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Purpose: To assess prognostic factors for local control in high-risk neuroblastoma patients treated with hyperfractionated 21-Gy total dose to consolidate remission achieved by dose-intensive chemotherapy and surgery., Patients and Methods: Patients with high-risk neuroblastoma in first remission received local radiotherapy (RT) totaling 21 Gy in twice-daily 1.5-Gy fractions. RT to the primary site followed dose-intensive chemotherapy and tumor resection; the target field encompassed the extent of tumor at diagnosis, plus 3-cm margins and regional lymph nodes. RT to distant sites followed radiologic evidence of response. Local failure was correlated with clinical factors (including other consolidative treatments) and biologic findings., Results: Of 99 consecutively irradiated patients followed for a median of 21.1 months from RT, 10 relapsed in or at margins of RT fields at 1 to 27 months (median, 14 months). At 36 months after RT, the probability of primary-site failure was 10.1% +/- 5.3%. No primary-site relapses occurred among the 23 patients whose tumors were excised at diagnosis, but there were three such relapses among the seven patients who were irradiated with evidence of residual disease in the primary site. Four of 18 patients with MYCN-amplified disease and serum lactate dehydrogenase greater than 1,500 U/L had local failures (23.4% +/- 10.7% risk at 18 months). Acute radiotoxicities were insignificant, but three of 35 patients followed for > or = 36 months had short stature from decreased growth of irradiated vertebra., Conclusion: Hyperfractionated 21-Gy RT is well tolerated and, together with dose-intensive chemotherapy and surgery, may help in local control of high-risk neuroblastoma. Extending the RT field to definitively encompass regional nodal groups may improve results. Visible residual disease may warrant higher RT dosing. Patients with biologically unfavorable disease may be at increased risk for local failure. RT to the primary site may not be necessary when tumors are excised at diagnosis.

Purpose: We have synthesized a series of hybrid polar compounds that induce differentiation and/or apoptosis of various transformed cells. These agents are also potent inhibitors of histone deacetylases (HDACs). Pyroxamide (suberoyl-3-aminopyridineamide hydroxamic acid) is a new member of this class of compounds that is currently under development as an anticancer agent. We investigated the activity of pyroxamide as an inducer of differentiation and/or apoptosis in transformed cells., Experimental Design and Results: Pyroxamide, at micromolar concentrations, induced terminal differentiation in murine erythroleukemia (MEL) cells and caused growth inhibition by cell cycle arrest and/or apoptosis in MEL, prostate carcinoma, bladder carcinoma, and neuroblastoma cells. Administration of pyroxamide (100 or 200 mg/kg/day) to nude mice at doses that caused little evident toxicity significantly suppressed the growth of s.c. CWR22 prostate cancer xenografts. Despite the potent growth-inhibitory effects of pyroxamide in this tumor model, serum prostate-specific antigen levels in control versus pyroxamide-treated mice were not significantly different. Pyroxamide is a potent inhibitor of affinity-purified HDAC1 (ID(50) = 100 nM) and causes the accumulation of acetylated core histones in MEL cells cultured with the agent. Human CWR22 prostate tumor xenografts from mice treated with pyroxamide (100 or 200 mg/kg/day) showed increased levels of histone acetylation and increased expression of the cell cycle regulator p21/WAF1, compared with tumors from vehicle-treated control animals., Conclusions: The findings suggest that pyroxamide may be a useful agent for the treatment of malignancy and that induction of p21/WAF1 in transformed cells by pyroxamide may contribute to the antitumor effects of this agent.

Background: Neuroblastoma is a common childhood cancer with a poor overall prognosis. Retinoic acids (RAs) have been studied as a potential therapy, showing promise in recurrent disease. The histone deacetylase inhibitor (HDACI) M-carboxycinnamic acid bishydroxamide (CBHA) is another potential therapy, which we recently described. Combinations of RAs and HDACIs currently under investigation display synergy in certain neoplasms. In this study, we evaluate the effect of combinations of RAs and HDACIs on human neuroblastoma cells., Procedure: Established cell lines were cultured in increasing concentrations of HDACIs, RAs, and combinations thereof. Following exposure, viable cell number was quantified by trypan blue dye exclusion on a hemacytometer. Cell cycle analysis was performed by propidium iodide staining and FACS., Results: All assayed HDACIs and RAs decreased viable cell number. Lower concentrations of each agent were effective when the two were combined. The primary reason for decreased cell number appears to be apoptosis following HDACI exposure and G1 arrest following RA exposure. Both effects are seen with cotreatment. Caspase inhibition abrogates the apoptotic response., Conclusions: CBHA causes apoptosis of human neuroblastoma in vitro, an effect that can add to the effects of RA. HDACIs and RAs inhibit neuroblastoma in significantly lower concentrations when used together than when used individually. Combination therapy may improve the ultimate efficacy while reducing the side effects of these agents in clinical use., (Copyright 2000 Wiley-Liss, Inc.)

Combination chemotherapy, often in conjunction with surgery and external radiotherapy, is utilized in most children with tumors of the genitourinary tract. These chemotherapeutic agents are capable of causing a variety of delayed toxicities. Common late complications include cardiotoxicity associated with prior exposure to an anthracycline, pulmonary dysfunction, infertility in males due to prior therapy with alkylating agents, and secondary leukemia in individuals treated with epipodophyllotoxins.

Objective: We sought to establish the outcome and optimal therapeutic sequence for patients with nonmetastatic Ewing sarcoma/primitive neuroectodermal tumor of the chest wall., Methods: Patients 30 years of age or younger with nonmetastatic Ewing sarcoma/primitive neuroectodermal tumor of the bone were randomly assigned to receive vincristine, doxorubicin, cyclophosphamide, and dactinomycin or those drugs alternating with ifosfamide and etoposide. Local control was obtained with an operation, radiotherapy, or both., Results: Fifty-three (13.4%) of 393 patients had primary tumors of the chest wall (all rib). Event-free survival at 5 years was 57% for the chest wall compared with 61% for other sites (P >.2). Ifosfamide and etoposide improved outcome in the overall group (5-year event-free survival, 68% vs 54%; P =.002), and a similar trend occurred in chest wall lesions (5-year event-free survival, 64% vs 51%). Patients with chest wall lesions had more attempts at initial surgical resection (30%) than those with other primary tumor sites (8%, P <.01). The attempt at initial resection for chest wall lesions did not correlate with size. Initial resections at other sites were restricted to smaller tumors. Initial resection resulted in negative pathologic margins in 6 of 16 patients, whereas the delayed resection resulted in negative margins in 17 of 24 patients (P =.05). Although there was no difference in survival by timing of the operation in rib lesions, a higher percentage of patients with initial surgical resection received radiation than those with resection after initial chemotherapy (P =. 13)., Conclusions: Although rib primary tumors are significantly larger than tumors found in other sites, their outcome is similar. We favor delayed resection whenever possible to minimize the number of patients requiring radiation therapy.

Background: Chest wall tumors of primitive neuroectodermal origin (PNET, Ewing's sarcoma [ES]) are rare and have a poor prognosis. Multimodality therapy has improved survival results, and long-term survival is possible. Whether adjuvant radiation therapy is uniformly beneficial remains unclear., Methods: A retrospective analysis of the authors' institutional experience between 1979 and 1998 was performed., Results: Twenty consecutive patients with PNET-ES of the chest wall were identified. The median age was 12 years (range, 2.5 to 21 years). Median follow-up was 3 years (range, 7 months to 19.4 years). Seven patients presented with a mass, 12 with pain, 1 with respiratory distress, and 1 with a neuropathy. Initial therapy consisted of biopsy and neoadjuvant chemotherapy followed by chest wall resection in 12 patients. Of the remaining 8 patients, 6 underwent biopsy, followed by chest wall resection and adjuvant chemotherapy, 1 underwent biopsy, chemotherapy, and resection of a lung nodule, and 1 underwent biopsy, chemotherapy, and a laminectomy and decompression procedure. All 20 patients were included in institutional-based trials using multiagent chemotherapy. Fifteen patients received radiation therapy with a median dose of 3,000 cGy. At last follow-up, 11 patients are alive and disease free, with a median survival of 7.5 years (range, 7 months to 19.4 years). Seven of 11 (64%) survivors had neoadjuvant therapy followed by chest wall resection. Seven of 11 (64%) survivors had radiation therapy. There was no surgical mortality. Twelve patients had treatment-related complications, 3 of which were related to surgical resection. There were no survivors among patients with recurrent disease. Three of the patients who died of disease had both local and distant recurrences, 4 patients had distant recurrence only, and one patient had local recurrence only. Only 4 of 9 (44%) patients who died were treated initially with chemotherapy followed by chest wall resection. All but 1 of those that died (89%) received initial radiation therapy. All 9 patients who did not survive received additional salvage radiotherapy as well., Conclusions: Long-term survival is possible with ES-PNET after complete chest wall resection. This may be facilitated by neoadjuvant chemotherapy. Long-term survival without radiation therapy is possible, and consideration of radiation therapy should be made on a case-by-case basis.

Deletion of the short arm of chromosome 1 is frequently observed in neuroblastoma (NB). We performed loss of heterozygosity (LOH) analysis of 120 well characterized NB to better define specific regions of 1p loss and any association with clinical and biological prognostic features (DNA index, MYCN, age, and stage). All categories of disease were represented including 7 ganglioneuromas, 8 stage 4S, 33 local-regional (stages 1, 2, and 3), and 72 stage 4 NB according to the International Neuroblastoma Staging System. Patients were consistently treated with stage-appropriate protocols at a single institution. Sixteen highly informative, polymorphic loci mapping to chromosome 1 were evaluated using a sensitive, semi-automated, fluorescent detection system. Chromosome arm 1p deletions were detected in all categories of tumor except ganglioneuroma. Frequent LOH was detected at two separate regions of 1p and distinct patterns of losses were associated with individual clinical/biological categories. Clinically aggressive stage 4 tumors were predominantly diploid with extensive LOH frequently detected in the region of 1ptel to 1p35 (55%) and at 1p22 (56%). The shortest region of overlap for LOH at 1p36 was between D1S548 and D1S1592 and for 1p22 was between D1S1618 and D1S2766. Local-regional tumors were mostly hyperdiploid with short regions of loss primarily involving terminal regions of 1p36 (42%). Most spontaneously regressing stage 4S tumors (7/8) were hyperdiploid without loss of 1p36 or 1p22. These findings suggest that genes located on at least two separate regions of chromosome arm 1p play a significant role in the biology of NB and that distinct patterns of 1p LOH occur in individual clinical/biological categories.

Background: Standard cytogenetic techniques are time-consuming and often not informative with solid tumors. In contrast, the reverse transcriptase-polymerase chain reaction (RT-PCR) is a readily available technique that can rapidly detect tumor-specific chromosomal rearrangements, even in small biopsy specimens. We present cases depicting the importance of including molecular diagnostic studies in the routine evaluation of pediatric solid tumors., Procedure: We used RT-PCR to detect chimeric transcripts specific for major pediatric solid tumors, including peripheral primitive neuroectodermal tumor (pPNET), alveolar rhabdomyosarcoma (ARMS), and desmoplastic small round-cell tumor (DSRCT). We reviewed six recent cases in which the initial diagnosis was changed by the results of RT-PCR., Results: Highly unusual or nonspecific clinical and/or histopathologic findings led to the initial diagnoses of neuroblastoma in three patients and DSRCT, leukemia, and carcinoma in one patient each. The final diagnoses after RT-PCR studies were pPNET in three patients, ARMS in two patients, and DSRCT in one patient. RT-PCR results led to early corrections in the diagnosis in two patients, but four patients received treatment not considered optimal for the neoplasms ultimately diagnosed, including three who, despite presenting with localized tumors that have a >70% cure rate with standard therapy, have died or are dying of disease., Conclusions: Molecular genetic studies on solid tumors can clarify the diagnosis in seemingly straightforward as well as in overtly problematic cases. These diagnostic distinctions are now critical as disease-specific and risk-directed therapies have emerged., (Copyright 1999 Wiley-Liss, Inc.)

Background: The identification of recently described nonrandom chromosomal defects specific for various small round-cell and spindle-cell sarcomas can eliminate diagnostic uncertainty arising from the clinical and histopathologic overlap of soft tissue neoplasms., Methods: A 26-year-old man presented with bulky abdominal-pelvic disease. Immunohistochemical and molecular studies on tumor were performed. Treatment was instituted using cycles of high-dose cyclophosphamide (4,200 mg/m2) with doxorubicin (75 mg/m2)., Results: Clinical findings pointed to desmoplastic small round-cell tumor. The tumor was histologically undifferentiated and immunoreactive for vimentin but negative for other markers. Reverse transcriptase-polymerase chain reaction revealed the SYT/SSX2 fusion transcript of the synovial sarcoma t(X;18) chromosomal rearrangement. The high-dose chemotherapy, plus surgery, achieved a complete remission, but recurrent disease emerged 13 months from diagnosis., Conclusions: This clinically unique case of synovial sarcoma highlights how the use of now readily available molecular techniques will allow more accurate appraisals of the incidence and anatomic distribution of soft tissue neoplasms-information that bears upon pathogenesis and treatment. This case confirms the utility of high-dose alkylator-based therapy for synovial sarcoma. It also demonstrates that with nonlocalized solid tumors, the eradication of minimal residual disease remains an elusive goal. One alternative involves immunologic attack against markers derived from tumor-specific chromosomal defects such as those found in our patient.

Background: Increased tumor neovascularity has been shown to correlate with poor prognosis in solid tumors., Methods: Microvessels were identified by factor VIII immunohistochemical staining. Analysis of microvessel counts, tumor characteristics, and resection details was performed on 119 primary, high-grade extremity soft tissue sarcomas (STS) and correlated with clinical outcome., Results: Tumor characteristics and resection details were analyzed and patient outcome was examined with respect to local recurrence, distant metastasis, and disease-specific survival. Factors found to be significant on univariate analysis for all outcome variables were positive microscopic margin and tumor size. A positive microscopic margin was found to be a significant risk factor for local recurrence (P = .03), distant metastasis (P = .006), and disease-specific survival (P = .004). A primary tumor greater than 10 cm in diameter was a poor prognostic factor for distant metastasis (P = .03) and disease-specific survival (P = .006) when compared to tumors smaller than 10 cm. Microvessel count did not correlate with survival nor did it predict distant metastasis or local recurrence. Histologic subtypes of STS that have a prominent vascular pattern as a diagnostic criterion (i.e., angiosarcoma, liposarcoma, hemangiopericytoma) form a subgroup of all STS. Neovascularity in these subtypes showed no relationship to clinical outcome., Conclusions: These data confirm the prognostic importance of microscopic margin and tumor size in high-grade extremity STS. Neovascularity measured by factor VIII staining had no prognostic significance in these mesenchymal tumors, in contradistinction to carcinomas. Alternatively, microvessel counts may not accurately represent the angiogenic capacity of STS. Therefore, patients with STS who are eligible for anti-angiogenesis clinical trials cannot be identified solely by microvessel count.

Objective: In this study, we sought analysis of minimal access procedures in pediatric and young adult oncology patients., Methods: Between 1990 and 1997, 84 patients underwent 93 minimal access procedures. Clinical, pathological, and operative details were analyzed., Results: There were 32 females and 52 males with a median age of 14 years (range 3 months to 31 years). The median body weight was 50 kg (range 6-94 kg). There were 47 thoracoscopic procedures and 46 laparoscopic procedures. Laparoscopic procedures included liver biopsy (21), diagnostic tumor biopsy (13), lymph node biopsy (4), cholecystectomy (4), oophoropexy (3), and kidney biopsy (1). Median hospital stay was 2 days (range 1-14 days). Six patients had their procedure converted to an open procedure (13%). Thoracoscopic procedures included diagnostic lung biopsy (22), mediastinal mass biopsy or resection (4), pleural biopsy (5), and pleurodesis (4). Eleven were converted to open thoracotomy (23%). Median hospital stay was 4 days (range 2-35 days). There were two complications after laparoscopy (4%) and three disease-related deaths. There were six complications after thoracoscopy (13%), and three disease-related deaths. Adequate tissue was obtained in all biopsy procedures., Conclusions: Children with cancer require operations for diagnosis and staging. Minimal access procedures are safe and effective and allow adjuvant therapy to begin earlier.

In human neuroblastoma cells in culture, three morphologically distinct types of cells are observed: neuroblastic N-type cells, Schwannian S-type cells, and intermediate I-type cells. To investigate the differences in gene expression between N-type LA1-55N and S-type LA1-5S cells of the human neuroblastoma cell line LA-N-1, we constructed a subtractive cDNA library from LA1-5S cells. One of the genes that are expressed more in S-type cells than in N-type cells was identified as previously undescribed and is the focus of this report. We cloned a full-length cDNA of this gene, p37NB, and determined its sequence. A homology search against the GenBank database showed that this was from a novel gene encoding a putative 37 kDa leucine-rich repeat (LRR) protein. Northern blot hybridization and RT-PCR showed that the p37NB gene was differentially expressed in S-type compared to N-type cells of a few neuroblastoma cell lines.

Background: Multiple endocrine neoplasia type 2 (MEN 2) is a group of related autosomal dominant cancer syndromes caused by mutations in the RET protooncogene. A subset of familial Hirschsprung's disease, aganglionic megacolon, is also caused by mutations in this gene., Methods: The authors performed mutation analysis of exons 10, 11, 13, and 16 of the RET gene is six established MTN 2 kindreds and in six patients with apparent sporadic disease, in order to correlate their genotypes and phenotypes., Results: One of these kindred's carried both Hirschsprung's disease and MEN 2A in conjunction with a cysteine-to-arginine substitution of codon 620 of the RET gene. One patient with apparently sporadic disease was found to have a germline M918T mutation. Patients with confirmed familial disease all carried pathologic germline mutations of RET., Conclusions: Several lines of evidence support a gain of function mechanism for tumorigenesis in the MEN 2 syndromes but a loss of function mechanism for aganglionosis in Hirschsprung's disease. The authors propose that a multihit mechanism can reconcile the apparent paradox of a single mutation that gives rise to both gain and loss of function disorders in a single patient.

Ten children with locally advanced or recurrent tumors were treated on a Phase I/II study to assess the feasibility and toxicity of intraoperative radiotherapy (IORT) for primary and recurrent pediatric solid malignancies at high risk for local recurrence. Eligible patients include all primary and recurrent pediatric solid tumors that are amenable to resection and have residual microscopic or gross disease after surgery. In all cases, after a gross tumor resection was performed, a flexible, transparent, multichannel applicator was placed and secured within the tumor bed. Once the position of the applicator was optimized, the applicator catheters were attached to the cables of a high-dose-rate remote afterloader, and 1,200 cGy prescribed to 0.5-1.0 cm from the applicator was delivered to the tumor bed via the remote afterloader. One patient with a malignant teratoma developed a peri-rectal abscess 1 month after treatment; no other complications were noted. The 2-year actuarial local recurrence-free and distant metastases-free survival were 80% and 59%, respectively, with a median follow-up of 12 months (range: 3-18 months). The preliminary results suggest that high-dose-rate IORT is a safe and feasible modality for pediatric tumors at high risk for local recurrence. Longer follow-up will be needed to assess fully the toxicity and efficacy of this approach.

Background: Hepatic regeneration and function after resection has been evaluated in adults, but long-term quantitative assessment has not been performed in children. Semiquantitative short-term evaluations, including radioisotope scans, have suggested that hepatic regeneration occurs quickly in children, but the effect of chemotherapy on hepatic regeneration has not been evaluated. Treating hepatoblastoma in children increasingly includes chemotherapy before resection, hence evaluating regeneration is critical., Study Design: A retrospective evaluation was done of ten children older than one year following anatomic hepatic resection for benign or malignant tumors. Three components were evaluated. First, hepatic function was evaluated by a series of tests of synthetic function. Second, the metabolic function of the liver was evaluated by measuring the hepatic conversion of lidocaine to its breakdown product, monoethylglycinexylidide (MEGX). Third, hepatic volume was assessed by magnetic resonance imaging scan., Results: All children were clinically well at the time of evaluation. Results of tests of synthetic function were essentially normal in all patients. Serum ammonia levels were mildly elevated in six patients. Hepatocellular enzymes were mildly elevated in several children, and the alkaline phosphatase level was mildly elevated in three. A lidocaine infusion study demonstrated normal levels of MEGX in all of the children except one with positive hepatitis C serology. Studies demonstrated that hepatic volumes were below but near the expected levels in most children. Sequential studies in six children demonstrated progressive growth of the livers. No adverse effect on hepatic size was noted in the children who received chemotherapy., Conclusions: The cohort of children had adequate regeneration and function of the liver following hepatic resection. No adverse effect of perioperative chemotherapy could be identified.

Purpose: The time course of hepatic volume regeneration and return of excretory and synthetic function was studied in eight children undergoing lobar or extended lobar liver resections for hepatoblastoma (n = 5), hepatoma (n = 1), and recurrent nephroblastoma (n = 2). Five patients received preoperative and all were administered postoperative chemotherapy. Whole-liver irradiation was administered to one patient. One additional patient who underwent an extended hepatic resection for benign disease and did not receive chemotherapy was included for comparison., Methods: A previously validated technique of computer-aided volume measurement was used to measure liver volumes from serial CT scans obtained after hepatic surgery. Normal liver volume as a function of age was determined from the literature and the time course of regeneration was compared to normal liver growth. Postoperative serum albumin, total bilirubin, serum glutamic oxaloacetic transaminase, and alkaline phosphatase levels were recorded and correlated with volume regeneration., Results: In six patients hepatic regeneration had progressed to normal volume by 90 days after resection (normal volume for age was achieved by 50 days in three patients). There was an initial rapid rate of regeneration (> 10 cc/day) which declined to a normal rate of less than 0.5 cc/day at 90 days after surgery. Two children with failure to thrive displayed the same pattern of rapid regeneration, attaining a volume appropriate for weight but less than that expected for age. The shape of the liver volume regeneration curve was similar in one additional patient undergoing an extended left lobectomy for benign disease. A brief rise in bilirubin occurred during the first week and a transient fall in serum albumin was followed by resumption of normal synthetic capacity within 6 weeks in all but two patients., Conclusions: Liver regeneration in children is a rapid process occurring despite the administration of cytotoxic agents and hepatic irradiation.

Tumor volume at diagnosis is an important prognostic factor and volume change may predict therapeutic response. However, the accuracy of in vivo tumor volume measurement has not been established. The purpose of this study was validation of a personal computer-based technique of in vivo volume determination. CT scans of 8 radiological phantoms and 25 neuroblastoma patients were digitized using three-dimensional reconstruction and volume determination software. Phantom volumes were calculated from known dimensions or direct measurement while tumor volumes were determined by water displacement at the time of complete gross resection. Comparison to tumor volume determination was performed using an ellipsoid geometric model. The standard deviation for computer-generated triplicate volume determinations varied from 0.1 to 5.6 cc (median = 0.6 cc). Linear regression analysis demonstrated a close correlation between computer-derived volumes and the volume measured at surgery (r = 0.99) with small variability. In contrast, the correlation coefficient between ellipsoid formula-derived and water displacement volumes was 0.93. Computer-generated tumor volume determination is reproducible, accurate, and easily obtained from hard copy scans. This technique provides a quantitative in vivo measurement for use as a prognostic or therapeutic response variable.

This review addresses the management of epithelial liver tumors of childhood and adolescence (hepatoblastoma and hepatocellular carcinoma), which constitute approximately 90% of primary liver malignancy in this age group. The epidemiology, pathology, clinical presentation, and diagnosis are given in order to appreciate differences in biological behavior of these two neoplasms and the need for a distinct therapeutic approach to each. The multidisciplinary treatment of hepatoblastoma has become increasingly refined and long-term survival can be expected in approximately 80% of patients. Where survival once depended solely on complete surgical resection, it is now also possible in patients with initially unresectable tumors due to effective cytoreductive chemotherapy. The problem of systemic relapse following complete surgical resection has been reduced although not eliminated by adjuvant chemotherapy programs. To date, the biological behavior of hepatocellular carcinoma prohibits complete resection in the majority of children and chemotherapy has not been effective. Early detection, development of new agents and techniques such as monoclonal antibodies and total hepatectomy with autologous transplantation in selected cases may offer hope for the future.

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and adolescence with 20% of the primary tumors anatomically located on extremities. It is a complicated entity that requires careful planning and coordination between the surgical oncologist and other members of the therapeutic team for successful treatment. Even with the most effective regimens more than 50% of patients will die from progressive, usually distant disease. Further progress may require new therapeutic agents or techniques. The surgical oncologist is a necessary and often prominent member of the team. Elements of the biological behavior, histopathology, clinical staging, and treatment of extremity rhabdomyosarcomas occurring in children are discussed. In particular, the importance of the alveolar subtype in determination of prognostic risk as well as new findings regarding the molecular biologic determinants of phenotypic behavior are mentioned. Finally, innovative methods of local control like regional arterial perfusion and rapid intraoperative brachytherapy are addressed.

Obstetrical sonography has helped diagnose and define the features of some congenital malformations and tumors. We present five fetal neuroblastomas detected by routine prenatal sonography. All were adrenal tumors diagnosed between 26 and 39 weeks gestation. All 5 tumors were completely resected postnatally and the patients have remained disease free from 2 months to 10 years after resection without adjuvant therapy. A literature review collated 16 other cases of fetal neuroblastoma detected by sonography between 29 and 38 weeks gestation. These cases included 1 cervical, 1 thoracic, and 14 adrenal tumors. Thirteen neonates had Evans stage I or II tumors, and three had more advanced disease. Eleven mothers did not have hypertension or preeclampsia during the pregnancy, and the neonates all had stage I or II disease. Four mothers had hypertension or preeclampsia. Three of these neonates had stage IV or IVS disease with liver metastases, and all three had fetal hydrops. Review of the congenital neuroblastoma literature documented 71 cases diagnosed soon after birth, and several of these cases had unusual features that could have been detected by prenatal ultrasound. Four of the tumors were so large that dystocia resulted and fetal dismemberment was required for delivery. Eight of the tumors metastasized to the placenta, and 1 metastasized to the umbilical cord with subsequent fetal death. We conclude that fetal neuroblastoma can be diagnosed by prenatal sonography. Accurate staging is difficult by sonography, but in mothers with no preeclampsia symptoms the chance of widely disseminated disease is small.(ABSTRACT TRUNCATED AT 250 WORDS)

A technique helpful in exposing the mucosal aspect of the gastroesophageal junction is described.

In prepubertal children, teratoma is a benign tumor, whereas in adolescents and adults, it behaves as a malignant neoplasm. Adult patients without evidence of metastases may be candidates for surveillance after orchiectomy, and those with low-volume or borderline retroperitoneal metastases thought to contain teratoma might best be managed by surgery, as teratomatous deposits do not respond to chemotherapy. Patients with larger retroperitoneal metastases may be given chemotherapy before surgery to reduce or eliminate other germ-cell elements. Teratomatous masses persisting after chemotherapy are excised by most clinicians, in part to obtain a pathologic diagnosis. In childhood tumors, inguinal orchiectomy or enucleation is sufficient if one is certain the lesion contains only teratoma.

This study aims to identify significant predictors of survival in pediatric and adolescent colorectal carcinoma. We retrospectively analyzed our experience with 29 histologically verified cases, of which 20 were resected for cure. Variables analyzed as predictors of survival included: (1) resectability, (2) regional nodal involvement, (3) depth of invasion, (4) grade, and (5) interval from symptom onset to diagnosis. Signet ring or anaplastic lesions were considered high grade. Survival curves were generated on both the overall group and those resected for cure. Multivariate analysis was performed on the overall group. The median age at diagnosis was 19 years (range, 10 to 21). Median follow-up in survivors was 4.7 years. Signet ring tumors occurred in 45% and another 24% were poorly differentiated. Seventy-six percent presented with regional lymph node metastases. The median survival for the overall group was 16 months, whereas that for those undergoing complete resection was 33 months. In patients undergoing resection for cure, grade (P = .005), regional nodal involvement (P = .007), and depth of invasion (P = .03) were significant predictors of outcome in univariate analysis. In the overall group these variables as well as resectability and distant metastases were significant in univariate analysis. In multivariate analysis high-grade lesions and lymph node involvement were highly correlated, as were resectability and metastases. Thus, either variable (but not both) of each pair added information to the multivariate model. In patients resected for cure, positive nodes or high histological grade became the only significant predictors of survival.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the appropriate role of surgical intervention in non-Hodgkin's lymphoma primary to the abdomen, we analyzed the effect of multiple prognostic determinants on event-free survival for patients entered into the CCG-551 study. Eighty-four patients were identified with abdominal lymphoma and of these adequate data for analysis was available on 68 (81%). Variables of interest included: extent of disease at diagnosis, completeness of resection, use of bowel resection, radiation to the primary site, and sex/age/race. The median age on study was 8 years; 79% of patients were white and 85% were male. Thirty-three patients (49%) presented with localized disease. Laparotomy was performed in 67 children (99%) with complete gross resection in 28 (42%). Of the 10 reported surgical complications, 8 occurred in those with extensive disease who were incompletely resected. Radiation to the primary site was given in 60% of patients with median dose of 2,000 cGy. Analysis was performed both for the overall group and for the subgroup receiving optimal chemotherapy for histopathology. Variables with significant predictive effect on event-free survival in univariate analysis included extent of disease (P less than or equal to .001), complete resection (P less than or equal to .002), and use of bowel resection (P less than or equal to .004). However, in multivariate analysis, only extent of disease was an independent predictor of outcome. The data support a role for complete operative excision of localized lymphomas especially when accomplished with bowel resection. Aggressive attempts at debulking extensive retroperitoneal or mesenteric lymphomas are contraindicated.