Cantrell''s pentalogy: a case report

Nine chemotherapy-naive women with recurrent (2 patients) or high risk factors (bilateral or extraovarian spread, poorly-differentiated tumor, age > or = 40 years at diagnosis, residual disease after surgery) granulosa-cell tumors were treated with cisplatin, cyclophosphamide with or without doxorubicin (PAC, PC) or cisplatin, etoposide and bleamycin (PVP-16B). Toxicity was acceptable and the most frequently encountered adverse reactions were WHO grade 3 gastrointestinal toxicity in 77% of patients, and grade 3 myelosuppression in 22% of cases. Clinical complete response was achieved in the 2 patients with recurrent disease. Five patients underwent second look surgery which documented: complete response in 3 patients, partial response in 1 patient and progressive disease in 1 case. Median survival was 85 months (range 14-103). Cisplatin-based cytotoxic regimens may be of benefit in the treatment of recurrent or high risk granulosa-cell tumors.     

Mediastinal teratomas: review of 15 pediatric cases

One hundred fifty-three children with a teratoma presented to one hospital between 1970 and March 1992. The clinical and pathological features of 15 patients with mediastinal teratomas are reviewed; six were newborn and nine aged from infancy to 13 years. Thirteen patients including the six newborns presented with respiratory distress and all 15 patients had a mass on chest radiograph. A definite diagnosis of teratoma was not made preoperatively in any of these patients. At operation, a median sternotomy was used to approach seven anterior tumors and a lateral thoracotomy performed in the other eight patients. Histologically two were mature, 10 had immature elements, and three were malignant teratomas. The patients with malignant tumors were all over 12 years of age and died within 6 months of treatment. All six neonates had immature teratomas. Raised serum alpha-fetoprotein levels provided useful markers in two patients with recurrent tumors. Three conclusions can be drawn: (1) mediastinal teratomas are rare in children and frequently are not diagnosed before operation; (2) in newborns these tumors may be immature and present with respiratory distress; and (3) a median sternotomy gives excellent exposure for anterior mediastinal tumors.     

Repetitive elements in the third intron of murine apolipoprotein A-I gene

PURPOSE: To review the long-term experience of helium ion therapy as a therapeutic alternative to enucleation for uveal melanoma, particularly with respect to survival, local control, and morbidity. METHODS AND MATERIALS: 347 patients with uveal melanoma were treated with helium ion RT from 1978-1992. A nonrandomized dose-searching study was undertaken, with doses progressively reduced from 80 GyE in five fractions to 48 GyE in four fractions, given in 3-15 days, mean of 7 days. RESULTS: Local control was achieved in 96% of patients, with no difference in the rate of local control being seen at 80, 70, 60, or 50 GyE in five fractions. At the lowest dose level of 48 GyE in four fractions, the local control rate fell to 87%. Fifteen of 347 patients (4%) had local regrowth in the eye requiring enucleation (12 patients), laser (1 patient) or reirradiation (2 patients). The time of appearance of local regrowth ranged from 4 months to 5 years posttreatment, with 85% occurring within 3 years. Of the 347 patients, 208 are alive as of May 1, 1997. The median follow up of all patients is 8.5 years, range 1-17 years. Kaplan-Maier (K-M) survival is 80% at 5 years, 76% at 10 years, and 72% at 15 years posttreatment. Patients with tumors not involving the ciliary body have a 15-year K-M survival of 80%. The results for patients whose tumors involved the ciliary body are poor, with a 15-year K-M survival of 43%. Seventy-five percent of patients with tumors at least 3.0 mm from the fovea and optic nerve, and initial ultrasound height less than 6.0 mm, retained vision of 20/200 or better posttreatment. Patients with tumors larger than 6 mm in thickness, or with tumors lying close to the optic nerve or fovea, have a reduced chance of retaining useful vision. The enucleation rate is 19%, 3% for local failure and 16% because of complications of the helium RT, particularly neovascular glaucoma, which occurred in 35% of patients. CONCLUSIONS: Local control and retention of the eye are excellent. Complications of therapy reduce vision and eye preservation. Twenty-four percent of patients manifested distant metastases 6 to 146 months posttreatment, mean of 43 months, median of 36 months. Late-appearing distant metastases do not appear to be caused by persistent tumor in the eye. The risk of metastases is high for patients with tumors greater than 7 mm in initial ultrasound height (37%), anterior tumors involving the ciliary body (47%), and in those with local failure (53%). Patients with tumors not involving the ciliary body and initial dimensions less than 10 mm had only an 8% chance of death from melanoma. A search for effective adjuvant therapy is needed for patients at high risk of metastases (large tumors, ciliary body involved, local regrowth in eye).     

Evaluation of risk factors for endometrial adenocarcinoma in women with diabetes, hypertension and obesity hospitalized for pathologic uterine hemorrhage around the age of postmenopause

The aim of the study was to investigate the incidence and risk factors for endometrial adenocarcinoma which are associated with abnormal bleeding patterns, overweight, a lower number of deliveries and a later menopause, diabetes mellitus and hypertension. A retrospective study (from 1991 to 1993) of 2887 women with pathological gynecological sings and symptoms was performed. Risk factors such as age, height, weight, Brock index, age of menopause, diabetes mellitus and hypertension, stage and cell type were analyzed. The patients were between 38 to 35 years old (average 53.9 +/- 10.2). They were divided into two subgroups: 259 patients below 85 years of age with a histologically confirmed neoplasm, and 2628 women hospitalised due to gynecological signs and symptoms which were not, however, diagnosed as neoplastic disorders. However, it is necessary to note the relationship between the typical age for these two characteristics and the typical age for endometrial cancer. Diabetes was found to be a strong factor whereas hypertension appears to be a relatively weak one for endometrial carcinoma. High Brock's index is also associated with ab increased risk of endometrial carcinoma.     

Risk of recurrent subarachnoid hemorrhage after complete obliteration of cerebral aneurysms

BACKGROUND and PURPOSE: The neck clipping of cerebral aneurysms is a well-established treatment for subarachnoid hemorrhage (SAH) caused by aneurysmal rupture. However, it is still unclear how great a risk of recurrence patients with a successfully treated aneurysm carry over a long-term period. METHODS: Of 425 patients with SAH surgically treated in Aizu Chuou Hospital from 1976 to 1994, 220 cases meeting the following criteria were studied: (1) all aneurysms detected by 3- or 4-vessel cerebral angiography were clipped, (2) complete obliteration of aneurysm(s) was confirmed by postoperative angiography, and (3) the patient survived >3 years. All patients were traced until January 1998 for recurrent SAH or death. The mean follow-up period was 9.9 (range, 3 to 21) years. RESULTS: Six patients (2.7%) had recurrent SAH, each with an interval ranging from 3 to 17 years (mean, 11 years) since the original treatment. In addition, 2 patients were found to have regrowth of the originally operated aneurysms. The cumulative recurrence rate of SAH, calculated using the Kaplan-Meier method, was 2.2% at 10 years and 9. 0% at 20 years after the original treatment. CONCLUSIONS: The recurrence rate was considerably higher than the previously reported risk of SAH in the normal population, and the rate increased with time. These data indicate that patients with ruptured cerebral aneurysms still carry higher risks for SAH in a long-term period, even after complete obliteration of the aneurysm, and that periodic examination to detect recurrent aneurysms may be indicated for such patients.     

Multidisciplinary treatment for a patient with recurrent thymoma associated with myasthenia gravis (MG), pure red cell aplasia (PRCA), and hypogammaglobulinemia

The patient is 62-year-old female. When she was 43 years old, MG occurred. At age of 49 years thymoma was found and complete thymectomy (stage III) and postsurgical irradiation were performed. At age of 57 years pleural dissemination of the thymoma was found. Chemotherapy was effective but did not obtain total tumor cell kill. Though chemotherapy has been repeated for each tumor regrowth, the regimen used at first recurrence became ineffective and the interval between tumor regrowth became shorter. This year, when she is 62 years old, PRCA and hypogammaglobulinemia were accompanied with the forth tumor regrowth.     

Reduced E-cadherin expression correlates with unfavorable prognosis in adenoid cystic carcinoma of salivary glands of the oral cavity

OBJECTIVE: To describe the epidemiology, diagnosis, risk factors, patient impact, and treatment strategies for recurrent Clostridium difficile-associated disease (CDAD). DESIGN: Data were collected as part of a blinded, placebo-controlled clinical trial testing a new combination treatment for recurrent CDAD. Retrospective data regarding prior CDAD episodes were collected from interviews and medical-chart review. Prospective data on the current CDAD episode, risk factors, and recurrence rates were collected during a 2-month follow-up. SETTINGS: National referral study. PARTICIPANTS: Patients with recurrent CDAD. INTERVENTIONS: Treatment with a 10-day course of low-dose (500 mg/d) or high-dose (2 g/d) vancomycin or metronidazole (1 g/d). RESULTS: Recurrent CDAD was found to have a lengthy course involving multiple episodes of diarrhea, abdominal cramping, nausea, and fever. CDAD may recur over several years despite frequent treatment with antibiotics. Recurrence rates were similar regardless of the choice or dose of antibiotic. Recurrent CDAD is not a trivial disease: patients may have multiple episodes (as many as 14), may require hospitalization, and the mean lifetime cost of direct medical care was $10,970 per patient. Fortunately, the disease does not become progressively more severe as the number of episodes increase. Two risk factors predictive for recurrent CDAD were found: increasing age and a decreased quality-of-life score at enrollment. CONCLUSIONS: Recurrent CDAD is a persistent disease that may result in prolonged hospital stays, additional medical costs, and rare serious complications.     

Field cancerization: why late "recurrent" ovarian cancer is not recurrent

OBJECTIVE: Late "recurrence" of ovarian cancer may result from either regrowth of dormant tumor cells or from development of a new cancer caused by the phenomenon of field cancerization. Clinically, some recurrent ovarian cancers show the same therapeutic sensitivities to chemotherapy and surgery as did the primary disease, whereas others are refractory to all therapy. We hypothesize that recurrent ovarian cancers are distinguishable on the basis of a molecular genetic fingerprint and that some are actually new primary cancers of the peritoneum rather than recurrent ovarian cancer. STUDY DESIGN: We constructed molecular genetic fingerprints of 13 paired primary and late recurrent ovarian cancers to study their clonal relationships. The tumor pairs were analyzed for p53 mutations and allelotypes, patterns of X-chromosome inactivation, loss of heterozygosity, and microsatellite instability at 12 different loci on 6 different chromosomes. Techniques used included single-strand conformational polymorphism mutation screening and polymerase chain reaction-based sequence analysis of the p53 locus, restriction digestion of the androgen receptor locus to determine X-chromosome inactivation, and polyacrylamide gel electrophoresis of highly polymorphic dinucleotide, trinucleotide, and tetranucleotide repeats. RESULTS: The average age at initial diagnosis for this cohort was 54.7 years (range 45.3 to 65.5). Mean interval to recurrence was 42.7 months (range 28 to 62). Molecular fingerprints were characterized for 4 to 8 informative loci per tumor pair. The fingerprints of 10 (77%) differed significantly, strongly suggesting that a second primary cancer had developed. The remaining 3 tumor pairs demonstrated identical allelotypes consistent with regrowth of dormant tumor cells. CONCLUSION: Our results are consistent with the "field cancerization" hypothesis of ovarian carcinogenesis but could also be explained by a polyclonal tumor origin, which contrasts with the currently accepted monoclonal theory of ovarian carcinogenesis. Late development of a new primary cancer may herald the proband as a member of a familial cancer phenotype. These studies provide a molecular genetic rationale that both explains and prognosticates the clinical course of recurrent ovarian cancer.     

Efficacy and safety of the stepped care medical treatment of ascites in liver cirrhosis: a randomized controlled clinical trial comparing two diets with different sodium content

The present work reports on a 20-year longitudinal study in Budapest. Eight-hundred-sixty-four subjects who considered themselves healthy, took part in the clinical examination that included women age 55 years and older, and men of 60 years older at the start of the study. The data of the 3080 clinical check-ups have been processed and analyzed. Diseases of the circulatory system occurred most frequently. Ischemic heart disease, cerebrovascular disease, and pulmonary emphysema showed a definite age-dependency. Cataract, fundus sclerosis, decline of visual acuity, as well as hyperplasia of prostate also proved to be age-dependent. The occurrence of osteoporosis and spondylarthrosis increased significantly with age. In the mentioned diseases, correlations were found between the frequency and the number of follow-up years. In relation to our study, we can state that the importance of the risk factors decrease with aging. The pathological effects of the risk factors occur in earlier in life and the truly endangered persons would not grow old.     

Biochemical and genetic analysis of variant C of caprine alpha s2-casein (Capra hircus)

Occurrence of any pubertal sign before eight years of age defines premature sexual development but does not always mean precocious puberty (PP); one should distinguish borderline physiological situations which need only a follow-up and frankly pathological situations which need very precise investigations and suitable treatment. The first situations are premature thelarche, pubarche and menarche in which the height and bone maturation, pelvic ultrasonography (US) are normal for age, avoiding hormonal investigations. Conversely in the second situation, the bone age is more advanced than the height age and the pelvic US displays ovarian activity and uterine development. The next step is the characterization of the level of the mechanism of puberty: hypothalamohypophysal or ovarian: in the first case gonadotropin levels are elevated after GnRH infusion, in the second case, depressed. The aetiological diagnosis are in true PP: brain tumors malformations or hamartoma even if negative idiopathic. At ovarian level: ovarian tumors or McCune Albright syndrome or recurrent cysts. The first etiology leads to use GnRH analog in the second the treatment is more delicate.     

A catalytic antibody that accelerates the hydrolysis of carbonate esters. Prediction of the binding-site structure of the substrate

A recurrent craniopharyngioma associated with moyamoya vessels was successfully treated by partial removal of the tumor via the transsphenoidal approach followed by gamma-knife radiosurgery. This 19-year-old man was first treated by partial tumor removal and radiotherapy (54Gy) at the age of 6 years. Growth hormone and human chorionic gonadotropin were given from the ages of 13 to 18 years. At ag 17 years, follow-up magnetic resonance imaging (MRI) revealed regrowth of the tumor. At the age of 19 years, he was readmitted for treatment of the enlarging remnant tumor. Neurological examination revealed bilateral blindness. MRI showed marked suprasellar, sphenoidal and bilateral cavernous sinus extension of the tumor. Angiography revealed stenosis of the right internal carotid artery and the M1 and A1 segments of the right cerebral arteries, as well as occlusion of the C3 segment of the left internal carotid artery. There were vault and ethmoidal moyamoya vessels. The patient underwent tumor removal via the transsphenoidal approach, instead of craniotomy, to avoid injury to the transdural anastomosis. The intrasellar solid tumor was partially removed. The tumor was then irradiated by the gamma knife. MRI 15 months after the treatment showed marked reduction of the tumor. The pathogenesis of the moyamoya phenomenon and the choice of the treatment in this patient are discussed.     

Offspring at high and low risk for depression and anxiety: mechanisms of psychiatric disorder

OBJECTIVES: To examine the effect of parental psychiatric diagnosis on the risk of psychiatric disorder in their offspring and to determine mediators and independent predictors of psychiatric disorder in offspring. METHOD: The sample consisted of 145 offspring (between the ages of 6 and 24 years, who were directly interviewed) of probands with early-onset (before age 30 years) major depressive disorder (MDD) without panic, panic disorder with and without major depression, and a normal, never psychiatrically ill control group who were part of a large study conducted to determine the relationship between panic disorder and major depression. RESULTS: The risk for offspring MDD was increased by proband recurrent early-onset MDD and coparent alcohol abuse. Chaotic family environment was the only independent predictor of dysthymia. The risk for offspring "any anxiety" disorder was increased by proband recurrent early-onset MDD and coparent impaired functioning. The association between MDD in proband and "panic spectrum" disorder in offspring was accounted for by chaotic family environment. CONCLUSION: Recurrent parental MDD has consistently been shown to be a strong risk factor for offspring MDD. Family environment plays an important role in low-level anxiety symptoms and dysthymia. Clinicians treating adults should be alert to risk factors for their offspring and to appropriate targets for early intervention.     

Tumor recurrence and hypertension persistence after successful pheochromocytoma operation

Pheochromocytoma is a catecholamine-secreting tumor and a rare cause of hypertension that is usually curable. However, pheochromocytoma may recur as a benign or malignant tumor, and hypertension may persist after successful surgical intervention. The frequency of and risk indicators for tumor recurrence and hypertension persistence after successful surgical intervention have not been adequately studied. We determined tumoral and blood pressure outcome in 129 patients followed-up from initial pheochromocytoma resection to death or to 1994 (796 patient-years). We assessed several candidate indicators for their predictive value for the risk of tumor recurrence or hypertension persistence. Recurrence was defined as the reappearance of disease after normalization of biochemical tests. Pheochromocytoma caused death or persistent or recurrent disease in 28 patients. Of the 114 with benign tumors at initial operation, pheochromocytoma recurred as a benign or malignant tumor 17 to 194 months after initial operation in 16 cases. Kaplan-Meier estimates of pheochromocytoma-free survival were 92% and 80% at 5 and 10 years, respectively. In the 98 living patients without recurrence, Kaplan-Meier estimates of hypertension-free survival were 74% and 45% at 5 and 10 years. In the Cox model, familial pheochromocytoma and a low ratio of plasma epinephrine to total catecholamines were independently associated with recurrence. Familial hypertension and age were similarly associated with hypertension persistence. After surgery for pheochromocytoma, patients should be followed-up indefinitely, especially those with familial tumors or a low epinephrine secretion. Pheochromocytoma should not unreservedly be considered a surgically remediable cause of hypertension.     

Late complications in remission from Cushing disease. Recurrence of tumor with reinfarction or transformation into a silent adenoma

Two of 4 patients who underwent spontaneous remission from Cushing disease (CD) demonstrated regrowth of the pituitary adenoma 2 and 5 years later. In the first patient, the recurrent tumor also secreted corticotropin, with subsequent relapse of fulminant cushingoid features. However, after 14 more months, it again became infarcted, and the patient underwent complete clinical remission, which has persisted for about 3 years. In the second patient, the regrowth of the tumor occurred silently, as no clinical cushingoid features or rise in cortisol levels were noticed. Because of its size, the tumor was resected and found to have immunoreactivity for corticotropin (silent corticotroph adenoma). About 4 years after the first operation, a second surgical procedure was performed because of massive regrowth of the tumor. Again, there was no concomitant elevation of cortisol levels or endocrinologic symptoms. This time, the tumor did not even stain for corticotropin. While spontaneous remission in CD is rare, recurrence is even rarer. Reremission of CD and the change from a corticotropin-secreting adenoma to a silent one are described herein for the first time (to our knowledge). These cases demonstrate that patients with CD have to receive careful follow-up, even if they undergo remission, and that the long-term outcome of such remission is unpredictable.     

Risk factors for restenosis after balloon angioplasty in focal iliac stenosis

BACKGROUND: The risk factors for restenosis after angioplasty have not yet been established because of the inconsistencies among treated lesions, differences in the techniques used, and variable end points. We evaluated the predictive variables relating to postangioplasty restenosis. METHODS: One hundred sixty-one transluminal balloon angioplasties were studied in 138 consecutive patients with focal iliac arterial stenosis (< or = 4 cm) caused by arteriosclerosis between January 1981 and December 1995. Restenosis was diagnosed on the basis of recurrent symptoms associated with an apparent drop in the ankle-brachial pressure index and angiographic visualization of restenosis. RESULTS: Being younger than 60 years (risk ratio 2.585) and poor runoff (risk ratio 2.328) were found to be important variables predicting restenosis by the Cox regression model. The restenosis-free patency rates were significantly better in patients older than 60 years of age (p = 0.0242), with good distal runoff (p = 0.0487), and without diabetes (p = 0.0111). CONCLUSIONS: Being younger than 60 years of age and poor distal runoff are important predictors of restenosis after iliac balloon angioplasty.     

Risk factors for incident and recurrent condylomata acuminata among men. A population-based study

BACKGROUND AND OBJECTIVES: The rapid increase in the number of physician office visits for condylomata acuminata and the association of human papillomavirus and cancer has prompted renewed interest in the epidemiology of this sexually-transmitted disease. Few epidemiologic studies have examined what risk factors are associated with condylomata acuminata in men. GOAL: To determine what factors may predispose a man to the occurrence of condylomata acuminata. STUDY DESIGN: A population-based case-control study was conducted among male members of a health maintenance organization. Patients were men 18 years or older who were seen for condyloma at one of four primary care clinics of Group Health Cooperative of Puget Sound between April 1, 1987 and September 30, 1991. Control subjects were frequency matched to the patients on clinic site, race, and age. In-person interviews were used to ascertain exposure histories from both patients and control subjects. RESULTS: Recurrent condyloma was reported by about one third of our patients. Patients with multiple partners were strongly associated with developing the disease. Several factors were either more strongly or only associated with recurrent disease. Other behavioral measures, such as recreational drug use, were also related the occurrence of condyloma. CONCLUSION: These results confirm the sexual-transmitted mechanism of condyloma in men. Exposure to multiple partners was associated with elevated risk of both recurrent and incident disease. Other cofactors may be involved in the etiology of condyloma.     

Local recurrence versus new primary: clinical analysis of 82 breast relapses and potential applications for genetic fingerprinting

PURPOSE: The purpose of this study was to perform a detailed clinical pathological analysis of breast relapses in patients treated with conservative surgery and radiation therapy in an effort to classify those relapses as true local recurrences or second primary tumors, and to assess the prognostic and therapeutic implications of such a classification system. METHODS AND MATERIALS: Of 990 patients treated with conservative surgery and radiation therapy at our facilities prior to December 1987, 82 patients have experienced a relapse in the conservatively treated breast as the primary site of failure. Patients were classified as having new primary tumors if they fulfilled any one of the following criteria: a) breast relapse occurring at a site distinctly removed from the original tumor; b) histology of the breast relapse compared with the original tumor consistent with a new primary; or c) DNA flow cytometry converting from an aneuploid primary to a diploid relapse. RESULTS: As of 2/92, with a median follow-up of 5.4 years from the time of breast relapse, the overall 5-year survival rate following breast relapse was 55%. Forty-seven patients were classified as true recurrences and 33 patients were classified as new primaries. Patients classified as true recurrences had a shorter median time to breast relapse than patients classified as new primaries (3.16 years vs. 5.42 years, p < .05) and an inferior post breast recurrence survival rate compared to patients classified as new primaries (36% vs. 89%, p < .05). Residual disease outside of the recurrent tumor bed was also noted to be more frequent in patients classified as true recurrences compared to patients classified as new primaries (48% vs. 16%, p < .05). CONCLUSION: Based on the clinical and pathological criteria outlined, it appears that a significant portion of patients experiencing a relapse in the conservatively treated breast may have new primary tumors as opposed to true local relapses. Distinction between a true recurrence and a new primary tumor may have significant prognostic implications. Uncertainties associated with the clinical and pathological criteria are presented and further investigations with genetic fingerprinting techniques to establish the clonality of breast relapses are presented and discussed.     

Intracranial meningiomas of the first two decades of life

Meningiomas arising in the first two decades of life are uncommon and their characteristics are controversial. Some authors believe meningiomas in younger patients occur in different locations, have more malignant histological features, and have a worse prognosis than those in adults. To address this controversy, the authors retrospectively reviewed 23 cases of meningiomas in patients under 21 years of age at diagnosis who were operated on at the University of Turin (1948 to 1990) or at the University of California, San Francisco (1970 to 1989). These tumors represented 2.9% of all tumors in this age group and 1.8% of all meningiomas during the study period at the two institutions. There were 14 males and nine females. The mean age at surgery was 13.3 +/- 5.6 years; nine cases occurred in the first decade and 14 in the second. The most common neurological symptoms were a focal neurological deficit (33%) and seizures (25%). Seventy percent of the tumors were supratentorial. A gross total resection was performed in 60% of the cases. Histologically, the majority (74%) of the tumors were meningothelial or mixed. An increased number of mitoses was observed in 33% of the tumors, focal necrosis in 29%, and invasion of adjacent brain in 14%; however, none of the tumors was classified as a Grade III (anaplastic) meningioma. All patients are alive without evidence of recurrent disease 3 to 22 years (mean +/- standard deviation: 10 +/- 7.3 years) after surgery. This study confirms the rarity of meningiomas of the first two decades of life and the absence of the female predominance associated with meningiomas in adults. The location and histological features of these tumors are similar to those in adults; they have a low recurrence rate, and the outcome and survival rate are excellent.     

Risk factors for familial and sporadic ovarian cancer among French Canadians: a case-control study

OBJECTIVE: The objective was to compare risk factors between familial and sporadic ovarian cancer by means of a case-control approach. STUDY DESIGN: We conducted a case-control study among French Canadian women in Montreal during 1995-1996. One hundred seventy women 20 to 84 years old with histologically confirmed diagnoses of primary ovarian carcinomas or borderline tumors were interviewed concerning their reproductive, family, and medical histories. During the same period 170 randomly selected population control subjects, frequency-matched to the case patients according to age and ethnic group, were also interviewed. Unconditional logistic regression methods were used for data analysis. RESULTS: The major factors influencing the risk of development of ovarian cancer were as follows: (1) family history of breast or ovarian cancer, (2) a late age at use of oral contraceptives (a protective effect), and (3) a late age at last childbirth (a protective effect for familial case patients only). CONCLUSION: These factors had equally great impacts in familial and sporadic cases, implying that the underlying mechanisms of carcinogenesis in sporadic and familial ovarian cancer may be similar and that hereditary ovarian cancer may be preventable.     

Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses

Small cell neuroendocrine carcinomas (SNECs) of the sinonasal tract are extremely uncommon tumors. We reviewed the clinicopathologic features of six cases of this neoplasm. There was no sex preponderance with three females and three males and a mean age at presentation of 51 years (range, 38 to 68). Two patients had disease limited to the nasal cavity, and in four the tumor involved the nasal cavity and maxillary or ethmoid sinuses. Involvement of the orbit was present in two patients. Surgery was the primary treatment. After a mean follow-up of 37 months, one patient died of local disease and liver metastases, four were alive with recurrent or metastatic disease, and one died of unrelated causes. The tumors were composed of sheets, nests, and trabeculae with extensive areas of necrosis and hemorrhage. The individual cells were small to intermediate in size and had scanty cytoplasm. The nuclei were oval or round and hyperchromatic with absent or inconspicuous nucleoli. Nuclear molding and crush artefact were present in five cases. All tumors had a high mitotic rate with frequent abnormal mitotic figures. All cases stained for Cam 5.2, neuron-specific enolase, and chromogranin. Five cases were positive for AE1:AE3, and four for synaptophysin. No case stained for S-100 protein, or neurofilaments. O-13 stained one case. No case contained EBV-RNA. SNECs of the nasal cavity and paranasal sinuses are aggressive tumors with pathological features similar to those of anaplastic small cell carcinomas of the lung. They exhibit morphological and immunophenotypic features different from olfactory neuroblastoma and should be distinguished from this tumor.