BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and com...BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective immunotherapy.AIM To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer models.METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 group.Tumor-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were evaluated.Real-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of time.The growth curves of tumors were drawn.RESULTS The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control group.Additionally,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA expression.Tumor volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic effect.CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer.展开更多
AIM: To retrospectively assess the effect of comprehensive cryosurgery (ablation of intraand extra-hepatic tumors) plus dendritic cell-cytokine-induced killer cell immunotherapy in metastatic hepatocellular cancer. ME...AIM: To retrospectively assess the effect of comprehensive cryosurgery (ablation of intraand extra-hepatic tumors) plus dendritic cell-cytokine-induced killer cell immunotherapy in metastatic hepatocellular cancer. METHODS: We divided 45 patients into cryo-immunotherapy (21 patients), cryotherapy (n = 12), immunotherapy (n = 5) and untreated (n = 7) groups. Overall survival (OS) after diagnosis of metastatic hepatocellular cancer was assessed after an 8-year follow-up. RESULTS: Median OS was higher following cryo-immu-notherapy (32 mo) or cryotherapy (17.5 mo; P < 0.05) than in the untreated group (3 mo) and was higher in the cryo-immunotherapy group than in the cryotherapy group (P < 0.05). In the cryo-immunotherapy group, median OS was higher after multiple treatments (36.5 mo) than after a single treatment (21 mo; P < 0.05). CONCLUSION: Cryotherapy and, especially, cryoimmunotherapy significantly increased OS in metastatic hepatocellular cancer patients. Multiple cryo-immunotherapy was associated with a better prognosis than single cryo-immunotherapy.展开更多
AIM: To study the therapeutic value of combination o cryosurgery and 125iodine seed implantation for locally advanced pancreatic cancer. METHODS: Forty-nine patients with locally advanced pancreatic cancer (males 36, ...AIM: To study the therapeutic value of combination o cryosurgery and 125iodine seed implantation for locally advanced pancreatic cancer. METHODS: Forty-nine patients with locally advanced pancreatic cancer (males 36, females 13), with a median age of 59 years, were enrolled in the study. Twelve patients had liver metastases. In all cases the tumors were considered unresectable after a comprehensive evaluation. Patients were treated with cryosurgery, which was performed intraoperatively or percutaneously unde guidance of ultrasound and/or computed tomography (CT), and 125iodine seed implantation, which was performed during cryosurgery or post-cryosurgery under guidance of ultrasound and/or CT. A few patients received regional celiac artery chemotherapy. RESULTS: Thirteen patients received intraoperative cryosurgery and 36 received percutaneous cryosurgery Some patients underwent repeat cryosurgery. 125Iodine seed implantation was performed during freezing procedure in 35 patients and 3-9 d after cryosurgery in 14 cases. Twenty patients, 10 of whom had hepaticmetastases received regional chemotherapy. At 3 mo after therapy, CT was repeated to estimate tumor response to therapy. Most patients showed varying degrees of tumor necrosis. Complete response (CR) of tumor was seen in 20.4% patients, partial response (PR), in 38.8%, stable disease (SD), in 30.6%, and progressive disease (PD), in 10.2%. Adverse effects associated with cryosurgery included upper abdomen pain and increased serum amylase. Acute pancreatitis was seen in 6 patients one of whom developed severe pancreatitis. All adverse effects were controlled by medical management with no poor outcome. There was no therapy-related mortality. During a median follow-up of 18 mo (range of 5-40), the median survival was 16.2 mo, with 26 patients (53.1%) surviving for 12 mo or more. Overall, the 6-, 12-, 24- and 36-mo survival rates were 94.9%, 63.1%, 22.8% and 9.5%, respectively. Eight patients had survival of 24 mo or more. The patient with the longest survival (40 mo) is still living without evidence of tumor recurrence. CONCLUSION: Cryosurgery, which is far less invasive than conventional pancreatic resection, and is associated with a low rate of adverse effects, should be the treatment of choice for patients with locally advanced pancreatic cancer. 125Iodine seed implantation can destroy the residual surviving cancer cells after cryosurgery. Hence, a combination of both modalities has a complementary effect.展开更多
Pancreatic carcinoma is a common cancer of the digestive system with a poor prognosis. It is characterized by insidious onset, rapid progression, a high degree of malignancy and early metastasis. Atpresent, radical su...Pancreatic carcinoma is a common cancer of the digestive system with a poor prognosis. It is characterized by insidious onset, rapid progression, a high degree of malignancy and early metastasis. Atpresent, radical surgery is considered the only curative option for treatment, however, the majority of patients with pancreatic cancer are diagnosed too late to undergo surgery. The sensitivity of pancreatic cancer to chemotherapy or radiotherapy is also poor. As a result, there is no standard treatment for patients with advanced pancreatic cancer. Cryoablation is generally considered to be an effective palliative treatment for pancreatic cancer. It has the advantages of minimal invasion and improved targeting, and is potentially safe with less pain to the patients. It is especially suitable in patients with unresectable pancreatic cancer. However, our initial findings suggest that cryotherapy combined with 125-iodine seed implantation, immunotherapy or various other treatments for advanced pancreatic cancer can improve survival in patients with unresectable or metastatic pancreatic cancer. Although these findings require further in-depth study, the initial results are encouraging. This paper reviews the safety and efficacy of cryoablation, including combined approaches, in the treatment of pancreatic cancer.展开更多
AIM:To investigate the therapeutic effect of radical treatment and palliative treatment in stage Ⅳ pancreatic cancer patients.METHODS:81 patients were enrolled in the study.Radical treatment was performed on 51 patie...AIM:To investigate the therapeutic effect of radical treatment and palliative treatment in stage Ⅳ pancreatic cancer patients.METHODS:81 patients were enrolled in the study.Radical treatment was performed on 51 patients,while 30 patients were put under palliative treatment.The procedural safety and interval survival for stage Ⅳ pancreatic cancer(IS-Ⅳ) was assessed by almost 2.5 years of follow-ups.The IS-Ⅳ of patients under the two kinds of treatment,and the effects of treatment timing and frequency on IS-Ⅳ,were compared.RESULTS:The IS-Ⅳ of patients who received radical treatment was significantly longer than those who received palliative treatment(P < 0.001).The IS-Ⅳ of patients who received delayed radical or palliative treatment was longer than those who received accordingly timely treatment(P = 0.0034 and 0.0415,respectively).Multiple treatments can play an important role in improving the IS-Ⅳ of patients who received radical treatment(P = 0.0389),but not for those who received palliative treatment(P = 0.99).CONCLUSION:The effect of radical treatment was significantly more obvious than that of palliative treatment,and multiple radical treatments may contribute more to patients than a single radical treatment.展开更多
BACKGROUND Locally advanced pancreatic cancer(LAPC)is a common malignant digestive system tumor that ranks as the fourth leading cause of cancer-related death in the world.The prognosis of LAPC is poor even after stan...BACKGROUND Locally advanced pancreatic cancer(LAPC)is a common malignant digestive system tumor that ranks as the fourth leading cause of cancer-related death in the world.The prognosis of LAPC is poor even after standard treatment.Irreversible electroporation(IRE)is a novel ablative strategy for LAPC.Several studies have confirmed the safety of IRE.To date,no prospective studies have been performed to investigate the therapeutic efficacy of conventional gemcitabine(GEM)plus concurrent IRE.AIM To compare the therapeutic efficacy between conventional GEM plus concurrent IRE and GEM alone for LAPC.METHODS From February 2016 to September 2017,a total of 68 LAPC patients were treated with GEM plus concurrent IRE(n=33)or GEM alone(n=35).Overall survival(OS),progression free survival(PFS),and procedure-related complications were compared between the two groups.Multivariate analyses were performed to identify any prognostic factors.RESULTS There were no treatment-related deaths.The technical success rate of IRE ablation was 100%.The GEM+IRE group had a significantly longer OS from the time of diagnosis of LAPC(19.8 mo vs 9.3 mo,P<0.0001)than the GEM alone group.The GEM+IRE group had a significantly longer PFS(8.3 mo vs 4.7 mo,P<0.0001)than the GEM alone group.Tumor volume less than 37 cm3 and GEM plus concurrent IRE were identified as significant favorable factors for both the OS and PFS.CONCLUSION Gemcitabine plus concurrent IRE is an effective treatment for patients with LAPC.展开更多
BACKGROUND We present the case of a 72-year-old female patient with gallbladder cancer(GBC)who developed in situ recurrence and liver metastases 9 mo after irreversible electroporation ablation and oral tegafur(a fluo...BACKGROUND We present the case of a 72-year-old female patient with gallbladder cancer(GBC)who developed in situ recurrence and liver metastases 9 mo after irreversible electroporation ablation and oral tegafur(a fluoropyrimidine derivative)chemotherapy,which failed to control the progression of the disease.The patient further developed metastases in the lymph nodes around the head of the pancreas.The patient had severe anemia,requiring weekly blood transfusions.The gallbladder tumor invaded the descending part of the duodenum,causing intestinal leakage and hepatic colonic adhesion.CASE SUMMARY The patient refused other treatments and began daily hydrogen inhalation therapy.After 1 mo of treatment,the gallbladder and liver tumors continued to progress,and intestinal obstruction occurred.After continuous hydrogen therapy and symptomatic treatments including gastrointestinal decompression and intravenous nutrition support,the intestinal obstruction was gradually relieved.Three months after hydrogen therapy,the metastases in the abdominal cavity gradually reduced in size,her anemia and hypoalbuminemia were corrected,lymphocyte and tumor marker levels returned to normal,and the patient was able to resume normal life.CONCLUSION This is the first report of an efficacy and safety study about hydrogen therapy in patient with metastatic GBC and a critical general condition,who has remained stable for more than 4 months.展开更多
BACKGROUND Pancreatic cancer has a poor prognosis;40%–50% of patients have liver metastases at the time of initial diagnosis and only 15%–20% undergo surgical resection. Irreversible electroporation(IRE) is a new, n...BACKGROUND Pancreatic cancer has a poor prognosis;40%–50% of patients have liver metastases at the time of initial diagnosis and only 15%–20% undergo surgical resection. Irreversible electroporation(IRE) is a new, non-thermal local ablation method for solid tumors, which can induce cell membrane permeabilization,resulting in unrecoverable nanoscale perforation and apoptotic cell death without damaging the structural components of tissues.CASE SUMMARY We report the case of a 66-year-old female patient with liver metastasis from pancreatic cancer with a pathological diagnosis of poorly differentiated adenocarcinoma. Carbohydrate antigen 19-9 was elevated to 420.3 U/m L.Computed tomography showed a pancreas mass of 2.7 cm × 2.5 cm and single liver metastasis of 1.4 cm × 1.1 cm in the S6 area. The patient underwent IRE and arterial infusion chemotherapy and received tegafur. The therapeutic effect of the combination treatment has been evaluated as complete response. To date, the patient has survived for > 12 mo and is receiving tegafur as maintenance therapy(at the time this case report was written).CONCLUSION IRE plus arterial infusion chemotherapy and tegafur may be synergistic,providing a reference for treating liver metastasis from pancreatic cancer.展开更多
Introduction Liver cancer remains a global health challenge,and its incidence is increasing worldwide.It is estimated that by 2025,more than one million individuals will be affected by liver cancer annually[1,2].In re...Introduction Liver cancer remains a global health challenge,and its incidence is increasing worldwide.It is estimated that by 2025,more than one million individuals will be affected by liver cancer annually[1,2].In recent years,ablation has become a widely accepted treatment option for patients with primary and secondary liver malignancies[3].The commonly used ablation method for liver cancer is thermal ablation,including radiofrequency ablation.展开更多
BACKGROUND Bronchial cysts are congenital malformations usually located in the mediastinum,and intrapulmonary localization is very rare.Cryoablation is a novel therapeutic approach that promotes tumor necrosis and sti...BACKGROUND Bronchial cysts are congenital malformations usually located in the mediastinum,and intrapulmonary localization is very rare.Cryoablation is a novel therapeutic approach that promotes tumor necrosis and stimulates anti-tumor immune responses.CASE SUMMARY This article reports a case of a 68-year-old male patient who was diagnosed with an intrapulmonary bronchogenic cyst by computed tomography examination and pathology,and the patient subsequently underwent cryoablation therapy and achieved complete response with after 3 months of follow-up.CONCLUSION Intrapulmonary bronchogenic cysts are very rare,cryoablation therapy is feasible,safe,and effective for intrapulmonary bronchial cysts.展开更多
BACKGROUND Irreversible electroporation(IRE)is a novel non-thermal ablation technology for unresectable tumors.Hypertension and tachycardia usually occur during the IRE.To date,there has been little explanation about ...BACKGROUND Irreversible electroporation(IRE)is a novel non-thermal ablation technology for unresectable tumors.Hypertension and tachycardia usually occur during the IRE.To date,there has been little explanation about this phenomenon.AIM To investigate the reasons of hypertension and tachycardia and appropriate preventive measures.METHODS IRE was performed under general anesthesia and neuromuscular blockade.Systolic blood pressures,diastolic blood pressures,heart rate,and the distance of the electrode from abdominal aorta and adrenal gland during IRE were recorded.RESULTS All of 78 patients underwent 96 IRE sessions,44(56.4%)patients occurred hypertension when the electrode was close to the abdominal aorta(<2.0 cm).The median systolic blood pressures and diastolic blood pressures was 194 and 108 mmHg.Furthermore,11(14.1%)patients occurred tachycardia when the electrode was close to the adrenal gland(<1.3 cm).The median heart rate of patients with tachycardia was 114 beats per minute.Furthermore,hypertension and tachycardia can be prevented with nicardipine and esmolol before treatment.CONCLUSION Intraoperative hypertension and tachycardia occur because electrodes close to the abdominal aorta(<2.0 cm)and adrenal glands(<1.3 cm),which can be prevented by preoperative treatment of vasoactive drugs.展开更多
AIM:To study the effect and tolerance of intraperitoneal perfusion of cytokine-induced killer(CIK) cells in combination with local radio frequency(RF) hyperthermia in patients with advanced primary hepatocellular carc...AIM:To study the effect and tolerance of intraperitoneal perfusion of cytokine-induced killer(CIK) cells in combination with local radio frequency(RF) hyperthermia in patients with advanced primary hepatocellular carcinoma(HCC).METHODS:Patients with advanced primary HCC were included in this study.CIK cells were perfused intraperitoneal twice a week,using 3.2 × 10 9 to 3.6 × 10 9 cells each session.Local RF hyperthermia was performed 2 h after intraperitoneal perfusion.Following an interval of one month,the next course of treatment was administered.Patients received treatment until disease progression.Tumor size,immune indices(CD3 +,CD4 +,CD3 + CD8 +,CD3 + CD56 +),alpha-fetoprotein(AFP) level,abdominal circumference and adverse events were recorded.Time to progression and overall survival(OS) were calculated.RESULTS:From June 2010 to July 2011,31 patients diagnosed with advanced primary HCC received intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia in our study.Patients received an average of 4.2 ± 0.6 treatment courses(range,1-8 courses).Patients were followed up for 8.3 ± 0.7 mo(range,2-12 mo).Following combination treatment,CD4 +,CD3 + CD8 + and CD3 + CD56 + cells increased from 35.78% ± 3.51%,24.61% ± 4.19% and 5.94% ± 0.87% to 45.83% ± 2.48%(P = 0.016),39.67% ± 3.38%(P = 0.008) and 10.72% ± 0.67%(P = 0.001),respectively.AFP decreased from 167.67 ± 22.44 to 99.89 ± 22.05 ng/mL(P = 0.001) and abdominal circumference decreased from 97.50 ± 3.45 cm to 87.17 ± 4.40 cm(P = 0.002).The disease control rate was 67.7%.The most common adverse events were low fever and slight abdominal erubescence,which resolved without treatment.The median time to progression was 6.1 mo.The 3-,6-and 9-mo and 1-year survival rates were 93.5%,77.4%,41.9% and 17.4%,respectively.The median OS was 8.5 mo.CONCLUSION:Intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia is safe,can efficiently improve immunological status,and may prolong survival in HCC patients.展开更多
AIM:To determine the safety and efficacy of efficacy of percutaneous cryosurgery for treatment of patients with hepatic colorectal metastases. METHODS: Three hundred and twenty-six patients with non-resectable hepatic...AIM:To determine the safety and efficacy of efficacy of percutaneous cryosurgery for treatment of patients with hepatic colorectal metastases. METHODS: Three hundred and twenty-six patients with non-resectable hepatic colorectal metastases underwent percutaneous cryosurgery under the guidance of ultrasound or CT. Follow-up was 1 mo after cryosurgery and then every 4 mo thereafter by assessment of tumor markers, liver ultrasonography, and abdominal CT. For lesions suspicious of recurrence, a liver biopsy was performed and subsequent repeat cryosurgery was given if histology was positive for cancer. RESULTS: All patients underwent a total of 526 procedures of cryosurgery. There were 151 patients who underwent repeat procedures of cryosurgery for recurrent tumors in the liver and extrahepatic places. At 3 mo after cryosurgery, carcinoembryonic antigen (CEA) levels in 197 (77.5%) patients who had elevated markers before cryosurgery decreased to normal range. Among 280 patients who received CT following-up, cryotreated lesions showed complete response (CR) in 41 patients (14.6%), partial response (PR) in 115 patients (41.1%), stable disease (SD) in 68 patients (24.3%) and progressive disease (PD) in 56 patients (20%). The recurrence rate was 47.2% during a median follow-up of 32 mo (range, 7-61). Sixty one percent of the recurrences were seen in liver only and 13.9% in liver and extrahepatic areas. The recurrence rate at cryotreated site was only 6.4% for all cases. During a median follow-up of 36 mo (7-62 mo), the median survival of all patient was 29 mo (range 3-62 mo). Overall survival was 78%, 62%, 41%, 34% and 23% at 1, 2, 3, 4 and 5 years, respectively, after the treatment. Patients with tumor size less than 3 cm, tumor in right lobe of liver, lower CEA levels (< 100 ng/dL) and post- cryosurgery TACE had higher survival rate. There wasno significant difference in terms of survival based on the number of tumors, pre-cryosurgery chemotherapy and the timing of the development of metastases (synchronous vs metachronous). Patients who underwent 2-3 procedures of cryosurgery had increased survival compared to patients who received cryosurgery once only. There was no intra-cryosurgery mortality. Main adverse effects, such as hepatic bleeding, cryoshock, biliary fistula, liver failure, renal insufficiency and liver abscess were only observed in 0.3%-1.5% of patients. CONCLUSION:Percutaneous cryosurgery was a safe modality for hepatic colorectal metastases. Rather than an alternative to resection, this technique should be regarded as a complement to hepatectomy and as an additional means of achieving tumor eradication when total excision is not possible.展开更多
BACKGROUND Solid pseudopapillary tumor(SPT) of the pancreas is a rare pancreatic tumor and 10% to 15% of cases are associated with metastasis. Cryoablation is a new method that can induce tumor necrosis, and treatment...BACKGROUND Solid pseudopapillary tumor(SPT) of the pancreas is a rare pancreatic tumor and 10% to 15% of cases are associated with metastasis. Cryoablation is a new method that can induce tumor necrosis, and treatment of tumors by cryoablation can cause anti-tumor immune responses.CASE SUMMARY A 16-year-old woman with SPT of the pancreas developed liver metastases 5.3 years after complete resection of the primary pancreatic tumor. She was admitted with chief complaints of abdominal pain in the upper abdomen and a weight loss of approximately 5 kg over 4 mo. Carbohydrate antigen(CA) 125,carcinoembryonic antigen, and CA 199 were normal. An abdominal computed tomography scan found multiple nodules in the right lobe of the liver that measured approximately 13.5 cm × 10.8 cm × 21.4 cm. Immunohistochemical staining results showed that CD10 and CD56 were positive, and the patient was diagnosed with SPT of the pancreas with liver metastasis. The patient underwent percutaneous cryoablation and interventional embolization. During the 5-year follow-up, the patient remained disease-free after cryoablation, with relatively normal immune function.CONCLUSION Herein, we for the first time report the treatment of liver metastasis from SPT of the pancreas using cryoablation plus interventional embolization, which could be a promising alternative therapy for pancreatic SPT liver metastasis.展开更多
Objective To study the causes of hypertension in solid tumors during surgery, and to explore the nursing methods of irreversible electroporation ablation therapy. Method choice in our hospital of malignant tumor patie...Objective To study the causes of hypertension in solid tumors during surgery, and to explore the nursing methods of irreversible electroporation ablation therapy. Method choice in our hospital of malignant tumor patients included in the study, these people are implemented irreversible electroporation ablation treatment, time is 2015.7 to 2021.6, a total of 30 cases, for these people before treatment and treatment after the relevant index data comparison, mainly including blood pressure level data and catecholamine levels. Results: After the implementation of the electric shock, the blood pressure of these people in the observation group increased rapidly, and 10 people had intraoperative hypertension, accounting for 66.7%. This ratio was compared to the other group (P <0.05). After receiving antihypertensive treatment (the treatment regimen was nicardipine and phenentolamine), the people with hypertension were relieved and their blood pressure became low, and the postoperative blood pressure in the two groups was not statistically significant, (P> 0.05). Second, after the end of the electric shock work, through the analysis of the immediate test results, finally found that in this group, with preoperative data, the peripheral blood adrenaline, dopamine levels are very different, the difference has statistical significance (P <0.05), and before and after treatment data show that in norepinephrine levels have no statistical significance (P> 0.05). Conclusion: patients in the irreversible electroporation ablation, intraoperative hypertension is likely to occur due to various factors, so we must pay attention to the intraoperative continuous monitoring of these patients, but also through the scientific care plan for treatment, in this way can well control the risk of hypertension encephalopathy, promote its physical recovery.展开更多
Vγ9Vδ2 T cells are promising candidates for cellular tumor immunotherapy.Due to their HLA-independent mode of action,allogeneic Vγ9Vδ2 T cells can be considered for clinical application.To apply allogeneic Vγ9Vδ...Vγ9Vδ2 T cells are promising candidates for cellular tumor immunotherapy.Due to their HLA-independent mode of action,allogeneic Vγ9Vδ2 T cells can be considered for clinical application.To apply allogeneic Vγ9Vδ2 T cells in adoptive immunotherapy,the methodology used to obtain adequate cell numbers with optimal effector function in vitro needs to be optimized,and clinical safety and efficacy also need to be proven.Therefore,we developed a novel formula to improve the expansion of peripheralγδT cells from healthy donors.Then,we used a humanized mouse model to validate the therapeutic efficacy of expandedγδT cells in vivo;furthermore,the expandedγδT cells were adoptively transferred into late-stage liver and lung cancer patients.We found that the expanded cells possessed significantly improved immune effector functions,including proliferation,differentiation,and cancer cell killing,both in vitro and in the humanized mouse model.Furthermore,a phase I clinical trial in 132 late-stage cancer patients with a total of 414 cell infusions unequivocally validated the clinical safety of allogeneic Vγ9Vδ2 T cells.Among these 132 patients,8 liver cancer patients and 10 lung cancer patients who received≥5 cell infusions showed greatly prolonged survival,which preliminarily verified the efficacy of allogeneic Vγ9Vδ2 T-cell therapy.Our clinical studies underscore the safety and efficacy of allogeneic Vγ9Vδ2 T-cell immunotherapy,which will inspire further clinical investigations and eventually benefit cancer patients.展开更多
Immunotherapy has limited efficacy against locally advanced pancreatic cancer(LAPC)due to the presence of an immunosuppressive microenvironment(ISM).Irreversible electroporation(IRE)can not only induce immunogenic cel...Immunotherapy has limited efficacy against locally advanced pancreatic cancer(LAPC)due to the presence of an immunosuppressive microenvironment(ISM).Irreversible electroporation(IRE)can not only induce immunogenic cell death,but also alleviate immunosuppression.This study aimed to investigate the antitumor efficacy of IRE plus allogeneicγδT cells in LAPC patients.A total of 62 patients who met the eligibility criteria were enrolled in this trial,then randomized into two groups(A:n=30 and B:n=32).All patients received IRE therapy and after receiving IRE,the group A patients received at least two cycles ofγδT-cell infusion as one course continuously.Group A patients had better survival than group B patients(median OS:14.5 months vs.11 months;median PFS:11 months vs.8.5 months).Moreover,the group A patients treated with multiple courses ofγδT-cell infusion had longer OS(17 months)than those who received a single course(13.5 months).IRE combined with allogeneicγδT-cell infusion is a promising strategy to enhance the antitumor efficacy in LAPC patients,yielding extended survival benefits.展开更多
BACKGROUND Irreversible electroporation(IRE)represents an innovative localized technique for tumor ablation,possessing the capacity to activate the immune response of the host.However,this method alone is inadequate t...BACKGROUND Irreversible electroporation(IRE)represents an innovative localized technique for tumor ablation,possessing the capacity to activate the immune response of the host.However,this method alone is inadequate to halt cancer progression,necessitating the integration of additional strategies to achieve effective immuno-therapy.AIM To investigate the effects and underlying mechanisms of antitumor immunity derived from the synergistic application of IRE and anti-programmed cell death protein 1(PD-1)therapy within a murine model of hepatocellular carcinoma.METHODS C57BL-6 mice with tumor growth were divided into four separate cohorts:Control group;IRE group;Anti-PD-1 group;And IRE+anti-PD-1 group.The infiltration levels of T,B,and natural killer cells within the tumors,as well as the plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-β),were evaluated.Real-time polymerase chain reaction was utilized to quantify the expression of cluster of differentiation(CD)8(a marker indicative of CD8+T cells)in the tumor specimens of the mice at various temporal intervals.Tumor growth trajectories were charted.RESULTS The results indicated that the IRE+anti-PD-1 group exhibited significantly heightened percentages of T lymphocyte infiltration,particularly CD4+and CD8+T cells,when compared to the control cohort.Additionally,this group displayed increased infiltration of natural killer and B cells,augmented cytokine levels,and elevated CD8 messenger RNA expression.A marked decrease in tumor volume was noted in the IRE+anti-PD-1 group,indicating enhanced therapeutic efficacy.CONCLUSION The combined application of IRE and checkpoint blockade elicits an antitumor immune response,leading to a more substantial reduction in tumor volume and improved therapeutic outcomes,thereby establishing a novel avenue for the ablation and immunotherapy of hepatocellular carcinoma.展开更多
Objective： To identify the underlying mechanisms of the protective effects of Dingxin Recipe （定心方, DXR）, a Chinese compound prescription that has been used clinically in China for more than 20 years, on ischemia...Objective： To identify the underlying mechanisms of the protective effects of Dingxin Recipe （定心方, DXR）, a Chinese compound prescription that has been used clinically in China for more than 20 years, on ischemia/reperfusion （I/R）-induced arrhythmias in rat model. Methods： A total of 30 rats were randomly divided into three groups： sham group, I/R group, and DXR-pretreated I/R （DXR-I/R） group. Rats in the DXR- I/R group were intragastrically administrated with DXR （12.5 g/kg per day） for consecutive 7 days, while rats in the sham and I/R groups were administrated with normal saline. Arrhythmias were introduced by I/R and electrocardiograms （ECG） were recorded. Two-dimensional （2-D） polyacrylamide gel electrophoresis and matrix- assisted laser desorption ionization time-of-flight mass spectrometry （MALDI-TOF MS） were used to identify differentially expressed proteins. Immunohistochemistry, real-time quantitative polymerase chain reaction （RQ- PCR）, Western blot, and enzyme-linked immunosorbent assay （ELISA） were performed to analyze proteins obtained in the above experiments. Results： DXR significantly reduced the incidence and mean duration of ventricular tachycardia and ventricular fibrillation and dramatically decreased the mortality, as well as arrhythmia score, compared with those of the I/R group. Among successfully identified proteins, prohibitin （PHB） and heart fatty acid binding protein （hFABP） were up-regulated in DXR-pretreated I/R rats compared with those of the I/R rats. In addition, compared with the I/R group, the level of glutathione （GSH） was elevated accompanied by reduced expressions of interleukin-6 （IL-6） and neutrophil infiltration in I/R rats with DXR pretreatment. Conclusions： DXR could alleviate I/R-induced arrhythmias, which might be related to increased expression of PHB. The enhanced expression of PHB prevented against the depletion of GSH and consequently inhibited apoptosis of cardiomyocytes. Furthermore, up-regulation of PHB might ameliorate I/R-induced cell death and leakage of hFABP by suppressing neutrophil infiltration and IL-6 expressions.展开更多
Wang Shu-he, or Wang Xi, was anoutstanding physician from Gaoping （Gaoping of Shanxi Province; another saying is Ji＇ning of Shandong Province） of Western Jin Dynasty who lived around the 3rd CeIltUi3T His major con...Wang Shu-he, or Wang Xi, was anoutstanding physician from Gaoping （Gaoping of Shanxi Province; another saying is Ji＇ning of Shandong Province） of Western Jin Dynasty who lived around the 3rd CeIltUi3T His major contribution was the 10 w）lumes of Mai.展开更多
基金Science and Technology Program of Guangzhou,No.202102010077International Science Foundation of Guangzhou Fuda Cancer Hospital,No.Y2020-ZD-03.
文摘BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective immunotherapy.AIM To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer models.METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 group.Tumor-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were evaluated.Real-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of time.The growth curves of tumors were drawn.RESULTS The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control group.Additionally,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA expression.Tumor volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic effect.CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer.
文摘AIM: To retrospectively assess the effect of comprehensive cryosurgery (ablation of intraand extra-hepatic tumors) plus dendritic cell-cytokine-induced killer cell immunotherapy in metastatic hepatocellular cancer. METHODS: We divided 45 patients into cryo-immunotherapy (21 patients), cryotherapy (n = 12), immunotherapy (n = 5) and untreated (n = 7) groups. Overall survival (OS) after diagnosis of metastatic hepatocellular cancer was assessed after an 8-year follow-up. RESULTS: Median OS was higher following cryo-immu-notherapy (32 mo) or cryotherapy (17.5 mo; P < 0.05) than in the untreated group (3 mo) and was higher in the cryo-immunotherapy group than in the cryotherapy group (P < 0.05). In the cryo-immunotherapy group, median OS was higher after multiple treatments (36.5 mo) than after a single treatment (21 mo; P < 0.05). CONCLUSION: Cryotherapy and, especially, cryoimmunotherapy significantly increased OS in metastatic hepatocellular cancer patients. Multiple cryo-immunotherapy was associated with a better prognosis than single cryo-immunotherapy.
基金The Science-development Grand of Science-technology Department of Guangdong Province Grand of Health Department of Guangdong Province
文摘AIM: To study the therapeutic value of combination o cryosurgery and 125iodine seed implantation for locally advanced pancreatic cancer. METHODS: Forty-nine patients with locally advanced pancreatic cancer (males 36, females 13), with a median age of 59 years, were enrolled in the study. Twelve patients had liver metastases. In all cases the tumors were considered unresectable after a comprehensive evaluation. Patients were treated with cryosurgery, which was performed intraoperatively or percutaneously unde guidance of ultrasound and/or computed tomography (CT), and 125iodine seed implantation, which was performed during cryosurgery or post-cryosurgery under guidance of ultrasound and/or CT. A few patients received regional celiac artery chemotherapy. RESULTS: Thirteen patients received intraoperative cryosurgery and 36 received percutaneous cryosurgery Some patients underwent repeat cryosurgery. 125Iodine seed implantation was performed during freezing procedure in 35 patients and 3-9 d after cryosurgery in 14 cases. Twenty patients, 10 of whom had hepaticmetastases received regional chemotherapy. At 3 mo after therapy, CT was repeated to estimate tumor response to therapy. Most patients showed varying degrees of tumor necrosis. Complete response (CR) of tumor was seen in 20.4% patients, partial response (PR), in 38.8%, stable disease (SD), in 30.6%, and progressive disease (PD), in 10.2%. Adverse effects associated with cryosurgery included upper abdomen pain and increased serum amylase. Acute pancreatitis was seen in 6 patients one of whom developed severe pancreatitis. All adverse effects were controlled by medical management with no poor outcome. There was no therapy-related mortality. During a median follow-up of 18 mo (range of 5-40), the median survival was 16.2 mo, with 26 patients (53.1%) surviving for 12 mo or more. Overall, the 6-, 12-, 24- and 36-mo survival rates were 94.9%, 63.1%, 22.8% and 9.5%, respectively. Eight patients had survival of 24 mo or more. The patient with the longest survival (40 mo) is still living without evidence of tumor recurrence. CONCLUSION: Cryosurgery, which is far less invasive than conventional pancreatic resection, and is associated with a low rate of adverse effects, should be the treatment of choice for patients with locally advanced pancreatic cancer. 125Iodine seed implantation can destroy the residual surviving cancer cells after cryosurgery. Hence, a combination of both modalities has a complementary effect.
文摘Pancreatic carcinoma is a common cancer of the digestive system with a poor prognosis. It is characterized by insidious onset, rapid progression, a high degree of malignancy and early metastasis. Atpresent, radical surgery is considered the only curative option for treatment, however, the majority of patients with pancreatic cancer are diagnosed too late to undergo surgery. The sensitivity of pancreatic cancer to chemotherapy or radiotherapy is also poor. As a result, there is no standard treatment for patients with advanced pancreatic cancer. Cryoablation is generally considered to be an effective palliative treatment for pancreatic cancer. It has the advantages of minimal invasion and improved targeting, and is potentially safe with less pain to the patients. It is especially suitable in patients with unresectable pancreatic cancer. However, our initial findings suggest that cryotherapy combined with 125-iodine seed implantation, immunotherapy or various other treatments for advanced pancreatic cancer can improve survival in patients with unresectable or metastatic pancreatic cancer. Although these findings require further in-depth study, the initial results are encouraging. This paper reviews the safety and efficacy of cryoablation, including combined approaches, in the treatment of pancreatic cancer.
基金Supported by The Hai Zhu District Scientific and Technologica Plan,No.2010-Y-27"Comprehensive Research of Pancreati Cancer Cryotherapy",Guangzhou,China
文摘AIM:To investigate the therapeutic effect of radical treatment and palliative treatment in stage Ⅳ pancreatic cancer patients.METHODS:81 patients were enrolled in the study.Radical treatment was performed on 51 patients,while 30 patients were put under palliative treatment.The procedural safety and interval survival for stage Ⅳ pancreatic cancer(IS-Ⅳ) was assessed by almost 2.5 years of follow-ups.The IS-Ⅳ of patients under the two kinds of treatment,and the effects of treatment timing and frequency on IS-Ⅳ,were compared.RESULTS:The IS-Ⅳ of patients who received radical treatment was significantly longer than those who received palliative treatment(P < 0.001).The IS-Ⅳ of patients who received delayed radical or palliative treatment was longer than those who received accordingly timely treatment(P = 0.0034 and 0.0415,respectively).Multiple treatments can play an important role in improving the IS-Ⅳ of patients who received radical treatment(P = 0.0389),but not for those who received palliative treatment(P = 0.99).CONCLUSION:The effect of radical treatment was significantly more obvious than that of palliative treatment,and multiple radical treatments may contribute more to patients than a single radical treatment.
基金Supported by International Science Foundation of Affiliated Fuda Cancer Hospital,Jinan University,No.Y2018-ZD-01.
文摘BACKGROUND Locally advanced pancreatic cancer(LAPC)is a common malignant digestive system tumor that ranks as the fourth leading cause of cancer-related death in the world.The prognosis of LAPC is poor even after standard treatment.Irreversible electroporation(IRE)is a novel ablative strategy for LAPC.Several studies have confirmed the safety of IRE.To date,no prospective studies have been performed to investigate the therapeutic efficacy of conventional gemcitabine(GEM)plus concurrent IRE.AIM To compare the therapeutic efficacy between conventional GEM plus concurrent IRE and GEM alone for LAPC.METHODS From February 2016 to September 2017,a total of 68 LAPC patients were treated with GEM plus concurrent IRE(n=33)or GEM alone(n=35).Overall survival(OS),progression free survival(PFS),and procedure-related complications were compared between the two groups.Multivariate analyses were performed to identify any prognostic factors.RESULTS There were no treatment-related deaths.The technical success rate of IRE ablation was 100%.The GEM+IRE group had a significantly longer OS from the time of diagnosis of LAPC(19.8 mo vs 9.3 mo,P<0.0001)than the GEM alone group.The GEM+IRE group had a significantly longer PFS(8.3 mo vs 4.7 mo,P<0.0001)than the GEM alone group.Tumor volume less than 37 cm3 and GEM plus concurrent IRE were identified as significant favorable factors for both the OS and PFS.CONCLUSION Gemcitabine plus concurrent IRE is an effective treatment for patients with LAPC.
文摘BACKGROUND We present the case of a 72-year-old female patient with gallbladder cancer(GBC)who developed in situ recurrence and liver metastases 9 mo after irreversible electroporation ablation and oral tegafur(a fluoropyrimidine derivative)chemotherapy,which failed to control the progression of the disease.The patient further developed metastases in the lymph nodes around the head of the pancreas.The patient had severe anemia,requiring weekly blood transfusions.The gallbladder tumor invaded the descending part of the duodenum,causing intestinal leakage and hepatic colonic adhesion.CASE SUMMARY The patient refused other treatments and began daily hydrogen inhalation therapy.After 1 mo of treatment,the gallbladder and liver tumors continued to progress,and intestinal obstruction occurred.After continuous hydrogen therapy and symptomatic treatments including gastrointestinal decompression and intravenous nutrition support,the intestinal obstruction was gradually relieved.Three months after hydrogen therapy,the metastases in the abdominal cavity gradually reduced in size,her anemia and hypoalbuminemia were corrected,lymphocyte and tumor marker levels returned to normal,and the patient was able to resume normal life.CONCLUSION This is the first report of an efficacy and safety study about hydrogen therapy in patient with metastatic GBC and a critical general condition,who has remained stable for more than 4 months.
文摘BACKGROUND Pancreatic cancer has a poor prognosis;40%–50% of patients have liver metastases at the time of initial diagnosis and only 15%–20% undergo surgical resection. Irreversible electroporation(IRE) is a new, non-thermal local ablation method for solid tumors, which can induce cell membrane permeabilization,resulting in unrecoverable nanoscale perforation and apoptotic cell death without damaging the structural components of tissues.CASE SUMMARY We report the case of a 66-year-old female patient with liver metastasis from pancreatic cancer with a pathological diagnosis of poorly differentiated adenocarcinoma. Carbohydrate antigen 19-9 was elevated to 420.3 U/m L.Computed tomography showed a pancreas mass of 2.7 cm × 2.5 cm and single liver metastasis of 1.4 cm × 1.1 cm in the S6 area. The patient underwent IRE and arterial infusion chemotherapy and received tegafur. The therapeutic effect of the combination treatment has been evaluated as complete response. To date, the patient has survived for > 12 mo and is receiving tegafur as maintenance therapy(at the time this case report was written).CONCLUSION IRE plus arterial infusion chemotherapy and tegafur may be synergistic,providing a reference for treating liver metastasis from pancreatic cancer.
基金supported by grants from the Development Project of the National Major Scientific Research Instrument(82027803)National Natural Science Foundation of China(81971623 and 82171937)Key Project of the Natural Science Foundation of Zhejiang Province(LZ20H180001)。
文摘Introduction Liver cancer remains a global health challenge,and its incidence is increasing worldwide.It is estimated that by 2025,more than one million individuals will be affected by liver cancer annually[1,2].In recent years,ablation has become a widely accepted treatment option for patients with primary and secondary liver malignancies[3].The commonly used ablation method for liver cancer is thermal ablation,including radiofrequency ablation.
文摘BACKGROUND Bronchial cysts are congenital malformations usually located in the mediastinum,and intrapulmonary localization is very rare.Cryoablation is a novel therapeutic approach that promotes tumor necrosis and stimulates anti-tumor immune responses.CASE SUMMARY This article reports a case of a 68-year-old male patient who was diagnosed with an intrapulmonary bronchogenic cyst by computed tomography examination and pathology,and the patient subsequently underwent cryoablation therapy and achieved complete response with after 3 months of follow-up.CONCLUSION Intrapulmonary bronchogenic cysts are very rare,cryoablation therapy is feasible,safe,and effective for intrapulmonary bronchial cysts.
基金Supported by International Science Foundation of Guangzhou Fuda Cancer Hospital,No.Y2022-MS-02.
文摘BACKGROUND Irreversible electroporation(IRE)is a novel non-thermal ablation technology for unresectable tumors.Hypertension and tachycardia usually occur during the IRE.To date,there has been little explanation about this phenomenon.AIM To investigate the reasons of hypertension and tachycardia and appropriate preventive measures.METHODS IRE was performed under general anesthesia and neuromuscular blockade.Systolic blood pressures,diastolic blood pressures,heart rate,and the distance of the electrode from abdominal aorta and adrenal gland during IRE were recorded.RESULTS All of 78 patients underwent 96 IRE sessions,44(56.4%)patients occurred hypertension when the electrode was close to the abdominal aorta(<2.0 cm).The median systolic blood pressures and diastolic blood pressures was 194 and 108 mmHg.Furthermore,11(14.1%)patients occurred tachycardia when the electrode was close to the adrenal gland(<1.3 cm).The median heart rate of patients with tachycardia was 114 beats per minute.Furthermore,hypertension and tachycardia can be prevented with nicardipine and esmolol before treatment.CONCLUSION Intraoperative hypertension and tachycardia occur because electrodes close to the abdominal aorta(<2.0 cm)and adrenal glands(<1.3 cm),which can be prevented by preoperative treatment of vasoactive drugs.
基金Supported by The National Natural Science Foundation of China,No.81273814
文摘AIM:To study the effect and tolerance of intraperitoneal perfusion of cytokine-induced killer(CIK) cells in combination with local radio frequency(RF) hyperthermia in patients with advanced primary hepatocellular carcinoma(HCC).METHODS:Patients with advanced primary HCC were included in this study.CIK cells were perfused intraperitoneal twice a week,using 3.2 × 10 9 to 3.6 × 10 9 cells each session.Local RF hyperthermia was performed 2 h after intraperitoneal perfusion.Following an interval of one month,the next course of treatment was administered.Patients received treatment until disease progression.Tumor size,immune indices(CD3 +,CD4 +,CD3 + CD8 +,CD3 + CD56 +),alpha-fetoprotein(AFP) level,abdominal circumference and adverse events were recorded.Time to progression and overall survival(OS) were calculated.RESULTS:From June 2010 to July 2011,31 patients diagnosed with advanced primary HCC received intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia in our study.Patients received an average of 4.2 ± 0.6 treatment courses(range,1-8 courses).Patients were followed up for 8.3 ± 0.7 mo(range,2-12 mo).Following combination treatment,CD4 +,CD3 + CD8 + and CD3 + CD56 + cells increased from 35.78% ± 3.51%,24.61% ± 4.19% and 5.94% ± 0.87% to 45.83% ± 2.48%(P = 0.016),39.67% ± 3.38%(P = 0.008) and 10.72% ± 0.67%(P = 0.001),respectively.AFP decreased from 167.67 ± 22.44 to 99.89 ± 22.05 ng/mL(P = 0.001) and abdominal circumference decreased from 97.50 ± 3.45 cm to 87.17 ± 4.40 cm(P = 0.002).The disease control rate was 67.7%.The most common adverse events were low fever and slight abdominal erubescence,which resolved without treatment.The median time to progression was 6.1 mo.The 3-,6-and 9-mo and 1-year survival rates were 93.5%,77.4%,41.9% and 17.4%,respectively.The median OS was 8.5 mo.CONCLUSION:Intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia is safe,can efficiently improve immunological status,and may prolong survival in HCC patients.
文摘AIM:To determine the safety and efficacy of efficacy of percutaneous cryosurgery for treatment of patients with hepatic colorectal metastases. METHODS: Three hundred and twenty-six patients with non-resectable hepatic colorectal metastases underwent percutaneous cryosurgery under the guidance of ultrasound or CT. Follow-up was 1 mo after cryosurgery and then every 4 mo thereafter by assessment of tumor markers, liver ultrasonography, and abdominal CT. For lesions suspicious of recurrence, a liver biopsy was performed and subsequent repeat cryosurgery was given if histology was positive for cancer. RESULTS: All patients underwent a total of 526 procedures of cryosurgery. There were 151 patients who underwent repeat procedures of cryosurgery for recurrent tumors in the liver and extrahepatic places. At 3 mo after cryosurgery, carcinoembryonic antigen (CEA) levels in 197 (77.5%) patients who had elevated markers before cryosurgery decreased to normal range. Among 280 patients who received CT following-up, cryotreated lesions showed complete response (CR) in 41 patients (14.6%), partial response (PR) in 115 patients (41.1%), stable disease (SD) in 68 patients (24.3%) and progressive disease (PD) in 56 patients (20%). The recurrence rate was 47.2% during a median follow-up of 32 mo (range, 7-61). Sixty one percent of the recurrences were seen in liver only and 13.9% in liver and extrahepatic areas. The recurrence rate at cryotreated site was only 6.4% for all cases. During a median follow-up of 36 mo (7-62 mo), the median survival of all patient was 29 mo (range 3-62 mo). Overall survival was 78%, 62%, 41%, 34% and 23% at 1, 2, 3, 4 and 5 years, respectively, after the treatment. Patients with tumor size less than 3 cm, tumor in right lobe of liver, lower CEA levels (< 100 ng/dL) and post- cryosurgery TACE had higher survival rate. There wasno significant difference in terms of survival based on the number of tumors, pre-cryosurgery chemotherapy and the timing of the development of metastases (synchronous vs metachronous). Patients who underwent 2-3 procedures of cryosurgery had increased survival compared to patients who received cryosurgery once only. There was no intra-cryosurgery mortality. Main adverse effects, such as hepatic bleeding, cryoshock, biliary fistula, liver failure, renal insufficiency and liver abscess were only observed in 0.3%-1.5% of patients. CONCLUSION:Percutaneous cryosurgery was a safe modality for hepatic colorectal metastases. Rather than an alternative to resection, this technique should be regarded as a complement to hepatectomy and as an additional means of achieving tumor eradication when total excision is not possible.
文摘BACKGROUND Solid pseudopapillary tumor(SPT) of the pancreas is a rare pancreatic tumor and 10% to 15% of cases are associated with metastasis. Cryoablation is a new method that can induce tumor necrosis, and treatment of tumors by cryoablation can cause anti-tumor immune responses.CASE SUMMARY A 16-year-old woman with SPT of the pancreas developed liver metastases 5.3 years after complete resection of the primary pancreatic tumor. She was admitted with chief complaints of abdominal pain in the upper abdomen and a weight loss of approximately 5 kg over 4 mo. Carbohydrate antigen(CA) 125,carcinoembryonic antigen, and CA 199 were normal. An abdominal computed tomography scan found multiple nodules in the right lobe of the liver that measured approximately 13.5 cm × 10.8 cm × 21.4 cm. Immunohistochemical staining results showed that CD10 and CD56 were positive, and the patient was diagnosed with SPT of the pancreas with liver metastasis. The patient underwent percutaneous cryoablation and interventional embolization. During the 5-year follow-up, the patient remained disease-free after cryoablation, with relatively normal immune function.CONCLUSION Herein, we for the first time report the treatment of liver metastasis from SPT of the pancreas using cryoablation plus interventional embolization, which could be a promising alternative therapy for pancreatic SPT liver metastasis.
文摘Objective To study the causes of hypertension in solid tumors during surgery, and to explore the nursing methods of irreversible electroporation ablation therapy. Method choice in our hospital of malignant tumor patients included in the study, these people are implemented irreversible electroporation ablation treatment, time is 2015.7 to 2021.6, a total of 30 cases, for these people before treatment and treatment after the relevant index data comparison, mainly including blood pressure level data and catecholamine levels. Results: After the implementation of the electric shock, the blood pressure of these people in the observation group increased rapidly, and 10 people had intraoperative hypertension, accounting for 66.7%. This ratio was compared to the other group (P <0.05). After receiving antihypertensive treatment (the treatment regimen was nicardipine and phenentolamine), the people with hypertension were relieved and their blood pressure became low, and the postoperative blood pressure in the two groups was not statistically significant, (P> 0.05). Second, after the end of the electric shock work, through the analysis of the immediate test results, finally found that in this group, with preoperative data, the peripheral blood adrenaline, dopamine levels are very different, the difference has statistical significance (P <0.05), and before and after treatment data show that in norepinephrine levels have no statistical significance (P> 0.05). Conclusion: patients in the irreversible electroporation ablation, intraoperative hypertension is likely to occur due to various factors, so we must pay attention to the intraoperative continuous monitoring of these patients, but also through the scientific care plan for treatment, in this way can well control the risk of hypertension encephalopathy, promote its physical recovery.
基金This work was supported by the Key Program of the National Natural Science Foundation of China(31830021)Major International Joint Research Program of China(31420103901)+12 种基金“111 project”(B16021)Scientific and Technological Plan of Guangdong Province(201704KW010)(Z.Y.)Fundamental Research Funds for the Central Universities,Natural Science Foundation of Guangdong Province,China(2020A1515010132)(Y.W.)General Research Fund,Research Grants Council of Hong Kong(17122519,17121214,17115015,and 17126317)(W.T.)Hong Kong SAR,ChinaThis work was also partially supported by the National Natural Science Foundation of China(31570898)the Natural Science Foundation of Guangdong Province,China(2016A030313112)(Z.X.)grant Ka 502/19-1 from the German Research Council(Deutsche Forschungsgemeinschaft)the Cluster of Excellence ExC 306“Inflammation-at-Interfaces”(Deutsche Forschungsgemeinschaft)(D.K.)Y.H.was supported by the China Postdoctoral Science Foundation(2017M622898)Y.X.was supported by the Postdoctoral Fund of the First Affiliated Hospital of Jinan University(809008)L.K.was supported by a long-term fellowship from the German Academic Exchange Service(DAAD)C.P.is the recipient of a grant from the Erich und Gertrud Roggenbruck Foundation.
文摘Vγ9Vδ2 T cells are promising candidates for cellular tumor immunotherapy.Due to their HLA-independent mode of action,allogeneic Vγ9Vδ2 T cells can be considered for clinical application.To apply allogeneic Vγ9Vδ2 T cells in adoptive immunotherapy,the methodology used to obtain adequate cell numbers with optimal effector function in vitro needs to be optimized,and clinical safety and efficacy also need to be proven.Therefore,we developed a novel formula to improve the expansion of peripheralγδT cells from healthy donors.Then,we used a humanized mouse model to validate the therapeutic efficacy of expandedγδT cells in vivo;furthermore,the expandedγδT cells were adoptively transferred into late-stage liver and lung cancer patients.We found that the expanded cells possessed significantly improved immune effector functions,including proliferation,differentiation,and cancer cell killing,both in vitro and in the humanized mouse model.Furthermore,a phase I clinical trial in 132 late-stage cancer patients with a total of 414 cell infusions unequivocally validated the clinical safety of allogeneic Vγ9Vδ2 T cells.Among these 132 patients,8 liver cancer patients and 10 lung cancer patients who received≥5 cell infusions showed greatly prolonged survival,which preliminarily verified the efficacy of allogeneic Vγ9Vδ2 T-cell therapy.Our clinical studies underscore the safety and efficacy of allogeneic Vγ9Vδ2 T-cell immunotherapy,which will inspire further clinical investigations and eventually benefit cancer patients.
基金supported by grants from the National Natural Science Foundation of China(no.81971895)the NSFC-Guangdong Joint Foundation of China(no.U1601225)the Guangdong Provincial Key Laboratory Construction Project of China(no.2017B030314034).
文摘Immunotherapy has limited efficacy against locally advanced pancreatic cancer(LAPC)due to the presence of an immunosuppressive microenvironment(ISM).Irreversible electroporation(IRE)can not only induce immunogenic cell death,but also alleviate immunosuppression.This study aimed to investigate the antitumor efficacy of IRE plus allogeneicγδT cells in LAPC patients.A total of 62 patients who met the eligibility criteria were enrolled in this trial,then randomized into two groups(A:n=30 and B:n=32).All patients received IRE therapy and after receiving IRE,the group A patients received at least two cycles ofγδT-cell infusion as one course continuously.Group A patients had better survival than group B patients(median OS:14.5 months vs.11 months;median PFS:11 months vs.8.5 months).Moreover,the group A patients treated with multiple courses ofγδT-cell infusion had longer OS(17 months)than those who received a single course(13.5 months).IRE combined with allogeneicγδT-cell infusion is a promising strategy to enhance the antitumor efficacy in LAPC patients,yielding extended survival benefits.
基金Supported by the Science and Technology Program of Guangzhou,No.202201020024.
文摘BACKGROUND Irreversible electroporation(IRE)represents an innovative localized technique for tumor ablation,possessing the capacity to activate the immune response of the host.However,this method alone is inadequate to halt cancer progression,necessitating the integration of additional strategies to achieve effective immuno-therapy.AIM To investigate the effects and underlying mechanisms of antitumor immunity derived from the synergistic application of IRE and anti-programmed cell death protein 1(PD-1)therapy within a murine model of hepatocellular carcinoma.METHODS C57BL-6 mice with tumor growth were divided into four separate cohorts:Control group;IRE group;Anti-PD-1 group;And IRE+anti-PD-1 group.The infiltration levels of T,B,and natural killer cells within the tumors,as well as the plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-β),were evaluated.Real-time polymerase chain reaction was utilized to quantify the expression of cluster of differentiation(CD)8(a marker indicative of CD8+T cells)in the tumor specimens of the mice at various temporal intervals.Tumor growth trajectories were charted.RESULTS The results indicated that the IRE+anti-PD-1 group exhibited significantly heightened percentages of T lymphocyte infiltration,particularly CD4+and CD8+T cells,when compared to the control cohort.Additionally,this group displayed increased infiltration of natural killer and B cells,augmented cytokine levels,and elevated CD8 messenger RNA expression.A marked decrease in tumor volume was noted in the IRE+anti-PD-1 group,indicating enhanced therapeutic efficacy.CONCLUSION The combined application of IRE and checkpoint blockade elicits an antitumor immune response,leading to a more substantial reduction in tumor volume and improved therapeutic outcomes,thereby establishing a novel avenue for the ablation and immunotherapy of hepatocellular carcinoma.
基金Supported by the National Natural Science Foundation of China (No.30572435 and No.81072776)Baiyun District Science and Technology Program(No.2010-KZ-39)
文摘Objective： To identify the underlying mechanisms of the protective effects of Dingxin Recipe （定心方, DXR）, a Chinese compound prescription that has been used clinically in China for more than 20 years, on ischemia/reperfusion （I/R）-induced arrhythmias in rat model. Methods： A total of 30 rats were randomly divided into three groups： sham group, I/R group, and DXR-pretreated I/R （DXR-I/R） group. Rats in the DXR- I/R group were intragastrically administrated with DXR （12.5 g/kg per day） for consecutive 7 days, while rats in the sham and I/R groups were administrated with normal saline. Arrhythmias were introduced by I/R and electrocardiograms （ECG） were recorded. Two-dimensional （2-D） polyacrylamide gel electrophoresis and matrix- assisted laser desorption ionization time-of-flight mass spectrometry （MALDI-TOF MS） were used to identify differentially expressed proteins. Immunohistochemistry, real-time quantitative polymerase chain reaction （RQ- PCR）, Western blot, and enzyme-linked immunosorbent assay （ELISA） were performed to analyze proteins obtained in the above experiments. Results： DXR significantly reduced the incidence and mean duration of ventricular tachycardia and ventricular fibrillation and dramatically decreased the mortality, as well as arrhythmia score, compared with those of the I/R group. Among successfully identified proteins, prohibitin （PHB） and heart fatty acid binding protein （hFABP） were up-regulated in DXR-pretreated I/R rats compared with those of the I/R rats. In addition, compared with the I/R group, the level of glutathione （GSH） was elevated accompanied by reduced expressions of interleukin-6 （IL-6） and neutrophil infiltration in I/R rats with DXR pretreatment. Conclusions： DXR could alleviate I/R-induced arrhythmias, which might be related to increased expression of PHB. The enhanced expression of PHB prevented against the depletion of GSH and consequently inhibited apoptosis of cardiomyocytes. Furthermore, up-regulation of PHB might ameliorate I/R-induced cell death and leakage of hFABP by suppressing neutrophil infiltration and IL-6 expressions.
文摘Wang Shu-he, or Wang Xi, was anoutstanding physician from Gaoping （Gaoping of Shanxi Province; another saying is Ji＇ning of Shandong Province） of Western Jin Dynasty who lived around the 3rd CeIltUi3T His major contribution was the 10 w）lumes of Mai.
