Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oncologic and functional outcome was reviewed in 21 consecutive patients who underwent limb salvaging surgery for periacetabular sarcoma using a new surgical approach and different types of reconstruction between 1972 and 1990. Histologic diagnosis in 86% showed osteosarcomas, chondrosarcomas, and Ewing's tumors. Age ranged from 10.0 to 61.5 years (mean age, 32.9 years). The resection margin was wide in 15 patients but marginal in 2 patients and intralesional in 4 patients. All of the latter patients died of their disease. In all cases where 3-dimensional imaging was used, wide resection margins could be achieved, whereas this was possible only in 50% of the cases with conventional imaging techniques. Seven patients died of their disease 3 to 15 months after surgery, 2 died of chemotherapy induced sepsis, and 2 patients died perioperatively. At followup, 8 patients had no evidence of disease (mean, 57.6 months; range, 12-190 months), and 2 patients were alive with disease. Fourteen patients could be observed for at least 12 months (mean, 41.1 months) and were functionally evaluated according to Enneking's criteria. If extensive resection was necessary, the best results were found if the defect had been reconstructed with a custom made prosthesis. The results were only satisfactory after implantation of saddle prostheses and poor with allografts or when no reconstruction of the bone defect was done.
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PMID:Limb salvage in periacetabular sarcomas: review of 21 consecutive cases. 889 49

The objective in this paper is to describe the severity and outcome of arterial occlusion complicating treatment of women with gynecologic cancer. A series of six patients who underwent amputation were identified. Acute arterial occlusions were seen in three patients. One patient suffered extensive thrombosis of the hand and wrist resulting in amputation 3 weeks after cytoreductive surgery and chemotherapy for Fallopian tube cancer. She had a history of pulmonary embolism and deep-vein thrombosis. This patient was thought to have thrombophilia. One elderly patient with known arteriosclerosis developed sepsis following radical deep excision and groin dissection for vulvar cancer and lost two digits presumably due to microemboli. One patient developed thrombosis of the femoral artery on the second day following cytoreductive surgery for ovarian cancer. She responded to anticoagulation therapy; however, necrosis remained in portions of the heel and toes. Three patients underwent amputation of a lower extremity when they developed chronic arterial insufficiency after pelvic radiotherapy. The patients were irradiated at the ages of 28, 30, and 35 years for cervix cancer in two patients and a low-grade retroperitoneal sarcoma in one patient. Two received neutron beam therapy and one received conventional photon beam therapy. All three had extensive late radiation morbidity to the bladder and rectum and had multiple prior surgeries. The amputations occurred at the ages of 48, 48, and 55 due to accelerated arteriosclerosis. Two patients died as a result of this complication. Acute and chronic arterial occlusions are rare yet dramatic complications of therapy for gynecologic cancer. This series illustrates the predisposing factors, presentation, and management of these unusual events.
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PMID:Arterial occlusion complicating treatment of gynecologic cancer: a case series. 889 66

Tumor necrosis factor (TNF) induces rapid necrosis in a variety of experimental neoplasms. However, its clinical application is limited by life-threatening systemic toxicity. Isolated limb perfusion (ILP) enables administration of large doses of TNF and cytotoxic drugs directly to the affected limb, avoiding systemic toxicity. We describe our experience in 20 consecutive patients (10 with melanoma and 10 with soft tissue sarcoma) treated with high-dose TNF and melphalan via ILP. ILP was performed via the external iliac (10 cases), femoral (2), popliteal (5) or brachial (3) vessels. Patients received 3-4 mg TNF to an upper, and 1-1.5 mg/kg to a lower extremity. Isolation efficiency was determined by injection of radiolabelled albumin. The procedure was successful in all 20 patients. Local complications included wound infection in 6 cases and hematoma in 2. 1 patient developed sepsis secondary to extensive necrosis of a large, secondarily infected tumor. The first 6 patients who underwent high-flow perfusion experienced systemic side-effects, mainly hypotension. These side-effects were eliminated when low-flow perfusion was introduced. The response rate was 100%. In the sarcoma group, 5/10 had complete response, and 5 partial response. Amputation or mutilating surgery was avoided in 9/10. Of the 10 with melanoma, 7 had complete, and 3 partial response. We conclude that administration of TNF via ILP is a safe and effective modality for treating advanced neoplasms of the limbs.
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PMID:[Isolated limb perfusion with tumor necrosis factor for malignancies of the limbs]. 894 May 15

Eleven patients, 13 to 76 (mean, 40) years of age, had granulocytic sarcoma of the female genital tract (FGT) (ovary, seven cases; vagina, three cases; cervix, one case). In nine cases, the FGT involvement was the initial clinical presentation of the disease, and in the other two cases, the FGT involvement was discovered during a relapse of acute myeloid leukemia. The tumors ranged from 0.5 to 14 (mean, 7.5) cm in greatest dimension. Two ovarian tumors were bilateral, and three were green. Microscopic examination revealed a predominantly diffuse pattern of growth, but cords and pseudoacinar spaces were also present focally in several cases. Sclerosis was seen in five tumors and was prominent in one. Prominent myeloid differentiation was readily recognizable on routinely stained sections in three cases, whereas the neoplastic cells in the other cases were primitive with only rare eosinophilic myelocytes. All 11 tumors were positive for chloroacetate esterase, nine of nine were strongly and diffusely positive for lysozyme, eight of eight for myeloperoxidase, seven of seven for CD68, and six of six for CD43. Examination of bone marrow or peripheral blood performed after the diagnosis of FGT involvement revealed acute myeloid leukemia in three of five cases. Two of these patients died of disease, 1 and 16 months after the initial diagnosis, and the third, who received chemotherapy, is alive and free of disease 8 months after the initial diagnosis. One of the two patients with negative bone marrow had recurrent granulocytic sarcoma 30 months after diagnosis and died of sepsis 1 month later; no residual disease was noted at autopsy. The other patient is alive and free of disease 18 months after the diagnosis. One of the four remaining patients with primary FGT involvement who did not have a bone marrow biopsy died of leukemia 24 months later; no follow-up information is available for the other three patients. One of the two patients with a prior diagnosis of acute myeloid leukemia was alive with disease 26 months later; follow-up is not available for the second patient. The diagnosis was often difficult in these cases, the most common problem being distinction from malignant lymphoma, but carcinoma, granulosa cell tumor, and, rarely, other tumors were considered. Immunohistochemical and enzyme histochemical staining were useful in establishing the diagnosis, although suspicion of the diagnosis on examination of routinely stained sections was of paramount importance.
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PMID:Granulocytic sarcoma of the female genital tract: a clinicopathologic study of 11 cases. 933 Dec 87

Docetaxel and ifosfamide have shown significant activity against a variety of solid tumours. This prompted a phase I trial on the combination of these drugs. This phase I study was performed to assess the feasibility of the combination, to determine the maximum tolerated dose (MTD) and the side effects, and to propose a safe schedule for further phase II studies. A total of 34 patients with a histologically confirmed solid tumour, who were not pretreated with taxanes or ifosfamide and who had received no more than one line of chemotherapy for advanced disease were entered into the study. Treatment consisted of docetaxel given as a 1-h infusion followed by ifosfamide as a 24-h infusion (schedule A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel doses ranged from 60 to 85 mg m(-2) and ifosfamide doses from 2.5 to 5.0 g m(-2). Granulocytopenia grade 3 and 4 were common (89%), short lasting and ifosfamide dose dependent. Febrile neutropenia and sepsis occurred in 17% and 2% of courses respectively. Non-haematological toxicities were mild to moderate and included alopecia, nausea, vomiting, mucositis, diarrhoea, sensory neuropathy, skin and nail toxicity and oedema. There did not appear to be any pharmacokinetic interaction between docetaxel and ifosfamide. One complete response (CR) (soft tissue sarcoma) and two partial responses (PRs) were documented. A dose of 75 mg m(-2) of docetaxel combined with 5.0 g m(-2) ifosfamide appeared to be manageable. Schedule A was advocated for further treatment.
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PMID:Phase I study on docetaxel and ifosfamide in patients with advanced solid tumours. 1064 11

Docetaxel is a new antimicrotubule agent that has been shown to be active against a variety of solid tumors. Ifosfamide is an alkylating drug that has demonstrated activity against non-small cell lung cancer, testicular cancer, breast cancer, and soft tissue sarcoma. This phase I study of the combination of these drugs was performed to assess the feasibility of using the two agents together, to determine the maximum tolerated dose and the side effects, and to propose a safe schedule for further phase II studies. Thirty-four patients with histologically confirmed solid tumors who had not been treated previously with taxanes or ifosfamide and who had received no more than one line of chemotherapy for advanced disease were entered into the study. Treatment consisted of docetaxel given as a 1-hour infusion followed by ifosfamide as a 24-hour infusion (schedule A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel doses ranged from 60 to 85 mg/m2 and ifosfamide doses from 2.5 to 5.0 g/m2. Grades 3 and 4 granulocytopenia were observed in 89% of courses and appeared to be of short duration and related to the ifosfamide dose. Febrile neutropenia and sepsis occurred in 17% and 2% of courses, respectively. Severe anemia and thrombocytopenia were uncommon. Nonhematologic toxicities were mild to moderate, and included alopecia, nausea, vomiting, mucositis, diarrhea, sensory neuropathy, skin and nail toxicity, hypersensitivity reactions, and edema. Schedule B appeared to induce more gastrointestinal toxicity than schedule A. One complete response in soft tissue sarcoma and two partial responses, one in cancer of unknown primary and the other in non-small cell lung cancer, were documented. The dose-limiting toxicity for schedule A was neutropenic fever at a dose of 85 mg/m2 docetaxel and 5 g/m2 ifosfamide. The dose-limiting toxicity for schedule B was neutropenic fever at a dose of 75 mg/m2 docetaxel and 4 g/m2 ifosfamide. A dose of 75 mg/m2 docetaxel combined with 5 g/m2 ifosfamide according to schedule A can be recommended for further studies.
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PMID:Docetaxel and ifosfamide in patients with advanced solid tumors: results of a phase I study. 953 8

Isolated granulocytic sarcoma (GS) has rarely been reported in a patient who underwent allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML). We report here a patient who developed an isolated GS after achieving hematologic and cytogenetic remission by donor lymphocyte infusion for the relapse of CML following BMT. The size of GS was slightly decreased after local irradiation of 1,500 cGy without further systemic chemotherapy or immunotherapy. He remained in hematologic and cytogenetic remission without systemic relapse of CML for 8 months. Thereafter, he died of sepsis. The appropriate treatment of GS and impact of its occurrence on prognosis following allogeneic BMT has yet to be determined.
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PMID:Granulocytic sarcoma as isolated extramedullary relapse after donor lymphocyte infusion in a patient with CML who relapsed after allogeneic bone marrow transplantation: a case report. 974 51

The development of pharmacological approaches for preventing the loss of muscle proteins would be extremely valuable for cachectic patients. For example, severe wasting in cancer patients correlates with a reduced efficacy of chemotherapy and radiotherapy. Pentoxifylline (PTX) is a very inexpensive xanthine derivative, which is widely used in humans as a haemorheological agent, and inhibits tumor necrosis factor transcription. We have shown here that a daily administration of PTX prevents muscle atrophy and suppresses increased protein breakdown in Yoshida sarcoma-bearing rats by inhibiting the activation of a nonlysosomal, Ca(2+)-independent proteolytic pathway. PTX blocked the ubiquitin pathway, apparently by suppressing the enhanced expression of ubiquitin, the 14-kDa ubiquitin conjugating enzyme E2, and the C2 20S proteasome subunit in muscle from cancer rats. The 19S complex and 11S regulator associate with the 20S proteasome and regulate its peptidase activities. The mRNA levels for the ATPase subunit MSS1 of the 19S complex increased in cancer cachexia, in contrast with mRNAs of other regulatory subunits. This adaptation was suppressed by PTX, suggesting that the drug inhibited the activation of the 26S proteasome. This is the first demonstration of a pharmacological manipulation of the ubiquitin-proteasome pathway in cachexia with a drug which is well tolerated in humans. Overall, the data suggest that PTX can prevent muscle wasting in situations where tumor necrosis factor production rises, including cancer, sepsis, AIDS and trauma.
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PMID:Manipulation of the ubiquitin-proteasome pathway in cachexia: pentoxifylline suppresses the activation of 20S and 26S proteasomes in muscles from tumor-bearing rats. 1036 54

This report summarizes our experience with the combination of mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) for patients with gynecological sarcomas. We reviewed the records of all patients who had received the MAID regimen for a gynecological sarcoma between 1993 and 2000. The MAID regimen was administered intravenously every 4 weeks in the hospital as follows: (1) mesna 1500 mg/m2/day x 4 days; (2) doxorubicin 15 mg/m2/day x 3 days; (3) ifosfamide 1500 mg/m2/day x 3 days; (4) dacarbazine 250 mg/m2/day x 3 days. The results of treatment with MAID were disappointing. Overall, the response rate was 9% with one complete response and one partial response (both in patients with uterine leiomyosarcoma). We did not observe any responses among the patients with carcinosarcomas of either ovarian or uterine origin. The median progression-free interval and survival were 11 months and 29 months, respectively. This regimen was associated with substantial toxicity (including a death from neutropenic sepsis) as well as high cost and inconvenience due to the requirement for inpatient administration. Although our study contains a limited number of patients with a variety of gynecological sarcomas, our review has led us to discontinue using MAID. It remains to be established if any combination chemotherapy regimen is better than single agent treatment.
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PMID:Mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) chemotherapy for gynecological sarcomas. 1244 53

The systemic side effects of isolated limb perfusion (ILP) with rhTNF alpha and melphalan are characterised by the induction of a systemic inflammatory response syndrome (SIRS). Procalcitonin (PCT), a serum marker of bacterial sepsis, was investigated with respect to its role in SIRS after TNF-ILP. Serum-PCT was analysed in 24 patients (12 male, 12 female), who treated by ILP for regionally metastasized melanoma (n = 8) or locally advanced soft tissue sarcoma (n = 16). Serum samples were analysed pre- and intraoperatively, and at defined intervals after reperfusion of the limb. In addition to PCT, serum IL-6 and IL-8 were analysed in 11 patients. PCT was significantly elevated over baseline after ILP with a maximum between 8 and 36 hours (p < 0.001). Even 96 hours after reperfusion, PCT was still significantly elevated as compared to baseline levels (p = 0.005). There was no correlation to the systemic leakage rate during the perfusion. IL-6 and IL-8 were also significantly increased after ILP (p = 0.001), but the maximum peaks of both cytokines were reached much earlier than for PCT (IL-8 max. at 1 hour and IL-6 max. at 4 hours after reperfusion). Serum procalcitonin is induced as part of the specific SIRS after ILP with rhTNF alpha and melphalan. It may be induced directly by rhTNF alpha or by different cytokines, as serum peaks of IL-6 and IL-8 are reached well before the peak of PCT. Determination of PCT prior to and after ILP with TNF might be useful to assess patients at risk of developing hyperdynamic shock.
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PMID:[Procalcitonin as marker of systemic inflammatory reaction after isolated extremity perfusion]. 1451 84


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