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Biliary tract cancer is a highly lethal disease composed of diverse epithelial tumors, of which incidence is increasing. Nearly two-thirds of patients with biliary tract cancer are in local advanced stage or metastasized at diagnosis. Systemic therapies are the primary treat-ment options, but the prognosis is poor. In recent years, the emergence of immune checkpoint inhibitors has changed the treatment prospects for advanced solid tumors, and multiple clinical trials and related studies have been conducted worldwide. Based on clinical experiences and pertinent researches in the field, the authors expound upon the research progress in immune checkpoint inhibitors treatment of advanced biliary tract cancer.
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Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4,2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.
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Tumor-infiltrating lymphocytes (TILs) are a heterogeneous subset of lymphocytes, mainly T cells, present in tumor parenchyma and stroma. After being digested and isolated from tumor tissue and then cultured in vitro for activation and multiplication, it can be infused back into the patient's body to kill tumor cells. TILs have the advantages of high diversity of TCR, excellent ability to infiltrate into tumor sites, and low toxicity and are considered promising for the treatment of malignant solid tumors. At present, TIL therapy has been tested as a second-line treatment in a variety of solid tumors and has achieved preliminary results. Although there is still no clinical cohort report on the application of TILs in biliary tract cancer (BTC), recent clinical reports on multiple cancers have provided information on the efficacy of TIL therapy in a small number of BTC patients, which preliminarily confirmed the safety and efficacy of TIL therapy. However, since BTC is generally considered an immunologically repulsive tumor in which most effector T cells are sequestered at the tumor edge, the antitumor effect of TILs in BTC remains difficult to predict. Combination therapy with different anti-tumor methods and the development of new techniques to modify cells to enhance the anti-tumor ability of TILs are possible directions for breakthrough in the future.
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Objective:To evaluate A modified Blumgart pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy.Methods:The clinical data of 81 patients undergoing laparoscopic pancreaticoduodenectomy in Zhengzhou University Affiliated Cancer Hospital from Jan 2019 to Jan 2022 were retrospectively analyzed. Among them, 26 patients underwent modified Blumgart anastomosis and 55 underwent conventional Blumgart anastomosis.The data of demographics, liver function, pancreatic texture, operational result and complications were compared between the two groups.Results:The preoperative data (body mass index, preoperative albumin, prealbumin, transaminase, total bilirubin) between two groups were comparable ( P>0.05). There was no significant difference in pancreatic texture, pancreatic duct diameter and intraoperative blood loss between the two groups ( P>0.05). The modified group had shorter total operation time ( P<0.05), shorter pancreaticojejunostomy time ( P<0.05), shorter postoperative hospital stay ( P<0.05). The incidence of total pancreatic fistula and biochemical fistula in the modified group were lower than those in the conventional group ( P<0.05). There was no significant difference in the incidence of B/C grade pancreatic fistula and bile leakage, postoperative bleeding, infection and delayed gastric emptying between the two groups ( P>0.05). Conlusions:The modified Blumgart pancreaticojejunostomy during laparoscopic pancreaticoduodenectomy is safe, easy to do and time saving. While the incidence of postoperative pancreatic fistula with clinical significance and other major complications were similar to traditional Blumgart procedure.
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Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in edaravone-induced attenuation of long-term cognitive impairment caused by long-time sedation with propofol in the neonatal rats.Methods:Eighty SPF healthy newborn Sprague-Dawley rats of both sexes, aged 7 days, weighing 15-20 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), propofol group (group P), edaravone+ propofol group (group EP) and Nrf2 inhibitor ML385+ edaravone+ propofol group (group MEP). Propofol 75 mg/kg was intraperitoneally injected once a day for 7 consecutive days in P group, EP group and MEP group, respectively, while the equal volume of medium/long chain fat emulsion injection was intraperitoneally injected in C group. Edaravone 3 mg/kg was intraperitoneally injected at 30 min before each propofol injection in EP and MEP groups, and ML385 15 mg/kg was intraperitoneally injected simultaneously in group MEP. The spontaneous activity was evaluated by the open field test on day 29 after birth, and the cognitive function was assessed by Morris water maze test on days 30-34 after birth. The rats were sacrificed after the end of water maze test, and brains were removed and hippocampal tissues were obtained for determination of reactive oxygen species (ROS) levels (by flow cytometry), superoxide dismutase (SOD) and malondialdehyde (MDA) levels (by enzyme-linked immunosorbent assay) and expression of Nrf2 and HO-1 (by Western blot) and for microscopic examination of the pathological changes in the hippocampal CA1 area (using HE staining). Results:There was no significant difference in the speed, distance and time of stay at the center of the open field among the four groups ( P>0.05). Compared with C group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the levels of MDA and ROS were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and the pathological injury was observed in the hippocampal CA1 region in group P. Compared with P group, the escape latency was significantly shortened, the number of crossing the original platform quadrant was increased, the levels of MDA and ROS in the hippocampus were decreased, the activity of SOD was increased, the expression of Nrf2 and HO-1 was up-regulated ( P<0.05), and the pathological injury in the hippocampal CA1 region was significantly alleviated in EP group. Compared with EP group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the levels of MDA and ROS were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and the pathological injury was aggravated in the hippocampal CA1 region in MEP group. Conclusions:The mechanism by which edaravone attenuates long-term cognitive impairment caused by long-time sedation with propofol is related to activation of Nrf2/HO-1 signaling pathway and inhibition of oxidative stress in the neonatal rats.
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Objective:To evaluate the role of Toll-like receptor 4 (TLR4)/nuclear transcription factor κB (NF-κB) signaling pathway in long-term cognitive impairment induced by multiple exposures to sevoflurane anesthesia in neonatal rats.Methods:Seventy-five SPF healthy newborn Sprague-Dawley rats of either sex, aged 6 days, weighing 12-20 g, were divided into 3 groups ( n=25 each) using a random number table method: control group (group C), multiple exposures to sevoflurane anesthesia group (group S) and TLR4 inhibitor plus multiple exposures to sevoflurane anesthesia group (group I+ S). The rats in group S and group I inhaled 3% sevoflurane for 2 h at 6, 7 and 8 days after birth. TLR4 inhibitor TAK-242 10 mg/kg was intraperitoneally injected before each exposure to sevoflurane in group I, and the equal volume of normal saline was given instead in the other two groups. The spontaneous activity was evaluated by open field test on day 29 after birth, and the cognitive function was assessed by Morris water maze test on days 30-34 after birth. After the behavioral test, the blood samples from the abdominal aorta were collected, and then the rats were sacrificed under deep anesthesia to isolate the hippocampal tissues for measurement of the levels of S100β and neuron-specific enolase (NSE) in serum and hippocampal interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α) (by enzyme-linked immunosorbent assay), expression of TLR4, NF-κB p65 and phosphorylated NF-κB p65 (p-NF-κB p65) (by Western blot) and for microscopic examination of the pathological changes of hippocampal CA1 region after HE staining. Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the TLR4 expression was up-regulated, the ratio of p-NF-κB p65/NF-κB p65 was increased, the levels of serum S100β protein and NSE and hippocampal IL-1β, IL-6 and TNF-α were increased ( P<0.05), and the pathological changes in the hippocampal CA1 region were aggravated in group S. Compared with group S, the escape latency was significantly shortened, the number of crossing the original platform was increased, TLR4 expression was down-regulated, the ratio of p-NF-κB p65/NF-κB p65 was decreased, the levels of S100β and NSE in serum and hippocampal IL-1β, IL-6 and TNF-α were decreased ( P<0.05), and the pathological changes in hippocampal CA1 area were significantly attenuated in group P. Conclusions:The mechanism by which multiple exposures to sevoflurane anesthesia induces long-term cognitive impairment is related to activation of TLR4/NF-κB signaling pathway and increase in hippocampal inflammatory responses in neonatal rats.
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Objective:To produce 68Ga and automatically synthesize 68Ga-labeled drugs based on low-energy medical cyclotron solid target system. Methods:68Zn was electroplated on the surface of the target by electrodeposition. According to the principle of 68Zn(p, n) 68Ga nuclear reaction, 68Zn was irradiated by the 10 MeV medical cyclotron solid target system (30 μA, 30 min) to produce 68Ga, and the activity, nuclear purity, half-life and content of metal impurities of purified product were determined. 68Ga-prostate specific membrane antigen (PSMA)-11 and 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) were synthesized automatically using 68Ga respectively, and the quality control analyses of drug properties, concentration, pH, radiochemical purity, sterility and bacterial endotoxin were carried out. Results:The electroplating mass of 68Zn was (43.71±0.87) mg ( n=35), the yield of 68Ga after irradiation was (10.96±0.67) GBq ( n=35), and the measured half-life was (67.64±0.06) min ( n=7). Only 511 keV energy peak was detected by the gamma spectrometer. After purification, (6.85±0.12) GBq ( n=35) of pure 68Ga was obtained, and the purification efficiency was (62.46±0.96)% (non-attenuated correction, n=35). The metal impurity contents of Zn and Fe were (0.18±0.06) and (1.25±0.43) μg/GBq ( n=5), which met the requirements of European Pharmacopoeia. Three batches of 68Ga-PSMA-11 and 68Ga-DOTATATE were automatically synthesized, with the yield, concentration and radiochemical purity of (3.54±0.14) and (2.74±0.20) GBq, (294.97±11.58) and (228.17±16.32) GBq/L, (99.73±0.11)% and (99.45±0.25)%, respectively. Both sterility and bacterial endotoxin were qualified. Conclusion:High-yield and qualified nuclide 68Ga and 68Ga-labeled drugs are successfully prepared through the low-energy medical cyclotron solid target system and the automated purification and synthesis module, which provide a strong guarantee for clinical practice.
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Objective:To investigate the efficacy and safety of comprehensive therapy in the treatment of advanced unresectable hepatocellular carcinoma.Methods:Clinical data of 34 patients with primary liver cancer admitted to Peking Union Medical College Hospital from Nov 2018 to Dec 2020 initially evaluated as unresectable were treated firstly by combined therapy and then underwent reevaluation for further management.Results:A total of 34 patients completed the integrative treatment, and no serious adverse events occurred. Among them, 6 patients were evaluated as partial remission, and underwent successful tumor resection, tumors in 7 patients were stable, and 21 patients suffered from disease progression.Conclusion:After comprehensive therapy, unresectable tumors in some patients could reduce and be rendered resection.
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Objective:To investigate the capability of 18F-FDG PET/CT imaging in monitoring combined immunotherapy response and detecting immune related adverse events (irAEs) in patients with advanced hepatobiliary carcinoma. Methods:From August 2018 to July 2019, 21 patients (14 males, 7 females, age (58.5±10.0) years) with advanced hepatobiliary carcinoma routinely underwent 66 18F-FDG PET/CT examinations in Peking Union Medical College Hospital. SUV max, the occurrence time and symptoms of irAEs were obtained and analyzed. Therapy response (complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), progressive metabolic disease (PMD)) was evaluated according to PET response criteria in solid tumors (PERCIST). Results:(1) Clinical results. Twenty-two irAEs occurred in 16 patients, while were not found in 5 patients. Six organs were involved, including thyroiditis(8), colitis(5), pneumonitis(4), rash(2), hepatitis(2), myositis and fasciitis(1). The appearance time of each irAEs were (103.0±58.0), (141.6±103.5), 34.0(6.0, 308.8), 9 and 117, 62 and 67, and 87 d after therapy, respectively. PET/CT detected all pneumonitis and myositis and fasciitis, but no rash and hepatitis were found. For colitis and thyroiditis, PET/CT detected 4 and 6 times respectively. (2) PET/CT signs of irAEs. Except thyroiditis, all irAEs lesions exhibited exudative changes in CT and high-avidity in PET. SUV max of the lesions were 9.0(7.9, 17.6) (colitis), 7.1±3.2 (thyroiditis), 5.3 and 8.6 (pneumonitis), 4.1 (myositis and fasciitis), respectively. (3) Therapy assessment. Among 21 patients, there were 7 for PMR, 9 for SMD, 5 for PMD, which were 7, 8, 1 in patients with irAEs and 0, 1, 4 in patients without irAEs. Conclusions:Patients with advanced hepatobiliary carcinoma can benefit from combined immunotherapy. 18F-FDG PET/CT can be used to evaluate the efficacy of immunotherapy by detecting the changes of tumor lesions and the occurrence of irAEs simultaneously. However, it is necessary to use CT to distinguish tumor progression from irAEs.
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Immune checkpoint inhibitors (ICIs) have shown significant efficacy in clinical trials and applications of various malignant tumors, and have been approved for clinical application in China. ICIs can cause immune-related adverse events (irAEs), which may affect any organs. Early identification and appropriate treatment can improve patient outcome. 18F-FDG PET/CT is capable of early detection of irAEs and provides effective clinical guidance. This article reviews the clinical application of 18F-FDG PET/CT in detecting irAEs, including typical imaging findings and research progress.
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ImmunoPET imaging, which combining the specificity of monoclonal antibody and high sensitivity of PET imaging, blazes new trails of molecular imaging modality. In recent years, clinical translation and application of immunoPET imaging strategies have been flourishing, as a result, facilitating early and non-invasive diagnosis of numerous human tumors, patient stratification before monoclonal antibody therapy and radiation dose estimation prior to radioimmunotherapy. Here, we summarize the most recent clinical evidence of immunoPET in tumor diagnosis and therapy.
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Objective:To prepare 89Zr labeled Daratumumab and evaluate its feasibility in the imaging diagnosis of multiple myeloma (MM). Methods:According to the principle of 89Y (p, n) 89Zr nuclear reaction, 89Zr was produced by cyclotron solid target system (30 μA, 1.5 h) and automatic purification module. The radionuclide purity, half-life and impurity metal ion concentration were detected. Desferrioxamine (DFO) was coupled with Daratumumab and then chelated with 89Zr to prepare 89Zr-DFO-Daratumumab. The quality control analyses of three consecutive batches were carried out. Pharmacokinetic evaluation and 89Zr-DFO-Daratumumab microPET/CT imaging were performed in normal rabbits and orthotopic myeloma mouse models, respectively. The SUV in situ myeloma and that in normal bone were compared by independent-sample t test. Results:About 560 MBq of 89Zr was obtained, and there were only two characteristic energy peaks of 89Zr (909 keV and 511 keV) by γ spectrometer. The half-life of 89Zr was 78.2 h, and the content of metal impurities was small. 89Zr-DFO-Daratumumab was prepared with pH of 7.2, radiochemical purity of more than 99%, good stability in vitro, and sterility and endotoxin tests were passed. Pharmacokinetic studies in rabbits showed that 89Zr-DFO-Daratumumab was gradually distributed from blood to liver, spleen, kidney and bone joints over time and metabolism. The results of microPET/CT imaging in orthotopic myeloma mouse models showed that the SUVs of 89Zr-DFO-daratumumab in situ myeloma were significantly higher than those in normal bone (2 h: 0.22±0.02 vs 0.06±0.00; 1 d: 0.38±0.01 vs 0.08±0.00; t values: 8.89, 21.90, both P=0.001). Conclusion:89Zr and 89Zr-DFO-daratumumab are successfully prepared, and relevant quality control and biological evaluation in vivo and in vitro are completed, which verify the feasibility of 89Zr-DFO-Daratumumab in the imaging diagnosis of MM, thus laying a foundation for clinical transformation.
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Objective:To investigate the optimal monochromatic level for evaluation of in-stent lumen after transjugular intrahepatic portosystemic shunt (TIPS) by dual-layer detector CT.Methods:Twenty-nine patients after TIPS were retrospectively enrolled who underwent abdomen enhanced examinations with portal venous phases by a dual-layer detector CT between December 2019 and July 2021. The mixed iterative image (conventional group) and monochromatic images (40 keV group, 50 keV group, 60 keV group and 70 keV group) were obtained by reconstruction. Circular regions of interest were placed in the in-stent of the cross-sectional reconstructed image and in the vertical spinal muscle on the same plane to obtain the corresponding average CT value and noise. The contrast to noise ratio (CNR) and signal to noise ratio (SNR) were calculated. Then 4-point scale was performed to evaluate image quality subjectively by 2 physicians blindly and separately. One-way ANOVA or Kruskal Wallis H rank-sum test was used for the overall analysis between groups, and LSD test or Dunn′s Bonforoni test was used for pairwise comparison within groups. Results:There was no significant difference in noise values among the 5 groups ( P>0.05). The difference of CNR and SNR between the 5 groups was statistically significant ( F=72.28, 56.45, P<0.001). The CNR and SNR in the 40 keV group were the highest, which were 50.4±15.7 and 59.3±18.4 respectively, and the difference was statistically significant ( P<0.001). Subjective scores showed statistically significant differences among the 5 groups (χ2=101.61, P<0.001). The score of the 40 keV group was higher than that of the 60 keV group, 70 keV group, and conventional group ( P<0.001), and there was no significant difference when compared with the subjective score of the 50 keV group ( P>0.05). Conclusions:The 40 keV monochromatic image of dual detector spectral CT is the best image to observe the lumen of the stent after TIPS.
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Objective:To investigate the kinetic metrics of 68Ga-fibroblast activation protein inhibitor (FAPI)-04 in pancreatic cancers and normal organs by using total-body PET dynamic imaging. Methods:From December 2020 to December 2021, 68Ga-FAPI-04 total-body PET/CT dynamic imaging were performed on 6 pancreatic cancer patients (3 males, 3 females, median age 55.5 years) in Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. Images were respectively analyzed. Manual delineations of volume of interests (VOIs) on multiple normal organs and pathological lesions were performed and time-to-activity curves (TACs) were generated. A reversible two-tissue compartment model (2TCM) was fitted for each tissue TAC. Rate constants including K1, k2, k3 and k4, and the total volume of distribution ( Vt) were obtained and compared by tissue types. Wilcoxon rank sum test and Spearman correlation analysis were used for data analysis. Results:Kinetic metrics varied significantly among normal organs and pancreatic cancer lesions ( z values: 2.00-1 240.00, all P<0.05). The highest K1 among lesions was observed in primary tumor (0.30 min -1), which was observed in the spleen (1.42 min -1) among normal organs. The highest k2 among lesions was observed in peritoneal metastases (0.24 min -1), which was observed in the spleen (2.59 min -1) among normal organs. Primary tumor showed the highest k3 of 0.17 min -1 among lesions, and the pancreas had the highest k3 of 0.16 min -1 among normal organs. Primary tumor had the highest k4 of 0.03 min -1 among lesions, and the heart, lungs, parotid glands had high k4(0.06 min -1) among normal organs. Vt were higher in pathological lesions compared to normal organs, with the highest in primary tumor (13.78 ml/cm 3). There were correlations between Vt in lesions and SUV mean( rs=0.86, P<0.001) or SUV max ( rs=0.77, P<0.001). Conclusion:The rate constants including K1, k2, k3 and k4, and Vt of 68Ga-FAPI-04 vary among normal organs and lesions.
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Objective:To evaluate the specificity of 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Ser-Asn-Thr-Arg-Val-Ala-Pro (SNTRVAP, VAP) molecular probe targeting glucose-regulated protein 78(GRP78) in vivo and in vitro and the feasibility of 68Ga-DOTA-VAP microPET/CT imaging in the diagnosis of GRP78-positive tumors. Methods:68Ga-DOTA-VAP was prepared by the combination of bifunctional chelating agent DOTA and VAP, followed by 68Ga labeling. Western blotting experiment was perfomed to detect the expression of GRP78 in U87MG, BxPC-3, and 293T cell lines, at the same time, cold polypeptide blocked experiments were conducted to verify the specific binding of 68Ga-DOTA-VAP to cells. U87MG and BxPC-3 subcutaneous transplantation tumor mouse models were established and the biodistribution of 68Ga-DOTA-VAP were explored in vivo. The imaging effect of 68Ga-DOTA-VAP in GRP78-positive tumor-bearing mouse models was evaluated by microPET/CT. Independent-sample t test, one-way analysis of variance and Dunnett t test were used for data analysis. Results:68Ga-DOTA-VAP was easily prepared with labeling yield and radiochemical purity >98%. It had good stability in vitro, and its radiochemical purity was still (98.27±0.22)% after 2 h. GRP78 was highly expressed in U87MG and BxPC-3 cells, but lowly expressed in 293T cells ((0.78±0.02), (0.53±0.05) and (0.36±0.03), F=102.22, P<0.001; t values: 0.43, 0.18, both P<0.01). The uptake of 68Ga-DOTA-VAP in U87MG cells was higher than that in BxPC-3 cells (5 154.00±216.70 vs 4 344.00±60.88; t=3.10, P=0.027). Excessive unlabeled VAP polypeptide could significantly reduce the uptake of 68Ga-DOTA-VAP both in U87MG and BxPC-3 cells (3 324.00±54.14, 3 270.00±131.10; t values: 8.19, 7.43, both P<0.01). The uptake of 68Ga-DOTA-VAP in U87MG tumor tissue was higher than that in BxPC-3 tumor tissue ((1.98±0.20) vs (1.30±0.08) percentage activity of injection dose per gram of tissue (%ID/g); t=5.48, P=0.005), while co-injection of excessive unlabeled VAP polypeptide significantly reduced the uptake in U87MG and BxPC-3 tumors ((0.99±0.02) and (0.62±0.05) %ID/g; t values: 8.32, 12.25, both P<0.05). MicroPET/CT imaging showed that 68Ga-DOTA-VAP could clearly display U87MG and BxPC-3 tumors, and U87MG had a better imaging effect. The tumors could not be clearly visualized after co-injection of excessive VAP polypeptide. Conclusion:68Ga-DOTA-VAP molecular probe binds with GRP78 specifically and can reflect the expression level of GRP78 in vivo, which may be a promising probe for the specific imaging diagnosis of GRP78-positive tumors.
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Purpose@#Platelet-related indices, including mean platelet volume (MPV) and plateletocrit (PCT), have been reported as new prognostic factors of overall survival (OS) in many cancers, but not yet in biliary tract cancer (BTC). We intended to assess these indices in predicting OS in BTC patients with the aim to build a new prognostic model for patients with BTC after surgical resection. @*Materials and Methods@#Survival analysis and time receiver operating characteristic analysis were applied to screen the platelet indices. Univariate and multivariate Cox analyses were used to identify independent prognostic factors and develop a new prognostic model. Harrell’s C-statistics, calibration curves, and decisive curve analysis were used to assess the model. @*Results@#MPV and platelet distribution width (PDW)/PCT showed the best prognostic accuracy among the platelet indices. In multivariable analysis, factors predictive of poor OS were presence of nodal involvement, Non-radical surgery, poor tumor differentiation, carbohydrate antigen 19-9 > 100 U/mL, MPV > 8.1 fl, and PDW/PCT > 190. The new model was found to be superior to the TNM staging system and our new staging system showed higher discriminative power. @*Conclusion@#MPV and PDW/PCT have high prognostic value in BTC patients, and the novel staging system based on these two indices showed good discrimination and accuracy compared with the American Joint Committee on Cancer 7th TNM staging system.
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The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.
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Purpose@#Platelet-related indices, including mean platelet volume (MPV) and plateletocrit (PCT), have been reported as new prognostic factors of overall survival (OS) in many cancers, but not yet in biliary tract cancer (BTC). We intended to assess these indices in predicting OS in BTC patients with the aim to build a new prognostic model for patients with BTC after surgical resection. @*Materials and Methods@#Survival analysis and time receiver operating characteristic analysis were applied to screen the platelet indices. Univariate and multivariate Cox analyses were used to identify independent prognostic factors and develop a new prognostic model. Harrell’s C-statistics, calibration curves, and decisive curve analysis were used to assess the model. @*Results@#MPV and platelet distribution width (PDW)/PCT showed the best prognostic accuracy among the platelet indices. In multivariable analysis, factors predictive of poor OS were presence of nodal involvement, Non-radical surgery, poor tumor differentiation, carbohydrate antigen 19-9 > 100 U/mL, MPV > 8.1 fl, and PDW/PCT > 190. The new model was found to be superior to the TNM staging system and our new staging system showed higher discriminative power. @*Conclusion@#MPV and PDW/PCT have high prognostic value in BTC patients, and the novel staging system based on these two indices showed good discrimination and accuracy compared with the American Joint Committee on Cancer 7th TNM staging system.
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Purpose@#The systemic inflammation response index (SIRI) has been reported to have prognostic ability in various solid tumors but has not been studied in gallbladder cancer (GBC). We aimed to determine its prognostic value in GBC. @*Materials and Methods@#From 2003 to 2017, patients with confirmed GBC were recruited. To determine the SIRI’s optimal cutoff value, a time-dependent receiver operating characteristic curve was applied. Univariate and multivariate Cox analyses were performed for the recognition of significant factors. Then the cohort was randomly divided into the training and the validation set. A nomogram was constructed using the SIRI and other selected indicators in the training set, and compared with the TNM staging system. C-index, calibration plots, and decision curve analysis were performed to assess the nomogram’s clinical utility. @*Results@#One hundred twenty-four patients were included. The SIRI’s optimal cutoff value divided patients into high (≥ 0.89) and low SIRI (< 0.89) groups. Kaplan-Meier curves according to SIRI levels were significantly different (p < 0.001). The high SIRI group tended to stay longer in hospital and lost more blood during surgery. SIRI, body mass index, weight loss, carbohydrate antigen 19-9, radical surgery, and TNM stage were combined to generate a nomogram (C-index, 0.821 in the training cohort, 0.828 in the validation cohort) that was significantly superior to the TNM staging system both in the training (C-index, 0.655) and validation cohort (C-index, 0.649). @*Conclusion@#The SIRI is an independent predictor of prognosis in GBC. A nomogram based on the SIRI may help physicians to precisely stratify patients and implement individualized treatment.
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Objective:To explore the clinical effects of computer navigation-assisted surgery in the precise resection of pelvic chondrosarcoma.Methods:A retrospective analysis of 54 patients who had computer-assisted surgery from Dec 2007 to Dec 2018, including 27 males and 27 females, was conducted. The average age was 34.00±1.41 years (range 23-72 years). There were 47 cases with primary tumors and 7 with recurrence cases. The tumors in 15 cases located in the ilium (region I), 35 in the acetabulum (region II), 1 in the pubic (region III), and 3 in the sacroiliac joint (region IV). A total of 45 cases (83.3%) underwent needle biopsy, and 4 cases (7.4%) had incision biopsy. Among 5 cases who did not have biopsy, two of them was diagnosed of malignant change of multiple osteochondromas, two cases were diagnosed of recurrent pelvic chondrosarcoma and one with pelvic malignant tumor by imaging examinations. Pathological grade was presented as following, 36 cases in grade I, 15 in grade II, and 3 in grade III. All operations were performed on the bases of preoperative design with computer navigation-assisted surgical technology. A total of 49 cases (90.7%) had limb salvage operations and 5 cases had amputations. The surgical margins were confirmed by gross appearance and the maximum diameter profile of the tumor. Univariate analysis was performed to compare recurrence rate of different preoperative tumor status, gender, tumor stage, biopsy method, tumor location, operation method and surgical margins.Results:There were 39 cases underwent extensive resection, 13 cases with marginal resection and 2 cases with intracapsular resection. In 52 cases (96.3%), the surgery was performed according to the preoperative plan of surgical resection margin. However, two cases (3.7%) was not performed based on the preoperative plan. All patients were followed-up for 84.00±93.34 months (range 12-150 months). During the follow-up, a total of 45 cases (83.3%) survived and 9 cases died from lung metastasis. Eight cases (14.8%, 8/54) had local recurrence of whom 7 (14.3%) were limb salvage cases and 1 (20.0%, 1/5) had amputation. There was significantly different in local recurrence rate (χ 2=17.022, P=0.001). The risk of recurrence of marginal resection was 8.222 times than that of extensive resection [95% CI (1.297, 52.140)]. According to the Musculoskeletal Tumor Society (MSTS) limb function evaluation system score, postoperative limb function recovery rate was 90.00%±4.71% (range 60.00%-100%). There were 13 cases (24.1%) had postoperative complications, including 7 cases (13.0%) of infection, 2 cases (3.7%) of operative area and deep vein thrombosis of lower extremity, and 4 cases (7.4%) of skin necrosis and delayed healing. Among 49 limb salvage patients, two of them had secondary amputation due to tumor recurrence, five had hemipelvectomy due to neurovascular tumor invasion. The final limb salvage rate was 77.8% (42/54). Conclusion:Computer navigation-assisted precise pelvic tumor resection is technically feasible. It could decrease recurrence rate and promote limb function recovery by improving the reliability of oncology evaluation and the accuracy of tumor resection with superior safety.