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Genetic study confirms recurrence of DCIS
SCIENCE AND MEDICINE
Challenges ahead for diabetes management respectively. Nevertheless, at followup, 21% of the 581 patients treated conventionally in DCCT had progression of retinopathy of at least three steps from the level measured at the end of DCCT, compared with only 6% of the 596 patients treated intensively during DCCT (N Engl J Med 2000; 342: 381–89). “It is clear”, says Jonathan Dowler (Moorfields Eye Hospital, London, UK), “that effective control of bloodglucose values is the key to preventing or at least delaying secondary microvascular complications”. But Dowler is less convinced by the arguments of Sandeep Vigan (University of Michigan, Ann Arbor, MI, USA) and colleagues who conclude in their study that retinal screening once every 3 years may be as successful in terms of outcome as annual screening in some patients with type II diabetes (JAMA 2000; 283: 889–96). The researchers suggest that tailoring of screening to individual circumstances may be better than blanket screening. But, says Dowler, screening is far from blanket anyway. “Perhaps only about 25% of the UK’s diabetic population receives systematic annual retinopathy checks”, he says. Oxygen and retinopathy of prematurity “Now that digital retinal Premature babies with moderate retinopathy of photography techniques prematurity (ROP) can be given modest extra allow distant evaluation oxygen without worsening their eye condition. Dale via telemedicine technolPhelps and colleagues (Strong Children’s Research ogy, the time is ripe for Center, University of Rochester, NY, USA) found more cost-effective, but that 41% of infants given supplemental oxygen not necessarily less freprogressed to severe ROP, compared with 48% of quent, screening.” those given no extra oxygen; a non-significant
ith cases of diabetes worldwide increasing, the need to control primary diabetes and to prevent microvascular complications such as retinopathy has never been greater. The newly published follow-up study to the Diabetes Control and Complications Trial (DCCT) confirms that intensive therapy for type I diabetes could help fulfil that need. In DCCT, 1441 patients were followed for 6·5 years and the risk of microvascular complications was shown to be lower in the patients treated intensively than in those treated conventionally. Intensive treatment involved three daily injections of insulin via an insulin pump, with the dose adjusted frequently; conventional treatment was one or two insulin injections per day, with only one blood-glucose measurement every 24 hours. At the end of the trial, all patients were offered intensive treatment for the next 4 years. During the trial, median glycosylated haemoglobin was 9·1% in patients treated conventionally and 7·2% in those treated intensively. This gap narrowed during the 4-year follow-up to 8·2% and 7·9%,
W
absence of invasive disease and in ipsalateral DCIS recurrences, found 16 months to 9·3 years later. In 17 tumour pairs, there was a high concordance in chromosomal alterations. In the final pair, there was no agreement between samples. Later lesions had more genetic changes than initial lesions but the degree of concordance was not dependent on the time interval before recurrence (J Natl Inst Cancer 2000; 92: 313–20). These results are “an important confirmation that these recurrences are the same tumour, sitting there quiescent and coming back at a much later time”, concludes Waldman. Jane Bradbury
Xavier Bosch
Kathryn Senior
Genetic study confirms recurrence of DCIS esearchers at the University of California San Francisco, USA, report that most recurrences of ductal carcinoma in situ (DCIS) are clonally related to the original lesion. Their data, they say, “explain the importance of wide surgical margins and/or radiation therapy during treatment of these noninvasive neoplasias”. Mammographic screening for breast cancer has led to a large increase in the diagnosis of DCIS, a lesion thought to be a precursor to invasive breast cancer. DCIS recurs after lumpectomy in 5–25% of cases, but are these recurrences residual or de novo disease? Frederic Waldman’s team examined chromosomal alterations in 18 DCIS lesions which occurred in the
THE LANCET • Vol 355 • February 19, 2000
S
ildenafil (Viagra) is active on the oesophageal smooth muscle of patients with achalasia, producing a decrease in lower-oesophageal-sphincter tone, residual pressure, and the amplitude of pressure waves, report Mauro Bortolotti and colleagues at the University of Bologna, Italy. Sildenafil selectively inhibits phosphodiesterase type 5. This increases the concentration of cyclic guanosine monophosphate, a second messenger for nitric oxide (NO), which in turn regulates smooth-muscle tone in the penile corpus cavernosum and in the lower oesophageal sphincter. In patients with achalasia—a disorder characterised by lower oesophageal sphincter hypertony, lack of lower oesophageal sphincter relaxation upon swallowing, and absence of peristalsis in the oesophageal body—NO synthesis from the non-adrenergic, non-cholinergic inhibitory neurons of the gastrooesophageal junction is impaired. 14 patients with idiopathic achalasia who had an oesophageal diameter of 5 cm or less were given either 50 mg sildenafil dissolved in water (seven patients) or placebo by direct infusion into the stomach. In the patients given sildenafil, lower-oesophageal-sphincter tone, residual pressure, and wave amplitude were significantly lower compared with basal measurements and with the placebo group. The inhibitory effect peaked at 15–20 minutes and lasted for less than an hour. However, the effect of sildenafil varied widely among patients. This high variability “could be explained by the fact that the pathological process of achalasia has not damaged the intrinsic neurons to the same degree in all patients”, say the researchers (Gastroenterology 2000; 118: 253–57). Now, says Bortolotti, “it would be interesting to experiment with sildenafil, or similar compounds acting on phosphodiesterase type 5, in other spastic motility disorders of the oesophagus and other sections of the gut, which are, or could be, ascribed to a functional impairment of nitrergic neurons”.
difference (Pediatrics 2000; 105: 295–310).
R
Sildenafil’s effects extended to additional organs
631
Challenges ahead for diabetes management respectively. Nevertheless, at followup, 21% of the 581 patients treated conventionally in DCCT had progression of retinopathy of at least three steps from the level measured at the end of DCCT, compared with only 6% of the 596 patients treated intensively during DCCT (N Engl J Med 2000; 342: 381–89). “It is clear”, says Jonathan Dowler (Moorfields Eye Hospital, London, UK), “that effective control of bloodglucose values is the key to preventing or at least delaying secondary microvascular complications”. But Dowler is less convinced by the arguments of Sandeep Vigan (University of Michigan, Ann Arbor, MI, USA) and colleagues who conclude in their study that retinal screening once every 3 years may be as successful in terms of outcome as annual screening in some patients with type II diabetes (JAMA 2000; 283: 889–96). The researchers suggest that tailoring of screening to individual circumstances may be better than blanket screening. But, says Dowler, screening is far from blanket anyway. “Perhaps only about 25% of the UK’s diabetic population receives systematic annual retinopathy checks”, he says. Oxygen and retinopathy of prematurity “Now that digital retinal Premature babies with moderate retinopathy of photography techniques prematurity (ROP) can be given modest extra allow distant evaluation oxygen without worsening their eye condition. Dale via telemedicine technolPhelps and colleagues (Strong Children’s Research ogy, the time is ripe for Center, University of Rochester, NY, USA) found more cost-effective, but that 41% of infants given supplemental oxygen not necessarily less freprogressed to severe ROP, compared with 48% of quent, screening.” those given no extra oxygen; a non-significant
ith cases of diabetes worldwide increasing, the need to control primary diabetes and to prevent microvascular complications such as retinopathy has never been greater. The newly published follow-up study to the Diabetes Control and Complications Trial (DCCT) confirms that intensive therapy for type I diabetes could help fulfil that need. In DCCT, 1441 patients were followed for 6·5 years and the risk of microvascular complications was shown to be lower in the patients treated intensively than in those treated conventionally. Intensive treatment involved three daily injections of insulin via an insulin pump, with the dose adjusted frequently; conventional treatment was one or two insulin injections per day, with only one blood-glucose measurement every 24 hours. At the end of the trial, all patients were offered intensive treatment for the next 4 years. During the trial, median glycosylated haemoglobin was 9·1% in patients treated conventionally and 7·2% in those treated intensively. This gap narrowed during the 4-year follow-up to 8·2% and 7·9%,
W
absence of invasive disease and in ipsalateral DCIS recurrences, found 16 months to 9·3 years later. In 17 tumour pairs, there was a high concordance in chromosomal alterations. In the final pair, there was no agreement between samples. Later lesions had more genetic changes than initial lesions but the degree of concordance was not dependent on the time interval before recurrence (J Natl Inst Cancer 2000; 92: 313–20). These results are “an important confirmation that these recurrences are the same tumour, sitting there quiescent and coming back at a much later time”, concludes Waldman. Jane Bradbury
Xavier Bosch
Kathryn Senior
Genetic study confirms recurrence of DCIS esearchers at the University of California San Francisco, USA, report that most recurrences of ductal carcinoma in situ (DCIS) are clonally related to the original lesion. Their data, they say, “explain the importance of wide surgical margins and/or radiation therapy during treatment of these noninvasive neoplasias”. Mammographic screening for breast cancer has led to a large increase in the diagnosis of DCIS, a lesion thought to be a precursor to invasive breast cancer. DCIS recurs after lumpectomy in 5–25% of cases, but are these recurrences residual or de novo disease? Frederic Waldman’s team examined chromosomal alterations in 18 DCIS lesions which occurred in the
THE LANCET • Vol 355 • February 19, 2000
S
ildenafil (Viagra) is active on the oesophageal smooth muscle of patients with achalasia, producing a decrease in lower-oesophageal-sphincter tone, residual pressure, and the amplitude of pressure waves, report Mauro Bortolotti and colleagues at the University of Bologna, Italy. Sildenafil selectively inhibits phosphodiesterase type 5. This increases the concentration of cyclic guanosine monophosphate, a second messenger for nitric oxide (NO), which in turn regulates smooth-muscle tone in the penile corpus cavernosum and in the lower oesophageal sphincter. In patients with achalasia—a disorder characterised by lower oesophageal sphincter hypertony, lack of lower oesophageal sphincter relaxation upon swallowing, and absence of peristalsis in the oesophageal body—NO synthesis from the non-adrenergic, non-cholinergic inhibitory neurons of the gastrooesophageal junction is impaired. 14 patients with idiopathic achalasia who had an oesophageal diameter of 5 cm or less were given either 50 mg sildenafil dissolved in water (seven patients) or placebo by direct infusion into the stomach. In the patients given sildenafil, lower-oesophageal-sphincter tone, residual pressure, and wave amplitude were significantly lower compared with basal measurements and with the placebo group. The inhibitory effect peaked at 15–20 minutes and lasted for less than an hour. However, the effect of sildenafil varied widely among patients. This high variability “could be explained by the fact that the pathological process of achalasia has not damaged the intrinsic neurons to the same degree in all patients”, say the researchers (Gastroenterology 2000; 118: 253–57). Now, says Bortolotti, “it would be interesting to experiment with sildenafil, or similar compounds acting on phosphodiesterase type 5, in other spastic motility disorders of the oesophagus and other sections of the gut, which are, or could be, ascribed to a functional impairment of nitrergic neurons”.
difference (Pediatrics 2000; 105: 295–310).
R
Sildenafil’s effects extended to additional organs
631