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Biomedical subjects

F O Stephens

Publications and source records attributed to F O Stephens.

At least 37 records · Page 2Linked to original sources
PubMed1991

Fibrosarcoma of metacarpal treated by combined therapy and immediate reconstruction with vascularized bone graft.

Fibrosarcomas of the bones of the hand are very rare entities. We present a case of low-grade fibrosarcoma of the left third metacarpal that was successfully treated by preoperative intraarterial chemotherapy, wide local excision, and immediate reconstruction with a vascularized bone graft from the ipsilateral radius. Excellent hand function has been preserved and the patient remains free of recurrence 5 years after presentation.

Adolescent↗
PubMed1991

IIB osteosarcoma. Current management, local control, and survival statistics--the Australian experience.

Current management of osteosarcoma at the authors' institution involves intraarterial induction chemotherapy using intermittent cycles of cisplatin and doxorubicin (Adriamycin), surgical resection with limb-sparing wherever possible, and adjuvant systemic chemotherapy (high-dose methotrexate with retrieval and doxorubicin). Twenty cases treated in this way between May 1983 and May 1989 are reviewed. There were 18 Stage IIB osteosarcomas and two Stage IIB malignant fibrous histiocytomas. Chemotherapeutic effect was evaluated in the resected tumors. There was little correlation between the clinical response to the induction chemotherapy and cell necrosis present in the resected tumor mass. Wide resection margins were achieved in 17 cases, a minimal margin in two, and a contaminated margin in one. Radiotherapy was used in these three cases where resection margin was in doubt. There were two local recurrences in these three cases. Four patients have died of their disease, and there was one treatment-related death. Overall probability of survival in this group of 20 patients has been expressed by the Kaplan-Meier method as 58%.

Adolescent↗
PubMed1990

Intraarterial induction chemotherapy in locally advanced stage III breast cancer.

Five-year results are reported on 27 patients with locally advanced breast cancer treated by intraarterial induction chemotherapy followed by radiotherapy and/or surgery with subsequent adjuvant chemotherapy. The cyclic infusion chemotherapy regimen was given over 3 to 6 weeks using Adriamycin (doxorubicin), 5-fluorouracil (5-FU), vincristine, and methotrexate in daily rotation. Regional and systemic side effects were minimal and temporary except in two patients in whom some skin discoloration has remained. Local tumor control and 5-year cures depended on two important factors: whether follow-up mastectomy was used after initial local tumor regression; and whether the carcinoma was classified as "inflammatory" with pathologic evidence of tumor invasion of dermal lymphatics. Of 16 patients with noninflammatory carcinoma treated by chemotherapy, radiotherapy, and mastectomy local tumor eradication was achieved in 15 and 5-year apparent cure in 11. Of six patients with noninflammatory carcinoma treated with chemotherapy and radiotherapy but no mastectomy 5-year local control was achieved in only three and 5-year apparent cure in three. Of five patients with pathologic inflammatory carcinoma local tumor control was achieved in only one and only this one patient has been a 5-year survivor apparently tumor-free.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Developments in surgical oncology: induction (neoadjuvant) chemotherapy--the state of the art.

The three established modalities for treatment of cancer are operative surgery, radiotherapy and chemotherapy. In the past, patients have been referred to clinics where experts in the appropriate discipline have usually advised management by one or other of the three modalities. In recent years it has become apparent that for some cancers in which good results have not been forthcoming by one therapeutic modality alone, improvements may well be made by integrating management using two or three forms of treatment, in a planned approach. Management of localized cancers in which a surgical operation is likely to play a major part has traditionally been carried out by surgeons. However, operative surgery alone may not provide optimal care so that surgical oncology has developed as a discipline often embracing combined treatment with either chemotherapy or radiotherapy or both. In managing advanced but localized cancers for which a surgical operation alone is unlikely to produce tumour eradication (or for which tumour eradication can only be achieved with a mutilating operation such as amputation) it has become increasingly recognized that reduction of tumour size and viability by using chemotherapy first may render many tumours more susceptible to total eradication by subsequent radiotherapy and/or surgical operation. Such treatment is often referred to as 'induction' or 'neo-adjuvant' chemotherapy. This paper summarizes the principles of use of induction chemotherapy with integrated follow-up radiotherapy and/or surgical operation.

Antineoplastic Agents↗
PubMed1990

Indications for surgical or radiological placement of cannulas for intra-arterial induction chemotherapy.

Intra-arterial chemotherapy achieves a higher concentration and increased total dose of drugs to a locally advanced cancer. This principle is increasingly being applied for pretreatment of advanced or aggressive localised tumours to make them more curable by subsequent radiotherapy. This is sometimes called "neo-adjuvant" chemotherapy but better called INDUCTION chemotherapy (Stephens 1989).

Antineoplastic Agents↗
PubMed1988

SPECT evaluation of arterial perfusion in regional chemotherapy.

Simultaneous emission and transmission tomography was performed after the injection of [99mTc]MAA in 30 patients undergoing intra-arterial chemotherapy to nonhepatic sites to determine the accuracy of catheter placement. The transmission and emission data were reconstructed in transverse, and optionally, coronal and sagittal planes. The correlation of the emission scan with the reconstructed transmission data allowed accurate anatomical localization of the infusate distribution. In seven patients, catheter placement resulted in perfusion to nontumor sites, and hence required repositioning. MAA accumulation was seen in the lungs of all patients, regardless of tumor site, indicating arterio-venous shunting of the MAA. The degree of uptake in the lungs was quantified from planar anterior/posterior thorax images in terms of injected dose in ten patients, with values of 5-50% of injected dose present in the lungs. The technique provides a noninvasive means of accurately determining regional perfusion of chemotherapeutic agents delivered intra-arterially.

Adult↗
PubMed1987

Regional chemotherapy with the use of cisplatin and doxorubicin as primary treatment for advanced sarcomas in shoulder, pelvis, and thigh.

Eight patients who had large sarcomas in the hip, thigh, or shoulder girdle have been described. Three had osteogenic sarcomas, and one each had Ewing's sarcoma, biphasic synovial sarcoma, pleomorphic liposarcoma, undifferentiated spindling sarcoma, and malignant fibrous histiocytoma. All eight tumors showed evidence of regression after intraarterial infusion of cisplatin and Adriamycin (doxorubicin) given over 48 hours at 3-week intervals, for a total of between three and seven courses. Tru-cut needle biopsy specimens of five of the lesions were normal after chemotherapy. However, after resection of the regressed fibrotic tumor in seven of the patients, four contained foci of probably viable malignant cells. These cell foci were intraosseous in three cases and in the wall of a cyst in one case. In the remaining case, tumor in the distribution of the infused artery regressed, but tumor in a region supplied by an artery that was not infused continued to enlarge. In one patient with osteogenic sarcoma in the pelvis, despite a good response to intraarterial chemotherapy that was followed by surgical resection and radiotherapy, tumor recurred in an adjacent area in tissues supplied by an artery not infused. A hindquarter amputation subsequently was required. With the exception of the two cases in which adequate tumor arterial infusion was not achieved, local primary tumor control was accomplished by intraarterial infusion chemotherapy followed by local resection or radiotherapy and local resection in all patients. Four patients are well without evidence of residual or metastatic sarcoma 3.5 years after presentation in the case of an osteogenic sarcoma of shoulder, 2.5 years after presentation in the case of a large pleomorphic liposarcoma of thigh and groin, 20 months after presentation in the case of lower-thigh malignant fibrous histiocytoma, and 1 year after presentation in a child with an osteogenic sarcoma of lower femur.

Adolescent↗
PubMed1987

Treatment of advanced and inaccessible sarcomas with continuous intra-arterial chemotherapy prior to definitive surgery or radiotherapy--a possible alternative to amputation or disabling radical surgery.

Four patients with advanced and inaccessible soft tissue sarcomas were treated with a regimen of intra-arterial chemotherapy followed by radiotherapy and/or surgical excision. Two of the patients had advanced sarcomas in the buttock and thigh regions which would otherwise have required hindquarter amputation in one case or disarticulation of the hip in the other case. These sarcomas responded significantly to intra-arterial chemotherapy to the extent that subsequent local surgery was effective in eradicating the residual tumours. No viable tumour cells were found in the resected specimens. In both patients amputation was avoided and local tumour eradication was achieved. In the other two patients, advanced and non-resectable sarcomas in the head were first treated with a similar regimen of intra-arterial chemotherapy. In both cases the tumours regressed in size prior to administration of local radiotherapy. After completion of chemotherapy and radiotherapy no viable tumour cells were detected in either lesion. In one case (originally a very extensive sarcoma of the jaw in a 5 year old child) a residual lump was resected but no viable tumour was detected in the resected specimen. These four patients represent our total experience with this plan of management. All responded well and there has been no evidence of local disease recurrence in any of the four patients. One patient (Case 2) did develop pulmonary and bone metastases from which she died 2 years later but the other three patients remain well with no evidence of residual disease, 11 years, 4 years and 20 months after presentation.

Adult↗
PubMed1986

The implantable "Infusaid" infusion pump. The Sydney experience using 5-fluorouracil.

The experience is reported of the use of the totally implantable "Infusaid" infusion pump in the treatment of 14 patients in our combined clinics for metastatic carcinoma in the liver by means of the antimetabolite 5-FU. At the time of this study the more active antimetabolite 5-FUDR was not available. A comparison is made of overseas reports of the use of 5-FUDR in the Infusaid infusion pump with the experience, in our clinic, of the use of 5-FU.

Australia↗
PubMed1986

A preliminary report on the suitability of sheep epidermal squamous cell carcinoma as a solid tumor model in the evaluation of intra-arterial methotrexate administration.

A preliminary study was undertaken to assess the sensitivity of sheep epidermal squamous cell carcinoma, in the head and neck region, to intra-arterial (IA) methotrexate (MTX) infusion. There was an objective tumor response (40-56% regression) in all three IA-infused sheep, whereas tumor progression was observed in all three animals treated intravenously (IV). Regional and systemic side effects were negligible in all cases. Technically, IA drug infusion in the sheep was an improvement on previous small animal models, with no problems related to arterial catheter insertion, blockage, or dislodgement, and tolerable infusion times being of markedly longer duration. The histological differentiation of moderately differentiated stage II lesions improved during therapy irrespective of clinical response, whilst the histology of well-differentiated stage III and IV tumors remained unchanged. Tumor cell cycle stage and ploidy characteristics, as determined by flow cytometric DNA analysis, were little affected by either mode of drug administration. It is concluded that sheep epidermal carcinoma is responsive to IA MTX, and that this animal model is the most appropriate yet utilised to study the comparative effects of IA and IV chemotherapy in the head and neck region.

Animals↗
PubMed1986

Ploidy and proliferative characteristics of sheep epidermal squamous cell carcinoma determined by flow cytometric DNA analysis.

Multiple biopsies from each of 22 primary sheep epidermal squamous cell carcinomas were analysed by flow cytometry to determine the G0/G1 modal DNA content ("ploidy") and cell cycle characteristics within each tumour. Ten of 12 tumours where aneuploidy was present demonstrated uniform intra-tumour aneuploid populations regardless of the site of biopsy. Increasing tumour volume (from stage I/II to stage III/IV lesions) was associated with increased histological variability and ultimate heterogeneity of G0/G1 DNA content, whilst the mean numbers of S phase cells decreased. These features were consistent with the effects of variable tissue hypoxia seen with changes in effective vascularity in developing tumours. Decreasing histological differentiation was associated with an increase in numbers of cells synthesising DNA within 44 biopsies with measurable S phase, and, in stage I/II biopsies, correlated with an increased incidence of aneuploidy.

Animals↗
PubMed1986

Intra-arterial chemotherapy given preoperatively in the management of carcinoma of the stomach.

Intra-arterial chemotherapy has been used preoperatively in treating patients with carcinoma of the stomach. The chemotherapy was given continuously for about one month with gastrectomy planned for three to four weeks after completion of chemotherapy. The agents used were 5-fluorouracil, Adriamycin (doxorubicin hydrochloride) and mitomycin C. The objective was to reduce the size and extent of the disease prior to subsequent surgical resection. Most of the patients had a partial response to the chemotherapy infusion. Two patients had an apparent complete response. For 16 patients who presented with the most advanced lesions, initially considered to be incurable, some palliation was achieved but long term results were not significantly changed. For 17 patients with locally invasive disease which would normally have been treated by gastrectomy alone, with an expectation of about 10 per cent five year survival time, long term results appear to have been significantly improved.

Adult↗
PubMed1984

Preoperative "basal" chemotherapy in the management of cancer of the stomach.

Twenty-seven patients with infiltrating gastric carcinoma received chemotherapy as the first stage in management to reduce tumour extent and viability in preparation for subsequent surgery. All patients who had received no previous treatment for their cancers were included in the study, regardless of the type or extent of the primary gastric lesion; there was no patient selection. In 25 patients chemotherapy was administered by intra-arterial infusion, while in two patients it was given intravenously. Of 21 patients who underwent repeat gastroscopy before surgery, 11 (52%) showed endoscopic improvement. Gastric resection was carried out in 24 of the 27 patients. The perioperative mortality was 11% (three of 27 patients). Of the 27 patients, 14 were initially assessed as having advanced incurable lesions. Only two of these remain well and apparently free of tumour. The other 13 patients were considered to have resectable and potentially curable lesions at the time of referral. Of these, 11 remain well and apparently free of tumour between one and five years after diagnosis; the other two patients in this group died from postoperative complications.

Adult↗
PubMed1983

Pharmacokinetics of intra-arterial chemotherapy.

Advanced or aggressive, but localised, malignancies can often be reduced to more curable proportions by the use of "basal chemotherapy", that is, using chemotherapy as the first mode of treatment, prior to definitive radiotherapy and/or surgical excision. In using anticancer agents, drug combinations, timing and methods of administration are employed which exploit differences between cancer cells and normal tissues and cells. One exploitable difference which is often overlooked is the fact that localised tumour is often supplied with blood by one artery; this can be cannulated so that the agents used can be delivered selectively in high concentration to the region containing the tumour. The advantage in delivering drugs regionally by intra-arterial infusion depends upon the size of the artery infused, the rate of excretion or detoxification of the agents used, the amount of the agent infused entering the tissues - especially from the first circulation, and especially the amount of agent entering the tissues which is biologically active against tumour cells. Taking all these factors into account, mathematical calculations indicated that under the worst possible circumstances infusion of anticancer agents intra-arterially should be at least 1.8 times more effective regionally than intravenous administration. In most situations and with most agents used the advantage would be significantly greater than this. These calculations are supported by evidence in the literature and by observations of a greater regional effect, albeit toxic, of intra-arterial administration of the agents. These effects include more pronounced loss of hair in the region of distribution of the artery infused, and increased skin and mucosal ulceration in the distribution of the artery infused. The disadvantage of using intra-arterial infusion delivery is the need for hospitalisation. Therefore, properly controlled, randomised clinical trials should be conducted to compare clinical results of intra-arterial and intravenous chemotherapy administration.

Antineoplastic Agents↗
PubMed1983

Cell cycle homogeneity in bone marrow samples from different sites: flow cytometric evaluation of multiple samples from sheep.

The distributions of cells in each of the phases of the cell cycle, determined by flow cytometry (FCM), were compared in multiple marrow trephine biopsy samples from 3 sites (both iliac bones and sternum) in 5 sheep. Within any one animal no significant differences could be found between the proportions of cells in the G0/G1, S or G2 + M phases of the cycle from different sites. Differences between animals were detected and these were consistent for any of the sites sampled. We conclude that the proliferative characteristics of marrow cells as determined by FCM in any one animal at one time are comparable at anatomically distinct marrow sites, and that a sample from one site is representative of the whole.

Animals↗