA1 inhibits the expression of MND1, which can directly bind to TKT to promote GC progression and reduce oxaliplatin sensitivity through the PI3K/AKT signaling pathway.

HS1BP3, transcriptionally regulated by ESR1, promotes hepatocellular carcinoma progression.

PURPOSE: To explore the role of HS1-binding protein 3 (HS1BP3) in hepatocellular carcinoma (HCC) and the potential mechanism. METHODS: The effect of HS1BP3 in the prognosis of HCC was analyzed. The influence of HS1BP3 silence on proliferation, migration, cell cycle, and apoptosis of HCC cells (Huh-7 and Sun-449) were evaluated. The upstream transcription factors of HS1BP3 were further explored. RESULTS: The high expression of HS1BP3 in HCC was significantly associated with poor prognosis. The silencing of HS1BP3 inhibited proliferation, invasion, migration, and promoted G1 phase cell cycle arrest and apoptosis of HCC cells. Estrogen receptors 1 (ESR1) inhibited proliferation and improved the prognosis of HCC via fusion with HS1BP3 promoter. CONCLUSION: HS1BP3 may serve as a novel tumor-promoting factor transcriptionally regulated by ESR1.

Preoperative prediction for lymph node metastasis in early gastric cancer by interpretable machine learning models: A multicenter study.

BACKGROUND: The presence of lymph node metastasis plays a decisive role in the selection of treatment options in patients with early gastric cancer. However, there is currently no established protocol to predict the risk of lymph node metastasis before/after endoscopic resection. The aim of this study was to develop and validate several machine learning algorithms for clinical practice. METHODS: A total of 2,348 patients with early gastric cancer were selected from 5 major tertiary medical centers. We applied 6 machine learning algorithms to develop lymph node metastasis prediction models for clinical feature variables. The partial dependence plots were used to explain the prediction of the models. The area under the receiver operating characteristic curve and area under the precision recall curve were measured to assess the detection performance. The R shiny interactive web application was used to translate the prediction model in a clinical setting. RESULTS: The incidence of lymph node metastasis in patients with early gastric cancer was 13.63% (320/2348) and significantly higher in young women, in the lower third of the stomach, with a size >2 cm, depressed type, poorly/nondifferentiated, lymphovascular invasion, nerve invasion, and submucosal infiltration. In terms of age, there is a nonlinear and younger trend. XGBOOST displayed the best predictive performance at the initial and postendoscopy evaluation. In addition, the machine learning algorithm was converted to a user-friendly web tool for patients and clinicians. CONCLUSION: XGBOOST can predict the risk of lymph node metastasis with best accuracy in patients with early gastric cancer. Our online web application may help determine the optimal best surgical option for patients with early gastric cancer.

Rare Metastasis of Gastric Cancer to the Thyroid Gland: A Case Report and Review of Literature.

Background: It is common for patients with gastric cancer to develop distant metastases in the liver, lung, bone, and brain. Although the thyroid also has an abundant blood supply, gastric cancer metastasis to the thyroid is uncommon. Due to the rarity of such metastasis, its clinical features are not well understood. Here, we present the case of a patient with gastric cancer metastasis to the thyroid treated at our hospital. Case Summary: We report the case of a 63-year-old female with a mass in the anterior neck and mild hoarseness for 6 months. The patient underwent proximal subtotal gastrectomy for Siewert III oesophagogastric junction cancer 6 years ago. Subsequently, she received 8 cycles of adjuvant chemotherapy. Her condition was stable until mild hoarseness developed for no apparent reason 6 months prior to presenting at our clinic. Both ultrasonography and computed tomography confirmed a heterogeneous mass in the right lobe of the thyroid gland. Blood thyroid function tests and tumor marker expression levels were normal. Thyroid malignancy was suspected, and the patient underwent a right thyroidectomy. During the surgery, a tumor was found that had invaded the right recurrent laryngeal nerve and trachea. H&E staining and immunohistochemistry results suggested that the cancer cells originated from gastric cancer. The patient was diagnosed with thyroid metastasis of gastric cancer. She refused further treatment and died within 6 months. Conclusion: Metastasis of gastric cancer to the thyroid is rare and is associated with a poor prognosis. Immunohistochemical diagnosis is essential for a conclusive diagnosis. For patients with a history of malignant tumors, the possibility of metastatic thyroid nodules should be ruled out when diagnosing thyroid nodules.

Percutaneous biliary stent with intraluminal brachytherapy versus palliative surgery in the management of extrahepatic cholangiocarcinoma.

BACKGROUND: To compare the efficacy and outcomes of self-expandable metallic stent combined with catheter-loaded iodine-125 seeds (SEMS-CL-125I) brachytherapy versus conventional palliative surgery (PS) in advanced extrahepatic cholangiocarcinoma (EHCC). METHODS: The retrospective analysis consisted of 101 advanced EHCC patients who received SEMS-CL-125I (n = 67) or underwent PS (n = 34). The clinical characteristics, postoperative complications and overall survival (OS) were compared between the two groups. RESULTS: Serum levels of bilirubin, transaminase, and albumin (ALB) were significantly improved at 1 month, 3 months, and 6 months postoperatively in both groups (all P < 0.05). At 1 month after operation, the level of ALB in SEMS-CL-125I group was significantly higher than that in PS group (39.07 ± 3.83 vs. 36.60 ± 5.58 g/L, P = 0.015). No statistically significant difference was found in postoperative overall complications between the two groups (P = 0.052). Length of hospital stay was significantly shorter (P < 0.001), hospital costs were significantly less (P < 0.001), and OS was significantly better (P = 0.029) in SEMS-CL-125I group compared to PS group. Multivariate analysis further identified PS (HR = 2.90, 95% CI 1.71-4.93, P < 0.001) and higher level of carbohydrate antigen 19-9 (HR = 2.67, 95% CI 1.36-3.79, P = 0.002) as independent predictors of worse OS. CONCLUSION: SEMS-CL-125I significantly improves outcomes compared with PS and could be a safe and effective treatment for advanced EHCC.

Albumin-bilirubin and platelet-albumin-bilirubin grades for hepatitis B-associated hepatocellular carcinoma in Child-Pugh A patients treated with radical surgery: A retrospective observational study.

Child-Pugh (CP) grade A patients with early stage hepatocellular carcinoma (HCC) are candidates for curative surgery, while some patients still have a poor outcome. The aim of this study was to investigate the prognostic values of 2 new evaluation models for liver function, named albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) grades, in CP grade A patients with HCC.In this retrospective cohort study, we reviewed 134 cases of CP grade A patients with hepatitis B-associated HCC who underwent radical surgery. ALBI and PALBI grades were calculated based on preoperative serologic examinations. Overall survival (OS) and recurrence-free survival (RFS) were estimated by Kaplan-Meier curve and Cox regression. The prognostic performances of the models were estimated by using the concordance index (C-index).During a median follow-up time of 27 months, 27.6% (37/134) of patients died and 26.1% (35/134) experienced recurrence. Kaplan-Meier analyses showed that ALBI and PALBI grades were significantly associated with OS and RFS. Multivariate analyses further revealed that both ALBI and PALBI grades were independent predictors for survival. Furthermore, the prognostic values of the combination of tumor size with ALBI (C-index = 0.754, 95% confidence interval [CI]: 0.675-0.849) or with PALBI (C-index = 0.762, 95% CI: 0.664-0.844) may be comparable with both Barcelona Clinic Liver Cancer and Cancer of Liver Italian Program staging systems.The ALBI and PALBI grades, in particular the combination with tumor size, are effective models for discriminating survival in CP grade A patients with HCC.

Biliary stenting alone versus biliary stenting combined with 125I particles intracavitary irradiation for the treatment of advanced cholangiocarcinoma.

We aimed to compare the efficacy of percutaneous transhepatic biliary stenting (PTBS) and PTBS combined with 125I particles implantation in the treatment of advanced extrahepatic cholangiocarcinoma (EHC). A total of 184 advanced EHC patients, who received PTBS (PTBS group) or PTBS combined with 125I particles implantation (PTBS + 125I group) from January 2012 to April 2017 in our department, were retrospectively reviewed. The improvement of jaundice and liver function was observed in both groups. The postoperative complications, risk of biliary re-obstruction, and overall survival (OS) were compared between the two groups. Amongst, 71 cases received PTBS and 113 had the additional implantation of 125I particles. The jaundice and liver function were significantly improved in all patients, especially in PTBS + 125I group. There was no significant difference in the risk of postoperative complications between the two groups. However, the risk of biliary re-obstruction significantly reduced in PTBS + 125I group (19.5% vs. 35.2%, p = 0.017). Kaplan Meier analysis showed that patients in PTBS + 125I group had a significantly better OS, both for hilar and distal cholangiocarcinoma. Univariate analysis demonstrated that preoperative levels of carbohydrate antigen 19-9 (CA19-9), total bilirubin, neutrophil count, lymphocyte count, and different therapeutic method were significant factors affecting OS. Multivariate analysis further identified the treatment of PTBS combined with 125I particles implantation as an independent protective prognostic factor (HR = 0.26, 95% CI: 0.17-0.39, p < 0.001). In conclusion, for patients with advanced EHC, PTBS combined with 125I particles implantation is superior to PTBS alone in improving liver function, inhibiting biliary re-obstruction, and prolonging survival time.

Nutritional prognostic scores in patients with hilar cholangiocarcinoma treated by percutaneous transhepatic biliary stenting combined with 125I seed intracavitary irradiation: A retrospective observational study.

We mainly aimed to preliminarily explore the prognostic values of nutrition-based prognostic scores in patients with advanced hilar cholangiocarcinoma (HCCA).We retrospectively analyzed 73 cases of HCCA, who underwent percutaneous transhepatic biliary stenting (PTBS) combined with I seed intracavitary irradiation from November 2012 to April 2017 in our department. The postoperative changes of total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and albumin (ALB) were observed. The preoperative clinical data were collected to calculate the nutrition-based scores, including controlling nutritional status (CONUT), C-reactive protein/albumin ratio (CAR), and prognostic nutritional index (PNI). Kaplan-Meier curve and Cox regression model were used for overall survival (OS) analyses.The serum levels of TBIL, DBIL, ALT, AST, and ALP significantly reduced, and ALB significantly increased at 1 month and 3 months postoperatively. The median survival time of the cohort was 12 months and the 1-year survival rate was 53.1%. Univariate analysis revealed that the statistically significant factors related to OS were CA19-9, TBIL, ALB, CONUT, and PNI. Multivariate analysis further identified CA19-9, CONUT, and PNI as independent prognostic factors.Nutrition-based prognostic scores, CONUT and PNI in particular, can be used as predictors of survival in unresectable HCCA.

Prognostic significance of preoperative prognostic nutritional index in hepatocellular carcinoma: a meta-analysis.

BACKGROUND: To date, epidemiological evidence of the association between preoperative prognostic nutritional index (PNI) and the prognosis of hepatocellular carcinoma (HCC) remains controversial. METHODS: A literature search was performed in the databases of PubMed, Embase, and Web of Science. Hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI) were extracted to estimate the association of preoperative PNI with overall survival (OS), disease-free survival (DFS), and postoperative recurrence of HCC, respectively. A random-effects model was used to calculate the pooled effect size. RESULTS: Thirteen studies with a total of 3,738 patients with HCC met inclusion criteria for this meta-analysis. It indicated that a lower level of preoperative PNI was a significant predictor of worse OS (HR = 1.82, 95%CI: 1.44-2.31) and DFS (HR = 1.49, 95% CI: 1.06-2.07). In addition, risk of postoperative recurrence was significantly higher in patients with a lower preoperative PNI (OR = 1.92, 95% CI: 1.33-2.76). Subgroup analysis based on therapeutic intent demonstrated a significant positive association between preoperative low PNI and worse OS for those patients undergoing surgical resection and for those undergoing TACE or non-surgical treatment. CONCLUSION: The current meta-analysis demonstrates that preoperative PNI is a prognostic marker in HCC.

Albumin-Bilirubin Grade as a Novel Predictor of Survival in Advanced Extrahepatic Cholangiocarcinoma.

AIM: Child-Pugh (CP) grade has been used to assess liver function and postoperative outcomes in biliary tract neoplasms. The aim of this study was to preliminarily explore the prognostic significance of an alternative model of liver function, called albumin-bilirubin (ALBI) grade, in patients with extrahepatic cholangiocarcinoma (EHC). METHODS: A total of 109 advanced EHC patients, who received percutaneous transhepatic biliary stenting combined with iodine-125 seed implantation from January 2012 to April 2017 in our department, were enrolled. Preoperative clinical data were collected to calculate the CP and ALBI grades. The performance of ALBI score in predicting postoperative death was compared with that of CP score by using the receiver operating characteristic (ROC) curve. Kaplan-Meier analysis and Cox regression model were performed for overall survival (OS) analysis. RESULTS: The median survival time of our cohort was 12 months, and the 1-year and 2-year survival rates were 56.9% and 12.8%, respectively. The area under the ROC curve of ALBI score for predicting death was significantly greater than the CP score (0.751, 95% CI: 0.641-0.861, P < 0.001 vs. 0.688, 95% CI: 0.567-0.809, P < 0.001). The univariate analysis revealed that the factors related to overall survival of EHC were carbohydrate antigen 19-9, total bilirubin, albumin, ALBI grade, and CP score. In multivariate analysis, ALBI grade (HR = 1.65, 95% CI: 1.04-2.61, P = 0.032), but not CP score, was identified as an independent prognostic model. CONCLUSION: We demonstrated that the ALBI grade could be used as a predictor of survival in unresectable EHC patients.