Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Centrifugal blood pumps drive blood flow by regulating blood flow rate,and have been widely used in clinical applications,including extracorporeal membrane oxygenation(ECMO),cardiopulmonary bypass(CPB),and extracorporeal circulation carbon dioxide removal(ECCO2R).However,because different structures and different forms of centrifugal pumps have different requirements for blood extracorporeal circulation in clinical application scenarios,blood pumps face different application conditions in clinical use.In this study,the effects of different structures of centrifugal pumps and different working conditions on blood damage are summarized for reference by relevant institutions and R&D personnel.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Objective:To compare the outcomes of percutaneous transhepatic one-step biliary fistulation (PTOBF) lithotripsy for type Ⅱa hepatolithiasis performed via the left or right lobe.Methods:A retrospective study was conducted on 79 patients with type Ⅱa hepatolithiasis treated in the First Affiliated Hospital of Guangzhou Medical University from January 2018 to December 2020, including 38 males and 41 females, aged (52.9±14.0) years. All patients had received PTOBF lithotripsy in single channel and divided into left lobe group ( n=40) and right lobe group ( n=39) according to different puncture approaches. Clinical data in immediate and final stone clearance rate, operation time of lithotripsy, intraoperative blood loss, postoperative complications (ascites, biliary tract infection), postoperative hospitalization time, reactive pleural effusion rate, the number of lithotripsy procedures and target bile duct dilatation diameter were compared between the two groups. Results:Compared with left lobe group, right lobe group had higher immediate stone clearance [51.3%(20/39) vs 22.5%(9/40)], less lithotripsy procedures [(2.4±1.0) vs (1.9±1.0)], but had longer postoperative hospitalization time [5(3, 6)d vs 3(2, 6)d] and higher reactive pleural effusion rate [23.1%(9/39) vs 2.5%(1/40)], the differences were all statistically significant (all P<0.05). No significant difference was found in target bile duct dilatation diameter, final stone clearance rate, intraoperative blood loss, postoperative complication rate, and operation time of lithotripsy (all P>0.05). Conclusions:Compared to the left lobe approach, right lobe approach could be prioritized in PTOBF lithotripsy for type Ⅱa hepatolithiasis, considering its higher immediate stone clearance and less lithotripsy procedures, but this surgical approach should pay attention to the occurrence of reactive pleural effusion.

Objective:Examining the risk factors for stone recurrence after percutaneous transhepatic one-step biliary fistulation (PTOBF) and lithotripsy for hepatic bile duct stones.Methods:The clinical data of 70 patients with hepatic bile duct stones combined with bile duct stenosis who underwent PTOBF lithotripsy at the First Hospital of Guangzhou Medical University from September 2016 to February 2023 were analyzed retrospectively, including 28 males and 42 females with the age of (48.9±17.5) years old. The patients were divided into two groups according to stone recurrence: recurrence group ( n=25) and non-recurrence group ( n=45). Clinical data such as age, gender, medical history, number of surgeries, and time with tube were recorded. Follow-up was performed by telephone and outpatient review. Multifactorial logistic regression was used to analyze the influencing factors of stone recurrence. Results:Univariate analysis showed statistically significant differences between the age, stone length diameter, number of stones, stage I undischarged stenosis, and number of surgeries between patients in the recurrent and non-recurrent groups (all P<0.05). Multifactorial logistic regression analysis showed that stone length ≥20 mm ( OR=4.389, 95% CI: 1.111-17.340, P=0.035), stage I undischarged stenosis ( OR=4.638, 95% CI: 1.170-18.385, P=0.029), and multiple number of operations ( OR=1.842, 95% CI: 1.031-3.290, P=0.039) had a high risk of stone recurrence after PTOBF lithotripsy in patients with hepatic bile duct stones. Conclusion:Stone length ≥20 mm, stage I unresolved stenosis, and number of surgeries were independent risk factors for stone recurrence in patients with hepatobiliary stones combined with bile duct stenosis after PTOBF and lithotripsy for hepatic bile duct stones.

Benign anastomotic stenosis remains a common complication after bilojejunal anastomosis. Its pathogenesis includes the histology of bile duct, bile erosion, and inappropriate choice of surgical anastomosis or suture materials. Biliojejunal anastomotic stenosis can be determined preoperatively by MRCP, CT, and three-dimensional image reconstruction. Surgery remains treatment of choice for most cases, including surgical reconstruction and minimally invasive treatment, while the incidence of restenosis, residual stone, and reoperation is still high. Surgeons are still in search of optimal treatment modality to avoid anastomotic stenosis. In this article, we review the literature and summarize the latest clinical progress in the diagnosis and treatment of biliojejunal anastomotic stenosis combined with hepatic ductal stones.

Objective:To evaluate the technical approach and application value of DynaCT biliary reconstruction with CT images fusion (DynaCT-CT fusion) for the treatment of complex hepatolithiasis.Methods:The data of 18 patients with complex hepatolithiasis admitted to the First Affiliated Hospital of Guangzhou Medical University from May 2022 to October 2022 were retrospectively analyzed, including 7 males and 11 females, aged (50.6±15.0) years. Preoperative DynaCT biliary reconstruction with CT images fusion was performed to guide the percutaneous transhepatic one-step biliary fistulation (PTOBF). The technical data, including the bile duct with stones identified by preoperative imaging, the actual bile duct with stones confirmed intraoperatively, the satisfied stone removal time for each targeted bile duct, the actual stone removal time for each targeted bile duct, the intraoperative identification of CT-negative stones, the postoperative complications and reoperation were analyzed.Results:In 18 patients, a total of 95 target bile ducts with stones were identified by preoperative DynaCT-CT fusion technology, involving the first, secondary and tertiary bile ducts. Preoperative CT identified 29 lesions of stones involving the first and secondary bile ducts. CT negative stones were confirmed in 5 patients by DynaCT-CT fusion. Bile duct stricture occurred in 12 patients. All procedures were completed without postoperative bile leakage or hemorrhage. A total of 82 lesions of stones were successfully removed with a removal time of (25.9±12.8) min. The satisfied stone removal time for each targeted bile duct was (10.1±7.6) min, and the actual stone removal time was (10.5±7.4) min. Immediate stone clearance was achieved in 13 patients. Biliary tract infection occurred in 2 patients, and 5 patients underwent reoperation for residual or recurrent stones.Conclusion:The DynaCT-CT fusion technology guided PTOBF is feasible and safe in patients with complex hepatolithiasis. It could effectively detect more stones, shorten the stone clearance time. DynaCT-CT fusion technology provides a new strategy for the treatment of hepatolithiasis.

Hepatolithiasis is a common disease in hepatobiliary surgery. The changes of bile dynamics in the biliary system, such as flow rate, pressure, viscosity, etc., play an important role in stone formation. In this paper, we introduce the bile fluid dynamics of the biliary system, analyze the influencing factors of bile dynamics change, the relationship between bile dynamics change and calculus, and the application of bile fluid dynamics in the treatment of hepatolithiasis, providing ideas and basis for the prevention and treatment of hepatolithiasis.

Liver cancer is one of the most common and fatal malignancies worldwide, with high mortality and morbidity. As an important tumor suppressor gene, p53 gene plays a key role in cell cycle regulation, cell growth and apoptosis of tumor cells. P53 gene mutations are closely related to the occurrence of liver cancer. At present, the treatment of liver cancer includes surgery, local treatment and systemic treatment. However, since most liver cancer patients are in advanced stages at the time of diagnosis, non-surgical treatment has become the best choice for the treatment of patients with intermediate and advanced liver cancer. But patients still have problems such as short survival and easy drug resistance. Therefore, the development of new treatment options is essential to improve the treatment outcomes of liver cancer patients. P53-related gene therapy products have great potential as drugs for the treatment of liver cancer. This article will briefly review the relationship between p53 gene and primary liver cancer, and explore its role in diagnosis and treatment, in order to provide a new direction for future clinical treatment.

Objective:To investigate the therapeutic effect of percutaneous transhepatic one-step biliary fistulation (PTOBF) combined with rigid choledochoscopy in the treatment of benign hepatic bile duct strictures.Methods:The clinical data of 46 patients with hepatic ductal stenosis and stones undergoing PTOBF combined with rigid choledochoscopy at the First Hospital of Guangzhou Medical University between September 2016 and September 2022 were retrospectively analyzed, including 20 males and 26 females, aged (48.5±17.6) years. The location of stones and strictures, stone retrieval rate, postoperative complications, stricture release rate, stone recurrence rate, and reoperation rate were analyzed to access the safety and effectiveness of this procedure.Results:A total of 58 sites of stenoses were found in 46 patients, and PTOBF lithotripsy combined with rigid choledochoscopy were performed for 77 times. The early postoperative complication rate was 19.6% (9/46), and the stenosis release rate was 93.5% (43/46). The mean follow-up time was (28.1±19.6) months, the complete stone retrieval rate was 91.3% (42/46), the stone recurrence rate was 19.6% (9/46), the reoperation rate was 8.7% (4/46), and the long-term postoperative complication rate was 6.5% (3/46).Conclusion:PTOBF combined with rigid choledochoscopic stenoplasty for benign hepatic duct strictures is a safe and feasible procedure to reduce the stone recurrence and long-term postoperative complications.