"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.

Apoptosis-resistant megakaryocytes produce large and hyperreactive platelets in response to radiation injury.

BACKGROUND: The essential roles of platelets in thrombosis have been well recognized. Unexpectedly, thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological, physical and chemical origins, which could be suffered by military personnel and civilians during chemical, biological, radioactive, and nuclear events. Especially, thrombosis is considered a major cause of mortality from radiation injury-induced thrombocytopenia, while the underlying pathogenic mechanism remains elusive. METHODS: A mouse model of radiation injury-induced thrombocytopenia was built by exposing mice to a sublethal dose of ionizing radiation (IR). The phenotypic and functional changes of platelets and megakaryocytes (MKs) were determined by a comprehensive set of in vitro and in vivo assays, including flow cytometry, flow chamber, histopathology, Western blotting, and chromatin immunoprecipitation, in combination with transcriptomic analysis. The molecular mechanism was investigated both in vitro and in vivo, and was consolidated using MK-specific knockout mice. The translational potential was evaluated using a human MK cell line and several pharmacological inhibitors. RESULTS: In contrast to primitive MKs, mature MKs (mMKs) are intrinsically programmed to be apoptosis-resistant through reprogramming the Bcl-xL-BAX/BAK axis. Interestingly, mMKs undergo minority mitochondrial outer membrane permeabilization (MOMP) post IR, resulting in the activation of the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway via the release of mitochondrial DNA. The subsequent interferon-ß (IFN-ß) response in mMKs upregulates a GTPase guanylate-binding protein 2 (GBP2) to produce large and hyperreactive platelets that favor thrombosis. Further, we unmask that autophagy restrains minority MOMP in mMKs post IR. CONCLUSIONS: Our study identifies that megakaryocytic mitochondria-cGAS/STING-IFN-ß-GBP2 axis serves as a fundamental checkpoint that instructs the size and function of platelets upon radiation injury and can be harnessed to treat platelet pathologies.

YY1 activates EMI2 and promotes the progression of cholangiocarcinoma through the PI3K/Akt signaling axis.

BACKGROUND: Cholangiocarcinoma (CCA) is one of the deadliest cancers of the digestive tract. The prognosis of CCA is poor and the 5-year survival rate is low. Bioinformatic analysis showed that early mitotic inhibitor 2 (EMI2) was overexpressed in CCA but the underlying mechanism is not known. METHODS: The data on bile duct carcinoma from TCGA and GEO databases were used to detect the expression of EMI2. The transcription factors of EMI2 were predicted using JASPAR and PROMO databases. Among the predicted transcription factors, YY1 has been rarely reported in cholangiocarcinoma, and was verified using the luciferase reporter gene assay. RT-PCR was performed to predict the downstream pathway of EMI2, and PI3K/Akt was suspected to be associated with it. Subsequently, in vivo and in vitro experiments were conducted to verify the effects of silencing and overexpressing EMI2 and YY1 on the proliferation, invasion, and metastasis of the bile duct cancer cells. RESULTS: EMI2 was highly expressed in CCA. Silencing EMI2 inhibited the proliferation, invasion, and migration of CCA cells, arrested cell cycle in the G1 phase, and promoted of apoptosis. The luciferase reporter gene assay showed that YY1 bound to the promoter region of EMI2, and after silencing YY1, the expression of EMI2 decreased and the progression of CCA was inhibited. Moreover, key proteins in the PI3K/Akt signaling pathway decreased after silencing EMI2. CONCLUSION: EMI2 may be one of the direct targets of YY1 and promotes the progression of CCA through the PI3K/Akt signaling pathway.

125I Intracavitary Irradiation Combined with 125I Seeds Implantation for Treatment of Locally Advanced Pancreatic Head Cancer: A Retrospective Analysis of 67 Cases.

BACKGROUND: Pancreatic cancer is an aggressive malignant tumor of the digestive system and the fourth leading cause of tumor-related death. Intracavitary 125I seed irradiation has been recently developed as a therapy for locally advanced pancreatic head carcinoma. However, there are still many limitations, and more investigations are needed in order to optimize this new treatment method. METHODS: Sixty-seven patients were included in our study; 41 cases treated by SEMS-CL-125I intracavular irradiation (SEMS-CL-125I group) and 26 cases treated by SEMS-CL-125I intracavular irradiation combined with 125I particle implantation in the tumor body (the combined group). Among the 67 patients, 43 were males and 24 were females, with an average age of 69.64±8.84 years. Tumor site size was determined based on the MRI or CT imaging scans, and the number and radius of 125I particle placement were calculated according to a specific formula. 125I particles were inserted into the tumor with a radius of 1.5 cm and a row spacing of 1 cm. The main postoperative biochemical indexes, imaging analysis, postoperative analgesia degree, median survival time and rate of complications were compared between the two groups. RESULTS: Jaundice and liver function improved in both groups after treatment for 6 months. The combined group did better. Kaplan-Meier analysis showed that patients in the combined group had a significantly better overall survival than those in the SEMS-CL-125I group. Patients in the combined group had less complications than those in the SEMS-CL-125I group (23.1% vs 34.1%), and the postoperative pain status of the combined group was improved (26.8% vs 53.8%). CONCLUSION: Compared with the SEMS-CL-125I intracavular irradiation alone, the combination of 125I seed implantation with solid tumor 125I seed implantation had a better therapeutic effect in LAPHC patients, with improved biochemical indicators, survival prognosis, pain relief, and fewer complications.