- Email: [email protected]
MRI for breast conservation surgery
Correspondence
We, the UNITAID board members representing non-governmental organisations (NGOs) and communities affected by HIV/AIDS, tuberculosis, and malaria, are writing to you to express our deep concern that BristolMyers Squibb (BMS) is to close a factory in France that manufactures a second-line antiretroviral medicine for children with HIV/AIDS who weigh less than 10 kg: buffered didanosine in the 25 mg formulation. Closing this factory means that 4000–7000 babies currently enrolled in treatment plans in developing countries through UNITAID could be left without the medicines they need. Didanosine is the last therapeutic option for these babies and without it they could die. We understand that closure of the plant will take place in June of this year, with no plans for resumption of production before April, 2011, at the earliest, when a new plant is due to open. Therefore there is likely to be a shortage of about 15 000 packs of didanosine 25 mg across all UNITAID beneficiary countries between now and when production is expected to resume in April, 2011. Currently, there is no alternative generic product that has been assessed by WHO and prequalified for use by UN agencies. We urge you, as the Chief Executive Officer of BMS, a company that prides itself on its high standards of corporate responsibility, to respond urgently to our concerns, outlining the steps you will take to avoid any treatment interruption. We would also like your confirmation that a BMS plant will resume production of this vital medicine in 2011. Supporting the NGOs and communities delegations: Action for Southern Africa; Act Up, Lusaka, Zambia; Africare; Agency for Community Care and Development; Asian Harm Reduction Network; Centre for Health Policy and Innovation; Coalition of Zambian Women Living with HIV/AIDS (COZWHA+); Coalition PLUS; Community Initiative for Tuberculosis, HIV/AIDS
www.thelancet.com Vol 375 June 26, 2010
& Malaria (CITAM+), Zambia; Consumer Information Network (CIN), Kenya; Ecumenical Pharmaceutical Network; Global AIDS Alliance; Health Action International (HAI) Africa; Health Access Network (HAN), Ghana; Health GAP (Global Access Project); IHA’s Medical and Social Foundation, India; Love Life Society; Médecins Sans Frontières; National Community of Women Living with HIV/AIDS in Uganda (NACWOLA); Network of Maharashtra People with HIV (NMP+); Positive Generation, Cameroon; Stop AIDS Campaign, UK; TB ACTION Group, Kenya; The Touch of Hope Foundation; and Universities Allied for Essential Medicines.
*Mohga Kamal-Yanni, Kim Nichols, Esther Tallah, Nelson Otwoma [email protected] Oxfam GB, Oxford OX4 2JY, UK (MK-Y); African Services Committee, New York, NY, USA (KN); Cameroon Coalition Against Malaria, Yaounde, Cameroon (ET); and National Empowerment Network of People Living with HIV/AIDS in Kenya, Nairobi, Kenya (NO)
MRI for breast conservation surgery In the COMICE trial (Feb 13, p 563),1 Lindsay Turnbull and colleagues found that preoperative breast MRI did not reduce the rate of re-excisions in women with primary breast cancer who were scheduled for wide local excision. The generalisability of these results is, mostly owing to very low inclusion in many centres, highly questionable. We showed that, in centres with experience, the rate of re-excisions in lobular cancers can be substantially reduced.2 Nevertheless, Turnbull and colleagues conclude “that MRI might not be necessary in this population of patients in terms of reduction of reoperation rates”. Irrespective of the validity, it is tempting to interpret their statement as “preoperative MRI is not indicated in patients with newly detected breast cancer”. However, the current indication for preoperative MRI, as endorsed by various organisations (eg, the American College of Radiology3 and the European Society of Breast Imaging), is not based on reduction of reoperation rates, but rather is a screening recommendation for the contralateral breast. Whereas residual disease in the ipsilateral breast can be effectively treated
with radiotherapy, tumours in the contralateral breast are basically left untreated when undetected. MRI screening of the contralateral breast has, at about 4%, the highest cancer yield of any type of breast cancer screening4 (2% contralateral carcinomas as reported in Turnbull and colleagues’ study is exceptionally low). Early detection of second cancers has been shown to result in increased survival (between 27% and 47%).5 Although that study did not assess preoperative MRI, its conclusions are unambiguous: second cancers should be detected at the earliest stage possible, which is effectively achieved by MRI. Consequently, because the effect of preoperative breast MRI on the ipsilateral breast is not detrimental, the indication is unchanged.
Published Online June 7, 2010 DOI:10.1016/S01406736(10)60940-3
We declare that we have no conflicts of interest.
*R M Mann, C Boetes [email protected] Science Photo Library
Open letter to Lamberto Andreotti, Chief Executive Officer, Bristol-Myers Squibb
Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen, Netherlands (RMM); and University Medical Centre Maastricht, Maastricht, Netherlands (CB) 1
2
3
4
5
Turnbull L, Brown S, Harvey I, et al. Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial. Lancet 2010; 375: 563–71. Mann RM, Loo CE, Wobbes T, et al. The impact of preoperative breast MRI on the re-excision rate in invasive lobular carcinoma of the breast. Breast Cancer Res Treat 2010; 119: 415–22. American College of Radiology. ACR practice guideline for the performance of contrastenhanced magnetic resonance imaging (MRI) of the breast. http://www.acr.org/ SecondaryMainMenuCategories/quality_ safety/guidelines/breast/mri_breast.aspx (accessed June 2, 2010). Brennan ME, Houssami N, Lord S, et al. Magnetic resonance imaging screening of the contralateral breast in women with newly diagnosed breast cancer: systematic review and meta-analysis of incremental cancer detection and impact on surgical management. J Clin Oncol 2009; 27: 5640–49. Houssami N, Ciatto S, Martinelli F, Bonardi R, Duffy SW. Early detection of second breast cancers improves prognosis in breast cancer survivors. Ann Oncol 2009; 20: 1505–10.
In the report by Lindsay Turnbull and colleagues,1 addition of MRI to the preoperative assessment of small breast cancers failed to reduce the reoperation rate, which reached around 19%. Among the tumours excised
Submissions should be made via our electronic submission system at http://ees.elsevier.com/ thelancet/
2213
Correspondence
AP
from 1623 patients, 44% were ductal carcinoma in situ (DCIS). As cited in the Article, a 2006–07 UK audit reveals that 17% of patients with primary breast cancer underwent reoperation for positive tumour margins. A review of 2564 patients with DCIS from a 2003–08 UK audit2 shows that conventional preoperative imaging undersized the extent of disease in 30% of patients. MRI has a higher sensitivity for DCIS than does mammoraphy, especially for DCIS with high nuclear grade.3 MRI perhaps provided the best assessment of the extent and location of such tumours in the breast, but this information could not be used efficiently in the operating theatre. An ideal clear margin has not been determined, despite its possible relation to the rates of reoperation and recurrence of the ipsilateral breast tumour.4 Obtaining a microscopic margin wide enough to protect from ipsilateral recurrence could result in unacceptably high reoperation rates and poor cosmetic results. When looking at short-term outcomes of breast-conserving surgery, analysis might have to be stratified by prespecified margin width. Given an annual risk of ipsilateral recurrence of 1–2%, long-term follow-up would be needed to confirm the accuracy of imaging and the feasibility of surgery. I declare that I have no conflicts of interest.
Tetsuji Fujita [email protected] Department of Surgery, Jikei University School of Medicine, Tokyo 105-8461, Japan 1
2
3
4
2214
Turnbull L, Brown S, Harvey I, et al. Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial. Lancet 2010; 375: 563–71. Thomas J, Evans A, Macartney J, et al. Radiological and pathological size estimations of pure ductal carcinoma in situ of the breast, specimen handling and the influence on the success of breast conservation surgery: a review of 2564 cases from the Sloane Project. Br J Cancer 2010; 102: 285–93. Kuhl CK, Schrading S, Bieling HB, et al. MRI for diagnosis of pure ductal carcinoma in situ: a prospective observational study. Lancet 2007; 370: 485–92. Benson JR, Jatoi I, Keisch M, Esteva FJ, Makris A, Jordan VC. Early breast cancer. Lancet 2009; 373: 1463–79.
Mah-Jong-related deep vein thrombosis The strategy game Mah-Jong is one of the most popular leisure activities in many Chinese communities, especially in rural areas and the residential districts of cities. The activity involves sitting still for long periods and deep concentration. We report a case of deep-vein thrombosis (DVT) associated with Mah-Jong. A 40-year-old woman presented to us in April, 2009, with pain and swelling in the left leg. She had played Mah-Jong for 8 h the previous night and had only drunk a small amount of soft drink during this time. She had no past health problems and no family history of DVT. However, she had been taking an oral contraceptive (desogestrel and ethinylestradiol) for 1 month. Her blood pressure was 115/90 mm Hg and there were no abnormal signs on heart and lung examination. Her left leg was diffusely firm and swollen. Laboratory analysis revealed: haemoglobin 106 g/L; white blood cell count 8·0×109 per L; platelet count 303×109 per L. Plasma lipoprotein concentrations, immunoglobin concentrations, and liver function tests were normal. Test for antiphospholipid antibody was negative. Activated partial thromboplastin time, prothrombin time, and thrombin time were all in the normal range; D-dimer concentration was 3·25 mg/L (normal 0·0–1·0 mg/L), and fibrin degradation product 6·2 mg/L (0·0–5·0 mg/L). Platelet aggregation assay was normal. Thrombophilia screening tests were negative. Colour duplex ultrasonography showed DVT extending from the left external iliac vein to the foretibial vein. The patient was diagnosed with DVT of the left leg, and lowmolecular-weight heparin (nadroparin 0·4 mL, two times per day) was started, lasting 2 weeks. Compression stockings were also used and aspirin (100 mg per day) was taken orally for
3 weeks and maintained for 2 months after hospital discharge. 2 weeks after admission to hospital, the patient’s left leg pain had completely resolved, and the swelling went down gradually. She was discharged home on May 12, 2009, and accepted warfarin (2·5 mg per day) as maintenance therapy. At present, she is asymptomatic and is followed up regularly. Our patient was relatively young (40 years), and had a potential risk factor for venous thrombosis—ie, oral contraceptive use. The attack of DVT was preceded by playing MahJong for 8 h. Could this have been a coincidence? Playing Mah-Jong is associated with prolonged immobility of the circulation of the lower limbs. It has been shown that during quiet sitting for 1 h, the haematocrit rises progressively with a concomitant rise in plasma protein concentration, attributed to blood-flow stasis and higher plasma viscosity.1 Dehydration owing to our patient’s low fluid intake during Mah-Jong playing might have increased the blood viscosity further. Long-term sitting has been related to thrombosis of the deep leg veins.2 Our patient’s condition is similar to “economy class syndrome”1 in its underlying pathophysiological mechanisms. However, the mechanisms of Mah-Jong-related DVT could be complicated by stress (especially when it involves monetary bets) and sleep deprivation, suggesting that MahJong-related DVT is distinct from classic economy class syndrome. We declare that we have no conflicts of interest.
*Guang-sen Zhang, Hong-ling Peng, Ming-yang Deng, Chang Shu, Rui-juan Li, Yang-ming Tang, Min-fei Pei [email protected] Division of Hematology (GSZ, HLP, MYD, RJL, YMT, MFP) and Division of Blood Vessel Surgery (CS), Second Xiang-Ya Hospital, Central South University, ChangSha, Hunan 410011, China 1 2
Moyses C. Economy class syndrome. Lancet 1988; 2: 1077. Homans J. Thrombosis of the deep leg veins due to prolonged sitting. N Engl J Med 1954; 250: 1449.
www.thelancet.com Vol 375 June 26, 2010
We, the UNITAID board members representing non-governmental organisations (NGOs) and communities affected by HIV/AIDS, tuberculosis, and malaria, are writing to you to express our deep concern that BristolMyers Squibb (BMS) is to close a factory in France that manufactures a second-line antiretroviral medicine for children with HIV/AIDS who weigh less than 10 kg: buffered didanosine in the 25 mg formulation. Closing this factory means that 4000–7000 babies currently enrolled in treatment plans in developing countries through UNITAID could be left without the medicines they need. Didanosine is the last therapeutic option for these babies and without it they could die. We understand that closure of the plant will take place in June of this year, with no plans for resumption of production before April, 2011, at the earliest, when a new plant is due to open. Therefore there is likely to be a shortage of about 15 000 packs of didanosine 25 mg across all UNITAID beneficiary countries between now and when production is expected to resume in April, 2011. Currently, there is no alternative generic product that has been assessed by WHO and prequalified for use by UN agencies. We urge you, as the Chief Executive Officer of BMS, a company that prides itself on its high standards of corporate responsibility, to respond urgently to our concerns, outlining the steps you will take to avoid any treatment interruption. We would also like your confirmation that a BMS plant will resume production of this vital medicine in 2011. Supporting the NGOs and communities delegations: Action for Southern Africa; Act Up, Lusaka, Zambia; Africare; Agency for Community Care and Development; Asian Harm Reduction Network; Centre for Health Policy and Innovation; Coalition of Zambian Women Living with HIV/AIDS (COZWHA+); Coalition PLUS; Community Initiative for Tuberculosis, HIV/AIDS
www.thelancet.com Vol 375 June 26, 2010
& Malaria (CITAM+), Zambia; Consumer Information Network (CIN), Kenya; Ecumenical Pharmaceutical Network; Global AIDS Alliance; Health Action International (HAI) Africa; Health Access Network (HAN), Ghana; Health GAP (Global Access Project); IHA’s Medical and Social Foundation, India; Love Life Society; Médecins Sans Frontières; National Community of Women Living with HIV/AIDS in Uganda (NACWOLA); Network of Maharashtra People with HIV (NMP+); Positive Generation, Cameroon; Stop AIDS Campaign, UK; TB ACTION Group, Kenya; The Touch of Hope Foundation; and Universities Allied for Essential Medicines.
*Mohga Kamal-Yanni, Kim Nichols, Esther Tallah, Nelson Otwoma [email protected] Oxfam GB, Oxford OX4 2JY, UK (MK-Y); African Services Committee, New York, NY, USA (KN); Cameroon Coalition Against Malaria, Yaounde, Cameroon (ET); and National Empowerment Network of People Living with HIV/AIDS in Kenya, Nairobi, Kenya (NO)
MRI for breast conservation surgery In the COMICE trial (Feb 13, p 563),1 Lindsay Turnbull and colleagues found that preoperative breast MRI did not reduce the rate of re-excisions in women with primary breast cancer who were scheduled for wide local excision. The generalisability of these results is, mostly owing to very low inclusion in many centres, highly questionable. We showed that, in centres with experience, the rate of re-excisions in lobular cancers can be substantially reduced.2 Nevertheless, Turnbull and colleagues conclude “that MRI might not be necessary in this population of patients in terms of reduction of reoperation rates”. Irrespective of the validity, it is tempting to interpret their statement as “preoperative MRI is not indicated in patients with newly detected breast cancer”. However, the current indication for preoperative MRI, as endorsed by various organisations (eg, the American College of Radiology3 and the European Society of Breast Imaging), is not based on reduction of reoperation rates, but rather is a screening recommendation for the contralateral breast. Whereas residual disease in the ipsilateral breast can be effectively treated
with radiotherapy, tumours in the contralateral breast are basically left untreated when undetected. MRI screening of the contralateral breast has, at about 4%, the highest cancer yield of any type of breast cancer screening4 (2% contralateral carcinomas as reported in Turnbull and colleagues’ study is exceptionally low). Early detection of second cancers has been shown to result in increased survival (between 27% and 47%).5 Although that study did not assess preoperative MRI, its conclusions are unambiguous: second cancers should be detected at the earliest stage possible, which is effectively achieved by MRI. Consequently, because the effect of preoperative breast MRI on the ipsilateral breast is not detrimental, the indication is unchanged.
Published Online June 7, 2010 DOI:10.1016/S01406736(10)60940-3
We declare that we have no conflicts of interest.
*R M Mann, C Boetes [email protected] Science Photo Library
Open letter to Lamberto Andreotti, Chief Executive Officer, Bristol-Myers Squibb
Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen, Netherlands (RMM); and University Medical Centre Maastricht, Maastricht, Netherlands (CB) 1
2
3
4
5
Turnbull L, Brown S, Harvey I, et al. Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial. Lancet 2010; 375: 563–71. Mann RM, Loo CE, Wobbes T, et al. The impact of preoperative breast MRI on the re-excision rate in invasive lobular carcinoma of the breast. Breast Cancer Res Treat 2010; 119: 415–22. American College of Radiology. ACR practice guideline for the performance of contrastenhanced magnetic resonance imaging (MRI) of the breast. http://www.acr.org/ SecondaryMainMenuCategories/quality_ safety/guidelines/breast/mri_breast.aspx (accessed June 2, 2010). Brennan ME, Houssami N, Lord S, et al. Magnetic resonance imaging screening of the contralateral breast in women with newly diagnosed breast cancer: systematic review and meta-analysis of incremental cancer detection and impact on surgical management. J Clin Oncol 2009; 27: 5640–49. Houssami N, Ciatto S, Martinelli F, Bonardi R, Duffy SW. Early detection of second breast cancers improves prognosis in breast cancer survivors. Ann Oncol 2009; 20: 1505–10.
In the report by Lindsay Turnbull and colleagues,1 addition of MRI to the preoperative assessment of small breast cancers failed to reduce the reoperation rate, which reached around 19%. Among the tumours excised
Submissions should be made via our electronic submission system at http://ees.elsevier.com/ thelancet/
2213
Correspondence
AP
from 1623 patients, 44% were ductal carcinoma in situ (DCIS). As cited in the Article, a 2006–07 UK audit reveals that 17% of patients with primary breast cancer underwent reoperation for positive tumour margins. A review of 2564 patients with DCIS from a 2003–08 UK audit2 shows that conventional preoperative imaging undersized the extent of disease in 30% of patients. MRI has a higher sensitivity for DCIS than does mammoraphy, especially for DCIS with high nuclear grade.3 MRI perhaps provided the best assessment of the extent and location of such tumours in the breast, but this information could not be used efficiently in the operating theatre. An ideal clear margin has not been determined, despite its possible relation to the rates of reoperation and recurrence of the ipsilateral breast tumour.4 Obtaining a microscopic margin wide enough to protect from ipsilateral recurrence could result in unacceptably high reoperation rates and poor cosmetic results. When looking at short-term outcomes of breast-conserving surgery, analysis might have to be stratified by prespecified margin width. Given an annual risk of ipsilateral recurrence of 1–2%, long-term follow-up would be needed to confirm the accuracy of imaging and the feasibility of surgery. I declare that I have no conflicts of interest.
Tetsuji Fujita [email protected] Department of Surgery, Jikei University School of Medicine, Tokyo 105-8461, Japan 1
2
3
4
2214
Turnbull L, Brown S, Harvey I, et al. Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial. Lancet 2010; 375: 563–71. Thomas J, Evans A, Macartney J, et al. Radiological and pathological size estimations of pure ductal carcinoma in situ of the breast, specimen handling and the influence on the success of breast conservation surgery: a review of 2564 cases from the Sloane Project. Br J Cancer 2010; 102: 285–93. Kuhl CK, Schrading S, Bieling HB, et al. MRI for diagnosis of pure ductal carcinoma in situ: a prospective observational study. Lancet 2007; 370: 485–92. Benson JR, Jatoi I, Keisch M, Esteva FJ, Makris A, Jordan VC. Early breast cancer. Lancet 2009; 373: 1463–79.
Mah-Jong-related deep vein thrombosis The strategy game Mah-Jong is one of the most popular leisure activities in many Chinese communities, especially in rural areas and the residential districts of cities. The activity involves sitting still for long periods and deep concentration. We report a case of deep-vein thrombosis (DVT) associated with Mah-Jong. A 40-year-old woman presented to us in April, 2009, with pain and swelling in the left leg. She had played Mah-Jong for 8 h the previous night and had only drunk a small amount of soft drink during this time. She had no past health problems and no family history of DVT. However, she had been taking an oral contraceptive (desogestrel and ethinylestradiol) for 1 month. Her blood pressure was 115/90 mm Hg and there were no abnormal signs on heart and lung examination. Her left leg was diffusely firm and swollen. Laboratory analysis revealed: haemoglobin 106 g/L; white blood cell count 8·0×109 per L; platelet count 303×109 per L. Plasma lipoprotein concentrations, immunoglobin concentrations, and liver function tests were normal. Test for antiphospholipid antibody was negative. Activated partial thromboplastin time, prothrombin time, and thrombin time were all in the normal range; D-dimer concentration was 3·25 mg/L (normal 0·0–1·0 mg/L), and fibrin degradation product 6·2 mg/L (0·0–5·0 mg/L). Platelet aggregation assay was normal. Thrombophilia screening tests were negative. Colour duplex ultrasonography showed DVT extending from the left external iliac vein to the foretibial vein. The patient was diagnosed with DVT of the left leg, and lowmolecular-weight heparin (nadroparin 0·4 mL, two times per day) was started, lasting 2 weeks. Compression stockings were also used and aspirin (100 mg per day) was taken orally for
3 weeks and maintained for 2 months after hospital discharge. 2 weeks after admission to hospital, the patient’s left leg pain had completely resolved, and the swelling went down gradually. She was discharged home on May 12, 2009, and accepted warfarin (2·5 mg per day) as maintenance therapy. At present, she is asymptomatic and is followed up regularly. Our patient was relatively young (40 years), and had a potential risk factor for venous thrombosis—ie, oral contraceptive use. The attack of DVT was preceded by playing MahJong for 8 h. Could this have been a coincidence? Playing Mah-Jong is associated with prolonged immobility of the circulation of the lower limbs. It has been shown that during quiet sitting for 1 h, the haematocrit rises progressively with a concomitant rise in plasma protein concentration, attributed to blood-flow stasis and higher plasma viscosity.1 Dehydration owing to our patient’s low fluid intake during Mah-Jong playing might have increased the blood viscosity further. Long-term sitting has been related to thrombosis of the deep leg veins.2 Our patient’s condition is similar to “economy class syndrome”1 in its underlying pathophysiological mechanisms. However, the mechanisms of Mah-Jong-related DVT could be complicated by stress (especially when it involves monetary bets) and sleep deprivation, suggesting that MahJong-related DVT is distinct from classic economy class syndrome. We declare that we have no conflicts of interest.
*Guang-sen Zhang, Hong-ling Peng, Ming-yang Deng, Chang Shu, Rui-juan Li, Yang-ming Tang, Min-fei Pei [email protected] Division of Hematology (GSZ, HLP, MYD, RJL, YMT, MFP) and Division of Blood Vessel Surgery (CS), Second Xiang-Ya Hospital, Central South University, ChangSha, Hunan 410011, China 1 2
Moyses C. Economy class syndrome. Lancet 1988; 2: 1077. Homans J. Thrombosis of the deep leg veins due to prolonged sitting. N Engl J Med 1954; 250: 1449.
www.thelancet.com Vol 375 June 26, 2010