Journal of the Royal Society of Medicine Volume 72 October 1979 appear to be gastric transposition (Ong & Lee 1960, Ranger 1971, Harrison 1972), colonic transposition (Fairman & John 1966, Goligher & Robin 1954), the deltopectoral flap (Bakamjian 1965) and a plastic tube, as reported by Mr D W Stuart in this issue (p 724). All of these methods are an enormous surgical tour de force and should certainly only be undertaken in a unit trained and equipped to undertake this type of surgery. Every method has advantages and disadvantages vis-a-vis the others. The main disadvantage of the visceral grafts is their high operative mortality: the overall reported hospital mortality of these procedures is 31.2% (Stell & Hawkes 1979). The main advantage of such methods is that they give the patient a very good swallow, compared to the methods using skin flaps, since up to 40% of patients undergoing the latter operation may require pharyngeal dilatation at some time in their postoperative period (Stell & Hawkes 1979). Fistulae are more common after the latter procedure, and the stay in hospital is also much longer. However, the main advantage of the method using skin flaps as compared to that using a viscus is that the operative mortality is lower and postoperative deaths do not occur in patients who have not previously been irradiated. The main advantage of replacement of the pharynx by a plastic tube, as described by Stuart (1966 and p 724), is that it is the least demanding of the techniques both for the patient and for the surgeon. It can thus be used for patients who would be unfit for a transposition of the stomach to the neck. Many of these patients develop a sinus because of breakdown of the overlying skin, but the advocates of this method state that this is a cosmetic deformity only, and that leakage of food and saliva does not occur. One of the main disadvantages of this technique appears to be the high incidence of local recurrences (30%/) which presumably indicates that the technique does not allow sufficient pharyngeal and/or oesophageal mucosa to be resected to ensure an adequate
margin. It is clear therefore that all the methods of replacing the pharynx have their disadvantages, although these vary between the different techniques. Furthermore, there is no difference between the survival rate reported after any of these procedures. The choice of procedure will therefore depend on local expertise and enthusiasm rather than on any clear superiority of one method over P M Stell any other. Professor of Otorhinolaryngology University of Liverpool References Bakanjian V Y
(1965) Plastic and Reconstructive Surgery 36, 173
0141-0768/79/100717A2/$01.00/0
717
Dalby J E (1964) Clinical Radiology 15, 251 DuncanW (1971) Journal of Laryngology and Otology 85, 1224 Fainnan H D & John H T (1966) Journal of Laryngology and Otology 80, 1091 Goligher J C & Robin I G (1954) British Journal of Surgery 42, 283 Harrison D F N (1972) Annals of Otology, Rhinology and Laryngology 81, 465 Kaplan I & Markowicz H (1964) British Journal of Plastic Surgery 17, 314 Macbeth R (1969) Journal of Laryngology and Otology 83, 119 Nakayama K, Yamamoto K, Tamiya T, Makino H, Odaka M, Odwada M & Takabaski H (1964) Surgery 55, 796 Ong G B (1970) Journal of the Royal College of Surgeons of Edinburgh 15, 250 OngG B & Lee T C (1960) British Journal of Surgery 48, 193 Pearson J G (1966) Clinical Radiology 17, 242 Ranger D (1971) Journal ofLaryngology and Otology 85, 1218 Steil P M, Carden D A, Hibbert J & Dalby J E (1978) Clinical Oncology 4, 215-226 SteU P M & Hawkes A C (1979) Proceedings of the National Cancer Institute, Milan (in press) Stuart D W (1966) Journal of Laryngology and Otology 80, 382 Wookey H (1947) British Journal of Surgery 35, 249
Management of mycosis fungoides Mycosis fungoides is an infiltration of the skin by thymus-derived (T) lymphocytes which eventually may prove fatal through dissemination to lymph glands and other organs. Stages of disease are now defined (van Scott & Kalmanson 1973, du Vivier, Harper et al. 1978) and it is generally accepted that late stage disease is resistant to therapy. Controversy surrounds the management ofthe early stages where the disease is limited to the skin. The Americans, on the basis of significant mortality figures (Epstein et al. 1972), have pioneered aggressive approaches to prevent extension of the disease. Whole body electron beam irradiation therapy (Fuks et al. 1973) or topical nitrogen mustard therapy (Van Scott & Kalmanson 1973) have been shown to produce long-term remissions. The British view has been conservative, arguing that the disease evolves slowly, frequently starts in middle years and that only a small minority have their lives shortened by the process (Samman 1976). The difference in experience regarding mortality is unexplained but may be one of selection at specialized centres. There is, however, considerable morbidity associated with this skin disease which may be extensive and intensely pruritic, and arguments in favour of treatment are hard to contend. Whole © 1979 The Royal Society of Medicine
718
Journal of the Royal Society of Medicine Volume 72 October 1979
body electron beam therapy has the advantage of not requiring maintenance therapy but is limited to a handful of centres in the world, where equipment and expertise are available. Daily whole-body applications by the patient of dilute solutions of nitrogen mustard (20 mg/100 ml) produce a gratifying response, complete clearing of early stage disease occurring within weeks. No systemic effects have been recorded and the treatment is simple for the patient to perform once this novel technique has been adequately explained. The major disadvantage of therapy is the development of cutaneous delayed hypersensitivity reactions in approximately 40% of patients and this has detracted from its use in the United Kingdom. Induction of tolerance by injection of minute doses of nitrogen mustard intravenously prior to treatment has been advocated by van Scott & Kalmanson (1973) but has not been found effective by others (Leshaw et al. 1977). On the other hand, once sensitization has occurred, topical desensitization by applying very dilute (10-3 mg/l00 ml) solutions of nitrogen mustard and gradually increasing until tolerance to 20 mg/100 ml is effected, works well in many cases (Constantine et al. 1975). It is not known how long topical nitrogen mustard should be continued to effect permanent clearing of the disease but Vonderheid et al. (1977) advise three years. To be balanced against this treatment is the finding that nitrogen mustard is probably an epidermal carcinogen (du Vivier, Vonderheid et al. 1978) although the lesions described were easily treated. There is unfortunately a similar risk theoretically associated with electron beam therapy and with the latest treatment, photochemotherapy. This latter approach, originally described in the United States (Gilchrest et al. 1976) and now adopted in the IlK (Hodge et al. 1977), involves taking 8-methoxypsoralen orally before exposure to longwave ultraviolet light (PUVA). Photoexcited psoralens bind with the pyrimidine bases of nucleic acids to inhibit DNA synthesis. Complete clearing of the eruption undoubtedly occurs, but treatment has to be maintained indefinitely in order to prevent relapse. A technical problem exists too in that certain areas are naturally shielded from irradiation, e.g. eyelids, behind the ears, axillae, finger webs, natal cleft and groin, and thus are difficult to treat. Perhaps more disturbingly
they may become sanctuary sites in that plaque and tumerous lesions may develop in areas which were uninvolved before PUVA therapy. It is almost as though the malignant T lymphocytes had been shifted from treated sites to the shielded areas. PUVA and nitrogen mustard therapy have been used in combination in particular in an attempt to prevent sensitization of the skin to nitrogen mustard, since the former inhibits lymphocyte phytohaemagglutinin responsiveness (Kruger et al. 1978).. This combination induces remissions but does not prevent contact dermatitis (du Vivier & Vollum 1978). Many important questions remain unresolved regarding the management of this condition, not least of which are what is the natural history of the disease, and does treatment of early stage disease influence the final outcome? The need for controlled trials is recognized but because of the slow metamorphosis of the disease they will take many years to provide answers and the denial of treatment to control patients would be hard to justify. Anthony du Vivier Consultant Dermatologist King's College Hospital, London SE5 9RS
References Constantine V S, Fuks Z Y & Farber E M (1975) Archives of Dermatology 111, 484-488 du Vivier A, Harper R, Vonderheid E & van Scott E J (1978) Cancer 42, 209-213 do Vivier A & Volum D (1978) British Medical Journal ii, 1300-1301 du Vivier A, Vonderheid E C, van Scott E J & Urbach F (1978) British Journal of Dermatology 99, 61-63 Epstein E, Levin D L, Croft J D & Lutzner M A (1972) Medicine 15, 61-72 Fuks Z Y, Bagshaw M A & Farber E M (1973) Cancer 32, 1385-1395 Gilchrest B A, Parrish J A, Tanenbaum L, Haynes H A & Fitzpatrick T B (1976) Cancer 38, 683-689 Hodge L, Veila Briffa D, Warn A P, Gange R W & Bleehen S (1977) British Medical Journal ii, 1257-1259 Kruger J P, Christophers E & Schlaak M (1978) British Journal of Dermatology 98, 141-144 Leshaw S, Simon R S & Baer R L (1977) Archives of Dermatology 113, 1406-1408 Samman P D (1976) Clinical and Experimental Dermatology 1, 197-214 van Scott E J & Kalmanson J D (1973) Cancer 32, 1, 18-30 Vonderheid E C, van Scott E J, Johnson W C, Grekin G A & Asbell S O (1977) Archives of Dermatology 113, 454-462
margin. It is clear therefore that all the methods of replacing the pharynx have their disadvantages, although these vary between the different techniques. Furthermore, there is no difference between the survival rate reported after any of these procedures. The choice of procedure will therefore depend on local expertise and enthusiasm rather than on any clear superiority of one method over P M Stell any other. Professor of Otorhinolaryngology University of Liverpool References Bakanjian V Y
(1965) Plastic and Reconstructive Surgery 36, 173
0141-0768/79/100717A2/$01.00/0
717
Dalby J E (1964) Clinical Radiology 15, 251 DuncanW (1971) Journal of Laryngology and Otology 85, 1224 Fainnan H D & John H T (1966) Journal of Laryngology and Otology 80, 1091 Goligher J C & Robin I G (1954) British Journal of Surgery 42, 283 Harrison D F N (1972) Annals of Otology, Rhinology and Laryngology 81, 465 Kaplan I & Markowicz H (1964) British Journal of Plastic Surgery 17, 314 Macbeth R (1969) Journal of Laryngology and Otology 83, 119 Nakayama K, Yamamoto K, Tamiya T, Makino H, Odaka M, Odwada M & Takabaski H (1964) Surgery 55, 796 Ong G B (1970) Journal of the Royal College of Surgeons of Edinburgh 15, 250 OngG B & Lee T C (1960) British Journal of Surgery 48, 193 Pearson J G (1966) Clinical Radiology 17, 242 Ranger D (1971) Journal ofLaryngology and Otology 85, 1218 Steil P M, Carden D A, Hibbert J & Dalby J E (1978) Clinical Oncology 4, 215-226 SteU P M & Hawkes A C (1979) Proceedings of the National Cancer Institute, Milan (in press) Stuart D W (1966) Journal of Laryngology and Otology 80, 382 Wookey H (1947) British Journal of Surgery 35, 249
Management of mycosis fungoides Mycosis fungoides is an infiltration of the skin by thymus-derived (T) lymphocytes which eventually may prove fatal through dissemination to lymph glands and other organs. Stages of disease are now defined (van Scott & Kalmanson 1973, du Vivier, Harper et al. 1978) and it is generally accepted that late stage disease is resistant to therapy. Controversy surrounds the management ofthe early stages where the disease is limited to the skin. The Americans, on the basis of significant mortality figures (Epstein et al. 1972), have pioneered aggressive approaches to prevent extension of the disease. Whole body electron beam irradiation therapy (Fuks et al. 1973) or topical nitrogen mustard therapy (Van Scott & Kalmanson 1973) have been shown to produce long-term remissions. The British view has been conservative, arguing that the disease evolves slowly, frequently starts in middle years and that only a small minority have their lives shortened by the process (Samman 1976). The difference in experience regarding mortality is unexplained but may be one of selection at specialized centres. There is, however, considerable morbidity associated with this skin disease which may be extensive and intensely pruritic, and arguments in favour of treatment are hard to contend. Whole © 1979 The Royal Society of Medicine
718
Journal of the Royal Society of Medicine Volume 72 October 1979
body electron beam therapy has the advantage of not requiring maintenance therapy but is limited to a handful of centres in the world, where equipment and expertise are available. Daily whole-body applications by the patient of dilute solutions of nitrogen mustard (20 mg/100 ml) produce a gratifying response, complete clearing of early stage disease occurring within weeks. No systemic effects have been recorded and the treatment is simple for the patient to perform once this novel technique has been adequately explained. The major disadvantage of therapy is the development of cutaneous delayed hypersensitivity reactions in approximately 40% of patients and this has detracted from its use in the United Kingdom. Induction of tolerance by injection of minute doses of nitrogen mustard intravenously prior to treatment has been advocated by van Scott & Kalmanson (1973) but has not been found effective by others (Leshaw et al. 1977). On the other hand, once sensitization has occurred, topical desensitization by applying very dilute (10-3 mg/l00 ml) solutions of nitrogen mustard and gradually increasing until tolerance to 20 mg/100 ml is effected, works well in many cases (Constantine et al. 1975). It is not known how long topical nitrogen mustard should be continued to effect permanent clearing of the disease but Vonderheid et al. (1977) advise three years. To be balanced against this treatment is the finding that nitrogen mustard is probably an epidermal carcinogen (du Vivier, Vonderheid et al. 1978) although the lesions described were easily treated. There is unfortunately a similar risk theoretically associated with electron beam therapy and with the latest treatment, photochemotherapy. This latter approach, originally described in the United States (Gilchrest et al. 1976) and now adopted in the IlK (Hodge et al. 1977), involves taking 8-methoxypsoralen orally before exposure to longwave ultraviolet light (PUVA). Photoexcited psoralens bind with the pyrimidine bases of nucleic acids to inhibit DNA synthesis. Complete clearing of the eruption undoubtedly occurs, but treatment has to be maintained indefinitely in order to prevent relapse. A technical problem exists too in that certain areas are naturally shielded from irradiation, e.g. eyelids, behind the ears, axillae, finger webs, natal cleft and groin, and thus are difficult to treat. Perhaps more disturbingly
they may become sanctuary sites in that plaque and tumerous lesions may develop in areas which were uninvolved before PUVA therapy. It is almost as though the malignant T lymphocytes had been shifted from treated sites to the shielded areas. PUVA and nitrogen mustard therapy have been used in combination in particular in an attempt to prevent sensitization of the skin to nitrogen mustard, since the former inhibits lymphocyte phytohaemagglutinin responsiveness (Kruger et al. 1978).. This combination induces remissions but does not prevent contact dermatitis (du Vivier & Vollum 1978). Many important questions remain unresolved regarding the management of this condition, not least of which are what is the natural history of the disease, and does treatment of early stage disease influence the final outcome? The need for controlled trials is recognized but because of the slow metamorphosis of the disease they will take many years to provide answers and the denial of treatment to control patients would be hard to justify. Anthony du Vivier Consultant Dermatologist King's College Hospital, London SE5 9RS
References Constantine V S, Fuks Z Y & Farber E M (1975) Archives of Dermatology 111, 484-488 du Vivier A, Harper R, Vonderheid E & van Scott E J (1978) Cancer 42, 209-213 do Vivier A & Volum D (1978) British Medical Journal ii, 1300-1301 du Vivier A, Vonderheid E C, van Scott E J & Urbach F (1978) British Journal of Dermatology 99, 61-63 Epstein E, Levin D L, Croft J D & Lutzner M A (1972) Medicine 15, 61-72 Fuks Z Y, Bagshaw M A & Farber E M (1973) Cancer 32, 1385-1395 Gilchrest B A, Parrish J A, Tanenbaum L, Haynes H A & Fitzpatrick T B (1976) Cancer 38, 683-689 Hodge L, Veila Briffa D, Warn A P, Gange R W & Bleehen S (1977) British Medical Journal ii, 1257-1259 Kruger J P, Christophers E & Schlaak M (1978) British Journal of Dermatology 98, 141-144 Leshaw S, Simon R S & Baer R L (1977) Archives of Dermatology 113, 1406-1408 Samman P D (1976) Clinical and Experimental Dermatology 1, 197-214 van Scott E J & Kalmanson J D (1973) Cancer 32, 1, 18-30 Vonderheid E C, van Scott E J, Johnson W C, Grekin G A & Asbell S O (1977) Archives of Dermatology 113, 454-462
