Prognostic factors affecting the success of conversion chemotherapy in patients with unresectable liver metastases from initially colorectal cancer / 中华胃肠外科杂志

Objective: To investigate the factors affecting the success of conversion therapy in patients with initially unresectable colorectal cancer liver metastases (CRLM) in order to provide evidence-based medical evidence for formulating individualized treatment strategies for patients. Methods: A retrospective case-control study was used in this study. Clinical data of 232 patients with initially unresectable CRLM receiving first-line systemic treatment in Sun Yat-sen University Cancer Center from January 2013 to January 2020 were collected, including 98 patients of successful conversion and 134 patients of failed conversion as control. Conversion therapy scheme: 38 patients received FOLFOXIRI regimen chemotherapy (irinotecan, oxaliplatin, calcium folinate and fluorouracil), 152 patients received FOLFOX regimen (oxaliplatin, calcium folinate and fluorouracil), 19 patients received FOLRIRI regimen (irinotecan, calcium folinate and fluorouracil), 23 patients received systemic chemotherapy combined with fluorouridine hepatic artery infusion chemotherapy; 168 patients received targeted therapy, including 68 of bevacizumab and 100 of cetuximab. Logistics analysis was used to compare the factors affecting the success of conversion therapy. The Kaplan-Meier method was used to calculate progression-free survival (PFS), and the Log-rank test was used for survival comparison. Results: Among 232 patients, 98 patients had successful conversions and 134 patients had failed conversions with a successful conversion rate of 42.2%, meanwhile 30 patients underwent simple hepatectomy and 68 underwent hepatectomy combined with intraoperative radiofrequency ablation. After first-line chemotherapy, 111 patients (47.8%) were partial remission, 57 patients (24.6%) were stable disease, and 64 patients (27.6%) were progression disease. During the median follow-up of 18.8 (1.0-87.9) months, 148 patients were dead or with tumor progression. The median PFS time of patients with successful conversion was longer than that of patients with failed conversion (31.0 months vs. 9.9 months, P<0.001). Univariate analysis found that the bilobar distribution of liver tumors (P=0.003), elevated baseline carcinoembryonic antigen (CEA) levels (P=0.024), tumor invasion of the portal vein (P=0.001), number of metastatic tumor>8 (P<0.001), non-FOLFOXIRI (P=0.005), and no targeted therapy (P=0.038) were high risk factors for the failed conversion therapy. The results of multivariate logistics analysis indicated that the number of metastatic tumor >8 (OR=2.422, 95%CI: 1.291-4.544, P=0.006), portal vein invasion (OR=2.727, 95%CI: 1.237-4.170, P=0.008) were the independent risk factors for failed conversion therapy, while FOLFOXIRI regimen (OR=0.300, 95%CI: 0.135-0.666, P=0.003) and targeted drugs (OR=0.411, 95%CI: 0.209-0.809, P=0.010) were independent protective factors for successful conversion therapy. Conclusions: The number of metastatic tumor and portal vein invasion are key factors that affect the outcomes of conversion therapy for initially unresectable CRLM. If a patient can tolerate chemotherapy, a combination program of three-drug and targeted therapy is preferred for the active conversion therapy.

Characteristics and Clinical Implication of UGT1A1 Heterozygous Mutation in Tumor / 中国肺癌杂志

BACKGROUND@#The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear.@*METHODS@#A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization.@*RESULTS@#There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not.@*CONCLUSIONS@#In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.

Chinese expert consensus on the clinical application of the Chinese modified triplet combination with irinotecan, oxaliplatin and continuous infusional 5-fluorouracil/leucovorin for colorectal cancer / 中华胃肠外科杂志

Colorectal cancer is the second most common malignant tumor in China. The FOLFOXIRI regimen, which combines 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan, is a high-intensity and highly effective chemotherapy regimen. However, the original regimen is poorly tolerated in Chinese patients. In order to promote the standardized and rational application of FOLFOXIRI regimen by clinicians in China, "

Effect of Bmi-1 Expression on Chemotherapy Sensitivity in THP-1 Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of Bmi-1 expression on the chemosensitivity of THP-1 cells and its relative mechanism.@*METHODS@#The pGenesil-2-Bmi-1 1 siRNA, p-MSCV-Bmi-1 plasmid was transfected into THP-1 cells to reduce or increase the expression of Bmi-1. The expression of Bmi-1 mRNA and protein was verified by PCR and Western blot. The effect of camptothecin (CPT) on the proliferation and chemosensitivity of THP-1 cells affected by Bmi-1 gene were detected by MTT assay. The expression of DNA double-strand breaks marker-γ-H2AX was detected by immunofluorescence assay. Mitochondrial membrane potential and apoptosis were observed by flow cytometry. The expression of Cytochrome C, Caspase 3, Bax and BCL-2 was detected by Western blot.@*RESULTS@#Silencing Bmi-1 could inhibit proliferation and enhance the sensitivity of THP-1 cells to CPT, while overexpressed Bmi-1 could promote the cell proliferation and attenucate sensitivity of THP-1 cells to CPT. Silencing Bmi-1 could enhance CPT-induced DNA double-strand breaks, decrease mitochondrial membrane potential and promote CPT-induced apoptosis. While increasing Bmi-1 gene expression could attenuate CPT-induced DNA double-strand breaks, enhamce mitochondrial membrane potential and significantly reduce CPT-induced apoptosis of cells.@*CONCLUSION@#Bmi-1 expression could influence the sensitivity of THP-1 cells to CPT, and its relative mechanism may relate to DNA double-strand breaks and endogenous apoptotic pathways.

Analysis on safety and preliminary efficacy of dose-modified regimen of 5-fluorouracil plus oxaliplatin and irinotecan (FOLFOXIRI) in advanced colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the safety and preliminary efficacy of dose-modified regimen of 5-fluorouracil plus oxaliplatin and irinotecan (mFOLFOXIRI) for patients with advanced colorectal cancer (CRC).</p><p><b>METHODS</b>Data of 312 CRC patients confirmed by pathology receiving triplet drug alone or combined with target therapy between October 2012 and December 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. CRC patients who had previously completed adjuvant therapy (or neoadjuvant therapy) within 6 months or palliative chemotherapy were excluded, meanwhile those with poor general condition (ECOG score > 2) or grade 2 neuropathy and allergy to oxaliplatin were excluded as well. Regimen of mFOLFOXIRI: oxaliplatin 85 mg/m² dissolved in 5% glucose solution 500 ml by intravenous infusion for 2 h; irinotecan 150 to 165 mg/m² dissolved in 0.9% sodium chloride 250 ml by intravenous infusion for 90 min; following intravenous infusion of leucovorin 400 mg/m² for 2 h, day 1; 5-FU 2800 mg/m², 48-h continuous intravenous infusion; once every 2 weeks. Therapy could be combined with a targeted drug, bevacizumab 5 mg/kg every two weeks; cetuximab 500 mg/m² every two weeks. Side effect was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 4.0.3). The objective response rate was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) after administering at least four cycles of chemotherapy.</p><p><b>RESULTS</b>The median age was 52 years (range 16-73) in the whole group; 113 patients (36.2%) had locally advanced CRC, and 199 (63.8%) had metastatic CRC. Most patients (274/312, 87.8%) did not receive any treatment earlier. There were a total of 1651 chemotherapy cycles in the whole group, with a median of 6(1-19) cycles. Of these 1651 cycles, 124 cycles of chemotherapy(7.5%) were dose-adjusted; 176 cycles of chemotherapy(10.7%) were delayed for median 5(3-13) days; 124 cycles(7.5%) required dose decrease. The overall relative dose intensity was >90%; the specific drug dose intensity was 93.6%(2620 mg×m⁻²×d⁻¹) for fluorouracil, 97.8%(83 mg×m⁻²×d⁻¹) for oxaliplatin, and 94.2%(155 mg×m⁻²×d⁻¹) for irinotecan. Twenty-three patients (7 of intestinal perforation, 7 of intestinal obstruction, 1 of grade 4 hematologic toxicity, and 8 of grade 3 fatigue) refused subsequent chemotherapy due to intolerable toxicity. Main grade 3 or 4 adverse events in patients were neutropenia in 69 cases (22.1%), fatigue in 35 cases (11.2%), and anemia in 28 cases (8.9%). Twenty serious adverse events (6.4%) occurred, including 13 patients of febrile neutropenia (4.2%), 7 patients of intestinal perforation (2.2%, 4 patients in upper rectum, 2 in sigmoid colon, and 1 in transverse colon cancer), and 9 of them had subsequent sepsis (2.9%). All the patients with intestinal perforation underwent emergency operation. No treatment-related deaths occurred. In 199 patients with metastatic CRC, because 22 patients did not receive image evaluation, the preliminary efficacy of 177 patients was actually evaluated. A total of 113 objective response events were observed. The overall response rate was 63.8%(113/177), partial response rate was 61.6%(109/177), clinically complete response rate was 2.3%(4/177), stable disease was 29.9% (53/177), progressive disease was 6.2%(11/177), and the disease control rate was 93.8%(166/177). In 127 patients receiving triplet drug, objective response rate was 40.9% for those with less than four cycles and 81.1% for those with more than four cycles (P<0.001).</p><p><b>CONCLUSION</b>The mFOLFOXIRI regimen with reduced dose can be safely used in advanced CRC and has achieved promising results in terms of short-term efficacy.</p>

Research hotspot and progress of preoperative chemoradiotherapy for rectal cancer / 中华胃肠外科杂志

Preoperative chemoradiotherapy (CRT) has become an important component of comprehensive treatment for rectal cancer. Although local recurrent risk has been remarkably reduced by CRT, distant metastasis remains the main cause of therapeutic failure. Therefore, more and more studies focused on controlling distant metastasis in order to prolong long-term survival. Recently, CRT has achieved certain progression in rectal cancer: (1)Patients with stage T3 should be classified into specific subgroups to formulate individualized treatment regimen. For stage T3a, it is feasible to perform surgery alone or administrate low intensity preoperative CRT; for stage T3b and T3c, conventional preoperative CRT should be performed in order to reduce the risk of recurrence postoperatively. (2)With regard to combined regimen for chemotherapy, oral capecitabine superiors to intravenous bolus 5-fluorouracil (5-FU) and is comparable to continuous intravenous infusion 5-FU with a better safety. Therefore, capecitabine is recommended for older patients and those with poor tolerance to chemotherapy. Compared to single 5-FU concurrent CRT, addition of oxaliplatin into preoperative CRT may result in a higher survival benefit in Chinese patients. As to the application of irinotecan, bevacizumab or cetuximab, unless there are more evidence to confirm their efficacy and safety from randomized controlled trial, they should not be recommended for adding to preoperative CRT routinely. (3)On the optimization in CRT pattern, the application values of induction chemotherapy before concurrent CRT, consolidation chemotherapy after concurrent CRT, neoadjuvant sandwich CRT, neoadjuvant chemotherapy alone and short-course preoperative radiotherapy remain further exploration. (4)On the treatment strategy for clinical complete response (cCR) after CRT, whether "wait and see" strategy is able to be adopted, it is still a hot topic with controversy.

Difference analysis of chemotherapy efficacy among different primary tumor sites in metastatic colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To analyze the relationship between primary tumor location and clinical response of chemotherapy in patients with metastatic colorectal cancer(mCRC).</p><p><b>METHODS</b>Clinical data of 721 mCRC patients who received first-line and second-line chemotherapy in Peking University Cancer Hospital between January 1996 and December 2011 were collected. All the patients were divided into 5 groups according to primary tumor location: ileocecum in 61 patients(8.5%), ascending colon or hepatic flexure in 126 patients (17.5%), transverse colon or splenic flexure in 26 patients (3.6%), descending or sigmoid colon in 172 patients (23.9%), rectum in 336 patients (46.6%). Outcomes of chemotherapy were evaluated by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1), including complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). The overall response rate (ORR) was counted with the total number of patients divided by the number of CR+PR. Differences in first-line and second-line chemotherapy efficacy among different primary tumor sites in metastatic colorectal cancer were compared by using Chi-square test.</p><p><b>RESULTS</b>Of the 571 patients receiving first-line chemotherapy, no one patient was classified as CR, while there were 190 as PR (33.3%), 277 as SD (48.5%) and 104 as PD (18.2%), with ORR 33.3% (190/571). The ORRs of patients with primary tumor located at ileocecum, ascending colon or hepatic flexure, transverse colon or splenic flexure, descending or sigmoid colon, rectum were 21.3% (10/47), 35.3% (36/102), 14.3% (3/21), 41.3% (57/138) and 31.9% (84/263), respectively, with statistically significant difference(P = 0.028). Difference of oxaliplatin-based first-line chemotherapy efficacy among different tumor sites was statistically significant(P = 0.009), while differences in irinotecan-based or single-agent 5-fluorouracil chemotherapy efficacy were not statistically significant (all P>0.05). In patients with primary tumor located at transverse colon or splenic flexure, irinotecan-based first-line chemotherapy had higher ORR than oxaliplatin-based or single-agent 5-fluorouracil chemotherapy, and the difference was statistically significant (P=0.042). There was no significant difference in the efficacy of different first-line chemotherapy regimens in patients with primary tumor located at other sites (all P>0.05). Of the 353 patients receiving second-line chemotherapy, no one patient was classified as CR, while there were 43 as PR (12.2%), 187 as SD (53.0%) and 123 as PD (34.8%), with ORR 12.2%(43/353). The ORRs of patients with primary tumor located at the ileocecum, the ascending colon or the hepatic flexure, the transverse colon or the splenic flexure, the descending or sigmoid colon, the rectum were 4.2%(1/24), 12.1%(8/66), 8.3%(1/12), 15.2%(12/79) and 12.3%(21/171) respectively, without statistically significant difference (P=0.686). Differences in second-line chemotherapy efficacy with the same regimen among different tumor sites were not statistically significant, and there were also no significant differences of efficacy of different second-line chemotherapy regimens in patients with the same tumor site (all P>0.05).</p><p><b>CONCLUSION</b>There are differences in first-line chemotherapy efficacy among different primary tumor sites in metastatic colorectal cancer, while their second-line chemotherapy efficacy is equivalent.</p>

Modified FOLFIRINOX for advanced pancreatic cancer: a tertiary center experience from China / 中华外科杂志

<p><b>OBJECTIVE</b>To explore efficacy and safety of modified FOLFIRINOX (mFOLFIRINOX) regimen by dose attenuation in locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer(MPC).</p><p><b>METHODS</b>Between April 2014 and October 2015, 35 patients with LAPC (n=18) or MPC (n=17) were treated with mFOLFIRINOX regimen (irinotecan 135 mg/m(2), oxaliplatin 68 mg/m(2), 5-FU 2 400 mg/m(2), no bolus of 5-FU, leucovorin 400 mg/m(2)) in the Second Affiliated Hospital of Zhejiang University School of Medicine. The primary end point was progression free survival. The second end points were overall survival, objective response rate, adverse effects, surgical resection rate for LAPC.</p><p><b>RESULTS</b>Among 35 patients, 6 patients (17.1%) who dropped out and received less than 2 cycles were excluded for response analysis. Among the other 29 patients, 9 patients had grade 3 or 4 adverse effects. No patients ceased treatment due to adverse effects. The 29 patients received 5 (2-13) cycles were evaluated by efficacy and found partial remission in 16 cases, stable disease in 10 cases, progression disease in 3 cases. Response rate was 55.2%. Nine patients with LAPC accomplished surgery after neoadjuvant treatment without perioperative complication and death, and 6 patients accepted R0 resection.</p><p><b>CONCLUSIONS</b>The mFOLFIRINOX regimen used in the study is well-tolerated in Chinese population with high treatment efficacy on patients with LAPC and MPC. Further investigation of efficacy and adverse effects on more advanced pancreatic cancer patients is necessary.</p>

Redução das desigualdades no uso de consultas médicas no Brasil: análise das regiões Nordeste e Sudeste entre 2003 e 2008 / Reduction of inequalities in medical visits in Brazil: analysis of the Northeastern and Southeastern regions between 2003 and 2008

OBJETIVO: Analisar as desigualdades socioeconômicas na utilização de consultas médicas (CM) no último ano no Brasil. MÉTODOS: Dados da Pesquisa Nacional por Amostra de Domicílios (≥ 20 anos de idade) das Regiões Nordeste (2003, n = 75.652 e 2008, n = 79.779) e Sudeste (2003, n = 76.029 e 2008, n = 79.356) foram analisados segundo CM. Compararam-se as prevalências de CM segundo as variáveis exploratórias demográficas e de saúde no primeiro (D1) e último (D10) decil de renda familiar per capita. As análises consideraram o desenho amostral complexo. RESULTADOS: A proporção de pessoas com CM aumentou no período na Região Nordeste (61,2 para 66,9%) e Sudeste (67,9 para 73,5%). A diferença absoluta de CM, segundo D1 e D10 no período, foi de 6,4 pontos percentuais (pp) no Nordeste e 4,2 pp no Sudeste. Houve importante redução das desigualdades entre os homens; naqueles sem doenças crônicas; naqueles que tinham uma percepção positiva da sua saúde e naqueles sem plano de saúde com direito a CM. A Região Sudeste ainda apresentou redução entre aqueles com apenas uma morbidade autorreferida (8 pp) e com percepção negativa da saúde (6 pp). CONCLUSÃO: Houve aumento de CM no Brasil. Observa-se ainda persistente desigualdade entre os mais pobres e os mais ricos, maior no Nordeste do que no Sudeste. Políticas para a redução da desigualdade em saúde mais eficazes e equânimes devem ser adotadas no Brasil. .

OBJECTIVE: To analyze the socioeconomic inequalities in medical visits (MV) in the past year in Brazil. METHODS: Data from adults aged ≥ 20 years old who participated in the Brazilian National Household Surveys and living in the Northeastern (2003; n = 75,652 and 2008, n = 79,779) and Southeastern (2003; n = 76,029 and 2008; n = 79,356) regions were analyzed according to MV. We compared MVs according to demographic and health variables in the first (D1) and last (D10) per capita family income deciles. All analyses considered the complex cluster design. RESULTS: The proportion of people who had MV during this period increased in the Northeastern (from 61.2 to 66.9%) and the Southeastern (from 67.9 to 73.5%) regions. The absolute difference (AD) in the use of MV, according to D1 and D10 in this period, was equal to 6.4 percentage points (pp) in the Northeastern and 4.2 pp in the Southeastern regions. Significant reduction in inequalities was observed among men without chronic diseases, in those who had a positive perception of their health, and among those without health insurance which included MV. The Southeastern region has also showed significant reduction among those with chronic disease (8 pp) and with negative health self-perception (6 pp). CONCLUSION: The increasing number of MVs was found in Brazil. However, persistent inequalities were observed between the poorest and the richest, higher in the Northeastern than in the Southeastern region. More effective and equitable policies to reduce health inequalities should be adopted in Brazil. .

Waiting times for surgical and diagnostic procedures in public hospitals in Mexico / Tiempos de espera para procedimientos quirúrgicos y diagnósticos en hospitales públicos de México

Objective. A retrospective evaluation of waiting times for elective procedures was conducted in a sample of Mexican public hospitals from the following institutions: the Mexican Institute for Social Security (IMSS), the Institute for Social Security and Social Services for Civil Servants (ISSSTE) and the Ministry of Health (MoH). Our aim was to describe current waiting times and identify opportunities to redistribute service demand among public institutions. Materials and methods. We examined current waiting times and productivity for seven elective surgical and four diagnostic imaging procedures, selected on the basis of their relative frequency and comparability with other national health systems. Results. Mean waiting time for the seven surgical procedures in the three institutions was 14 weeks. IMSS and ISSSTE hospitals showed better performance (12 and 13 weeks) than the MoH hospitals (15 weeks). Mean waiting time for the four diagnostic procedures was 11 weeks. IMSS hospitals (10 weeks) showed better average waiting times than ISSSTE (12 weeks) and MoH hospitals (11 weeks). Conclusion. Substantial variations were revealed, not only among institutions but also within the same institution. These variations need to be addressed in order to improve patient satisfaction.

Objetivo. Se llevó a cabo una evaluación retrospectiva de los tiempos de espera para procedimientos electivos en una muestra de hospitales públicos en México de las siguientes instituciones: Instituto Mexicano del Seguro Social (IMSS), Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE) y Secretaría de Salud (SS). El propósito era describir la situación actual en materia de tiempos de espera e identificar oportunidades de redistribución de la demanda de servicios entre instituciones públicas. Material y métodos. Se analizaron los tiempos de espera y la productividad para siete procedimientos quirúrgicos y cuatro procedimientos diagnósticos seleccionados sobre la base de su frecuencia relativa y comparabilidad con otros sistemas de salud nacionales. Resultados. El tiempo de espera promedio para los siete procedimientos quirúrgicos en las tres instituciones fue de 14 semanas. Los hospitales del IMSS y el ISSSTE mostraron un mejor desempeño (12 y 13 semanas) frente a los hospitales de la SS (15 semanas). El tiempo de espera promedio para los cuatro procedimientos diagnósticos fue de 11 semanas. Los hospitales del IMSS mostraron un tiempo de espera promedio mejor (10 semanas) que los hospitales del ISSSTE (12 semanas) y la SS (11 semanas). Conclusión. Se identificaron variaciones importantes no sólo entre instituciones sino también al interior de cada una de ellas. Estas variaciones deben atenderse para así mejorar la satisfacción de los usuarios de los servicios.

Anticancer effect of SN-38 combined with sorafenib on hepatocellular carcinoma in vitro and its mechanism / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the anticancer effect and its mechanism of SN-38 combined with sorafenib on hepatocellular cancer cell lines HepG-2 and BEL-7402.</p><p><b>METHODS</b>SRB colorimetry was employed to measure the viability of HepG-2 and BEL-7402 cells after the treatment of SN-38 with sorafenib. Propidium iodide flow cytometric assay and DAPI staining were used to evaluate the apoptosis of HCC cells. Western blotting was conducted to detect the expression level of apoptosis-related and DNA damage-related proteins.</p><p><b>RESULTS</b>SRB colorimetry showed the synergistic anticancer activities of SN-38 combined with sorafenib, with a combination index of <0.9. The apoptotic rates of HepG-2 cells in control, 60 nmol/L SN-38, 2.5μmol/L sorafenib and combination groups were 4.25%±2.45%, 28.95%±10.75%, 3.49%±2.49% and 53.19%±11.21%, respectively(P<0.05). Western blotting showed that the combination of these two drugs increased the enzymolysis of PARP, Caspase-8 and Caspase-3, and promoted the expression levels of p53, p21 and γ-H2AX significantly.</p><p><b>CONCLUSION</b>SN-38 and sorafenib have synergistic anticancer activity on hepatocellular carcinoma cells in vitro with the augmentation of apoptosis.</p>

Association of UGT1A1 (*28, *60 and * 93) polymorphism with the adverse reactions of irinotecan chemotherapy in extensive stage small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the correlation between UGT1A1 (*28, *60 and * 93) polymorphism and the adverse reactions in small cell lung cancer patients after irinotecan chemotherapy.</p><p><b>METHODS</b>Clinical data of 58 small cell lung cancer patients in extensive stage treated in our hospital were retrospectively analyzed. Polymerase chain reaction was used to amplify the UTG, and direct sequencing was performed to determine the UGT polymorphism. The adverse reactions ≥ grade 3 after irinotecan chemotherapy in patients with different UGT genotype were analyzed.</p><p><b>RESULTS</b>Amongthe 58 patients with extensive stage small cell lung cancer, there were 45 (77.6%) cases of wild type UGT1A1*28, 40 (69.0%) cases of wild type UGT1A1* 93, 38 (65.5%) cases of wild type UGT1A1*60, 18 cases of mutation in UGT1A1* 93 and 20 cases of mutation in UGT1A1*60. In UGT1A1 promoter position 28, there were 8 (13.8%) cases of TA5 mutation and 5 (8.6%) cases of TA7 mutation. Among the patients with TA5 mutation, 5 cases had ≥ grade 3 diarrhea, 3 cases had ≥ grade 3 leucopenia and 3 cases had ≥ grade 3 neutropenia, while among the patients with UGT1A1 * 93 mutation, 7 cases had ≥ grade 3 diarrhea, 6 cases had ≥ grade 3 leucopenia and 4 cases had ≥ grade 3 neutropenia.</p><p><b>CONCLUSIONS</b>TA5 and UGT1A1* 93 mutation increase the risk of diarrhea and ≥ grade 3 leukopenia and neutropenia, however, wild type UGT1A1 (*28, * 93, *60) and mutant UGT1A1*60 do not increase those risks. Further prospective study in a larger number of patients is needed to clarify the association between UGT1A1*28, UGT1A1* 93 and UGT1A1*60 polymorphism and adverse reactions of irinotecan, and to help clinicians in choosing a better therapeutic modality for personalized chemotherapy to improve curative effect and reduce adverse reactions.</p>

Rapidly Growing Interval Colon Cancer / 대한소화기학회지

No abstract available.

Efficacy and Safety of FOLFIRI as Second-line Chemotherapy in Advanced Gastric Cancer / 대한소화기학회지

No abstract available.

Efficacy and Safety of FOLFIRI after Failure of FOLFOX-4 in Advanced Gastric Cancer / 대한소화기학회지

BACKGROUND/AIMS: The purpose of this study was to investigate the efficacy and safety of irinotecan based FOLFIRI chemotherapy as a second-line treatment after failure of FOLFOX-4 chemotherapy in patients with advanced gastric cancer. METHODS: Fifty-two patients who were pathologically diagnosed with unresectable gastric cancer and received FOLFIRI chemotherapy after failure of FOLFOX-4 chemotherapy between September 2005 and February 2012 were enrolled in this study. Data were collected by retrospectively reviewing the medical records. The response to chemotherapy was assessed every 3 cycles by World Health Organization criteria and long term survival was analyzed. The toxicities were evaluated for every course of chemotherapy according to National Cancer Institution (NCI) toxicity criteria version 3.0. RESULTS: Median age of the patients was 57 years. Median overall survival (OS) and time to progression (TTP) were 7.8 and 5 months, respectively. The number of patients showing complete remission, partial remission, stable disease, and progressive disease were 0 (0.0%), 9 (17.3%), 30 (57.7%), and 13 (25.0%), respectively. The overall response rate was 17.3%. During a total of 345 cycles, anemia worse than NCI toxicity grade 3 occurred in 2.9%, leukopenia in 20.3%, neutropenia in 12.2%, and thrombocytopenia in 1.5%. Patients with less organ involvement by metastasis, less than 34 U/mL of CA 19-9 and good responsiveness to third cycle of second line chemotherapy were associated with longer OS and TTP. CONCLUSIONS: FOLFIRI chemotherapy has a modest efficacy with acceptable toxicities in patients with advanced gastric cancer as a second-line treatment. Further well-controlled studies are needed to elucidate the efficacy of FOLFIRI chemotherapy as second-line treatment in patients with advanced stomach cancer.

Clinical efficacy observation of cetuximab combined with chemotherapy in the treatment of metastatic colorectal carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy of cetuximab plus chemotherapy in the treatment of metastatic colorectal carcinoma.</p><p><b>METHODS</b>Clinicopathological data of 128 patients with metastatic colorectal cancer admitted in the Department of Oncology, Chinese PLA General Hospital from 2008 to June 2012 were analyzed retrospectively. Among them, 91 patients received cetuximab as the first-line therapy and 37 in the second-line or more-line therapy. The chemotherapy regimens included oxaliplatin-based therapy (FOLFOX/XELOX), irinotecan-based therapy (FOLFIRI/XELIRI) and fluorouracil-based therapy (Xeloda). The efficacy was evaluated according to RECIST 1.0 criteria. The remission rate, control rate and time to disease progression were compared among patients receiving cetuximab combined with different chemotherapy regimens in different periods.</p><p><b>RESULTS</b>The disease control rate of cetuximab applied in the first-line treatment was higher than that of the second-line or more-line [85.9% (61/71) vs. 59.3% (16/27), P=0.004]. The disease control rate of the group treated with cetuximab plus oxaliplatin-based chemotherapy was much higher compared to the other two groups [91.1% (41/45) vs. 68.1% (32/47), 4/6, P=0.021]. But there were no significant differences among three regimens in the terms of overall response rate (all P>0.05). The median time to progression of groups with cetuximab plus irinotecan, oxaliplatin or capecitabine was 7.8 months, 8.5 months and 5.2 months respectively. The median time to progression of cetuximab combined with chemotherapy in the first-line treatment and the second-line or more-line was 8.2 and 7.7 months respectively. However, the differences were not statistically significant (P>0.05).</p><p><b>CONCLUSIONS</b>Cetuximab in combination with oxaliplatin-based chemotherapy is recommended as the first-line application in the treatment of metastatic colorectal carcinoma patients, because it is helpful to improve the rate of disease control.</p>

Effect of Shengjiang Xiexin Decoction on the Repair of Damaged Rat Intestinal Mucosa after Irinotecan Chemotherapy / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of Shengjiang Xiexin Decoction (SXD) on the intestinal mucosal and functional cells of rats after irinotecan (CPT-11) chemotherapy.</p><p><b>METHODS</b>Totally 24 healthy Sprague-Dawley (SD) male rats were divided into three groups, the normal control group, the CPT-11 group, the SXD combined CPT-11 group according to random digit table, 8 in each group. CPT-11 was injected at the daily dose of 150 mg/kg to rats in the CPT-11 group and the SXD combined CPT-11 group from the caudal vein on the 4th day, once daily for 2 successive days to duplicate delayed diarrhea model. Equal volume of normal saline was injected to rats in the normal control group from the caudal vein. SXD at 2 g/mL (10 g/kg body weight) was administered to rats in the SXD combined CPT-11 group by gastrogavage for 9 successive days. Deionized water was administered to rats in the CPT-11 group and the normal control group. Diarrhea was observed at 48, 60, 72, 84, 96, and 108 h to calculate the incidence rate of diarrhea. Meanwhile, scoring for diarrhea was performed by referring methods of Akinobu Kurita. Rats were killed on day 10, ileum, cecum, and colon tissues were collected and fixed in 10% formalin solution. HE staining was performed. Intestinal mucosa injuries were graded under light microscope according to the criterion of Chiu's score. The expressions of goblet cells and Paneth cells were observed by PAS stain. Enteroendocrine cells were observed by immunohistochemical CgA staining. Positive cells were counted and cumulative optical density (IOD) analyzed by Image-Pro-Plus 6.0.</p><p><b>RESULTS</b>No diarrhea occurred in rats of the normal control group at each time point. The incidence rate of diarrhea was 75.0% (6/8) at 48 h, 100.0% (8/8) at 60 h, 100.0% (8/8) at 72 h, 87.5% (7/8) at 84 h, 75.0% (6/8) at 96 h, and 75.0% (6/8) at 108 h in the CPT-11 group. The incidence rate of diarrhea was 25.0% (2/8) at 48 h, 50.0% (4/8) at 60 h, 12.5% (1/8) at 72 h, 0.0% (0/8) at 84 h in the SXD combined CPT-11 group. Compared with the same group at 60 h, scores for diarrhea at 48, 84, 96, and 108 h obviously decreased in the CPT-11 group, and scores for diarrhea at 48, 72, 84, 96, and 108 h obviously decreased in the SXD combined CPT-11 group (P < 0.05, P < 0.01). Compared with the same group at 72 h, scores for diarrhea at 84, 96, and 108 h obviously decreased in the CPT-11 group (P < 0.05, P < 0.01). Compared with the normal control group, scores for diarrhea increased in the CPT-11 group at each time point (P < 0.01); grading of ileum, cecum, and colon mucosal tissues increased (P < 0.05, P < 0.01); expressions of ileum and cecum mucosal epithelial goblet cells obviously decreased (P < 0.05); the number and expressions of ileum and cecum mucosal epithelial Paneth cells increased (P < 0.01). Expressions of ilium endocrine cells increased, while those of cecum and colon endocrine cells decreased in the CPT-11 group (P < 0.01). Compared with the CPT-11 group, scores for diarrhea were obviously lowered (P < 0.05, P < 0.01), grading of ileum, and cecum mucosal tissues decreased (P < 0.05, P < 0.01); expressions of ileum, cecum, and colon mucosal epithelial goblet cells obviously increased (P < 0.05, P < 0.01); the number and expressions of ileum cecum mucosal epithelial Paneth cells increased (P < 0.05); expressions of cecum and colon endocrine cells increased (P < 0.05, P < 0.01) in the SXD combined CPT-11 group.</p><p><b>CONCLUSION</b>SXD played roles in preventing and treating CPT-11 induced delayed diarrhea by improving CPT-11 chemotherapy induced apoptosis and necrosis of intestinal mucosal and functional cells.</p>

FOLFIRI combined with bevacizumab as first-line treatment for metastatic colorectal cancer patients with hyperbilirubinemia after UGT1A1 genotyping

To report a metastatic colorectal cancer patient with hyperbilirubinemia treated with a combination of bevacizumab and FOLFIRI [5-fluorouracil, leucovorin, and irinotecan] using uridine diphosphate glucuronosyl transferase [UGT1A1] genotyping.Clinical Presentation and Intervention: A 46-year-old male was diagnosed with rectosigmoid colon cancer with liver metastases and hyperbilirubinemia presenting with severe jaundice. UGT1A1 genotyping was used before therapy to ascertain whether genotype-adjusted dosages of irinotecan plus bevacizumab could alleviate the toxicity. Then, the patient was treated with FOLFIRI. The FOLFIRI regimen was successfully used in this patient without concerns regarding toxicity

Antitumor efficacy of irinotecan-loaded galactosyl modified lipid bilayer-coated mesoporous silica nanoparticles against hepatocellular carcinoma cells / 药学学报

The purpose of this study is to prepare galactosyl modified lipid bilayer-coated mesoporous silica nanoparticles (GPEM) to enhance the antitumor efficacy against hepatocellular carcinoma cells. The irinotecan (CPT-11) loaded mesoporous silica nanoparticles (MSNs) was coated with the Gal-P123 modified functional lipid bilayer by thin-film dispersion method. Nanoparticles were characterized with particle size, zeta potential, morphology and drug release in vitro. Afterwards, the cell uptake, intracellular concentration of CPT-11, cell apoptosis rate and cytotoxicity were evaluated on human hepatocellular carcinoma cell line Huh-7. The results showed that MSNs were coated with intact lipid bilayers and the nanoparticles had clear core-shell structure. GPEM is stable with the mean particle size of (78.01 +/- 2.04) nm. The low leakage rate in normal physiological conditions in vitro is contributed to the protection of stable lipid bilayer, and the fast drug release in acid environment due to the destruction of the lipid bilayer. On the cell level, the vector could improve the intracellular CPT-11 concentration by 4 times because of the functional lipid bilayer. The high CPT-11 concentration led to the increasement of apoptosis rate by 48.6%, and the reduction of half maximal inhibitory concentration (IC50) values of CPT-11 by 2 times, indicating stronger cell cytotoxicity.

Chemotherapy with or without irinotecan in patients with advanced or recurrent gastric cancer: a meta-analysis of randomized controlled trials / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Studies have shown that irinotecan can improve survival in patients with advanced or recurrent gastric cancer, but the overall benefit of irinotecan in the treatment of advanced or recurrent gastric cancer remains controversial. The aim of this study was to evaluate the benefits and risks of irinotecan for survival in patients with advanced or recurrent gastric cancer. Method We searched PubMed, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major conferences for relevant clinical trials. We included randomized controlled trials that reported on the efficacy and safety of irinotecan in patients with advanced or recurrent gastric cancer. Outcomes were analyzed by survival rate, objective response rate (ORR), and toxicity. Furthermore, the analysis was further stratified by factors that could affect the treatment effects.</p><p><b>RESULTS</b>Eight trials recruiting 1 546 patients with advanced or recurrent gastric cancer were included in the analysis. Overall, irinotecan therapy was associated with a 6% improvement in survival rate, but this difference was not statistically significant (odds ratio (OR) 0.94; 95% confidence interval (95% CI) 0.70-1.27; P = 0.69). However, irinotecan therapy had more frequent ORR than irinotecan-free arm (OR 1.70; 95% CI 1.34-2.17; P < 0.001). Furthermore, irinotecan therapy was associated with a clinically and statistically significant increase in the risk for declined hemoglobin, hyponatremia, and diarrhea, but it also protected against thrombocytopenia risk when compared with irinotecan-free therapy.</p><p><b>CONCLUSIONS</b>There is no evidence to support the use of irinotecan therapy in patients with advanced or recurrent gastric cancer; however, given the significant advantage in ORR irinotecan therapy using combination regimens may be considered for further evaluation in subsets of patients who may benefit from this treatment.</p>