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The current study was performed to examine temporal trends and compare overall survival (OS) in patients undergoing radical cystectomy (RC) or bladder-preservation therapy (BPT) for muscle-invasive urothelial carcinoma of the bladder.The authors reviewed the National Cancer Data Base to identify patients with AJCC stage II to III urothelial carcinoma of the bladder from 2004 through 2013. Patients receiving BPT were stratified as having received any external-beam radiotherapy (any XRT), definitive XRT (50-80 grays), and definitive XRT with chemotherapy (CRT). Treatment trends and OS outcomes for the BPT and RC cohorts were evaluated using Cochran-Armitage tests, unadjusted Kaplan-Meier curves, adjusted Cox multivariate regression, and propensity score matching, using increasingly stringent selection criteria.A total of 32,300 patients met the inclusion criteria and were treated with RC (22,680 patients) or BPT (9620 patients). Of the patients treated with BPT, 26.4% (2540 patients) and 15.5% (1489 patients), respectively, were treated with definitive XRT and CRT. Improved OS was observed for RC in all groups. After adjustments with more rigorous statistical models controlling for confounders and with more restrictive BPT cohorts, the magnitude of the OS benefit became attenuated on multivariate (any XRT: hazard ratio [HR], 2.115 [95% confidence interval [95% CI], 2.045-2.188]; definitive XRT: HR, 1.870 [95% CI, 1.773-1.972]; and CRT: HR, 1.578 [95% CI, 1.474-1.691]) and propensity score (any XRT: HR, 2.008 [95% CI, 1.871-2.154]; definitive XRT: HR, 1.606 [95% CI, 1.453-1.776]; and CRT: HR, 1.406 [95% CI, 1.235-1.601]) analyses.In the National Cancer Data Base, receipt of BPT was associated with decreased OS compared with RC in patients with stage II to III urothelial carcinoma. Increasingly stringent definitions of BPT and more rigorous statistical methods adjusting for selection biases attenuated observed survival differences. Cancer 2017;123:4337-45. © 2017 American Cancer Society.

Primary extradural meningiomas (PEMs) represent about 2% of all meningiomas and are often encountered by non-neurosurgeons. These lesions typically present as enlarging, painless, benign masses that can be surgically cured. Imaging is critical for defining involvement of adjacent structures; however, diagnosis depends on classic histologic patterns. Treatment for benign PEMs (WHO I) consists of resection with wide margins, whereas adjuvant therapy after resection of atypical (WHO II) or malignant (WHO III) PEMs should be considered. By using the collective experience from our comprehensive cancer center, including neuro-oncologists, neuroradiologists, and neurosurgeons, in addition to a complete literature review, the authors have established treatment guidelines not previously reported. This manuscript describes key features of these challenging tumors to aid in diagnosis, presents the largest published review of all reported PEMs (n = 163), and provides salient treatment guidelines to surgeons unfamiliar with these challenging tumors.

BACKGROUND The use of minimally invasive surgery (MIS) in pediatric cancer is a matter of debate. The diagnostic and ablative roles of MIS were evaluated in a consecutive series of children with malignancies. METHODS A prospective study, including all patients, who underwent abdominal and thoracic surgery for confirmed or highly suspected pediatric cancer was performed from September, 2000, to December, 2005. An interdisciplinary panel approved the indication for minimally invasive or conventional surgery. RESULTS At a single institution, 301 operations were performed on 276 children with cancer. A minimally invasive approach was attempted in 90 of these patients (30%) and successfully employed in 69 (77%) of the operations. However, 21 operations (23%) were converted to an open approach. Regarding the abdominal operations attempted laparoscopically, 41 abdominal operations for biopsy or staging purposes were attempted laparoscopically (53%), but 6 were converted. In all, 139 abdominal resections were performed and 24 were attempted laparoscopically. Ten of these (42%) were converted. In 34 thoracic operations requiring biopsy, thoracoscopy was attempted in 14 (41%) and was successful in all but 1 (93%). Fifty-one thoracic tumors were resected and the thoracoscopic approach was attempted in 11 (22%) and successful in 7 (14%). Conversions from a minimally invasive operation to an open procedure occurred mainly due to limited visibility. Three bleeding complications occurred with 1 patient requiring a blood transfusion. In addition, 1 small bowel injury occurred with immediate laparoscopic closure. There were no port site recurrences after a median of 39 months. CONCLUSIONS MIS is a reliable diagnostic tool for pediatric abdominal and thoracic malignancy. The role of ablative MIS in pediatric cancer remains limited. Cancer 2007. © 2007 American Cancer Society.

BACKGROUND Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) allows detailed imaging of both intramural and extramural structures of the gastrointestinal (GI) tract and also allows tissue samples to be obtained from masses and lesions in the GI tract. The objective of the current study was to determine the diagnostic utility of EUS-FNA in evaluating intramural and extramural GI tract lesions. METHODS The authors evaluated all EUS-FNA specimens of GI tract lesions obtained over a 30-month period (from August 2000 to February 2003). Samples of pancreatic and intrabdominal/mediastinal lymph nodes were excluded from the study. A single endosonographer performed all procedures. An attending cytopathologist also was present on site to assess specimen adequacy. Cytologic diagnoses were analyzed for correlations with final diagnoses, which were based on histologic examination of biopsied/resected pathology materials and/or clinical follow-up findings. RESULTS Sixty-two EUS-FNA specimens of intramural and extramural GI tract lesions were obtained from a total of 60 patients. The mean patient age was 58.8 years (standard deviation, 15.3 years). Thirty-six patients (60%) were male, and 24 (40%) were female. Twenty-eight patients had surgical pathologic evaluation of the corresponding lesions. The remaining 32 patients were followed clinically for a mean duration of 9.5 months (standard deviation, 7.7 months). The anatomic sites of the lesions were as follows: esophagus in 23 patients (37%), stomach in 13 patients (21%), duodenum in 15 patients (24%), and rectum/sigmoid in 11 patients (18%). It is noteworthy that 29 patients (43%) previously had experienced unsuccessful attempts at tissue diagnosis by endoscopic forceps biopsy. Of the 62 EUS-FNA specimens, 43, 4, and 15 were reported as being positive for a neoplasm, suspicious, and benign, respectively. Neoplastic lesions included carcinoma (n = 24), gastrointestinal stromal tumor (GIST; n = 18), neuroendocrine neoplasm (n = 2), and lymphoma (n = 1). There were two cases of endometriosis, three foregut duplication cysts, and one case of diverticulosis. There were two lesions that yielded false-negative findings (one gastric lymphoma and one GIST) secondary to sampling or interpretive error. There also were three cases that yielded false-positive findings (one case of endometriosis, one case of duodenal diverticula with smooth muscle hyperplasia, and one case of normal pancreas, which presented as a periduodenal mass). The sensitivity, specificity, and diagnostic accuracy of EUS-FNA in diagnosing GI tract neoplastic lesions were 89%, 88%, and 89%, respectively. CONCLUSIONS EUS-FNA provides accurate tissue diagnosis in a wide variety of extraintestinal mass lesions and intramural GI tumors, particularly in patients for whom previous endoscopic forceps biopsy was unsuccessful in establishing a diagnosis. Cancer (Cancer Cytopathol) 2004. © 2004 American Cancer Society.

BACKGROUND Desmoid tumors are mesenchymal nonmetastasizing neoplasms. Although rare in the general population, they are a common extracolonic manifestation of familial adenomatous polyposis (FAP). Because of high tumor recurrence rates, surgery has been less than satisfactory in the treatment of desmoid tumors. In the current study, high doses of tamoxifen in combination with sulindac were used to treat severe desmoid tumors to avoid surgery. METHODS Since 1992, 25 patients at Heinrich Heine University (Dusseldorf, Germany) were treated with a combination of tamoxifen and sulindac. In the current study, 17 patients with FAP-associated and 8 patients with sporadic desmoid tumors received 120 mg of tamoxifen and 300 mg of sulindac daily. Every 6 months, the protracted course of desmoid growth was measured by computed tomography and/or magnetic resonance imaging scans. Tumor responses were characterized as progressive disease, stable disease (SD), partial regression (PR), and complete regression (CR). RESULTS Of the group of patients who received tamoxifen and sulindac as a primary treatment, all three patients with sporadic desmoid tumors demonstrated cessation of growth, and 10 of the 13 patients with FAP-associated tumors achieved either a PR or CR. In the sporadic desmoid tumor group, eight of nine patients developed tumor recurrences after undergoingsurgery at other institutions. Of these, two patients had SD and two patients had a PR to CR. CONCLUSIONS The patients with desmoid tumors who were managed conservatively with high-dose tamoxifen and sulindac had the best outcome. Desmoid tumor recurrence after surgery was high and in the FAP-associated tumor group, therapy with tamoxifen and sulindac was found to be less successful. Based on this experience, the authors recommended high-dose tamoxifen and sulindac as the primary treatment for patients with FAP-associated desmoid tumors. However, to our knowledge, the best approach after surgical intervention for patients with sporadic desmoid tumors remains to be determined. Cancer 2004. © 2003 American Cancer Society.

Radiation enteritis is one of the most feared complications of abdominal and pelvic radiation. Once its occurs, the process is relentless and may result in the patient's death. Available treatment is only supportive. Recent progress in molecular biology has shed some light on the pathogenesis of radiation enteritis and other diseases that are characterized by excessive fibrosis. New treatment modalities may be devised to improve the outcome of patients who are affected with this complication.A literature search was used to identify the common denominator between many radiation-induced fibrotic conditions and other sclerotic diseases. Factors that affect the disease process and possible therapeutic interventions were evaluated.The hyperstimulation of transforming growth factor beta1 (TGF-beta1) leads to increased fibrosis and, ultimately, organ failure. Interferon gamma (IFN-gamma) inhibits the effects of TGF-beta1 in the nucleus. The fibrotic process may be reverted by IFN-gamma in various pathologic conditions.Radiation enteritis and other radiation-induced, long-term complications are characterized by excessive stimulation of TGF-beta1. Preliminary studies suggest that IFN-gamma may be effective in the treatment of patients with radiation-induced cutaneous fibrosis. IFN-gamma should be considered in Phase I-II studies to assess its toxicity and efficacy in the treatment of patients with radiation enteritis.

BACKGROUND Testicular and paratesticular involvement is a less familiar feature in neuroblastoma and its prognostic impact is unclear. METHODS The records of 1076 male patients in the German cooperative neuroblastoma treatment trials were searched for patients with testicular or paratesticular involvement. RESULTS The authors found 11 children with paratesticular or testicular involvement at the time of manifestation of the disease, 3 children with testicular involvement at the time of relapse, and 1 infant with testicular involvement at the time of progression of neuroblastoma from International Neuroblastoma Staging System (INSS) Stage 4S to Stage 4. In de novo disease, the age of manifestation did not exceed 12 months. Two children had paratesticular involvement per continuitatem by growth of a primary tumor through the inguinal channel. All others had distant primary tumor. Prognosis appeared more favorable for infants (3 of 9 died) than for older children (5 of 6 died), for children with involvement of testes and < 10% involvement of bone marrow (2 of 8 died) than for children with other distant metastasis (6 of 7 died), and for children with intrascrotal involvement at first diagnosis (4 of 11 died) than for children with intrascrotal involvement during relapse of the disease (all 4 children died). CONCLUSIONS Paratesticular or testicular metastasis does not per se indicate unfavorable outcome and is compatible with INSS Stage 4S in infants. The age at diagnosis and the time of manifestation during disease contributed to the prognosis in those patients. Cancer 2000;88:2636–41. © 2000 American Cancer Society.

BACKGROUND This study was conducted to determine if pelvic computed tomography (CT) should routinely be appended to abdominal CT in the workup of patients with breast carcinoma. METHODS The abdominal-pelvic CTs of 139 breast carcinoma patients (195 exams) were reviewed. Scans were grouped by indication and whether pelvic pathology was known before CT. Pelvic CT results were correlated with their effect on patient management. RESULTS Among the 119 patients without pre-CT evidence of pelvic disease, a nonosseous pelvic metastasis was identified in only 1; this patient also had liver metastases and management was not changed. No unsuspected pelvic CT finding altered therapy for breast carcinoma. However, three patients underwent surgery for asymptomatic masses discovered on pelvic CT; all were benign. CONCLUSIONS Pelvic CT is unlikely to affect the management of patients with breast carcinoma by detecting occult metastatic disease. Cancer 1997; 79:500-4. © 1997 American Cancer Society.

BACKGROUND. After chemotherapy for a metastatic nonseminomatous germ cell tumor, pulmonary masses may be seen on a computed tomography scan. These residual masses may contain one of three histologic elements: necrosis, mature teratoma, or cancer. Because surgical resection of masses containing only necrosis is unnecessary, the authors aimed to predict the histology of these residual masses. METHODS. Six study groups contributed patient data on a total of 215 patients undergoing thoracotomy after cisplatin-based induction chemotherapy for metastatic testicular nonseminomatous germ cell tumors. Logistic regression analysis was used to estimate the probability of necrosis, mature teratoma, and cancer in relation to predictors known before thoracotomy. RESULTS. The pulmonary mass histology was necrosis in 116 patients (54%), mature teratoma in 70 (33%), and cancer in 29 (13%). Necrosis was found at thoracotomy in 89% of those patients with necrosis at retroperitoneal lymph node dissection (RPLND). Other predictors included the primary tumor histology, prechemotherapy tumor marker levels, change in mass size during chemotherapy, and the presence of a single, unilateral mass. Multivariate combination of predictors yielded reliable models (goodness-of-fit tests, P > 0.20), which discriminated necrosis well from other histologies, especially if RPLND histology was available (area under the receiver operating characteristic curve, 0.86). CONCLUSIONS. This analysis indicated subgroups of patients with a high probability of necrosis and a low risk of cancer for whom close follow-up of the residual pulmonary mass might be considered. In most patients, a RPLND should be performed before a thoracotomy is considered, because the probability of necrosis is generally higher at thoracotomy than at RPLND and the histology at RPLND is a strong predictor of the histology at thoracotomy. (C) 1997 American Cancer Society.

Background. Lymphoproliferative disorders that occur in patients receiving cyclosporine for immunosuppression after solid organ transplantation typically are B-cell neoplasms associated with Epstein-Barr virus (EBV), which may be polyclonal or monoclonal in origin. Although these tumors may have partial B-cell differentiation, (manifested as plasmacytoid features), terminal differentiation to plasma cells that secrete a monoclonal immunoglobulin is rare. The case of a patient who developed a posttransplantation lymphoproliferative disorder that was composed of multiple plasmacytomas located in the abdomen and urinary bladder after liver transplantation is presented. The patient also had high levels of an immunoglobulin-Gk monoclonal paraprotein. Methods. The plasmacytoma was examined for the presence of EBV by both polymerase chain reaction and in situ hybridization, and the possibility of a codon-12 mutation in the ras gene was investigated by digestion of DNA amplification products with the HpaII-restriction endonuclease. Results. Epstein-Barr virus genomes were demonstrated by DNA amplification of sequences in the long, internal, direct repeat region, and in situ hybridization showed expression of EBV RNA transcripts that annealed to an EBER-1 probe. Immunohistochemistry showed clonally restricted expression of K light chains but failed to reveal evidence of expression of the latent membrane protein 1 encoded by EBV. Mutations of codon-12 in the H-ras gene were not detected. Conclusions. Resolution of the tumor and the paraprotein after radiation and reduction of immunosuppression indicates that terminal plasmacytic differentiation does not necessarily portend an unfavorable prognosis, even in a clonal lesion.

Background. Sporadic desmoid tumors occur mainly in the abdominal wall and in extraabdominal sites. Desmoid tumors in patients with familial adenomatous polyposis (FAP) usually occur in the abdominal wall and in the bowel mesentery. Surgical resection of desmoids in patients with FAP has been controversial. Methods. A retrospective review of patients with FAP and desmoid tumors treated from 1950 to 1991 was performed. Patients were evaluated for gender, age, site of desmoid tumors, treatment, recurrence, and survival. Results. Twenty-one of 24 patients underwent 60 surgical procedures related to the desmoid tumors. Seven of nine patients who underwent potentially curative surgery had recurrences; three were reresected. Major morbidity after palliative or curative surgery was 47%. Five patients were alive with no evidence of disease at a median of 198 months, 10 patients were alive with disease at a median of 102 months, and 5 patients died with disease at a median of 31 months after diagnosis. Conclusions. Desmoid tumors are common in patients with FAP. Unresectability and recurrence are more common than cure. Palliative and curative resections have a high morbidity. Surgery should be reserved for those patients with symptomatic mesenteric desmoids.

BACKGROUND: A scoring algorithm of site-specific disease recurrence after cystectomy for urothelial carcinoma was designed. METHODS: Identified were 1388 patients who underwent radical cystectomy for nonmetastatic urothelial carcinoma between 1980 and 1998. Clinical, surgical, and pathologic features were evaluated for associations with 4 locations of site-specific disease recurrence: upper urinary tract, abdomen/pelvis, thoracic region, and bone. Recurrence-free survival rates were estimated using the Kaplan-Meier method. Cox proportional hazards models were fit to test associations with disease recurrence. RESULTS: A total of 493 (35.5%) patients experienced at least 1 recurrence. There were 67, 388, 143, and 145 patients with recurrences to the upper tract, abdomen/pelvis, thoracic region, and bone at a median of 3.1 years, 1.1 years, 1.3 years, and 1.0 years, respectively. Pathologic T4 stage (hazard ratio [HR], 2.84; P = .006), positive ureteral margins (HR, 5.71; P < .001), and multifocality (HR, 2.07; P = .009) were found to be independent predictors of upper tract recurrence. Pathologic T3 (HR, 2.30; P < .001) and T4 stage (HR, 3.55; P < .001), lymph node invasion (HR, 1.97; P < .001), extent of lymphadenectomy (pNx [HR, 1.66; P = .002] and

BACKGROUND. The purposes of this study were to evaluate efficacy and toxicity of the combination of carboplatin, gemcitabine, and capecitabine in patients with carcinoma of unknown primary site (CUP). METHODS. Patients with CUP received carboplatin AUC 5 mg/mL a minute intravenously Day 1, gemcitabine 1000 mg/m 2 intravenously Days 1 and 8, and capecitabine 1600 mg/m 2 orally in divided doses, Days 1–14 of a 21-day cycle for up to 8 cycles. The primary endpoint of the study was objective response rate by intent-to-treat analysis. RESULTS. Thirty-three patients were treated (median age, 58 years; men:women ratio, 19:14). Most patients had a baseline performance status of 1. The objective response rate was 39.4% (95% CI, 22.9%–57.9%) in all patients, 36.4% in 22 patients with well to moderately differentiated adenocarcinoma, and 40.0% in 20 patients with liver metastases. Median progression-free survival time was 6.2 months (95% CI, 5.4%–8.0%), and median survival time was 7.6 months (95% CI, 6.3–14.1). One and 2-year survival rates were 35.6% and 14.2%, respectively. The most frequent grade 3 adverse events were neutropenia (67%), thrombocytopenia (48%), and anemia (33%). CONCLUSIONS. The combination of carboplatin, gemcitabine, and capecitabine is active in CUP, especially in patients with liver metastases. This regimen may be a potential therapy for CUP patients with good performance status, particularly those with a suspected origin below the diaphragm. Cancer 2007;110:770–5. � 2007 American Cancer Society.

BACKGROUND Intraabdominal desmoplastic small round cell tumors (IDSRCT) are uncommon but aggressive tumors that occur in young males. To the authors' knowledge, only limited data are available on the natural history and optimal treatment of this disease. METHODS The authors reviewed 12 patients with IDSRCT who were treated at their institution between January 1991 and December 2001. RESULTS All patients were males, with a median age of 26 years. All patients were symptomatic at the time of presentation, with a mean duration of symptoms of 2 months. Common presenting symptoms and signs were abdominal pain (67% of patients), palpable abdominal mass (58% of patients), abdominal distension (42% of patients), and hepatomegaly (33% of patients). Six patients (50%) had distant metastases at presentation. Five patients underwent biopsy only. Surgical resection was attempted in seven patients and included macroscopic total resection in three patients and debulking in four patients. All of those patients subsequently developed recurrent or progressive disease, which required a second operation in six patients. Overall, 6 patients (50%) developed symptomatic intestinal obstruction requiring surgical management, and 3 patients (25%) developed ureteral obstruction. All 12 patients received multiagent chemotherapy. Seven patients (55%) also received radiation therapy. The median survival of patients who underwent surgical resection was 34 months, whereas the median survival of patients who underwent biopsy alone was 14 months. One patient remained alive 72 months after he underwent complete resection of primary and recurrent tumors, and 1 patient remained alive with disease 32 months after he underwent complete resection of a primary tumor. CONCLUSIONS Patients with IDSRCT presented with a short duration of nonspecific symptoms, and the disease was fatal almost uniformly, regardless of the treatment modality used. Surgical resection may prolong survival in some patients. Cancer 2005. © 2005 American Cancer Society.

BACKGROUND Neuroblastoma (NB) occurs rarely during adolescence, and information is scarce on its characteristics and clinical course in this age group. METHODS Patients with NB who were included in the Italian Neuroblastoma Registry were considered for the current study. The clinical characteristics and survival of adolescents (age at diagnosis between 10 yrs and 18 yrs) were compared with those of children (ages 1–9 yrs). Infants (age < 1 yr) were excluded because of their well known favorable clinical course. RESULTS Between 1116 children and 53 adolescents who were evaluated, no differences were documented with regard to the primary tumor site and the prevalence of advanced stage at diagnosis. If only patients with Stage IV NB were considered, then adolescents were less likely to be diagnosed with bone/bone marrow metastases (77%) compared with children (94%; P = 0.038), but adolescents were more likely to have metastases at unusual sites, such as the lung parenchyma or the central nervous system (23% vs. 7%, respectively; P = 0.005). With regard to biologic characteristics, adolescents did not differ significantly from children, although they always had a lower prevalence of unfavorable markers. In particular, MYCN amplification was documented in 21% of children and in 11% of adolescents (P = 0.173). At age 10 years, adolescents had a 20% overall survival rate and a 22% event-free survival rate. Adolescents who had resectable disease had a 73% overall survival rate, which was worse compared with the rate among children with the same disease stage (89%), although the difference did not reach statistical significance (P = 0.159). No differences in survival were observed among patients with Stage IV NB, and adolescents had a probability of survival almost identical to that among children (6% vs. 16%, respectively; P = 0.481). However, when the analysis was restricted to events that occurred after patients developed a recurrence, even if the final outcome was poor for both groups, the difference was statistically significant (P = 0.022) mostly because of the more indolent disease course observed among the adolescents. This effect was even more evident for patients with Stage IV NB. When the 6-year cut-off point was used to separate children from adolescents, a significantly worse overall survival rate (P = 0.036) was documented for adolescents who had resectable disease (81% vs. 93% in children). CONCLUSIONS NB in adolescents had clinical and biologic characteristics similar to those observed among children. The clinical course of NB probably is correlated significantly with age at diagnosis, but information is scarce on the role of the biologic risk factors in this age group. The authors were able to identify a group of patients with a cut-off age between 6 years and 10 years that had a more indolent course but a worse prognosis. Cancer 2006. © 2006 American Cancer Society.

In the current study, the authors aim to evaluate clinical features and treatment results observed in patients from the German and Italian studies who had nonmetastatic abdominal rhabdomyosarcomas (RMS).One hundred sixty-one patients were observed; 78 registered in the German studies between October 1980 and August 1995, and 83 registered in the Italian studies between April 1975 and December 1995. The age range of the patients was 0-18 years (median, 4 yrs). The distribution of tumor sites was as follows: 32 intraperitoneal, 42 retroperitoneal, 75 pelvic, and 12 not otherwise specified (NOS). Most patients had a large and invasive primary mass (26 T1b, 114 T2b). The breakdown in histology was as follows: 116 embryonal, 34 alveolar, and 11 other (leiomyomatous, pleomorphic, and NOS); all cases were staged according to the Intergroup Rhabdomyosarcoma Studies (IRS) system. Nine Group I patients were treated after surgery with chemotherapy (CT) (radiotherapy [RT] was delivered to treat alveolar RMS in the 1991 German and 1988 Italian studies); 19 Group II patients received CT + RT (40-44 Gy); 133 Group III patients underwent neoadjuvant CT +/- surgery and/or RT (54 Gy) + CT. Different CT regimens (based primarily on the administration of vincristine, dactinomycin, doxorubicin, and cyclophosphamide or ifosfamide) were adopted. RT was not recommended for patients age3 years.The 10-year overall survival (OS) and progression-free survival (PFS) were 47.2% and 43.9%, respectively. The OS was related significantly to the following variables: histology (alveolar, 29.4% vs. nonalveolar, 52.1% [P = 0.0156]), tumor size (5 cm, 42.1% vs.5 cm, 81% [P = 0.005]), age (10 yrs, 51.4% vs.or= 10 yrs, 27.8% [P = 0.02]), complete surgery at diagnosis or after CT (+/-RT) (70.4% vs. 34.4% without it [P = 0.0015]). Most patients who achieved the delayed local control had responded well to neoadjuvant CT.Tumor size, histology, age, and initial or delayed achievement of local control were important prognostic factors. Most relapsed patients had unfavorable outcomes.

BACKGROUND Recently, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has emerged as a diagnostic adjunct for small pancreatic lesions and abdominal and mediastinal lymph node diseases. DESIGN. During a 21-month period, we performed 179 EUS-FNAs in 166 consecutive patients; these data are the subject of this study. An average of 2.6 needle passes were obtained and aspiration was performed most commonly in the pancreas (162 cases, 91%). The FNA smears were reviewed using six diagnostic categories (negative for malignancy/nondiagnostic [NND], atypia, suspicious for malignancy, benign tumor/cyst, neuroendocrine neoplasm [NEN], and carcinoma). The review diagnosis was correlated with the histologic diagnosis made on resection or surgical biopsy specimens in 70 cases. Up to 17 months of clinical follow-up were sought for the cases with a negative or inconclusive FNA diagnosis and no diagnostic tissue confirmation (81 cases). RESULTS The review FNA diagnoses were as follows: NND (49 cases), atypia (17 cases), suspicious for malignancy (12 cases), benign tumor/cyst excluding NEN (10 cases), NEN (6 cases), carcinoma (85 cases). Follow-up methods included resection (49 cases), surgical biopsy (21 cases), repeat FNA or brushing cytology (28 cases), and clinical follow-up only (81 cases). Of the 49 NND cases, 23 (47%) had positive follow-up results (i.e., false-negative diagnosis) that were confirmed by tissue diagnosis (resection/surgical biopsy in 11 cases [48%] and repeat FNA/brushing in 12 cases [52%]). These included pancreatic/ampullary adenocarcinoma in 20 cases, esophageal squamous carcinoma in 1 case, and NEN in 2 cases. Follow-up also revealed carcinoma in all 12 suspicious cases and 13 pancreatic adenocarcinomas and 1 microcystic adenoma in 14 of the 17 atypical cases. Overall, repeat computed tomography (CT)-guided FNA samples yielded a definite diagnosis in four atypical and seven NND cases, whereas EUS-FNA results provided a definite diagnosis in three cases in which CT-guided FNA failed and in two cases in which ampullary biopsy failed. No false-positive cases were identified. The false-negative rate due to inadequate sampling was 13.2%. Sensitivity (including cases with inadequate cellularity and nondiagnsotic aspirates) was 81.7% and specificity was 100%. None of the factors evaluated (lesion characteristics, aspiration site, and tumor type) significantly influenced diagnostic results. CONCLUSION EUS-FNA is a valuable diagnostic and staging tool with high specificity and sensitivity. Negative or nondiagnostic cases on EUS-FNA require further diagnostic work for a definitive diagnosis when clinical or radiographic findings do not correlate with the FNA results. Cancer (Cancer Cytopathol) 2002. © 2002 American Cancer Society.

Desmoplastic small round cell tumor (DSRCT) is a high-grade malignant tumor that has a predilection for adolescent males and usually affects the abdominal cavity. The cytology literature regarding DSRCT, including aspirates and ascitic fluid, is limited. To the authors' knowledge, findings in ThinPrep slides have not been described previously.Seven cytologic specimens from five patients with histologically confirmed DSRCT were reviewed. Five specimens were fine-needle aspiration biopsies (FNABs), (liver, flank soft tissue, abdomen, and two resected colons [pericolic]) and two specimens were ascitic fluid. Cytologic features were studied in ThinPrep slides and direct smears, which included hematoxylin and eosin, Papanicolaou, and Quik-Dip stains.All specimens showed moderate to high cellularity. The tumor cells were arranged singly and in clusters. The cells demonstrated high nuclear/cytoplasmic ratios, granular chromatin reminiscent of small cell carcinoma, usually inconspicuous nucleoli, smooth to irregular nuclear membranes, and frequent nuclear molding. The cytoplasm was scant to moderate, pale blue, and occasionally vacuolated. Pseudorosettes were observed in six specimens. One ThinPrep slide and the direct smears contained cells with perinuclear, cytoplasmic densities. Stromal fragments were present in the direct smears but were uncommon in ThinPrep. Three specimens were diagnosed as being consistent with DSRCT. Two specimens were diagnosed as malignant small cell tumor. Molecular studies performed on histologic material in four cases confirmed the presence of the diagnostic translocation, t(11;22)(p13;q12).DSRCT may be diagnosed accurately in cytology specimens. Characteristic cytologic features include granular chromatin, smooth to irregular nuclear membranes, nuclear molding, cytoplasmic vacuoles, pseudorosettes, and metachromatic stroma. Cytoplasmic densities may be observed in direct smears and ThinPrep slides.

Patients with malignant endocrine pancreatic tumors (EPTs) are responsive to combinations of chemotherapy with streptozotocin and 5-fluorouracil/doxorubicin, whereas patients with malignant carcinoids are not. For both categories of patients, alpha-interferon and/or somatostatin analogs can produce long-lasting responses. Cisplatin in combination with etoposide has been suggested to be effective in patients with malignant neuroendocrine carcinomas. The authors used this therapy as second-line or third-line treatment in patients with poorly differentiated and/or rapidly progressing disease.Thirty-six patients with histopathologically verified malignant neuroendocrine tumors were included: Eighteen tumors were of foregut origin, of which 5 were atypical, and 15 tumors were EPTs, of which 4 were poorly differentiated endocrine carcinomas. Three tumors were of midgut origin. The median patient age was 47.5 years. The median duration of disease from the time of diagnosis was 12 months. All patients had metastatic disease. Thirty of 36 patients had received previous treatment. Etoposide was given at a dose of 100 mg/m(2) per day for 3 days, and cisplatin was given at a dose of 45 mg/m(2) on Days 2 and 3 as a continuous intravenous infusion that was repeated every 4 weeks.Ten of 18 patients with foregut carcinoids (56%) responded radiologically and/or biochemically, with a median duration of 9 months; and 7 of 14 patients with EPTs (50%) responded radiologically and/or biochemically, with a median duration of 9 months. No difference in response was seen between patients with atypical or typical foregut carcinoids or between patients with well differentiated or poorly differentiated endocrine pancreatic carcinoma. Nineteen of 36 patients (53%) experienced World Health Organization (WHO) Grade 1-2 nephrotoxicity, and 23 patients (64%) suffered from WHO Grade 3-4 neutropenia.The combination of cisplatin and etoposide can produce significant responses in patients with heavily pretreated and poorly differentiated/rapidly progressing neuroendocrine tumors. The toxicity is considerable, and nephrotoxicity is the dose limiting factor.

BACKGROUND Gastrointestinal stromal tumor (GIST) has only recently been distinguished histologically and immunochemically from morphologically similar neoplasms of the abdomen. METHODS The authors reviewed 15 cytologic cases of GIST (14 fine-needle aspiration [FNA] specimens and 1 peritoneal fluid specimen) and compared them with 23 cases of leiomyosarcoma (LMS) arising in the abdomen or pelvis (all FNAs). Immunochemistry (IC) was performed on both the cytologic and subsequent tissue specimens if sufficient specimen was available. RESULTS Cytologic samples of GISTs typically showed irregularly outlined clusters of uniform spindle cells that were spread easily without crush artifact. The cells had wispy cytoplasm with long, delicate, filamentous extensions (13 cases; 87%). A prominent vascular pattern was common (9 cases; 60%); pleomorphism (1 case; 7%) was uncommon. The LMSs showed three-dimensional, tightly cohesive, sharply marginated syncytia of spindle cells, often with nuclear crush artifact. The cytoplasm/stroma had a distinct wiry, refractile appearance (21 cases; 91%); delicate filamentous cytoplasmic extensions (5 cases; 22%) and prominent vessels (3 cases; 13%) were less common. LMSs more commonly exhibited pleomorphism (14 cases; 61%). Epithelioid cytomorphology, mitoses, and necrosis occasionally were observed in both tumor types. IC for c-kit (on cytologic material) was positive in 10 of 10 cases of GIST (usually diffuse and strong) and 2 of 19 cases of LMS (focal). CD34 positivity favored GIST (4 of 9 cases) over LMS (1 of 19 cases). Smooth muscle actin was positive in 20 of 20 LMSs (strong and diffuse) and 6 of 10 GISTs (usually focal). Desmin was positive in 12 of 20 LMSs and was only focally positive in 1 of 11 GISTs. Correlation of IC results was excellent between cytologic and tissue specimens. CONCLUSIONS Delicate cytoplasmic processes; a prominent vascular pattern; a lack of nuclear pleomorphism; and a c-kit-positive, desmin-negative immunoprofile are characteristic features of GIST and help distinguish these tumors from LMS in cytologic specimens. Cancer (Cancer Cytopathol) 2001;93:276–287. © 2001 American Cancer Society.

The authors conducted a randomized Phase III trial of three treatment regimens for patients with residual, nonmeasurable, intra-abdominal metastatic disease after undergoing resection for primary colorectal carcinoma.To be eligible for this study, patients had to be both free of other malignancies and capable of starting their therapy within 3-6 weeks after surgery. They were required to have an Eastern Cooperative Oncology Group performance status3; to be chemotherapy, radiation, and immunotherapy naïve; to have adequate bone marrow, renal, and hepatic function; and to provide written, informed consent. The patients were divided into two cohorts: patients with no demonstrable hepatic metastasis (Group A) and patients with hepatic metastasis (Group B).The 229 patients in Group A were randomized to receive either 5-fluorouracil (5-FU) (n = 116 patients) or 5-FU with levamisole (n = 113 patients). The median survival (15.4 months and 15.3 months, respectively, for Groups A and B) was virtually identical. The two groups also were similar in terms of time to treatment progression, which was 7.9 months for group that received 5-FU alone 7.7 months for the group that received levamisole with 5-FU. The 168 patients in Group B with hepatic metastasis underwent a three-way randomization: 5-FU alone (n = 60 patients), 5-FU with levamisole (n = 54 patients), and 5-FU with hepatic irradiation (n = 54 patients). The median overall survival for the three treatment arms were similar, with 17.3 months for the group that received 5-FU alone, 16 months for the group that received 5-FU with levamisole, and 14.4 months for the group that received hepatic irradiation in addition to 5-FU: The time to treatment failure was 6.7 months, 6.8 months, and 8.3 months, respectively, for the three groups. The toxicity experienced by patients was as expected with the regimens, and no differences were observed between any of the treatment groups. The primary toxicities were hematologic and gastrointestinal. There was one treatment-related death due to adult respiratory distress syndrome, which occurred on the first day of the fourth cycle of 5-FU and levamisole. Other Grade 4 toxicities included nine patients with Grade 4 leukopenia, one patient with Grade 4 sepsis, and one patient with Grade 4 gastrointestinal toxicity, including blood loss and diarrhea.This study showed no treatment advantage for any of the combined modalities over 5-FU alone in this group of patients with intra-abdominal, nonmeasurable disease.

Somatostatin receptors are present on many types of epithelial tumors, and ligands targeting these receptors are used to treat patients with neuroendocrine malignancies. Preclinical studies have demonstrated the presence of somatostatin receptors on a variety of mesenchymal tumors by in vitro receptor autoradiography. The use of radiolabeled somatostatin analogs to assess the presence of somatostatin receptors in vivo has been established, but use of this technique to evaluate human sarcomas has not been reported previously.Seventeen patients (13 females and 4 males) with metastatic sarcoma underwent imaging via somatostatin-receptor scintigraphy. Scans were performed using indium -111 pentetreotide. Planar studies and single photon emission computed tomography imaging were performed at 4 and 24 hours, and results of scintigraphy were correlated with computed tomography findings.Twelve of 17 scans showed increased uptake in regions of known metastatic disease. There was no apparent correlation with scan positivity and patient age, histology, site of disease, or duration of diagnosis.Seventy-one percent of patients with advanced soft-tissue sarcomas had positive scintigraphy scans demonstrating tumor expression of somatostatin receptors subtype 2 in vivo. Imaging with indium-111 pentetreotide could be studied as an adjunct to conventional imaging modalities for assessment of sarcoma patients. Further research is needed to determine the prognostic implications of somatostatin receptor subtype 2 positivity, including larger studies to evaluate any potential correlation with metastatic behavior and other clinical outcomes.

Despite the excellent prognosis for neuroblastoma 4S (NBL 4S; with S indicating "special"), 10-25% of these patients nevertheless do not survive. Since the first description of this subgroup of disseminated neuroblastoma with a favorable natural outcome, treatment modalities have become milder. Current treatment strategies range from observation with supportive care to full cycles of chemotherapy, radiation therapy, and/or surgical removal of the primary tumor.A recent case of NBL 4S seen at the Sophia Children's Hospital led the authors to review their patient charts from 1971 onward, as well as the literature, for the treatment modalities used and the outcome in treated versus nontreated patients.In addition to the presented case and five additional cases from the authors' patient files, the literature contained 113 reported cases. Of a total of 119 cases, 33 patients died, 12 as a result of hepatomegaly with renal impairment and/or respiratory failure. All but 1 of these patients were diagnosed in the first 4 weeks of life. Of the 33 patients who died, 45% progressed to Stage 4 metastatic disease (15 of 33), a finding that appeared to be unrelated to age. N-myc amplification data were available in 30 cases. Seventeen patients hador = 3 gene copies; 12% of these patients (2 of 17) died. In the N-myc-amplified group of patients with3 gene copies, 69% (9 of 13) died and another patient progressed to Stage 4 with short follow-up.The data presented here suggest an important role for age as a prognostic factor. The very young NBL 4S patient (age4 weeks at diagnosis) was at high risk of dying of (respiratory) complications as a result of massive hepatomegaly. In contrast, disease progression to Stage 4 appears to be unrelated to age, but is strongly related to the presence of biologic markers in the tumor. The authors propose a therapeutic approach for very young patients and for those with unfavorable biology.

External beam irradiation (PBRT), especially in children, is limited by the radiosensitivity of normal tissues. Local control remains a problem in abdominopelvic childhood malignancies. Intraoperative electron irradiation (IOERT) has the potential to increase the dose to the tumor, thereby improving local control, without increasing treatment morbidity.Between February 1983 and October 1990, 11 children received IOERT as part of a multidisciplinary treatment program for locally advanced primary or recurrent abdominopelvic malignancies. The 7 boys and 4 girls ranged in age from 2-18 years. Tumor histologies included four neuroblastomas, two desmoid tumors, and one each of the following: embryonal rhabdomyosarcoma, synovial cell sarcoma, neurofibrosarcoma, malignant fibrous histiocytoma, and paraganglioma. Single radiation doses of 10-25 grays were delivered using 6-15-megaelectron volt electron beams to 1-5 IOERT fields. All patients also underwent EBRT and six received chemotherapy.Eight patients (73%) were alive and disease free at a median follow-up of 99 months (range, 37-126 months). All eight patients who underwent gross total resection were locally controlled. Three patients required surgical intervention for IOERT-related complications and two patients developed neuropathies.IOERT as part of a multidisciplinary treatment approach in patients with locally advanced pediatric malignancies appears to enhance local control in those patients in whom a gross total resection is possible. The long term survival rate was encouraging. Further study, with a larger number of patients, appears warranted to more carefully delineate the efficacy and tolerance of IOERT in the pediatric population.

This study was conducted to determine if pelvic computed tomography (CT) should routinely be appended to abdominal CT in the workup of patients with breast carcinoma.The abdominal-pelvic CTs of 139 breast carcinoma patients (195 exams) were reviewed. Scans were grouped by indication and whether pelvic pathology was known before CT. Pelvic CT results were correlated with their effect on patient management.Among the 119 patients without pre-CT evidence of pelvic disease, a nonosseous pelvic metastasis was identified in only 1; this patient also had liver metastases and management was not changed. No unsuspected pelvic CT finding altered therapy for breast carcinoma. However, three patients underwent surgery for asymptomatic masses discovered on pelvic CT; all were benign.Pelvic CT is unlikely to affect the management of patients with breast carcinoma by detecting occult metastatic disease.

Intraabdominal desmoplastic small cell tumor is a rare malignancy that has only recently been described. In the adult population, it is usually seen in young males. The tumor appears to arise as a dominant mass or masses in the abdominal cavity, particularly in the pelvic region, without a clear visceral origin. Multiple small tumor nodules may be found attached to the peritoneal surface. Visceral metastases occur late in the clinical course, ultimately leading to the patient's death. Five young adults with intraabdominal desmoplastic small cell tumors were treated with aggressive chemotherapy.Charts of five patients treated between 1990 and 1995 were reviewed. The diagnosis of desmoplastic small cell tumor was made on the basis of typical clinical and radiographic findings, light microscopy showing hyperchromatic cells surrounded by a desmoplastic stroma, and immunohistochemistry demonstrating markers of epithelial and mesenchymal differentiation. Patients were treated with aggressive combination chemotherapy consisting of alternating regimens similar to those used as testis cancer salvage therapy.Four of the five patients demonstrated a partial response to chemotherapy. Two of the responding patients had surgery with the intent of removing all residual disease, but this was successful in only one case. All patients have died from their cancer.Intraabdominal desmoplastic small cell tumors are sensitive to combination chemotherapy. It appears that treatment offers good palliation and may prolong survival in isolated cases. However, even the patients managed with the most aggressive medical and surgical approaches are not cured and ultimately die of their disease.

BACKGROUND Recent research suggests that patients' appraisal of somatic symptoms is more closely related to emotional variables (particularly negative affect) than to their actual health as determined by external criteria. METHODS Sixty surgical cancer patients who at the time of a routine follow-up examination filled out the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire-C30, which included a positive/negative affect scale and a scale tapping into experienced social stigma. Patients' health status was determined in two ways: the examining physician gave a global judgement on a standardized scale at the end of the examination, and an additional two external physicians later rated the patients based on the findings listed in the medical record. RESULTS Patients' reports of somatic symptoms were strongly correlated with two measures of negative affect (r = 0.75 and r = 0.65, respectively) and with experienced social stigma (r = 0.51). In contrast, the correlations between reported symptoms and the examining or external physicians' ratings were considerably weaker (r = 0.31 and r = 0.19). According to a multiple linear regression with 6 predictors, negative affect was the best single predictor of symptom reporting (beta = 0.68; P < 0.001) and global quality of life (beta = 0.48; P < 0.001). Factor analysis yielded a dimension of somatopsychosocial distress that accounted for 44.1% of the variance and is comprised of reported symptoms (factor loading = 0.86), negative affect (0.90 and 0.82), experienced social stigma (0.74), and global quality of life (0.70). Physicians' ratings and positive affect constituted two additional separate factors. CONCLUSIONS Cancer patients' reporting of somatic symptoms by means of a standardized quality of life questionnaire is closely related to emotional and social distress and is not equivalent to health status as determined from a clinical perspective. Researchers and practitioners have to be aware of this fact when interpreting quality of life data. Furthermore, negative affect deserves attention as an important signal for intervention in tumor follow-up programs. Cancer 1996;77:983-95.

Background. A staging laparotomy still is considered the gold standard to detect occult abdominal involvement in Hodgkin's disease. Computed tomography and ultrasound are routinely available for diagnostic imaging. To the authors' knowledge, the exact contribution of ultrasound for the staging of Hodgkin's disease has not been reported in a large series of patients before this study. Methods. The diagnostic accuracy of abdominal ultrasound was compared with that of computed tomography and laparotomy in 100 patients with biopsy-proven Hodgkin's disease. Liver, spleen, paraaortic, and iliac lymph nodes were evaluated separately. Results. Seventeen patients had a higher disease stage after surgery (17%). Considering only patients without known abdominal disease (supradiaphragmatic involvement), 14/79 (18%) had a positive staging laparotomy. Ultrasound had superior sensitivity for detecting splenic involvement with Hodgkin's disease (sensitivity, 63% compared with 37% for computed tomography). The specificity of both methods for detecting splenic disease was identical (99% vs. 96%). Inhomogeneities of structure or small nodular infiltrates were detected preferentially by ultrasound. Hepatic involvement also was visualized better by ultrasound than by computed tomography. Lymph nodes at the splenic hilus were recognized by both methods with identical sensitivity (64% vs. 62%). Paraaortic and iliac lymph nodes were recognized with greater sensitivity by computed tomography than by ultrasound (sensitivity, 93% and 100% vs. 77% and 67%, respectively). Conclusions. These results indicate that ultrasound and computed tomography each have their weaknesses and strengths and therefore should be combined, if possible. Ultrasound is the fastest and least invasive method and has particular accuracy for detecting splenic involvement, whereas computed tomography is more accurate in detecting involvement of paraaortic or iliac lymph node. If cost is important in the staging of Hodgkin's disease and if computed tomography is considered the standard, patients whose results are negative by computed tomography should be examined by ultrasound, focusing on splenic texture and size. Even in the era of combined modality treatment, surgical staging may be necessary to detect occult abdominal disease in a certain number of cases.

Sporadic desmoid tumors occur mainly in the abdominal wall and in extraabdominal sites. Desmoid tumors in patients with familial adenomatous polyposis (FAP) usually occur in the abdominal wall and in the bowel mesentery. Surgical resection of desmoids in patients with FAP has been controversial.A retrospective review of patients with FAP and desmoid tumors treated from 1950 to 1991 was performed. Patients were evaluated for gender, age, site of desmoid tumors, treatment, recurrence, and survival.Twenty-one of 24 patients underwent 60 surgical procedures related to the desmoid tumors. Seven of nine patients who underwent potentially curative surgery had recurrences; three were reresected. Major morbidity after palliative or curative surgery was 47%. Five patients were alive with no evidence of disease at a median of 198 months, 10 patients were alive with disease at a median of 102 months, and 5 patients died with disease at a median of 31 months after diagnosis.Desmoid tumors are common in patients with FAP. Unresectability and recurrence are more common than cure. Palliative and curative resections have a high morbidity. Surgery should be reserved for those patients with symptomatic mesenteric desmoids.

Although somewhat controversial, there are data to suggest that patients with ovarian cancer may experience a survival advantage if the dose intensity of platinum-containing regimens can be maximized. Administration of chemotherapeutic agents via the intraperitoneal route offers the opportunity to increase dose intensity of several chemotherapeutic agents.The authors conducted a Phase I trial of intraperitoneal carboplatin and etoposide in combination with granulocyte macrophage colony stimulating factor (GM-CSF) in an attempt to determine the maximum tolerated dose of carboplatin. The starting dose for carboplatin was 300 mg/m2 and for etoposide 400 mg/m2. The dose of carboplatin was escalated while the etoposide was maintained at the initial dose. The total dose of each agent was calculated and given daily over 3 days in amounts equal to one-third of the total dose. On day 1 of therapy, one-third of the dose was mixed in 2 liters of dextrose (D5W) and administered intraperitoneally (IP) as rapidly as possible. On Days 2 and 3, one-third of the dose was mixed in 1 liter of D5W and administered similarly. GM-CSF was begun on Day 4 as a subcutaneous injection at a dose of 500 micrograms/m2/d.Unacceptable hematologic toxicity was encountered at a carboplatin dose of 800 mg/m2; therefore, a carboplatin dose of 600 mg/m2 is recommended for Phase II studies. An overall response rate of 54% with a complete response rate of 17% was observed in patients with ovarian cancer. The overall response rate for all patients was 45%.Because of the significant toxicity encountered in this study, it is recommended that this regimen be used only in the context of a clinical study. The recommended Phase II study dose for this combination is carboplatin 600 mg/M2 and a total dose of etoposide 400 mg/M2 total dose given as three equal parts IP over 3 days. GM-CSF should begin on Day 4 at a dose of 500 micrograms/m2/day subcutaneously and should continue until the absolute neutrophil count is greater than 1000 granulocytes on 3 successive days.

BACKGROUND In vitro, tissue culture-associated differentiation assays have facilitated the identification of multiple tumor-cell types. METHODS We have investigated the capability of differentiation of three extraosseous Ewing's sarcoma cell lines toward a neural and muscular direction by in vitro stimulation with dibutyryl cyclic adenosine-monophosphate (db cAMP) and 5-azacytidine, respectively. RESULTS Elongation of cytoplasmic processes and increase of neural markers chromogranin, S-100 protein, and glial fibrillary acidic protein were observed after db cAMP treatment of these lines and neurosecretory granules as well as myelin figures were demonstrated ultrastructurally. These results support the existence of several pathways of neural differentiation in vitro--neuroblastic, Schwannian, and central glial--in stages of maturation more advanced than those previously reported in Ewing's sarcoma of bone. The cell lines showed no definitive myoblastic differentiation after 5-azacytidine treatment. CONCLUSIONS These data suggest that these three extraosseous Ewing's sarcoma cell lines configurate a heterogeneous group of tumors with respect to capability of differentiation into the neural lineage, arrested at more advanced stages of neural crest development than Ewing's sarcoma of bone and without capability of myoblastic differentiation with 5-azacytidine.

Reports on lymphoid malignancy and its treatment in children infected with human immunodeficiency virus (HIV) are limited.Antibodies to Epstein-Barr virus (EBV) were detected by indirect immunofluorescence. DNA was extracted from peripheral blood lymphocytes or biopsy specimens. Polymerase chain reaction was run using primers for EBV. Reaction products underwent Southern blot analysis to confirm EBV specificity. Tumor clonality was assessed by immunohistochemistry and by Southern blot analysis of immunoglobulin heavy-chain and T-cell receptor beta-gene rearrangement.Within 1 year, non-Hodgkin's lymphoma (NHL) was diagnosed in four children infected with HIV. All four were EBV-seropositive and had detectable EBV DNA in peripheral blood lymphocytes. The EBV-linked disorders lymphoid interstitial pneumonia and recurrent parotid enlargement preceded NHL in three and two of the children, respectively. In all four patients, NHL involved at one time the central nervous system (CNS). All three tested NHL tissues were positive for EBV DNA: A 12-week course of chemotherapy given to two children resulted in rapid tumor regression. One of these children experienced meningeal relapse and died 16 months after diagnosis. The other child, who in addition received local irradiation of the affected eye and who underwent surgical removal of the involved ovaries, has been in continuous remission for 20 months.EBV-associated NHL may be seen more frequently in pediatric patients with HIV. Treatment protocols taking into account NHL propensity for the CNS in this age group need to be developed.

Twenty-six patients with desmoid tumors of the extremities (n = 20) or trunk (n = 6) have been treated since 1977. Nine of these were referred with primary tumors and 17 with recurrent tumors.The tumor was removed in all patients, and 10 received adjuvant radiation. Five patients (19%) developed local recurrence; one of them was lost to follow-up, and the remaining four patients had the recurrence controlled with surgical resection or resection plus adjuvant radiation.All 25 patients who have been followed are alive and disease-free at a mean follow-up of 84 months (median, 81 months). None with extremity tumors (n = 20) required an amputation. The estimated survival rate for the entire group is 95% at 42 months.Desmoid tumor of the trunk or extremities treated with surgical resection, supplemented selectively by adjuvant radiation, can be controlled locally in the majority (96%) of patients.

Desmoid tumors are the source of significant morbidity and mortality in patients with Gardner syndrome.The authors present a case report and review of the literature.A young woman with an extensive abdominal desmoid had a prolonged response to doxorubicin after she did not respond to more conventional treatments.To the authors' knowledge, this is the first report of the successful treatment of desmoids with doxorubicin used as a single agent. Reports of the efficacy of chemotherapy in these and related tumors are reviewed.

Thirty-nine patients with advanced measurable metastatic colorectal carcinoma were entered in a clinical trial of recombinant alpha-2a-interferon (r alpha-2a-IFN) and continuous-infusion 5-fluorouracil (5-FU). Patients had not been treated previously with chemotherapy and had bidimensionally measurable disease.A course of therapy consisted of a 5-day continuous infusion of 5-FU, 750 mg/m2/day, with r alpha-2a-IFN, 9 x 10(6) IU, subcutaneously, on days 1, 3 and 5 of the 5-FU infusion. A course of therapy was repeated every 15 days, and patients were examined for response after receiving four courses of therapy.One patient had a complete response, and 11 patients experienced partial responses, for an overall response rate of 31% (95% confidence interval [CI], 17-48%). The median duration of response was 7.5 months (range, 2-13 months). Fifty-two percent of the patients entered in this trial are alive at time of this writing, with a median follow-up duration of 12.2 months (range, 6-24 months). Grade 3-4 toxicities included mucositis (nine patients), diarrhea (two patients), granulocytopenia (two patients), and fatigue (three patients).This regimen of 5-FU with r alpha-2a-IFN administration does not appear to be superior to previously published schedules of 5-FU with r alpha-2a-IFN or to other methods that modulate 5-FU.

Among 22,816 inguinal hernia repairs done between 1950 and 1988, 15 patients (0.07%) had metastatic tumors found within their hernias. Inguinal herniation was the initial sign of cancer in six patients. A palpable inguinal mass (53%) and abdominal or groin pain (67%) were the most common presenting sign and symptom, respectively. Primary tumor sites included the gastrointestinal tract (40%), ovary (20%), prostate (13%), mesothelium (13%), and unknown sites (13%). The median patient survival was 20 months and depended on the primary tumor site. Grossly apparent inguinal hernia sac abnormalities should be examined microscopically to avoid missing the diagnosis of metastatic cancer, but routine histologic examination of all hernia sacs is not warranted.

Transabdominal ultrasonography was done in patients with gynecologic malignancies to detect paraaortic and pelvic lymphadenopathy. Of the 78 patients who underwent ultrasonic examination of pelvic lymph nodes, pelvic lymphadenopathy was detected in 24, of whom ultrasound-guided percutaneous fine-needle aspiration biopsies (FNAB) were done in 16. Of these 16 patients, the results of 13 biopsies were positive. Of the 41 patients who underwent ultrasonographic examination of the paraaortic lymph nodes, 27 had paraaortic lymphadenopathy. Ultrasound-guided percutaneous FNAB were done in 26 of these 27 patients, with positive findings in 21 of the 26. It was concluded that ultrasound-guided percutaneous FNAB is useful in detecting metastatic lymph nodes in gynecologic malignancies.

A comprehensive statistical analysis of relapses to lung and abdomen and of deaths due to tumor that occurred among 1466 patients with nonmetastatic, favorable histology (FH) Wilms' tumor entered on the Third National Wilms' Tumor Study (NWTS-3) was undertaken. In addition to lymph node involvement, age at diagnosis and tumor size as measured by the weight of the excised specimen were the most important determinants of outcome. The effects of tumor size were most apparent for patients with localized (Stage I) disease; age effects were found for patients with regional (Stage II or III) disease. The presence of microscopic tumor in the margin of surgical resection was an independent predictor of abdominal recurrence and death in the latter group. Although the report of the surgeon of diffuse soilage of the peritoneal cavity from tumor spilled or cut across in the course of nephrectomy was highly correlated with outcome, it was not possible to establish an independent prognostic role for such a finding after adjustment for the aforementioned factors. Patients with intralobar nephrogenic rests (ILNR) had a favorable survival outlook even after accounting for their generally younger ages and lower stages.

The authors report the clinicopathologic and neuroimaging findings in ten children with primary abdominal or thoracic neuroblastoma who relapsed in the central nervous system (CNS) without evidence of concurrent intracranial extension from adjacent bone, dura, or dural sinus metastases. At diagnosis, the patients ranged in age from 0.3 to 4.5 years (median, 2 years). Their times to CNS relapse ranged from 2 to 34 months from diagnosis. In seven patients the relapse occurred from 1 to 14 months after elective discontinuation of therapy. In four patients, the CNS relapse was the primary (isolated) adverse event. Four patients could not be treated at the time of relapse, and they died within 7 days of progressive CNS disease. In the remaining group, craniospinal irradiation with or without administration of a platinum compound and an epipodophyllotoxin caused complete CNS remissions lasting 4, 5, 16, and 62+ months. Neuroimaging and autopsy findings indicated that cerebrospinal fluid is the major pathway for neuraxis dissemination by neuroblastoma cells. There was no evidence of dural penetration in any patient. The possibility of relapse in the neuraxis should be considered for any patient with neuroblastoma who had neurologic deterioration. A combination of craniospinal radiation and administration of a platinum compound and an epipodophyllotoxin will induce complete responses in some patients with neuraxis involvement by neuroblastoma, but the risk of subsequent failure outside the CNS remains high.

From January 1971 to December 1986, 521 patients with Hodgkin's disease were evaluated and treated at the Yale University School of Medicine or one of its close affiliates. A total of 258 patients had pathologic stage (PS) I or II disease, with 239 patients having Hodgkin's disease above the diaphragm (ADHD) and 19 patients having Hodgkin's disease below the diaphragm (BDHD). A comparison of patients with BDHD versus patients with ADHD showed that patients with BDHD were older (mean age, 42 versus 28 years of age, P = 0.005), were initially seen less often with nodular sclerosis subtype (32% versus 77%, P = 0.00001), and had a higher male: female ratio (2.8 versus 1.2, P = 0.12). Ten patients with BDHD (53%) had positive findings at staging laparotomy (0 of 4 clinical stage [CS] IA patients and 10 of 15 (67%) CS II patients). Radiation therapy alone was the initial treatment of choice for 74% of patients with BDHD versus 94% of the patients with ADHD. There was no statistical difference in the overall survival or relapse-free survival rates for patients with BDHD versus ADHD (10-year survival rates, BDHD = 73% and ADHD = 81%). However, patients with BDHD who initially had intra-abdominal disease had a statistically significant increase in death rate (60%) due to Hodgkin's disease compared with patients with BDHD who initially had only peripheral nodal disease (0%). Treatment recommendations for patients with BDHD should be tailored to the specific clinical presentation of each patient. For most PS IA/IIA patients initially seen with peripheral nodal disease, radiation therapy alone is a successful treatment program. However, combined modality therapy should be the treatment of choice for patients with BDHD initially seen with intra-abdominal disease.

One hundred forty-nine patients with poor risk nonseminomatous germ cell tumors (NSGCT) treated between 1975 and 1988 were studied. Patients were considered poor risk if they had an extragonadal primary site or testicular NSGCT with low predicted probability of achieving a complete response (CR). Primary sites were the testis (99 patients), retroperitoneum (18 patients), and mediastinum (32 patients). Patients with mediastinal NSGCT had lower human chorionic gonadotropin (HCG) (P less than 0.0001) and lactate dehydrogenase (LDH) levels (P less than 0.0001), and more frequent yolk sac elements (P = 0.002). CR rates were 38% for mediastinal, 61% for retroperitoneal, and 38% for testicular primary sites. Mediastinal NSGCT patients more frequently required resection of residual malignancy to attain a CR (6 of 12). Mediastinal NSGCT had the worst event-free survival (P = 0.02). Cox regression analysis identified brain or liver metastases as the most important predictor of event-free survival in poor risk patients. Retroperitoneal NSGCT often have a poor outcome due to advanced presentation, but the likelihood of a CR to therapy can be predicted using criteria applicable to testicular primary tumors. Therefore, not all retroperitoneal NSGCT are poor risk, and retroperitoneal tumors are probably of occult testicular origin. Mediastinal NSGCT have distinct clinical and pathologic features, do not respond as well to chemotherapy, relapse more frequently, and have the worst survival. The likelihood of a CR cannot be predicted using criteria developed for primary testicular tumors, suggesting that mediastinal primary NSGCT is a distinct clinical entity.

The second and third examples of clear cell carcinoma of the inguinal region arising from endometriosis are reported. In one patient a right inguinal mass was excised along with an inguinal lymph node dissection. The tumor recurred in the retroperitoneum and was removed, and postoperative radiation therapy was administered. The patient died of recurrent tumor after 11 years. The other patient was treated by excision of a left inguinal mass and an inguinal lymph node dissection and was alive without recurrence 4 years and 8 months later.

From 1956 to 1987, 60 patients with either lymphangiogram-staged or laparotomy-staged I-II lower torso presentations of Hodgkin's disease were treated with radiation with or without Mustargen (mechlorethamine), vincristine, procarbazine, and prednisone (MOPP). In 22 with inguinal/femoral or pelvic disease and 24 with abdominal disease, treatment consisted of radiation only. Fourteen other patients with abdominal disease received MOPP chemotherapy before radiotherapy. In 11, the chemotherapy was limited to two cycles. At 10 years, the determinate survival and freedom from progression rates for all patients were 82% and 72%, respectively. For patients with inguinal/femoral or pelvic disease who were treated with radiation only, the corresponding rates were 90% and 86%. For patients with abdominal disease who received radiation only, the determinate survival and the freedom from progression rates were only 66% and 50%, respectively. However, corresponding results for 14 patients with abdominal disease who were treated with MOPP and radiation were 100% and 92% (P = 0.033 and P = 0.009, respectively.

An example of the rare papillary cystic tumor of the pancreas was diagnosed cytologically by aspiration of the primary neoplasm. Subsequently, it metastasized, proving its low-grade malignant behavior. Diagnostic cytomorphologic features included abundant straight and branched papillary tissue fragments, and uniform, pale nuclei with folds or grooves. Although the primary tumor had a typical histologic appearance, metastases demonstrated increased nuclear pleomorphism and hyperchromasia, bizarre tumor giant cells, and an increased mitotic rate. Vimentin was diffusely positive, whereas neuron-specific enolase and somatostatin were focally and weakly reactive. Neurosecretory and zymogen granules were absent ultrastructurally. By flow cytometric study, the tumor was aneuploid (DNA Index = 1.3).

The term "inflammatory myofibrohistiocytic proliferation" (IMP) has been proposed to replace the conventional designations of plasma cell granuloma and inflammatory pseudotumor. Three cases of extrapulmonary IMP in children are reported, including an intracerebral lesion which has been formerly undescribed. In children, IMP may be associated with microcytic hypochromic anemia, hypergammaglobulinemia, and high erythrocyte sedimentation rate. In this clinical setting, differentiation of a rapidly growing but benign IMP from a bona fide sarcoma is of paramount importance.

We reviewed 238 fine needle aspiration biopsies (FNA) of intraabdominal or retroperitoneal (IA/RP) masses in 192 patients with known or suspected lymphoma. A limited battery of immunocytochemical stains, including kappa (k) and lambda (l) light chains and Leu-4, was performed in 104 aspirates. On hundred twenty-eight of the FNA were diagnostic of or consistent with lymphoma, and three were diagnostic of carcinoma. Twenty-eight were considered negative for malignancy and 79 were suspicious for lymphoma or were nondiagnostic. For 135 of the FNA, a histologic biopsy specimen was available for comparison purposes. Overall, only one false-positive result was seen in a specimen lacking immunocytochemical data. The sensitivity of FNA lymphoma diagnosis was 66%. False-negative results due to sampling error were not uncommon, giving a predictive value of a negative result as 42%. The classification of the lymphomas by FNA was identical to that of the surgical biopsy in 86% of specimens and concurrently discrepant in 6%. We conclude that the routine performance of immunocytochemical studies on FNA of IA/RP masses is a feasible and valuable technique. Whereas suboptimal sensitivity and sampling error may make a negative diagnosis unreliable, lymphoma marker studies (combined with morphology) allow for an accurate and confident diagnosis and subclassification of lymphoma in the majority of cases.

Although survival of children with abdominal neuroblastoma seems at this time to be unrelated to the therapeutic effort, a method of management according to the stage of disease has been developed. Seventy-three percent of patients have metastases at the time of diagnosis. Survival is best in children under 1 year of age. Survival by stage of disease drops progressively from 90% in Stage I disease to 2.4% in Stage IV disease. Irradiation therapy seems unrelated to survival in Stage I, II, and IV disease, while chemotherapy has not been shown to alter survival rates in any stage. Surgical removal of the tumor is still the primary therapy; irradiation is of significant benefit in patients with Stage III disease.

The ganglioside composition of neuroblastoma samples from 53 patients was determined. Tumor sites included the adrenals (15), and the thoracic (20), abdominal (15), and pelvic (3) areas. Age of the patients at the time of surgery ranged from 1 day to over 10 years and the Stage of the tumors from A to D. Differences in ganglioside patterns were observed, with neuroblastomas from patients who were either disease positive or dead of disease tending to have more monosialogangliosides and fewer gangliotetraose gangliosides of the B series (formula; see text) than tumors from patients who were disease-free. More specifically, six of the seven patients lacking GT1b died of disease, suggesting that the absence of GT1b is indicative of a poor prognosis.

Diagnostic B-scan ultrasonography has the capacity to evaluate many potential sites of abdominal and pelvic involvement by Hodgkin's disease and non-Hodgkin's lymphoma. The varying ultrasonographic features of lymphomatous involvement in the peritoneal cavity and retroperitoneal space are described and potential diagnostic pitfalls are discussed.