Cholecystohepatic shunt pathway reduces secondary bile acid accumulation to enhance natural killer T cell-mediated anti-hepatocellular carcinoma immunity.

BACKGROUND AND AIM: The impact of cholecystectomy, which blocks the cholecystohepatic shunt pathway (CHSP), on the prognosis of patients with hepatocellular carcinoma (HCC) is unclear. Hepatic secondary bile acids (BAs) inhibit natural killer T (NKT) cell-mediated immunity against HCC, and the regulation of homeostasis of hepatic secondary BAs is controlled by the CHSP. However, the influence of CHSP on NKT cell-mediated immunity against HCC remains unclear. METHODS: The clinical data of hospitalized patients undergoing HCC resection were collected. Meanwhile, an in situ HCC mouse model was established, and the CHSP was augmented using oleanolic acid (OA). RESULTS: After 1:1 propensity score matching, Cox regression analysis revealed that cholecystectomy was an independent risk factor for HCC recurrence after hepatectomy (P = 0.027, hazard ratio: 1.599, 95% confidence interval: 1.055-2.422). Experimentally, when OA enhanced CHSP, a significant decrease was observed in the accumulation of secondary BAs in the livers of mice. Additionally, a significant increase was observed in the levels of C-X-C ligand 16 and interferon γ in the serum and tumor tissues. Further, the percentage of C-X-C receptor 6 (+) NKT cells in the tumor tissues increased significantly, and the growth of liver tumors was inhibited. CONCLUSIONS: This clinical study revealed that cholecystectomy promoted the recurrence after radical hepatectomy in patients with HCC. Preserving the normal-functioning gallbladder as much as possible during surgery may be beneficial to the patient's prognosis. Further investigation into the mechanism revealed that CHSP enhanced NKT cell-mediated immunity against HCC by reducing the hepatic accumulation of secondary BAs.

Castleman Disease Misdiagnosed as Pancreatic Neuroendocrine Tumor by Fine Needle Aspiration Biopsy.

Castleman disease (CD) is a lymphoproliferative disorder that rarely occurs in the pancreas. We reported a 46-year-old man was admitted to our hospital due to recurrent minor epigastric pain for 7 days. The abdominal enhanced CT showed irregular foci in the body of the pancreas with abundant blood supply considered a neuroendocrine tumor. The patient was subsequently diagnosed with pancreatic neuroendocrine tumor by an ultrasound-guided fine needle aspiration biopsy. Therefore, he underwent an open pancreatic mass resection. The ultimate diagnosis was CD and belonged to hyaline vascular type based on the postoperative pathology. After a 13-month follow-up, no recurrence of abdominal pain or lesions was observed. This case suggests that fine needle aspiration biopsy is not conclusive and unsuitable for pancreatic CD and highlights the importance of routine pathology due to the absence of typical signs and symptoms.

A Case of Insidious Onset of Kimura Disease-associated Immunoglobulin A Nephropathy without Eosinophil Infiltration in the Renal Tissue.

Kimura disease (KD), also known as eosinophilic lymphogranuloma, is a rare chronic inflammatory or allergic disease. It can present with immune-related diseases such as nephrotic syndrome, asthma, and ankylosing spondylitis. In this study, we report a case of KD combined with immunoglobulin A nephropathy that first presented as a mass in the inguinal region, followed by recurrent renal involvement. Previous reports suggested that renal involvement caused by KD was due to direct infiltration of eosinophils; however, in this case, no eosinophil infiltration was found in the renal tissue after renal biopsy. This observation reminds us to approach the case from an immune-related molecular perspective to investigate the exact cause of renal damage due to KD.

Castleman disease of the pancreas mimicking pancreatic malignancy on 68Ga-DOTATATE and 18F-fluorodeoxyglucose positron emission tomography/computed tomography: A case report.

BACKGROUND: Castleman disease is an uncommon nonclonal lymphoproliferative disorder, which frequently mimics both benign and malignant abnormalities in several regions. Depending on the number of lymph nodes or regions involved, Castleman disease (CD) varies in diagnosis, treatment and prognosis. It rarely occurs in the pancreas alone without any distinct clinical feature and tends to be confused with pancreatic paraganglioma (PGL), neuroendocrine tumors (NETs), and primary tumors, thus impeding proper diagnosis and treatment. CASE SUMMARY: A 28-year-old woman presented with a lesion on the neck of the pancreas, detected by ultrasound during a health examination. Physical examination and laboratory findings were normal. The mass showed hypervascularity on enhanced computed tomography (CT), significantly increased 18F-fluorodeoxyglucose uptake on positron emission tomography (PET)/CT, and slightly increased somatostatin receptor (SSTR) expression on 68Ga-DOTATATE PET/CT, suggesting no distant metastases and subdiagnoses such as pancreatic PGL, NET, or primary tumor. Intraoperative pathology suggested lymphatic hyperplasia, and only simple tumor resection was performed. The patient was diagnosed with the hyaline vascular variant of CD, which was confirmed by postoperative immunohistochemistry. The patient was discharged successfully, and no recurrence was observed on regular review. CONCLUSION: High glucose uptake and slightly elevated SSTR expression are potentially new diagnostic features of CD of the pancreas.

Effectiveness of radiofrequency ablation versus transarterial chemoembolization for recurrent hepatocellular carcinoma: A meta-analysis.

Background: Both transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are effective methods for the treatment of recurrent hepatocellular carcinoma (RHCC). Thus far, it is unclear which method is more satisfactory in short- and long-term survival benefits. Purpose: To compare the overall survival (OS) and complications of TACE and RFA used for the management of RHCC. Material and Methods: A literature search was carried out using PubMed, the Cochrane Library and, Embase databases, and Google Scholar, keywords including "RHCC," "TACEC," and "RFA" with a cutoff date of 30 April 2021. Used Review Manager software was to calculate short- and long-term OS. The clinical outcomes are major complications and complete response (CR). Results: Finally, nine clinical trials met the research standard, including 1326 subjects, of which 518 received RFA and 808 received TACE. The analysis showed that patients who underwent RFA had significantly higher 1-, 3-, and 5-year OS (OR1-year = 1.92, 95% confidence interval (CI) = 1.27-2.91, p = .002; OR3-year = 1.64, 95% CI = 1.30-2.08, p <.0001; OR5-year = 3.22, 95% CI = 1.34-7.72, p=.009). Besides, the patients who chose RFA had an obvious higher rate of CR than those receiving TACE (OR = 33.75, 95% CI = 1.73-658.24, p = .002). However, the major complications were consistency between these two groups. Conclusion: Our study discovered that RFA had greater CR and incidence in both the short-term and long-term OS than TACE. In addition, obvious difference was not found in major complications in these two methods.

Obeticholic acid and 5ß-cholanic acid 3 exhibit anti-tumor effects on liver cancer through CXCL16/CXCR6 pathway.

Hepatocellular carcinoma (HCC) is the most common type of liver malignancy with a high incidence and mortality rate. Previous in vitro and in vivo studies have confirmed that liver sinusoidal endothelial cells (LSEC) secrete CXCL16, which acts as a messenger to increase the hepatic accumulation of CXCR6+ natural killer T (NKT) cells and exert potent antitumor effects. However, evidence for this process in humans is lacking and its clinical significance is still unclear. In this study, by dissecting the human HCC single-cell RNA-seq data, we verified this process through cellphoneDB. NKT cells in patients with high expression of CXCL16 exhibited a higher activation state and produced more interferon-γ (IFN-γ) compared with those with low expression. We next investigated the signaling pathways between activated (CD69 high) and unactivated NKT cells (CD69 low) using NKT cell-developmental trajectories and functional enrichment analyses. In vivo experiments, we found that farnesoid X receptor agonist (obeticholic acid) combined with the takeda G protein coupled receptor 5 antagonist (5ß-cholanic acid 3) exhibited significant tumor suppressive effects in the orthotopic liver tumor model and this result may be related to the CXCL16/CXCR6 axis. In conclusion, our study provides the basis and potential strategies for HCC immunotherapy based on NKT cells.