Effects of high-dose glucose-insulin-potassium on acute coronary syndrome patients receiving reperfusion therapy:a meta-analysis

BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion therapy.METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs).RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio [RR] 0.57,95% confidence interval [95% CI]:0.35 to 0.94,P=0.03) and the risk of heart failure(RR 0.48,95% CI:0.25 to 0.95,P=0.04) and improved the left ventricular ejection fraction(LVEF)(mean difference [MD] 2.12,95% CI:0.40 to 3.92,P=0.02) at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95% CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95% CI:1.74 to 47.29,P=0.009) and hypoglycemia(RR 6.50,95% CI:1.28 to 33.01,P=0.02) but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD) activity but not glutathione peroxidase(GSH-Px) or catalase(CAT) activity.CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering eflcacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.

High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding:A meta-analysis

AIM:To evaluate the efficacy of high-dose proton pump inhibitors(PPIs)vs low-dose PPIs for patients with upper gastrointestinal bleeding.METHODS:PubMed,Embase,the Cochrane Library,and Web of Science were searched to identify relevant randomized controlled trials(RCTs).Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis.The primary endpoint was rebleeding;secondary endpoints were patient numbers that needed surgery,and mortality.The meta-analysis was performed with a fixed effects model or random effects model.RESULTS:Nine eligible RCTs including 1342 patients were retrieved.The results showed that high-dose intravenous PPI was not superior to low-dose intra-venous PPI in reducing rebleeding[odds ratio(OR)= 1.091,95%confidential interval(CI):0.777-1.532],need for surgery(OR=1.522,95%CI:0.643-3.605) and mortality(OR=1.022,95%CI:0.476-2.196).Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients(OR=0.831,95%CI,0.467-1.480)and European patients(OR=1.263,95%CI:0.827-1.929).CONCLUSION:Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.

Predictors of post-treatment stenosis in cervical esophageal cancer undergoing high-dose radiotherapy

AIM To evaluate toxicity and treatment outcome of highdose radiotherapy(RT) for cervical esophageal cancer(CEC).METHODS We reviewed a total of 62 consecutive patients who received definitive RT for stage Ⅰ to Ⅲ cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local(occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed.RESULTS Grade 1, 2, and 3 esophagitis occurred in 19(30.6%), 39(62.9%), and 4 patients(6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients(25.8%) developed post-RT stenosis, of which 7 cases(43.8%) were malignant. Four patients(6.5%) developed tracheoesophageal fistula(TEF), of which 3(75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4(P = 0.001), complete circumference involvement(P < 0.0001), stenosis at diagnosis(P = 0.024), and endoscopic complete response(P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis(P = 0.003). A higher dose(≥ 60 Gy) was not associated with occurrence of postRT stenosis or TEF. With a median follow-up of 24.3(range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival(OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement(P = 0.023), stenosis at diagnosis(P < 0.0001), and occurrence of post-RT stenosis or TEF(P < 0.001) in univariate analysis, while stenosis at diagnosis(P = 0.004) and occurrence of post-RT stenosis or TEF(P = 0.023) were significant in multivariate analysis. CONCLUSION Chemoradiation for CEC was well tolerated, and a higher dose was not associated with stenosis. Patients with complete circumferential involvement require close follow-up.

High-dose interferon-α2b induction therapy in combination with ribavirin for treatment of chronic hepatitis C in patients with non-response or relapse after interferon-a monotherapy

AIM： To evaluate the daily high-dose induction therapy with interferon-α2b （IFN-α2b） in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse, based on the assumption that the viral burden would decline faster, thus increasing the likelihood of higher response rates in this difficult-totreat patient group. METHODS： Seventy patients were enrolled in this study. Treatment was started with 10 NU IFN-α2b daily for 3 wk, followed by IFN-α2b 5 NU/TIW in combination with ribavirin （1 000-1 200 mg/d） for 21 wk. In case of a negative HCV RNA PCR, treatment was continued until wk 48 （IFN-α2b 3MU/TIW＋1000-1200 mg ribavirin/daily）. RESULTS： The dose of IFN-α2b or ribavirin was reduced in 16% of patients because of hematologic side effects, and treatment was discontinued in 7% of patients. An early viral response （EVR） was achieved in 60% of patients. Fifty percent of all patients achieved an end-oftreatment response （EOT） and d0% obtained a sustained viral response （SVR）. Patients with no response had a significantly lower response rate than those with a former relapse （SVR 30% vs 53%; P=0.049）. Furthermore, lower response rates were observed in patients infected with genotype la/b than in patients with non-1-genotype （SVR 28% vs7d%; P=0.001）. As a significant predictive factor for a sustained response, a rapid initial decline of HCV RNA could be identified. No patient achieving a negative HCV-RNA PCR at wk 18 or later eventually eliminated the virus. CONCLUSION： Daily high-dose induction therapy with interferon-α2b is well tolerated and effective for the treatment of non-responders and relapsers, when interferon monotherapy fails. A fast decline of viral load during the first 12 wk is strongly associated with a sustained viral response.

Dose-individualization Efficiently Maintains Sufficient Exposure to Methotrexate without Additional Toxicity in High-dose Methotrexate Regimens for Pediatric Acute Lymphoblastic Leukemia

Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.

The Experience of Pain and Anxiety in Cervical Cancer Patients Undergoing Multiple Fraction High-Dose Rate Brachytherapy: A Prospective Observational Study

Purpose: To evaluate the anxiety and pain levels of cervical cancer patients undergoing intracavitary multifraction high-dose rate (HDR) brachytherapy, as part of a process to develop guidelines for quality patient-centered care. Methods: Cervical cancer patients (n = 31) undergoingmultiple fraction HDR brachytherapy treatment at the National Institute of Oncology in Rabat (Morocco) completed ratings of pain and anxiety intensity using 11-point verbal analog scales, at 6 key time points over 2 brachytherapy insertion procedures and 4 brachytherapy fractions. Women were evaluated for psychological status at baseline before starting the brachytherapy process using the Hospital Anxiety and Depression Scale (HADS). Scores were grouped as follows: 0 - 7 = normal, 8 - 10 = borderline, 11 - 21 = abnormal. Factors that could affect anxiety levels such as education level, relationship status, number of pregnancies and prior surgical history were documented. Results: Between July and August 2020, 31 women with a median age of 49.6 years were evaluated (range: 27 - 70). The HADS score identified depression in 5 patients (16.1%) and anxiety in 12 patients (38.7%). Throughout both treatment procedures, anticipatory anxiety was reported, with a maximum intensity in the operating room during spinal anesthesia (3.23 ± 1.7) and during applicator insertion (2.97 ± 2.4). Moderate-to-severe anxiety scores were reported in 25.8% and 22.6% of patients respectively. Level of education showed a significant correlation with anxiety scores (p = 0.027). Pain increased significantly during the procedure (p ± 1.4) and applicator removal (4.74 ± 1.5) turned out to be the most painful parts of the procedure. No correlation was found between pain and anxiety levels. Conclusion: Intracavitary multifraction high-dose rate brachytherapy is associated with mild to moderate levels of pain and anxiety, although a subset of patients reported more severe symptoms and may require additional medical and psychological support, with particular emphasis on bed-rest duration and applicator removal. The development of effective interventions (both pharmacological and non-pharmacological) is needed to improve women’s experiences of brachytherapy for locally advanced cervical cancer.

Very-high-dose olanzapine for treatment-resistant schizophrenia

Treatment-resistant schizophrenia has an extremely negative impact on mental health and social life. If clozapine, the gold standard treatment, fails, there are very few options left. The literature suggests that high-dose olanzapine (20 - 60 mg/day) is a possible alternative. We report two cases in which very high doses of olanzapine were administered, with significant clinical improvements above 60 mg/day. Clinical, metabolic and cardiac tolerance was good. This report highlights the usefulness of very-high-dose olanzapine in treatment-resistant schizophrenia. The main hypotheses concerning the psychopharmacological mechanisms of very-high-dose olanzapine are discussed.

Comparison of High-Dose Dexamethasone and Prednisone for Initial Treatment of Adult Primary Immune Thrombocytopenia

Prednisone is the most common first-line treatment for adult primary immune thrombocytopenia (ITP). However, the best initial therapeutic approach is still a matter of debate. Prior studies have shown that high-dose dexamethasone (HD-DXM) produces a high sustained efficacy not achieved by conventional prednisone therapy. However, the definition of response widely differs between individual reports, and this heterogeneity makes comparison of the efficacy difficult. The aim of our study was to compare the therapeutic outcomes of a conventional dose of prednisone with HD-DXM for adult ITP patients as initial therapy. Thirty patients treated with prednisone and 22 patients treated HD-DXM were retrospectively analyzed. No significant differences between the HD-DXM and prednisone groups were observed for the rates of complete response (68% vs. 70%) and response (18% vs. 17%). However, 1 year probability of sustained response was significantly greater in the HD-DXM group than in the prednisone group (78% vs. 38%;P = 0.008). No adverse events necessitating discontinuation of treatment were observed in either group. Our retrospective analysis showed that initial treatment with HD-DXM produced longer response duration compared to a conventional dose of prednisone. Randomized clinical trials are warranted to establish the optimal initial steroid therapy for adult ITP.

A New Variant of Combined Pulmonary Fibrosis and Emphysema from Long-Term High-Dose of Glucocorticoid Therapy: A Case Report

Recent studies have described the combination of both pulmonary emphysema and idiopathic interstitial lung disease (ILDs) by means of high-resolution computed axial tomography (HRCT). Definition of this syndrome was first named by Cottin as combined pulmonary fibrosis and emphysema (CPFE). Functional and radiological findings have showed that these patients are suffering from severe breathlessness, but whose pulmonary functional tests revealed no signs of obstruction, normal static lung volumes, and depressed DLco, most with a history of smoking [1] [2]. The radiological and endoscopic studies especially show that these patients have both areas of upper-lobe predominant emphysema and lesions compatible with fibrosis in both lung bases [3]. No prior research has reported any cases of such condition in person with no prior history of smoking as well as long-term high-dose of glucocorticoid therapy. In this case report, we discuss the presentation, diagnosis, and management of a 53-year-old non-smoker with increasing shortness of breath with a long-term high-dose of glucocorticoid therapy discovered to have an abnormal variant or presentation of CPFE. The cause of disease was attributed to a certain history of smoking in most studies;other potential risk factors have yet to be properly analyzed. This clinical report features a special case about the problem and solution surrounding this issue.

白屈菜碱对小鼠肺癌细胞皮下移植瘤生长和血管生成的抑制作用及其机制

目的:探讨白屈菜碱对肺癌移植瘤小鼠肿瘤生长和血管生成的影响,并阐明其作用机制。方法:选取32只健康C57BL/6小鼠,制备Lewis肺癌移植瘤小鼠模型。将小鼠随机分为模型组(0.9%氯化钠)、低剂量白屈菜碱组(25 mg·kg^(-1)白屈菜碱)、高剂量白屈菜碱组(50 mg·kg^(-1)白屈菜碱)和阳性对照组(60 mg·kg^(-1)环磷酰胺),每组8只。称量各组小鼠移植瘤质量并计算抑瘤率,计算各组小鼠胸腺指数和脾脏指数,采用酶联免疫吸附测定(ELISA)法检测各组小鼠血清中白细胞介素2(IL-2)、γ干扰素(INF-γ)和肿瘤坏死因子α(TNF-α)水平,免疫组织化学法检测各组小鼠肿瘤组织中血管内皮生长因子(VEGF)蛋白表达情况并计算微血管密度(MVD)及VEGF蛋白表达评分,Westernblotting法检测各组小鼠肿瘤组织中核因子κB(NF-κB)和缺氧诱导因子1α(HIF-1α)蛋白表达水平。结果:与模型组比较,低和高剂量白屈菜碱组及阳性对照组小鼠移植瘤质量均降低(P<0.05);与低剂量白屈菜碱组比较,高剂量白屈菜碱组和阳性对照组小鼠移植瘤质量均降低(P<0.05),抑瘤率均升高(P<0.05);与高剂量白屈菜碱组比较,阳性对照组小鼠移植瘤质量均降低(P<0.05),抑瘤率升高(P<0.05)。与模型组比较,低和高剂量白屈菜碱组及阳性对照组小鼠脾脏指数和胸腺指数均升高(P<0.05);与低剂量白屈菜碱组比较,高剂量白屈菜碱组和阳性对照组小鼠脾脏指数及胸腺指数均升高(P<0.05);与高剂量白屈菜碱组比较,阳性对照组小鼠脾脏指数和胸腺指数均升高(P<0.05)。ELISA法,与模型组比较,低和高剂量白屈菜碱组及阳性对照组小鼠血清中IL-2、INF-γ和TNF-α水平均升高(P<0.05);与低剂量白屈菜碱组比较,高剂量白屈菜碱组和阳性对照组小鼠血清中IL-2、INF-γ和TNF-α水平均升高(P<0.05);与高剂量白屈菜碱组比较,阳性对照组小鼠血清中IL-2、INF-γ和TNF-α水平均升高(P<0.05)。与模型组比较,低和高剂量白屈菜碱组及阳性对照组小鼠肿瘤组织MVD降低(P<0.05);与低剂量白屈菜碱组比较,高剂量白屈菜碱组和阳性对照组小鼠肿瘤组织MVD降低(P<0.05);与高剂量白屈菜碱组比较,阳性对照组小鼠肿瘤组织中MVD降低(P<0.05)。与模型组比较,低和高剂量白屈菜碱组及阳性对照组小鼠肿瘤组织中VEGF蛋白表达量减少;与低剂量白屈菜碱组比较,高剂量白屈菜碱组和阳性对照组小鼠肿瘤组织中VEGF蛋白表达量减少;与高剂量白屈菜碱组比较,阳性对照组小鼠肿瘤组织中VEGF蛋白表达量减少;模型组、低剂量白屈菜碱组、高剂量白屈菜碱组和阳性对照组小鼠肿瘤组织VEGF蛋白表达评分比较差异有统计学意义(P<0.05)。Western blotting法,与模型组比较,低和高剂量白屈菜碱组及阳性对照组小鼠肿瘤组织中NF-κB和HIF-1α蛋白表达水平降低(P<0.05);与低剂量白屈菜碱组比较,高剂量白屈菜碱组和阳性对照组小鼠肿瘤组织中NF-κB和HIF-1α蛋白表达水平降低(P<0.05);与高剂量白屈菜碱组比较,阳性对照组小鼠肿瘤组织中NF-κB和HIF-1α蛋白表达水平降低(P<0.05)。结论:白屈菜碱能够抑制Lewis肺癌移植瘤小鼠肿瘤组织生长、保护免疫器官和抑制肿瘤血管生成,可能通过靶向NF-κB/HIF-1α信号通路和下调NF-κB及HIF-1α蛋白表达水平发挥治疗作用。

ALL患儿大剂量甲氨蝶呤化疗和亚叶酸解救治疗期间红细胞内叶酸和甲氨蝶呤代谢的变化

目的 探讨急性淋巴细胞白血病(ALL)儿童在给予大剂量甲氨蝶呤(HDMTX)化疗和亚叶酸(LV)解救后红细胞(REC)内叶酸(FA)和甲氨蝶呤(MTX)代谢产物的变化。方法 2021年5月至2022年12月,前瞻性测定72例ALL儿童在HDMTX开始前(T0)和LV解救停止后(T1)红细胞内叶酸(REC-FA)和REC内MTX聚谷氨酸盐(REC MTX-PG_(2-5))的水平。结果 在T0和T1之间,REC MTC-PG_(2-5)和REC-FA水平显著增加(P<0.001),ΔT1-T0值分别为180.50(79.50,362.00)nmol/L和92.52(60.96,117.01)nmol/L;这是由于5-甲基四氢叶酸(THF)水平增加(P<0.001),其ΔT1-T0值为172.50(76.50,361.00)nmol/L,而非甲基THF水平没有变化(P>0.05)。REC-FA在T0和T1之间增加(P<0.001),结果不受年龄、性别、MTHFR677C>T基因型、ALL表型和T0血浆FA水平的显著影响。MTX诱导的≥3级口腔粘膜炎与REC MTX-PG_(2-5)ΔT1-T0更高以及REC 5-甲基THF、REC-FA水平和REC-FA/REC MTX-PG_(2-5)ΔT1-T0更低有关(P<0.05)。结论 ALL儿童经HDMTX化疗和LV解救治疗后,REC-FA水平积累,表明LV可恢复细胞内叶酸库;另一方面REC-FA水平的增加似乎对REC内MTX水平没有太大影响。

Nutritional management and autism spectrum disorder:A systematic review

BACKGROUND Autism spectrum disorder(ASD)presents unique challenges related to feeding and nutritional management.Children with ASD often experience feeding difficulties,including food selectivity,refusal,and gastrointestinal issues.Various interventions have been explored to address these challenges,including dietary modifications,vitamin supplementation,feeding therapy,and behavioral interventions.AIM To provide a comprehensive overview of the current evidence on nutritional management in ASD.We examine the effectiveness of dietary interventions,vitamin supplements,feeding therapy,behavioral interventions,and mealtime practices in addressing the feeding challenges and nutritional needs of children with ASD.METHODS We systematically searched relevant literature up to June 2024,using databases such as PubMed,PsycINFO,and Scopus.Studies were included if they investigated dietary interventions,nutritional supplements,or behavioral strategies to improve feeding behaviors in children with ASD.We assessed the quality of the studies and synthesized findings on the impact of various interventions on feeding difficulties and nutritional outcomes.Data extraction focused on intervention types,study designs,participant characteristics,outcomes measured,and intervention effectiveness.RESULTS The review identified 316 studies that met the inclusion criteria.The evidence indicates that while dietary interventions and nutritional supplements may offer benefits in managing specific symptoms or deficiencies,the effectiveness of these approaches varies.Feeding therapy and behavioral interventions,including gradual exposure and positive reinforcement,promise to improve food acceptance and mealtime behaviors.The findings also highlight the importance of creating supportive mealtime environments tailored to the sensory and behavioral needs of children with ASD.CONCLUSION Nutritional management for children with ASD requires a multifaceted approach that includes dietary modifications,supplementation,feeding therapy,and behavioral strategies.The review underscores the need for personalized interventions and further research to refine treatment protocols and improve outcomes.Collaborative efforts among healthcare providers,educators,and families are essential to optimize this population's nutritional health and feeding practices.Enhancing our understanding of intervention sustainability and long-term outcomes is essential for optimizing care and improving the quality of life for children with ASD and their families.

PhaseⅡstudy of oxaliplatin combined with S-1 and leucovorin(SOL)for Chinese patients with metastatic colorectal cancer

Background:Fluoropyrimidine and oxaliplatin are widely used for patients with colorectal cancer.This phase II study was conducted to evaluate the efficacy and safety of the combination of S-1,oxaliplatin,and leucovorin(SOL) in the treatment of Chinese patients with metastatic colorectal cancer(mCRC).Methods:Eligible patients with untreated mCRC from four hospitals in China received intravenous oxaliplatin(85 mg/m2) on day 1,oral S-1 twice daily(80-120 mg per day) on day 1-7,and leucovorin twice daily(50 mg per day)simultaneously with S-1,every 2 weeks.Results and discussion:Forty patients were enrolled in our study.In total,296 cycles of SOL were administered.The overall response rate was 50.0%.At a median follow-up of 27 months,progression-free survival and overall surviva were 7.0 months(95%confidence interval[CI]6.0-10.6 months) and 22.2 months(95%CI 15.1-29.3 months),respectively.The most common grade 3/4 non-hematological adverse events were diarrhea(n = 8,20.0%),nausea(n = 3,7.5%),and vomiting(n = 3,7.5%).The most common grade 3/4 hematological toxicities were thrombocytopenia(n = 3,7.5%),neutropenia(n = 1,2.5%),and abnormal alanine transaminase/aspartate transaminase levels(n = 1,2.5%).There was one treatment-related death.Conclusions:The data indicate that the SOL regimen is effective and moderately tolerated in Chinese patients with mCRC.Trial registration:Clinical trial

Bevacizumab plus infusional 5-fluorouracil,leucovorin and irinotecan for advanced colorectal cancer that progressed after oxaliplatin and irinotecan chemotherapy:A pilot study

AIM： To evaluate the combination of bevacizumab with infusional 5-fluorouracil （5-FU）, leucovorin （LV） and irinotecan （FOLFIRI） in patients with advanced colorectal cancer （CRC） pretreated with combination regimens including irinotecan and oxaliplatin. METHODS： Fourteen patients （median age 56 years） with advanced CRC, all having progressed after oxaliplatin- and irinotecan-based combination chemotherapy, were enrolled in this study. Patients were treated with 2 h infusion of irinotecan 150 mg/m2 on d 1, plus bevacizumab 5 mg/kg iv infusion for 90 min on d 2, and iv injection of LV 20 mg/m2 followed by a bolus of 5-FU 400 mg/m2 and then 22 h continuous infusion of 600 mg/m2 given on two consecutive days every 14 d. RESULTS： The median number of cycles of chemotherapy was six （range 3-12）. The response rate was 28.5%, one patient had a complete response, and three patients had a partial response. Eight patients had stable disease. The median time to progression was 3.9 mo （95% CI 2.0-8.7）, and the median overall survival was 10.9 mo （95% CI 9.6-12.1）. Grade 3/4 neutropenia occurred in five patients, and two of these developed neutropenic fever. Grade 3 hematuria and hematochezia occurred in one. Grade 2 proteinuria occurred in two patients. However, hypertension, bowel perforation or thromboembolic events did not occur in a total of 90 cycles. CONCLUSION： Bevacizumab with FOLFIRI is well tolerated and a feasible treatment in patients with heavily treated advanced CRC.

Oxaliplatin,Fluorouracil and Leucovorin (FOLFOX) as First-line Chemotherapy for Metastatic or Recurrent Colorectal Cancer Patients

OBJECTIVE To investigate the efficiency and safety of the oxaliplatin, fluorouracil （5-FU） and leucovorin regimen （FOLFOX）in previously untreated patients with metastatic or recurrent colorectal cancer. METHODS Previously untreated patients with metastatic or recurrent colorectal cancer received 100 mg/m^2 of oxaliplatin intravenously （Ⅳ） over 2 h on day 1, and Ⅳ 400 mg/m^2 of leucovorin over 2 h followed by a bolus of 400 mg/m^2 of 5-FU. Then 2,600-3,000 mg/m^2 of 5-FU was administered by continuous infusion over 46 h. RESULTS An evaluated response rate was determined for 97 of 105 treated patients. The overall response rate was 35.1%, 9 patients （9.3%） had a complete response and 25 patients （25.8%） a partial response. Thirtytwo patients （33.0%） developed stable disease and 32.0% of the patients progressed. The median time to progression （TTP） was 7.7 months and the median overall survival 20.5 months. One and 2-year survival rates were 68% and 32%. Toxic effects based on the National Cancer Institute-Common Toxicity Criteria （NCI-CTC）, reaching grade 3/4 were： neutropenia 12.3%, anemia 11.3%, vomiting 4.1% and diarrhea 7.2%. Grade 3 neuropathy was 5.1%. The overall survival rate of patients who had received a radical resection was superior to the patients who had not received a operation, or had received a palliative resection （P=0.0658）. The serum levels of CEA, ALP and LDH had no relationship with survival （P〉0.05）. CONCLUSION The FOLFOX regimen containing oxaliplatin, 5-FU plus leucovorin was an efficacious regimen with good tolerability in previously untreated metastatic or recurrent colorectal cancer patients.

Multicenter Analysis of mFOLFOX6 with Oxaliplatin Stop-and-Go Strategy Using Oral Uracil-Tegafur with Leucovorin for Unresectable Colorectal Cancer in Elderly Patients

Background: This study evaluated the tolerability and efficacy of intermittent oxaliplatin treatment based on mFOLFOX6 using oral uracil-tegafur(UFT) and leucovorin(LV) maintenance therapy in the treatment of elderly patients with advanced colorectal cancer. Methods: Ten non-elderly patients (70 years) with advanced/recurrent colorectal cancer were enrolled in this prospective, multicenter cooperative group clinical trial. The mFOLFOX6 regimen was administered for eight cycles with maintenance therapy with oral UFT/LV treatment until progression. In cases with disease progression, mFOLFOX6 was reintroduced. Results: Grade 2 peripheral neuropathy was noted in 30.0% and 25.0% of the elderly and non-elderly patients, respectively. The observed time to treatment failure (TTF) was 6.3 months in the elderly patients and 6.4 months in the non-elderly patients. The disease control rate was 83.3% in each group. Conclusion: Our new stop-and-go strategy using oral UFT/LV is well-tolerated and effective even in elderly patients.

Oxaliplatin combined with 5-fluorouracil, leucovorin regimen for patients with advanced colorectal cancer

Objective： To observe the efficacy and tolerability of continuously infusing 5-fluorouracil （5-FU） / folic acid combined with oxaliplatin （L-OHP/5-FU/LV regimen） as first line treatment in advanced colorectal cancer. Methods： 23 patients of advanced colorectal cancer were treated with 5-FU 500 mg/d, civ, d 1-d5, d8-d12, leucovorin 100 mg/d, iv gtt, d1, d8, folic acid tablet 60 mg/d, po, d2-d5, d9-d12, and oxaliplatin 65 mg/（m^2·d）, iv gtt, dl, d8, repeated every 21 days （one cycle）. The effect was evaluated after two cycles. Results： Complete response in 2 cases and partial response in 10 cases were observed with an overall response rate of 47.18%. Adverse effects were mainly grade 1-2, including nausea, vomiting, diarrhea, dental ulcer, peripheral neuritis and myelosuppression. Conclusion： L-OHP/5-FU/LV regimen is an effective and better tolerated alternative treatment in advanced colorectal cancer and yields promising clinical application.

Effects of oxaliplatin, leucovorin and fluorouracil on serum tumor markers, VEGF, CRP and matrix metalloproteinases in patients with advanced esophageal cancer

Objective: To investigate the effects of oxaliplatin, leucovorin and fluorouracil on serum tumor markers, VEGF, CRP and matrix metalloproteinases in patients with advanced esophageal cancer. Methods: From March 2012 to March 2017 a total of 248 patients with advanced esophageal cancer were selected as the study subjects. According to random data table, they were divided into control group (n=123) and observation group (n=125) according to random data table. The control group was treated with cisplatin combined with fluorouracil, leucovorin chemotherapy, and patients in the observation group received oxaliplatin, leucovorin and fluorouracil chemotherapy, all patients were treated for 2 cycles. The changes of serum tumor markers, VEGF, CRP and matrix metalloproteinase levels in the two groups before and after treatment was compared. Results: Before treatment, there was no significant difference of the levels of serum CA125, CA19-9, CEA, VEGF, CRP, MMP-2 and MMP-9 between the control group and the observation group. Compared with the group before treatment, the levels of CA125, CA19-9, CEA, VEGF, CRP, MMP-2 and MMP-9 in the two groups were significantly lower. After treatment, the level of CA125, CA19-9, CEA, VEGF, CRP, MMP-2 and MMP-9 in the observation group was significantly lower than those of the control group. Conclusion:Oxaliplatin, leucovorin and fluorouracil chemotherapy can effectively reduce the levels of serum tumor markers, VEGF, CRP and matrix metalloproteinase in patients with advanced esophageal cancer, it has important clinical value.

Clinical outcomes of newly diagnosed primary central nervous system lymphoma treated with zanubrutinib-based combination therapy

BACKGROUND High-dose methotrexate(HD-MTX)combined with other chemotherapeutic agents is an effective treatment for patients with newly diagnosed primary central nervous system lymphoma(PCNSL);however,some patients have adverse reactions.AIM To retrospectively evaluate disease outcomes and mutational profiles in newly diagnosed PCNSL patients treated with a zanubrutinib/HD-MTX combination regimen.METHODS Nineteen newly diagnosed PCNSL patients were treated with zanubrutinib/HDMTX until disease progression,intolerable toxicities,or physician/patientdirected withdrawal.Safety and efficacy were assessed per the CTCAE v5.0 and RECIST v1.1 criteria,respectively.The primary endpoint was the objective response rate(ORR),and the secondary endpoints were progression-free survival,overall survival(OS),and safety.RESULTS The median follow-up duration was 14.7 mo(range,3.9–30 mo).The ORR for all patients was 84.2%,and 2-year progression-free-and OS rates were 75.6%and 94.1%,respectively.All patients completed the induction phase,and nine patients underwent autologous stem cell transplantation as consolidation therapy,resulting in an ORR of 88.9%.Ten patients received zanubrutinib as maintenance therapy and achieved an ORR of 80%.All patients showed an acceptable safety profile.The sequencing results for cerebrospinal fluid(CSF)and tumor tissue showed that PIM1 mutations were the most frequent genetic alterations.Circulating tumor DNA was correlated with disease relapse and response.CONCLUSION Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients.Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden.

Is Escalated Radiation Dose in Definitive Chemoradiotherapy Better for Inoperable Esophageal Carcinoma? A Meta-Analysis and Systematic Review

Purpose: This study aimed to compare the survival benefits between different total radiation doses in definitive chemoradiotherapy (dCRT) for inoperable esophageal carcinoma (EC) based on modern radiotherapy techniques. Methods: A systematic review was performed by searching the databases of PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science. All studies published prior to November 30, 2022, comparing radiation dose and disease-related outcomes in EC patients. The hazard ratio (HR) and odds ratio (OR) were used to describe the risk of outcomes and toxicities. Results: Seven prospective trials involving 1124EC patients were enrolled for analyses. The results revealed that the effect on overall survival (HR = 0.99, 95% CI = 0.85 - 1.16, P = 0.94), local progression-free survival (HR = 0.83, 95% CI = 0.58 - 1.17, P = 0.29), local regional progression-free survival (HR = 0.94, 95% CI = 0.76 - 1.17, P = 0.61), progression-free survival (HR = 0.90, 95% CI = 0.71 - 1.13, P = 0.35) was similar in the high-dose and standard-dose groups. Additionally, a high radiation dose exhibited a potential disadvantage in respiratory toxicities when compared with a standard dose (4.8% vs 2.2%, OR 2.11, P = 0.06). Conclusions: The efficacy of the HD group (≥60 Gy) and the SD group (approximately 50 Gy) for inoperable local advanced EC was similar. However, the HD group exhibited a high radiation dose exhibited a potential disadvantage in respiratory toxicities when compared with a standard dose. Simultaneously, the final results of several ongoing prospective trials regarding the optimal radiation dose in dCRT are awaited.