A 23-year-old male presented with a three-week-history of crampy abdominal pain and melaena.Colonoscopy revealed a friable mass filling the entire lumen of the cecum;histologically,it was classified as perivascular ep...A 23-year-old male presented with a three-week-history of crampy abdominal pain and melaena.Colonoscopy revealed a friable mass filling the entire lumen of the cecum;histologically,it was classified as perivascular epithelioid cell tumor(PEComa).An magnetic resonance imaging scan showed,in addition to the primary tumor,two large mesenteric lymph node metastases and four metastatic lesions in the liver.The patient underwent right hemicolectomy and left hemihepatectomy combined with wedge resections of metastases in the right lobe of the liver,the resection status was R0.Subsequently,the patient was treated with sirolimus.After 4 mo of adjuvant mammalian target of rapamycin inhibition he developed two new liver metastases and a local pelvic recurrence.The visible tumor formations were again excised surgically,this time the resection status was R2 with regard to the pelvic recurrence.The patient was treated with 12 cycles of doxorubicin and ifosfamide under which the disease was stable for 9 mo.The clinical course was then determined by rapid tumor growth in the pelvic cavity.Second line chemotherapy with gemcitabine and docetaxel was ineffective,and the patient died 23 mo after the onset of disease.This case report adds evidence that,in malignant PEComa,the mainstay of treatment is curative surgery.If not achievable,the effects of adjuvant or palliative chemotherapy are unpredictable.展开更多
Objective: A pilot study to test the feasibility andefficacy of high dose IFO and standard dose ADR andDTIC with G-CSF support in treatment of advanced softtissue sarc0ma (STS). Methods: 35 patients of no priorchemoth...Objective: A pilot study to test the feasibility andefficacy of high dose IFO and standard dose ADR andDTIC with G-CSF support in treatment of advanced softtissue sarc0ma (STS). Methods: 35 patients of no priorchemotherapy with methetatic or locally advancedunresecfable STS were treated by this regimen, including 18rhabdomyosarromas, 7 malignant fibrous histiocytomas, 2neurofibrosarcomas, 2 fibrosarcomas, 2 leiomyosarcomas, 2synoviosarcomas, and 2 malignant hemangiopericytomas.IFO dose was 2 g/m2 on day 1-5 (with mesna uroprotection),ADR 50mg/m2 on day 1 and DTIC 250 mg/m2 on day 1-5.G-CSF (2 μg/d) was administered on day 6 to 15 or untilrecovery of leukocytes account. The cycles were repeatedevery 3 weeks. Result: There were five complete responses(CR including pathologic CR) and eleven partial responsesfor overall 46% objective response rate- Most responseswere observed within two cycles. The median survival was15 months. Following CR, two patients remain disease freeat 45 and 28 months, respectively. 6/120 (5%) cycles werecomplicated by grade IV neutropenia, 46/120 (38%) cycleshad grade III neutropenia. No patients had treatmentrelated deaths. Nonhematologic toxicity consistedpredominantly of anorexia and vomiting. No other severetoxicities were seen, especially no severe cardiotoxicity.Concluson: This regimen is well tolerated and hassubstantial benefits for patients with advanced soft tissuesarcomas.展开更多
<div style="text-align:justify;"> <span style="font-family:Verdana;">Ovarian carcinosarcoma composed of high-grade carcinoma and sarcoma is an extremely rare neoplasm and typically occu...<div style="text-align:justify;"> <span style="font-family:Verdana;">Ovarian carcinosarcoma composed of high-grade carcinoma and sarcoma is an extremely rare neoplasm and typically occurs in postmenopausal women aged over 60 years. A 73-year-old female, gravida three para three, presented to our hospital with right lower abdominal pain. Right pelvic solid tumor with ascites was detected on pelvic ultrasound examination. She underwent hysterectomy, bilateral salpingo-oophorectomy and partial omentectomy, but the tumor had invaded to the right ureter, and some fragile tumor could not be taken (sub-optimal surgery). On the imprint and ascitic cytology specimens during operation, atypical cells suggestive of adenocarcinoma and spindle atypical cells with immunocytochemically vimentin positive were found. The resected tumor was histopathologically carcinosarcoma consisted of serous adenocarcinoma, chondrosarcoma and fibrosarcoma. Immunohistochemical analysis revealed that adenocarcinoma cells were positive for AE1/AE3 and fibrosarcoma cells stained with vimentin. The final diagnosis was the right ovarian carcinosarcoma (stage pT3CNxMx). Microsatellite instability was stable and BRCA1/2 mutations could not be found in the carcinosarcoma cells. The patient was given four cycles of chemotherapy with paclitaxel, carboplatin and bevacizumab regimen, and thereafter she was treated with the ifosfamide and cisplatin because of slight elevation of serum CA125.</span> </div>展开更多
Intraperitoneal carcinomatosis(PC)may occur with several tumor entities.The prognosis of patients suffering from PC is usually poor.Present treatment depends on the cancer entity and includes systemic chemotherapy,rad...Intraperitoneal carcinomatosis(PC)may occur with several tumor entities.The prognosis of patients suffering from PC is usually poor.Present treatment depends on the cancer entity and includes systemic chemotherapy,radiation therapy,hormonal therapy and surgical resection.Only few patients may also benefit from hyperthermic intraperitoneal chemotherapy with a complete tumor remission.These therapies are often accompanied by severe systemic side-effects.One approach to reduce side effects is to target chemotherapeutic agents to the tumor with carrier devices.Promising experimental results have been achieved using drug-eluting beads(DEBs).A series of in vitro and in vitro experiments has been conducted to determine the suitability of their extravascular use.These encapsulation devices were able to harbor CYP2B1producing cells and to shield them from the hosts immune system when injected intratumorally.In this way ifosfamide-which is transformed into its active metabolites by CYP2B1-could be successfully targeted into pancreatic tumor growths.Furthermore DEBs can be used to target chemotherapeutics into the abdominal cavity for treatment of PC.If CYP2B1 producing cells are proven to be save for usage in man and if local toxic effects of chemotherapeutics can be controlled,DEBs will become promising tools in compartmentbased anticancer treatment.展开更多
BACKGROUND Ovarian undifferentiated carcinomas are significantly rare and have an aggressive clinical course.Surgical resection is the only curative treatment in early-stage ovarian undifferentiated carcinomas that ha...BACKGROUND Ovarian undifferentiated carcinomas are significantly rare and have an aggressive clinical course.Surgical resection is the only curative treatment in early-stage ovarian undifferentiated carcinomas that has a favorable prognosis.In case of recurrent and metastatic disease,palliative chemotherapy is the only available treatment.However,the effectiveness of standard chemotherapy regimen is not well-known,specifically in the case of extra-ovarian spread.We report an ovarian undifferentiated carcinoma of recurrent and inoperable advanced stage that was successfully treated with high-dose combination chemotherapy.CASE SUMMARY A 52-year-old woman presented with a 1-mo history of right lower quadrant and epigastric pain.A computed tomography(CT)scan of the abdomen revealed a multicystic mass with extensive internal necrosis of the right ovary without evidence of metastatic disease.A total hysterectomy with bilateral salpingooophorectomy and omentectomy was performed,but the surgery had a positive resection margin.Pathologically,it was diagnosed as ovarian undifferentiated carcinoma with sarcomatoid change.Although adjuvant chemotherapy was planned,it was delayed for 6 wk because of postoperative recovery,and the patient complained of abdominal pain.A CT scan and positron emission tomography-CT revealed a huge mass with multiple nodules in the pelvic cavity and para-aortic lymph node metastasis.Instead of standard therapy such as paclitaxel and platinum,combined chemotherapy with etoposide,ifosfamide,and cisplatin was administered.The patient experienced no recurrence for 5 years.CONCLUSION This is a case of metastatic ovarian undifferentiated carcinoma with sarcomatoid change that was successfully treated with high-dose combination cytotoxic chemotherapy.展开更多
Oxazaphosphorines,with the most representative members including cyclophosphamide,ifosfamide,and trofosfamide,constitute a class of alkylating agents that have a broad spectrum of anticancer activity against many mali...Oxazaphosphorines,with the most representative members including cyclophosphamide,ifosfamide,and trofosfamide,constitute a class of alkylating agents that have a broad spectrum of anticancer activity against many malignant ailments including both solid tumors such as breast cancer and hematological malignancies such as leukemia and lymphoma.Most oxazaphosphorines are prodrugs that require hepatic cytochrome P450 enzymes to generate active alkylating moieties before manifesting their chemotherapeutic effects.Meanwhile,oxazaphosphorines can also be transformed into non-therapeutic byproducts by various drug-metabolizing enzymes.Clinically,oxazaphosphorines are often administered in combination with other chemotherapeutics in adjuvant treatments.As such,the therapeutic efficacy,off-target toxicity,and unintentional drug–drug interactions of oxazaphosphorines have been long-lasting clinical concerns and heightened focuses of scientific literatures.Recent evidence suggests that xenobiotic receptors may play important roles in regulating the metabolism and clearance of oxazaphosphorines.Drugs as modulators of xenobiotic receptors can affect the therapeutic efficacy,cytotoxicity,and pharmacokinetics of coadministered oxazaphosphorines,providing a new molecular mechanism of drug–drug interactions.Here,we review current advances regarding the influence of xenobiotic receptors,particularly,the constitutive androstane receptor,the pregnane X receptor and the aryl hydrocarbon receptor,on the bioactivation and detoxification of oxazaphosphorines,with a focus on cyclophosphamide and ifosfamide.展开更多
文摘A 23-year-old male presented with a three-week-history of crampy abdominal pain and melaena.Colonoscopy revealed a friable mass filling the entire lumen of the cecum;histologically,it was classified as perivascular epithelioid cell tumor(PEComa).An magnetic resonance imaging scan showed,in addition to the primary tumor,two large mesenteric lymph node metastases and four metastatic lesions in the liver.The patient underwent right hemicolectomy and left hemihepatectomy combined with wedge resections of metastases in the right lobe of the liver,the resection status was R0.Subsequently,the patient was treated with sirolimus.After 4 mo of adjuvant mammalian target of rapamycin inhibition he developed two new liver metastases and a local pelvic recurrence.The visible tumor formations were again excised surgically,this time the resection status was R2 with regard to the pelvic recurrence.The patient was treated with 12 cycles of doxorubicin and ifosfamide under which the disease was stable for 9 mo.The clinical course was then determined by rapid tumor growth in the pelvic cavity.Second line chemotherapy with gemcitabine and docetaxel was ineffective,and the patient died 23 mo after the onset of disease.This case report adds evidence that,in malignant PEComa,the mainstay of treatment is curative surgery.If not achievable,the effects of adjuvant or palliative chemotherapy are unpredictable.
文摘Objective: A pilot study to test the feasibility andefficacy of high dose IFO and standard dose ADR andDTIC with G-CSF support in treatment of advanced softtissue sarc0ma (STS). Methods: 35 patients of no priorchemotherapy with methetatic or locally advancedunresecfable STS were treated by this regimen, including 18rhabdomyosarromas, 7 malignant fibrous histiocytomas, 2neurofibrosarcomas, 2 fibrosarcomas, 2 leiomyosarcomas, 2synoviosarcomas, and 2 malignant hemangiopericytomas.IFO dose was 2 g/m2 on day 1-5 (with mesna uroprotection),ADR 50mg/m2 on day 1 and DTIC 250 mg/m2 on day 1-5.G-CSF (2 μg/d) was administered on day 6 to 15 or untilrecovery of leukocytes account. The cycles were repeatedevery 3 weeks. Result: There were five complete responses(CR including pathologic CR) and eleven partial responsesfor overall 46% objective response rate- Most responseswere observed within two cycles. The median survival was15 months. Following CR, two patients remain disease freeat 45 and 28 months, respectively. 6/120 (5%) cycles werecomplicated by grade IV neutropenia, 46/120 (38%) cycleshad grade III neutropenia. No patients had treatmentrelated deaths. Nonhematologic toxicity consistedpredominantly of anorexia and vomiting. No other severetoxicities were seen, especially no severe cardiotoxicity.Concluson: This regimen is well tolerated and hassubstantial benefits for patients with advanced soft tissuesarcomas.
文摘<div style="text-align:justify;"> <span style="font-family:Verdana;">Ovarian carcinosarcoma composed of high-grade carcinoma and sarcoma is an extremely rare neoplasm and typically occurs in postmenopausal women aged over 60 years. A 73-year-old female, gravida three para three, presented to our hospital with right lower abdominal pain. Right pelvic solid tumor with ascites was detected on pelvic ultrasound examination. She underwent hysterectomy, bilateral salpingo-oophorectomy and partial omentectomy, but the tumor had invaded to the right ureter, and some fragile tumor could not be taken (sub-optimal surgery). On the imprint and ascitic cytology specimens during operation, atypical cells suggestive of adenocarcinoma and spindle atypical cells with immunocytochemically vimentin positive were found. The resected tumor was histopathologically carcinosarcoma consisted of serous adenocarcinoma, chondrosarcoma and fibrosarcoma. Immunohistochemical analysis revealed that adenocarcinoma cells were positive for AE1/AE3 and fibrosarcoma cells stained with vimentin. The final diagnosis was the right ovarian carcinosarcoma (stage pT3CNxMx). Microsatellite instability was stable and BRCA1/2 mutations could not be found in the carcinosarcoma cells. The patient was given four cycles of chemotherapy with paclitaxel, carboplatin and bevacizumab regimen, and thereafter she was treated with the ifosfamide and cisplatin because of slight elevation of serum CA125.</span> </div>
文摘Intraperitoneal carcinomatosis(PC)may occur with several tumor entities.The prognosis of patients suffering from PC is usually poor.Present treatment depends on the cancer entity and includes systemic chemotherapy,radiation therapy,hormonal therapy and surgical resection.Only few patients may also benefit from hyperthermic intraperitoneal chemotherapy with a complete tumor remission.These therapies are often accompanied by severe systemic side-effects.One approach to reduce side effects is to target chemotherapeutic agents to the tumor with carrier devices.Promising experimental results have been achieved using drug-eluting beads(DEBs).A series of in vitro and in vitro experiments has been conducted to determine the suitability of their extravascular use.These encapsulation devices were able to harbor CYP2B1producing cells and to shield them from the hosts immune system when injected intratumorally.In this way ifosfamide-which is transformed into its active metabolites by CYP2B1-could be successfully targeted into pancreatic tumor growths.Furthermore DEBs can be used to target chemotherapeutics into the abdominal cavity for treatment of PC.If CYP2B1 producing cells are proven to be save for usage in man and if local toxic effects of chemotherapeutics can be controlled,DEBs will become promising tools in compartmentbased anticancer treatment.
基金the National Research Foundation of Korea,funded by the Ministry of Science,ICT,and Future Planning,No.NRF-2017R1D1A1B04031741and grants from the Chosun University Hospital,No.2019.
文摘BACKGROUND Ovarian undifferentiated carcinomas are significantly rare and have an aggressive clinical course.Surgical resection is the only curative treatment in early-stage ovarian undifferentiated carcinomas that has a favorable prognosis.In case of recurrent and metastatic disease,palliative chemotherapy is the only available treatment.However,the effectiveness of standard chemotherapy regimen is not well-known,specifically in the case of extra-ovarian spread.We report an ovarian undifferentiated carcinoma of recurrent and inoperable advanced stage that was successfully treated with high-dose combination chemotherapy.CASE SUMMARY A 52-year-old woman presented with a 1-mo history of right lower quadrant and epigastric pain.A computed tomography(CT)scan of the abdomen revealed a multicystic mass with extensive internal necrosis of the right ovary without evidence of metastatic disease.A total hysterectomy with bilateral salpingooophorectomy and omentectomy was performed,but the surgery had a positive resection margin.Pathologically,it was diagnosed as ovarian undifferentiated carcinoma with sarcomatoid change.Although adjuvant chemotherapy was planned,it was delayed for 6 wk because of postoperative recovery,and the patient complained of abdominal pain.A CT scan and positron emission tomography-CT revealed a huge mass with multiple nodules in the pelvic cavity and para-aortic lymph node metastasis.Instead of standard therapy such as paclitaxel and platinum,combined chemotherapy with etoposide,ifosfamide,and cisplatin was administered.The patient experienced no recurrence for 5 years.CONCLUSION This is a case of metastatic ovarian undifferentiated carcinoma with sarcomatoid change that was successfully treated with high-dose combination cytotoxic chemotherapy.
基金supported in part by the National Institute of Health Grant(R01,DK061652)a Seed Grant from University of Maryland Greenebaum Cancer Center。
文摘Oxazaphosphorines,with the most representative members including cyclophosphamide,ifosfamide,and trofosfamide,constitute a class of alkylating agents that have a broad spectrum of anticancer activity against many malignant ailments including both solid tumors such as breast cancer and hematological malignancies such as leukemia and lymphoma.Most oxazaphosphorines are prodrugs that require hepatic cytochrome P450 enzymes to generate active alkylating moieties before manifesting their chemotherapeutic effects.Meanwhile,oxazaphosphorines can also be transformed into non-therapeutic byproducts by various drug-metabolizing enzymes.Clinically,oxazaphosphorines are often administered in combination with other chemotherapeutics in adjuvant treatments.As such,the therapeutic efficacy,off-target toxicity,and unintentional drug–drug interactions of oxazaphosphorines have been long-lasting clinical concerns and heightened focuses of scientific literatures.Recent evidence suggests that xenobiotic receptors may play important roles in regulating the metabolism and clearance of oxazaphosphorines.Drugs as modulators of xenobiotic receptors can affect the therapeutic efficacy,cytotoxicity,and pharmacokinetics of coadministered oxazaphosphorines,providing a new molecular mechanism of drug–drug interactions.Here,we review current advances regarding the influence of xenobiotic receptors,particularly,the constitutive androstane receptor,the pregnane X receptor and the aryl hydrocarbon receptor,on the bioactivation and detoxification of oxazaphosphorines,with a focus on cyclophosphamide and ifosfamide.