- Email: [email protected]
Oestrogen replacement therapy and ovarian cancer
CORRESPONDENCE
sensitivity for diagnosis of carcinoma in lymph nodes is more than 90% with no complications. We recommend this procedure to clinicians involved in the management of lung cancer. Anthony Ryan, John Banks, *S Ashley Roberts Departments of *Clinical Radiology and Respiratory Medicine, Singleton Hospital, Swansea NHS Trust, Swansea SA2 8QA, UK 1 2
3
4
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Yung RC, Orens JB. Radicalism in therapy of lung cancer Lancet 2001; 357: 1306–07. Roberts SA. Obtaining tissue from the mediastinum: endoscopic ultrasound guided transoesophageal biopsy. Thorax 2000; 55: 983–85. Gress FG, Savides TJ, Sandier A, et al. Endoscopic ultrasonography, fine needle aspiration biopsy guided by endoscopic ultrasonography and computed tomography in the preoperative staging of non-small-cell lung cancer: a comparison study. Ann Intern Med 1997; 127: 604–12. Serna DL, Aryan HE, Chang KJ, et al. An early comparison between endoscopic ultrasound guided fine needle aspiration and mediastinoscopy for diagnosis of mediastinal malignancy. Am Surg 1998; 64: 1014–18. Roberts SA, Davies G, Howell S, Banks J. Endoscopic ultrasound guided biopsy of sub-carinal lymph nodes. Clin Radiol 2000; 55: 832–36.
influenza virus, about 33% of patients undergo amantadine treatment. We could detect six resistant viruses (3·4%) in 179 isolates from children before the treatment in the 1999/2000 season, but in neither the 1998/99 nor the 2000/01 season in Niigata, Japan. Therefore, circulation of drug-resistant viruses was not so high in the community even with excess use of amantadine. We support the fact that amantadine has an important part to play in the battle against an influenza pandemic. However, we request a monitoring system to survey resistant viruses, and to investigate their frequency, clinical importance, and likelihood of transmission. *Hiroshi Suzuki, Reiko Saito, Hitoshi Oshitani Department of Public Health, Niigata University School of Medicine, Niigata 951-8510, Japan (e-mail: [email protected]) 1 2
3
Excess amantadine use and resistant viruses Sir—Peter Tooley (Aug 25, p 670)1 argues about the misconceptions on the use of amantadine in a future pandemic of influenza because of its side-effects and the development of resistance. When the influenza emergency arises, the potential for the rapid emergence and dissemination of resistant viruses needs to be studied, especially in relation to strategies for antiviral use and spread to unprimed populations.2 The risk of adverse drug effects is an additional concern. However, their effects have been incompletely defined. About 1·54% of 1813 isolates in UK, and 0·8% of 2017 viruses collected in 43 countries and territories were drugresistant.3,4 This finding suggests that the circulation of drug-resistant viruses is actually quite rare. From 1993 to 1998, before the approval of amantadine for treatment of influenza virus infections, we could not identify any resistant virus among 55 isolates at 27 sentinel surveillance sites in Niigata, Japan.5 However, after the drug’s approval in 1998, 1·3, 2·2, and 0·7 million courses of treatment (100 mg daily for 5 days) were used for the 1998/99 to 2000/01 seasons in Japan. In the 1999/2000 season, 1·6% of the total Japanese population (around 126 million) was estimated to undergo amantadine treatment; when 5% of the total population of Japan is infected with
1910
4
5
Tooley P. Unprepared for an influenza pandemic. Lancet 2001; 358: 670–71. Monto A. Prospects for pandemic influenza control with currently available vaccines and antivirals. J Infect Dis 1997; 176 (suppl 1): 32–37. Dawson J. Neuraminidase inhibitor and amantadine. Lancet 2000; 355: 2254. Ziegler T, Hemphill ML, Ziegler ML, et al. Low incidence of rimantadine resistance in field isolates of influenza A viruses. J Infect Dis 1999; 180: 935–39. Masuda H, Suzuki H, Oshitani H, et al. Incidence of Amantadine-resistant influenza A viruses in sentinel surveillance sites and nursing homes in Niigata, Japan. Microbiol Immunol 2000; 44: 833–39.
Oestrogen replacement therapy and ovarian cancer Sir—In their Aug 11 commentary, Noel Weiss and Mary Anne Rossing1 offer much needed advice to clinicians on the potential link between oestrogen replacement therapy and ovarian cancer. However, the potential for damage by Rodriguez and colleagues’ report,2 to which they refer, was highlighted by the fact that selected data from that publication were printed in the UK national lay press. Doctors were presented with confusing information, and women who were taking or considering hormone replacement therapy (HRT) were alarmed. Doctors and patients need detailed information to assess the potential risks and benefits of HRT. Weiss and Rossing make several valid points, but Rodriguez and colleagues’ report raises wider issues, which need to be addressed. Rodriguez and colleagues studied 211 581 fit, non-hysterectomised, postmenopausal US women. The women had taken oral oestrogen
replacement therapy after age 35 years (oestrogen only use was common in the USA for women with or without an intact uterus at that time). Treatment with oestrogen plus progestogen was not investigated. The women were followed up until 1996 (14 years). 944 died of ovarian cancer (0·45%). The researchers compared ovarian mortality with the effect of oestrogen replacement therapy among women who had never used treatment, those using treatment at baseline, and previous but not current users, and for total accumulated years of treatment use. Risk of ovarian cancer death was reported as higher in users at baseline and slightly higher for previous users than never users. A doubling of risk with duration of use of 10 years or more was suggested, but at beseline only 22% had ever used oestrogen replacement therapy (24% current, 76% previous users). The mean duration of therapy use was 6 years in users at baseline, and 4 years among previous users, which provides very small numbers for 10 or more years use data. Only 66 of 944 women who died of ovarian cancer had used HRT for 10 or more years. The mean relative risk was significant in previous users (1·59) and baseline users (2·2), compared with never users, but 95% CI for all groups were wide and numbers small. Most of these women took unopposed oestrogen in the 1970s and early 80s. Powerful synthetic oestrogens were commonly used. Rodriguez and colleagues acknowledge that the data might not, therefore, be relevant to current practice. However, the study is still seriously underpowered to make the conclusions it does. However, the media picked up one claim. The report states that the effects of oestrogen replacement therapy on ovarian cancer persist for up to 29 years after cessation of use; no data support this claim. The best that can be said about the Rodriguez and colleagues’ results is that long-term high-dose unopposed oestrogen replacement therapy might increase the risk of ovarian cancer. There is no evidence that modern lowdose oestrogen and progestogen combinations have this effect. This message must be conveyed to prescribing doctors, advising nurses, and enquiring patients. Stuart V Drew Old Postings, North Street, Rogate, Petersfield, Hants GU31 5HG, UK 1
2
Weiss NS, Rossing MA. Oestrogenreplacement therapy and risk of ovarian cancer. Lancet 2001; 358: 438. Rodriguez C, Patel AV, Calle EE, et al. Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women. JAMA 2001; 285: 1460–65.
THE LANCET • Vol 358 • December 1, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
sensitivity for diagnosis of carcinoma in lymph nodes is more than 90% with no complications. We recommend this procedure to clinicians involved in the management of lung cancer. Anthony Ryan, John Banks, *S Ashley Roberts Departments of *Clinical Radiology and Respiratory Medicine, Singleton Hospital, Swansea NHS Trust, Swansea SA2 8QA, UK 1 2
3
4
5
Yung RC, Orens JB. Radicalism in therapy of lung cancer Lancet 2001; 357: 1306–07. Roberts SA. Obtaining tissue from the mediastinum: endoscopic ultrasound guided transoesophageal biopsy. Thorax 2000; 55: 983–85. Gress FG, Savides TJ, Sandier A, et al. Endoscopic ultrasonography, fine needle aspiration biopsy guided by endoscopic ultrasonography and computed tomography in the preoperative staging of non-small-cell lung cancer: a comparison study. Ann Intern Med 1997; 127: 604–12. Serna DL, Aryan HE, Chang KJ, et al. An early comparison between endoscopic ultrasound guided fine needle aspiration and mediastinoscopy for diagnosis of mediastinal malignancy. Am Surg 1998; 64: 1014–18. Roberts SA, Davies G, Howell S, Banks J. Endoscopic ultrasound guided biopsy of sub-carinal lymph nodes. Clin Radiol 2000; 55: 832–36.
influenza virus, about 33% of patients undergo amantadine treatment. We could detect six resistant viruses (3·4%) in 179 isolates from children before the treatment in the 1999/2000 season, but in neither the 1998/99 nor the 2000/01 season in Niigata, Japan. Therefore, circulation of drug-resistant viruses was not so high in the community even with excess use of amantadine. We support the fact that amantadine has an important part to play in the battle against an influenza pandemic. However, we request a monitoring system to survey resistant viruses, and to investigate their frequency, clinical importance, and likelihood of transmission. *Hiroshi Suzuki, Reiko Saito, Hitoshi Oshitani Department of Public Health, Niigata University School of Medicine, Niigata 951-8510, Japan (e-mail: [email protected]) 1 2
3
Excess amantadine use and resistant viruses Sir—Peter Tooley (Aug 25, p 670)1 argues about the misconceptions on the use of amantadine in a future pandemic of influenza because of its side-effects and the development of resistance. When the influenza emergency arises, the potential for the rapid emergence and dissemination of resistant viruses needs to be studied, especially in relation to strategies for antiviral use and spread to unprimed populations.2 The risk of adverse drug effects is an additional concern. However, their effects have been incompletely defined. About 1·54% of 1813 isolates in UK, and 0·8% of 2017 viruses collected in 43 countries and territories were drugresistant.3,4 This finding suggests that the circulation of drug-resistant viruses is actually quite rare. From 1993 to 1998, before the approval of amantadine for treatment of influenza virus infections, we could not identify any resistant virus among 55 isolates at 27 sentinel surveillance sites in Niigata, Japan.5 However, after the drug’s approval in 1998, 1·3, 2·2, and 0·7 million courses of treatment (100 mg daily for 5 days) were used for the 1998/99 to 2000/01 seasons in Japan. In the 1999/2000 season, 1·6% of the total Japanese population (around 126 million) was estimated to undergo amantadine treatment; when 5% of the total population of Japan is infected with
1910
4
5
Tooley P. Unprepared for an influenza pandemic. Lancet 2001; 358: 670–71. Monto A. Prospects for pandemic influenza control with currently available vaccines and antivirals. J Infect Dis 1997; 176 (suppl 1): 32–37. Dawson J. Neuraminidase inhibitor and amantadine. Lancet 2000; 355: 2254. Ziegler T, Hemphill ML, Ziegler ML, et al. Low incidence of rimantadine resistance in field isolates of influenza A viruses. J Infect Dis 1999; 180: 935–39. Masuda H, Suzuki H, Oshitani H, et al. Incidence of Amantadine-resistant influenza A viruses in sentinel surveillance sites and nursing homes in Niigata, Japan. Microbiol Immunol 2000; 44: 833–39.
Oestrogen replacement therapy and ovarian cancer Sir—In their Aug 11 commentary, Noel Weiss and Mary Anne Rossing1 offer much needed advice to clinicians on the potential link between oestrogen replacement therapy and ovarian cancer. However, the potential for damage by Rodriguez and colleagues’ report,2 to which they refer, was highlighted by the fact that selected data from that publication were printed in the UK national lay press. Doctors were presented with confusing information, and women who were taking or considering hormone replacement therapy (HRT) were alarmed. Doctors and patients need detailed information to assess the potential risks and benefits of HRT. Weiss and Rossing make several valid points, but Rodriguez and colleagues’ report raises wider issues, which need to be addressed. Rodriguez and colleagues studied 211 581 fit, non-hysterectomised, postmenopausal US women. The women had taken oral oestrogen
replacement therapy after age 35 years (oestrogen only use was common in the USA for women with or without an intact uterus at that time). Treatment with oestrogen plus progestogen was not investigated. The women were followed up until 1996 (14 years). 944 died of ovarian cancer (0·45%). The researchers compared ovarian mortality with the effect of oestrogen replacement therapy among women who had never used treatment, those using treatment at baseline, and previous but not current users, and for total accumulated years of treatment use. Risk of ovarian cancer death was reported as higher in users at baseline and slightly higher for previous users than never users. A doubling of risk with duration of use of 10 years or more was suggested, but at beseline only 22% had ever used oestrogen replacement therapy (24% current, 76% previous users). The mean duration of therapy use was 6 years in users at baseline, and 4 years among previous users, which provides very small numbers for 10 or more years use data. Only 66 of 944 women who died of ovarian cancer had used HRT for 10 or more years. The mean relative risk was significant in previous users (1·59) and baseline users (2·2), compared with never users, but 95% CI for all groups were wide and numbers small. Most of these women took unopposed oestrogen in the 1970s and early 80s. Powerful synthetic oestrogens were commonly used. Rodriguez and colleagues acknowledge that the data might not, therefore, be relevant to current practice. However, the study is still seriously underpowered to make the conclusions it does. However, the media picked up one claim. The report states that the effects of oestrogen replacement therapy on ovarian cancer persist for up to 29 years after cessation of use; no data support this claim. The best that can be said about the Rodriguez and colleagues’ results is that long-term high-dose unopposed oestrogen replacement therapy might increase the risk of ovarian cancer. There is no evidence that modern lowdose oestrogen and progestogen combinations have this effect. This message must be conveyed to prescribing doctors, advising nurses, and enquiring patients. Stuart V Drew Old Postings, North Street, Rogate, Petersfield, Hants GU31 5HG, UK 1
2
Weiss NS, Rossing MA. Oestrogenreplacement therapy and risk of ovarian cancer. Lancet 2001; 358: 438. Rodriguez C, Patel AV, Calle EE, et al. Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women. JAMA 2001; 285: 1460–65.
THE LANCET • Vol 358 • December 1, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.