- Email: [email protected]
Vascular endothelial growth factor platelet counts and renal cancer
Folkestone earlier this century. We have seen a patient who acquired enteric fever in another seaside town but, although she carried the organism for over 50 years, she does not seem to have transmitted infection to others. In her case, however, the long-term sequelae mean that she cannot be classified as a healthy carrier. In August, 1998, a 72-year-old woman was admitted for investigation of increasing right loin pain, urinary frequency, night sweats, and weight loss. She had a long history of recurrent urinary tract infections and had a staghorn calculus in her right, non-functioning kidney. Imaging showed a mass in the upper pole of the right kidney suggestive of tumour. Her urine grew a coliform, but her fever did not respond to appropriate antimicrobials and her condition deteriorated, and so a radical nephrectomy was performed. Histopathological examination revealed that the renal tissue was almost completely replaced by a squamouscell carcinoma, with a prominent inflammatory response surrounding a large staghorn calculus. Despite adjuvant radiotherapy, 3 months later she developed evidence of extensive retroperitoneal recurrence and she died at home a month later. Preliminary investigations identified the coliform from her urine as a Salmonella sp, but it came as a surprise when the Laboratory of Enteric Pathogens (LEP), Colindale, identified the organism as Salmonella paratyphi B, since we had no recent local cases of paratyphoid fever and she had not left the southwest peninsula for many years. On further questioning, however, she revealed that she had acquired paratyphoid fever during an outbreak in Woolacombe, North Devon, in 1946. This outbreak was extensively investigated and traced to the wife of an ice-cream seller, who was herself a healthy carrier. 2 Review of our laboratory records showed that our patient had had several urine cultures carried out between 1995 and 1998, most of which yielded mixed bacterial growth of questionable significance. On only one occasion, in 1997, had a Salmonella sp been isolated, although on this occasion LEP had been unable to identify it to species level. However, records at LEP showed that she had grown S paratyphi B in stools in 1967. We are not sure whether documented carriage of enteric fever salmonellae for 52 years is a record. However, in this lady’s case it probably led ultimately to her death. Although we cannot prove the
THE LANCET • Vol 353 • June 26, 1999
sequence of events, we suspect that the presence of the organism in her urinary tract may have contributed to the formation of the staghorn calculus, and that the resulting chronic inflammation led ultimately to the development of a squamous-cell carcinoma. In this sense, she was certainly not a “healthy carrier”. Fortunately, as far as we are aware, she did not give rise to a single secondary case during these 52 years. We thank J C Hammonds for permission to report this case, M Barlow and K Cliffe for providing epidemiological information, and T Riordan and L Ward for providing background to the Woolacombe outbreak.
Esther McLarty, *D A B Dance Department of Urology, and *Plymouth Public Health Laboratory, Derriford Hospital, Plymouth PL6 8DH, UK 1
Mortimer PP. Mr N the milker, and Dr Koch’s concept of the healthy carrier. Lancet 1999; 353: 1354–56. 2 Moore B. The detection of paratyphoid carriers in towns by the means of sewage examination. Monthly Bulletin of the Ministry of Health and the Public Health Laboratory Service, vol 6. London: PHLS, 1948: 241–48.
Vascular endothelial growth factor platelet counts and renal cancer Sir—Kenneth O’Byrne and colleagues (May 1, p 1494)1 report the poor outlook of patients with renal cancer and raised serum concentrations of vascular endothelial growth factor (VEGF-SL). They found a positive correlation of VEGF-SL and the platelet count in peripheral blood and concluded that VEGF-SL reflects VEGF released from platelets during blood clotting and circulating free VEGF. Their normal range for VEGF-SL was 62–707 pg/mL VEGF. To keep the substantial range in values to a minimum the concentration of immunoreactive VEGF in serum can be adjusted to the platelet count. We measured the VEGF concentrations in serum and in corresponding plasma samples in 16 patients with cancer who were undergoing adjuvant chemotherapy with a commercially available ELISA. We also found (May 1, p 1529) 2 a strong correlation between peripheral blood platelet counts and serum concentration of VEGF, which allowed the prediction of platelet derived VEGF in serum. We calculated the amount of VEGF released from 106 platelets (VEGFPLT): the normal value was 1·74 pg (95% CI 1·36–2·11 pg, 56 samples) in patients with no measurable VEGF in plasma
samples—ie, in whom virtually no f r e e immunoreactive VEGF was circulating in the blood. If in-vivo platelet destruction occurred (platelet transfusions, patients with sepsis) VEGF in plasma was increased (mean 56 pg/mL [range 26–237]). In those patients, VEGFPLT was 2·79 pg (2·27–3·30, 68 samples, p=0·0003). In a woman with breast cancer VEGFPLT was normal when she was in remission, but increased by three-fold at the time of relapse.* Thus, raised VEGFPLT values may indicate the release of VEGF from platelets in vivo or from other sources, probably from tumour cells. It would be useful to reanalyse the data reported by O’Byrne and colleagues by comparing VEGFPLT and the course of the disease in their patients. *Data available from the authors, on request.
*Eberhard Gunsilius, Andreas L Petzer, Guenther Gastl Division of Haematology and Oncology, University Hospital, 6020 Innsbruck, Austria (e-mail: [email protected]) 1
2
O’Byrne KJ, Dobbs N, Propper D, Smith K, Harris AL. Vascular endothelial growth factor platelet counts, and prognosis in renal cancer. Lancet 1999; 353: 1494–95. Gunsilius E, Petzer AL, Gastl G. Space flight and growth factors. Lancet 1999; 3 5 3 : 1529.
Unethical promotion of lactose-free for mula Sir—In its promotional leaflets for its lactose-free formula Similac LF, Abbott Laboratories says that “SIMILAC LF, the new approach for the treatment of babies with: symptoms of lactose intolerance, babies experience diarrhoea 1–3 times in their first year of life and develop lactose intolerance”, and “unexplained fussiness, requiring special treatment until the symptoms stop”. WHO has since 1981 imposed restrictions on the promotion of artificial milk formulae. And the International Code of marketing of Breast-milk Substitutes states (article 7.2) that, “information provided by manufacturers and distributors to health professionals regarding products within the scope of this code should be restricted to scientific and factual matters”. Nonetheless, Abbott has made unjustified claims, without scientific grounds, that mislead physicians. First, it should not label its product a “new approach” for lactose intolerance because the only treatment for this condition is a lactose-free
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THE LANCET • Vol 353 • June 26, 1999
sequence of events, we suspect that the presence of the organism in her urinary tract may have contributed to the formation of the staghorn calculus, and that the resulting chronic inflammation led ultimately to the development of a squamous-cell carcinoma. In this sense, she was certainly not a “healthy carrier”. Fortunately, as far as we are aware, she did not give rise to a single secondary case during these 52 years. We thank J C Hammonds for permission to report this case, M Barlow and K Cliffe for providing epidemiological information, and T Riordan and L Ward for providing background to the Woolacombe outbreak.
Esther McLarty, *D A B Dance Department of Urology, and *Plymouth Public Health Laboratory, Derriford Hospital, Plymouth PL6 8DH, UK 1
Mortimer PP. Mr N the milker, and Dr Koch’s concept of the healthy carrier. Lancet 1999; 353: 1354–56. 2 Moore B. The detection of paratyphoid carriers in towns by the means of sewage examination. Monthly Bulletin of the Ministry of Health and the Public Health Laboratory Service, vol 6. London: PHLS, 1948: 241–48.
Vascular endothelial growth factor platelet counts and renal cancer Sir—Kenneth O’Byrne and colleagues (May 1, p 1494)1 report the poor outlook of patients with renal cancer and raised serum concentrations of vascular endothelial growth factor (VEGF-SL). They found a positive correlation of VEGF-SL and the platelet count in peripheral blood and concluded that VEGF-SL reflects VEGF released from platelets during blood clotting and circulating free VEGF. Their normal range for VEGF-SL was 62–707 pg/mL VEGF. To keep the substantial range in values to a minimum the concentration of immunoreactive VEGF in serum can be adjusted to the platelet count. We measured the VEGF concentrations in serum and in corresponding plasma samples in 16 patients with cancer who were undergoing adjuvant chemotherapy with a commercially available ELISA. We also found (May 1, p 1529) 2 a strong correlation between peripheral blood platelet counts and serum concentration of VEGF, which allowed the prediction of platelet derived VEGF in serum. We calculated the amount of VEGF released from 106 platelets (VEGFPLT): the normal value was 1·74 pg (95% CI 1·36–2·11 pg, 56 samples) in patients with no measurable VEGF in plasma
samples—ie, in whom virtually no f r e e immunoreactive VEGF was circulating in the blood. If in-vivo platelet destruction occurred (platelet transfusions, patients with sepsis) VEGF in plasma was increased (mean 56 pg/mL [range 26–237]). In those patients, VEGFPLT was 2·79 pg (2·27–3·30, 68 samples, p=0·0003). In a woman with breast cancer VEGFPLT was normal when she was in remission, but increased by three-fold at the time of relapse.* Thus, raised VEGFPLT values may indicate the release of VEGF from platelets in vivo or from other sources, probably from tumour cells. It would be useful to reanalyse the data reported by O’Byrne and colleagues by comparing VEGFPLT and the course of the disease in their patients. *Data available from the authors, on request.
*Eberhard Gunsilius, Andreas L Petzer, Guenther Gastl Division of Haematology and Oncology, University Hospital, 6020 Innsbruck, Austria (e-mail: [email protected]) 1
2
O’Byrne KJ, Dobbs N, Propper D, Smith K, Harris AL. Vascular endothelial growth factor platelet counts, and prognosis in renal cancer. Lancet 1999; 353: 1494–95. Gunsilius E, Petzer AL, Gastl G. Space flight and growth factors. Lancet 1999; 3 5 3 : 1529.
Unethical promotion of lactose-free for mula Sir—In its promotional leaflets for its lactose-free formula Similac LF, Abbott Laboratories says that “SIMILAC LF, the new approach for the treatment of babies with: symptoms of lactose intolerance, babies experience diarrhoea 1–3 times in their first year of life and develop lactose intolerance”, and “unexplained fussiness, requiring special treatment until the symptoms stop”. WHO has since 1981 imposed restrictions on the promotion of artificial milk formulae. And the International Code of marketing of Breast-milk Substitutes states (article 7.2) that, “information provided by manufacturers and distributors to health professionals regarding products within the scope of this code should be restricted to scientific and factual matters”. Nonetheless, Abbott has made unjustified claims, without scientific grounds, that mislead physicians. First, it should not label its product a “new approach” for lactose intolerance because the only treatment for this condition is a lactose-free
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