- Email: [email protected]
Syndrome X in testicularcancer survivors
CORRESPONDENCE
We did not exclude deaths thought to be due to other factors than the delivery method, since exclusions after randomisation may lead to bias. Also, the additional benefits of a policy of planned caesarean at term might be because labour and prolonged pregnancy are avoided, not just because difficult delivery is reduced. *Mary E Hannah, Walter J Hannah, Andrew Willan Department of Obstetrics and Gynaecology, Sunnybrook and Women’s College Health Sciences Centre, University of Toronto, Ontario, M5G 1N8, Canada (e-mail: [email protected])
Sir—As a doctor in a less-developedcountry clinic that has no surgical facilities, I found the conclusion of Mary Hannah and colleagues’ report1 very worrying. They imply that planned caesarean section should be the worldwide standard method for delivery of singleton breech fetuses. In the many less-wealthy countries in which most of the world’s population live and give birth, the availability of caesarean section is limited. Women may have to take long journeys on difficult roads, if and when transport is available. There can also be high financial cost. Surgery is not free to poor people, only to the well-off or well insured. Facilities and expertise for caesarean sections on exhausted patients might not yield the optimistically low mortality and morbidity suggested by Hannah and colleagues. I suspect that may of the caesareans in less-developed countries are not done by specialist-trained obstetricians, but by medical generalists. 39 caesareans (one or more of whom may die from the delayed surgery or sepsis) to improve one fetal outcome sounds like a very shocking price to pay for those of us who see women every day who expect 15–20% of their children to die in infancy despite our best efforts to support them. The survivors of surgery have to deal with the prospect of the next five to ten pregnancies in their normal environment, hampered by the worry that their scar is going to rupture and require further, even more urgent, surgical intervention or lead to death. Some women who have had three or four children delivered, some of whom have died because of the high infant mortality in their countries, find that after the second or third caesarean, surgeons decided they must quietly tie the fallopian tubes to avoid future surgery made difficult through previous assorted scars. In The Gambia, the average woman is expected to have six or seven babies. To have fewer is commonly a source of serious anxiety or embarrassment, both to her and to her
228
family. Loss of a child is a source of grief not of shame. Loss of fertility is another matter. Very few of the trial’s collaborative group come from the resource-poor areas of the world, where safe surgery is so hard to find. Before the struggling nations of the world are shamed (unnecessarily) into inflicting a breech-caesarean policy on their women, I suggest a major rejoinder to the article be published. Skills for vaginal delivering of breech babies must not be lost, and doctors the world over must continue to disagree with a policy of inflicting caesarean scars because it suits the practice of the richer nations. James Erskine PO Box 86 Banjul, The Gambia 1
Hannah ME, Hannah WJ, Hewson SA, Hodnett ED, Saigal S, Willan AR, for the Term Breech Trial Collaborative Group. Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial. Lancet 2000; 356: 1375–83.
Sir—The report by Mary Hannah and colleagues1 gives no information about the number of women eligible to be recruited. In some centres, fewer than 1% of eligible women were recruited. Randomised trials are generally judged as the gold standard for providing information on clinical issues, but low recruitment rates can lead to substantial bias. For example, an obstetrician might recruit a woman to the trial only if he or she was uncertain about the optimum method of delivery. Uncertainty might lead to an adverse outcome for the child. In Sweden, a register-based nationwide survey2 has shown a nonsignificant association between term breech presentation and very low intrapartum and early neonatal mortality rates (0·9 per 1000 livebirths for vaginal delivery, 0·5 per 1000 livebirths for caesearan section, relative risk 1·81). The Swedish numbers were not analysed by intention to treat, but the intrapartum and early neonatal mortality rates for vaginal births were much lower than those for countries in the low national perinatal mortality rate group of Hannah and colleagues. If Hannah and colleagues’ results did not arise through recruitment bias, and countries such as the UK cannot match the Swedish numbers, the causes of adverse perinatal outcome with breech presentation must be investigated, especially failure to recognise and treat intrapartum hypoxia.3 Ian P Stuart Department of Obstetrics and Gynaecology, Diana, Princess of Wales Hospital, Grimsby DN32 2BA, UK
1
2
3
Hannah ME, Hannah WJ, Hewson SA, Hodnett ED, Saigal S, Willan AR, for the Term Breech Trial Collaborative Group. Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial. Lancet 2000; 356: 1375–83. Lindqvist A, Norden-Lindeberg S, Hanson U. Perinatal mortality and route of delivery in term breech presentations. Br J Obstet Gynaecol 1997; 104: 1288–91. CESDI. 7th Annual Report. London: Maternal and Child Health Research Consortium, 2000.
Syndrome X in testicularcancer survivors Sir—In their report, Mervi Taskinen and colleagues (Sept 16, p 993)1 describe impaired glucose tolerance and dyslipidaemia as late effects after bone-marrow transplantation in childhood. Close monitoring of long-term survivors of bone-marrow transplantations showed insulin resistance and prompted the study. Taskinen and colleagues describe a high frequency of the core signs of syndrome X2 in long-term survivors of bone-marrow transplantation. The importance of the findings, as noted in the accompanying Commentary by Gérard Socié,3 is that this syndrome might, in these survivors, increase the risk for cardiovascular disease and affect their quality of life and ultimate outlook. Moreover, several risk factors of this syndrome can be treated if recognised. The frequency of the core signs of syndrome X in the bonemarrow-transplanted survivors was higher than in a small group of leukaemia survivors treated with only chemotherapy. However, the leukaemia group was investigated only 3 years after treatment, whereas the median follow-up of the transplanted patients was 10·8 years. This difference in follow-up duration could have altered the outcome of the comparison. Taskinen and colleagues also note that hypogonadism was an important factor associated with insulin resistance. This long-term side-effect related to chemotherapy and radiotherapy might be important in the pathogenesis of syndrome X. However, they do not address the possible effect of different schedules and doses of the administered cytotoxic therapy on the frequency of the syndrome. In long-term survivors of disseminated testicular cancer, we saw that many developed a cardiovascular risk-factor profile similar to that of syndrome X after non-ablative chemotherapy.4 Five patients were
THE LANCET • Vol 357 • January 20, 2001
For personal use only. Not to be reproduced without permission of The Lancet.
CORRESPONDENCE
Characteristic*
Insulin/glucose ratio‡ Insulin Glucose Triglycerides HDL-cholesterol Total cholesterol Total cholesterol/HDL-cholesterol ratio Testosterone Systolic blood pressure Diastolic blood pressure Body-mass index
Chemotherapy group (n=62)
Stage I group (n=40)
Normal value
Median (range) or mean (SD)
Median (range) or mean (SD)
<22 <10 mU/L <7·8 mmol/L <2·3 mmol/L >0·9 mmol/L <5·2 mmol/L <5 >11 nmol/L 聿150 mm Hg 聿95 mm Hg 聿27·8 kg/m2
16·5 (4·5–83·0) 10·5 (2·9–48·0) 4·8 (2·2–10·0) 2·2 (2·3) 1·0 (0·3) 6·2 (1·2) 6·8 (3·0) 16·1 (5·9–25·0) 137 (18) 90 (12) 25·8 (3·6)
11·7 (5·6–38) 7·7 (3·3–24) 4·7 (4·0–7·2) 1·4 (0·8) 1·1 (0·3) 5·6 (1·2) 5·5 (1·9) 18 (10–31) 123 (14) 82 (11) 25·7 (3·5)
p†
0·015 0·013 0·75 0·02 0·16 0·03 0·02 0·023 <0·001 0·003 0·68
*All lipid and hormone samples taken after an overnight fast. †Chemotherapy group versus Stage I group. Mann-Whitney U test for medians and Student’s t test for means. ‡Fasting insulin (pmol/L) divided by fasting glucose (mmol/L).
Characteristics of long-term survivors of testicular cancer
long-term survivors of disseminated testicular cancer cured with cisplatin combination chemotherapy and several developed late coronary-artery disease. We followed up 62 survivors of metastatic testicular cancer treated with orchidectomy plus chemotherapy cardiovascular risk factors and metabolic changes (median follow-up 14 years [range 10–20], median age at time of follow-up investigation 41 years [30–50]). A high proportion had core signs of syndrome X. 16 (26%) patients were insulin resistant (22% had a fasting blood insulin [pmol/L] to glucose [mmol/L] ratio >22 and 4% developed diabetes after treatment), 25% had raised fasting triglycerides (>2·3 mmol/L), 35% had a decreased fasting HDL cholesterol (<0·90 mmol/L), and 39% had newly developed hypertension. Furthermore, 24% developed microalbuminuria. To establish whether these metabolic changes were related to the cisplatin combination chemotherapy, we compared these 62 patients with 40 patients with stage I testicular cancer cured by orchidectomy only, with comparable age and follow-up duration. The results are summarised in the table.5 The core signs of syndrome X were more pronounced in long-term survivors treated with cisplatin combination chemotherapy than in those treated with orchidectomy only. Although the two treatment groups had signs of subclinical hypogonadism (persisting Leydig-cell dysfunction with raised concentrations of luteinising hormone in 19% of chemotherapy patients and 15% of orchidectomy patients), testosterone concentrations were lower in the chemotherapy group. Moreover, in chemotherapy-treated patients insulin concentration and insulin to glucose ratio correlated negatively with serum testosterone concentrations (r =⫺0·496, p<0·001, and r =⫺0·433, p=0·001, respectively).
THE LANCET • Vol 357 • January 20, 2001
These data provide evidence that long-term survivors of metastatic testicular cancer can develop an unfavourable profile of cardiovascular risk factors resembling syndrome X. Furthermore, this syndrome can occur in long-term survivors of nonablative chemotherapy without a bonemarrow transplantation. Administered cisplatin combination chemotherapy and subclincial hypogonadism seem to be important factors in its pathogenesis. *Jourik A Gietema, Martin T Meinardi, Winette T A van der Graaf, Dirk Th Sleijfer Division of Medical Oncology, Department of Internal Medicine, University Hospital, PO Box 30.001, 9700 RB Groningen, Netherlands (e-mail: [email protected]) 1
2
3
4
5
Taskinen M, Saarinen-Pihkala UM, Hovi L, Lipsanen-Nyman M. Impaired glucose tolerance and dyslipidaemia as late effects after bone-marrow transplantation in childhood. Lancet 2000; 356: 993–97. Reaven GM. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595–607. Socié G. Is syndrome “X” another late complication of bone-marrow transplantation? Lancet 2000; 356: 957–58. Meinardi MT, Gietema JA, Van Veldhuisen DJ, et al. Treatment related cardiovascular morbidity in longterm survivors of metastatic testicular cancer. J Clin Oncol 2000; 18: 1725–32. Meinardi MT, Gietema JA, Van der Graaf WTA, et al. Long-term vascular and metabolic sequelae of chemotherapy for metastatic testicular cancer: a comparison with long-term survivors of stage I disease. Proc ASCO 2000; 19: 331a.
term survivors of bone-marrow transplantation done in childhood. These two observations point out the outstanding importance of very longterm follow-up of patients treated for cancer, whatever age, diagnosis, or treatment. In patients with cancer, significant associations have been reported between insulin resistance and total body irradiation,1 growth hormone and we report deficiency2 hypogonadism, and now with cisplatin Gietema and colleagues and our data seem to sugest hypogonadism as the common denominator. The role of cancer itself in the development of insulin resistance should not be forgotten. In several studies insulin resistance already present at diagnosis of cancer has been reported.3,4 At the cellular level, all these associations can be hard to explain, especially because the pathophysiology of insulin resistance still remains unsolved. We believe that the cause of insulin resistance in cancer survivors might be multifactorial. The time elapsed after cancer treatment seems to be essential for the full blossom of the metabolic syndrome in cancer survivors, as Gietema and colleagues also point out. The message of Gietema and colleagues’ observation and the earlier studies should be evident. The signs of insulin resistance, dyslipdaemias, hypertension, and cardiovascular diseases should actively be searched for in long-term survivors of cancer. In addition, knowing that the treatment options of insulin resistance have been disappointing, childhood patients and their parents should be informed on the importance of prevention of excess weight and other risk factors for cardiovascular diseases, such as smoking. *Mervi Taskinen, Ulla Saarinen-Pihkala, Liisa Hovi, Marita Lipsanen-Nyman Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland (e-mail: [email protected]) 1
Authors’ reply 2
Sir—Jourik Gietema and colleagues report a clinically important finding of increased risk of coronary-artery disease in middle-aged longterm survivors of disseminated testicular cancer. The signs of the metabolic syndrome seem to be clustered in this group of patients, as we saw in our young long-
3
4
Lorini R, Cortona L, Scaramuzza A, et al. Hyperinsulinemia in children and adolescents after bone marrow transplantation. Bone Marrow Transplant 1995; 15: 873–77. Talvensaari KK, Lanning M, Tapannainen P, Knip M. Long-term survivors of childhood cancer have increased risk of manifesting the metabolic syndrome. J Clin Endocrinol Metab 1996; 81: 3051–55. Heber D, Byerley LO, Chi J, et al. Pathophysiology of malnutrition in the adult cancer patient. Cancer 1986; 58 (suppl 8): S167–73. Lundholm K, Holm G, Schersten T. Insulin resistance in patients with cancer. Cancer Res 1978; 38: 4665–70.
229
For personal use only. Not to be reproduced without permission of The Lancet.
We did not exclude deaths thought to be due to other factors than the delivery method, since exclusions after randomisation may lead to bias. Also, the additional benefits of a policy of planned caesarean at term might be because labour and prolonged pregnancy are avoided, not just because difficult delivery is reduced. *Mary E Hannah, Walter J Hannah, Andrew Willan Department of Obstetrics and Gynaecology, Sunnybrook and Women’s College Health Sciences Centre, University of Toronto, Ontario, M5G 1N8, Canada (e-mail: [email protected])
Sir—As a doctor in a less-developedcountry clinic that has no surgical facilities, I found the conclusion of Mary Hannah and colleagues’ report1 very worrying. They imply that planned caesarean section should be the worldwide standard method for delivery of singleton breech fetuses. In the many less-wealthy countries in which most of the world’s population live and give birth, the availability of caesarean section is limited. Women may have to take long journeys on difficult roads, if and when transport is available. There can also be high financial cost. Surgery is not free to poor people, only to the well-off or well insured. Facilities and expertise for caesarean sections on exhausted patients might not yield the optimistically low mortality and morbidity suggested by Hannah and colleagues. I suspect that may of the caesareans in less-developed countries are not done by specialist-trained obstetricians, but by medical generalists. 39 caesareans (one or more of whom may die from the delayed surgery or sepsis) to improve one fetal outcome sounds like a very shocking price to pay for those of us who see women every day who expect 15–20% of their children to die in infancy despite our best efforts to support them. The survivors of surgery have to deal with the prospect of the next five to ten pregnancies in their normal environment, hampered by the worry that their scar is going to rupture and require further, even more urgent, surgical intervention or lead to death. Some women who have had three or four children delivered, some of whom have died because of the high infant mortality in their countries, find that after the second or third caesarean, surgeons decided they must quietly tie the fallopian tubes to avoid future surgery made difficult through previous assorted scars. In The Gambia, the average woman is expected to have six or seven babies. To have fewer is commonly a source of serious anxiety or embarrassment, both to her and to her
228
family. Loss of a child is a source of grief not of shame. Loss of fertility is another matter. Very few of the trial’s collaborative group come from the resource-poor areas of the world, where safe surgery is so hard to find. Before the struggling nations of the world are shamed (unnecessarily) into inflicting a breech-caesarean policy on their women, I suggest a major rejoinder to the article be published. Skills for vaginal delivering of breech babies must not be lost, and doctors the world over must continue to disagree with a policy of inflicting caesarean scars because it suits the practice of the richer nations. James Erskine PO Box 86 Banjul, The Gambia 1
Hannah ME, Hannah WJ, Hewson SA, Hodnett ED, Saigal S, Willan AR, for the Term Breech Trial Collaborative Group. Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial. Lancet 2000; 356: 1375–83.
Sir—The report by Mary Hannah and colleagues1 gives no information about the number of women eligible to be recruited. In some centres, fewer than 1% of eligible women were recruited. Randomised trials are generally judged as the gold standard for providing information on clinical issues, but low recruitment rates can lead to substantial bias. For example, an obstetrician might recruit a woman to the trial only if he or she was uncertain about the optimum method of delivery. Uncertainty might lead to an adverse outcome for the child. In Sweden, a register-based nationwide survey2 has shown a nonsignificant association between term breech presentation and very low intrapartum and early neonatal mortality rates (0·9 per 1000 livebirths for vaginal delivery, 0·5 per 1000 livebirths for caesearan section, relative risk 1·81). The Swedish numbers were not analysed by intention to treat, but the intrapartum and early neonatal mortality rates for vaginal births were much lower than those for countries in the low national perinatal mortality rate group of Hannah and colleagues. If Hannah and colleagues’ results did not arise through recruitment bias, and countries such as the UK cannot match the Swedish numbers, the causes of adverse perinatal outcome with breech presentation must be investigated, especially failure to recognise and treat intrapartum hypoxia.3 Ian P Stuart Department of Obstetrics and Gynaecology, Diana, Princess of Wales Hospital, Grimsby DN32 2BA, UK
1
2
3
Hannah ME, Hannah WJ, Hewson SA, Hodnett ED, Saigal S, Willan AR, for the Term Breech Trial Collaborative Group. Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial. Lancet 2000; 356: 1375–83. Lindqvist A, Norden-Lindeberg S, Hanson U. Perinatal mortality and route of delivery in term breech presentations. Br J Obstet Gynaecol 1997; 104: 1288–91. CESDI. 7th Annual Report. London: Maternal and Child Health Research Consortium, 2000.
Syndrome X in testicularcancer survivors Sir—In their report, Mervi Taskinen and colleagues (Sept 16, p 993)1 describe impaired glucose tolerance and dyslipidaemia as late effects after bone-marrow transplantation in childhood. Close monitoring of long-term survivors of bone-marrow transplantations showed insulin resistance and prompted the study. Taskinen and colleagues describe a high frequency of the core signs of syndrome X2 in long-term survivors of bone-marrow transplantation. The importance of the findings, as noted in the accompanying Commentary by Gérard Socié,3 is that this syndrome might, in these survivors, increase the risk for cardiovascular disease and affect their quality of life and ultimate outlook. Moreover, several risk factors of this syndrome can be treated if recognised. The frequency of the core signs of syndrome X in the bonemarrow-transplanted survivors was higher than in a small group of leukaemia survivors treated with only chemotherapy. However, the leukaemia group was investigated only 3 years after treatment, whereas the median follow-up of the transplanted patients was 10·8 years. This difference in follow-up duration could have altered the outcome of the comparison. Taskinen and colleagues also note that hypogonadism was an important factor associated with insulin resistance. This long-term side-effect related to chemotherapy and radiotherapy might be important in the pathogenesis of syndrome X. However, they do not address the possible effect of different schedules and doses of the administered cytotoxic therapy on the frequency of the syndrome. In long-term survivors of disseminated testicular cancer, we saw that many developed a cardiovascular risk-factor profile similar to that of syndrome X after non-ablative chemotherapy.4 Five patients were
THE LANCET • Vol 357 • January 20, 2001
For personal use only. Not to be reproduced without permission of The Lancet.
CORRESPONDENCE
Characteristic*
Insulin/glucose ratio‡ Insulin Glucose Triglycerides HDL-cholesterol Total cholesterol Total cholesterol/HDL-cholesterol ratio Testosterone Systolic blood pressure Diastolic blood pressure Body-mass index
Chemotherapy group (n=62)
Stage I group (n=40)
Normal value
Median (range) or mean (SD)
Median (range) or mean (SD)
<22 <10 mU/L <7·8 mmol/L <2·3 mmol/L >0·9 mmol/L <5·2 mmol/L <5 >11 nmol/L 聿150 mm Hg 聿95 mm Hg 聿27·8 kg/m2
16·5 (4·5–83·0) 10·5 (2·9–48·0) 4·8 (2·2–10·0) 2·2 (2·3) 1·0 (0·3) 6·2 (1·2) 6·8 (3·0) 16·1 (5·9–25·0) 137 (18) 90 (12) 25·8 (3·6)
11·7 (5·6–38) 7·7 (3·3–24) 4·7 (4·0–7·2) 1·4 (0·8) 1·1 (0·3) 5·6 (1·2) 5·5 (1·9) 18 (10–31) 123 (14) 82 (11) 25·7 (3·5)
p†
0·015 0·013 0·75 0·02 0·16 0·03 0·02 0·023 <0·001 0·003 0·68
*All lipid and hormone samples taken after an overnight fast. †Chemotherapy group versus Stage I group. Mann-Whitney U test for medians and Student’s t test for means. ‡Fasting insulin (pmol/L) divided by fasting glucose (mmol/L).
Characteristics of long-term survivors of testicular cancer
long-term survivors of disseminated testicular cancer cured with cisplatin combination chemotherapy and several developed late coronary-artery disease. We followed up 62 survivors of metastatic testicular cancer treated with orchidectomy plus chemotherapy cardiovascular risk factors and metabolic changes (median follow-up 14 years [range 10–20], median age at time of follow-up investigation 41 years [30–50]). A high proportion had core signs of syndrome X. 16 (26%) patients were insulin resistant (22% had a fasting blood insulin [pmol/L] to glucose [mmol/L] ratio >22 and 4% developed diabetes after treatment), 25% had raised fasting triglycerides (>2·3 mmol/L), 35% had a decreased fasting HDL cholesterol (<0·90 mmol/L), and 39% had newly developed hypertension. Furthermore, 24% developed microalbuminuria. To establish whether these metabolic changes were related to the cisplatin combination chemotherapy, we compared these 62 patients with 40 patients with stage I testicular cancer cured by orchidectomy only, with comparable age and follow-up duration. The results are summarised in the table.5 The core signs of syndrome X were more pronounced in long-term survivors treated with cisplatin combination chemotherapy than in those treated with orchidectomy only. Although the two treatment groups had signs of subclinical hypogonadism (persisting Leydig-cell dysfunction with raised concentrations of luteinising hormone in 19% of chemotherapy patients and 15% of orchidectomy patients), testosterone concentrations were lower in the chemotherapy group. Moreover, in chemotherapy-treated patients insulin concentration and insulin to glucose ratio correlated negatively with serum testosterone concentrations (r =⫺0·496, p<0·001, and r =⫺0·433, p=0·001, respectively).
THE LANCET • Vol 357 • January 20, 2001
These data provide evidence that long-term survivors of metastatic testicular cancer can develop an unfavourable profile of cardiovascular risk factors resembling syndrome X. Furthermore, this syndrome can occur in long-term survivors of nonablative chemotherapy without a bonemarrow transplantation. Administered cisplatin combination chemotherapy and subclincial hypogonadism seem to be important factors in its pathogenesis. *Jourik A Gietema, Martin T Meinardi, Winette T A van der Graaf, Dirk Th Sleijfer Division of Medical Oncology, Department of Internal Medicine, University Hospital, PO Box 30.001, 9700 RB Groningen, Netherlands (e-mail: [email protected]) 1
2
3
4
5
Taskinen M, Saarinen-Pihkala UM, Hovi L, Lipsanen-Nyman M. Impaired glucose tolerance and dyslipidaemia as late effects after bone-marrow transplantation in childhood. Lancet 2000; 356: 993–97. Reaven GM. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595–607. Socié G. Is syndrome “X” another late complication of bone-marrow transplantation? Lancet 2000; 356: 957–58. Meinardi MT, Gietema JA, Van Veldhuisen DJ, et al. Treatment related cardiovascular morbidity in longterm survivors of metastatic testicular cancer. J Clin Oncol 2000; 18: 1725–32. Meinardi MT, Gietema JA, Van der Graaf WTA, et al. Long-term vascular and metabolic sequelae of chemotherapy for metastatic testicular cancer: a comparison with long-term survivors of stage I disease. Proc ASCO 2000; 19: 331a.
term survivors of bone-marrow transplantation done in childhood. These two observations point out the outstanding importance of very longterm follow-up of patients treated for cancer, whatever age, diagnosis, or treatment. In patients with cancer, significant associations have been reported between insulin resistance and total body irradiation,1 growth hormone and we report deficiency2 hypogonadism, and now with cisplatin Gietema and colleagues and our data seem to sugest hypogonadism as the common denominator. The role of cancer itself in the development of insulin resistance should not be forgotten. In several studies insulin resistance already present at diagnosis of cancer has been reported.3,4 At the cellular level, all these associations can be hard to explain, especially because the pathophysiology of insulin resistance still remains unsolved. We believe that the cause of insulin resistance in cancer survivors might be multifactorial. The time elapsed after cancer treatment seems to be essential for the full blossom of the metabolic syndrome in cancer survivors, as Gietema and colleagues also point out. The message of Gietema and colleagues’ observation and the earlier studies should be evident. The signs of insulin resistance, dyslipdaemias, hypertension, and cardiovascular diseases should actively be searched for in long-term survivors of cancer. In addition, knowing that the treatment options of insulin resistance have been disappointing, childhood patients and their parents should be informed on the importance of prevention of excess weight and other risk factors for cardiovascular diseases, such as smoking. *Mervi Taskinen, Ulla Saarinen-Pihkala, Liisa Hovi, Marita Lipsanen-Nyman Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland (e-mail: [email protected]) 1
Authors’ reply 2
Sir—Jourik Gietema and colleagues report a clinically important finding of increased risk of coronary-artery disease in middle-aged longterm survivors of disseminated testicular cancer. The signs of the metabolic syndrome seem to be clustered in this group of patients, as we saw in our young long-
3
4
Lorini R, Cortona L, Scaramuzza A, et al. Hyperinsulinemia in children and adolescents after bone marrow transplantation. Bone Marrow Transplant 1995; 15: 873–77. Talvensaari KK, Lanning M, Tapannainen P, Knip M. Long-term survivors of childhood cancer have increased risk of manifesting the metabolic syndrome. J Clin Endocrinol Metab 1996; 81: 3051–55. Heber D, Byerley LO, Chi J, et al. Pathophysiology of malnutrition in the adult cancer patient. Cancer 1986; 58 (suppl 8): S167–73. Lundholm K, Holm G, Schersten T. Insulin resistance in patients with cancer. Cancer Res 1978; 38: 4665–70.
229
For personal use only. Not to be reproduced without permission of The Lancet.