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SIOP treatment guidelines for renal tumours in small infants: fact or fantasy?
European Journal of Surgical Oncology 2000; 26: 567–570 doi:10.1053/ejso.2000.0948, available online at http://www.idealibrary.com on
SIOP treatment guidelines for renal tumours in small infants: fact or fantasy? N. S. Levie∗, J. de Kraker†, J. P. M. Bo¨kkerink‡, I. M. Appel¶ and D. C. Aronson∗ ∗Department of Paediatric Surgery and †Department of Paediatric Oncology, Emma Children’s Hospital, Academical Medical Center, University of Amsterdam; ‡Department of Paediatric Oncology, University Hospital Nijmegen and ¶Department of Oncology, Sophia Children’s Hospital, Rotterdam, The Netherlands
Aims: Since as far back as 1980, SIOP (Socie´te´ Internationale d’Oncologie Pe´diatrique) have advocated primary nephrectomy (PN) only for unilateral renal tumours in patients Ζ6 months of age. Patients aged 7–12 months have been pre-treated with chemotherapy before nephrectomy is performed. The aims of this study were: (1) to evaluate how the SIOP guidelines for infants 0–6 months and 7–12 months of age were followed in three Dutch centres for Paediatric Oncology before and after 1980, and (2) to carry out an inventory of the incidence of benign tumours in this patient population below 12 months of age. Methods: Retrospective analysis of 67 patients under 12 months of age (1969–1995) with a unilateral renal tumour at diagnosis was carried out. Demographics, pathology, staging and treatment variables were analysed. Results: Of 67 patients, 39 were male and 28 female. Twenty-six (39%) infants were 0–6 months of age (group A) and 41 (61%) were 7–12 months old (group B). In group A there were five patients (19%) with congenital mesoblastic nephroma (CMN), out of which one was still-born and therefore received no treatment, and 21 patients with a unilateral Wilms’ tumour (WT). Fourteen of the 25 patients (56%) were treated with PN, including four patients with CMN. In group B there was one patient (2%) with CMN and 40 patients with WT. Thirteen of the patients (31%) were treated with PN. A total of 15 patients were treated before 1980 and 26 after 1980. Eight of 15 (53%) patients were treated with PN before 1980 and 21/26 (81%) were pre-treated after 1980, according to the protocol. Conclusion: Despite the SIOP recommendations, only 56% of patients Ζ6 months were treated with PN. The percentage of pre-treated patients in group B increased after changing the protocol in 1980 to 81%. In the age group included in the SIOP studies the protocol had been used significantly more often compared to the group included in the guidelines only. The known excellent survival rate justifies a primary nephrectomy approach in the youngest age group, however, in cases of a large tumour, pre-operative chemotherapy in reduced doses may still be considered. In our study fewer CMN were found (19%) than reported in the SIOP studies (20–70%), most likely due to a low registration rate, as a consequence of excluding this very young age group (0–6 months) from the SIOP protocol. 2000 Harcourt Publishers Ltd Key words: nephroblastoma; Wilms’ tumour; congenital mesoblastic nephroma; renal tumour.
Introduction Wilms’ tumours (nephroblastoma) are the most common renal tumours in infancy,1 and the fourth commonest malignant solid tumours in children from 0–14 years. It affects approximately one child per 10 000 children of less than 15 years of age, worldwide.2 In neonates, about 25% of renal tumours are benign Congenital Mesoblastic Nephroma (CMN) (Fig. 1).3 In infants aged 0–6 months Correspondence to: D. C. Aronson, MD, Department of Paediatric Surgery, Emma Children’s Hospital AMC, Academical Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. Fax: +31 (20) 566-4440. 0748–7983/00/060567+04 $35.00/0
this percentage is reported to be 29%,4 and it usually presents below the age of 3 months. Before 1980, patients Ζ12 months of age were excluded from the SIOP nephroblastoma protocol because of the—scarcely reported—high incidence of benign tumours and the fear of morbidity (i.e. venoocclusive disease) after chemotherapy in small infants. As a guideline for treatment, primary nephrectomy had been advocated in these patients. Since 1980, age as an exclusion criterion was changed from below 12 months to below 6 months. From this date, infants aged 7–12 months have been included in the SIOP-protocol and have been pretreated with chemotherapy before surgery. The aims of this study were: (1) to evaluate how the SIOP guidelines for infants 0–6 months and 7–12 months of age were followed 2000 Harcourt Publishers Ltd
568
N. S. Levie et al.
Fig. 1. (A) Mesoblastic Nephroma: classical (leiomyomatous) type. The tumour shows a fascicular arrangement of long, interwoven bundles of leiomyoma-like cells with long vesicular nuclei with blunt ends. There are some entrapped tubules. (B) Non-anaplastic Nephroblastoma (Blastemal predominant). The tumour is mainly composed of blastema with few tubules.
Table 1. Post-surgical Wilms’ tumour staging used by the SIOP Stage I: Stage II:
Stage III:
Stage IV:
Tumour limited to the kidney and completely excised. The tumour has not ruptured or punctured before excision. Tumour extending outside the kidney, but completely excised. Local extension of the tumour, in particular penetration into perirenal and/or peripelvic tissues beyond the capsule of the tumour, invasion of the hilar nodes and/or peri-aortic nodes, invasion of the renal vessels outside the kidney or thrombosis caused by the tumour, or invasion in the ureter. Incomplete excision, without haematogenous metastases; tumour biopsy taken before or during surgery, tumour rupture before or during surgery, peritoneal metastases which are not simple tumour adhesions of stage II, lymph node invasion beyond the local regional nodes. Distant metastases involving lungs, liver, bones, brain, etc.
in three Dutch centres for Paediatric Oncology before and after 1980, and (2) to carry out an inventory on the incidence of benign tumours in this patient population below 12 months of age.
using the chi-squared test, with the level of significance at 0.05.
Results Patients and methods From 1969–1995, 67 patients below 12 months of age with an unilateral renal tumour were identified in three different centres (the Emma Children’s Hospital AMC, Amsterdam (AMC), the University Hospital Nijmegen (UHN) and the Sophia Children’s Hospital, Rotterdam (SCH) through the SIOP-database in the SIOP-office in Amsterdam, The Netherlands. Thirty-eight of these patients were treated after 1980. According to age at diagnosis, patients were divided into group A (age 0–6 months) and group B (age 7–12 months). Data regarding demographics, pathology, staging and treatment were obtained from the medical charts, the operating reports and the office notes in the various centres. All patients were staged according to the SIOP staging system, which is shown in Table 1. Significance was tested
Of the 67 infants studied (44 at AMC, 13 at UHN and 10 at SCH), 39 were male and 28 female. Group A contained 26 patients (39%) and group B 41 patients (61%). In Group A, pathology showed the presence of CMN in five patients (19%), of whom one was still-born, and a unilateral Wilms’ tumours (WT) in 21 patients. Tumour staging is shown in Table 2. Of the 25 patients with a unilateral tumour, 14 (56%) were treated with primary nephrectomy (CMN: four stage I; WT: six stage I, one stage II, three stage III), nine patients (36%) were treated with primary chemotherapy (WT; six stage I, one state II, two stage III), and two with primary radiotherapy (both stage III WT, and treated at the start of the study period) (see Table 3). Eight patients (28%), including two with CMN, had surgery only and are still in complete remission. In group B one patient had a CMN (2%) and 40 were Wilms’ tumour cases. Tumour staging is shown in Table 2.
569
Guidelines for renal tumours in small infants Table 2. The stage distribution per group. Group A: patients age 0–6 months, group B patients age 7–12 months. Patients were staged after surgery according to the SIOP staging system Group A
Group B
Wilms’ tumours (n=61)
stage I stage II stage III stage IV total
12 2 7 0 21
26 7 6 1 40
CMN (n=6)
stage I stage III
5 —
— 1
Table 3. Number of patients treated with PN or pre-treatment in group A Group A
Total
Prim. Nephrect. Pre-treatment Total
14 (56%) 11 (44%) 25
Table 4. Number of patients treated with PN or pre-treatment in group B Group B Prim. Nephrect. Pre-treatment Total
SIOP 1, 2, 5 SIOP 6, 9, 93-01 (<1980) (>1980) 8 (53%) 7 (47%) 15
5 (19%) 21 (81%) 26
Total 13 (32%) 28 (68%) 41
Fifteen patients were treated before 1980, of whom eight (53%) were treated with PN. The patient with CMN (stage III) was treated with pre-operative CT and two patients with a Wilms’ tumour with pre-operative RT (one stage I, one stage III) before 1980. After 1980, 26 patients were treated, of whom 21 (81%) were treated with primary CT, according to the treatment protocol. The number of patients treated with PN or primary CT or RT, before or after 1980, are shown in Table 4. Chemotherapy was given in 39/41 (95%) of the patients. In group B, there is no significant difference found in using the protocol or not before and after 1980 (P=0.063; RR 1.51; CI 0.91–2.52). In the age group included in the SIOP protocol (group B after 1980) the use of the protocol was 21/26 (81%). This is statistically significantly higher compared to the frequency in the group included in the guidelines only (0–6 months of age and 7–12 months of age, treated before 1980). In this group the percentage of patients treated according to the guidelines was 55% (22/40).
from the SIOP-treatment protocol and, as a guideline, primary nephrectomy was advocated, whenever possible, in these patients. In our study this guideline was applied in 56% of cases in group A. The reason for this low percentage is unclear, but may reflect (1) the reluctance to perform primary surgery in view of the necessity for larger tumour resections with the increased chance for ruptures, and (2) the experienced safety of chemotherapy in reduced doses with relatively low incidence of toxic late effects in previous SIOP studies. This experience was also the reason for including infants aged 7–12 months in the protocol in 1980. In group B, before 1980, the guideline to perform primary nephrectomy had been applied in 53% of cases. After 1980, the protocol to pre-treat these patients with chemotherapy, has been applied in 81% of cases. In retrospect, there is no evident explanation found to explain why the protocol was applied in such a low percentage of the patients. The difference between 53% and 81% is not statistically significant, probably due to the small numbers involved. Comparing the age group included in the SIOP treatment protocol (group B after 1980) to the group not included (group A, and B before 1980), the protocol seemed to be used more frequently than the guideline. Apparently a protocol may be more thoroughly followed than a guideline, provided that the registration rate in both groups is equal. The incidence of CMN has been documented to vary between 20–50%3,5 in all primary renal tumours of children younger than 12 months of age. The incidence seems to increase over the various consecutive SIOP studies. In SIOP1, 2 and 5 the percentage of CMN was reported to be 16%3 in all infants, and SIOP-6 showed an incidence of 29% in infants <6 months of age.4 In SIOP-9, 48% CMN was reported in infants <6 months of age.5 This picture probably does not reflect a true increase of the incidence in CMN, but may be due to a more accurate central review. In our data, the incidence of CMN was 19% in patients <6 months of age. This rather low percentage may, most likely, be due to a low registration rate, as a consequence of the exclusion of the very young age group (0–6 months) from the treatment protocol. In summary, from our evaluation of the application of the SIOP protocol, the percentage of patients over 6 months who were not pre-treated seems rather high, although presently it is known that the pre-operative chemotherapy of the SIOP protocols is safe for children of this age and weight. However, the protocol seemed to be followed better than the guideline. In view of the 55% of cases in which the guideline was followed its effect seems more to be a fantasy than a fact. As shown in the literature, the excellent survival rate still justifies a primary nephrectomy approach in the youngest age group.1,4,6
References Discussion SIOP Wilms’ tumour-1, 2 and 5 trials excluded patients <12 months of age and these patients were treated with primary nephrectomy, whenever possible. From 1980 (SIOP-6) till to date, only patients <6 months of age have been excluded
1 Corn BW, Goldwein JW, Evans I, D’Angio GJ. Outcomes in low-risk babies treated with half-dose chemotherapy according to the Third National Wilms’ Tumor Study. J Clin Oncol 1992; 10: 1305–9. 2 Breslow N, Olshan A, Beckwith JB, Green DM. Epidemiology of Wilms’ tumor. Med Pediatr Oncol 1993; 21: 172–81.
570
N. S. Levie et al.
3 Coppes MJ. Wilms’ tumor, a compilation of clinical and molecular characteristics. PhD Thesis, University of Amsterdam, 1992. 4 Coppes MJ, Tournade MF, Lemerle J, et al. Preoperative care of infants with nephroblastoma. The SIOP 6 experience. Cancer 1992; 69: 2721–5. 5 Godzinski J, Tournade MF, de Kraker J, et al. Importance of the
intraabdominal tumour extension at surgery for renal tumours in patients younger than 6 months. The SIOP nephroblastoma study no-9. Med Pediatr Oncol 1997; 29: 323–4. 6 Ritchey M, Azizkhan R, Beckwith B, et al. Neonatal Wilms’ tumor. J Ped Surgery 1995; 30: 856–9. Accepted for publication 26 January 2000
World Wide Web Search Engines (I) The Internet is now a mature and massive information resource, whose use by the public is increasingly purposeful rather than curiosity driven. The Search Engine is the first entry point for many users of the World Wide Web, seeking general or specific information. A Search Engine is a computer data base which references a significant proportion of the Internet’s Web Sites and their content, along with the Web addresses and hot links to specific sites. A typical Search Engine is a Web Site which provides a search box on its front page, into which the query word or phrase is typed. Each query is governed by simple rules to help refine and focus the search. The Search Engine will present a list of sites containing the search phrase, with a direct link to each site in the list. Queries about common items may generate a massive and unmanageable numbers of responses. The searches are usually structured so that the most popular Web Sites are listed first in the search results. The technology behind these searches is so fast that the results of even the most arcane research enquiries are commonly retrieved in a few seconds. The absolute size of the public Web is uncertain at any time, but it is now believed to be approaching one billion pages of information. Protected, controlled access and commercial sites, intranets and extranets may contain still larger data resources. Automatic search engines compile their data bases in one of two principal ways, which are not mutually exclusive. The Engines use powerful software to scan or ‘crawl’ the Web continuously, cataloguing in intelligent ways every significant word, phrase and Web address for rapid and interactive retrieval. Examples of such systems include FAST (alltheweb.com), AltaVista (altavista.com) and Google (google.com). Some of the principal search engines rely on human operators to index and catalogue the Web content in useful ways. Examples include Yahoo (yahoo.com) and Open Directory (dmoz.org). Other Search Engines may be regionally based, such as Voila from France Telecom (voila.com); offer more personalized functions, or offer unique search functions and data analysis models which produce more or less structured search results. For example, Direct Hit (directhit.com) ranks the web sites selected through other search engines for frequency of use and hence for their general utility. There are now some 15 ‘headline’ search engines in the public domain, and some 350 other engines and directories listed. Most are free to use, although some specialist companies charge for personalized searches. The web site searchenginewatch.com provides an excellent review of all the principal Search Engines with supporting documentation and direct links to each one. This is a good starting point for professional users who wish to make best use of these extraordinary powerful research tools.
SIOP treatment guidelines for renal tumours in small infants: fact or fantasy? N. S. Levie∗, J. de Kraker†, J. P. M. Bo¨kkerink‡, I. M. Appel¶ and D. C. Aronson∗ ∗Department of Paediatric Surgery and †Department of Paediatric Oncology, Emma Children’s Hospital, Academical Medical Center, University of Amsterdam; ‡Department of Paediatric Oncology, University Hospital Nijmegen and ¶Department of Oncology, Sophia Children’s Hospital, Rotterdam, The Netherlands
Aims: Since as far back as 1980, SIOP (Socie´te´ Internationale d’Oncologie Pe´diatrique) have advocated primary nephrectomy (PN) only for unilateral renal tumours in patients Ζ6 months of age. Patients aged 7–12 months have been pre-treated with chemotherapy before nephrectomy is performed. The aims of this study were: (1) to evaluate how the SIOP guidelines for infants 0–6 months and 7–12 months of age were followed in three Dutch centres for Paediatric Oncology before and after 1980, and (2) to carry out an inventory of the incidence of benign tumours in this patient population below 12 months of age. Methods: Retrospective analysis of 67 patients under 12 months of age (1969–1995) with a unilateral renal tumour at diagnosis was carried out. Demographics, pathology, staging and treatment variables were analysed. Results: Of 67 patients, 39 were male and 28 female. Twenty-six (39%) infants were 0–6 months of age (group A) and 41 (61%) were 7–12 months old (group B). In group A there were five patients (19%) with congenital mesoblastic nephroma (CMN), out of which one was still-born and therefore received no treatment, and 21 patients with a unilateral Wilms’ tumour (WT). Fourteen of the 25 patients (56%) were treated with PN, including four patients with CMN. In group B there was one patient (2%) with CMN and 40 patients with WT. Thirteen of the patients (31%) were treated with PN. A total of 15 patients were treated before 1980 and 26 after 1980. Eight of 15 (53%) patients were treated with PN before 1980 and 21/26 (81%) were pre-treated after 1980, according to the protocol. Conclusion: Despite the SIOP recommendations, only 56% of patients Ζ6 months were treated with PN. The percentage of pre-treated patients in group B increased after changing the protocol in 1980 to 81%. In the age group included in the SIOP studies the protocol had been used significantly more often compared to the group included in the guidelines only. The known excellent survival rate justifies a primary nephrectomy approach in the youngest age group, however, in cases of a large tumour, pre-operative chemotherapy in reduced doses may still be considered. In our study fewer CMN were found (19%) than reported in the SIOP studies (20–70%), most likely due to a low registration rate, as a consequence of excluding this very young age group (0–6 months) from the SIOP protocol. 2000 Harcourt Publishers Ltd Key words: nephroblastoma; Wilms’ tumour; congenital mesoblastic nephroma; renal tumour.
Introduction Wilms’ tumours (nephroblastoma) are the most common renal tumours in infancy,1 and the fourth commonest malignant solid tumours in children from 0–14 years. It affects approximately one child per 10 000 children of less than 15 years of age, worldwide.2 In neonates, about 25% of renal tumours are benign Congenital Mesoblastic Nephroma (CMN) (Fig. 1).3 In infants aged 0–6 months Correspondence to: D. C. Aronson, MD, Department of Paediatric Surgery, Emma Children’s Hospital AMC, Academical Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. Fax: +31 (20) 566-4440. 0748–7983/00/060567+04 $35.00/0
this percentage is reported to be 29%,4 and it usually presents below the age of 3 months. Before 1980, patients Ζ12 months of age were excluded from the SIOP nephroblastoma protocol because of the—scarcely reported—high incidence of benign tumours and the fear of morbidity (i.e. venoocclusive disease) after chemotherapy in small infants. As a guideline for treatment, primary nephrectomy had been advocated in these patients. Since 1980, age as an exclusion criterion was changed from below 12 months to below 6 months. From this date, infants aged 7–12 months have been included in the SIOP-protocol and have been pretreated with chemotherapy before surgery. The aims of this study were: (1) to evaluate how the SIOP guidelines for infants 0–6 months and 7–12 months of age were followed 2000 Harcourt Publishers Ltd
568
N. S. Levie et al.
Fig. 1. (A) Mesoblastic Nephroma: classical (leiomyomatous) type. The tumour shows a fascicular arrangement of long, interwoven bundles of leiomyoma-like cells with long vesicular nuclei with blunt ends. There are some entrapped tubules. (B) Non-anaplastic Nephroblastoma (Blastemal predominant). The tumour is mainly composed of blastema with few tubules.
Table 1. Post-surgical Wilms’ tumour staging used by the SIOP Stage I: Stage II:
Stage III:
Stage IV:
Tumour limited to the kidney and completely excised. The tumour has not ruptured or punctured before excision. Tumour extending outside the kidney, but completely excised. Local extension of the tumour, in particular penetration into perirenal and/or peripelvic tissues beyond the capsule of the tumour, invasion of the hilar nodes and/or peri-aortic nodes, invasion of the renal vessels outside the kidney or thrombosis caused by the tumour, or invasion in the ureter. Incomplete excision, without haematogenous metastases; tumour biopsy taken before or during surgery, tumour rupture before or during surgery, peritoneal metastases which are not simple tumour adhesions of stage II, lymph node invasion beyond the local regional nodes. Distant metastases involving lungs, liver, bones, brain, etc.
in three Dutch centres for Paediatric Oncology before and after 1980, and (2) to carry out an inventory on the incidence of benign tumours in this patient population below 12 months of age.
using the chi-squared test, with the level of significance at 0.05.
Results Patients and methods From 1969–1995, 67 patients below 12 months of age with an unilateral renal tumour were identified in three different centres (the Emma Children’s Hospital AMC, Amsterdam (AMC), the University Hospital Nijmegen (UHN) and the Sophia Children’s Hospital, Rotterdam (SCH) through the SIOP-database in the SIOP-office in Amsterdam, The Netherlands. Thirty-eight of these patients were treated after 1980. According to age at diagnosis, patients were divided into group A (age 0–6 months) and group B (age 7–12 months). Data regarding demographics, pathology, staging and treatment were obtained from the medical charts, the operating reports and the office notes in the various centres. All patients were staged according to the SIOP staging system, which is shown in Table 1. Significance was tested
Of the 67 infants studied (44 at AMC, 13 at UHN and 10 at SCH), 39 were male and 28 female. Group A contained 26 patients (39%) and group B 41 patients (61%). In Group A, pathology showed the presence of CMN in five patients (19%), of whom one was still-born, and a unilateral Wilms’ tumours (WT) in 21 patients. Tumour staging is shown in Table 2. Of the 25 patients with a unilateral tumour, 14 (56%) were treated with primary nephrectomy (CMN: four stage I; WT: six stage I, one stage II, three stage III), nine patients (36%) were treated with primary chemotherapy (WT; six stage I, one state II, two stage III), and two with primary radiotherapy (both stage III WT, and treated at the start of the study period) (see Table 3). Eight patients (28%), including two with CMN, had surgery only and are still in complete remission. In group B one patient had a CMN (2%) and 40 were Wilms’ tumour cases. Tumour staging is shown in Table 2.
569
Guidelines for renal tumours in small infants Table 2. The stage distribution per group. Group A: patients age 0–6 months, group B patients age 7–12 months. Patients were staged after surgery according to the SIOP staging system Group A
Group B
Wilms’ tumours (n=61)
stage I stage II stage III stage IV total
12 2 7 0 21
26 7 6 1 40
CMN (n=6)
stage I stage III
5 —
— 1
Table 3. Number of patients treated with PN or pre-treatment in group A Group A
Total
Prim. Nephrect. Pre-treatment Total
14 (56%) 11 (44%) 25
Table 4. Number of patients treated with PN or pre-treatment in group B Group B Prim. Nephrect. Pre-treatment Total
SIOP 1, 2, 5 SIOP 6, 9, 93-01 (<1980) (>1980) 8 (53%) 7 (47%) 15
5 (19%) 21 (81%) 26
Total 13 (32%) 28 (68%) 41
Fifteen patients were treated before 1980, of whom eight (53%) were treated with PN. The patient with CMN (stage III) was treated with pre-operative CT and two patients with a Wilms’ tumour with pre-operative RT (one stage I, one stage III) before 1980. After 1980, 26 patients were treated, of whom 21 (81%) were treated with primary CT, according to the treatment protocol. The number of patients treated with PN or primary CT or RT, before or after 1980, are shown in Table 4. Chemotherapy was given in 39/41 (95%) of the patients. In group B, there is no significant difference found in using the protocol or not before and after 1980 (P=0.063; RR 1.51; CI 0.91–2.52). In the age group included in the SIOP protocol (group B after 1980) the use of the protocol was 21/26 (81%). This is statistically significantly higher compared to the frequency in the group included in the guidelines only (0–6 months of age and 7–12 months of age, treated before 1980). In this group the percentage of patients treated according to the guidelines was 55% (22/40).
from the SIOP-treatment protocol and, as a guideline, primary nephrectomy was advocated, whenever possible, in these patients. In our study this guideline was applied in 56% of cases in group A. The reason for this low percentage is unclear, but may reflect (1) the reluctance to perform primary surgery in view of the necessity for larger tumour resections with the increased chance for ruptures, and (2) the experienced safety of chemotherapy in reduced doses with relatively low incidence of toxic late effects in previous SIOP studies. This experience was also the reason for including infants aged 7–12 months in the protocol in 1980. In group B, before 1980, the guideline to perform primary nephrectomy had been applied in 53% of cases. After 1980, the protocol to pre-treat these patients with chemotherapy, has been applied in 81% of cases. In retrospect, there is no evident explanation found to explain why the protocol was applied in such a low percentage of the patients. The difference between 53% and 81% is not statistically significant, probably due to the small numbers involved. Comparing the age group included in the SIOP treatment protocol (group B after 1980) to the group not included (group A, and B before 1980), the protocol seemed to be used more frequently than the guideline. Apparently a protocol may be more thoroughly followed than a guideline, provided that the registration rate in both groups is equal. The incidence of CMN has been documented to vary between 20–50%3,5 in all primary renal tumours of children younger than 12 months of age. The incidence seems to increase over the various consecutive SIOP studies. In SIOP1, 2 and 5 the percentage of CMN was reported to be 16%3 in all infants, and SIOP-6 showed an incidence of 29% in infants <6 months of age.4 In SIOP-9, 48% CMN was reported in infants <6 months of age.5 This picture probably does not reflect a true increase of the incidence in CMN, but may be due to a more accurate central review. In our data, the incidence of CMN was 19% in patients <6 months of age. This rather low percentage may, most likely, be due to a low registration rate, as a consequence of the exclusion of the very young age group (0–6 months) from the treatment protocol. In summary, from our evaluation of the application of the SIOP protocol, the percentage of patients over 6 months who were not pre-treated seems rather high, although presently it is known that the pre-operative chemotherapy of the SIOP protocols is safe for children of this age and weight. However, the protocol seemed to be followed better than the guideline. In view of the 55% of cases in which the guideline was followed its effect seems more to be a fantasy than a fact. As shown in the literature, the excellent survival rate still justifies a primary nephrectomy approach in the youngest age group.1,4,6
References Discussion SIOP Wilms’ tumour-1, 2 and 5 trials excluded patients <12 months of age and these patients were treated with primary nephrectomy, whenever possible. From 1980 (SIOP-6) till to date, only patients <6 months of age have been excluded
1 Corn BW, Goldwein JW, Evans I, D’Angio GJ. Outcomes in low-risk babies treated with half-dose chemotherapy according to the Third National Wilms’ Tumor Study. J Clin Oncol 1992; 10: 1305–9. 2 Breslow N, Olshan A, Beckwith JB, Green DM. Epidemiology of Wilms’ tumor. Med Pediatr Oncol 1993; 21: 172–81.
570
N. S. Levie et al.
3 Coppes MJ. Wilms’ tumor, a compilation of clinical and molecular characteristics. PhD Thesis, University of Amsterdam, 1992. 4 Coppes MJ, Tournade MF, Lemerle J, et al. Preoperative care of infants with nephroblastoma. The SIOP 6 experience. Cancer 1992; 69: 2721–5. 5 Godzinski J, Tournade MF, de Kraker J, et al. Importance of the
intraabdominal tumour extension at surgery for renal tumours in patients younger than 6 months. The SIOP nephroblastoma study no-9. Med Pediatr Oncol 1997; 29: 323–4. 6 Ritchey M, Azizkhan R, Beckwith B, et al. Neonatal Wilms’ tumor. J Ped Surgery 1995; 30: 856–9. Accepted for publication 26 January 2000
World Wide Web Search Engines (I) The Internet is now a mature and massive information resource, whose use by the public is increasingly purposeful rather than curiosity driven. The Search Engine is the first entry point for many users of the World Wide Web, seeking general or specific information. A Search Engine is a computer data base which references a significant proportion of the Internet’s Web Sites and their content, along with the Web addresses and hot links to specific sites. A typical Search Engine is a Web Site which provides a search box on its front page, into which the query word or phrase is typed. Each query is governed by simple rules to help refine and focus the search. The Search Engine will present a list of sites containing the search phrase, with a direct link to each site in the list. Queries about common items may generate a massive and unmanageable numbers of responses. The searches are usually structured so that the most popular Web Sites are listed first in the search results. The technology behind these searches is so fast that the results of even the most arcane research enquiries are commonly retrieved in a few seconds. The absolute size of the public Web is uncertain at any time, but it is now believed to be approaching one billion pages of information. Protected, controlled access and commercial sites, intranets and extranets may contain still larger data resources. Automatic search engines compile their data bases in one of two principal ways, which are not mutually exclusive. The Engines use powerful software to scan or ‘crawl’ the Web continuously, cataloguing in intelligent ways every significant word, phrase and Web address for rapid and interactive retrieval. Examples of such systems include FAST (alltheweb.com), AltaVista (altavista.com) and Google (google.com). Some of the principal search engines rely on human operators to index and catalogue the Web content in useful ways. Examples include Yahoo (yahoo.com) and Open Directory (dmoz.org). Other Search Engines may be regionally based, such as Voila from France Telecom (voila.com); offer more personalized functions, or offer unique search functions and data analysis models which produce more or less structured search results. For example, Direct Hit (directhit.com) ranks the web sites selected through other search engines for frequency of use and hence for their general utility. There are now some 15 ‘headline’ search engines in the public domain, and some 350 other engines and directories listed. Most are free to use, although some specialist companies charge for personalized searches. The web site searchenginewatch.com provides an excellent review of all the principal Search Engines with supporting documentation and direct links to each one. This is a good starting point for professional users who wish to make best use of these extraordinary powerful research tools.