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Minimally invasive nephrectomy for Wilms tumors in children – data from SIOP 2001
Journal of Pediatric Surgery xxx (2014) xxx–xxx
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Minimally invasive nephrectomy for Wilms tumors in children – data from SIOP 2001 Steven W. Warmann a,⁎, 1, Jan Godzinski b, 1, Harm van Tinteren c, Hugo Heij d, Mark Powis e, Bengt Sandstedt f, Norbert Graf g, Jörg Fuchs aThe Surgical Panel of the SIOP Renal Tumor Strategy Group a
Department of Pediatric Surgery and Pediatric Urology, University Children's Hospital Tuebingen, Germany Department of Pediatric Surgery, Marciniak Hospital, Wroclaw and Chair of Emergency Medicine, Medical University, Wroclaw, Poland Comprehensive Cancer Centre, Amsterdam, The Netherlands d Pediatric Surgical Center of Amsterdam (ECH-AMC/VUmc), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands e Department of Paediatric Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom f Childhood Cancer Research Unit, Astrid Lindgren's Children's Hospital, Karolinska Institutet, Stockholm, Sweden g Department of Pediatric Hematology and Oncology, University Hospital Homburg/Saar, Germany b c
a r t i c l e
i n f o
Article history: Received 18 February 2014 Received in revised form 4 June 2014 Accepted 5 June 2014 Available online xxxx Key words: Nephroblastoma Laparoscopy Tumor resection
a b s t r a c t Purpose: To analyse the surgical and oncological outcome of minimally invasive surgery (MIS) for tumor nephrectomy in Wilms tumor (WT) patients. Methods: WT patients from the SIOP 2001 trial, undergoing MIS for tumor nephrectomy were analyzed with regard to demographic characterization, surgical specifications, complications, and outcome. Results: There were 24 children matching the inclusion criteria. Median age at operation was 40.35 months (14.3–65.4). All patients received preoperative chemotherapy. Median tumor volume was 177.5 ml at diagnosis (46.5–958) and 73.0 ml at surgery (3.8–776). There was one surgical complication (splenic injury), no intraoperative tumor rupture occurred. Abdominal stage was I in 14, II in 7, and III in 3 patients. Adequate lymph node sampling was performed in only 2 patients. One local relapse occurred. Event-free survival was 23/24, overall survival was 24/24, median follow up was 47 months (2–114). Conclusions: We present the largest series so far of minimally invasive nephrectomies for nephroblastoma based on a multinational trial. Treatment results were comparable to those of open surgery; however, experience of operating surgeons was generally high. Discipline of lymph node sampling was inadequate. Based on this analysis a prospective study on MIS in nephroblastoma is planned by the SIOP Renal Tumor Study Group. © 2014 Elsevier Inc. All rights reserved.
Surgery plays a key role as local treatment for nephroblastoma. The guidelines for resection of Wilms tumors (WT) have been well established and have by now been thoroughly analyzed [1–4]. From the surgical point of view, complete tumor resection is one of the main prognostic factors in the treatment of WT [3,4]. For many years, open nephrectomy was the common surgical approach in unilateral cases. However, alternative surgical concepts have been introduced during recent years and are meanwhile used to a relevant extent. Minimally invasive surgical (MIS) procedures are regularly used in pediatric surgery for standard as well as complex operations [5,6]. This approach is especially relevant in pediatric urologic operations of the upper urinary tract [7,8]. MIS also plays a certain role in pediatric surgical oncology although the exact relevance in most entities has not yet been
determined [9–11]. The use of MIS in patients suffering from WT has been reported in singular cases [12–14], however, a systematic analysis has not been undertaken so far and by now there are no evidence based data available. This is of importance since the minimally invasive approach seems to be increasingly used. Current treatment protocols do not contain surgical guidelines or recommendations concerning indications and contraindications for MIS in WT. In this study we systematically assessed for the first time the role of MIS in the treatment of Wilms tumors based on a multicenter prospective data registration. The outcome parameters were technical/surgical aspects (including tumor rupture, lymph node sampling, and complications), as well as oncological measures (event-free survival and overall survival). 1. Materials and methods
⁎ Corresponding author at: Dpt. of Pediatric Surgery and Pediatric Urology, University Children's Hospital Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany. Tel.: +49 7071 2986 621; fax: +49 7071 294 046. E-mail address: [email protected] (S.W. Warmann). 1 SW Warmann and J Godzinski share equal first authorship.
1.1. Patients Patients with newly diagnosed nephroblastoma were registered in the multicenter trial SIOP 2001 by participating institutions. We
http://dx.doi.org/10.1016/j.jpedsurg.2014.06.005 0022-3468/© 2014 Elsevier Inc. All rights reserved.
Please cite this article as: Warmann SW, et al, Minimally invasive nephrectomy for Wilms tumors in children – data from SIOP 2001, J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.06.005
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S.W. Warmann et al. / Journal of Pediatric Surgery xxx (2014) xxx–xxx
retrospectively analyzed all children suffering from unilateral WT who underwent laparoscopic tumor resection between June 2001 and July 2013. Data were obtained from the central SIOP 2001 data base in Amsterdam/The Netherlands. Patients' characteristics, surgical data as well as clinical and oncological outcome measures were assessed. The multi-institutional study was approved by the Institutional Review Board of the Ärztekammer des Saarlandes, Germany (No. 136/01). 1.2. Treatment All patients registered within the above cited time frame were to be treated following the SIOP 2001 protocol guidelines. According to this protocol, patients older than 6 months should receive neoadjuvant chemotherapy depending on the tumor stratification: Actinomyin D/Vincristin (AV) over 4 weeks in localized cases, Actinomycin D/Vincristin/Doxorubicin (AVD) over 6 weeks in metastasized cases. The recommended doses were: Actinomycin D 45 μg/kg once every 2nd week, Vincristin 1.5 mg/m 2 once every week, Doxorubicin 50 mg/m 2 every 4 weeks. Doses should be
reduced to 2/3 in cases of body weight below 12 kg (and further to 1/2 if poorly tolerated). Tumor response to initial chemotherapy was defined comparing volume at diagnosis and volume at surgery. Primary tumor response was assigned as complete response (CR: complete disappearance of the tumor), partial response (PR: volume regression more than 50%), stable disease (SD: volume regression between 0 and 50%), and progressive disease (PD: volume increase under chemotherapy). Neoadjuvant chemotherapy was to be followed by resection of the primary tumor as local treatment [3,15]. According to the protocol, laparoscopy was not banned as approach for tumor nephrectomy. The postoperative treatment strategy (chemotherapy ± radiotherapy and treatment of possible metastases) depended on the postoperative staging and the histological risk stratification [16,17].
2. Results 2.1. Population demographics (Table 1) The total number of registered patients within SIOP 2001 during the study period of this analysis was 4763, 4220 of the patients had nephroblastoma. Overall there were 24 children undergoing MIS for Wilms Tumor resection during the study period, 16 female and 8 male patients. Of all patients, 11 were enrolled from the Children's Cancer and Leukaemia Group (CCLG) in the UK, 7 from the Society of Pediatric Oncology and Hematology (GPOH) in Germany, 5 from the French Society against cancers in children and adolescents (SFCE) in France, and 1 from the Brazilian Wilms Tumor Study Group(GCBTTW) in Brazil. Median age of patients at diagnosis was 39.35 months (range 11.9–63.9). Tumor localization was on the right side in 14 patients and on the left side in 10 patients. The median tumor volume at diagnosis was 177.5 ml (range 46.5–958). Localized tumors were present in 22 children, metastatic tumors in 2 (lung metastases in 1 patient and abdominal metastases in 1 patient, Table 1).
Table 1 Patients’ demographic data. Gender: F = female, M = male; Side: L = left, R = right; Neoadjuvant chemotherapy: AV = 4 weeks Actinomycin D + Vincristin; AVD = 6 weeks Actionomycin D + Vincristin + Doxorubicin. n.d. = no data.
Fig. 1. Clinical example: minimally invasive tumor nephrectomy for nephroblastoma in a boy. Right-sided Wilms' tumor, which was treated with neoadjuvant chemotherapy (actinomycin D + Vincristin) for 4 weeks. The tumor showed good response to treatment. Because of infiltration of the renal pelvis, the decision for tumor nephrectomy was taken. Patient's age at surgery was 23.5 months. A) MRI scan of tumor at diagnosis showing a lower pole renal mass infiltrating the renal pelvis (size 9.5 × 9.5 × 8.3 cm, sagittal view). B) MRI scan after neoadjuvant chemotherapy showing tumor regression (size 3.9 × 3.4 × 3.0 cm, sagittal view). C) Patient after surgery (4 ports plus Pfannenstiel incision for removal of the bag with the resected specimen). D) Resected specimen. Histological workup revealed an intermediate risk nephroblastoma (regressive subtype with less than 10% vital compounds), resection status R0, lymph nodes were negative. Patient is without evidence for disease after 2 years follow-up.
Pat. No.
Gender
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
F F F M F F F M F M F M M F M M M F F F F F F F
Age at diagnosis [M]
Side
51.6 63.9 39.7 33.2 34.2 51.8 32.9 36.4 41.2 44.5 44.1 42.3 60.9 11.9 46.5 22.4 44.9 13.3 24.1 14.0 39.0 23.0 56.0 21.0
L L R L R L R R R R L L R R L R L R R L R L R R
Neoadjuvant chemotherapy
Tumor volume [ml] Initially
At surgery
AV AV AV AVD AVD AV AV AV AV AV AV AV AVD n.d. AVD AV AV AV AV AV AV AV AV AV
251.7 177.1 177.8 582.2 154.3 52.8 46.5 69.3 50.3 593.0 93.0 317.0 883.0 346.3 958.0 69.3 789.0 734.0 370.0 171.0 170.0 170.0 162.0 300.0
65.9 n.d. 94.1 71.9 12.8 4.2 12.9 6.6 6.4 88.0 23.0 110.9 254.0 n.d. 3.8 92.2 776.0 102.6 158.0 207.0 58.0 77.0 74.0 15.0
Please cite this article as: Warmann SW, et al, Minimally invasive nephrectomy for Wilms tumors in children – data from SIOP 2001, J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.06.005
S.W. Warmann et al. / Journal of Pediatric Surgery xxx (2014) xxx–xxx
2.2. Chemotherapy/radiotherapy Before operation, all children received neoadjuvant chemotherapy (19 × AV, 4 × AVD, no data for 1 patient). The median tumor volume regressed under chemotherapy from initially 177.5 ml (range 46.5– 883) to 73.0 ml (3.8–776, Table 1). Taken together there was partial response to chemotherapy in 18 tumors, stable disease in 2 tumors, and progressive disease in 2 tumors (no data for 1 patient). All children except one received postoperative chemotherapy (12 × AV, 9×AVD, 2 × other regimens). Postoperative local radiotherapy was applied in 2 children (Table 2).
3
Pathologically, there were positive margins in the 2 cases, in which the operating surgeon also had regarded the capsule as not being intact. Additionally, there were pathologically positive margins in one case, in which the surgeon had regarded the capsule as intact. Local tumor stage according to SIOP was I in 14, II in 7, and III in 3 instances. Reasons for stage III were positive margins in all three cases, in one of them there were also positive lymph nodes and in another one there was preoperative tumor rupture additionally. Histological workup according to SIOP classification revealed intermediate risk histology in 20 (13× regressive, 4× mixed, 3× stromal subtype), and high-risk histology in 3 tumors (all blastemal subtype). There were no data for 1 case).
2.3. Surgical and pathological data (Tables 1–2) All patients underwent transperitoneal laparoscopic tumor nephrectomy (Fig. 1). The median age of patients at surgery was 40.35 months (range 14.3–65.4). Before surgery the median tumor volume on imaging was 73 ml (3.8–776). There was one preoperative tumor rupture (patient #15). Among the operating surgeons, there were 17 with pediatric surgery as subspecialty (no data for 7 cases). During the 2 previous years the number of nephrectomies for WT performed within the listed institutions was more than 10 in 7, 6–10 in 8, and 1–5 in 2 instances (no data in 7). The number of tumor nephrectomies for WT performed by the listed operating surgeon during the previous 2 years was more than 10 in 5 cases, 6–10 in 8 cases, and 1–5 in 4 cases (no data in 7 cases). Complete tumor nephrectomy was performed in all children. There was one intraoperative complication (splenic injury, surgically managed by splenectomy). No conversion to open surgery had to be carried out. The median value of largest tumor diameter was 5.0 cm (2.8–12), median weight of resected specimen was 134 g (47–730). According to the operating surgeon the tumor capsule was grossly intact in 17 specimens, operating surgeons were uncertain in 3 cases, and they regarded the capsule as not being intact in 2 cases (no data for 2 cases). Tumors were removed from the abdominal cavity using a Pfannenstiel incision in 6 cases or using an anterior transverse abdominal incision in 1 case (no data given for 17 patients). Table 2 Surgical and pathological data. Tumor histology: IR = intermediate risk, HR = high risk; blast. = blastemal predominant subtype, regr. = regressive type, mixed = mixed subtype, stromal = stromal predominant subtype; Tumor margins: Neg. = histologically free margins, Pos. = histologically detectable tumor cells on margins. Pat. No.
Age at surgery [M]
Largest Tumor diameter [cm]
Specimen weight [g]
Local tumor stage
Tumor histology
Tumor margins
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
53.6 65.4 40.7 34.2 35.7 52.8 33.8 37.4 42.2 45.5 46.6 43.3 62.4 14.9 48.5 22.5 46.4 14.3 25.6 15.0 40.0 27.5 57.5 23.5
4.4 5.0 6.0 5.5 3.8 3.0 3.0 2.8 4.0 7.5 4.0 6.5 9.5 5.0 4.0 6.8 12.0 n.d. n.d. 8.5 5.5. 6.5 7.2 3.5
125 n.d. 157 169 68 91 134 56 190 177 98 254 323 53 105 134 730 n.d. n.d. 310 157 136 47 63
I I II II III I I I II II II I I III III II I I I II I I I I
HR (blast.) IR (regr.) IR (regr.) IR (regr.) IR (regr.) IR (regr.) IR (mixed) IR (regr.) IR (mixed) IR (regr.) IR (mixed) HR (blast.) HR (blast.) IR (regr.) IR (regr.) IR (regr.) IR (mixed) IR (regr.) IR (stromal) IR (stromal) IR(regr.) IR (stromal) n.d. IR (regr.)
Neg. Neg. Neg. Neg. Pos. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Pos. Pos. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg.
2.4. Lymph nodes Lymph nodes (LN) were sampled in 15 of the 24 patients. Numbers of sampled nodes differed between 0 and 11. Positive LN were observed in 5 patients (Table 3). 2.5. Oncological outcome One local relapse occurred in one patient (patient No. 12). In this patient initial treatment consisted of 4 weeks AV, histological subtype was blastemal. The tumor had shown partial response under neoadjuvant chemotherapy, local stage was I, there were 3 lymph nodes sampled (all negative). Postoperative treatment consisted of AVD; no local irradiation was applied. The relapse occurred 8.5 months after surgery. After a median follow-up of 47 months (2–114) all patients were in complete remission, resulting so far in an event-free survival of 23/24 and an overall survival of 24/24 (Table 3). 3. Discussion Minimally invasive techniques are well established in pediatric surgery. Urology represents one major field within this field. Laparoscopic procedures have become the standard approach for several operations on the upper urinary tract. This especially includes pyeloplasties and nephrectomies for benign pathologies [9,18,19]. In adults, MIS is regularly used for the surgical treatment of renal malignancies [20]. In children, Wilms tumors (WT) are more and more often resected laparoscopically, however, only infrequent analyses have been published by now, mostly reporting on small patients' cohorts [12–14,21,22]. Very recently, Varlet et al. published the first multi center study on 17 children undergoing laparoscopic nephrectomy for renal malignancies. This study included 15 children with WT [23]. Guidelines and recommendations for minimally invasive techniques and criteria for their use have commonly not been included in the multicenter treatment protocols so far. On its meeting in Rome in 2012, the surgical panel of the SIOP Renal Tumor Study Group (RTSG) found it important to retrospectively analyze respective data of the most recent study (SIOP 2001) in order to define recommendations and guidelines for MIS in nephroblastoma to be included in the upcoming new treatment protocol. Based on these guidelines a prospective data acquisition and evaluation is then to be undertaken within the next trial. The present study retrospectively analyzed data, which were obtained from various countries worldwide. Several limiting aspects of the analyses have to be considered. The patient number is small and general conclusions are thus difficult to draw. Furthermore, follow-up in some patients is short with respect to an oncological analysis. Nevertheless, we are presenting the largest cohort of respective patients with important implications. The main purpose of this study was not to present a complete evaluation but rather to build up a basis for the further prospective analysis of MIS for nephroblastoma as stated above.
Please cite this article as: Warmann SW, et al, Minimally invasive nephrectomy for Wilms tumors in children – data from SIOP 2001, J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.06.005
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S.W. Warmann et al. / Journal of Pediatric Surgery xxx (2014) xxx–xxx
Table 3 Data on lymph nodes and oncological outcome. LN sampled = total number of biopsied lymph nodes, LN positive = total number of lymph nodes containing tumor cells; *: lymph node sampling was documented by surgeon in patient No. 23; however, biopsies did not contain LN material; Postop Chemotherapy: AV-1 = Actinomycin-D + Vincristin, AVD = Actinomycin-D + Vincristin + Doxorubicin, VCCD = VP-16 + Cyclophosphamid + Carboplatin + Doxorubicin; Outcome: NED = No evidence of disease. Pat. No.
LN sampled
LN positive
Postoperative chemotherapy
Postoperative Radiotherapy
Relapse
Outcome
Follow-up [M]
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
2 n.d. n.d. 6 0 11 0 5 2 1 1 3 0 1 2 n.d. 0 0 0 4 1 2 0* 1
2 4 2 0 0 0 0 0 0 0 1 0 1 0 0 0 -* 0
AVD AV-1 None VCCD AVD AV-1 AV-1 AV-1 AVD AVD AVD AVD VCCD AVD AVD AVD AV-1 AV-1 AV-1 AV-1 AV-1 AV-1 AV-1 AV-1
+ + -
+ -
NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED
114 50 19 81 72 46 37 30 114 81 68 68 62 54 52 48 46 36 31 33 19 13 13 2
By the time the study, from which the analyzed data were collected, was set up, MIS did not play a great role in pediatric oncology and urology. Many technical improvements, surgical advances, and innovations of MIS in children have only been introduced during recent years through which MIS for nephroblastoma became more and more feasible. As a consequence, the number of laparoscopic WT operations was altogether low in the present study. Although feasibility is not the main aim of surgery in oncological patients, it seems very likely that the rate of laparoscopic nephrectomies for WT will further increase. Another limitation of the present study results from the data collection. Many relevant details of surgical procedures were not recorded because MIS did not play a relevant role at the time when the collection modalities of surgical data were established. For example there was no information about why surgeons chose the laparoscopic approach or why they didn't. Details of the operative technique were regularly lacking including trocar number and positioning, insufflation parameters, modality of specimen removal, and others. Furthermore, it is not known whether the removed kidneys were extracted in a bag without breakage (to allow an adequate pathologic evaluation), because this information was not considered in the surgical form. This information will be included in the next study. The same holds true for the extent of surgical incision to allow excision of the bag. With these experiences in mind, the surgical data acquisition will be adapted and improved for the next trial. Despite the cited limitations there were numerous relevant aspects drawn from the analyzed data. There is an ongoing debate about indications and the general role of MIS in nephroblastoma. The SIOP 2001 protocol commonly recommends neoadjuvant chemotherapy in unilateral Wilms tumors except in patients younger than 6 months or older than 16 years. All children in this study received chemotherapy before surgery. Arguments pro and contra chemotherapy before operation have been thoroughly discussed between different Study Groups. Following the SIOP protocol, the rate of intraoperative ruptures with spillage of tumor cells is lower after neoadjuvant chemotherapy compared to primary surgery due to tumor shrinking and encapsulation [3]. This certainly holds true in MIS and therefore the authors emphasize the recommendations of preoperative chemotherapy before laparoscopic WT resection. There
is a relevant difference of approaching nephroblastoma between different study trials. This mainly concerns the use of upfront surgery in North America (COG) without neodadjuvant chemotherapy in tumors that seem resectable. However, because of the stated risks of intraoperative tumor rupture and subsequent spillage, MIS should only be considered in Wilms tumors after initial chemotherapy. Furthermore, large tumors are an important issue because – once they become dissected and more and more liberated – they are potentially difficult to handle intra-abdominally. In such cases there is a relevant risk for rupture with subsequent tumor spillage. Herein, the ipsilateral border of the vertebral corpuses seems to be a certain limit. In addition, visualization and management of the renal pedicle is relevantly restricted in such cases. Recently, there has been a discussion about a possible overlapping of indications for MIS and nephron sparing surgery (NSS) in nephroblastoma. From the pure technical point of view, minimally-invasive resection of a kidney with a small tumor nodule is certainly similar to a standard MIS nephrectomy for benign reasons in children. However, oncological and functional considerations have to be taken strongly into account at this point. Recent studies indicate that NSS in unilateral WT is associated with a comparable oncological outcome as classical tumor nephrectomies [24–26]. At the same time there is growing evidence that late effects after tumor nephrectomy result in renal failure to a relevant degree; this seems not as much to be the case after NSS in unilateral WT [26–30]. The discussion process within the surgical panel of the SIOP RTSG therefore resulted in the recommendation that MIS and NSS should not interfere in terms of surgical approach: If feasible according to the guidelines of the SIOP Wilms Tumor protocol [31], NSS should be performed. If NSS is not feasible and the decision for tumor nephrectomy has been established, MIS may be chosen as surgical approach but only by those surgeons that have a substantial expertise in oncologic pediatric surgery, pediatric urology, and minimally invasive surgery. Lymph node (LN) sampling was not sufficient in the present study. Adequate sampling of LN is precondition for correct tumor staging, risk stratification, and a correct treatment approach for WT patients in order to minimize the risk for a local relapse [3,32]. Ehrlich et al. clearly have shown that LN metastases and microscopic residual disease have a negative impact on Overall- and Event Free-Survival in
Please cite this article as: Warmann SW, et al, Minimally invasive nephrectomy for Wilms tumors in children – data from SIOP 2001, J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.06.005
S.W. Warmann et al. / Journal of Pediatric Surgery xxx (2014) xxx–xxx
WT patients (stage III, favorable histology) [32]. These aspects are especially important with regard to MIS. The adequate number of LN to be sampled (more than 6) has been determined previously [16,17], indicating an inadequate LN sampling in the present study. Because of the above stated limits of data collection in the analyzed study, the reasons for this were not recorded. Deficits of the discipline of LN sampling in WT surgery have been previously reported analyzing the open surgical approach [3]. These deficits seem even more severe in MIS. Because of the small total number of patients, a statistical negative impact of the inadequate sampling could not be calculated. Nevertheless, the laparoscopic approach for WT nephrectomy can only be accepted provided that the common oncological guidelines are strictly respected. Technical aspects of the operative approach must never be reason for compromises concerning the correct way of performing WT surgery. A thorough analysis of the role of MIS in WT surgery is mandatory, especially since there are already reports on the combined use with NSS, which underline further possible problems [33]. MIS for WT surgery is a challenging procedure requiring exceptional expertise by the operating surgeon. The correct establishment of indications together with a careful patient selection is essential. The outcome of patients in the presented study was so far excellent; however certain limitations of the study have to be taken into consideration. The general guidelines for WT surgery have to be strictly and consequently respected, especially with regard to LN sampling. The future prospective evaluation of MIS for WT will bring further insight into the role of MIS in surgery for nephroblastoma. Acknowledgement The following members of the SIOP RTSG surgical panel made general contributions to this study: Beata Sznajder, Georges Audry, Giovanni Cecchetto, Frédèric Gauthier, Bruce Okoye, Dietrich von Schweinitz, Jan de Kraker †. References [1] Ladd WE. Embryoma of the kidney (Wilms' Tumor). Ann Surg 1938;108:885–902. [2] Gross RE, Neuhauser EB. Treatment of mixed tumors of the kidney in childhood. Pediatrics 1950;6:843–52. [3] Fuchs J, Kienecker K, Furtwängler R, et al. Surgical aspects in the treatment of patients with unilateral wilms tumor a report from the SIOP 93-01/German Society of Pediatric Oncology and Hematology. Ann Surg 2009;249:666–71. [4] Ritchey ML, Shamberger RC, Haase G, et al. Surgical complications after primary nephrectomy for Wilms' tumor: report from the National Wilms' tumor Group. J Am Coll Surg 2001;192:63–8. [5] Frutos MD, Abrisqueta J, Lujan J, et al. Randomized prospective study to compare laparoscopic appendectomy versus umbilical single-incision appendectomy. Ann Surg 2013;257:413–8. [6] Yamataka A, Lane GJ, Cazares J. Laparoscopic surgery for biliary atresia and choledochal cysts. Semin Pediatr Surg 2012;21:201–10. [7] Fuchs J, Luithle T, Warmann SW, et al. Laparoscopic surgery on upper urinary tract in children younger than 1 year: technical aspects and functional outcome. J Urol 2009;182:1561–8. [8] Luithle T, Szavay P, Fuchs J. Single-incision laparoscopic nephroureterectomy in children of all age groups. J Pediatr Surg 2013;48:1142–6.
†
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Deceased.
Please cite this article as: Warmann SW, et al, Minimally invasive nephrectomy for Wilms tumors in children – data from SIOP 2001, J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.06.005
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Minimally invasive nephrectomy for Wilms tumors in children – data from SIOP 2001 Steven W. Warmann a,⁎, 1, Jan Godzinski b, 1, Harm van Tinteren c, Hugo Heij d, Mark Powis e, Bengt Sandstedt f, Norbert Graf g, Jörg Fuchs aThe Surgical Panel of the SIOP Renal Tumor Strategy Group a
Department of Pediatric Surgery and Pediatric Urology, University Children's Hospital Tuebingen, Germany Department of Pediatric Surgery, Marciniak Hospital, Wroclaw and Chair of Emergency Medicine, Medical University, Wroclaw, Poland Comprehensive Cancer Centre, Amsterdam, The Netherlands d Pediatric Surgical Center of Amsterdam (ECH-AMC/VUmc), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands e Department of Paediatric Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom f Childhood Cancer Research Unit, Astrid Lindgren's Children's Hospital, Karolinska Institutet, Stockholm, Sweden g Department of Pediatric Hematology and Oncology, University Hospital Homburg/Saar, Germany b c
a r t i c l e
i n f o
Article history: Received 18 February 2014 Received in revised form 4 June 2014 Accepted 5 June 2014 Available online xxxx Key words: Nephroblastoma Laparoscopy Tumor resection
a b s t r a c t Purpose: To analyse the surgical and oncological outcome of minimally invasive surgery (MIS) for tumor nephrectomy in Wilms tumor (WT) patients. Methods: WT patients from the SIOP 2001 trial, undergoing MIS for tumor nephrectomy were analyzed with regard to demographic characterization, surgical specifications, complications, and outcome. Results: There were 24 children matching the inclusion criteria. Median age at operation was 40.35 months (14.3–65.4). All patients received preoperative chemotherapy. Median tumor volume was 177.5 ml at diagnosis (46.5–958) and 73.0 ml at surgery (3.8–776). There was one surgical complication (splenic injury), no intraoperative tumor rupture occurred. Abdominal stage was I in 14, II in 7, and III in 3 patients. Adequate lymph node sampling was performed in only 2 patients. One local relapse occurred. Event-free survival was 23/24, overall survival was 24/24, median follow up was 47 months (2–114). Conclusions: We present the largest series so far of minimally invasive nephrectomies for nephroblastoma based on a multinational trial. Treatment results were comparable to those of open surgery; however, experience of operating surgeons was generally high. Discipline of lymph node sampling was inadequate. Based on this analysis a prospective study on MIS in nephroblastoma is planned by the SIOP Renal Tumor Study Group. © 2014 Elsevier Inc. All rights reserved.
Surgery plays a key role as local treatment for nephroblastoma. The guidelines for resection of Wilms tumors (WT) have been well established and have by now been thoroughly analyzed [1–4]. From the surgical point of view, complete tumor resection is one of the main prognostic factors in the treatment of WT [3,4]. For many years, open nephrectomy was the common surgical approach in unilateral cases. However, alternative surgical concepts have been introduced during recent years and are meanwhile used to a relevant extent. Minimally invasive surgical (MIS) procedures are regularly used in pediatric surgery for standard as well as complex operations [5,6]. This approach is especially relevant in pediatric urologic operations of the upper urinary tract [7,8]. MIS also plays a certain role in pediatric surgical oncology although the exact relevance in most entities has not yet been
determined [9–11]. The use of MIS in patients suffering from WT has been reported in singular cases [12–14], however, a systematic analysis has not been undertaken so far and by now there are no evidence based data available. This is of importance since the minimally invasive approach seems to be increasingly used. Current treatment protocols do not contain surgical guidelines or recommendations concerning indications and contraindications for MIS in WT. In this study we systematically assessed for the first time the role of MIS in the treatment of Wilms tumors based on a multicenter prospective data registration. The outcome parameters were technical/surgical aspects (including tumor rupture, lymph node sampling, and complications), as well as oncological measures (event-free survival and overall survival). 1. Materials and methods
⁎ Corresponding author at: Dpt. of Pediatric Surgery and Pediatric Urology, University Children's Hospital Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany. Tel.: +49 7071 2986 621; fax: +49 7071 294 046. E-mail address: [email protected] (S.W. Warmann). 1 SW Warmann and J Godzinski share equal first authorship.
1.1. Patients Patients with newly diagnosed nephroblastoma were registered in the multicenter trial SIOP 2001 by participating institutions. We
http://dx.doi.org/10.1016/j.jpedsurg.2014.06.005 0022-3468/© 2014 Elsevier Inc. All rights reserved.
Please cite this article as: Warmann SW, et al, Minimally invasive nephrectomy for Wilms tumors in children – data from SIOP 2001, J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.06.005
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S.W. Warmann et al. / Journal of Pediatric Surgery xxx (2014) xxx–xxx
retrospectively analyzed all children suffering from unilateral WT who underwent laparoscopic tumor resection between June 2001 and July 2013. Data were obtained from the central SIOP 2001 data base in Amsterdam/The Netherlands. Patients' characteristics, surgical data as well as clinical and oncological outcome measures were assessed. The multi-institutional study was approved by the Institutional Review Board of the Ärztekammer des Saarlandes, Germany (No. 136/01). 1.2. Treatment All patients registered within the above cited time frame were to be treated following the SIOP 2001 protocol guidelines. According to this protocol, patients older than 6 months should receive neoadjuvant chemotherapy depending on the tumor stratification: Actinomyin D/Vincristin (AV) over 4 weeks in localized cases, Actinomycin D/Vincristin/Doxorubicin (AVD) over 6 weeks in metastasized cases. The recommended doses were: Actinomycin D 45 μg/kg once every 2nd week, Vincristin 1.5 mg/m 2 once every week, Doxorubicin 50 mg/m 2 every 4 weeks. Doses should be
reduced to 2/3 in cases of body weight below 12 kg (and further to 1/2 if poorly tolerated). Tumor response to initial chemotherapy was defined comparing volume at diagnosis and volume at surgery. Primary tumor response was assigned as complete response (CR: complete disappearance of the tumor), partial response (PR: volume regression more than 50%), stable disease (SD: volume regression between 0 and 50%), and progressive disease (PD: volume increase under chemotherapy). Neoadjuvant chemotherapy was to be followed by resection of the primary tumor as local treatment [3,15]. According to the protocol, laparoscopy was not banned as approach for tumor nephrectomy. The postoperative treatment strategy (chemotherapy ± radiotherapy and treatment of possible metastases) depended on the postoperative staging and the histological risk stratification [16,17].
2. Results 2.1. Population demographics (Table 1) The total number of registered patients within SIOP 2001 during the study period of this analysis was 4763, 4220 of the patients had nephroblastoma. Overall there were 24 children undergoing MIS for Wilms Tumor resection during the study period, 16 female and 8 male patients. Of all patients, 11 were enrolled from the Children's Cancer and Leukaemia Group (CCLG) in the UK, 7 from the Society of Pediatric Oncology and Hematology (GPOH) in Germany, 5 from the French Society against cancers in children and adolescents (SFCE) in France, and 1 from the Brazilian Wilms Tumor Study Group(GCBTTW) in Brazil. Median age of patients at diagnosis was 39.35 months (range 11.9–63.9). Tumor localization was on the right side in 14 patients and on the left side in 10 patients. The median tumor volume at diagnosis was 177.5 ml (range 46.5–958). Localized tumors were present in 22 children, metastatic tumors in 2 (lung metastases in 1 patient and abdominal metastases in 1 patient, Table 1).
Table 1 Patients’ demographic data. Gender: F = female, M = male; Side: L = left, R = right; Neoadjuvant chemotherapy: AV = 4 weeks Actinomycin D + Vincristin; AVD = 6 weeks Actionomycin D + Vincristin + Doxorubicin. n.d. = no data.
Fig. 1. Clinical example: minimally invasive tumor nephrectomy for nephroblastoma in a boy. Right-sided Wilms' tumor, which was treated with neoadjuvant chemotherapy (actinomycin D + Vincristin) for 4 weeks. The tumor showed good response to treatment. Because of infiltration of the renal pelvis, the decision for tumor nephrectomy was taken. Patient's age at surgery was 23.5 months. A) MRI scan of tumor at diagnosis showing a lower pole renal mass infiltrating the renal pelvis (size 9.5 × 9.5 × 8.3 cm, sagittal view). B) MRI scan after neoadjuvant chemotherapy showing tumor regression (size 3.9 × 3.4 × 3.0 cm, sagittal view). C) Patient after surgery (4 ports plus Pfannenstiel incision for removal of the bag with the resected specimen). D) Resected specimen. Histological workup revealed an intermediate risk nephroblastoma (regressive subtype with less than 10% vital compounds), resection status R0, lymph nodes were negative. Patient is without evidence for disease after 2 years follow-up.
Pat. No.
Gender
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
F F F M F F F M F M F M M F M M M F F F F F F F
Age at diagnosis [M]
Side
51.6 63.9 39.7 33.2 34.2 51.8 32.9 36.4 41.2 44.5 44.1 42.3 60.9 11.9 46.5 22.4 44.9 13.3 24.1 14.0 39.0 23.0 56.0 21.0
L L R L R L R R R R L L R R L R L R R L R L R R
Neoadjuvant chemotherapy
Tumor volume [ml] Initially
At surgery
AV AV AV AVD AVD AV AV AV AV AV AV AV AVD n.d. AVD AV AV AV AV AV AV AV AV AV
251.7 177.1 177.8 582.2 154.3 52.8 46.5 69.3 50.3 593.0 93.0 317.0 883.0 346.3 958.0 69.3 789.0 734.0 370.0 171.0 170.0 170.0 162.0 300.0
65.9 n.d. 94.1 71.9 12.8 4.2 12.9 6.6 6.4 88.0 23.0 110.9 254.0 n.d. 3.8 92.2 776.0 102.6 158.0 207.0 58.0 77.0 74.0 15.0
Please cite this article as: Warmann SW, et al, Minimally invasive nephrectomy for Wilms tumors in children – data from SIOP 2001, J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.06.005
S.W. Warmann et al. / Journal of Pediatric Surgery xxx (2014) xxx–xxx
2.2. Chemotherapy/radiotherapy Before operation, all children received neoadjuvant chemotherapy (19 × AV, 4 × AVD, no data for 1 patient). The median tumor volume regressed under chemotherapy from initially 177.5 ml (range 46.5– 883) to 73.0 ml (3.8–776, Table 1). Taken together there was partial response to chemotherapy in 18 tumors, stable disease in 2 tumors, and progressive disease in 2 tumors (no data for 1 patient). All children except one received postoperative chemotherapy (12 × AV, 9×AVD, 2 × other regimens). Postoperative local radiotherapy was applied in 2 children (Table 2).
3
Pathologically, there were positive margins in the 2 cases, in which the operating surgeon also had regarded the capsule as not being intact. Additionally, there were pathologically positive margins in one case, in which the surgeon had regarded the capsule as intact. Local tumor stage according to SIOP was I in 14, II in 7, and III in 3 instances. Reasons for stage III were positive margins in all three cases, in one of them there were also positive lymph nodes and in another one there was preoperative tumor rupture additionally. Histological workup according to SIOP classification revealed intermediate risk histology in 20 (13× regressive, 4× mixed, 3× stromal subtype), and high-risk histology in 3 tumors (all blastemal subtype). There were no data for 1 case).
2.3. Surgical and pathological data (Tables 1–2) All patients underwent transperitoneal laparoscopic tumor nephrectomy (Fig. 1). The median age of patients at surgery was 40.35 months (range 14.3–65.4). Before surgery the median tumor volume on imaging was 73 ml (3.8–776). There was one preoperative tumor rupture (patient #15). Among the operating surgeons, there were 17 with pediatric surgery as subspecialty (no data for 7 cases). During the 2 previous years the number of nephrectomies for WT performed within the listed institutions was more than 10 in 7, 6–10 in 8, and 1–5 in 2 instances (no data in 7). The number of tumor nephrectomies for WT performed by the listed operating surgeon during the previous 2 years was more than 10 in 5 cases, 6–10 in 8 cases, and 1–5 in 4 cases (no data in 7 cases). Complete tumor nephrectomy was performed in all children. There was one intraoperative complication (splenic injury, surgically managed by splenectomy). No conversion to open surgery had to be carried out. The median value of largest tumor diameter was 5.0 cm (2.8–12), median weight of resected specimen was 134 g (47–730). According to the operating surgeon the tumor capsule was grossly intact in 17 specimens, operating surgeons were uncertain in 3 cases, and they regarded the capsule as not being intact in 2 cases (no data for 2 cases). Tumors were removed from the abdominal cavity using a Pfannenstiel incision in 6 cases or using an anterior transverse abdominal incision in 1 case (no data given for 17 patients). Table 2 Surgical and pathological data. Tumor histology: IR = intermediate risk, HR = high risk; blast. = blastemal predominant subtype, regr. = regressive type, mixed = mixed subtype, stromal = stromal predominant subtype; Tumor margins: Neg. = histologically free margins, Pos. = histologically detectable tumor cells on margins. Pat. No.
Age at surgery [M]
Largest Tumor diameter [cm]
Specimen weight [g]
Local tumor stage
Tumor histology
Tumor margins
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
53.6 65.4 40.7 34.2 35.7 52.8 33.8 37.4 42.2 45.5 46.6 43.3 62.4 14.9 48.5 22.5 46.4 14.3 25.6 15.0 40.0 27.5 57.5 23.5
4.4 5.0 6.0 5.5 3.8 3.0 3.0 2.8 4.0 7.5 4.0 6.5 9.5 5.0 4.0 6.8 12.0 n.d. n.d. 8.5 5.5. 6.5 7.2 3.5
125 n.d. 157 169 68 91 134 56 190 177 98 254 323 53 105 134 730 n.d. n.d. 310 157 136 47 63
I I II II III I I I II II II I I III III II I I I II I I I I
HR (blast.) IR (regr.) IR (regr.) IR (regr.) IR (regr.) IR (regr.) IR (mixed) IR (regr.) IR (mixed) IR (regr.) IR (mixed) HR (blast.) HR (blast.) IR (regr.) IR (regr.) IR (regr.) IR (mixed) IR (regr.) IR (stromal) IR (stromal) IR(regr.) IR (stromal) n.d. IR (regr.)
Neg. Neg. Neg. Neg. Pos. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Pos. Pos. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg.
2.4. Lymph nodes Lymph nodes (LN) were sampled in 15 of the 24 patients. Numbers of sampled nodes differed between 0 and 11. Positive LN were observed in 5 patients (Table 3). 2.5. Oncological outcome One local relapse occurred in one patient (patient No. 12). In this patient initial treatment consisted of 4 weeks AV, histological subtype was blastemal. The tumor had shown partial response under neoadjuvant chemotherapy, local stage was I, there were 3 lymph nodes sampled (all negative). Postoperative treatment consisted of AVD; no local irradiation was applied. The relapse occurred 8.5 months after surgery. After a median follow-up of 47 months (2–114) all patients were in complete remission, resulting so far in an event-free survival of 23/24 and an overall survival of 24/24 (Table 3). 3. Discussion Minimally invasive techniques are well established in pediatric surgery. Urology represents one major field within this field. Laparoscopic procedures have become the standard approach for several operations on the upper urinary tract. This especially includes pyeloplasties and nephrectomies for benign pathologies [9,18,19]. In adults, MIS is regularly used for the surgical treatment of renal malignancies [20]. In children, Wilms tumors (WT) are more and more often resected laparoscopically, however, only infrequent analyses have been published by now, mostly reporting on small patients' cohorts [12–14,21,22]. Very recently, Varlet et al. published the first multi center study on 17 children undergoing laparoscopic nephrectomy for renal malignancies. This study included 15 children with WT [23]. Guidelines and recommendations for minimally invasive techniques and criteria for their use have commonly not been included in the multicenter treatment protocols so far. On its meeting in Rome in 2012, the surgical panel of the SIOP Renal Tumor Study Group (RTSG) found it important to retrospectively analyze respective data of the most recent study (SIOP 2001) in order to define recommendations and guidelines for MIS in nephroblastoma to be included in the upcoming new treatment protocol. Based on these guidelines a prospective data acquisition and evaluation is then to be undertaken within the next trial. The present study retrospectively analyzed data, which were obtained from various countries worldwide. Several limiting aspects of the analyses have to be considered. The patient number is small and general conclusions are thus difficult to draw. Furthermore, follow-up in some patients is short with respect to an oncological analysis. Nevertheless, we are presenting the largest cohort of respective patients with important implications. The main purpose of this study was not to present a complete evaluation but rather to build up a basis for the further prospective analysis of MIS for nephroblastoma as stated above.
Please cite this article as: Warmann SW, et al, Minimally invasive nephrectomy for Wilms tumors in children – data from SIOP 2001, J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.06.005
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Table 3 Data on lymph nodes and oncological outcome. LN sampled = total number of biopsied lymph nodes, LN positive = total number of lymph nodes containing tumor cells; *: lymph node sampling was documented by surgeon in patient No. 23; however, biopsies did not contain LN material; Postop Chemotherapy: AV-1 = Actinomycin-D + Vincristin, AVD = Actinomycin-D + Vincristin + Doxorubicin, VCCD = VP-16 + Cyclophosphamid + Carboplatin + Doxorubicin; Outcome: NED = No evidence of disease. Pat. No.
LN sampled
LN positive
Postoperative chemotherapy
Postoperative Radiotherapy
Relapse
Outcome
Follow-up [M]
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
2 n.d. n.d. 6 0 11 0 5 2 1 1 3 0 1 2 n.d. 0 0 0 4 1 2 0* 1
2 4 2 0 0 0 0 0 0 0 1 0 1 0 0 0 -* 0
AVD AV-1 None VCCD AVD AV-1 AV-1 AV-1 AVD AVD AVD AVD VCCD AVD AVD AVD AV-1 AV-1 AV-1 AV-1 AV-1 AV-1 AV-1 AV-1
+ + -
+ -
NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED NED
114 50 19 81 72 46 37 30 114 81 68 68 62 54 52 48 46 36 31 33 19 13 13 2
By the time the study, from which the analyzed data were collected, was set up, MIS did not play a great role in pediatric oncology and urology. Many technical improvements, surgical advances, and innovations of MIS in children have only been introduced during recent years through which MIS for nephroblastoma became more and more feasible. As a consequence, the number of laparoscopic WT operations was altogether low in the present study. Although feasibility is not the main aim of surgery in oncological patients, it seems very likely that the rate of laparoscopic nephrectomies for WT will further increase. Another limitation of the present study results from the data collection. Many relevant details of surgical procedures were not recorded because MIS did not play a relevant role at the time when the collection modalities of surgical data were established. For example there was no information about why surgeons chose the laparoscopic approach or why they didn't. Details of the operative technique were regularly lacking including trocar number and positioning, insufflation parameters, modality of specimen removal, and others. Furthermore, it is not known whether the removed kidneys were extracted in a bag without breakage (to allow an adequate pathologic evaluation), because this information was not considered in the surgical form. This information will be included in the next study. The same holds true for the extent of surgical incision to allow excision of the bag. With these experiences in mind, the surgical data acquisition will be adapted and improved for the next trial. Despite the cited limitations there were numerous relevant aspects drawn from the analyzed data. There is an ongoing debate about indications and the general role of MIS in nephroblastoma. The SIOP 2001 protocol commonly recommends neoadjuvant chemotherapy in unilateral Wilms tumors except in patients younger than 6 months or older than 16 years. All children in this study received chemotherapy before surgery. Arguments pro and contra chemotherapy before operation have been thoroughly discussed between different Study Groups. Following the SIOP protocol, the rate of intraoperative ruptures with spillage of tumor cells is lower after neoadjuvant chemotherapy compared to primary surgery due to tumor shrinking and encapsulation [3]. This certainly holds true in MIS and therefore the authors emphasize the recommendations of preoperative chemotherapy before laparoscopic WT resection. There
is a relevant difference of approaching nephroblastoma between different study trials. This mainly concerns the use of upfront surgery in North America (COG) without neodadjuvant chemotherapy in tumors that seem resectable. However, because of the stated risks of intraoperative tumor rupture and subsequent spillage, MIS should only be considered in Wilms tumors after initial chemotherapy. Furthermore, large tumors are an important issue because – once they become dissected and more and more liberated – they are potentially difficult to handle intra-abdominally. In such cases there is a relevant risk for rupture with subsequent tumor spillage. Herein, the ipsilateral border of the vertebral corpuses seems to be a certain limit. In addition, visualization and management of the renal pedicle is relevantly restricted in such cases. Recently, there has been a discussion about a possible overlapping of indications for MIS and nephron sparing surgery (NSS) in nephroblastoma. From the pure technical point of view, minimally-invasive resection of a kidney with a small tumor nodule is certainly similar to a standard MIS nephrectomy for benign reasons in children. However, oncological and functional considerations have to be taken strongly into account at this point. Recent studies indicate that NSS in unilateral WT is associated with a comparable oncological outcome as classical tumor nephrectomies [24–26]. At the same time there is growing evidence that late effects after tumor nephrectomy result in renal failure to a relevant degree; this seems not as much to be the case after NSS in unilateral WT [26–30]. The discussion process within the surgical panel of the SIOP RTSG therefore resulted in the recommendation that MIS and NSS should not interfere in terms of surgical approach: If feasible according to the guidelines of the SIOP Wilms Tumor protocol [31], NSS should be performed. If NSS is not feasible and the decision for tumor nephrectomy has been established, MIS may be chosen as surgical approach but only by those surgeons that have a substantial expertise in oncologic pediatric surgery, pediatric urology, and minimally invasive surgery. Lymph node (LN) sampling was not sufficient in the present study. Adequate sampling of LN is precondition for correct tumor staging, risk stratification, and a correct treatment approach for WT patients in order to minimize the risk for a local relapse [3,32]. Ehrlich et al. clearly have shown that LN metastases and microscopic residual disease have a negative impact on Overall- and Event Free-Survival in
Please cite this article as: Warmann SW, et al, Minimally invasive nephrectomy for Wilms tumors in children – data from SIOP 2001, J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.06.005
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WT patients (stage III, favorable histology) [32]. These aspects are especially important with regard to MIS. The adequate number of LN to be sampled (more than 6) has been determined previously [16,17], indicating an inadequate LN sampling in the present study. Because of the above stated limits of data collection in the analyzed study, the reasons for this were not recorded. Deficits of the discipline of LN sampling in WT surgery have been previously reported analyzing the open surgical approach [3]. These deficits seem even more severe in MIS. Because of the small total number of patients, a statistical negative impact of the inadequate sampling could not be calculated. Nevertheless, the laparoscopic approach for WT nephrectomy can only be accepted provided that the common oncological guidelines are strictly respected. Technical aspects of the operative approach must never be reason for compromises concerning the correct way of performing WT surgery. A thorough analysis of the role of MIS in WT surgery is mandatory, especially since there are already reports on the combined use with NSS, which underline further possible problems [33]. MIS for WT surgery is a challenging procedure requiring exceptional expertise by the operating surgeon. The correct establishment of indications together with a careful patient selection is essential. The outcome of patients in the presented study was so far excellent; however certain limitations of the study have to be taken into consideration. The general guidelines for WT surgery have to be strictly and consequently respected, especially with regard to LN sampling. The future prospective evaluation of MIS for WT will bring further insight into the role of MIS in surgery for nephroblastoma. Acknowledgement The following members of the SIOP RTSG surgical panel made general contributions to this study: Beata Sznajder, Georges Audry, Giovanni Cecchetto, Frédèric Gauthier, Bruce Okoye, Dietrich von Schweinitz, Jan de Kraker †. References [1] Ladd WE. Embryoma of the kidney (Wilms' Tumor). Ann Surg 1938;108:885–902. [2] Gross RE, Neuhauser EB. Treatment of mixed tumors of the kidney in childhood. Pediatrics 1950;6:843–52. [3] Fuchs J, Kienecker K, Furtwängler R, et al. Surgical aspects in the treatment of patients with unilateral wilms tumor a report from the SIOP 93-01/German Society of Pediatric Oncology and Hematology. Ann Surg 2009;249:666–71. [4] Ritchey ML, Shamberger RC, Haase G, et al. Surgical complications after primary nephrectomy for Wilms' tumor: report from the National Wilms' tumor Group. J Am Coll Surg 2001;192:63–8. [5] Frutos MD, Abrisqueta J, Lujan J, et al. Randomized prospective study to compare laparoscopic appendectomy versus umbilical single-incision appendectomy. Ann Surg 2013;257:413–8. [6] Yamataka A, Lane GJ, Cazares J. Laparoscopic surgery for biliary atresia and choledochal cysts. Semin Pediatr Surg 2012;21:201–10. [7] Fuchs J, Luithle T, Warmann SW, et al. Laparoscopic surgery on upper urinary tract in children younger than 1 year: technical aspects and functional outcome. J Urol 2009;182:1561–8. [8] Luithle T, Szavay P, Fuchs J. Single-incision laparoscopic nephroureterectomy in children of all age groups. J Pediatr Surg 2013;48:1142–6.
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Deceased.
Please cite this article as: Warmann SW, et al, Minimally invasive nephrectomy for Wilms tumors in children – data from SIOP 2001, J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.06.005