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Ectopic lymphoid structures termed tertiary lymphoid structures (TLSs) have an immunomodulatory function and positively affect prognosis in certain cancers. However, their clinical relevance and prognostic utility in perihilar cholangiocarcinoma (pCCA) are unknown. Therefore, determining the involvement and prognostic utility of TLSs in pCCA is the aim of this study. Ninety-three patients with surgically resected pCCA were included retrospectively. Hematoxylin and eosin and immunohistochemical staining identified and classified the TLSs, and multiplex immunofluorescence determined the TLS composition in the pCCA sample. The correlations between clinical features and TLSs were analyzed using either Fisher’s exact test or the Chi-squared test. Recurrence-free survival (RFS) and overall survival (OS) correlations with TLSs were analyzed using Cox regression and Kaplan–Meier analyses. We identified TLSs in 86% of patients with pCCA, including lymphoid aggregates (6.45%), primary (13.98%) and secondary follicles (65.59%). Patients with intra-tumoral secondary follicle-like TLSs (S-TLSs) had better OS (p = 0.003) and RFS (p = 0.0313). The multivariate analysis identified the presence of S-TLSs as a good independent prognostic indicator for OS but not for RFS. Interestingly, the presence of S-TLS only indicated better 5-year OS in 54 patients without lymph node metastasis (LNM−, p = 0.0232) but not in the 39 patients with lymph node metastasis (LNM+, p = 0.1244). Intra-tumoral S-TLSs predicted longer OS in patients with surgically resected pCCA, suggesting intra-tumoral S-TLSs’ contribution to effective antitumor immunity and that S-TLSs hold promise for diagnostic and therapeutic development in pCCA.

BackgroundEmerging evidence has shown that exosome microRNAs (miRNAs) regulate the development of hepatocellular carcinoma (HCC). Here, the influences of miR-4800-3p on the progression of HCC were explored.Materials and MethodsThe expression of miR-4800-3p in the exosome derived by transforming growth factor beta 1 (TGF-β1)-treated HCC cells and the serum exosome isolated from HCC patients were identified by real-time PCR. The effects of TGF-β1 and the influences of Huh7-secreted exosomes and the effects of miR-4800-3p combined with/without STK25 on cell functions were explored using the EdU assay cloning experiments, wound healing assay, and Transwell assay. The corresponding molecular mechanisms were further detected using Western blot and real-time PCR assays. The combination of miR-4800-3p and STK25 was verified by the dual-luciferase and RNA pulldown assays. The influences of miR-4800-3p on the growth and epithelial–mesenchymal transformation (EMT) of implanted tumors were tested in vivo and further confirmed by Western blot.ResultsThe miR-4800-3p expression was highly expressed in both exosomes derived by TGF-β1-treated HCC cells and the serum exosomes of HCC patients. In the cases of treatment with both Huh7-derived exosomes, the level of miR-4800-3p expression was highest, and the treatment of TGF-β1 could greatly promote the proliferation, stemness, migration, and invasion of HCC cells via upregulating the markers of stemness and EMT, including CD44, CD133, OCT4, N-cadherin, E-cadherin, and ZO-1. Similar results could be obtained when miR-4800-3p was overexpressed in HCC cells. Furthermore, downregulation of STK25 expression, a direct target gene of miR-4800-3p, could greatly rescue the malignant biological behaviors aggravated by overexpression of miR-4800-3p. This was achieved by suppressing the expression of CD44, CD133, OCT4, N-cadherin, and PCNA and activating the Hippo pathway while increasing E-cadherin and ZO-1. Similar results were also obtained in vivo that knockdown of miR-4800-3p expression suppressed tumor growth induced by Huh7-derived exosomes by mediating the EMT markers and the Hippo signaling pathway.ConclusionExosomal miR-4800-3p could accelerate HCC development by regulating the Hippo signal by targeting STK25, which could be used as a new therapeutic target for HCC treatment.

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Background: En bloc resection of the uncinate process of the pancreas represents the most important yet difficult step in laparoscopic pancreaticoduodenectomy (LPD), given the risk of major intraoperative bleeding which often necessitates the conversion to open surgery. We therefore developed the intermittent superior mesenteric artery occlusion (ISMAO) technique as a means of blood flow control during uncinate process resection, and investigated its role in LPD. Methods: Consecutive patients who underwent LPD at the Department of Biliary and Pancreatic Surgery, Sun Yat-sen Memorial Hospital between August 2020 and May 2022 were enrolled. Patients were divided into 2 groups, the ISMAO and non-ISMO group. Parameters such as operation time, intraoperative blood loss volume, conversion rate to open surgery, R0 resection rate, bowel function recovery time, postoperative hospital stay length, and rate of postoperative complications (including pancreatic fistula, delayed gastric emptying, and postoperative bleeding) were compared. Results: A total of 51 patients were included, of whom 22 (43.1%) underwent ISMAO. Significantly shorter mean operation time was observed in the ISMAOgroup compared to the non-ISMAO group (349.8 ± 84.9 min vs. 533.5 ± 105.9 min; P < 0.001). In addition, ISMAO associated with significantly lower intraoperative blood loss volume [112.5 (87.5-200.0) mL vs. 400.0 (250.0-600.0) mL; P < 0.001], and significantly lower conversion rate to open surgery (4.54% vs. 26.0%; P = 0.0485). R0 resection rate in the ISMAO group was significantly higher (95.5% vs. 79.3%; P = 0.0485). No significant differences were observed in postoperative hospital stay length, bowel function recovery time, and postoperative complication rate between the groups. Conclusions: ISMAO represents a novel blood flow control technique for en bloc resection of the uncinate process. Our study demonstrated its role in improving surgical safety and reducing intraoperative bleeding, and suggests its potential as a standard surgical procedure in LPD.

Biliary adenofibroma is an extremely rare benign liver tumor, but it may be a precancerous lesion of cholangiocarcinoma. So far, only 29 cases have been reported in the literature. A 30-year-old woman was admitted to our department for upper abdomen mass. The computed tomography scan showed a huge cystic and partly substantial mass between the left lobe of the liver and the descending duodenum, which was considered to be an exophytic tumor derived from the left lobe of the liver. Laparoscopic liver segment IVb resection and cholecystectomy were performed. Microscopic examination showed that the tumor was composed of glandular cavities of varying sizes and fibrous interstitium. The glandular cavity was covered with cubic or columnar epithelium without atypia. Some of the mesenchymal cells are myofibroblast-like and spindle-shaped with red-stained cytoplasm. The mesenchymal cells in some areas proliferate densely with moderate atypia. It was considered to be an atypical biliary adenofibroma with focal necrosis and active cell proliferation which may have malignant transformation potential. There was no recurrence and metastasis at a 6-month follow-up. Biliary adenofibroma is a rare benign tumor derived from the bile duct, but it may progress to malignancy and develop distant metastasis. It is difficult to distinguish it from other liver tumors through imaging examination and the gold standard of diagnosis is histopathological examination. Close clinical follow-up is recommended.