Albumin-Lymphocyte-Globulin-C-Reactive Protein Index as a Novel Prognostic Biomarker for Hepatocellular Carcinoma After Hepatectomy.

INTRODUCTION: This study evaluated the performance of the albumin-lymphocyte-globulin-C-reactive protein (CRP) (ALGC) index as a novel prognostic biomarker for hepatocellular carcinoma (HCC) after hepatectomy. METHODS: Patients (n=178) who underwent hepatectomy for HCC (July 2010 - December 2021) were analyzed. The ALGC index was calculated as [(albumin × lymphocyte) / (CRP × globulin × 104)]. Patients were divided into a low ALGC group (<1.82; n=81) and a high ALGC group (≥1.82; n=97). The association of the ALGC index with survival was assessed by univariate and multivariate analyses. RESULTS: The median overall survival (OS) was 100 (range: 1-149) months with 1-, 3-, and 5-year OS rates of 91.6%, 81.2%, and 64.2%, respectively. In univariate analysis, ALGC index (<1.82), alpha-fetoprotein (≥25 ng/mL), tumor size (≥3.5 cm), microvascular invasion, and multiple tumors were associated with shorter OS. ALGC index (<1.82) (hazard ratio [95% confidence interval]) (2.48 [1.407-4.513]; P=0.001) and multiple tumors (1.92 [1.070-3.356]; P=0.029) were independent predictors of OS in multivariate analysis. CONCLUSION: ALGC index is a novel prognostic biomarker for HCC after hepatectomy. It may assist in treatment stratification and better management of patients with HCC.

Preoperative Myosteatosis and Prognostic Nutritional Index Predict Survival in Older Patients With Resected Biliary Tract Cancer.

Background/Aim: Sarcopenia accompanied by systemic inflammation is associated with poor prognosis in patients with cancer. This study evaluated the prognostic significance of sarcopenia (myopenia and myosteatosis) and systemic inflammatory markers in older patients (aged ≥80 years) with resected biliary tract cancer. Patients and Methods: Patients who underwent resection for biliary tract cancer between July 2010 and January 2023 at the NHO Fukuyama Medical Center were retrospectively reviewed. Preoperative computed tomography measured myopenia and myosteatosis, using the psoas muscle index and modified intramuscular adipose tissue content. Associations between clinicopathological characteristics, inflammation-based prognostic scores, and overall survival were analyzed using Cox proportional hazards models. Results: Univariate analysis revealed low C-reactive protein-to-albumin ratio (<0.125), low prognostic nutritional index (<42), low modified intramuscular adipose tissue content, higher T-stage (T3-4), lymph node metastasis, and postoperative complications associated with worse overall survival in older patients (aged ≥ 80 years) with resected biliary tract cancer (n=48). Multivariate analysis identified low prognostic nutritional index (<42) (p=0.007), low modified intramuscular adipose tissue content (p=0.015), higher T-stage (T3-4) (p<0.001), lymph node metastasis (p=0.001), and postoperative complications (p=0.017) as independent predictors of overall survival. Conclusion: Preoperative myosteatosis and low prognostic nutritional index are independent prognostic factors for overall survival in older patients (aged ≥80 years) with resected biliary tract cancer. These factors may be useful for risk stratification and clinical decision-making. Early interventions, such as nutritional support and physical exercise, may improve outcomes after resection of biliary tract cancer.

Predictive values of sarcopenia and systemic inflammation-based markers in advanced hepatocellular carcinoma after hepatectomy.

BACKGROUND: Sarcopenia accompanied by systemic inflammation is associated with poor prognosis in patients with advanced hepatocellular carcinoma (HCC). However, the effect of sarcopenia combined with systemic inflammation on the prognosis of patients with advanced HCC who underwent hepatectomy is unclear. This study aimed to evaluate the effect of sarcopenia and inflammation on the prognosis of patients with advanced HCC. METHODS: This retrospective study included 151 patients recruited between July 2010 and December 2022. We defined advanced HCC as that presenting with vascular invasion or tumor size ≥2 cm or multiple tumors. Sarcopenia was assessed using the psoas muscle index. Preoperative inflammatory markers were used by calculating the prognostic nutritional index, albumin-globulin ratio (AGR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio. Cox regression analysis was performed to determine the prognostic factors for overall survival. RESULTS: Of 151 patients, sarcopenia occurred in 84 (55.6 %). Sarcopenia was significantly associated with male sex, older age, body mass index (<25 kg/m2), and a higher NLR. In the multivariate analysis, AGR <1.25 (hazard ratio [HR], 2.504; 95% confidence interval [CI]: 1.325-4.820; p < 0.05); alpha-fetoprotein levels ≥25 ng/mL (HR, 1.891; 95% CI: 1.016-3.480; p = 0.04); and sarcopenia (HR, 1.908; 95% CI: 1.009-3.776; p < 0.05) were independent predictors of overall survival. The sarcopenia and low AGR groups had significantly worse overall survival than either the non-sarcopenia and high AGR or sarcopenia and low AGR groups. CONCLUSION: Sarcopenia and AGR are independent prognostic factors in patients with advanced HCC. Thus, sarcopenia may achieve a better prognostic value when combined with AGR.

Prognostic Significance of Sarcopenia and Systemic Inflammatory Markers in Biliary Tract Cancer: A Retrospective Cohort Study.

PURPOSE: To evaluate the prognostic significance of sarcopenia and systemic inflammatory markers in patients with surgically resected biliary tract cancer (BTC). METHODS: Between July 2010 and December 2022, 146 patients were recruited. Sarcopenia was assessed using the psoas muscle index. Preoperative inflammatory markers were used to calculate the prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Cox regression analysis was performed to determine prognostic factors for overall survival (OS) and recurrence-free survival (RFS). P < 0.05 was considered statistically significant. RESULTS: Sixty-four patients had sarcopenia. Sarcopenia was associated with body mass index (< 22 kg/m2), lymph node metastasis, and low PNI (< 42). R1/R2 resection (P = 0.02), sarcopenia (P < 0.001), lymph node metastasis (P = 0.007), intrahepatic cholangiocarcinoma (P < 0.001), and low PNI (P = 0.01) were independent predictors of OS, while male sex (P = 0.04), R1/R2 resection (P < 0.001), lymph node metastasis (P = 0.005), intrahepatic cholangiocarcinoma (P < 0.001), tumor differentiation (other than well; P = 0.003), and low PNI (P = 0.03) were independent predictors of RFS. Patients were stratified into no sarcopenia and high PNI (≥ 42; A), sarcopenia or low PNI (B), and sarcopenia and low PNI (C) groups. Group C had worse OS than the other two groups (P < 0.001 and P = 0.02, respectively). CONCLUSION: Sarcopenia is associated with the PNI. Sarcopenia and the PNI are independent prognostic factors among patients with resected BTC. Sarcopenia may have better prognostic value when combined with the PNI.

Viral uptake and pathophysiology of the lung endothelial cells in age-associated severe SARS-CoV-2 infection models.

Thrombosis is the major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the pathology of vascular endothelial cells (ECs) has received much attention. Although there is evidence of the infection of ECs in human autopsy tissues, their detailed pathophysiology remains unclear due to the lack of animal model to study it. We used a mouse-adapted SARS-CoV-2 virus strain in young and mid-aged mice. Only mid-aged mice developed fatal pneumonia with thrombosis. Pulmonary ECs were isolated from these infected mice and RNA-Seq was performed. The pulmonary EC transcriptome revealed that significantly higher levels of viral genes were detected in ECs from mid-aged mice with upregulation of viral response genes such as DDX58 and IRF7. In addition, the thrombogenesis-related genes encoding PLAT, PF4, F3 PAI-1, and P-selectin were upregulated. In addition, the inflammation-related molecules such as CXCL2 and CXCL10 were upregulated in the mid-aged ECs upon viral infection. Our mouse model demonstrated that SARS-CoV-2 virus entry into aged vascular ECs upregulated thrombogenesis and inflammation-related genes and led to fatal pneumonia with thrombosis. Current results of EC transcriptome showed that EC uptake virus and become thrombogenic by activating neutrophils and platelets in the aged mice, suggesting age-associated EC response as a novel finding in human severe COVID-19.

Suspected Accidental Infiltration of Rocuronium During General Anesthesia Induction: A Case Report.

There are few reports on rocuronium infiltration under general anesthesia. We report a case of suspected accidental rocuronium infiltration during anesthesia induction. A 25-year-old woman with autism spectrum disorder, intellectual disability, and epilepsy was scheduled for the extraction of 4 impacted third molars under general anesthesia. After induction with sevoflurane, an intravenous (IV) line was established in the left cephalic vein. Rocuronium was administered; however, subcutaneous swelling at the IV site was observed immediately. Spontaneous ventilations were maintained until additional rocuronium was administered via a new IV line. After heat pack application, the swelling disappeared 60 minutes after infiltration, and no tissue damage was observed. A strategy was developed to continue neuromuscular monitoring until recovery occurred. Acceleromyography was used, and the train-of-4 ratios at 99, 130, and 140 minutes after infiltration were 0.79, 0.91, and 1.0, respectively. Sugammadex was administered to prevent neuromuscular blockade recurrence. The patient was extubated once adequate return of muscle function and consciousness were observed. No neuromuscular block prolongation or recurrence were observed postoperatively. When rocuronium infiltration is suspected, it is important to eliminate swelling at the infiltration site and determine a management strategy based on neuromuscular monitoring.

Pyrolysis and steam gasification properties of mangroves.

The rising atmospheric CO2 emissions from the burning of fossil fuels remains a global concern. Mangrove forests, which are important for global biodiversity, are known for their high carbon fixation capacity. However, the characteristics of the pyrolysis and gasification of mangroves remain unclear. Thus, this study focused on mangroves' basic pyrolysis and steam gasification properties for use as a gasification fuel. Three mangrove species: Rhizophora mucronata, Bruguiera cylindrica, and Avicennia marina, were used as experimental samples. In addition, three species of land wood were used for comparison: Eucalyptus, Japanese cedar, and Japanese cypress. In addition to the raw sample, a demineralized sample was used for each sample to account for the influence of the alkali and alkaline earth metals (AAEMs) on pyrolysis and steam gasification. Thermogravimetric analysis was performed to obtain thermogravimetric curves of mangroves and land wood. A laboratory-scale instrument for pyrolysis and gasification using a batch-type horizontal electric furnace was also used at 800 °C in an inert and steam atmosphere. The char yield of raw mangroves was high and independent of the Klason lignin content, suggesting that AAEMs influence char formation during the initial pyrolysis of the mangroves. The results of pyrolysis and gasification under steam atmosphere showed that the H2 production ratio (Steam/Inert) from mangroves was 2.52-5.33, compared to 1.76-2.35 for land woods, the addition of steam significantly enhanced the steam gasification of mangroves. Mangroves contain relatively large amounts of AAEMs, which indicates their potential as a gasification feedstock.

Preoperative C-reactive protein-to-albumin ratio as a prognostic factor in biliary tract cancer: A systematic review and meta-analysis.

BACKGROUND: The preoperative C-reactive protein-to-albumin ratio is a novel inflammation-based prognostic marker in various cancers. However, its prognostic role in biliary tract cancer is unknown. We conducted a systematic review and meta-analysis to evaluate the prognostic value of preoperative C-reactive protein-to-albumin ratio in biliary tract cancer. METHODS: A systematic search of the literature for studies evaluating the prognostic value of C-reactive protein-to-albumin ratio in patients undergoing surgery for biliary tract cancer was conducted, and a random effects meta-analysis of overall survival and recurrence-free survival was performed. RESULTS: Nine studies with 1292 participants were included. The preoperative C-reactive protein-to-albumin ratio negatively correlated with overall survival (hazard ratio, 2.44 [95% confidence interval: 1.98-2.90]; P < .001) and recurrence-free survival (hazard ratio, 2.73 [95% confidence interval: 2.01-3.70]; P < .001). Subgroup analysis showed that an elevated preoperative C-reactive protein-to-albumin ratio predicted poor overall survival, regardless of the cutoff value, sample size, histological type, and treatment. CONCLUSION: An elevated preoperative C-reactive protein-to-albumin ratio is significantly associated with poor prognosis in patients undergoing surgery for biliary tract cancer. The C-reactive protein-to-albumin ratio may be an independent prognostic biomarker for overall survival and recurrence-free survival in patients undergoing surgery for biliary tract cancer.

C-reactive Protein-to-Albumin Ratio Predicts Conversion from Laparoscopic to Open Cholecystectomy in Acute Cholecystitis.

BACKGROUND/AIM: The aim of this study was to identify predictors of conversion from laparoscopic to open cholecystectomy, and to determine whether pre-operative C-reactive protein-to-albumin ratio (CAR) can predict conversion from laparoscopic to open cholecystectomy, in patients with acute cholecystitis diagnosed according to the Tokyo Guidelines 2018. PATIENTS AND METHODS: We retrospectively analysed 231 patients who underwent laparoscopic cholecystectomy for acute cholecystitis between January 2012 and March 2022. Two hundred and fifteen (93.1%) patients were included in the laparoscopic cholecystectomy group; sixteen (6.9%) patients were included in the conversion from laparoscopic to open cholecystectomy group. RESULTS: In univariate analysis, significant predictors of conversion from laparoscopic to open cholecystectomy included the interval between symptom onset and surgery (>72 h), C-reactive protein (≥15.0 mg/l) and albumin (<3.5 mg/l) levels, pre-operative CAR (≥5.54), gallbladder wall thickness (≥5 mm), pericholecystic fluid collection, and pericholecystic fat hyperdensity. In multivariate analysis, elevated pre-operative CAR (≥5.54) and the interval between symptom onset and surgery (>72 h) were independent predictors of conversion from laparoscopic to open cholecystectomy. CONCLUSION: Pre-operative CAR as a predictor of conversion from laparoscopic to open cholecystectomy may be useful for pre-operative risk assessment and treatment planning.

Lymphocyte-to-C-Reactive Protein Ratio Predicts Prognosis in Patients With Colorectal Liver Metastases Post-hepatic Resection: A Retrospective Study.

BACKGROUND/AIM: Preoperative systemic inflammation has been reported to predict survival in patients with various cancer types. In patients with colorectal liver metastasis (CRLM), the prognosis is poor despite therapeutic advances in the field. Here, we aimed to evaluate the prognostic role of the lymphocyte-to-C-reactive protein (CRP) ratio (LCR) in patients with CRLM after hepatic resection. PATIENTS AND METHODS: This retrospective study included 104 patients who underwent hepatic resection for CRLM between October 2010 and 2021 at the National Hospital Organization Fukuyama Medical Center, Hiroshima, Japan. The association between clinicopathological variables, including various inflammatory biomarkers [LCR, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), CRP-to-albumin ratio (CAR), and prognostic nutritional index (PNI)], and overall survival of the patients was investigated using univariate and multivariate analyses. RESULTS: The optimal cut-off values for each biomarker by receiver-operating characteristic analysis were as follows: LCR: 12,720; PLR: 150; NLR: 4; CAR: 0.023; and PNI: 44.8. The 1-, 3-, and 5-year overall survival rates were 97.0%, 71.3%, and 56.8%, respectively. On univariate analysis, LCR<12, 720, PLR<0.14, body mass index <24 kg/m2, carbohydrate antigen 19-9 ≥37 U/ml, multiple tumours, and largest hepatic tumour ≥5 cm were significant factors predictive of poorer survival. The multivariate analysis revealed that LCR<12, 720 (hazard ratio=2.156, 95% confidence interval=1.060-4.509, p=0.034) and multiple tumours (HR=2.336, 95% CI=1.125-4.925, p=0.023) were independent predictors of poor overall survival. CONCLUSION: LCR may be an independent prognostic predictor in patients after hepatic resection for CRLM. Therefore, the assessment of LCR as a biomarker may help in treatment planning.

Preoperative lymphocyte-to-C-reactive protein ratio predicts hepatocellular carcinoma recurrence after surgery.

Purpose: This study was performed to determine the prognostic value of lymphocyte-to-CRP ratio after curative resection for hepatocellular carcinoma. Methods: Between July 2010 and October 2021, 173 consecutive patients (144 male, 29 female) who underwent surgical resection for pathologically confirmed hepatocellular carcinoma were included in this retrospective study. Cox regression analysis was used to evaluate the relationship between clinicopathological characteristics and recurrence-free survival (RFS) and overall survival (OS). A P-value of <0.05 was considered statistically significant. Results: The patients (mean age, 71 years) were stratified into high (≥9,500, n = 108) and low (<9,500, n = 65) lymphocyte-to-CRP ratio groups. The low lymphocyte-to-CRP ratio group had significantly worse RFS and OS. Low lymphocyte-to-CRP ratio (hazard ratio [HR], 1.865; 95% confidence interval [CI], 1.176-2.960; P = 0.008), multiple tumors (HR, 3.333; 95% CI, 2.042-5.343; P < 0.001), and microvascular invasion (HR, 1.934; 95% CI, 1.178-3.184; P = 0.009) were independently associated with RFS, whereas low albumin-to-globulin ratio (HR, 2.270; 95% CI, 1.074-4.868; P = 0.032), α-FP of ≥25 ng/mL (HR, 2.187; 95% CI, 1.115-4.259; P = 0.023), and poor tumor differentiation (HR, 2.781; 95% CI, 1.041-6.692; P = 0.042) were independently associated with OS. Lymphocyte-to-CRP ratio had a higher area under the curve (0.635) than other inflammation-based markers (0.51-0.63). Conclusion: Lymphocyte-to-CRP ratio is superior to other inflammation-based markers as a predictor of RFS in patients with surgically resected hepatocellular carcinoma.

C-reactive protein to albumin ratio predicts difficult laparoscopic cholecystectomy in patients with acute cholecystitis diagnosed according to the Tokyo Guidelines 2018.

INTRODUCTION: Difficult laparoscopic cholecystectomy (DLC) may increase the risk of complications and extend the duration of hospitalization. The aims of this study were to evaluate the predictive value of C-reactive protein/albumin ratio (CAR) for DLC in patients with acute cholecystitis (AC) diagnosed according to the Tokyo Guidelines 2018 and to develop a preoperative predictive model for DLC. METHODS: We retrospectively analyzed 205 patients who had laparoscopic cholecystectomy for AC between January 2012 and December 2020. We defined DLC cases as having one of the following factors: blood loss ≥50 mL, operative time ≥150 minutes, or conversion to open surgery. We classified the remaining cases into the non-DLC group. RESULTS: Overall, 127 (62.0%) and 78 (38.0%) patients were grouped into the DLC and non-DLC groups, respectively. Patients in the DLC group had: higher severity grade, which was assessed using the Tokyo Guidelines 2018; higher incidence of postoperative complications; and more hospitalization days than those in the non-DLC group. Multivariate analysis revealed that male, CAR (≥3.20), and pericholecystic fat hyperdensity on computed tomography (CT) were independent predictors of DLC. We developed a predictive scoring system for DLC based on these three factors (cutoff value, 2.0; area under the curve, 0.75; sensitivity, 71.7%; and specificity, 70.5%). CONCLUSION: CAR could predict DLC independently in AC patients. We identified male gender, CAR, and pericholecystic fat hyperdensity on CT as predictive factors for DLC and established a preoperative prediction system based on these three factors.

SMAD4 Germline Pathogenic Variant-Related Gastric Juvenile Polyposis with Adenocarcinoma Treated with Laparoscopic Total Gastrectomy: A Case Report.

BACKGROUND Juvenile polyposis syndrome is an uncommon, autosomal-dominant hereditary disease that is distinguished by multiple polyps in the stomach or intestinal tract. It is associated with a high risk of malignancy. Pathogenic variants in SMAD4 or BMPR1A account for 40% of all cases. CASE REPORT A 49-year-old woman underwent esophagogastroduodenoscopy because of exacerbation of anemia. She had numerous erythematous polyps in most parts of her stomach. Based on biopsy findings, juvenile polyposis syndrome (JPS) was suspected morphologically, but there was no evidence of malignancy. Colonoscopy showed stemmed hyperplastic polyps and an adenoma; video capsule endoscopy revealed no lesions in the small intestine. After preoperative surveillance, laparoscopic total gastrectomy with D1 lymph node dissection was performed to prevent malignant transformation. The pathological diagnosis was juvenile polyp-like polyposis with adenocarcinoma. In addition, a germline pathogenic variant in the SMAD4 gene was detected with genetic testing. CONCLUSIONS JPS can be diagnosed with endoscopy and genetic testing. Further, appropriate surgical management may prevent cancer-related death in patients with this condition.