We hypothesize that a cylinder implant made of multilayer Poly-lactic-co-glycolic-acid (PLGA) membrane can be a method for controlled and extended drug release. We fashioned a multilayer cylindrical implant termed STI...We hypothesize that a cylinder implant made of multilayer Poly-lactic-co-glycolic-acid (PLGA) membrane can be a method for controlled and extended drug release. We fashioned a multilayer cylindrical implant termed STID100 that released doxorubicin for 3 weeks in an orthotopic 4T1 breast cancer model in Balb/C mice. This implant starts as a thin doxorubicin-embedded PLGA membrane, and is then rolled into a cylinder containing an air gap between the membrane layers. Its controlled sustained release delivered 2× the amount of the intravenous (IV) equivalent of doxorubicin, inhibited the primary tumor, and prevented lung metastasis. Importantly it did not cause weight loss, splenomegaly, or cardiac toxicity vs systemically administrated doxorubicin. This favorable safety profile is further substantiated by the finding of no detectable plasma doxorubicin in multiple time points during the 3-week period, and low tumor doxorubicin concentration. The implant system delivered to the specification of an ideal pharmacological paradigm might offer a better coverage of the local tumor, significantly preventing metastatic spread with less drug toxicity to many vital organs, compared to the traditional pharmacology of IV route. The profile of STID made it an attractive therapeutic alternative in metastatic tumor prevention, pain management and many other diverse clinical scenarios.展开更多
BACKGROUND Gallbladder cancer(GC)is a common malignant tumor and one of the leading causes of cancer-related death worldwide.It is typically highly invasive,difficult to detect in the early stages,and has poor treatme...BACKGROUND Gallbladder cancer(GC)is a common malignant tumor and one of the leading causes of cancer-related death worldwide.It is typically highly invasive,difficult to detect in the early stages,and has poor treatment outcomes,resulting in high mortality rates.The available treatment options for GC are relatively limited.One emerging treatment modality is hyperthermic intraperitoneal chemotherapy(HIPEC).HIPEC involves delivering heated chemotherapy directly into the abdominal cavity.It combines the strategies of surgical tumor resection and localized chemotherapy administration under hyperthermic conditions,aiming to enhance the concentration and effectiveness of drugs within the local tumor site while minimizing systemic toxicity.AIM To determine the effects of cytoreductive surgery(CRS)combined with HIPEC on the short-term prognosis of patients with advanced GC.METHODS Data from 80 patients treated at the Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine between January 2018 and January 2020 were retrospectively analyzed.The control group comprised 44 patients treated with CRS,and the research group comprised 36 patients treated with CRS combined RESULTS The baseline data of the research and control groups were similar(P>0.05).Six days after surgery,the alanine aminotransferase,aspartate aminotransferase,total bilirubin,and direct bilirubin levels significantly decreased compared to the preoperative levels in both groups(P<0.05).However,the values did not differ between the two groups six days postoperatively(P>0.05).Similarly,the postoperative creatinine and blood urea nitrogen levels were significantly lower than the preoperative levels in both groups(P<0.05),but they did not differ between the groups six days postoperatively(P>0.05).Furthermore,the research group had fewer postoperative adverse reactions than the control group(P=0.027).Finally,a multivariate Cox analysis identified the tumor stage,distant metastasis,and the treatment plan as independent factors affecting prognosis(P<0.05).The three-year survival rate in the study group was higher than that in the control group(P=0.002).CONCLUSION CRS combined with HIPEC lowers the incidence of adverse reactions and improves survival in patients with advanced GC.展开更多
Gastric cancer ranks as the fifth most common malignant tumor worldwide and is the third most common cause of cancer-related death. For advanced gastric cancer (AGC), neoadjuvant chemotherapy (NAC) can reduce its stag...Gastric cancer ranks as the fifth most common malignant tumor worldwide and is the third most common cause of cancer-related death. For advanced gastric cancer (AGC), neoadjuvant chemotherapy (NAC) can reduce its stage, increase the rate of radical resection, improve response to treatment, reduce the risk of local recurrence and improve survival rate. Regional arterial infusion chemotherapy (RAIC) is a form of NAC that involves directly injecting chemotherapeutic drugs into the tumor site through the tumor-feeding artery. RAIC increases the local drug concentration around the tumor, thereby improving the therapeutic responses and reducing the adverse effects of the drugs. In recent years, RAIC has attracted increasing attention. This article summarizes the basic principles, procedure, chemotherapy regimens, adverse drug reactions and complications, clinical applications and response evaluation of RAIC in the treatment of AGC.展开更多
Objective:To study the effect of systemic intravenous chemotherapy combined with regional arterial perfusion chemoembolization on the malignancy of locally advanced gastric cancer. Methods:A total of 90 patients with ...Objective:To study the effect of systemic intravenous chemotherapy combined with regional arterial perfusion chemoembolization on the malignancy of locally advanced gastric cancer. Methods:A total of 90 patients with primary gastric cancer who received treatment in Tianyou Hospital Affiliated to Wuhan University of Science & Technology between January 2014 and May 2016 were collected and divided into control group and observation group according to the random number table method, 45 cases in each group. The control group of patients received routine systemic intravenous chemotherapy + surgical treatment, and the observation group of patients received systemic intravenous chemotherapy combined with local arterial perfusion chemoembolization + surgical treatment. Levels of tumor markers and angiogenesis factors in serum as well as the expression of oncogenes and tumor suppressor genes in gastric cancer tissue were compared between the two groups of patients before and after chemotherapy.Results:Before chemotherapy, the levels of tumor markers and angiogenesis factors in serum as well as the expression of oncogenes and tumor suppressor genes in gastric cancer tissue were not significantly different between the two groups of patients;after chemotherapy, serum CEA, CA724, CA242, AFP, VEGF, Ang-2, COX2 and PD-ECGF levels of observation group were lower than those of control group, andiASPP, p130Cas, ERBB2 and C-myc mRNA expression in gastric cancer tissue were lower than those of control group while GKN1, p16, PTEN, TSPYL5 and merlin mRNA expression in gastric cancer tissue were higher than those of control group.Conclusions: Preoperative systemic intravenous chemotherapy combined with regional arterial perfusion chemoembolization can effectively reduce the malignancy of locally advanced gastric cancer and provide favorable conditions for the operation.展开更多
Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in pati...Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase Ⅱ-Ⅲ studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition,proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients.展开更多
Chemotherapy is the mainstay of treatment for advanced pancreatic cancer(stageⅢ/Ⅳ).However,conventional systemic intravenous chemotherapy(SIC)has been unsatisfactory for pancreatic cancer.In recent years,regional ar...Chemotherapy is the mainstay of treatment for advanced pancreatic cancer(stageⅢ/Ⅳ).However,conventional systemic intravenous chemotherapy(SIC)has been unsatisfactory for pancreatic cancer.In recent years,regional arterial infusion chemotherapy(RAIC)has been clinically used as a new chemotherapy regimen for the treatment of advanced pancreatic cancer,but its efficacy is controversial.The purpose of this study was to evaluate the clinical efficacy and safety of RAIC.We searched literatures in databases such as PubMed,EMBASE,Cochrane Library,Web of Science,and CNKI.After screening,this meta-analysis finally included 9 randomized controlled trials(RCTs)with 444 patients(230 RAIC and 214 SIC).We used the Cochrane Risk of Bias 2.0 tool to assess risk of bias for included RCTs.Outcomes were overall survival(OS),overall response rate(ORR),adverse events rate(AER),and pain remission rate.Outcome indicators used relative risk(RR)and its 95%confidence interval(CI)as effect analysis statistics.The results showed that RAIC had some advantages over SIC in terms of ORR,OS,incidence of leukopenia,and pain remission.In conclusion,compared with SIC,RAIC has better clinical efficacy and lower toxicity in the treatment of advanced pancreatic cancer.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
Purpose:This study aims at reporting the experience of a cancer hospital’s multiprofessional team with surgery patients in performing cytoreductive surgeries associated with hyperthermic intraperitoneal chemotherapy....Purpose:This study aims at reporting the experience of a cancer hospital’s multiprofessional team with surgery patients in performing cytoreductive surgeries associated with hyperthermic intraperitoneal chemotherapy.Methods:It is a reporting about the experience of the multiprofessional team at AC Camargo Cancer Center’s surgery center,which operates in cytoreductive surgeries with hyperthermic intraperitoneal chemotherapy,thus guaranteeing the surgery patient’s safety.Results:No safety report for the surgery patient subjected to intraperitoneal hypothermic chemotherapy was found in the literature.Therefore,the surgery center’s multiprofessional team’s practice was based on standards for manipulating chemotherapeutic agents and for safely administering medication.A checklist was elaborated for cytoreductive surgeries with hyperthermic intraperitoneal chemotherapy based on the surgery patient safety protocol and the institution’s multiprofessional team’s experience.Conclusions:From the multiprofessional team’s experiences in cytoreductive surgeries with hyperthermic intraperitoneal chemotherapy,the importance of elaborating a checklist to promote the quality of assistance and guarantee patient safety during the entire intraoperative phase became evident.展开更多
文摘We hypothesize that a cylinder implant made of multilayer Poly-lactic-co-glycolic-acid (PLGA) membrane can be a method for controlled and extended drug release. We fashioned a multilayer cylindrical implant termed STID100 that released doxorubicin for 3 weeks in an orthotopic 4T1 breast cancer model in Balb/C mice. This implant starts as a thin doxorubicin-embedded PLGA membrane, and is then rolled into a cylinder containing an air gap between the membrane layers. Its controlled sustained release delivered 2× the amount of the intravenous (IV) equivalent of doxorubicin, inhibited the primary tumor, and prevented lung metastasis. Importantly it did not cause weight loss, splenomegaly, or cardiac toxicity vs systemically administrated doxorubicin. This favorable safety profile is further substantiated by the finding of no detectable plasma doxorubicin in multiple time points during the 3-week period, and low tumor doxorubicin concentration. The implant system delivered to the specification of an ideal pharmacological paradigm might offer a better coverage of the local tumor, significantly preventing metastatic spread with less drug toxicity to many vital organs, compared to the traditional pharmacology of IV route. The profile of STID made it an attractive therapeutic alternative in metastatic tumor prevention, pain management and many other diverse clinical scenarios.
基金Shanghai Pudong New Area Health Commission’s Excellent Young Medical Talent Training Plan,No.PWRq2020-68Shanghai Pudong New Area Health Commission Discipline Leader Training Project,No.PWRd2020-16Shanghai Pudong New Area Science and Technology Development Fund,No.PKJ2020-Y36.
文摘BACKGROUND Gallbladder cancer(GC)is a common malignant tumor and one of the leading causes of cancer-related death worldwide.It is typically highly invasive,difficult to detect in the early stages,and has poor treatment outcomes,resulting in high mortality rates.The available treatment options for GC are relatively limited.One emerging treatment modality is hyperthermic intraperitoneal chemotherapy(HIPEC).HIPEC involves delivering heated chemotherapy directly into the abdominal cavity.It combines the strategies of surgical tumor resection and localized chemotherapy administration under hyperthermic conditions,aiming to enhance the concentration and effectiveness of drugs within the local tumor site while minimizing systemic toxicity.AIM To determine the effects of cytoreductive surgery(CRS)combined with HIPEC on the short-term prognosis of patients with advanced GC.METHODS Data from 80 patients treated at the Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine between January 2018 and January 2020 were retrospectively analyzed.The control group comprised 44 patients treated with CRS,and the research group comprised 36 patients treated with CRS combined RESULTS The baseline data of the research and control groups were similar(P>0.05).Six days after surgery,the alanine aminotransferase,aspartate aminotransferase,total bilirubin,and direct bilirubin levels significantly decreased compared to the preoperative levels in both groups(P<0.05).However,the values did not differ between the two groups six days postoperatively(P>0.05).Similarly,the postoperative creatinine and blood urea nitrogen levels were significantly lower than the preoperative levels in both groups(P<0.05),but they did not differ between the groups six days postoperatively(P>0.05).Furthermore,the research group had fewer postoperative adverse reactions than the control group(P=0.027).Finally,a multivariate Cox analysis identified the tumor stage,distant metastasis,and the treatment plan as independent factors affecting prognosis(P<0.05).The three-year survival rate in the study group was higher than that in the control group(P=0.002).CONCLUSION CRS combined with HIPEC lowers the incidence of adverse reactions and improves survival in patients with advanced GC.
文摘Gastric cancer ranks as the fifth most common malignant tumor worldwide and is the third most common cause of cancer-related death. For advanced gastric cancer (AGC), neoadjuvant chemotherapy (NAC) can reduce its stage, increase the rate of radical resection, improve response to treatment, reduce the risk of local recurrence and improve survival rate. Regional arterial infusion chemotherapy (RAIC) is a form of NAC that involves directly injecting chemotherapeutic drugs into the tumor site through the tumor-feeding artery. RAIC increases the local drug concentration around the tumor, thereby improving the therapeutic responses and reducing the adverse effects of the drugs. In recent years, RAIC has attracted increasing attention. This article summarizes the basic principles, procedure, chemotherapy regimens, adverse drug reactions and complications, clinical applications and response evaluation of RAIC in the treatment of AGC.
文摘Objective:To study the effect of systemic intravenous chemotherapy combined with regional arterial perfusion chemoembolization on the malignancy of locally advanced gastric cancer. Methods:A total of 90 patients with primary gastric cancer who received treatment in Tianyou Hospital Affiliated to Wuhan University of Science & Technology between January 2014 and May 2016 were collected and divided into control group and observation group according to the random number table method, 45 cases in each group. The control group of patients received routine systemic intravenous chemotherapy + surgical treatment, and the observation group of patients received systemic intravenous chemotherapy combined with local arterial perfusion chemoembolization + surgical treatment. Levels of tumor markers and angiogenesis factors in serum as well as the expression of oncogenes and tumor suppressor genes in gastric cancer tissue were compared between the two groups of patients before and after chemotherapy.Results:Before chemotherapy, the levels of tumor markers and angiogenesis factors in serum as well as the expression of oncogenes and tumor suppressor genes in gastric cancer tissue were not significantly different between the two groups of patients;after chemotherapy, serum CEA, CA724, CA242, AFP, VEGF, Ang-2, COX2 and PD-ECGF levels of observation group were lower than those of control group, andiASPP, p130Cas, ERBB2 and C-myc mRNA expression in gastric cancer tissue were lower than those of control group while GKN1, p16, PTEN, TSPYL5 and merlin mRNA expression in gastric cancer tissue were higher than those of control group.Conclusions: Preoperative systemic intravenous chemotherapy combined with regional arterial perfusion chemoembolization can effectively reduce the malignancy of locally advanced gastric cancer and provide favorable conditions for the operation.
基金Supported by National Natural Science Foundation of China,No.81220108023,No.81370064 and No.81572329Fundamental Research Funds for the Central Universities,No.20620140729+1 种基金Jiangsu Provincial Program of Medical Sciences,No.BL2012001Distinguished Young Investigator Project of Nanjing,No.JQX12002
文摘Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase Ⅱ-Ⅲ studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition,proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients.
基金This study was supported in part by the Natural Science Foundation of Shandong Province,China(ZR2020MH256)the Medical Health Science and Technology Project of Shandong Provincial Health Commission(2019WS386).
文摘Chemotherapy is the mainstay of treatment for advanced pancreatic cancer(stageⅢ/Ⅳ).However,conventional systemic intravenous chemotherapy(SIC)has been unsatisfactory for pancreatic cancer.In recent years,regional arterial infusion chemotherapy(RAIC)has been clinically used as a new chemotherapy regimen for the treatment of advanced pancreatic cancer,but its efficacy is controversial.The purpose of this study was to evaluate the clinical efficacy and safety of RAIC.We searched literatures in databases such as PubMed,EMBASE,Cochrane Library,Web of Science,and CNKI.After screening,this meta-analysis finally included 9 randomized controlled trials(RCTs)with 444 patients(230 RAIC and 214 SIC).We used the Cochrane Risk of Bias 2.0 tool to assess risk of bias for included RCTs.Outcomes were overall survival(OS),overall response rate(ORR),adverse events rate(AER),and pain remission rate.Outcome indicators used relative risk(RR)and its 95%confidence interval(CI)as effect analysis statistics.The results showed that RAIC had some advantages over SIC in terms of ORR,OS,incidence of leukopenia,and pain remission.In conclusion,compared with SIC,RAIC has better clinical efficacy and lower toxicity in the treatment of advanced pancreatic cancer.
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Purpose:This study aims at reporting the experience of a cancer hospital’s multiprofessional team with surgery patients in performing cytoreductive surgeries associated with hyperthermic intraperitoneal chemotherapy.Methods:It is a reporting about the experience of the multiprofessional team at AC Camargo Cancer Center’s surgery center,which operates in cytoreductive surgeries with hyperthermic intraperitoneal chemotherapy,thus guaranteeing the surgery patient’s safety.Results:No safety report for the surgery patient subjected to intraperitoneal hypothermic chemotherapy was found in the literature.Therefore,the surgery center’s multiprofessional team’s practice was based on standards for manipulating chemotherapeutic agents and for safely administering medication.A checklist was elaborated for cytoreductive surgeries with hyperthermic intraperitoneal chemotherapy based on the surgery patient safety protocol and the institution’s multiprofessional team’s experience.Conclusions:From the multiprofessional team’s experiences in cytoreductive surgeries with hyperthermic intraperitoneal chemotherapy,the importance of elaborating a checklist to promote the quality of assistance and guarantee patient safety during the entire intraoperative phase became evident.