Efficacy and safety of neoadjuvant chemotherapy combined with PD-1 antibody for esophageal squamous cell carcinoma in the real world / 中华肿瘤杂志

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with programmed death-1 (PD-1) antibody in operable, borderline or potentially resectable locally advanced esophageal squamous cell carcinoma(ESCC) in the real world. Methods: The study retrospectively analyzed 28 patients with operable or potentially resectable locally advanced ESCC patients treated with preoperative chemotherapy combined with PD-1 inhibitor in Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 2020 to March 2021. According to the clinical TNM staging system of the 8th edition of the American Joint Committee on Cancer, there were 1, 15, 10, 1 and 1 case of stage Ⅱ, Ⅲ, ⅣA, ⅣB and unknown stage respectively. The treatment was two cycle of dual drug chemotherapy regimen including taxane plus platinum or fluorouracil combined with PD-1 antibody followed by tumor response assessment and surgery if the patient was eligible for resection. Results: Of the 28 patients, 1, 2, 3 and 4 cycles of chemotherapy combined with PD-1 antibody treatment completed in 1, 21, 5, and 1 patient, respectively. Objective response rate (ORR) was 71.4% (20/28), and disease control rate (DCR) was 100% (28/28). The incidence of adverse events exceeding grade 3 levels was 21.4% (6/28), including 3 neutropenia, 1 leukopenia, 1 thrombocytopenia and 1 immune hepatitis. There was no treatment-related death. Of the 23 patients underwent surgery, R0 resection rate was 87.0% (20/23), 13 patients had down staged to the T1-2N0M0 I stage, the pCR rate was 17.3% (4/23), and the pCR rate of primary tumor was 21.7% (5/23). Four patients received definitive chemoradiotherapy. One patient rejected surgery and other treatment after achieved PR response. Conclusion: Neoadjuvant chemotherapy combined PD-1 inhibitor is safe and has high efficacy in operable, borderline or potentially resectable locally advanced ESCC, and it is a promising regimen.

Real-world study on the efficacy and prognostic predictive biomarker of patients with metastatic non-small cell lung cancer treated with programmed death-1/programmed death ligand 1 inhibitors / 中华肿瘤杂志

Objective: To describe the actual efficacy of programmed death-1 (PD-1)/ programmed-death ligand 1 (PD-L1) inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) and explore potential prognostic predictive biomarkers. Methods: Patients with metastatic NSCLC who were treated with PD-1/PD-L1 inhibitors at Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2019, either as monotherapy or in combination with other agents, were consecutively enrolled into this study. We retrospectively collected the data of demographics, clinical information and pathologic assessment to evaluate the therapeutic efficacy and conduct the survival analysis. Major endpoint of our study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: The ORR of 174 patients who underwent PD-1/PD-L1 inhibitor was 28.7%, and the DCR was 79.3%. Immune-related adverse events (irAEs) occurred in 23 patients (13.2%). Brain metastasis, line of treatment, and treatment patterns were associated with the ORR of metastatic NSCLC patients who underwent immunotherapy (P<0.05). After a median follow-up duration of 18.8 months, the median PFS was 10.5 months (ranged from 1.5 to 40.8 months) while the median OS was not reached. The 2-year survival rate was estimated to be 63.0%. The pathologic type was related with the PFS of metastatic NSCLC patients who underwent immunotherapy (P=0.028). Sex, age, brain metastasis and autoimmune diseases were associated with OS (P<0.05). Analysis of the receptor characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) predicting ORR of immunotherapy in metastatic NSCLC showed that the areas under the curve of NLR before immunotherapy (NLR(C0)), NLR after one cycle of immunotherapy (NLR(C1)) and ΔNLR were 0.600, 0.706 and 0.628, respectively. Multivariate logistic regression analysis showed that NLR(C1) was an independent factor of the ORR of metastatic NSCLC patients who underwent immunotherapy (OR=0.161, 95% CI: 0.062-0.422), and the efficacy of combination therapy was better than that of single agent (OR=0.395, 95% CI: 0.174-0.896). The immunotherapy efficacy in patients without brain metastasis was better than those with metastasis (OR=0.291, 95% CI: 0.095-0.887). Multivariate Cox regression analysis showed that NLR(C1) was an independent influencing factor of PFS of metastatic NSCLC patients after immunotherapy (HR=0.480, 95% CI: 0.303-0.759). Sex (HR=0.399, 95% CI: 0.161-0.991, P=0.048), age (HR=0.356, 95% CI: 0.170-0.745, P=0.006) were independent influencing factors of OS of metastatic NSCLC patients after immunotherapy. Conclusions: PD-1/PD-L1 inhibitors are proved to be efficacious and have tolerable toxicities for patients with metastatic NSCLC. Patients at advanced age could still benefit from immunotherapy. Brain metastasis is related to compromised response. Earlier application of immunotherapy in combination with other modalities enhances the efficacy without elevating risk of irAEs. NLR(C1) is an early predictor of clinical outcome. The OS of patients younger than 75 years may be improved when treated with immunotherapy.

Comparison of different types of endovascular mechanical embolectomy in acute ischemic stroke

SUMMARY Background: To compare the treatment efficacy of different types of endovascular mechanical embolectomy in acute ischemic stroke (AIS). Material and Methods: A total of 89 patients with AIS were selected in our hospital from January 2014 to January 2016 and divided into tPA group (n=27), tPA+Trevo group (n=30) and tPA+Solitaire FR group (n=32) for different treatments. Treatment effectiveness was evaluated using NIHSS and mRS system. The NIHSS score, vascular recanalization rate and postoperative complications were compared among groups. Results: The NIHSS score of the tPA group was significantly lower than that of other two groups at 1 d after the operation (p < 0.05), but it was significantly higher than that of other two groups at 3 d and 3 w after the operation (p < 0.05). After the treatment, no significant difference in NIHSS score was found between the tPA+Trevo and tPA Solitaire FR groups. The revascularization rate was significantly higher, but the mortality rate in 90 d was significantly lower in the tPA+Trevo and tPA+Solitaire FR groups than that in the tPA group (p < 0.05), and no significant difference was found between the tPA+Trevo and tPA+Solitaire FR groups. The incidence rate of symptomatic intracranial hemorrhage was significantly lower in the tPA+Solitaire FR group than that in tPA+Trevo group (p < 0.05) or tPA group (p < 0.01). Significantly more patients with mRS no higher than 2 points were found in the tPA+Trevo and tPA+Solitaire FR groups than those in tPA group (p < 0.05), and no significant difference was found between the tPA+Trevo and tPA+Solitaire FR groups. Conclusion: TPA+Solitaire FR is a type of thrombectomy that is superior to tPA and tPA+Trevo in the treatment of patients with AIS.

RESUMO OBJETIVO Comparar a eficácia do tratamento de diferentes tipos de embolectomia mecânica endovascular em acidente vascular cerebral isquêmico agudo (AIS). MATERIAL E MÉTODOS Um total de 89 pacientes com AIS foi selecionado em nosso hospital de janeiro de 2014 a janeiro de 2016, e os pacientes foram divididos em: grupo tPA (n = 27), tPA + grupo Trevo (n = 30) e grupo tPA + Solitaire FR (n = 32) para diferentes tratamentos. A eficácia do tratamento foi avaliada usando NIHSS e sistema mRS. Escore NIHSS, taxa de recanalização vascular e complicações pós-operatórias foram comparados entre os grupos. RESULTADOS A pontuação NIHSS do grupo tPA foi significativamente menor do que a dos outros dois grupos em um dia após a operação (p < 0,05), mas foi significativamente maior do que nos outros dois grupos em três dias e três semanas após a operação (p < 0,05). Após o tratamento, não houve diferença significativa no escore NIHSS entre o grupo tPA + Trevo e o grupo tPA Solitaire FR. A taxa de revascularização foi significativamente maior, mas a taxa de mortalidade em 90 dias foi significativamente menor nos grupos tPA + Trevo e tPA + Solitaire FR do que no grupo tPA (p < 0,05) e não houve diferença significativa entre os grupos tPA + Trevo e tPA + Solitaire FR. A taxa de incidência de hemorragia intracraniana sintomática foi significativamente menor no grupo tPA + Solitaire FR do que no grupo tPA + Trevo (p < 0,05) ou no grupo tPA (p < 0,01). Significativamente mais pacientes com mRS não maiores que 2 pontos foram encontrados no grupo tPA + Trevo e tPA + Solitaire FR do que no grupo tPA (p < 0,05), e nenhuma diferença significativa foi encontrada entre os grupos tPA + Trevo e tPA + Solitaire FR. Conclusão O tPA + Solitaire FR é um tipo de trombectomia superior ao tPA e tPA + Trevo no tratamento de pacientes com EIA.

Application value of urine modified nucleoside's detection in prognosis of bladder transitional cell carcinoma / 中华泌尿外科杂志

Objective To study the application value of modified urine nucleoside's detection in prognosis of patients with bladder cancer. Methods We enrolled 85 patients with bladder transitional cell carcinoma confirmed by pathological examination.The 85 patients fulfilled one-year follow-up visit after TUR-BT and were reviewed every three months.The 85 patients did not relapse in the first third month after operation.At the sixth month after operation,20 cases relapsed.18 cases and 19 cases relapsed at the ninth month and the twelfth month after operation.Patients with recurrence added up to 57 cases as the recurrent group.The remaining 28 cases did not relapse at one year after operation as the no recurrent group.Of the 85 cases,55 cases were in T(is) - T1,while 30 cases were in T2 - T4.Of the 85 cases,27 cases were with G1,40 cases were with G2 and 18 cases were with G3.In T(is) -T1,there were 35 cases in recurrent group,while there were 20 cases in the no recurrent group.In T2 -T4,there were 22 cases in recurrent group,while there were 8 cases in the no recurrent group.There were 50 normal people in the control group.Highperformance liquid chromatography/electrospray ionization-quadrupole-time-of-flight mass spectromerry was used to measure the levels of change of two urine modified nucleosides (M1A,1-MeI) which the patients with bladder cancer had different pathology grades,clinical stages,before or after operation and recurrence or no recurrence. Results The levels at third month after operation in no recurrent group ( M1A:3.24 ± 0.40,1 -MeI:5.73 ± 0.67 ) were significantly lower than that before operation ( M 1A:4.34 ± 0.98,1-MeI:14.22 ± 4.05,P ＜ 0.005 ),and remained in low status at another time points after operation.The levels at the third month after operation in recurrent group (M1A:3.31 ±0.33,1-MeI:5.67 ±0.55) were significantly lower than that before operation ( M1A:4.32 ± 1.19,1-MeI:14.31 ± 4.12,P ＜ 0.005 ),which was on the rise and indicating a high level approaching the condition before operation.According to the time point before the operation,recurrent group and no recurrent group were higher than control group (M1A:2.91 ±0.84,1-MeI:5.56 ± 1.25,P ＜ 0.01 ).The levels at the sixth month,ninth month and twelfth month after operation in recurrent group ( M 1A referring to 4.04 ± 0.48,4.11 ± 0.47,4.09 ± 0.53 ;1-MeI referring to1 1.46 ± 1.34,12.14 ± 1.22,12.33 ± 1.27) were the highest (P ＜ 0.01 ).The levels of change of two urine modified nucleosides between pathology grade and clinical stage had no statistical difference ( P ＞ 0.01 ).The levels in recurrence group in T(is) - T1 ( M1 A:5.92 ± 1.28,1-MeI:20.01 ± 8.53 )were higher than the levels in no recurrent group ( M1A:4.02 ±1.22,1 -MeI:11.21 ± 6.45,P ＜ 0.05 ),which was the same in T2 - T4. Conclusion Urine modified nucleosides detection offer a certain clinical value the prognostic of operated bladder cancer patients.

Nuclear factor κB and IKB expression and calcium deposition of atherosclerotic plaques in apolipoprotein E and low density lipoprotein receptor knockout mice / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the histopathological features, nuclear factor-κB (NFκB) and IKB expressions as well as calcium deposition of atherosclerosis plaques (AS) in apolipoprotein E (ApoE) and low density lipoprotein receptor (LDLR) knockout mice (ApoE(-/-), LDLR(-/-)fed high-fat diet.</p><p><b>METHODS</b>Eight C57BL/6J mice fed with normal diet were used as control, 32 ApoE(-/-) mice and LDLR(-/-) mice were divided into normal diet and high-fat diet groups (n = 8 each). After 4 months, aorta was collected for morphologic (HE, Oil Red O, Von Kossa) and immunohistochemistry (nuclear factor-κB, IKB, macrophage surface molecule-3, α-smooth action protein) analysis.</p><p><b>RESULTS</b>Degree of AS in ApoE(-/-) and LDLR(-/-) mice fed with high-fat diet were significantly severer than those fed with normal diet and AS was more significant in ApoE(-/-) mice than in LDLR(-/-) mice. NFκB and IKB expressions in high-fat diet group were significantly higher than the normal diet group (P < 0.05). Double-labeling of NFκB revealed dominant expression in smooth muscle cells. Calcium deposition was significantly more in ApoE(-/-) mice fed with high-fat diet than mice fed with normal diet (P < 0.05) and was similar in LDLR(-/-) mice fed with high and normal diet (P > 0.05).</p><p><b>CONCLUSION</b>High-fat diet contributes to the formation of AS plagues in ApoE(-/-) and LDLR(-/-) mice joined by upregulated NFκB and IKB expressions and calcium deposition.</p>

Clinical analysis of childhood and adolescent Hodgkin's lymphoma: a report of 88 cases / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to investigate the clinicopathological characteristics, effective treatment and prognosis in childhood and adolescent Hodgkin's lymphoma.</p><p><b>METHODS</b>A total of 88 patients with childhood and adolescent Hodgkin's lymphoma were treated in the Cancer Hospital of CAMS from 1998 to 2005. The clinicopathological and follow-up data of the patients were retrospectively reviewed. The survival rate was calculated by Kaplan-Meier method and compared by log-rank test. COX multivariate prognosis analysis was performed.</p><p><b>RESULTS</b>The 2-year event-free survival rate of the 88 patients was 86.4%, the 5-year event-free survival rate was 61.4%, and the 5-year overall survival rate was 95.5%. Univariate analysis showed that the stage of disease (P = 0.033), "B" symptoms (P = 0.028), bulky disease (P = 0.007), splenomegaly (P = 0.050), LDH elevation (P = 0.020), chemotherapy regimen (P = 0.003) were prognostic factors in the 5-year event-free survival rate. Splenomegaly (P = 0.039), LDH elevation (P = 0.033), chemotherapy regimen (P = 0.008) were prognostic factors of 5-year overall survival rate. Multivariate analysis showed that chemotherapy regimen (P = 0.033), stage of disease (P = 0.023), LDH elevation (P = 0.008), "B" symptoms (P = 0.044), bulky disease (P = 0.009) were independent prognostic factors of 5-year event-free survival rate. The chemotherapy regimen (P = 0.012) and LDH elevation (P = 0.046) were independent prognostic factors of 5-year overall survival rate.</p><p><b>CONCLUSIONS</b>The non-ABVD chemotherapy regimen, stage IV disease, LDH elevation, associated with "B" symptoms and bulky disease are independent prognostic factors of 5-year event-free survival rate. LDH elevation and non-ABVD chemotherapy regimen are independent prognostic factors of 5-year overall survival rate.</p>

Outcome of de-mucosalized ileocystoplasty combined with strengthened pelvic floor in patients with neurogenic bladder / 中华泌尿外科杂志

Objective To assess the outcome of de-epithelialied ileocystoplasty combined with strengthened pelvic floor in patients with neurogenic bladder.Methods Twelve patients (9 male,3 female) aged from 18 -27 years (averaged 25 years) with neurogenic bladder received de-mucosalized seromuscular ileocystoplasty combined with strengthened pelvic floor,and were evaluated by urodynamic parmeters,upper urinary tract image appearance,and serum creatinine before and one year after operation.Results After operation,the max cystometric capacity (412 ± 32 ml),bladder compliance (26.2 ± 4.0ml/H2O),relative safety cystometric capacity (368 ±26 ml) and max flow rate (20 ±3 ml/s) were respectively significantly higher than those preoperation(247 ±27 ml,4.4 ± 1.2 ml/cm H2O,206 ±24 ml,11 ±2ml/s,P ＜ 0.05).Moreover,the post voided residual (26 ± 8 ml) and detmsor leakage point pressure (17.8 ±3.6 cm H2O) were significantly lower than those of preoperation (136 ± 25 ml,63.1 ± 4.9cm H2O,P ＜0.05).The vesicoureteral reflux disappeared in five (63％) cases,and was relieved in the remaining three cases.Of the five cases with renal insufficiency,three (60％) cases had normal serum creatinine level,none had increased serum creatinine levels.After operation,late healing occurred in two ( 17％ ) cases,intestinal obstruction in one (8％),vesicoabdominal fistula in one (8％),and no cases had mucous urine.Clean intermittent self-catheterization was performed in one case (8％) to empty the bladder due to a fever resulting from urinary tract infection,the remaining 12 (92％) cases could empty their bladders through abdominal pressure.Conclusions De-mucosalized seromuscular ileocystoplasty combined with strengthened pelvic floor results in a good outcome for the patients with neurogenic bladder.

Clinical characteristics and treatment of desmoplastic small round cell tumor / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics and treatment of desmoplastic small round cell tumor.</p><p><b>METHODS</b>Five patients with DSRCT were diagnosed and treated in our Hospital from January 1999 to May 2009. Forty-eight cases with complete clinical data were collected and reviewed from 23 published reports. Therefore totally 53 patients with DSRCT were analysed. The survival rate was calculated by Kaplan-Meier method and compared by log-rank test.</p><p><b>RESULTS</b>The median age of all cases was 23 (1.5 - 66) years old at the time of diagnosis. 75.5% of patients were male. The most common presenting complaint was intra-abdominal mass or pain (77.4%). In 46 patients (86.8%), the primary tumor was located in the abdomen or pelvis. Fifteen (28.3%) had positive lymph nodes or distant parenchymal metastases. The median follow-up was 1.8 years (range, 0.1 - 10.0 years). The overall 1-, 3- and 5-year survivals were 45.8%, 20.8% and 5.7%, respectively. Forty-seven patients underwent surgery. Complete tumor resection was significantly correlated with long survival. The 1- and 3-year survival rates were 70.5% and 53.7% in patients treated with complete tumor resection compared to 37.2% and 4.8% in the incomplete tumor resection cohort (P = 0.0020). Thirty-four patients received chemotherapy and the 1- and 3-year survival rates were 60.1% and 35.2%, respectively, however, only 29.7% and 12.7% in patients without chemotherapy (P = 0.0396). Twelve patients had radiotherapy and the 1- and 3-year survival rates were 75.0% and 38.9%, respectively, compared with 36.9% and 14.8% in those without radiotherapy (P = 0.0314).</p><p><b>CONCLUSION</b>Complete tumor resection results in improved survival in patients with DSRCT. Chemotherapy and radiotherapy correlate with improved patient outcome. Multimodal therapy may improve the survival in patients with DSRCT.</p>

Assessment of the protective effect of calcium-magnesium infusion and glutathione on oxaliplatin-induced neurotoxicity / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the efficacy of calcium-magnesium (Ca/Mg) infusion and glutathione (GSH) for preventing the neurotoxicity induced by oxaliplatin.</p><p><b>METHODS</b>This is a randomized, double blind, placebo controlled clinical trail. The patients receiving FOLFOX4 chemotherapy for their solid tumor were randomized to receive Ca/Mg, GSH or normal saline with chemotherapy simultaneously. The incidence and severity of oxaliplatin-induced neurotoxicity were observed. The ECOG performance status was recorded and compared among the 3 groups.</p><p><b>RESULTS</b>Ninety-three patients admitted in our department from Mar 2006 to Dec 2007 were entered into this study, including 29 patients in the Ca/Mg group, 33 in the GSH group and 31 in the chemotherapy alone group. The incidences of acute neurotoxicity were 82.8%, 90.9% and 93.5%, respectively. At the third cycle, the incidences of grade 1-2 chronic neurotoxicity were 37.9%, 48.5% and 42.0%, respectively. No grade 3 neuropathy was observed. After 6 cycles, the incidence of grade 1-2 neuropathy was increased to 68.2%, 88.9% and 85.2%, respectively. A lower percentage was observed in Ca/Mg arm without a statistically significant difference, and grade 3 neuropathy occurred in 5 patients. After 9 cycles, the incidence of grade 1-2 neuropathy was increased to 81.3%, 90.0% and 92.9%, respectively. Grade 3 neuropathy occurred in another 2 patients. No statistically significant difference was observed among the 3 arms. Changes of patient's ECOG score after chemotherapy were similar.</p><p><b>CONCLUSION</b>This study didn't provide evidence that Ca/Mg infusion and GSH can prevent the oxaliplatin-induced neurotoxicity.</p>