AIM To evaluate the efficiency and safety of hepatic artery infusion chemotherapy(HAIC) using raltitrexed or 5-fluorouracil for colorectal cancer(CRC) liver metastasis(CRCLM).METHODS A retrospective analysis of patien...AIM To evaluate the efficiency and safety of hepatic artery infusion chemotherapy(HAIC) using raltitrexed or 5-fluorouracil for colorectal cancer(CRC) liver metastasis(CRCLM).METHODS A retrospective analysis of patients with unresectable CRCLM who failed systemic chemotherapy and were subsequently treated with HAIC at our institute from May 2013 to April 2015 was performed. A total of 24 patients were treated with 5-fluorouracil, and 18 patients were treated with raltitrexed. RESULTS The median survival time(MST) from diagnosis of CRC was 40.8 mo in the oxaliplatin plus raltitrexed(TOMOX) arm and 33.5 mo in the oxaliplatin plus 5-fluorouracil(FOLFOX) arm(P = 0.802). MST from first HAIC was 20.6 mo in the TOMOX arm and 15.4 mo in the FOLFOX arm(P = 0.734). Median progression-free survival(PFS) from first HAIC was 4.9 mo and 6.6 mo, respectively, in the TOMOX arm and FOLFOX arm(P= 0.215). Leukopenia(P = 0.026) was more common in the FOLFOX arm, and hepatic disorder(P = 0.039) was more common in the TOMOX arm. There were no treatment-related deaths in the TOMOX arm and one treatment-related death in the FOLFOX arm. Analysis of prognostic factors indicated that response to HAIC was a significant factor related to survival.CONCLUSION No significant difference in survival was observed between the TOMOX and FOLFOX arms. HAIC treatment with either TOMOX or FOLFOX was demonstrated as an efficient and safe alternative choice.展开更多
AIM: To study the distribution and stability of antisense oligodeoxynucleotide (ASODN) in Walker-256 cells and their distribution in liver, lung and kidney tissues after being infused alone or mixed with lipiodol via ...AIM: To study the distribution and stability of antisense oligodeoxynucleotide (ASODN) in Walker-256 cells and their distribution in liver, lung and kidney tissues after being infused alone or mixed with lipiodol via hepatic artery in a rat liver tumor model.METHODS: 5'-Isothiocyananate (FITC)-labeled vascular endothelial growth factor (VEGF) ASODN was added into Walker-256 cell culture media. Its distribution in cells was observed by fluorescence microscope at different time points. Walker-256 carcinosarcoma was transplanted into Wistar rat liver to establish a liver cancer model. 5'-FITC-labeled VEGF ASODN mixed with (mixed group, n = 6) or without (TAI group, n = 6)ultra-fluid lipiodol was administrated via hepatic artery.Frozen samples of liver, lung and kidney tissue were taken from rats after 1, 3 and 6 d, respectively. The distribution of ASODN was observed under fluorescent microscope.RESULTS: ASODN could enter cytoplasm within 2 h and nuclei within 6 h. Accumulation of ASODN reached the peak point in nuclei at 12 h, and then disappeared gradually. No fluorescence could be seen in cells at 48 h. In vivo experiment, on d 1 and 3 the fluorescence staining in liver was stronger in mixed group than in TAI group and more fluorescence could be detected in lung and kidney in TAI group than in mixed group. On d 6, no fluorescence could be detected in TAI group, but faint fluorescence could be seen in mixed group. ASODN could be seen in cancer cells and normal hepatic cells. In mixed group, ASODN was mainly distributed in liver tumor tissues.CONCLUSION: ASODN can transfect Walker-256 cells.ASODN mixed with lipiodol infusion via hepatic artery can be used in the treatment of HCC.展开更多
Newer systemic therapies for hepatocellular carcinoma(HCC)have led to growing interest in combining hepatic arterial infusion chemotherapy(HAIC)with systemic treatments.To evaluate the effectiveness and safety of HAIC...Newer systemic therapies for hepatocellular carcinoma(HCC)have led to growing interest in combining hepatic arterial infusion chemotherapy(HAIC)with systemic treatments.To evaluate the effectiveness and safety of HAIC and combination therapies in treating advanced HCC,a network meta-analysis was conducted by Zhou et al.The study included data from 44 articles.HAIC was superior in overall survival(OS),progression-free survival(PFS),and response rates compared to transarterial chemoembolization and sorafenib.Moreover,combinations of HAIC with other treatments and single agents(e.g.,lenvatinib,ablation,anti-programmed cell death 1 therapy,radiotherapy)provided better OS and PFS outcomes than HAIC alone.In this editorial,we will discuss the study findings,the strengths and weaknesses of the metanalysis,and future advances in the field of HAIC for advanced HCC.展开更多
Objective To evaluate the toxic effects and efficacy of the intra-arterial chrono-chemotherapy on patients with liver metastasis arised from colorectal cancer. Methods Chemotherapy of 42 patients were randomly divided...Objective To evaluate the toxic effects and efficacy of the intra-arterial chrono-chemotherapy on patients with liver metastasis arised from colorectal cancer. Methods Chemotherapy of 42 patients were randomly divided into group A (n = 20) with continuously constant arterial infusion, and group B (n = 22) with arterial chrono-modulated infusion. And the toxic effects and efficacy of two groups were compared. Results A significant difference was found in the toxic effects of digestive system between the two groups. The treatment response was similar in the two groups. Conclusions Intra-arterial chrono-chemotherapy may decrease the toxic effects and improve the life quality of these patients. (J Intervent Radiol, 2006, 15: 487-490)展开更多
Objective:To explore the influence on liver function of hepatic artery interventional chemoembolization combined reduced glutathione therapy for elderly patients with advanced liver cancer.Methods:A total of 120 cases...Objective:To explore the influence on liver function of hepatic artery interventional chemoembolization combined reduced glutathione therapy for elderly patients with advanced liver cancer.Methods:A total of 120 cases of elderly patients with advanced liver cancer from digestive surgery in-patient department of our hospital during the period of January 2014 and January 2016 were selected as the research object, the patients were divided into two groups by using the random number table method,each for 60 cases.The control group were given conventional drugs chemotherapy, the study group were given hepatic artery interventional chemoembolization combined reduced glutathione therapy, serum liver function indexes of Direct Bilirubin(DBil), Total Bilirubin(TBil), Aspartate Transaminase(AST) and Alanineamino Transferase (ALT)were detected by using automatic biochemical analyzer. Results: The clinical remission rate of study group was significantly higher than the control group, the recurrence rate was obviously lower than the control group,compared between the two groups with statistically significant differences. The average survival time of study group (29.36±6.25) months, was significantly longer than the control group (18.02±4.16) months .Before the treatment, serum DBil, TBil, AST and ALT levels compared between the two groups with no statistically significant differences,after the treatment,the indexes of study group was significantly lower than the control group. The indexes levels compared between pre-therapy and post-therapy in study group with no statistically significant differences, while the indexes levels of post-therapy in the control group were significantly higher than those pre-therapy. Before the treatment, the life quality score compared between the two groups with no statistically significant differences, after treatment,the score of all patients were significantly higher than those pre-therapywhich the score of study group was significantly higher than the control group.The incidence rate of drug adverse reactions compared between the two groups with no statistically significant differences.Conclusion: The clinical efficacy of hepatic artery interventional chemoembolization combined reduced glutathione therapy for elderly patients with advanced liver cancer is satisfying, and helps to significantly improve liver function, improve life quality, it is worth popularization and application in the clinical practice.展开更多
Background:The aim of the study was to investigate the efficacy of continuous transcatheter arterial infusion chemotherapy combined with transarterial chemoembolization(TACE)for the treatment of advanced pancreatic ca...Background:The aim of the study was to investigate the efficacy of continuous transcatheter arterial infusion chemotherapy combined with transarterial chemoembolization(TACE)for the treatment of advanced pancreatic cancer with liver metastasis.Methods:Sixty patients with advanced pancreatic cancer and liver metastases were enrolled in this study.In the treatment group,31patients underwent continuous transcatheter arterial infusion chemotherapy combined with TACE regional arterial thermal perfusion,whereas 29 patients included in the control group received intravenous chemotherapy with gemcitabine and S-1.All patients received maintenance chemotherapy with S-1 after 4 cycles of the study regimen.Treatment efficacy,quality of life,survival,and toxicity were evaluated.Results:Efficacy was better in the treatment group than in the control group,as reflected by the objective remission,partial remission,and disease progression rates(all P<0.05).The Eastern Cooperative Oncology Group and Numerical Rating Scale pain scores were also higher in the treatment group(both P<0.05).In survival analysis,the 1-year overall survival rates in the treatment and control groups were64.516%and 10.345%,respectively,whereas the median overall survival times were 16 and 6 months,respectively(both P<0.05).The6-month progression-free survival rates in the treatment and control groups were 77.419%and 13.790%,respectively,and the median progression-free survival times were 12 and 3 months,respectively(both P<0.05).The rates of hematological and nonhematological toxicological adverse effects were also lower in the treatment group(both P<0.05).Although the rate of liver dysfunction was higher in the treatment group,this finding had no adverse effects on prognosis.Conclusions:Continuous transcatheter arterial infusion chemotherapy combined with TACE regional arterial perfusion chemotherapy resulted in better efficacy and safety outcomes in patients with pancreatic cancer and liver metastasis,suggesting its utility as a reference method for the clinical treatment of advanced pancreatic cancer.展开更多
Large bowel cancer is a worldwide public health challenge.More than one third of patients present an advanced stage of disease at diagnosis and the liver is the most common site of metastases.Selection criteria for ea...Large bowel cancer is a worldwide public health challenge.More than one third of patients present an advanced stage of disease at diagnosis and the liver is the most common site of metastases.Selection criteria for early diagnosis,chemotherapy and surgery have been recently expanded.The definition of resectability remains unclear.The presence of metastases is the most significant prognostic factor.For this reason the surgical resection of hepatic metastases is the leading treatment.The most appropriate resection approach remains to be defined.The two step and simultaneous resection processes of both primary and metastases have comparable survival long-term outcomes.The advent of targeted biological chemotherapeutic agents and the development of loco-regional therapies(chemoembolization,thermal ablation,arterial infusion chemotherapy) contribute to extend favorable results.Standardized evidence-based protocols are missing,hence optimal management of hepatic metastases should be single patient tailored and decided by a multidisciplinary team.This article reviews the outcomes of resection,systemic and loco-regional therapies of liver metastases originating from large bowel cancer.展开更多
Objective:To compare the efficacy of sorafenib plus hepatic arterial infusion chemotherapy(HAIC)with oxaliplatin to that of sorafenib alone in patients with advanced hepatocellular carcinoma(HCC).Methods:This was a re...Objective:To compare the efficacy of sorafenib plus hepatic arterial infusion chemotherapy(HAIC)with oxaliplatin to that of sorafenib alone in patients with advanced hepatocellular carcinoma(HCC).Methods:This was a retrospective,single-center trial.Between April 3,2017 and July 2,2018,104 patients with Child-Pugh A and advanced HCC received either 400 mg of sorafenib orally twice daily plus HAIC with oxaliplatin(oxaliplatin 85 mg/m^2,every 3 weeks via repetitive catheterization)(n=46,soraOXA group)or 400 mg of only sorafenib orally twice daily(n=58,sorafenib group).Overall survival,progression-free survival,objective response rate,and treatment-related adverse events were compared.Results:The median overall survival was 9.37 months(95%CI,7.05-11.68)in the soraOXA group versus 4.8 months(95%CI,2.98-6.62)in the sorafenib group(HR 0.46[95%CI,0.29-0.72];P<0.001).The soraOXA group also showed a higher objective response rate(16[34.8%]vs 1[1.7%];P<0.001)and a longer progressionfree survival rate(5.5 months[95%CI,2.32-8.68]vs 2.4 months[95%CI,1.65-3.15],HR 0.54[95%CI,0.36-0.81],P=0.003)than the sorafenib group.There was no significant difference in the overall incidence of any grade adverse events,grade 3/4 adverse events,serious adverse events,or incidence of treatment termination due to adverse events between the two groups.Conclusion:Compared with sorafenib alone,sorafenib plus HAIC with oxaliplatin showed favorable treatment outcomes in patients with advanced HCC.The merits of this approach need to be established with a prospective trial.展开更多
BACKGROUND Obstruction or fullness after feeding is common in gastric cancer(GC)patients,affecting their nutritional status and quality of life.Patients with digestive obstruction are generally in a more advanced stag...BACKGROUND Obstruction or fullness after feeding is common in gastric cancer(GC)patients,affecting their nutritional status and quality of life.Patients with digestive obstruction are generally in a more advanced stage.Existing methods,including palliative gastrectomy,gastrojejunostomy,endoluminal stent,jejunal nutrition tube and intravenous chemotherapy,have limitations in treating these symptoms.AIM To analyze the efficacy of continuous gastric artery infusion chemotherapy(cGAIC)in relieving digestive obstruction in patients with advanced GC.METHODS This study was a retrospective study.Twenty-nine patients with digestive obstruction of advanced GC who underwent at least one cycle of treatment were reviewed at The Second Affiliated Hospital of Zhejiang University School of Medicine.The oxaliplatin-based intra-arterial infusion regimen was applied in all patients.Mild systemic chemotherapy was used in combination with local treatment.The clinical response was evaluated by contrast-enhanced computed tomography using Response Evaluation Criteria In Solid Tumors(RECIST)criteria.Digestive tract symptoms and toxic effects were analyzed regularly.A comparison of the Karnofsky Performance Status(KPS)score and Stooler’s Dysphagia Score before and after therapy was made.Univariate survival analysis and multivariate survival analysis were also performed to explore the key factors affecting patient survival.RESULTS All patients finished cGAIC successfully without microcatheter displacement,as confirmed by arteriography.The median follow-up time was 24 mo(95%CI:20.24-27.76 mo).The overall response rate was 89.7%after cGAIC according to the RECIST criteria.The postoperative Stooler’s Dysphagia Score was significantly improved.Twentytwo(75.9%)of the 29 patients experienced relief of digestive obstruction after the first two cycles,and 13(44.8%)initially unresectable patients were then considered radically resectable.The median overall survival time(mOS)was 16 mo(95%CI:9.32-22.68 mo).Patients who received radical surgery had a significantly longer mOS than other patients(P value<0.001).Multivariate Cox regression analysis indicated that radical resection after cGAIC,intravenous chemotherapy after cGAIC,and immunotherapy after cGAIC were independent predictors of mOS.None of the patients stopped treatment because of adverse events.CONCLUSION cGAIC was effective and safe in relieving digestive obstruction in advanced GC,and it could improve surgical conversion possibility and survival time.展开更多
AIM: To elucidate anticancer effects of transcatheter arterial infusion chemotherapy(TAI) in patients with hepatocellular carcinoma(HCC). METHODS: Data from a total of 95 patients with HCC who received TAI were analyz...AIM: To elucidate anticancer effects of transcatheter arterial infusion chemotherapy(TAI) in patients with hepatocellular carcinoma(HCC). METHODS: Data from a total of 95 patients with HCC who received TAI were analyzed retrospectively. The efficacy of TAI was evaluated according to the Response Evaluation Criteria in Cancer of the Liver. Overall survival was calculated from the date of initial treatment to the date of death or last follow-up. Survival curves were calculated by the Kaplan-Meier method, and differences in survival were evaluated by the log rank test. Clinical variables that were identified as statistically different by a univariate analysis were included into the Cox proportional hazard regression model for multivariate analysis. A prognostic index based on the regression coefficients derived from variables identified by the multivariate analysis was constructed. Stratification of the patients was conducted using this prognostic index. RESULTS: The patient group was comprised of 76 men and 19 women with an average age of 68 years(range: 37-82 years). Six patients(6.3%) showedcomplete response and 18 patients(18.9%) showed partial response, for an overall response rate of 25.2%. The median overall survival was 27.6 mo, and the proportions of survivors at 1, 2, and 5 years were 67.4%, 54.0%, and 17.4%, respectively. Multivariate analysis demonstrated that no prior transcatheter arterial chemoembolization, lactate dehydrogenase < 230 IU/L, and performance status of 0 were the independent favorable prognostic factors. The development of a 0-3-point prognostic score index was based on the sum of these three prognostic factors. Subsequently, the patients were categorized into three groups: those with a good(prognostic index = 0-1; n = 54), intermediate(prognostic index = 2; n = 26), or poor(prognostic index = 3; n = 15) prognosis. The median survival times in these three groups were 41.0, 21.2, and 6.8 mo, respectively(P < 0.01). CONCLUSION: Our simple prognostic index may be helpful for management of patients in determining treatment strategies for advanced HCC in the era of molecularly targeted therapy.展开更多
Background: The regional chronomodulated hepatic arterial infusion chemotherapy (HAIC) is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, especially for th...Background: The regional chronomodulated hepatic arterial infusion chemotherapy (HAIC) is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, especially for the conversion into resectability. Aim: To demonstrate that chronomodulated HAI triplet chemotherapy according to OPTILIV protocol is well tolerated and displayed high antitumor activity in this heavily-pretreated patient. Case Presentation: A 54 years old patient from Russia was treated for a tumor in the ascending colon presented with 13 hepatic metastases ranging from 0.3 to 2.7 cm in diameter. He underwent a laparoscopic right hemicolectomy, 12 cycles of FOLFIRINOX combined to bevacizumab for the last 5 cycles, resulting in a partial response according to CT scan. It was decided to perform a two-stage hepatectomy at Paul Brousse hospital: left partial hepatectomy allowed the excision of 9 lesions. Radio frequency ablation was performed in 2 nodular lesions. Afterwards, the patient received 5 cycles of chronomodulated triplet chemotherapy into the hepatic artery, according to the OPTILIV protocol design, yet without cetuximab, because of the KRAS mutation in the liver metastases, with a partial re-sponse. The patient could then undergo the second stage of the planned right hepatectomy, which turned out to be an R0 resection followed by receiving three courses of chronomodulated HAIC. Disease progression was documented after 3 months. Chronomodulated FOLFIRI chemotherapy was re-started intravenously, in combination with Aflibercept and it was associated with further disease progression. The genetic analysis of our patient’s cancer revealed a high level of MSI. The patient was included in the Phase 2 CheckMate-142 trial and received nivolumab 3 mg/kg every 2 weeks within 3 months. Treatment was discontinued due to ineffectiveness. Then the patient underwent radiotherapy geared towards reduction of pain. Afterwards, the patient died from the disease progression 2 years after the beginning of treatment. Conclusion: In this article, the authors report a clinical case with chronomodulated HAIC as rescue therapy in a heavily pretreated patient with metastatic colorectal cancer, allowing to achieve an objective response despite prior progression on FOLFIRINOX (the same triplet chemo by IV route). This strategy permitted to overcome drug resistance and to perform further complete resection of the liver me-tastases with prolonged patient survival. Thus, chronomodulated HAI is useful in patients with liver metastases from colorectal cancer and de-serves to be further assessed prospectively in clinical trials chemotherapy.展开更多
Background Hepatic arterial infusion chemotherapy for liver metastases is under evaluation because of the high target dose and low general toxicity. To investigate the efficacy and safety of a Folfox4 regimen administ...Background Hepatic arterial infusion chemotherapy for liver metastases is under evaluation because of the high target dose and low general toxicity. To investigate the efficacy and safety of a Folfox4 regimen administered through a combined hepatic arterial and systemic infusion for the first-line treatment of colorectal cancer (CRC) with unresectable liver metastases. Methods Twenty-seven CRC patients with unresectable hepatic metastases and no prior chemotherapy were enrolled into the study. They received a Folfox4 regimen; 1st day: HAl of oxaliplatin 85 mg/m2 and L-folinic acid 200 mg/m2, followed by a bolus hepatic arterial injection of 5-fluorouracil 400 mg/m2, then continuous HAl of 5-FU 600 mg/m2; 2nd day: infusion of L-folinic acid 200 mg/m2 i.v. followed by an intravenous bolus injection of 5-Fluorouraci1400 mg/m2, then continuous infusion of 5-fluorouracil 600 mg/m2 i.v. The patients received HAl during the odd cycles, and the intravenous administration of the same Folfox4 regimen during the even cycles. Results A total of 236 treatment cycles were given with a median of 10 cycles. The therapy generated the following results after six treatment cycles: complete response (CR) 1/27 (3.7%), partial response (PR) 17/27 (63.0%), stable disease (SD) 6/27 (22.2%), and progress disease (PD) 3/27 (11.1%). Five patients had hepatectomy. The serum levels of both carcinoembryonic antigen (CEA) and CA19-9 were significantly reduced (P〈0.05). A median time to progression of 11 months and a median overall survival of 24 months were documented. The major adverse events included grade 1/2 nausea/vomiting, upper abdominal pain, peripheral neuropathy, and neutropenia/thrombocytopenia. Conclusions The Folfox4 regimen administered through combined hepatic arterial and systemic infusions is efficacious and safe for the treatment of CRC with unresectable liver metastases, and it facilitates the control of local lesions.展开更多
The development of liver metastases is a common clinical entity in the clinical course of colorectal cancer. For patients with isolated liver involvement, surgical resection is the only treatment that can provide a ch...The development of liver metastases is a common clinical entity in the clinical course of colorectal cancer. For patients with isolated liver involvement, surgical resection is the only treatment that can provide a chance of prolonged survival and cure. However, most of these patients are not initially eligible for the surgery. Selected patients with initially considered to have unresectable disease may become resectable after systemic(che-motherapy ± biological therapy) and loco-regional treatment modalities including hepatic arterial infusion. Patients who have colorectal liver metastases ideally should be referred to a multidisciplinary cancer care team in order to identify the most optimal management approach.展开更多
Surgical resection is the only option of cure for patients with metastatic colorectal cancer(CRC). However, the risk of recurrence within 18 mo after metastasectomy is around 75% and the liver is the most frequent sit...Surgical resection is the only option of cure for patients with metastatic colorectal cancer(CRC). However, the risk of recurrence within 18 mo after metastasectomy is around 75% and the liver is the most frequent site of relapse. The current international guidelines recommend an adjuvant therapy after surgical resection of CRC metastases despite the lower level of evidence(based on the quality of studies in this setting). However, there is still no standard treatment and the effective role of an adjuvant therapy remains controversial. The aim of this review is to report the state-of-art of systemic chemotherapy and regional chemotherapy with hepatic arterial infusion in the management of patients after resection of metastases from CRC, with a literature review and meta-analysis of the relevant randomized controlled trials.展开更多
BACKGROUND Fistula formation is a severe adverse event related to antiangiogenetic agents such as bevacizumab and inferior mesenteric arteriovenous fistula(IMAVF) is a result of acquired factor, especially colon surge...BACKGROUND Fistula formation is a severe adverse event related to antiangiogenetic agents such as bevacizumab and inferior mesenteric arteriovenous fistula(IMAVF) is a result of acquired factor, especially colon surgery. However, IMAVF occurs very rarely and there are few reports in patients during chemotherapy. We report a case of a patient who developed IMAVF during treatment with bevacizumab in metastatic colorectal cancer(mCRC) after colon surgery.CASE SUMMARY An 81-year-old man was diagnosed with descending colon cancer and underwent left hemicolectomy without any complications. He was definitely diagnosed with high-risk stage 2 and received tegafur-uracil plus leucovorin as adjuvant chemotherapy. Three years and 6 mo after the operation, the cancer relapsed with peritoneal dissemination. The patient underwent CyberKnife radiosurgery targeting the recurrent tumor and received chemotherapy with S-1 plus bevacizumab. At 1 year after chemotherapy, he complained of severe diarrhea, which is suspected drug-induced colitis. As diarrhea worsened despite the termination of treatment, he underwent colonoscopy and computed tomography (CT) scans that revealed edematous change from sigmoid to rectosigmoid colon. CT scans also revealed an aneurysm adjacent to the inferior mesenteric vein and multidetector CT angiography showed the IMAVF. Elective angiography confirmed the diagnosis of an IMAVF and it was successfully treated by arterial embolization. The patient resumed chemotherapy with only S-1 6 mo after embolization.CONCLUSION Clinicians should keep in mind the probability of severe diarrhea arose from IMAVF in mCRC patients treated with bevacizumab.展开更多
Objective:To assess the methodological quality of clinical research on Chinese medicine(CM)applied by infra-arterial infusion in treating primary liver cancer(PLC).Methods:Cochrane Central Register of Controlled...Objective:To assess the methodological quality of clinical research on Chinese medicine(CM)applied by infra-arterial infusion in treating primary liver cancer(PLC).Methods:Cochrane Central Register of Controlled Trials(CENTRAL),PubMed,and three Chinese databases,including Chinese BioMedical Database(CBM),China National Knowledge Infrastructure(CNKI)and China Academic Journal(VIP)were searched.Chinese articles were also searched manually in 16 journals.Two reviewers independently selected studies,the quality of literatures were assessed according to the Cochrane Collaboration method of quality assessment.Results:A total of 14 articles met the inclusion criteria for this review.Only three of these articles described the randomization method used.None of the studies was blinded.All of the articles didn't report the calculation of the sample size.Only six studies mentioned adverse reactions.All of the studies were of grade C according to the Cochrane Collaboration method.Six studies reported results of survival,and only two of these reported better efficacy in the treatment groups.Conclusions:The quality of studies concerned intra-arterial infusion of CM in treating with PLC was poor and the exact effect of these medicines still need evaluation.Well designed RCTs with large sample sizes,adequate follow-up data and reliable methods of assessment are needed to better appraise the real effect of CMs in the treatment of PLC patients.展开更多
Colorectal cancer liver metastases (CLM) treatment is very important given the high incidence of colorectal cancer with liver metastases, which are primarily treated by surgical resection. Transformational therapy s...Colorectal cancer liver metastases (CLM) treatment is very important given the high incidence of colorectal cancer with liver metastases, which are primarily treated by surgical resection. Transformational therapy such as systemic chemotherapy, hepatic arterial infusion (HAl), portal vein embolization (PVE), ablation therapy, and targeted therapy, should be applied to CLM patients who are unable to undergo immediate surgery to improve patients' survival and quality of life.展开更多
基金Supported by Capital Medical Development and Scientific Research Fund,China,No.2014-2-2154
文摘AIM To evaluate the efficiency and safety of hepatic artery infusion chemotherapy(HAIC) using raltitrexed or 5-fluorouracil for colorectal cancer(CRC) liver metastasis(CRCLM).METHODS A retrospective analysis of patients with unresectable CRCLM who failed systemic chemotherapy and were subsequently treated with HAIC at our institute from May 2013 to April 2015 was performed. A total of 24 patients were treated with 5-fluorouracil, and 18 patients were treated with raltitrexed. RESULTS The median survival time(MST) from diagnosis of CRC was 40.8 mo in the oxaliplatin plus raltitrexed(TOMOX) arm and 33.5 mo in the oxaliplatin plus 5-fluorouracil(FOLFOX) arm(P = 0.802). MST from first HAIC was 20.6 mo in the TOMOX arm and 15.4 mo in the FOLFOX arm(P = 0.734). Median progression-free survival(PFS) from first HAIC was 4.9 mo and 6.6 mo, respectively, in the TOMOX arm and FOLFOX arm(P= 0.215). Leukopenia(P = 0.026) was more common in the FOLFOX arm, and hepatic disorder(P = 0.039) was more common in the TOMOX arm. There were no treatment-related deaths in the TOMOX arm and one treatment-related death in the FOLFOX arm. Analysis of prognostic factors indicated that response to HAIC was a significant factor related to survival.CONCLUSION No significant difference in survival was observed between the TOMOX and FOLFOX arms. HAIC treatment with either TOMOX or FOLFOX was demonstrated as an efficient and safe alternative choice.
文摘AIM: To study the distribution and stability of antisense oligodeoxynucleotide (ASODN) in Walker-256 cells and their distribution in liver, lung and kidney tissues after being infused alone or mixed with lipiodol via hepatic artery in a rat liver tumor model.METHODS: 5'-Isothiocyananate (FITC)-labeled vascular endothelial growth factor (VEGF) ASODN was added into Walker-256 cell culture media. Its distribution in cells was observed by fluorescence microscope at different time points. Walker-256 carcinosarcoma was transplanted into Wistar rat liver to establish a liver cancer model. 5'-FITC-labeled VEGF ASODN mixed with (mixed group, n = 6) or without (TAI group, n = 6)ultra-fluid lipiodol was administrated via hepatic artery.Frozen samples of liver, lung and kidney tissue were taken from rats after 1, 3 and 6 d, respectively. The distribution of ASODN was observed under fluorescent microscope.RESULTS: ASODN could enter cytoplasm within 2 h and nuclei within 6 h. Accumulation of ASODN reached the peak point in nuclei at 12 h, and then disappeared gradually. No fluorescence could be seen in cells at 48 h. In vivo experiment, on d 1 and 3 the fluorescence staining in liver was stronger in mixed group than in TAI group and more fluorescence could be detected in lung and kidney in TAI group than in mixed group. On d 6, no fluorescence could be detected in TAI group, but faint fluorescence could be seen in mixed group. ASODN could be seen in cancer cells and normal hepatic cells. In mixed group, ASODN was mainly distributed in liver tumor tissues.CONCLUSION: ASODN can transfect Walker-256 cells.ASODN mixed with lipiodol infusion via hepatic artery can be used in the treatment of HCC.
文摘Newer systemic therapies for hepatocellular carcinoma(HCC)have led to growing interest in combining hepatic arterial infusion chemotherapy(HAIC)with systemic treatments.To evaluate the effectiveness and safety of HAIC and combination therapies in treating advanced HCC,a network meta-analysis was conducted by Zhou et al.The study included data from 44 articles.HAIC was superior in overall survival(OS),progression-free survival(PFS),and response rates compared to transarterial chemoembolization and sorafenib.Moreover,combinations of HAIC with other treatments and single agents(e.g.,lenvatinib,ablation,anti-programmed cell death 1 therapy,radiotherapy)provided better OS and PFS outcomes than HAIC alone.In this editorial,we will discuss the study findings,the strengths and weaknesses of the metanalysis,and future advances in the field of HAIC for advanced HCC.
文摘Objective To evaluate the toxic effects and efficacy of the intra-arterial chrono-chemotherapy on patients with liver metastasis arised from colorectal cancer. Methods Chemotherapy of 42 patients were randomly divided into group A (n = 20) with continuously constant arterial infusion, and group B (n = 22) with arterial chrono-modulated infusion. And the toxic effects and efficacy of two groups were compared. Results A significant difference was found in the toxic effects of digestive system between the two groups. The treatment response was similar in the two groups. Conclusions Intra-arterial chrono-chemotherapy may decrease the toxic effects and improve the life quality of these patients. (J Intervent Radiol, 2006, 15: 487-490)
文摘Objective:To explore the influence on liver function of hepatic artery interventional chemoembolization combined reduced glutathione therapy for elderly patients with advanced liver cancer.Methods:A total of 120 cases of elderly patients with advanced liver cancer from digestive surgery in-patient department of our hospital during the period of January 2014 and January 2016 were selected as the research object, the patients were divided into two groups by using the random number table method,each for 60 cases.The control group were given conventional drugs chemotherapy, the study group were given hepatic artery interventional chemoembolization combined reduced glutathione therapy, serum liver function indexes of Direct Bilirubin(DBil), Total Bilirubin(TBil), Aspartate Transaminase(AST) and Alanineamino Transferase (ALT)were detected by using automatic biochemical analyzer. Results: The clinical remission rate of study group was significantly higher than the control group, the recurrence rate was obviously lower than the control group,compared between the two groups with statistically significant differences. The average survival time of study group (29.36±6.25) months, was significantly longer than the control group (18.02±4.16) months .Before the treatment, serum DBil, TBil, AST and ALT levels compared between the two groups with no statistically significant differences,after the treatment,the indexes of study group was significantly lower than the control group. The indexes levels compared between pre-therapy and post-therapy in study group with no statistically significant differences, while the indexes levels of post-therapy in the control group were significantly higher than those pre-therapy. Before the treatment, the life quality score compared between the two groups with no statistically significant differences, after treatment,the score of all patients were significantly higher than those pre-therapywhich the score of study group was significantly higher than the control group.The incidence rate of drug adverse reactions compared between the two groups with no statistically significant differences.Conclusion: The clinical efficacy of hepatic artery interventional chemoembolization combined reduced glutathione therapy for elderly patients with advanced liver cancer is satisfying, and helps to significantly improve liver function, improve life quality, it is worth popularization and application in the clinical practice.
基金supported by the Scientific Research Project of Traditional Chinese Medicine Administration of Guangdong Province(No.20222174)。
文摘Background:The aim of the study was to investigate the efficacy of continuous transcatheter arterial infusion chemotherapy combined with transarterial chemoembolization(TACE)for the treatment of advanced pancreatic cancer with liver metastasis.Methods:Sixty patients with advanced pancreatic cancer and liver metastases were enrolled in this study.In the treatment group,31patients underwent continuous transcatheter arterial infusion chemotherapy combined with TACE regional arterial thermal perfusion,whereas 29 patients included in the control group received intravenous chemotherapy with gemcitabine and S-1.All patients received maintenance chemotherapy with S-1 after 4 cycles of the study regimen.Treatment efficacy,quality of life,survival,and toxicity were evaluated.Results:Efficacy was better in the treatment group than in the control group,as reflected by the objective remission,partial remission,and disease progression rates(all P<0.05).The Eastern Cooperative Oncology Group and Numerical Rating Scale pain scores were also higher in the treatment group(both P<0.05).In survival analysis,the 1-year overall survival rates in the treatment and control groups were64.516%and 10.345%,respectively,whereas the median overall survival times were 16 and 6 months,respectively(both P<0.05).The6-month progression-free survival rates in the treatment and control groups were 77.419%and 13.790%,respectively,and the median progression-free survival times were 12 and 3 months,respectively(both P<0.05).The rates of hematological and nonhematological toxicological adverse effects were also lower in the treatment group(both P<0.05).Although the rate of liver dysfunction was higher in the treatment group,this finding had no adverse effects on prognosis.Conclusions:Continuous transcatheter arterial infusion chemotherapy combined with TACE regional arterial perfusion chemotherapy resulted in better efficacy and safety outcomes in patients with pancreatic cancer and liver metastasis,suggesting its utility as a reference method for the clinical treatment of advanced pancreatic cancer.
文摘Large bowel cancer is a worldwide public health challenge.More than one third of patients present an advanced stage of disease at diagnosis and the liver is the most common site of metastases.Selection criteria for early diagnosis,chemotherapy and surgery have been recently expanded.The definition of resectability remains unclear.The presence of metastases is the most significant prognostic factor.For this reason the surgical resection of hepatic metastases is the leading treatment.The most appropriate resection approach remains to be defined.The two step and simultaneous resection processes of both primary and metastases have comparable survival long-term outcomes.The advent of targeted biological chemotherapeutic agents and the development of loco-regional therapies(chemoembolization,thermal ablation,arterial infusion chemotherapy) contribute to extend favorable results.Standardized evidence-based protocols are missing,hence optimal management of hepatic metastases should be single patient tailored and decided by a multidisciplinary team.This article reviews the outcomes of resection,systemic and loco-regional therapies of liver metastases originating from large bowel cancer.
基金supported by National Key R&D Program of China(2017YFA0505803)National Natural Science Foundation of China(No.81625017,No.81572385)National Science and Technology Major Project of China(2018ZX10302205).
文摘Objective:To compare the efficacy of sorafenib plus hepatic arterial infusion chemotherapy(HAIC)with oxaliplatin to that of sorafenib alone in patients with advanced hepatocellular carcinoma(HCC).Methods:This was a retrospective,single-center trial.Between April 3,2017 and July 2,2018,104 patients with Child-Pugh A and advanced HCC received either 400 mg of sorafenib orally twice daily plus HAIC with oxaliplatin(oxaliplatin 85 mg/m^2,every 3 weeks via repetitive catheterization)(n=46,soraOXA group)or 400 mg of only sorafenib orally twice daily(n=58,sorafenib group).Overall survival,progression-free survival,objective response rate,and treatment-related adverse events were compared.Results:The median overall survival was 9.37 months(95%CI,7.05-11.68)in the soraOXA group versus 4.8 months(95%CI,2.98-6.62)in the sorafenib group(HR 0.46[95%CI,0.29-0.72];P<0.001).The soraOXA group also showed a higher objective response rate(16[34.8%]vs 1[1.7%];P<0.001)and a longer progressionfree survival rate(5.5 months[95%CI,2.32-8.68]vs 2.4 months[95%CI,1.65-3.15],HR 0.54[95%CI,0.36-0.81],P=0.003)than the sorafenib group.There was no significant difference in the overall incidence of any grade adverse events,grade 3/4 adverse events,serious adverse events,or incidence of treatment termination due to adverse events between the two groups.Conclusion:Compared with sorafenib alone,sorafenib plus HAIC with oxaliplatin showed favorable treatment outcomes in patients with advanced HCC.The merits of this approach need to be established with a prospective trial.
基金The study was reviewed and approved by the Ethics Committee of The Second Affiliated Hospital of Zhejiang University School of Medicine(Approval No.I2020001737).
文摘BACKGROUND Obstruction or fullness after feeding is common in gastric cancer(GC)patients,affecting their nutritional status and quality of life.Patients with digestive obstruction are generally in a more advanced stage.Existing methods,including palliative gastrectomy,gastrojejunostomy,endoluminal stent,jejunal nutrition tube and intravenous chemotherapy,have limitations in treating these symptoms.AIM To analyze the efficacy of continuous gastric artery infusion chemotherapy(cGAIC)in relieving digestive obstruction in patients with advanced GC.METHODS This study was a retrospective study.Twenty-nine patients with digestive obstruction of advanced GC who underwent at least one cycle of treatment were reviewed at The Second Affiliated Hospital of Zhejiang University School of Medicine.The oxaliplatin-based intra-arterial infusion regimen was applied in all patients.Mild systemic chemotherapy was used in combination with local treatment.The clinical response was evaluated by contrast-enhanced computed tomography using Response Evaluation Criteria In Solid Tumors(RECIST)criteria.Digestive tract symptoms and toxic effects were analyzed regularly.A comparison of the Karnofsky Performance Status(KPS)score and Stooler’s Dysphagia Score before and after therapy was made.Univariate survival analysis and multivariate survival analysis were also performed to explore the key factors affecting patient survival.RESULTS All patients finished cGAIC successfully without microcatheter displacement,as confirmed by arteriography.The median follow-up time was 24 mo(95%CI:20.24-27.76 mo).The overall response rate was 89.7%after cGAIC according to the RECIST criteria.The postoperative Stooler’s Dysphagia Score was significantly improved.Twentytwo(75.9%)of the 29 patients experienced relief of digestive obstruction after the first two cycles,and 13(44.8%)initially unresectable patients were then considered radically resectable.The median overall survival time(mOS)was 16 mo(95%CI:9.32-22.68 mo).Patients who received radical surgery had a significantly longer mOS than other patients(P value<0.001).Multivariate Cox regression analysis indicated that radical resection after cGAIC,intravenous chemotherapy after cGAIC,and immunotherapy after cGAIC were independent predictors of mOS.None of the patients stopped treatment because of adverse events.CONCLUSION cGAIC was effective and safe in relieving digestive obstruction in advanced GC,and it could improve surgical conversion possibility and survival time.
文摘AIM: To elucidate anticancer effects of transcatheter arterial infusion chemotherapy(TAI) in patients with hepatocellular carcinoma(HCC). METHODS: Data from a total of 95 patients with HCC who received TAI were analyzed retrospectively. The efficacy of TAI was evaluated according to the Response Evaluation Criteria in Cancer of the Liver. Overall survival was calculated from the date of initial treatment to the date of death or last follow-up. Survival curves were calculated by the Kaplan-Meier method, and differences in survival were evaluated by the log rank test. Clinical variables that were identified as statistically different by a univariate analysis were included into the Cox proportional hazard regression model for multivariate analysis. A prognostic index based on the regression coefficients derived from variables identified by the multivariate analysis was constructed. Stratification of the patients was conducted using this prognostic index. RESULTS: The patient group was comprised of 76 men and 19 women with an average age of 68 years(range: 37-82 years). Six patients(6.3%) showedcomplete response and 18 patients(18.9%) showed partial response, for an overall response rate of 25.2%. The median overall survival was 27.6 mo, and the proportions of survivors at 1, 2, and 5 years were 67.4%, 54.0%, and 17.4%, respectively. Multivariate analysis demonstrated that no prior transcatheter arterial chemoembolization, lactate dehydrogenase < 230 IU/L, and performance status of 0 were the independent favorable prognostic factors. The development of a 0-3-point prognostic score index was based on the sum of these three prognostic factors. Subsequently, the patients were categorized into three groups: those with a good(prognostic index = 0-1; n = 54), intermediate(prognostic index = 2; n = 26), or poor(prognostic index = 3; n = 15) prognosis. The median survival times in these three groups were 41.0, 21.2, and 6.8 mo, respectively(P < 0.01). CONCLUSION: Our simple prognostic index may be helpful for management of patients in determining treatment strategies for advanced HCC in the era of molecularly targeted therapy.
文摘Background: The regional chronomodulated hepatic arterial infusion chemotherapy (HAIC) is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, especially for the conversion into resectability. Aim: To demonstrate that chronomodulated HAI triplet chemotherapy according to OPTILIV protocol is well tolerated and displayed high antitumor activity in this heavily-pretreated patient. Case Presentation: A 54 years old patient from Russia was treated for a tumor in the ascending colon presented with 13 hepatic metastases ranging from 0.3 to 2.7 cm in diameter. He underwent a laparoscopic right hemicolectomy, 12 cycles of FOLFIRINOX combined to bevacizumab for the last 5 cycles, resulting in a partial response according to CT scan. It was decided to perform a two-stage hepatectomy at Paul Brousse hospital: left partial hepatectomy allowed the excision of 9 lesions. Radio frequency ablation was performed in 2 nodular lesions. Afterwards, the patient received 5 cycles of chronomodulated triplet chemotherapy into the hepatic artery, according to the OPTILIV protocol design, yet without cetuximab, because of the KRAS mutation in the liver metastases, with a partial re-sponse. The patient could then undergo the second stage of the planned right hepatectomy, which turned out to be an R0 resection followed by receiving three courses of chronomodulated HAIC. Disease progression was documented after 3 months. Chronomodulated FOLFIRI chemotherapy was re-started intravenously, in combination with Aflibercept and it was associated with further disease progression. The genetic analysis of our patient’s cancer revealed a high level of MSI. The patient was included in the Phase 2 CheckMate-142 trial and received nivolumab 3 mg/kg every 2 weeks within 3 months. Treatment was discontinued due to ineffectiveness. Then the patient underwent radiotherapy geared towards reduction of pain. Afterwards, the patient died from the disease progression 2 years after the beginning of treatment. Conclusion: In this article, the authors report a clinical case with chronomodulated HAIC as rescue therapy in a heavily pretreated patient with metastatic colorectal cancer, allowing to achieve an objective response despite prior progression on FOLFIRINOX (the same triplet chemo by IV route). This strategy permitted to overcome drug resistance and to perform further complete resection of the liver me-tastases with prolonged patient survival. Thus, chronomodulated HAI is useful in patients with liver metastases from colorectal cancer and de-serves to be further assessed prospectively in clinical trials chemotherapy.
文摘Background Hepatic arterial infusion chemotherapy for liver metastases is under evaluation because of the high target dose and low general toxicity. To investigate the efficacy and safety of a Folfox4 regimen administered through a combined hepatic arterial and systemic infusion for the first-line treatment of colorectal cancer (CRC) with unresectable liver metastases. Methods Twenty-seven CRC patients with unresectable hepatic metastases and no prior chemotherapy were enrolled into the study. They received a Folfox4 regimen; 1st day: HAl of oxaliplatin 85 mg/m2 and L-folinic acid 200 mg/m2, followed by a bolus hepatic arterial injection of 5-fluorouracil 400 mg/m2, then continuous HAl of 5-FU 600 mg/m2; 2nd day: infusion of L-folinic acid 200 mg/m2 i.v. followed by an intravenous bolus injection of 5-Fluorouraci1400 mg/m2, then continuous infusion of 5-fluorouracil 600 mg/m2 i.v. The patients received HAl during the odd cycles, and the intravenous administration of the same Folfox4 regimen during the even cycles. Results A total of 236 treatment cycles were given with a median of 10 cycles. The therapy generated the following results after six treatment cycles: complete response (CR) 1/27 (3.7%), partial response (PR) 17/27 (63.0%), stable disease (SD) 6/27 (22.2%), and progress disease (PD) 3/27 (11.1%). Five patients had hepatectomy. The serum levels of both carcinoembryonic antigen (CEA) and CA19-9 were significantly reduced (P〈0.05). A median time to progression of 11 months and a median overall survival of 24 months were documented. The major adverse events included grade 1/2 nausea/vomiting, upper abdominal pain, peripheral neuropathy, and neutropenia/thrombocytopenia. Conclusions The Folfox4 regimen administered through combined hepatic arterial and systemic infusions is efficacious and safe for the treatment of CRC with unresectable liver metastases, and it facilitates the control of local lesions.
文摘The development of liver metastases is a common clinical entity in the clinical course of colorectal cancer. For patients with isolated liver involvement, surgical resection is the only treatment that can provide a chance of prolonged survival and cure. However, most of these patients are not initially eligible for the surgery. Selected patients with initially considered to have unresectable disease may become resectable after systemic(che-motherapy ± biological therapy) and loco-regional treatment modalities including hepatic arterial infusion. Patients who have colorectal liver metastases ideally should be referred to a multidisciplinary cancer care team in order to identify the most optimal management approach.
文摘Surgical resection is the only option of cure for patients with metastatic colorectal cancer(CRC). However, the risk of recurrence within 18 mo after metastasectomy is around 75% and the liver is the most frequent site of relapse. The current international guidelines recommend an adjuvant therapy after surgical resection of CRC metastases despite the lower level of evidence(based on the quality of studies in this setting). However, there is still no standard treatment and the effective role of an adjuvant therapy remains controversial. The aim of this review is to report the state-of-art of systemic chemotherapy and regional chemotherapy with hepatic arterial infusion in the management of patients after resection of metastases from CRC, with a literature review and meta-analysis of the relevant randomized controlled trials.
文摘BACKGROUND Fistula formation is a severe adverse event related to antiangiogenetic agents such as bevacizumab and inferior mesenteric arteriovenous fistula(IMAVF) is a result of acquired factor, especially colon surgery. However, IMAVF occurs very rarely and there are few reports in patients during chemotherapy. We report a case of a patient who developed IMAVF during treatment with bevacizumab in metastatic colorectal cancer(mCRC) after colon surgery.CASE SUMMARY An 81-year-old man was diagnosed with descending colon cancer and underwent left hemicolectomy without any complications. He was definitely diagnosed with high-risk stage 2 and received tegafur-uracil plus leucovorin as adjuvant chemotherapy. Three years and 6 mo after the operation, the cancer relapsed with peritoneal dissemination. The patient underwent CyberKnife radiosurgery targeting the recurrent tumor and received chemotherapy with S-1 plus bevacizumab. At 1 year after chemotherapy, he complained of severe diarrhea, which is suspected drug-induced colitis. As diarrhea worsened despite the termination of treatment, he underwent colonoscopy and computed tomography (CT) scans that revealed edematous change from sigmoid to rectosigmoid colon. CT scans also revealed an aneurysm adjacent to the inferior mesenteric vein and multidetector CT angiography showed the IMAVF. Elective angiography confirmed the diagnosis of an IMAVF and it was successfully treated by arterial embolization. The patient resumed chemotherapy with only S-1 6 mo after embolization.CONCLUSION Clinicians should keep in mind the probability of severe diarrhea arose from IMAVF in mCRC patients treated with bevacizumab.
文摘Objective:To assess the methodological quality of clinical research on Chinese medicine(CM)applied by infra-arterial infusion in treating primary liver cancer(PLC).Methods:Cochrane Central Register of Controlled Trials(CENTRAL),PubMed,and three Chinese databases,including Chinese BioMedical Database(CBM),China National Knowledge Infrastructure(CNKI)and China Academic Journal(VIP)were searched.Chinese articles were also searched manually in 16 journals.Two reviewers independently selected studies,the quality of literatures were assessed according to the Cochrane Collaboration method of quality assessment.Results:A total of 14 articles met the inclusion criteria for this review.Only three of these articles described the randomization method used.None of the studies was blinded.All of the articles didn't report the calculation of the sample size.Only six studies mentioned adverse reactions.All of the studies were of grade C according to the Cochrane Collaboration method.Six studies reported results of survival,and only two of these reported better efficacy in the treatment groups.Conclusions:The quality of studies concerned intra-arterial infusion of CM in treating with PLC was poor and the exact effect of these medicines still need evaluation.Well designed RCTs with large sample sizes,adequate follow-up data and reliable methods of assessment are needed to better appraise the real effect of CMs in the treatment of PLC patients.
文摘Colorectal cancer liver metastases (CLM) treatment is very important given the high incidence of colorectal cancer with liver metastases, which are primarily treated by surgical resection. Transformational therapy such as systemic chemotherapy, hepatic arterial infusion (HAl), portal vein embolization (PVE), ablation therapy, and targeted therapy, should be applied to CLM patients who are unable to undergo immediate surgery to improve patients' survival and quality of life.