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Background: Vedolizumab is a biologic, which inhibits leukocyte adhesion in the gut and is used to treat ulcerative colitis (UC) and Crohn's disease (CD). Little is known of the surgical outcomes in patients treated with vedolizumab. We reviewed the postoperative complications in a cohort of pediatric UC and CD patients treated with vedolizumab., Methods: We identified pediatric UC and CD patients treated with vedolizumab at our institution from 2014 to 2016. We compared postoperative outcomes in the vedolizumab exposed group to a cohort of vedolizumab naïve patients who required diverting ileostomy., Results: Of the 31 patients who were treated with vedolizumab, 13 patients required surgery. Eight of 13 (62%) vedolizumab exposed patients had a postoperative complication, including mucocutaneous separation at the stoma (3), readmission for pain/dehydration (2), bowel obstruction at the ostomy, and intraoperative colonic perforation. In comparison, four of 16 (25%) vedolizumab naive patients had a postoperative complication, including readmission for ileus and for high stoma output with mucocutaneous separation. p=0.07., Conclusions: At our institution, patients treated with vedolizumab prior to surgery have a high prevalence of postoperative complications, notably mucocutaneous separation of the stoma. A prospective, multicenter study is needed to determine if these observed complications are attributable to vedolizumab., Level of Evidence: Level III., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Laparoscopic techniques have been applied to restorative proctocolectomy since the early 2000's. We have employed a technique for laparoscopic-assisted total proctocolectomy (TPC) and ileal pouch anal anastomosis (IPAA) for the treatment of children with ulcerative colitis (UC)., Methods: We retrospectively reviewed 68 laparoscopic-assisted TPCs and 39 open TPCs performed at our institution for UC between January 1997 and February 2011. Case duration, postoperative length of stay, and complications of the two groups were compared, and multivariable analysis was applied., Results: The two groups were comparable with respect to gender, age, and postoperative length of stay. Total abdominal colectomy (TAC) duration was significantly longer in the laparoscopic-assisted group (P < .001). Complications were similar in the laparoscopic and open group, although small bowel obstruction (SBO) was significantly less frequent in the laparoscopic group (log-rank test = 8.88, P = .003). Kaplan-Meier estimated freedom from SBO at 1 year follow-up is 99% for patients treated laparoscopically (95% CI: 98%-100%) and 76% for those undergoing an open surgical approach (95% CI: 64%-88%)., Conclusions: The significantly lower SBO rate, low complication rates, and equivalent length of stay favor use of the laparoscopic-assisted approach for TPC and IPAA in children., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To determine whether performing adrenalectomy at the time of nephrectomy for unilateral Wilms tumor impacts clinical outcome., Methods: We reviewed information on all patients enrolled on National Wilms Tumor Study-4 and -5. Data were abstracted on patient demographics, tumor characteristics, surgical and pathologic status of the adrenal gland, and patient outcomes. The primary endpoints were intraoperative spill and five-year event-free survival (EFS) in patients who did or did not undergo adrenalectomy., Results: Of 3825 patients with complete evaluable data, the adrenal was left in situ in 2264 (57.9%) patients, and was removed completely in 1367 patients (36.7%) or partially in 194 patients (5.2%). Of the adrenal glands removed, 68 (4.4%) contained tumor. Adrenal involvement was more common in patients with stage 3 (9.8%) than stage 2 disease (1.9%; p < 0.0001). After controlling for stage and histopathology, five-year EFS was similar whether or not the adrenal gland was removed (p = 0.48), or involved with tumor (p = 0.81); however, intraoperative spill rates were higher in patients undergoing adrenalectomy (26.1% vs 15.5%, p < 0.0001), likely due to larger tumor size or technical factors. No patient had clinical evidence of adrenal insufficiency or tumor recurrence in the adrenal gland during follow-up (median 9.9 years)., Conclusions: Sparing the adrenal gland during nephrectomy for unilateral Wilms tumor was not associated with a higher incidence of intraoperative spill and was associated with a similar oncologic outcome, on a per-stage basis, with cases where the adrenal was removed. Thus, adrenalectomy should not be considered mandatory during radical nephrectomy for Wilms tumor., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: The primary purpose of this study was to investigate the relationship between Pediatric Ulcerative Colitis Activity Index (PUCAI) and operative management. We also specifically evaluated those patients receiving tacrolimus for their disease., Methods: A retrospective review (1/06-1/11) identified ulcerative colitis patients (≤21 years old) undergoing restorative proctocolectomy with rectal mucosectomy and ileal pouch-anal anastomosis. Main outcomes included pre-operative PUCAI, combined versus staged procedure, and postoperative complications. Patients receiving tacrolimus within 3 months of surgical intervention were identified. PUCAI at tacrolimus induction and medication side effects were also noted., Results: Sixty patients were identified. Forty-two (70%) underwent combined and 18 (30%) had staged procedures. Pre-operative PUCAI was lower for combined versus staged patients (p = < 0.001). Furthermore, a higher pre-operative PUCAI strongly correlated with the likelihood of undergoing a staged procedure (p < 0.001). Forty-four patients (73%) received tacrolimus. Significant improvement in their PUCAI was noted from induction to pre-operative evaluation (p < 0.001). Minor and reversible side effects occurred in 46% of patients receiving tacrolimus, but complication rates were not significantly different., Conclusions: There is a very strong correlation between the PUCAI and the likelihood of undergoing a staged procedure. A significant improvement in PUCAI occurs following preoperative tacrolimus therapy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Laparoscopic techniques have been applied to restorative proctocolectomy since the early 2000s. We have employed a technique for laparoscopic-assisted total proctocolectomy (TPC) and ileal pouch anal anastomosis (IPAA) for the treatment of children with ulcerative colitis (UC)., Methods: A total of 68 children underwent laparoscopic-assisted TPCs at our institution from June 2003 to February 2011. The patients ranged from 5 to 22 years of age. We progressively modified our surgical approach in positioning, equipment use, and operative technique., Results: A total of 68 children underwent laparoscopic-assisted TPC within the 8-year time period. Two major complications occurred (2/68=3%) consisting of 1 duodenal injury and 1 small bowel injury. There were 6 minor complications (6/68=9%), including 5 stoma revisions and 1 port site hernia. There were no superficial wound infections. There were no reported cases of pouch fistulas, anastomotic breakdown, or neurovascular injuries., Conclusions: Our surgical technique is safe and effective in treating children with UC., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: The aim of the study was to determine the prognostic impact of lymph node (LN) involvement and sampling in patients with Wilms tumor (WT) and the minimum number of LNs needed for accurate staging., Methods: We reviewed all patients with unilateral, nonmetastatic WT enrolled in the National Wilms Tumor Study 4 or 5. Data were abstracted on patient demographics, tumor histology, staging, number of LNs sampled, and disease-specific and overall patient outcomes., Results: A total of 3409 patients had complete information on LN sampling. Five-year event-free survival (EFS) was lower in patients with nodal disease (P < .001); the effect of LN positivity was greater for patients with anaplastic (P = .047) than with favorable histology (P = .02). The likelihood of obtaining a positive LN was higher when sampling at least 7 LNs. However, after controlling for tumor histology and stage, the number of LNs sampled did not predict EFS variations (P = .75). Among patients with stage II disease, patients with LN sampling (P = .055) had improved EFS, largely reflecting poorer EFS in patients with anaplastic tumors (P = .03)., Conclusions: Lymph node sampling is particularly important for patients with stage II anaplastic WT. Although the likelihood of finding a positive LN was greater when more than 7 LNs were sampled, EFS was not impacted by the number of LNs sampled., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to evaluate recurrence and survival outcomes in pediatric adrenal cortical neoplasms., Methods: A 90-year retrospective review of children with adrenal cortical neoplasms was performed using multivariate Cox regression analysis to identify factors associated with recurrence and tumor-related mortality., Results: The evaluable cohort included 29 patients. Twenty-seven underwent resection. Twenty-two (81%) had localized disease, and 5 (19%) had locally advanced disease (all received chemotherapy and 2 of 5 were cured). Two patients presenting with metastatic disease died despite treatment. There were 4 recurrences; all patients died. Tumor-related mortality was 24% (7/29). Kaplan-Meier freedom from recurrence was 85% at 1 year (95% confidence interval, 75%-95%). Multivariate Cox regression revealed that older age (P = .01), higher mitotic rate (P = .005), and necrosis (P < .001) were independent predictors of tumor-related death. Higher mitotic rate (P = .007) and larger tumor size (P = .03) were significant predictors of tumor recurrence., Conclusion: Risk factors for poor outcomes in patients with adrenocortical tumors include older age, higher mitotic rate, higher percent necrosis, and larger tumor size. Therefore, the presence of these factors may warrant consideration of adjuvant chemotherapy, even in the absence of advanced disease., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background/purpose: Thyroidectomy is the primary therapy for thyroid cancer and an established treatment of hyperthyroidism. Because of the relative rarity of these conditions in childhood, few single-institution series exist in the pediatric literature. Here we analyze our institution's experience to assess patient demographics, operative risks, and the role of preoperative testing., Methods: This is a retrospective chart review of 175 consecutive patients not older than 18 years who underwent thyroid surgery at Children's Hospital Boston from 1970 to 2004., Results: The most common indication for thyroidectomy was thyroid nodules (83%), followed by hyperthyroidism (7%) and goiter (7%). For children referred for nodules, we observed a peak incidence in adolescence and a female to male ratio of 3.7:1. Cancer was found in 36%, with papillary thyroid cancer the most common subtype (85%). Operative complications were rare, with permanent hypocalcemia in 2 (4.7%) of 43 patients who underwent bilateral resection for thyroid nodules (no cases of permanent hypocalcemia in other procedures). Permanent unilateral vocal cord paralysis was documented in 2 children after the resection of malignant nodules., Conclusions: Pediatric thyroidectomy can be performed with low operative risk. Because permanent hypocalcemia remains an obligate risk of bilateral thyroidectomy, we recommend the routine use of preoperative fine-needle aspiration to guide the extent of initial surgical resection, reserving near-total thyroidectomy for those cases where cytology is positive for malignancy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Primary lung tumors in children are rare. A wide range of histopathologic tumor types occurs. The incidence of these lesions and their outcomes are still largely unknown. This study aims to determine the incidence of different primary lung tumors in children and to contribute data leading to the development of evidence-based treatment models., Methods: A single institution retrospective review was performed with institutional review board approval. Patients were included if they had primary, nonhematologic lung tumors. Simple squamous papillomas subjected to endoscopic biopsy and not resected, and vascular lesions associated with multisystem lesions, such as hereditary hemorrhagic telangiectasia, were excluded. Medical records and pathologic material for patients from 1918 to 2008 were reviewed., Results: Forty patients were identified (23 boys, 17 girls) with a mean age of 9.6 years (range, 3 months to 19 years). Fourteen distinct histopathologic tumor types were identified. The most common tumor types were carcinoid (8), inflammatory myofibroblastic tumor (7), and pleuropulmonary blastoma (6). Rare pediatric lung tumors including small cell carcinoma, adenocarcinoma, and pulmonary capillary hemangiomatosis were also seen. The mortality rate was 17.5% (7) in our series. Chemotherapy was used in 23% (9) and radiation in 20% (8) of the patients. Of the 33 survivors, 28 had follow-up with a median duration of 29.5 months (mean, 63.2 months; range, 1-471 months)., Conclusions: Primary lung tumors in children are rare and histopathologically diverse. The tumor spectrum involves many types not seen in adults, and unlike adults, patients rarely have a history of exposure to external predisposing factors. Although complete resection remains the standard for treatment of most tumors, addition of adjuvant therapy is dependent on both tumor stage and histopathologic type., (Copyright 2010 Elsevier Inc. All rights reserved.)

In the past decade, rapid technical developments and advancements of multidetector computed tomography (MDCT) have revolutionized the preoperative imaging evaluation of thoracic vascular and tracheobronchial anomalies and abnormalities in infants and children. Multidetector computed tomography enables noninvasive, rapid, high-resolution, and 3-dimensional (3D) imaging of the thorax in pediatric patients that provides comprehensive preoperative surgical guidance for pediatric surgeons. With the increasing availability of MDCT and 3D imaging, a practical review is needed for the pediatric surgeon of the evolving role of these techniques in the preoperative evaluation of surgical lesions in infants and children. This article focuses on the review of advantages and disadvantages of MDCT in comparison to other imaging modalities, 2D and 3D imaging postprocessing techniques, and MDCT and 3D imaging appearance of various thoracic vascular and tracheobronchial anomalies and abnormalities in pediatric patients. The primary aim of this article was to facilitate the pediatric surgeons' ability to successfully incorporate MDCT and 3D imaging as a routine preoperative imaging tool for the evaluation of thoracic surgical lesions in infants and children., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: The rarity and histopathologic diversity of primary pancreatic neoplasms in children have made it difficult to predict prognosis and to develop optimal management protocols., Methods: A 90-year (1918-2007), single institution, retrospective review of all patients with neoplastic pancreatic masses was performed., Results: Eighteen patients were identified with 7 distinct histopathologic subtypes. The most common were gastroenteropancreatic neuroendocrine, solid pseudopapillary, and acinar tumors. There were 6 benign and 12 malignant tumors. Six patients had disease outside the pancreas at their initial operation. There were 7 deaths (41%), 2 related to the initial operation, 3 from disease progression, 1 from a small bowel obstruction, and 1 from necrotizing pancreatitis. Five deaths were in patients with extrapancreatic disease found at initial operation. The median duration of follow-up for the 10 survivors was 41 months., Conclusion: In adults, pancreatic ductal adenocarcinoma is by far the most common histopathologic subtype, with other subtypes more common in children. Stage is an important prognostic factor. Long-term disease-free survival in childhood pancreatic malignancies is achievable with complete surgical resection, prognosis, and adjuvant treatment, depending on the histopathologic type.

Focal nodular hyperplasia (FNH) is a benign, poorly understood hepatic tumor that is rare in children. Although there is no evidence for malignant degeneration, FNH can occur adjacent to a malignancy. Here, the case of a 4-year-old boy with a hepatic mass and history of stage IV neuroblastoma is presented. Initial imaging and core-needle biopsy were consistent with FNH. However, after left lateral segmentectomy, pathologic examination revealed a malignant tumor most consistent with small cell undifferentiated hepatoblastoma as well as 3 foci of FNH in the surrounding parenchyma.

This study used retrospective review of patients with critical airway due to compression by an anterior mediastinal mass treated at a single pediatric teaching institution. Diagnostic workup is reviewed with a focus on diagnostic biopsy. Algorithm for streamlining the choice of biopsy technique and minimizing invasive procedures is suggested.

Purpose: We reviewed the long-term local tumor control in patients with bilateral Wilm's tumor (BWT) who received no definitive surgical therapy to one kidney after complete radiographic resolution after initial chemotherapy., Methods: National Wilm's Tumor Study 4 (NWTS-4) enrolled 3335 patients (pts) during the period August 1986 to August 1994. There were 188 pts with BWT or 5.6% of the total enrolled. The treatment records and imaging reports were reviewed to ascertain those children who had documented tumors without definitive surgical therapy after initial treatment. Patients who did not have renal surgery because of progression of tumor were excluded from this study., Results: Eleven children had no definitive surgical treatment of renal lesions in one kidney (right, 6; left, 5) after initial treatment with chemotherapy and/or radiation therapy. The pretreatment size of the lesions were less than 3 cm (4 pts), 3 to 6 cm (5 pts), more than 6 cm (1 pt), and unknown (1 pt). Prechemotherapy biopsy was performed in 6 of 11 patients. Lesions were less than 3 cm (1 pt), 3 to 6 cm (3 pts), more than 6 cm (1 pt), and unknown (1 pt). Four biopsy specimens showed favorable Wilm's histologic findings. One lesion (4 cm) showed an intralobar nephrogenic rest, another lesion of unknown size was read as favorable histologic findings vs perilobar nephrogenic rest. Biopsy was not performed on 5 lesions (4 pts, <1 cm; 1 pt, 3cm). Only 2 children in this study received radiation treatment. One child received 1050 cGy whole abdominal radiation, and 1 child received 1060 cGy to the left flank postnephrectomy. Radiation therapy was not given to any patient because of failure of the tumor to respond to chemotherapy. Five patients received treatment regimen EE-4A, dactinomycin, and vincristine. The duration of therapy ranged from 24 to 102 weeks for an average of 55.6 weeks. Three patients received treatment regimen DD-4A, dactinomycin, vincristine, and doxorubicin for 28, 52, and 52 weeks, respectively. Three patients received 2 separate regimens of chemotherapy. One child was treated with dactinomycin, vincristine, and cyclophosphamide for 60 weeks and then received regimen EE-4A for 24 weeks. Another patient received regimen EE-4A for 16 weeks and then regimen DD4-A for 36 weeks. One child received regimen EE-4-A for 12 weeks and then regimen DD4A for 40 weeks. Management of the contralateral kidney was complete nephrectomy in all 11 patients. There were no local relapses in the renal tumor bed. All patients were alive at a median follow-up of 9 years (range, 9 months to 15 years)., Conclusion: Children with synchronous BWT or Wilm's tumor and contralateral nephrogenic rests that have radiographic resolution, after initial treatment, have a low risk for local relapse. These children should be followed by serial imaging.

Background: Rib lesions in the pediatric population are rare but significant processes and are often neoplastic., Methods: All patients with primary rib lesions evaluated by the Department of Surgery at Children's Hospital Boston from 1992 to 2005 were studied. The patient's diagnosis, sex, symptoms and their duration, radiologic evaluation, biopsy status, surgical procedure, and follow-up were assessed., Results: Thirty-three patients, ages 3 to 23 years (median, 12.7 years), were evaluated. Sixteen patients (48%) had benign and 17 (52%) had malignant lesions. Within the benign cohort of 16 patients, there were 6 osteochondromas, 4 aneurysmal bone cysts, and 2 fibrous dysplasias as well as 1 of each of the following: enchondroma, periosteal chondroma, eosinophilic granuloma, and chondrophyte. Within the malignant cohort of 17 patients, 13 were diagnosed with Ewing's sarcoma, 3 with osteogenic sarcoma, and 1 with chondrosarcoma. The sex distribution for the malignant group was 11 (65%) females and 6 (35%) males., Conclusions: Rib tumors are rare entities in the pediatric population. However, a significant number of rib lesions are malignant. Therefore, proper diagnosis and expeditious treatment are critical.

Background: Extension of Wilms' tumor into the ureter is a rare event. We reviewed the National Wilms' Tumor Study Group (NWTSG) database to define the clinical presentation, associated pathologic features, and clinical outcome of these patients., Methods: Records of children identified to have ureteral extension of Wilms' tumor enrolled in NWTS-3, 4, and 5 were reviewed. Presenting symptoms, diagnostic studies, histopathologic findings, operation performed, and outcome were recorded. The NWTS-5 surgical data were prospectively collected as part of the quality assurance program., Results: Forty-five children were identified with ureteral extension. For NWTS-5, the incidence of ureteral extension was 2%. Clinical presentations were gross hematuria in 22 patients, 2 had passage of tissue per urethra, and 1 child had a urethral mass. The remainder had nonspecific presentations. Ureteral extension was seen on preoperative imaging in 14 patients, intraoperatively in 22, and on pathologic examination in 9 patients. Hydronephrosis was noted in 12 patients, and there was nonfunction of the kidney in another 8. Laterality of the tumor was right side in 26 and left in 19. Cystoscopy was performed in 12 children. Findings included tumor seen at the ureteral orifice in 6 patients and bleeding from the orifice in one child. All patients had radical nephrectomy including partial ureterectomy. The ureteral margin was positive in 3 patients, including 2 of the 7 with separate removal of the ureteral extension. The number of patients in each clinical stage was as follows: stage I, 10; stage II, 18; stage III, 14; and stage IV, 3. The tumor extended into the proximal ureter in 23 patients, distal ureter in 13, 7 had extension into the bladder, and 1 had urethral involvement. The level of ureteral extension was not clearly noted in the 45th child. The median follow-up was 96 months. Overall, 41 of 45 patients were alive at last contact. There were 3 deaths because of tumor in patients with unfavorable histologic tumors, and 1 because of treatment toxicity in a child with favorable histologic findings., Conclusions: Ureteral extension occurs in approximately 2% of patients with Wilms' tumor. The diagnosis should be suspected in patients with gross hematuria, hydronephrosis, or nonfunctioning kidney. Cystoscopy with retrograde ureterogram may aid in preoperative diagnosis in these patients. Preoperative diagnosis is important because complete resection of the involved portion of ureter at the time of nephrectomy can avoid residual disease and the need for second surgery or radiation therapy.

Purpose: The purpose of this article is to describe the outcomes of the pouches of 14 children with ulcerative colitis (UC) who were pretreated with calcineurin inhibitors before they underwent their ileal pouch anal anastomosis (IPAA) surgery., Methods: An institutional review board-approved retrospective review of the charts of consecutive patients with UC treated with calcineurin inhibitors before undergoing IPAA surgery at a tertiary pediatric center between 1998 and 2003 was performed. The primary endpoint was pouch outcome after at least 2 years of follow-up (healthy pouch, acute pouchitis, chronic refractory pouchitis, or pouch failure); the secondary endpoints were early postoperative complications, number of stages, and time between stages., Results: Fourteen of 53 consecutive patients who underwent IPAA for UC were treated with calcineurin inhibitors before their surgery (26%; 6 with cyclosporine and 8 with tacrolimus). All 14 patients were concomitantly treated with systemic steroids. Ten patients (71%) were also taking 6-mercaptopurine or azathioprine, and 9 (64%) were also taking mesalamine. Three patients (21%) had healthy pouches with no clinical evidence of pouchitis, 6 (43%) had at least one episode of acute pouchitis (average of 2 episodes per year), 3 (21%) had chronic relapsing pouchitis, and 2 (14%) were later determined to have Crohn's disease. There was no pouch failure. Two patients (14%) had an early postoperative complication (intraabdominal abscess, anastomotic stricture). Five patients (36%) had a 2-staged procedure, and 8 (64%) had a 3-staged procedure. For the 2-staged procedures, the mean time between the first and second stages was 3.14 months (range, 3-4 months). For the 3-staged procedures, the mean time between the first and second stages was 4.25 months (range, 2-6 months) and that between the second and third stages was 4 months (range, 2.5-6 months)., Conclusions: In this series, chronic pouchitis was an infrequent complication among children who were pretreated with calcineurin inhibitors. Calcineurin inhibitor use did not lead to or portend increased early postoperative complications or affect the number or duration of surgical stages. Further studies are required to determine if preoperative calcineurin inhibitors improve pouch outcomes or facilitate the performance of 2-staged procedures.

Purpose: The purpose of this study was to evaluate whether initial diagnostic technique influenced the ability to identify anaplastic histology, to determine the time interval to diagnosis of anaplasia, and to delineate the incidence of discordant pathology in bilateral Wilms' tumor. We hypothesized that delay in diagnosis of anaplasia could affect time to appropriate surgery and intensive multimodality therapy., Methods: One hundred eight-nine children were enrolled in the fourth National Wilms' Tumor Study with synchronous bilateral tumors, 27 of whom were eventually shown to have anaplastic histology. Initial diagnostic technique, time interval to diagnosis of anaplasia, and the incidence of discordant pathology were determined., Results: Anaplasia was identified in 0 of 7 tumors by core needle biopsy, 3 of 9 tumors by open wedge biopsy, and in 7 of 9 cases by partial or complete nephrectomy. The mean duration of first chemotherapy regimen (DD or EE) was 20, 39, and 36 weeks, respectively, before anaplasia was identified at second surgery. Discordant pathology between bilateral tumors was identified on final tissue diagnosis in 20 patients. Only 4 patients had anaplastic tumors in both kidneys., Conclusions: Core needle biopsy did not identify anaplasia in 7 of 7 children. Open biopsy or partial/complete nephrectomy identified anaplasia at initial diagnostic procedure in 10 of 18 children. Twenty of 24 patients at final tissue diagnosis had discordant pathology between the 2 kidneys. Earlier interval incisional biopsy or resection may identify anaplastic histology and limit the duration of chemotherapy targeted to favorable histology for children with bilateral Wilms' tumor and anaplasia.

Background: To provide guidelines for future cooperative group trials, we reviewed the outcomes of children with bilateral Wilms' tumors (BWTs) treated on National Wilms Tumor Study-4 (NWTS-4) who had progressive or nonresponsive disease (PNRD)., Methods: NWTS-4 enrolled 3335 patients from August 1986 to September 1994 including 188 patients with BWT (5.6%). Treatment and outcome data were collected on patients with BWT. Treatment guidelines were outlined in the protocol, but patients were not on study., Results: Thirty-eight children with BWT had PNRD. Preoperative chemotherapy was given for a median of 7 months (range, 2-29 months) before definitive resection. After the initial chemotherapy regimen, 36 children went on to a second regimen, and of these, 21 children received a third regimen before resection. Eleven patients received irradiation to one or both kidneys. Pathology at resection revealed previously undiagnosed anaplasia in 3 patients (2 diffuse and 1 focal) treated for 14, 15, and 15 months before resection. A fourth patient developed a diffusely anaplastic tumor 13 months after therapy. Other pathological findings included rhabdomyomatous (4 patients) or differentiated stromal elements (10 patients) and complete necrosis (1 patient). Ten kidneys from 7 patients lacked biopsy at presentation or pathology review of those specimens., Conclusions: BWT patients with PNRD received prolonged courses of chemotherapy. Early and sequential biopsies to establish the reason for failure to respond should be obtained. This will identify anaplastic tumors managed best by early nephrectomy and intensive chemotherapy and will also distinguish differentiated tumors that are best managed with early resection, but less intensive therapy after nephrectomy.

Background/purpose: Computed tomography (CT) of the chest with its increased sensitivity frequently identifies lesions not visible on chest radiograph. Treatment of such lesions is controversial. A recent review suggests that patients with Wilms' tumor with pulmonary lesions detected only by CT, who were treated with dactinomycin and vincristine, have an inferior outcome compared with those who also received pulmonary radiation therapy (RT) and doxorubicin. It is important to determine if these small lesions seen only on CT represent metastatic disease and whether patients with these lesions require RT and/or doxorubicin for optimal outcome., Methods: Patients with Wilms' tumor with lung metastasis, registered on National Wilms' Tumor Study 5, were reviewed, and those with CT-only lesions who had a radiology and surgical checklist submitted were identified. The treatment regimens of these patients and the histological findings of the pulmonary lesions are presented. We analyzed the pathological findings by whether the patients had single or multiple lesions., Results: Of 2498 patients registered on National Wilms' Tumor Study 5, 252 had pulmonary metastases. Of these patients, 129 (5.2%) had CT-only lesions (<1 cm). Forty-two of these patients (20 boys and 22 girls) underwent lung biopsy at the discretion of the attending physicians. The local tumor stages in these patients were stage I (7%), II (34%), and III (59%). The treatment stages in these patients were stage I (n = 3, 2 drugs), II (n = 3, 2 drugs), III (n = 12, 3 drugs); and IV (n = 24, 3 drugs + RT). There were 16 patients with isolated lung lesions and 26 with multiple lesions, average size 5.8 +/- 0.5 mm. Of 16 isolated lesions, 13 patients (82%) and 69% (18/26) with multiple lesions had tumor on biopsy. Of the 24 who received RT, 8 had a negative biopsy and, thus, may not have needed the RT. Five of 6 treated with just 2 drugs may have been undertreated. Nine of 12 treated with 3 drugs had tumor on biopsy., Conclusions: Computed tomography-only pulmonary lesions are not invariably tumor, demonstrating the need for histopathological confirmation. Biopsy remains critical until radiographic techniques allow differentiation between benign and malignant lesions to optimally direct therapy.

Background/purpose: The treatment approach for patients with high-risk neuroblastoma has been one of dose intensification chemotherapy and aggressive treatment of the primary tumor. Local tumor control is examined in high-risk patients treated with tandem stem cell transplant, aggressive surgery, and selected radiation therapy (XRT)., Methods: Seventy-six patients with high-risk stage III/IV neuroblastoma were treated on a standard protocol incorporating aggressive surgical resection with or without local XRT followed by tandem high-dose chemotherapy and stem cell rescue. Patients were evaluated for degree of surgical resection, site of progression, and outcome., Results: Overall event-free survival for the series is 56%. Forty-eight had gross total resection, 12 had greater than 90% resection, 10 had 50% to 90% resection, and 6 had biopsy only or no surgery. Surgical complications occurred in 29% with no deaths. There were no isolated local failures. Two patients had local recurrence after gross total resection. Surgeon assessment of completeness of resection agreed with postoperative radiological findings 66% of the time., Conclusion: Aggressive surgical treatment with local XRT and myeloablative chemotherapy with stem cell rescue provides excellent local control in high-risk neuroblastoma, although distant failures, particularly osseous, remain a problem. Poor correlation exists between the surgeon's perception of completeness of resection and findings on postoperative imaging studies.

Background: Inflammatory myofibroblastic tumors (IMTs) are neoplasms that are highly vascularized, have an intermediate prognosis, and are associated with infiltration, obstruction, local recurrence, and rare metastasis. Resection of large IMTs can lead to substantial morbidity and even mortality. Anecdotal experience suggests that nonsteroidal anti-inflammatory drugs may eradicate large IMTs or shrink them to a more readily resectable size and configuration. To support the hypothesis that nonsteroidal anti-inflammatory drugs are antiangiogenic for IMTs by interfering with vascular endothelial growth factor (VEGF) signaling via cyclooxygenase 2 (COX-2) inhibition, IMT specimens were immunohistochemically examined for expression of COX-2 enzyme and VEGF., Methods: The diagnosis of IMT was confirmed in all 18 cases comprising the study. Intensity of COX-2 and VEGF staining was graded, and staining uniformity was examined. ALK-1 protein expression, found in up to two thirds of IMTs, was also determined., Results: COX-2 and VEGF expression were identified in all tissue examined, with staining intensity varying independently. ALK-1 protein expression was identified in 33% of specimens. Its presence was not related to the intensity of COX-2 or VEGF staining., Conclusions: Our data suggest that the mediators of angiogenesis, VEGF and COX-2, are present and may play an important role in the growth of IMTs.

Background/purpose: Surgical technique impacts both local tumor stage and risk of local recurrence in Wilms' tumor. A surgical quality assurance program was part of National Wilms' Tumor Study-5 to assess protocol compliance., Methods: Surgical checklists, operative, and pathology reports were reviewed concurrently to arrive at the final local tumor stage. If a protocol violation occurred, a letter was sent to the responsible surgeon. Tumor laterality, extent, type of resection, contralateral exploration, node involvement, spills, and local recurrence were reviewed. Relative risk and logistic regression analyses were performed., Results: There were 1305 nephrectomies. Lymph node sampling was not performed in 117 (9%) patients: stage I, 41 (11.5%), stage II, 57 (12%), and stage III, 19 (4%). Of importance, 41% (187/457) of stage III cases were designated stage III solely on the basis of positive lymph nodes. Tumor spill occurred in 19.3% (253/1305) of children. Fifty-four local spills were in stage II tumors and 97 in stage III. Diffuse spill occurred in 102 patients with stage III tumors. Seventeen preoperative and 13 intraoperative biopsies were performed. Intraoperative tumor rupture was the most common cause of tumor spill accounting for 139 (55%) spills. Nineteen (7.5%) children were upstaged, receiving more intensive therapy because of spill. Included in the group were 3 of 17 preoperative biopsies and 5 of 13 intraoperative biopsies. Spills (13/253) were determined to be avoidable. Eight were biopsies, 5 because tumor was transected in the renal vein (4) or ureter (1). In stage II patients where lymph nodes were not sampled, there is an increase in local relapse rate that did not achieve statistical significance because of the small number of events., Conclusions: Although most surgeons complied with the surgical guidelines, numerous deviations were identified including failure to sample lymph nodes (117 cases) and unnecessary biopsies leading to tumor spill (30 cases). Protocol violations have an adverse impact on tumor staging, potentially increasing the risk for local tumor recurrence or intensity and toxicity of therapy.

Background/purpose: Cystic partially differentiated nephroblastoma (CPDN) is a rare variant of Wilms' tumor thought to be more favorable than standard nephroblastoma. The purpose of this report is to examine the outcome of children with CPDN, after nephrectomy, treated with vincristine and dactinomycin based chemotherapy (+/- doxorubicin) or no chemotherapy., Methods: Patients were registered with the National Wilms' Tumor Study Group (NWTSG) and data were collected prospectively. All patients had central review by the NWTSG Pathology Center to confirm the diagnosis of CPDN., Results: Twenty-one patients were identified with a diagnosis of CPDN. Thirteen patients received chemotherapy, and 8 patients did not. In the chemotherapy group the stage distribution was as follows: stage I (n = 10), stage II (n = 2), stage V (n = 1). In the no-chemotherapy group, all 8 patients were stage I. All patients had complete tumor resection. There were no cases of disease progression or recurrence in any patient. In patients receiving chemotherapy, 30% (n = 4) had toxicities causing dose reduction., Conclusions: The outcome of patients with CPDN is favorable with 100% survival rate and no recurrences. For stage I patients, treatment with complete tumor resection appears to be as efficacious as nephrectomy plus chemotherapy. Stage II patients also have excellent outcome when treated with tumor resection and postoperative vincristine and dactinomycin.

Background/purpose: An increased incidence of Wilms tumor has been noted in patients with a horseshoe kidney. These represent a difficult diagnostic and therapeutic challenge. The charts of all National Wilms Tumor Study Group (NWTSG) patients with Wilms tumor occurring in a horseshoe kidney were reviewed., Methods: From 1969 to 1998, 8,617 patients were enrolled in the NWTSG. Forty-one patients were found to have a Wilms tumor arising in a horseshoe kidney for an incidence of 0.48%. Their records were reviewed retrospectively., Results: Horseshoe kidney was not recognized preoperatively in 13 patients, 10 of whom were evaluated with computed tomography (CT). Four of the 10 also had renal ultrasonography and one an intravenous pyelogram (IVP). Two of the 13 were evaluated with an IVP only, and the last had no preoperative imaging studies performed. Stage at presentation was stage I, 10 pts; stage II, 10; stage III, 12; stage IV, 6; stage V, 3. Primary surgical resection was performed in 26 patients, including 23 nephrectomies and 3 partial nephrectomies. Fifteen children were treated with preoperative chemotherapy after initial biopsy of the tumor. The mean total remaining renal parenchyma after all operations (excluding treatment of relapses) was approximately 75%. Surgical complications occurred in 14.6% of patients, including 2 urine leaks, 2 ureteral obstructions, and 1 ureteral injury. Two patients had transient renal failure., Conclusions: The diagnosis of horseshoe kidney often was missed on preoperative imaging. Accurate preoperative diagnosis is important in planning the operative approach and may help to decrease complications related to transection of the urinary collecting system. Although 37% of patients with Wilms tumor arising in a horseshoe kidney were judged inoperable at initial exploration, all were amenable to resection after chemotherapy., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Separation of thoracopagus conjoined twins with a single heart and the twin reversed arterial perfusion sequence yielded a single surviving infant with a protuberant heart covered by ribs and soft tissue from the nonsurviving twin. At 13 months of age, the heart was relocated in the chest after caudal mobilization of the diaphragms. The protective tissue cage was removed and a normal chest contour established. This technique also may be useful in the treatment of thoracic ectopia cordis., (Copyright 2002 by W.B. Saunders Company.)