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Objective:To assess the clinical efficacy of sequential radical surgery after immune and targeted therapy in downstaging patients with initially unresectable hepatocellular carcinoma.Methods:Data were prospectively collected from December 2018 to July 2022 on patients with initially unresectable hepatocellular carcinoma which were downstaged to undergo sequential surgery after treatment with immune and targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital. There were 79 patients, with 69 men and 10 women, aged (53.0±10.9) years, being enrolled into this study. The Kaplan-Meier method was used to calculate the survival rate, and the log-rank test was used for survival rate comparison. Univariate and multivariate Cox regression were used to analyze factors influencing patient prognosis.Results:There were 7 patients (8.9%) with China Liver Cancer Staging (CNLC) Ⅰb, Ⅱa, Ⅱb who had insufficient residual liver volume or tumor rupture before the downstaging therapy, and 38 patients (48.1%) with CNLC Ⅲa and 34 patients (43.0%) with CNLC Ⅲb. These 79 patients underwent R 0 resection after 3-20 cycles (median 5 cycles) of immune and targeted therapy. Based on the modified response evaluation criteria in solid tumor, the results of preoperative imaging assessment were: complete remission in 12 patients (15.2%), partial remission in 50 patients (63.3%), stable disease in 15 patients (19.0%), and disease progression in 2 patients (2.5%). The overall survival rates of patients at 1, 2, and 3 years after diagnosis were 96.1%, 83.5%, and 76.6%; and the recurrence-free survival rates at 1, 2, and 3 years after surgery were 62.1%, 52.9%, and 34.7%, respectively. On multivariate Cox regression analysis, patients with a preoperative alpha-fetoprotein >20 μg/L ( HR=2.816, 95% CI: 1.232-6.432, P=0.014) and a high proportion of pathological residual tumors ( HR=1.015, 95% CI: 1.004-1.026, P=0.006) had a higher risk of postoperative recurrence; and patients with a high proportion of pathological residual tumors ( HR=1.028, 95% CI: 1.007-1.049, P=0.007) and preoperative alpha-fetoprotein >400 μg/L ( HR=4.099, 95% CI: 1.193-14.076, P=0.025) had a higher risk of death. Conclusion:Immunotherapy combined with targeted therapy and sequential surgery for patients with initially unresectable hepatocellular carcinoma provided long-term survival benefits. Elevated preoperative alpha-fetoprotein and a high proportion of pathological residual tumor were independent risk factors for recurrence-free survival and overall survival in this group of patients.
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Objective:To study the safety and efficacy of a treatment protocol using immune checkpoint inhibitors (ICIs) and antiangiogenic targeted drugs (AATDs) in converting 41 patients with initially unresectable to resectable hepatocellular carcinoma (HCC).Methods:The data of 41 patients with initially unresectable HCC treated with immunotherapy combined with targeted therapy from December 2018 to April 2021 in Chinese PLA General Hospital were analysed. There were 34 males and 7 females, aged (51.8±10.7) years. The clinical characteristics, conversion to resectable HCC, adverse drug reactions, surgical data and postoperative complications were analysed. Patients were followed-up by outpatients clinics or telephone calls.Results:There were 5 patients with Chinese Liver Cancer Staging (CNLC)-Ⅰb, 4 with CNLC-Ⅱ, 28 with CNLC-Ⅲa and 4 with CNLC-Ⅲb before the treatment protocol. Among them, 28 patients had portal vein tumor thrombosis (PVTT) and 4 had retroperitoneal lymph node metastases. All patients had a mean tumor diameter of (9.16±4.43) cm before and (6.49±4.69) cm after the treatment protocol. The latter was based on the last assessment before hepatectomy. The efficacy of the treatment protocol in converting unresectable to resectable HCC was assessed by the modified Response Evaluation Criteria in Solid Tumors after 3-15 cycles (median dose cycles, 5) of protocal therapy: 15 patients achieved a complete response; 15 patients achieved a partial response; 6 patients had a stable disease, and 5 patients had a progressive disease. 21 patients (51.2%) experienced adverse reactions associated with drug treatment, which resolved with symptomatic treatment or brief discontinuation of the therapy. All patients underwent successful hepatectomy. Postoperative complications of grade Ⅱ or higher occurred in 9 patients (22.0%). The cumulative overall survival rates at 6 months, 1 year and 2 years from diagnosis were 100.0%, 92.6% and 64.7% respectively. The cumulative overall survival rates at 6 months, 1 year and 2 years after surgery were 95.1%, 74.7% and 60.8%, and the recurrence-free survival rates at 6 months, 1 year and 2 years after surgery were 87.8%, 56.7% and 48.6%, respectively.Conclusions:This study provided preliminary evidences that surgical resection after immunotherapy combined with targeted therapy in patients with initially unresectable HCC was safe and efficacious.
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Objective@#To investigate clinical, pathological and immunohistochemical features of pancreatic acinar cell carcinoma.@*Methods@#A retrospective review of surgical and pathological databases between 2011 and 2016 at PLA General Hospital was collected and 14 cases of acinar cell carcinoma (ACC) of the pancreas were identified. EnVision immunohistochemistry was used to detect the expression of Trypsin, bcl-10 and cytokeratin(CK) proteins.@*Results@#The patients included nine cases of pure ACC, 3 cases of mixed acinar ductal carcinoma, 1 case of mixed acinar-neuroendocrine carcinoma and acinar-ductal-neuroendocrine carcinoma, respectively. Tumors involved different anatomic locations of the pancreas, including eight involving the head of pancreas, four in the body and tail, one in the uncinate process and one in a heterotopic pancreas. Two patients had lymph node and liver metastases before surgery. Microscopically, the tumor was hypercellular with less fibroblastic proliferation and tumor cells arranged in acinar or solid pattern. The well differentiated tumor cells showed eosinophilic, granular cytoplasm with single prominent nucleoli, while the poorly differentiated tumor cells tended to grow in solid sheets. Immunohistochemically, the tumor cells were positive for pan-cytokeratin (14/14), Trypsin (12/14) and bcl-10 (11/14). Stains for CK7 and CK19 were negative (11/14 and 3/4). According to the pTNM staging, there were 7 cases at stageⅠ, 3 at stage ⅡA, 3 at stage Ⅲ and 1 at stage Ⅳ. With average postoperative follow-up of 6-58 months, the median disease-free survival time was 16 months.@*Conclusions@#Pancreatic acinar cell carcinoma is a rare and relatively indolent malignant tumor with characteristic histopathological and immunohistochemical features. Accurate pathological diagnosis plays an important role in patients′ treatment and evaluation of prognosis.
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Objective@#To explore the value of CT texture analysis (CTTA) in differentiating the pathological grade of urothelial carcinoma of the bladder (UCB).@*Methods@#A total of 53 lesions from 43 patients with bladder cancer confirmed by postoperative pathology were retrospectively analyzed, including 27 cases of high-grade urothelial carcinoma (HGUC) and 26 cases of low-grade urothelial carcinoma (LGUC). All the patients took pelvic CT and enhanced scanning in the same CT scanner with same scanning parameters. Lesions on both plain and enhanced CT images were delineated on software by two radiologists to extract the corresponding volumes of interest (VOI) and then 92 parameters based on feature classes were generated. The average values of two radiologists were obtained. The difference parameters between HGUC group and LGUC group were screened by nonparametric test, and the receiver operating characteristic (ROC) was drawn. The corresponding optimal thresholds were determined and diagnostic effect was assessed.@*Results@#Nine difference texture parameters between HGUC group and LGUC group were selected, including 5 parameters on unenhanced images, namely, skewness, root mean squared, cluster shade, zone percentage and large area high gray level emphasis. There were 4 parameters on enhanced images, namely, skewness, kurtosis, cluster shade and zone percentage. The largest area under curve of 0.840±0.058 (95% CI 0.726-0.955) was obtained from skewness generated by VOI of unenhanced images. The cut-off value of skewness was 0.186 5, which permitted the diagnosis of HGUC with sensitivity of 92.59%, specificity of 73.08%, positive predictive value of 78.13%, negative predictive value of 90.48% and accuracy of 83.02%.@*Conclusion@#CTTA can effectively distinguish between LGUC and HGUC. Skewness from unenhanced CT images had the optimal diagnostic performance.
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@#To investigate the effect of combination of schisandrin B and doxorubicin on the pharmacokinetic behavior of doxorubicin in SD rats. An LC-MS/MS method was established for the determination of doxorubicin and its main metabolite doxorubicinol in SD rats plasma. Separation was performed on Agilent Eclipse XDB-C18 column(100 mm×2. 1 mm, 3. 5 μm)using 0. 1% formic acid solution and acetonitrile as mobile phase with a liner gradient program. The ion transitions were performed under ESI position model at m/z 544. 2→397. 3(doxorubicin), m/z 546. 2→399. 2(doxorubicinol), m/z 528. 2→381. 2(daunorubicin, internal standard). Calibration curves of doxorubicin(0. 500-500 ng/mL)and doxorubicinol(0. 200-50. 0 ng/mL)showed good linear regression. The precision and accuracy met the requirements. The variation coefficient of extraction recovery and matrix effect was less than 15%. The AUC0-t of doxorubicin were(605. 69±145. 84)and(564. 53±23. 99)ng ·h/mL in alone and combined group, respectively. The AUC0-t of doxorubicinol were(26. 69±13. 41)and(29. 00±2. 78)ng ·h/mL, respectively. Results indicated that, schisandrin B had not affected the pharmacokinetic behavior of doxorubicin in SD rats.
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@#The aim of this paper was to investigate the absorption mechanism of silybin(SLB)in Caco-2 cells. Concentrations of samples in the study were determined by developing LC/MS/MS method of SLB, propranolol and atenolol in HBSS buffer to calculate apparent permeability coefficient(Papp). When Caco-2 cells were cultured to the 21st day, the TEER were above 350 Ω ·cm2. The Papp of Lucifer yellow was far less than 1 × 10-7 cm/s. As the positive control drugs, The Papp of atenolol and propranolol were similar to those reported in the literature, indicating that the Caco-2 monolayer model was successfully established in this experiment. The Papp(AP-BL) of SLB at 5, 20, and 50 μg/mL were all more than 2×10-6 cm/s, which showed that SLB was a moderately permeable drug. The efflux ratio was greater than 2 indicating the efflux transporter may be involved in the absorption process of SLB. The Papp of silybin-N-meglumine was similar to that of SLB, suggesting that salt formation did not alter the membrane permeability of SLB. In conclusion, the membrane permeability of SLB is good, and its solubility is low. SLB is a BCS class 2 drug. The release of SLB in the gastrointestinal tract is an important factor in its absorption process.
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Objective@#To investigate the expression of ERG, Fli-1, CD34, CD31 and factor Ⅷ-related antigen(FⅧRAg) in hepatic malignant vascular tumors.@*Methods@#A retrospective analysis was conducted on 63 cases of primary hepatic malignant vascular tumors and 31 cases of hepatic other malignant spindle cell tumors collected during January 1986 to January 2014. EnVision method was used to detect the expression of ERG, Fli-1, CD34, CD31, FⅧRAg.@*Results@#Sixty-three cases of malignant vascular tumors, including 24 cases of angiosarcoma, 38 cases of epithelioid hemangioendothelioma and 1 case of hepatic Kaposi′s sarcoma. All of the cases were positive for ERG(100.0%, 63/63). Positive rate of Fli-1, CD34, CD31, FⅧRAg was 96.8% (61/63), 87.3% (55/63), 81.0% (51/63) and 41.3% (26/63), respectively. In other hepatic malignant spindle cell tumors, the positive rate of ERG, Fli-1, CD34, CD31 and FⅧRAg was 3.2% (1/31), 19.4% (6/31), 19.4% (6/31), 9.7%(3/31) and 3.2%(1/31), respectively.The sensitivity of ERG, Fli-1, CD34, CD31, FⅧRAg was 100.0%, 96.8%, 87.3%, 81.0% and 41.3%, respectively.The specificity was 96.8%, 80.6%, 80.6%, 90.3% and 96.8%, respectively.@*Conclusion@#ERG is a more sensitive and specific diagnostic marker for hepatic malignant vascular tumors in comparison to Fli-1, CD34, CD31 and FⅧRAg.
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Objective To explore imaging manifestations of hepatic epithelioid hemangioendothelioma (HEH). Methods CT and MR images in 14 patients with HEH proven by histopathology were retrospectively analyzed. Plain and two-phase contrast-enhanced CT scan were performed in 5 cases, non-contrast and multiphase contrast-enhanced MR scan were performed in 7 cases, CT and MRI were both performed in 2 cases. Characteristics of CT and MR T2WI images were classified and analyzed. All lesions were classified into three types:multiple, diffuse and solitary form. Results (1) Multiple form of HEH:228 lesions were found in 11 patients, including 178 lesions on MRI and 50 lesions on CT. On T2WI, three or two layered-target-signs with hyperintensity core were found in 79.2% (141/178) of the lesions. Three layer-target-sign included hyperintensity core, hypointensity rim and slightly high signal halo from the inside out. Two layer-target-sign included hyperintensity core and slightly high signal halo from the inside out. Characteristics of dynamic contrast-enhanced scan included peripheral two or three layered-rim-like enhancement in 66.3%( 118/178) of the lesions;peripheral, gradual rim-like enhancement with enhanced core in 27.0%( 48/178) of the lesions;heterogeneously mild enhancement in 2.2%( 4/178) of the lesions;centripetal enhancement in 4.5%( 8/178) of the lesions. Fifty lesions were found in CT, which showed low density nodules or masses with clear margins. Two-layered-black-target sign were found in 42 lesions in contrast-enhanced images, white-target sign were found in 3 cases, and centripetal enhancement was found in 5 cases. (2) Diffuse form of HEH:in one of the two cases of this type, the lesions could not be separated from normal liver parenchyma, gradual enhancements were found along with the vessels in the center of the lesions. (3) Solitary form of HEH: one case, the lesion showed heterogeneous density in non-contrast CT images and gradual enhancement in contrast-enhanced images. Conclusions We found some imaging characteristics of HEH. Two or three layered-target-sign on T2WI and black-target sign, white-target sign on contrast-enhanced images were unique imaging features of HEH.
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Objective To investigate the effects of inhibition of adenosine monophosphate -activated protein kinase (AMPK) on expressions of cytochrome c (CytC) and caspase -3 and apoptosis in the cerebral cortex after cerebral ischemia-reperfusion injury in mice. Methods Thirty-six male C57BL/6 mice w ere randomly divided into three groups, a sham operation group, a ischemia -reperfusion group, and a AMPK inhibitor group, 12 in each group. A model of middle cerebral artery occlusion w as induced by suture method. The AMPK inhibitor compound C ( 20 mg/kg) w as injected intraperitonealy in the AMPK inhibitor group, the equal volume normal saline w as injected intraperitonealy in the sham operation group and the ischemia-reperfusion group w hen a thread w as inserted. Immunohistochemical staining w as used to detect the expression levels of CytC and caspase-3 and TUNEL method w as used to detect apoptosis at 24 h after ischemia-reperfusion. Results Compared w ith the ischemia-reperfusion group, the numbers of CytC (28.86 ±9.65/HP vs.58.86 ±9.65/HP; t = 7.615, P = 0.030 ) and caspase-3 (7.16 ±5.85/HP vs. 14.36 ±7.85/HP; t =2.548, P =0.035), and TUNEL (67.14 ±8.55/HP vs.95.00 ±13.51/HP; t = 6.891, P = 0.030) positive cels in the cerebral cortex w ere reduced significantly in the AMPK inhibitor group. Conclusion Inhibition of AMPK activity after cerebral ischemia-reperfusion may decrease apoptosis by dow nregulating the expressions of CytC and caspase -3, and play a neuroprotective effect.
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Objective To investigate the effects of of inhibition of AMP-activated protein kinase (AMPK) on cytochrome c (CytC) expression in the cortex and hippocampus after focal cerebral ischemia-reperfusion in mice. Methods Thirty-six male C57BL/6 mice were randomly divided into 3 groups: a sham operation group, an ischemia-reperfusion group, and a compound C group (n = 12 in each group). The mice of the compound C group were intraperitonealy injected an AMPK specific inhibitor compound C (20 mg/kg) at the time of ischemia. A model of middle cerebral artery occlusion was induced by a modified suture method. After 24 h of reperfusion, Western blot was used to detect the expression levels of AMPK, phosphorylated-AMPK (p-AMPK), and cytoplasm CytC in the cortex and hippocampus in the ischemic side. Results p-AMPK/MPK levels in the cortex in the sham operation group, ischemia-reperfusion group, and compound C group were 0. 701 ± 0. 197, 1. 408 ± 0. 322, and 0. 930 ± 0. 229, respectively (F = 12. 000, P =0. 001); p-AMPK/MPK levels in the hippocampus were 0. 685 ± 0. 228, 1. 507 ± 0. 418, and 0. 964 ± 0. 378, respectively ( F = 8. 530, P = 0. 003 ); p-AMPK/AMPK levels both in the cortex ( P < 0. 001 ) and hippocampus (P = 0. 001) in the ischemia-reperfusion group were significantly higher than those in the sham operation group, p-AMPK/AMPK levels both in the cortex (P = 0. 005) and hippocampus (P = 0. 017) in the compound C group were significantly lower than those in the ischemia-reperfusion group. CytC levels in the cortex in the sham operation group, ischemia-reperfusion group, and compound C group were 0. 496 ±0. 278, 1. 461 ± 0. 321, and 1. 018 ± 0. 175, respectively (F = 19. 915, P < 0. 001); CytC levels in the hippocampus were 0. 511 ± 0. 257, 1. 610 ± 0. 441, and 0. 921 ± 0. 228 (F = 17. 795, P < 0. 001); CytC levels both in the cortex (P < 0. 001) and hippocampus (P < 0. 001) in the ischemia-reperfusion group were significantly higher than those in the sham operation group, while CytC levels both in the cortex (P = 0. 011) and hippocampus (P = 0. 002) in the compound C group were significantly lower than those in the ischemia-reperfusion group. Conclusion Inhibition of the AMPK may down-regulate the cytoplasm CytC expression in the cortex and hippocampus after cerebral ischemia-reperfusion in mice.
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<p><b>OBJECTIVE</b>To summarize the features of clinical manifestations, laboratory tests and imaging findings of patients with cardiac amyloidosis (CA).</p><p><b>METHODS</b>A total of 60 CA patients (including 41 male and 19 female patients) from 4 centers admitted between May, 2012 and November, 2013 were included in the study. The demographic data, medical history, clinical manifestations, laboratory test data, ECG, cardiac ultrasound, and cardiac magnetic resonance (CMR) imaging of the patients were analyzed.</p><p><b>RESULTS</b>Two-thirds of the 60 CA patients, were middle-aged or elderly men, and 47% of the patients had AL-CA. The clinical manifestations included exertional dyspnea (73%), pedal edema (47%), hypotension (47%), and hypertrophy of the tongue (22%); abnormal laboratory test results included albuminuria (53%) and liver (15%) and kidney (28%) dysfunction; blood routine, urine and serum immunoglobulin quantification and immunofixation electrophoresis could help the screening of AL-CA. Kidney (53%) and liver (15%) involvement was common, and 86% of AL-CA patients had kidney involvement. Typical ECG characteristics included poor R wave progression (35%), low voltage in limb leads (33%), and a pseudo infarct Q wave (30%); the latter two were more frequent in AL-CA. The characteristics of ultrasound findings included left ventricle thickening (100%), left atrial enlargement (87%) and enhanced echo of the myocardial granules(92%), and diastolic dysfunction was obvious in all the CA patients regardless of the systolic function. The DT and E/e' of the mitral annulus could be used as an index to evaluate diastolic dysfunction in early stage of the disease. Left ventricular (LV) global subendocardial late gadolinium enhancement (LGE, 81%) accompanied by right ventricular (RV) and atrial LGE was the typical characteristic of CMR, and the range of LGE in the RV and the two atria was wider in AL-CA than in non-AL-CA. NT-proBNP (97%) and cardiac troponin (53%) in CA patients were both elevated, which helped in diagnosing and assessing the severity of cardiac involvement, according to which 50% of the patients were found to be at a high risk, 43% at an intermediate risk, and 7% at a low risk.</p><p><b>CONCLUSION</b>The combination of the features of clinical, laboratory tests and imaging findings of CA have important diagnostic and prognostic value for CA.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , Amyloidosis , Diagnosis , Pathology , Cardiomyopathies , Diagnosis , Pathology , Electrocardiography , Immunoglobulin Light-chain Amyloidosis , Magnetic Resonance ImagingABSTRACT
Death of nerve cells after cerebral ischemia have a variety of forms,including cell necrosis occurs immediately in ischemic core area and the subsequent apoptosis and autophagy induced by oxidative stress and inflammatory response in the course of reperfusion.After cerebral ischemia,a variety of different molecular mechanisms eventually lead to cell death,and the process involves several signaling pathways.Intervention of different forms and mechanisms of cell death may alleviate cell death after cerebral ischemia.
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Objective To identify the imaging characteristics of calcifying pseudoneoplasms of the neuraxis (CAPNON) and do literature review.Methods Five patients of pathologically-proved CAPNON underwent preoperative MR examination,among which 4 underwent CT scan,2 underwent DSA examination and 1 underwent SPECT. All imaging data were retrospectively analyzed with the emphasis on imaging characteristics.Results Five patients of CAPNON with the diameter of 1.5 to 5.0 cm were found in five patients ( Male 4 ; Female 1 ; age 25 to 60 years old ).Three lesions were located in the skull base,one was located in the cervical spine and one in the foramen magnum and upper cervical segment. All patients underwent MRI examination and 4 of them also took CT scanning.On plain CT,all lesions showed obvious calcification.On T1WI all masses showed hypointensity,and on T2WI 4 of the lesions showed iso- or hypointensity and 1 heterogeneous signal intensity. On contrast-enhanced MR images, peripheral enhancement was demonstrated in 3 lesions,homogeneous enhancement was found in case and one lesion showed no enhancement. The pathologic analysis indicated that inside the lesions were abundant calcification,fibroepithelial tissue and mucoid matrix and no edema was detected around the lesions.Conclusions CAPNON displayed the predilection to male adults and the neuraxis was the predilection site.Calcification on CT images,hypointensity on MR images and peripheral enhancement will be helpful for the diagnosis of CAPNON,but the final confirmation still needs the pathologic results.