Induction chemotherapy: to downgrade aggressive cancers to improve curability by surgery and/or radiotherapy.

Induction chemotherapy can be effective in reducing locally advanced or aggressive cancers to improve their prospects of cure by planned follow-up surgery and/or radiotherapy. Systemic (intravenous) delivery is the simplest and most readily available method of administering induction chemotherapy. In some situations, a greater chemotherapy impact can be achieved by delivering a more concentrated dose of effective anti-cancer agents into the arterial blood supply of the cancer. Intra-arterial (i.a.) chemotherapy may or may not be advantageous. To achieve an advantage, the tumour must be fully contained in tissue supplied by one or more arteries that can be effectively cannulated and infused. The cancer must also be one known to respond better to concentrated chemotherapy and the agents used must be effective in the state in which they are delivered. The advantages must outweigh the likely increased risks of regional toxicity and experienced personnel and appropriate specialized equipment must be available to reduce any risk of mistakes made by the more exacting techniques of delivery. In general, systemic chemotherapy is most appropriate in treating tumours without a single artery of supply; when certain agents that are inactive until modified in body tissues (such as cyclophosphamide or DTIC) are to be used; when satisfactory responses can be achieved safely and more easily by systemic delivery; when technical skills and facilities for regional delivery are not available; or when the patient's general health, poor co-operation or long-term prognosis precludes the additional complexity of regional delivery. Intra-arterial infusion may have advantages in treating some locally advanced malignancies in the head and neck, a limb, some invasive stomach cancers and some breast cancers. Primary and some metastatic liver cancers, some pelvic cancers and possibly pancreatic malignancies may also respond well to initial direct chemotherapy infusion and are the subject of several studies. Closed circuit perfusion (Creech-Krementz), chemofiltration infusion and "stop-flow" perfusion (Aigner) and regional limb infusion (Thompson) are more complex techniques aimed at even greater localized initial tissue chemotherapy concentrations over a short time span. These are the subject of ongoing studies in highly specialized units. Their use is designed to achieve tumour responses in treating such malignancies as melanoma, some sarcomas or pancreatic cancer that usually show a poor response to standard systemic chemotherapy.

The rising incidence of breast cancer in women and prostate cancer in men. Dietary influences: a possible preventive role for nature's sex hormone modifiers - the phytoestrogens (review).

The rise in breast cancer in women and prostate cancer in men in Western societies this century, stimulated a search for any possibly reversible aetiological associations common to both. Apart from more citizens living to an older age the most significant associated factor in common is the dietary practices of communities most at risk, particularly a decreasing Western dependence on plant foods with increasing dietary animal fats. Plant foods, especially legumes like soy, contain phytoestrogens (plant oestrogens). They are natural hormone modifying agents and give balance to levels of circulating hormones in both sexes. Animal fats hinder hormone modulation. They retain and slowly release unwanted stored hormones. To reverse this situation Western communities could revert to Asian type diets with high soy content but a more practical approach might be to add concentrated soy or other phytoestrogen product to a fat reduced Western diet.

The increased incidence of cancer of the pancreas: is there a missing dietary factor? Can it be reversed?

There has been a disturbing increase in the incidence of pancreas cancer, especially in Western countries, during the present century. The only well-established aetiological factor of well-documented significance is the greater incidence of this cancer in tobacco smokers of all communities. Otherwise the reason for the increased incidence is not known but the pattern of increase has some similarities to the increased incidence of breast cancer in women and prostate cancer in men in Western communities. There is now well-documented evidence that the increase in breast and prostate cancers is at least partly related to diet. Typical modern Western diets have a low content of the naturally occurring plant hormones, the phyto-oestrogens, that are still plentiful in traditional diets of Asians and other communities with a low incidence of both breast and prostate cancer. This paper presents evidence to support the hypothesis that the increased incidence of pancreas cancer in Western communities may also be related to the relatively low dietary content and protective qualities of the naturally occurring plant hormones and related compounds. This paper presents evidence to support that hypothesis.

Systemic or regional chemotherapy: does it matter and should surgeons be involved?

TNF (tumour necrosis factor) is a new immunological anti-cancer agent which is too toxic for systemic use and relatively ineffective when used alone, but remarkably effective when used in closed circuit perfusion techniques together with other anti-cancer agents. Several studies have shown that when TNF is used with melphalan in closed circuit perfusion treatment for multiple melanoma metastases confined to a limb, a response rate of 80% can be achieved compared to a best response rate of 40% with melphalan alone. These findings confirm the difference in tumour responses which can be achieved with the appropriate use of regional chemotherapy in treatment of locally advanced tumours and the importance of surgical oncologists and vascular radiologists in maintaining and developing skills in integrated regional cancer treatment.

Breast cancer: aetiological factors and associations (a possible protective role of phytoestrogens).

BACKGROUND: In spite of many known and suspected factors associated with the risk of breast cancer there has until recently been no explanation for its continuing increase in women of Western societies over recent decades or why there has not been an equivalent increase in women of most Asian and other less Westernized societies. It has long been suspected that a significant factor has been an increasing change of diet in Western societies from one predominantly vegetarian to one with a high content of meat and dairy products as well as 'refined' foods. Although diet has long been suspected there has otherwise been no real explanation as to the mechanism of the change in incidence of breast cancer. METHODS: A comprehensive literature review has been made of aetiological factors and associations concerning breast cancer to determine whether any consistent trend can explain the rising incidence in Western societies. RESULTS: There are a number of likely contributory factors but there is now accumulating evidence that the single most important difference is that people having a vegetarian diet have a high intake of legumes and other plant foods containing a variety of lignans and isoflavonoids. These appear to have an important role as nature's sex hormone modulators. These agents appear to be biologically active in a number of ways not yet completely understood but they do have both a weak oestrogenic effect and an anti-oestrogenic competitive effect, thus reducing the potential carcinogenic action of prolonged oestrogen activity. A probable additional benefit of such diets could be the role of dietary fibre. CONCLUSIONS: A major problem of Western diets may not be the presence of meat or dairy products in the diet but the absence of desirable ingredients of vegetarian diets, namely dietary fibre and certain plant lignans and isoflavonoids. A modification of diet to include a greater proportion of fibre and soy or other leguminous plant food should be studied. Alternatively addition of more fibre and lignans and especially isoflavonoids to traditional Western diets would seem worthy of serious investigation. Such influences appear to have their greatest impact early in life and therefore could be especially important for girls and young women in Western societies.

Phytoestrogens and prostate cancer: possible preventive role.

Phytoestrogens are biologically active plant compounds with both oestrogenic and antioestrogenic actions, and communities whose diets are rich in phytoestrogens have a lower incidence of prostate cancer. A 66-year-old man took phytoestrogen 160 mg (4 x 40-mg tablets) daily for one week before radical prostatectomy for moderately high-grade adenocarcinoma. The resected specimen showed prominent apoptosis, typical of a response to high-dose oestrogen therapy and suggestive of tumour regression. There were no adverse side effects. Studies of the effects of phytoestrogens in prostate cancer may be warranted.

Newer approaches to regional cancer therapy through tumour immunology: is there a 'breakthrough'?

Eagerly awaited 'breakthroughs' in immunological treatment have in the past been disappointingly unsuccessful in changing the outlook for most patients with otherwise incurable cancers. Many hopeful agents have been studied in therapeutic trials but each in turn has proven to be largely disappointing. One of the latest products of immunological research, tumour necrosis factor (TNF) was found to be too toxic for systemic use but has been found to be highly effective in improving the results of treatment of melanoma when used in a closed-circuit perfusion system in combination with another chemotherapeutic agent. In the past the use of closed-circuit perfusion has been confined to limbs, but techniques have recently been developed to apply closed-circuit perfusion to liver, pelvic organs, and some abdominal regions including pancreas. The potential for studies of TNF in combination with chemotherapy in closed-circuit perfusion treatment of otherwise resistant cancers in these organs and tissue regions has been greatly expanded. In many cancer treatment centres in the past there has been a reluctance to use and to acknowledge the benefits of regional delivery of anti-cancer chemotherapy. The need for these techniques in the safe and effective use of TNF has further confirmed the importance of these methods in comprehensive cancer treatment centres, and the need for further studies and better understanding of the use of regional and closed-circuit perfusion methods.

Induction chemotherapy via hepatic artery for gallbladder carcinoma.

The prognosis after surgery for carcinoma of the gallbladder remains poor. Treatment failure is frequently due to loco-regional recurrence in the adjacent liver and regional lymph nodes. We report a case of gallbladder carcinoma with proven involvement of the cystic duct node (Nevin stage IV). Pre-operative intra-arterial induction chemotherapy using two cycles of cisplatin, 5-fluorouracil, doxorubicin and mitomycin C was administered via the common hepatic artery. A radical cholecystectomy was performed 4 weeks later, and histological examination of the resected specimen showed a near total response, with no residual nodal disease. The patient remains well and free of disease 3 years later. Intra-arterial induction chemotherapy warrants further evaluation.

Induction (neo-adjuvant) chemotherapy: systemic and arterial delivery techniques and their clinical applications.

Induction chemotherapy is a well tried method of improving the cure prospects of locally advanced or aggressive primary cancers. It is most simply administered by systemic (intravenous) delivery but for some cases a greater chemotherapy impact is both desirable and achievable with the use of a more concentrated regional delivery technique. Any advantage of regional chemotherapy will depend upon the type of tumour to be treated, its site and blood supply, the most effective doses, concentrations and exposure periods of the preferred agents to be used and the relative risks of systemic and regional toxicity and the techniques of delivery. In general, systemic chemotherapy is most appropriate in treating tumours without a single artery of supply; when certain agents which are inactive until modified in body tissues (such as cyclophosphamide or DTIC) are to be used; when satisfactory responses can be achieved more easily by systemic delivery; when technical skills and facilities for regional delivery are not available; or when the patient's general health, co-operation or long-term prognosis precludes the additional complexity of regional delivery. Intra-arterial infusion may have advantages in treating head and neck, gastric, liver, some locally advanced breast, limb, pelvic and possibly pancreatic malignancies. More complex techniques to achieve short-term highly concentrated chemotherapy include closed circuit perfusion; chemofiltration infusion and 'stop flow' perfusion; and regional limb infusion. These should remain the subject of ongoing studies in highly specialized units which treat tumours such as melanoma or pancreatic cancer which respond poorly to lower chemotherapy concentrations.

Pilonidal sinus: management objectives.

In spite of a number of ingenious operative and non-operative techniques in the management of pilonidal sinus no single technique can be relied upon to prevent recurrence of this benign yet troublesome condition. Once thought to be a congenital condition it is now appreciated that pilonidal sinus most often an acquired condition due to accumulation of tough, bristly hair penetrating the skin, or local hair growing into a skin crevice, pit or abnormal follicle. The most common site is the upper natal cleft but the condition may occur in other sites especially where there is a crevice or irregularity of skin surface with pressure or suction applied to that region. Most surgical procedures have been designed to eradicate the existing sinus and the crevice in which hair tends to accumulate. However, without the presence of hair there can be no pilonidal sinus and, in the past, little attention has been given to preventing the re-accumulation of hair in the troublesome site; hence the risk of recurrence. Management objectives should be directed not only at eradicating the obvious lesion present but also to preventing recurrence of aetiological factors; especially the re-accumulation or re-growth of hair.

The role of regional chemotherapy in gastric cancer.

Pre-operative intra-arterial chemotherapy has given impressive response rates in gastric cancer patients, and high survival rates longer term. The technique is demanding in skills and resources, but further studies using more effective drugs and less demanding regimens are in progress.

Comparison of intra-arterial versus intravenous 5-fluorouracil administration on epidermal squamous cell carcinoma in sheep.

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.

Developments in surgical oncology--past, present, and future trends.

The historical development of integrated treatment programs for locally advanced or aggressive cancers, for which the results of surgical excision or radiotherapy are unsatisfactory, is reviewed. Chemotherapy should be used first (induction chemotherapy), while tumour vasculature is intact; intra-arterial infusion gives a greater regional effect. Central residual tumour may be eradicated by subsequent radiotherapy and/or surgery. Regional induction chemotherapy is particularly useful in treating locally advanced stage III breast cancer, locally advanced head and neck cancer, gastric cancer, and locally advanced sarcomas and melanomas of the limbs. A team approach, involving surgical and medical oncologists, radiotherapists, immunologists, and others should improve the results in these patients.