Metastatic liver cancer: no cause for nihilism.
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Biomedical subjects
Publications and source records attributed to F O Stephens.
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Clinical evidence that intra-arterial chemotherapy is more effective in regressing head and neck cancers than equivalent intravenous doses is lacking. Intra-arterial versus intravenous 5-fluorouracil infusion was compared in a naturally occurring, auricular epidermal squamous cell cancer in sheep. Of 18 lesions infused intra-arterially and of 18 infused intravenously with the same dose, 39 and 11%, respectively responded objectively (over 50% regression); mean (S.E.) tumour volume reduction was 37(23) and 18(22)%, respectively. There was a statistically significant difference in the mean tumour response and in numbers of tumours regressing by at least 40% of tumour volume (50% of intra-arterial treated tumours compared with 11% of intravenous treated lesions) after the 16 day total infusion time in favour of intra-arterial treatment. Technically, the intra-arterial route in this model was an improvement on previous small animal models. These findings lend support to the need for continuing clinical study of intra-arterial infusion.
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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.
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%.
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.
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.
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).
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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.
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.
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.
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.
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.
Results of preoperative assessment procedures and subsequent staging laparotomy are evaluated in 32 consecutive patients who presented with extra-abdominal Hodgkin's disease which was not already known to be in an advanced stage. Disease was found in the abdominal cavity of 10 of the 27 patients who presented with disease above the diaphragm, and of two of the five patients in whom disease presented in the inguinal nodes. In patients who initially presented with disease above the diaphragm, the spleen was involved in all 10 cases where abdominal disease was detected. Lymphography was not found to be reliable as a diagnostic aid in doubtful cases. Neither liver nor spleen scans were found to be helpful in assessment of these patients.
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