Surgical treatment of primary neurogenic mediastinal tumors

In the years 1968-1989 out of 300 patients with surgically treated mediastinal tumors in 63 (21%) they were of neurogenic origin. Eighteen of these (29%) proved to be malignant. These tumors occurred in 23 males and 40 females, age range 14 months-67 years (mean 36 years). In all 45 patients with benign tumors and in 12 (66.7%) with malignant tumors the tumors were totally resected. In 4 patients the tumor was only partially resected in further two only a biopsy of the lesion was taken. During postoperative period one patient with a malignant tumor died. Ten (71.4%) patients survived 5 years with malignant lesions, while only 8 (61.5%) survived ten years. All patients that underwent resection of the benign tumor survived 10 years.     

The role of cytotoxic chemotherapy in the management of aggressive and malignant pituitary tumors

Pituitary tumors are mostly benign lesions, although 5-35% are locally invasive. A small number exhibit a more aggressive course, infiltrating dura, bone and sinuses, and are designated highly aggressive. However, the presence of metastases separate from the pituitary in the central nervous system or at a distance is necessary to designate pituitary tumors as carcinomas, i.e. truly malignant. When conventional therapeutic modalities fail, systemic chemotherapy remains the last option. We report seven such patients, three with highly aggressive and four with malignant pituitary tumors (n=4) four women; median age, 32 yr; range, 23-48 yr), who received one or more courses of chemotherapy with lomustine and 5-fluorouracil (median, two courses; range, one to six courses). Three patients with systemic metastatic disease had a shorter survival (median, 5 months; range, 1-14 months) than the one patient with central nervous system metastases alone (10 yr). A patient with an aggressive nonmetastatic prolactinoma who initially responded to chemotherapy died from another nondisease-associated cause. Two patients, one with an aggressive and one with a metastatic tumor, achieved symptomatic improvement with a median duration of 6 months. A hormonal reduction greater than 50% was observed in two of seven patients; only one patient who had an aggressive tumor obtained an objective tumor response. The median survival from the time of initiation of chemotherapy in patients with malignant tumors ranged from 3-65 months. Two patients with malignant tumors developed disease progression while receiving chemotherapy; no patient with extracranial metastases showed a response. Treatment was well tolerated, with minimal individual side-effects. Three patients with no response to initial treatment received different chemotherapeutic regimens with no additional response. All patients with metastatic malignant tumors eventually died. Treatment with cytotoxic chemotherapy is noncurative, and current experience is limited. Until another more specific form of treatment is available, chemotherapy may still be of some value in patients with highly aggressive and malignant pituitary tumors, at least in achieving a temporary remission or delay in progression. The combination of lomustine/5-fluorouracil proved easy to administer with minimal toxicity, although the response rate was only 14%. Until a more specific treatment is found, an optimal chemotherapeutic regimen needs to be established.     

Special diagnostic problems in primary malignant bone tumors

The diagnosis of primary malignant bone tumors, which only account for 1% of malignancies in humans, represents quite a challenge for the pathologist. Apart from the often overlapping morphology between different entities, heterogeneity within one and the same tumor has to be kept in mind. Furthermore, in most cases the diagnosis must be established based on small biopsy specimens and occasionally even on frozen sections. In this context detailed clinical information including the patient's age and exact localization of the tumor, as depicted by X-ray or MRI, are essential requirements for a correct diagnosis. In addition, multiple biopsies from different tumor sites may be of help. For example, 25% of osteogenic sarcomas (OSA) are chondroplastic. Others may contain areas similar to fibrosarcoma (FSA) or malignant fibrous histiocytoma (MFH). Since 90% of OSA occur in the second decade of life whereas chondrosarcomas, FSA and MFH usually manifest after the age of 40 years, a biopsy solely composed of malignant chondromatous tissue obtained from a tibial lesion of a 10-year-old child should most likely be considered as part of an OSA. In the differential diagnosis of the so-called small, round cell tumors, which include Ewing sarcoma, malignant lymphoma and small-cell OSA, immunohistochemical staining of the paraffin-embedded material and a molecular biological/genetic work-up of frozen material are most helpful. In this paper the histomorphological characteristics and criteria for differential diagnosis of the most common primary malignant bone tumors are discussed.     

Ovarian neoplasms in children

OBJECTIVE: To review the clinical presentation, treatment, and outcome in a series of children with ovarian neoplasms. DESIGN: A retrospective review of the medical records in a case series of 29 girls with ovarian neoplasms. The length of follow-up ranged from 6 months to 7 1/2 years and averaged 3.0 years in the girls with malignant tumors. SETTING: The patients were treated at a large referral children's hospital. PATIENTS: Twenty-nine girls with ovarian neoplasms were treated from 1976 to 1992. The average age of the patients was 10 years and ranged from 2 to 16 years. MAIN OUTCOME MEASURES: The principal outcomes examined were mortality and surgical morbidity. RESULTS: The most common presenting symptoms for these ovarian tumors in pediatric patients included chronic abdominal pain, an abdominal mass, or distention. Three girls presented with precocious puberty or hirsutism. In 27 cases, the tumor was a primary ovarian lesion. In two patients, the ovarian mass was the presenting finding for a stage IV non-Hodgkin's lymphoma. Seventeen tumors were benign and 12 were malignant. Tumors originating from the germ-cell line predominated (n = 17). Seven of the 10 ovarian malignant neoplasms were stage I at the time of diagnosis. All but one of the girls with malignant tumors received either adjunctive radiation therapy or multiple-agent chemotherapy. Two girls with sex cord/stromal cell tumors who presented with stage I disease ultimately developed widespread metastases. Both girls with large epithelial tumors survived. All of the girls with benign tumors and seven (70%) of 10 with malignant lesions survived. CONCLUSION: Ovarian tumors are unusual lesions in the pediatric population. Unlike in adults, such neoplasms generally originate from the germ-cell line. Whereas most ovarian tumors in girls are benign, some children have malignant tumors that are very aggressive and do not respond well to adjuvant therapy. In particular, malignant sex cord/stromal cell tumors, even when they present at an early stage, may behave unpredictably.     

Resection, biopsy, and survival in malignant glial neoplasms. A retrospective study of clinical parameters, therapy, and outcome

Between July, 1984, and October, 1988, 263 patients (163 male, 100 female), aged from 4 to 83 years (mean 52 years), with malignant brain gliomas underwent surgical procedures: stereotactic biopsy in 160 and resection in 103 patients. There were 170 grade IV astrocytomas, 17 grade IV mixed oligoastrocytomas, 44 grade III astrocytomas, 22 grade III mixed oligoastrocytomas, and 10 malignant oligodendrogliomas. Overall median survival time was 30.1 weeks for grade IV gliomas, 87.7 weeks for grade III gliomas, and 171.3 weeks for malignant oligodendrogliomas. Multivariate analysis in 218 newly diagnosed cases revealed that the variables most strongly correlated with survival time were: tumor grade, patient age, seizures as a first symptom, a Karnofsky Performance Scale score of less than 70%, tumor resection, and a radiation therapy dose greater than 50 Gy. The proportions of patients receiving tumor resection versus biopsy in each of these prognosis factor groups were similar. Since most of the 22 patients with midline and brain-stem tumors were treated with biopsy alone, these were excluded. Considering 196 newly diagnosed patients with cortical and subcortical tumors, grade IV glioma patients undergoing resection of the contrast-enhancing mass (as evidenced on computerized tomography and magnetic resonance imaging) and postoperative external beam radiation therapy lived longer than those undergoing biopsy only and radiation therapy (median survival time 50.6 weeks and 33.0 weeks, respectively; Smirnov test, p = 0.0380). However, survival in patients with resected grade III gliomas was no better than in those with biopsied grade III lesions (p = 0.746). The authors conclude that, in selected grade IV gliomas, resection of the contrast-enhancing mass followed by radiation therapy is associated with longer survival times than radiation therapy after biopsy alone.     

Expression of the verotoxin receptor glycolipid, globotriaosylceramide, in ovarian hyperplasias

The presence of cell surface receptor glycolipid, globotriaosylceramide (Gb3), is essential to confer susceptibility to the E. coli-derived verotoxin (VT). Our earlier studies showed that Gb3 is expressed in ovarian carcinoma cell lines. The Gb3 content of normal ovary, benign and malignant primary ovarian tumors, and their metastases have now been compared by verotoxin thin-layer chromatogram (TLC) overlay of the glycolipid tissue extracts. FITC-labeled VT1 B subunit binding to frozen tumor sections was also monitored histochemically. Low to undetectable levels of Gb3 were found in "normal" ovarian tissue. Gb3 was markedly increased in both benign and malignant tumors, suggesting that increased Gb3 may be related to proliferation, rather than malignancy per se. Mucinous tumors showed the least Gb3 elevation; serous tumors were variable, showing higher levels of Gb3 in less differentiated malignant tumors. By far the highest Gb3 content was observed for secondary ovarian metastases and tumors refractory to chemotherapy. Frozen sections of neoplastic ovarian tissue overlaid with fluorescein-conjugated VT1 B subunit show extensive binding to tumor cells, particularly in poorly differentiated samples and blood vessels adjacent to, and within, the tumor mass. Tumor foci were stained but stromal tissue was consistently negative both in primary tumors and metastases. VT staining of well-differentiated primary ovarian tumor sections was weak, corresponding to their low Gb3 content, but strong staining was observed in sections from a highly differentiated primary tumor from a patient who was unexpectedly refractory to clinical chemotherapy. These studies suggest that verotoxin/Gb3 targeting may provide the basis for new treatments for ovarian cancer.     

MIB-1 labeling indices in benign, aggressive, and malignant meningiomas: a study of 90 tumors

Predicting tumor behavior in meningiomas based on histology alone has been problematic. This study retrospectively compares histology and MIB-1 (cell proliferation marker) labeling indices (LI) in benign, aggressive, and malignant meningiomas. Six histological features, including mitoses, necrosis, loss of pattern, hypervascularity/hemosiderin deposition, prominent nucleoli, and nuclear pleomorphism, were compared in 90 meningiomas (Fisher's exact test). Tumors with two or more of the above features were designated as aggressive meningiomas. Malignant meningiomas were characterized by brain invasion or metastasis. The MIB-1 LIs (% positive tumor cell nuclei) were compared between the three groups (Kruskal-Wallis test, Wilcoxon two-sample test). Of the benign meningiomas (n=37; mean age, 54 years), 41% had one of the six histological features, with nuclear pleomorphism (n=10) being the most frequent. The aggressive tumors (n=29; mean age, 61 years) were characterized by nuclear pleomorphism (n=28), mitoses (n=20), necrosis (n=16), loss of pattern (n=16), prominent nucleoli (n=6), and hypervascularity/hemosiderin deposition (n=5). Malignant tumors (n=24; mean age, 59 years) were characterized by nuclear pleomorphism (n=22), mitoses (n=21), loss of pattern (n=21), necrosis (n=21), nucleoli (n=17), and hypervascularity/hemosiderin deposition (n=3). Significant differences were found between the aggressive and malignant groups with regard to loss of pattern, necrosis, and nucleoli (P=.0043, .011, and .00029, respectively). Mean MIB-1 LIs for the benign, aggressive, and malignant groups were 1.0% (range, 0 to 5.5%),5.5% (range, 0.1 to 32.5%), and 12.0% (range, 0.3 to 32.5%), respectively. Differences in the mean MIB-1 LI between groups were statistically significant, with P values of <.0001 (benign v aggressive) and .0012 (aggressive v malignant). Mean MIB-1 LIs for recurrent versus nonrecurrent tumors were 7.1% (range, 0 to 32.5%) versus 3.8% (range, 0 to 20.9%) (P=.32). The mean MIB-1 LI for patients who were alive with or without tumor was 6.2% (range, 0 to 32.5%) versus a mean MIB-1 LI of 14.2% (range, 2.8% to 32.5%) for patients who died of or with tumor (P=.0013). In conclusion, (1) There is a statistically significant difference in the increasing MIB-1 LI means between benign, aggressive, and malignant meningiomas and between patients who were alive versus those who died; (2) there is some overlap in MIB-1 LI ranges between groups, which warrants caution in interpreting an individual MIB-1 LI in a given tumor.     

Survival of infants with malignant astrocytomas. A Report from the Childrens Cancer Group

BACKGROUND: Very young children with central nervous system malignant brain tumors have a poor prognosis. As compared with older children, survival is less likely, and those children who do survive frequently have severe impairment of growth and cognitive abilities, resulting partly from treatment with radiotherapy. Therefore, an intensive chemotherapeutic regimen was used to treat children younger than 2 years of age with a diagnosis of malignant astrocytomas. PATIENTS AND METHODS: Thirty-nine children younger than 24 months of age who were diagnosed with malignant astrocytoma were treated on a Childrens Cancer Group protocol with an eight-drug chemotherapeutic regimen (vincristine, carmustine, procarbazine, hydroxyurea, cisplatin, cytosine arabinoside, prednisone, and dimethyl-triazenoimidazole-carboxamide) after surgery and postoperative staging. Radiation therapy was to be deferred until the completion of chemotherapy. RESULTS: The objective response rate after two cycles of chemotherapy was 24%. Most patients did not receive radiotherapy. Progression-free survival (PFS) and survival at 3 years was 36% (standard error, 8%) and 51% (8%), respectively. The PFS of those children with anaplastic astrocytoma was 44% (11%), significantly better than that of glioblastoma multiforme (GBM) (0%). Extent of resection was not associated significantly with PFS, but tumors within the cerebral hemispheres were associated with a more favorable prognosis. Tumor progression occurred locally in almost all cases and early in treatment (median PFS, 8 months). CONCLUSION: Chemotherapy appears to be effective primary adjuvant treatment for some very young children with anaplastic astrocytomas. Overall, however, survival remains poor, especially for children with GBM. Strategies to improve outcome require early intervention, because tumor progression occurs soon after diagnosis in the majority of patients.     

Barrett's esophagus: pathogenesis, epidemiology, functional abnormalities, malignant degeneration, and surgical management

Barrett's esophagus (i.e. columnar epithelial metaplasia in the distal esophagus) is an acquired condition that in most patients results from chronic gastroesophageal reflux. It is a disorder of the white male in the Western world with a prevalence of about 1/400 population. Due to the decreased sensitivity of the columnar epithelium to symptoms, Barrett's esophagus remains undiagnosed in the majority of patients. Gastroesophageal reflux disease in patients with Barrett's esophagus has a more severe character and is more frequently associated with complications as compared with reflux patients without columnar mucosa. This appears to be due to a combination of a mechanically defective lower esophageal sphincter, inefficient esophageal clearance function, and gastric acid hypersecretion. Excessive reflux of alkaline duodenal contents may be responsible for the development of complications (i.e., stricture, ulcer, and dysplasia). Therapy of benign Barrett's esophagus is directed towards treatment of the underlying reflux disease. Barrett's esophagus is associated with a 30- to 125-fold increased risk for adenocarcinoma of the esophagus. The reasons for the dramatic rise in the incidence of esophageal adenocarcinoma, which occurred during the past years, are unknown. High grade dysplasia in a patient with columnar mucosa is an ominous sign for malignant degeneration. Whether an esophagectomy should be performed in patients with high grade dysplasia remains controversial. Complete resection of the tumor and its lymphatic drainage is the procedure of choice in all patients with a resectable carcinoma who are fit for surgery. In patients with tumors located in the distal esophagus, this can be achieved by a transhiatal en-bloc esophagectomy and proximal gastrectomy. Early adenocarcinoma can be cured by this approach. The value of multimodality therapy in patients with advanced tumors needs to be shown in randomized prospective trials.     

Failure of the polyethylene after bipolar hemiarthroplasty of the hip. A report of five cases

Due to the difficulties in separating malignant and benign ovarian cysts by transvaginal ultrasound and other techniques, there is a need for biochemical markers in serum or cyst fluids. In the present study we have evaluated the levels of the chemokine interleukin-8 (IL-8) in ovarian cysts. IL-8 is known to be expressed in the normal ovary and to influence proliferation and angiogenesis of several nonovarian types of tumors. Cyst fluids from benign (n = 15) and malignant (n = 13) ovarian tumors were analyzed. The levels of IL-8 were found to be significantly (13-fold) higher in cyst fluids from malignant tumors (18.1 +/- 7.5 ng/ml; mean +/- SE) compared to benign cysts (1.3 +/- 0.7 ng/ml). The plasma levels of IL-8 were considerably lower (2.9 and 0.3% of levels in benign and malignant cyst fluids, respectively) than in cyst fluids. No difference in the plasma levels of patients with benign or malignant tumor could be detected. In contrast, the levels of CA 125 were significantly higher in plasma of patients with malignant disease with the inverse relation in cyst fluids. In conclusion, the levels of IL-8 are markedly elevated in cyst fluid from malignant tumors compared to benign. This specific increase indicates a role for this cytokine in ovarian tumor biology.     

Prophylactic gene therapy for cancer

BACKGROUND: Epithelial ovarian tumors of borderline malignancy are different from benign tumors and malignant neoplasms. They exist with relatively benign clinical course, younger age and better prognosis as compared with invasive malignant carcinomas. Most of them are discovered at early stage, for example, stage Ia. This retrospective review evaluates the clinical features, treatments and prognosis of 48 patients with borderline malignancy of ovarian tumors. METHODS: Forty-eight patients with ovarian tumors of borderline malignancy, aged from 14 to 69 years (mean: 39.2 years; median: 36 years), were retrospectively studied. The histopathologic diagnosis was based on the morphologic criteria published by Tazelaar et al. in 1985. All cases, including 16 cases diagnosed before 1985, were pathologically reviewed. All information of clinical stage, surgical intervention and prognosis was achieved by reviewing hospital record or contacting patients by telephone. Two patients were lost to follow up. One patient died of sepsis resulting from another operation for another gynecological cancer. Totally forty-five patients were included for evaluation. RESULTS: Thirty-nine of the 48 patients (81.3%) were at stage Ia, 6 cases (12.5%) were at stage Ib, 2 cases (4.1%) were at stage Ic, and the remaining one patient (2.1%) was at state IIIc. Thirty-four patients (71%) were with mucinous cystadenoma of borderline malignancy, 11 cases (23%) were of serous type, and 3 patients (6%) were of mixed serous and mucinous type. Twenty-two patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH and BSO), but one of them remained partial ovary due to young age (27 y/o). Twelve patients were treated with unilateral oophorectomy or unilateral salpingo-oophorectomy (USO). Twelve patients underwent USO and wedge resection of contralateral ovary. One case underwent debulking surgery. One patient underwent enucleation of ovarian tumor and biopsy of contralateral ovary. Eighteen patients were treated with chemotherapy after operation. One patient developed recurrence 4 months after the primary operation. Excluding two cases lost to follow up and one case with surgical mortality for another gynecological cancer, forty-five patients were alive and were followed from 9 months to 165 months. (median: 48 months; mean: 46 months) CONCLUSIONS: Most of the patients were at the early stage of disease when first diagnosed, 81.3% were at stage Ia and only one case was at stage IIIc. Sixty-three percent of our patients underwent surgical treatment alone while the rest of them (37%) had post-operative chemotherapy with either alkeran or PAC. The use of adjuvant chemotherapy seemed unwarranted as there was no difference in survival between those with and without it. (P > 0.05) The low recurrent rate of 2% in our patients again confirmed the 9 P relative benign clinical course of this disease.     

Struma ovarii or malignant ovarian goiter. A case

BACKGROUND: We report a case of follicular struma ovarii observed in an ovary teratoma without metastatic dissemination. CASE REPORT: A right ovarian tumor was discovered at ultrasound examination in a 31-year-old woman complaining of low abdominal pain. The patient underwent laparoscopic exploration and a 4-cm cystic mass of the right ovary was removed. Microscopic examination showed a malignant struma ovarii of the follicular type with vascular space invasion; other teratomous elements were identified. Immunohistochemical staining for thyroglobulin confirmed the nature of the tumor. The patient was treated by complete right ovariectomy followed by total thyroidectomy and administration of radioactive iodine (99 mCi I-131). Repeat I-131 body scan performed at 6 months was normal. DISCUSSION: Struma ovarii is a rare type of ovarian teratoma, consisting mainly of thyroid tissue. The incidence of malignant struma ovarii is below 1% and fewer than two dozen cases with distant metastases have been reported. The major problem associated with struma ovarii has been the establishment of criteria for malignancy.     

Subdiaphragmatic and intrathoracic paraspinal malignant peripheral nerve sheath tumors: a clinicopathologic study of 25 patients and 26 tumors

BACKGROUND: To determine the effects of anatomic site on the presentation and diagnosis of malignant peripheral nerve sheath tumors (MPNSTs) and on the treatment and outcomes of the patients, the authors initiated a study of these tumors at different sites. An earlier report described MPNSTs of the buttock and lower extremity, and the current series analyzes those presenting at intrathoracic (IT) and subdiaphragmatic (SD) paraspinal sites. METHODS: The authors reviewed data on patients with paraspinal MPNSTs who were seen at Memorial Hospital during the period 1960-1995 and for whom histologic slides were available. Various clinicopathologic parameters and their effects on patient outcomes were examined. RESULTS: Twenty-five patients with 26 tumors were evaluated. Seven tumors were IT and 19 were SD; 60% of the patients had neurofibromatosis type 1 (NF1). Most patients presented with pain, and a diagnostic delay (of 3 months to 2 years) was often noted. Mean tumor sizes for SD and IT tumors were 14.3 cm and 6.6 cm, respectively. Most MPNSTs were composed of spindle cells in fascicles. Twenty-seven percent exhibited divergent differentiation. Twenty-four tumors were high grade, and a low grade component was identified in 8 tumors. Surgical resection was attempted for 23 tumors (88%), but complete resection was achieved in only 6 cases (23%). Eighty percent of the patients died of their tumors, 2-year and 5-year survival rates were 35% and 16%, and median survival was 8.5 months. Significant prognostic factors were tumor size <5 cm, the presence of a low grade component, and complete tumor resection. CONCLUSIONS: Paraspinal MPNSTs have more aggressive behavior than peripherally located tumors, mainly because of the difficulty encountered in resecting them completely. Prognoses of patients with MPNST at this site appear to be affected by resection status, tumor size, and tumor grade.     

Functional stereotactic surgery for hemiballism

BACKGROUND: The clinical outcome of patients with ovarian serous tumors of low malignant potential (LMP) remains controversial, especially for those with extraovarian disease. We retrospectively reviewed our experience to study this question further, to assess the safety of conservative management of patients with limited disease, and to determine whether exophytic ovarian surface tumor was predictive of tumor recurrence. METHODS: The clinical and pathologic records of 76 patients with ovarian serous LMP tumors accessioned at the Cleveland Clinic Foundation from 1979 to 1990 were reviewed. International Federation of Gynecology and Obstetrics (FIGO) staging was retrospectively assigned, follow-up information obtained, and clinicopathologic correlations made. RESULTS: An exophytic ovarian surface component was present in 39 of 76 patients (51%). Stage II or III disease was present in 28 of 74 staged patients (38%). Follow-up information was available on 66 patients, ranging from 8 to 264 months (mean, 99 months). Twenty-five patients of 66 patients with follow-up information (38%) received adjuvant therapy. Only 1 patient (1.5%) developed progressive disease; she died of widespread invasive serous carcinoma. Two of 18 conservatively managed patients (11%) developed "recurrent" disease, including 1 patient with a second primary serous LMP tumor of the preserved ovary and 1 patient with an incidentally discovered microscopic serosal implant. There were no other recurrences in the study group, which included four patients with stromal microinvasion and one with lymph node involvement. CONCLUSIONS: The long term outcome of serous LMP tumors is extremely favorable. Exophytic ovarian surface tumor did not serve as a predictor for subsequent peritoneal implants. Conservative surgical management in young patients with localized disease is supported and the use of adjuvant therapy in the initial management of patients with advanced tumors is further questioned.     

Cyclic adenosine 3',5'-monophosphate-binding proteins in human ovarian cancer: correlations with clinicopathological features

The regulatory subunits of protein kinase A, or cyclic AMP-binding proteins, were measured in a series of 107 human ovarian tumors (89 malignant, 7 borderline, and 11 benign tumors) and related to tumor clinicopathological features and patient survival. Total cyclic AMP-binding protein levels were not significantly different between malignant tumors and either borderline or benign tumors. However, serous tumors showed significantly higher levels of total cyclic AMP-binding proteins than other malignant tumors (P = 0.007). Poorly differentiated tumors also possessed significantly higher levels of binding proteins as compared with well/moderately differentiated tumors (P < 0.01). Retrospective analysis of follow-up data also revealed a significant trend for patients with high tumor cyclic AMP-binding proteins to have poorer survival (P = 0.03). Individual binding proteins were identified by photoaffinity labeling, and the RI (Mr 48,000) protein was expressed as a percentage of total cyclic AMP-binding proteins detected. The percentage of the RI protein was not significantly different among malignant, borderline, or benign pathologies and was not associated with tumor stage, differentiation, or debulk status. The percentage of RI was significantly increased in serous tumors compared to other common epithelial malignancies (P = 0.01). In malignant tumors there was a significant positive correlation between the percentage of the RI protein and total cyclic AMP-binding proteins (P = 0.01). These data indicate that high tumor levels of cyclic AMP-binding proteins are associated with serous histology, poor differentiation, and poor patient survival.     

Percutaneous ethanol injection under general anesthesia for hepatocellular carcinoma: 3 year survival in 112 patients

OBJECTIVE: The aim of this study was to determine whether the expression of thymidine phosphorylase by ovarian cancer cells correlates with the density of microvessels within the tumor, and with ultrasound-derived indices of blood flow. METHODS: Transvaginal ultrasonography with color Doppler imaging and pulsed Doppler spectral analysis was used to scan patients with an overt ovarian mass immediately before laparotomy. Sections of malignant tumors were analyzed for the cellular expression of thymidine phosphorylase and the intratumoral density of microvessels by immunohistochemistry using monoclonal antibodies to thymidine phosphorylase and factor VIII-related antigen, respectively. The main outcome measures were the histological classification of the tumor, the stage of the disease, whether or not the tumor cells were positive or negative for thymidine phosphorylase, the microvessel count and the peak systolic velocity (PSV). RESULTS: Forty-two tumors were studied (three of low malignant potential, 29 epithelial, four granulosa cell, two germ cell and four metastatic); 18 were stage I, six stage II, 11 stage III and three stage IV. Twenty-seven tumors (64%) were classified as thymidine phosphorylase-positive. The proportion of stage I tumors that was thymidine phosphorylase-positive (44%) was significantly lower (p = 0.022) than the corresponding value for stages II-IV (85%), but the values for microvessel count and PSV were similar. The microvessel count in thymidine phosphorylase-positive tumors was significantly higher than in thymidine phosphorylase-negative tumors (p = 0.005). Similarly, the PSV was significantly higher in thymidine phosphorylase-positive tumors (p = 0.009). There was a significant correlation between the microvessel count and the PSV (r = 0.354, p = 0.022). CONCLUSIONS: The expression of thymidine phosphorylase by malignant tumor cells is associated with an increase in microvessel density and PSV in patients with ovarian cancer.     

Prognostic features of teratomas with malignant transformation: a clinicopathological study of 21 cases

PURPOSE: Teratomas with malignant transformation comprise up to 6% of metastatic teratomas. The prognosis of patients with these tumors can vary considerably. We delineate factors that may be related to prognosis in a cohort of men with teratoma with malignant transformation. MATERIALS AND METHODS: We analyzed pathological features, treatment, response, recurrence, time to recurrence, subsequent followup and survival for 21 patients (median age 28 years) diagnosed with teratoma with malignant transformation during a 7-year period at our institution. RESULTS: Malignant nongerm cell elements were present in the primary tumor in 11 cases (52%). Of 18 patients with testicular primaries 17 (94%) presented with metastatic disease. Despite aggressive treatment with surgery and chemotherapy 17 of 21 cases (81%) recurred (median time 6 months). Overall, 5 patients (24%) died of disease (median survival 23 months), 5 (24%) are alive with metastases (median followup 41 months) and 11 (52%) have no evidence of disease (median followup 50 months). Progression/recurrence was substantially greater for 2 of 2 cases with a mediastinal origin, 3 of 4 with rhabdomyosarcomatous differentiation and 5 of 6 with neural differentiation compared with the remainder of the cohort (p < 0.05). CONCLUSIONS: Teratomas with malignant transformation are usually metastatic at presentation, have a high recurrence rate and are more aggressive than teratomas without malignant transformation. Prognosis is especially poor for mediastinal teratomas with malignant transformation and for those with neural or rhabdomyosarcomatous differentiation. Complete surgical resection of residual or recurrent disease appears to offer the best chance for prolonged survival.     

Differential expression of estrogen receptor-alpha and -beta messenger RNAs as a potential marker of ovarian carcinogenesis

Although estrogen receptor (ER)-alpha is expressed in both benign and malignant ovarian tumors, the role of ER in ovarian carcinogenesis of epithelial tumors is still unknown. In view of the recent characterization of ER-beta, a second form of ER that seems to be highly expressed in ovaries, we reexamined this issue by studying the relative expression of ER-alpha and -beta in human ovarian tumor progression. We developed a competitive PCR assay based on coamplification of the two ERs in target nucleotide sequences displaying a high homology (exons 3 and 4). Coamplification experiments with varying amounts of plasmids containing ER-alpha and -beta cDNAs showed that this assay was reliable for discriminating as little as a 2-fold difference in the initial ER-alpha:ER-beta cDNA ratio. The relative expression of ER-alpha compared with ER-beta mRNAs was studied in human ovarian cancer cell lines (n = 5) and in normal ovaries (n = 6), then in human benign and malignant tumor samples including ovarian cysts (n = 24), borderline tumors (n = 3), and cancers (n = 10). In normal ovaries, ER-beta mRNA was the predominant ER form, whereas in ovarian cancer cell lines ER-alpha mRNA was markedly increased as compared with ER-beta. In benign and borderline tumors, ER-beta mRNA was detected in 78% of tumors, whereas ER-alpha mRNA was detected in 29%. In ovarian carcinomas, both ER-alpha and -beta mRNAs were expressed in 80% of tumors. The ER-alpha:ER-beta mRNA ratio was >1 in only one cyst sample (4%). In contrast, the ER-alpha:ER-beta mRNA ratio was markedly increased in ovarian cancers because 60% showed an ER-alpha:ER-beta mRNA >1. In situ hybridization experiments showed overlapping tissular distribution of ER-beta and -alpha expression in cancers and cysts, with a main localization in the epithelium and only a low level of expression in stromal cells. In summary, we found an increase in the ER-alpha:ER-beta mRNA ratio in ovarian carcinomas as compared with normal ovaries and cysts. These data suggest that overexpression of ER-alpha relative to ER-beta mRNA may be a marker of ovarian carcinogenesis.     

UV irradiation of polystyrene pipets releases PCR inhibitors

Wilms' tumor is a renal tumor that develops in childhood and is one of the most common malignant tumors in children under 5 years old. Bone metastases are extremely rare in Wilms' tumor, with only two reported cases in adults. We report the case of a patient who underwent nephrectomy for Wilms' tumor at the age of 10 years and presented with a bone mass in his left femur 13 years later.     

Ovarian masses in the pediatric patient

Ovarian masses in the pediatric patient are uncommon. Children with ovarian tumors, however, pose diagnostic and therapeutic challenges because their presentation can mimic other more common intraabdominal disorders and their tumor histology varies widely. The refinement of surgical techniques and the advent of more effective chemotherapy in the past 25 years has increased overall survival rates from approximately 20% to 70%, thus improving the outcome for girls with malignant tumors. This article summarizes the current evaluation and management of ovarian masses in childhood and reviews pertinent pathology.