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Management of childhood soft-tissue sarcomas
659
meningitis.1,2 Nonetheless, the reports of mycoplasmal or ureaplasmal CSF infection that have appeared lately prompt us to suggest that these have been but a small fraction of the most severe cases, the vast majority going undiagnosed. Our findings,’ the above
case-reports,5,’ the one CSF isolate in the study by Shaw et al, and the potential for severe neurological handicap reinforces our belief in the importance of looking for mycoplasmas in the CNS. We recommended that mycoplasmas should be sought in the CSF of any infant with progressive hydrocephalus, with radiographic or other evidence of congenital infection, or with CSF pleocytosis. We stopped short of recommending routine mycoplasmal culture of all CSF specimens on grounds of cost and because there are not enough epidemiological data to support or refute such a policy. Shaw et al do not state how many infants with two
intraventricular haemorrhage and/or progressive hydrocephalus were cultured for mycoplasmas, what other CSF abnormalities were identified, or whether any of the babies had been previously discharged. Shaw et al thought that their 1 infected infant might have acquired ureaplasma infection within hospital or iatrogenically, but there is no published evidence that such transmission is important; the most likely route was spread from the respiratory tract. Some babies in our studies acquired the organisms in utero, with CNS invasion in some. Our study1 prompted us to wonder if mycoplasmal CSF isolates were unique to the hospital population sampled or whether they were typical of newborn babies in general. In a second study’ 318 babies, predominantly full-term, who had been born in one of four suburban community hospitals and who had had lumbar puncture for clinical indications, had CSF cultured for mycoplasmas. M hominis was isolated from 9 and U urealyticum from 5, while only 3 CSF specimens were positive (0-9%) for routine bacterial pathogens. We still think that systemic mycoplasmal infections in the newborn deserve consideration as possible causes of CNS disease in infants. Departments of Microbiology and Pediatrics, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
KEN B. WAITES DENNIS T. CROUSE GAIL H. CASSELL
1. Waites KB, Rudd PT, Crouse DT, et al. Chronic Ureaplasma urealyticum and Mycoplasma hominis infections of the central nervous system in preterm infants. Lancet 1988; i. 17-21. 2. Davies PA, Gothefors LA. Bacteremia, infections of the central nervous and respiratory systems. In: Bacterial infections of the fetus and newborn infant. Philadelphia: WB Saunders, 1984: 122-42. 3. Cassell GH, Waites KB, Crouse DT, et al. Association of Ureaplasma urealyticum infection of the lower respiratory tract with chronic lung disease and death in very-low-birthweight infants. Lancet 1988; ii: 240-45. 4. Waites KB, Crouse DT, Philips JB, et al. Ureaplasmal pneumonia and sepsis associated with persistent pulmonary hypertension of the newborn. Pediatrics 1989; 83: 84-89 5. Gilbert GL, Lawe F, Macinnes SJ. Chronic Mycoplasma hominis infection complicating severe intraventricular hemorrhage in a premature neonate. Pediatr Infect Dis J 1988; 7: 817-18. 6. McDonald JC, Moore D. Mycoplasma hominis meningitis in a premature infant. Pediatr Infect Dis J 1988; 7: 795-98. 7. Waites KB, Duffy LB, Crouse DT, et al. Mycoplasmal infections of cerebrospinal fluid in newborn infants from a community hospital population. Pediatr Infect Dis J
(in press).
Management
of childhood soft-tissue
initial intensive chemotherapy, aggressive and often mutilating surgery, and wide-field irradiation can be avoided in this highly chemosensitive tumour. Early studies by SIOPI (often cited) had disappointing results, with high local relapse rates and poor subsequent cure. Nevertheless, the results showed that local disease control was no better in children receiving early extensive surgery and/or radiation than in those who received primary chemotherapy with surgery and/or radiation to residual tumour volumes. With current, more intensive chemotherapy regimens and the option of effective second-line chemotherapy the situation seems to be changing. It is difficult to compare results with the IRS studies because of differences in staging systems and therefore only crude survival can be taken as an indicator of outcome. In IRS II, which ran between 1978 and 1984, the overall 5-year survival was 62%. With shorter follow-up, the more recent IRS III study has a 3 year survival of 73%. Analysis of the SIOP malignant mesenchymal tumours 1984 study (1984-89) shows an overall survival at 4 years of 64% and 70% at 3 years (Flamant F, personal communication). Although for certain subgroups the local relapse rate remains higher in the SIOP study, possibly because of omission of elective radiotherapy, the salvage rate of up to a third of patients seems to compensate for this. It is hoped that further intensification of front-line chemotherapy may reduce the local relapse rate. The issue of adverse late effects is now a major consideration in the design of paediatric cancer treatment programmes. The "conservative" European approach with conservation of organs and normal tissue is hoped to ultimately prove comparable with the "conservative" American approach retaining an admittedly proven therapeutic strategy but with inevitable sequelae. Royal Marsden Hospital, Sutton, Surrey SM2 5PT, UK
C. R. PINKERTON
Birmingham Children’s Hospital, Birmingham
M. C. G. STEVENS
F, Rodary C, Voute PA, Otten J. Primary chemotherapy in the treatment of rhabdomyosarcoma m children. trial of the International Society of Pediatric Oncology (SIOP): preliminary results. Radiother Oncol 1985; 3: 227-36. 2. Maurer H, Gehan E, Hays D, Newton W, Tefft M. Intergroup rhabdomyosarcoma study (IRS)-II: a final report. Med Ped Oncol 1988; 16: 414-15. 3. Maurer H, Gehan E, Cnst W, et al. International rhabdomyosarcoma study (IRS)-III: a preliminary report of overall outcome. Med Ped Oncol 1989; 17: 310. 1. Flamant
Rarity of neuroblastoma in East Africa SiR,—Dr Lucas and Dr Fischer (Jan 13, p 115) dispute my claim (Oct 21, p 978) that neuroblastoma is rare in five East African countries. They contend that the accuracy of diagnoses has greatly deteriorated since the 1960s, and that instead of relative frequencies Wilms’tumour would be a good yardstick against which to measure the frequency of neuroblastoma (when studies are not populationbased). I have used Wilms’tumour in this way since 1973, but in my report I chose to use the more familiar relative frequency (percentage of all childhood cancers), following the lead of the International Agency for Research on Cancer.1 RATIO OF NEUROBLASTOMA (Nb) TO WILMS’ TUMOUR (WT) IN EAST AFRICA
sarcomas
SIR,-In his review of Pizzo and Poplack’s Principles and Practice of Oncology, Dr Plowman (Feb 10, p 318) suggests that the chapter on rhabdomyosarcoma clearly exemplified "the better management" of this tumour in the United States than in Europe and that doctors entering patients in the current European SIOP (Societe Internationale d’Oncologie Pediatrique) trial should study carefully the survival figures from the Intergroup Rhabdomyosarcoma studies (IRS). Pediatric
For those readers unfamiliar with the transatlantic debate about the management of childhood soft-tissue sarcomas and to reassure other "Europeans" who are entering patients in the present SIOP study further information might be of interest. The controversy centres around the issue of whether, by giving
!ARC=)nternat!ona!
Agency
for
Research
Against Cancer, UH = University Hospital *Ref 1, tref 2, tref 3
on
Cancer, UICC -International Union
meningitis.1,2 Nonetheless, the reports of mycoplasmal or ureaplasmal CSF infection that have appeared lately prompt us to suggest that these have been but a small fraction of the most severe cases, the vast majority going undiagnosed. Our findings,’ the above
case-reports,5,’ the one CSF isolate in the study by Shaw et al, and the potential for severe neurological handicap reinforces our belief in the importance of looking for mycoplasmas in the CNS. We recommended that mycoplasmas should be sought in the CSF of any infant with progressive hydrocephalus, with radiographic or other evidence of congenital infection, or with CSF pleocytosis. We stopped short of recommending routine mycoplasmal culture of all CSF specimens on grounds of cost and because there are not enough epidemiological data to support or refute such a policy. Shaw et al do not state how many infants with two
intraventricular haemorrhage and/or progressive hydrocephalus were cultured for mycoplasmas, what other CSF abnormalities were identified, or whether any of the babies had been previously discharged. Shaw et al thought that their 1 infected infant might have acquired ureaplasma infection within hospital or iatrogenically, but there is no published evidence that such transmission is important; the most likely route was spread from the respiratory tract. Some babies in our studies acquired the organisms in utero, with CNS invasion in some. Our study1 prompted us to wonder if mycoplasmal CSF isolates were unique to the hospital population sampled or whether they were typical of newborn babies in general. In a second study’ 318 babies, predominantly full-term, who had been born in one of four suburban community hospitals and who had had lumbar puncture for clinical indications, had CSF cultured for mycoplasmas. M hominis was isolated from 9 and U urealyticum from 5, while only 3 CSF specimens were positive (0-9%) for routine bacterial pathogens. We still think that systemic mycoplasmal infections in the newborn deserve consideration as possible causes of CNS disease in infants. Departments of Microbiology and Pediatrics, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
KEN B. WAITES DENNIS T. CROUSE GAIL H. CASSELL
1. Waites KB, Rudd PT, Crouse DT, et al. Chronic Ureaplasma urealyticum and Mycoplasma hominis infections of the central nervous system in preterm infants. Lancet 1988; i. 17-21. 2. Davies PA, Gothefors LA. Bacteremia, infections of the central nervous and respiratory systems. In: Bacterial infections of the fetus and newborn infant. Philadelphia: WB Saunders, 1984: 122-42. 3. Cassell GH, Waites KB, Crouse DT, et al. Association of Ureaplasma urealyticum infection of the lower respiratory tract with chronic lung disease and death in very-low-birthweight infants. Lancet 1988; ii: 240-45. 4. Waites KB, Crouse DT, Philips JB, et al. Ureaplasmal pneumonia and sepsis associated with persistent pulmonary hypertension of the newborn. Pediatrics 1989; 83: 84-89 5. Gilbert GL, Lawe F, Macinnes SJ. Chronic Mycoplasma hominis infection complicating severe intraventricular hemorrhage in a premature neonate. Pediatr Infect Dis J 1988; 7: 817-18. 6. McDonald JC, Moore D. Mycoplasma hominis meningitis in a premature infant. Pediatr Infect Dis J 1988; 7: 795-98. 7. Waites KB, Duffy LB, Crouse DT, et al. Mycoplasmal infections of cerebrospinal fluid in newborn infants from a community hospital population. Pediatr Infect Dis J
(in press).
Management
of childhood soft-tissue
initial intensive chemotherapy, aggressive and often mutilating surgery, and wide-field irradiation can be avoided in this highly chemosensitive tumour. Early studies by SIOPI (often cited) had disappointing results, with high local relapse rates and poor subsequent cure. Nevertheless, the results showed that local disease control was no better in children receiving early extensive surgery and/or radiation than in those who received primary chemotherapy with surgery and/or radiation to residual tumour volumes. With current, more intensive chemotherapy regimens and the option of effective second-line chemotherapy the situation seems to be changing. It is difficult to compare results with the IRS studies because of differences in staging systems and therefore only crude survival can be taken as an indicator of outcome. In IRS II, which ran between 1978 and 1984, the overall 5-year survival was 62%. With shorter follow-up, the more recent IRS III study has a 3 year survival of 73%. Analysis of the SIOP malignant mesenchymal tumours 1984 study (1984-89) shows an overall survival at 4 years of 64% and 70% at 3 years (Flamant F, personal communication). Although for certain subgroups the local relapse rate remains higher in the SIOP study, possibly because of omission of elective radiotherapy, the salvage rate of up to a third of patients seems to compensate for this. It is hoped that further intensification of front-line chemotherapy may reduce the local relapse rate. The issue of adverse late effects is now a major consideration in the design of paediatric cancer treatment programmes. The "conservative" European approach with conservation of organs and normal tissue is hoped to ultimately prove comparable with the "conservative" American approach retaining an admittedly proven therapeutic strategy but with inevitable sequelae. Royal Marsden Hospital, Sutton, Surrey SM2 5PT, UK
C. R. PINKERTON
Birmingham Children’s Hospital, Birmingham
M. C. G. STEVENS
F, Rodary C, Voute PA, Otten J. Primary chemotherapy in the treatment of rhabdomyosarcoma m children. trial of the International Society of Pediatric Oncology (SIOP): preliminary results. Radiother Oncol 1985; 3: 227-36. 2. Maurer H, Gehan E, Hays D, Newton W, Tefft M. Intergroup rhabdomyosarcoma study (IRS)-II: a final report. Med Ped Oncol 1988; 16: 414-15. 3. Maurer H, Gehan E, Cnst W, et al. International rhabdomyosarcoma study (IRS)-III: a preliminary report of overall outcome. Med Ped Oncol 1989; 17: 310. 1. Flamant
Rarity of neuroblastoma in East Africa SiR,—Dr Lucas and Dr Fischer (Jan 13, p 115) dispute my claim (Oct 21, p 978) that neuroblastoma is rare in five East African countries. They contend that the accuracy of diagnoses has greatly deteriorated since the 1960s, and that instead of relative frequencies Wilms’tumour would be a good yardstick against which to measure the frequency of neuroblastoma (when studies are not populationbased). I have used Wilms’tumour in this way since 1973, but in my report I chose to use the more familiar relative frequency (percentage of all childhood cancers), following the lead of the International Agency for Research on Cancer.1 RATIO OF NEUROBLASTOMA (Nb) TO WILMS’ TUMOUR (WT) IN EAST AFRICA
sarcomas
SIR,-In his review of Pizzo and Poplack’s Principles and Practice of Oncology, Dr Plowman (Feb 10, p 318) suggests that the chapter on rhabdomyosarcoma clearly exemplified "the better management" of this tumour in the United States than in Europe and that doctors entering patients in the current European SIOP (Societe Internationale d’Oncologie Pediatrique) trial should study carefully the survival figures from the Intergroup Rhabdomyosarcoma studies (IRS). Pediatric
For those readers unfamiliar with the transatlantic debate about the management of childhood soft-tissue sarcomas and to reassure other "Europeans" who are entering patients in the present SIOP study further information might be of interest. The controversy centres around the issue of whether, by giving
!ARC=)nternat!ona!
Agency
for
Research
Against Cancer, UH = University Hospital *Ref 1, tref 2, tref 3
on
Cancer, UICC -International Union