Lung cancer histologic type in the surveillance, epidemiology, and end results registry versus independent review.

Because few studies have assessed the accuracy of lung cancer histologic diagnoses reported by state cancer registries, we examined whether the Iowa Surveillance, Epidemiology, and End Results Cancer Registry (i.e., the Iowa Cancer Registry)-reported lung cancer histologic diagnoses were reliable. We investigated agreement between lung cancer histologic types reported for 413 patients with lung cancer by the Iowa Cancer Registry and those obtained through an independent review of diagnostic slides. Among lung cancer histologic types, small-cell carcinoma had the highest sensitivity (94.1%, 95% confidence interval [CI] = 85.6% to 98.4%), positive predictive value (94.1%, 95% CI = 85.6% to 98.4%), negative predictive value (98.8%, 95% CI = 96.9% to 99.7%), and highest percent exact agreement (98.0%, 95% CI = 96.6% to 99.4%). The lowest sensitivity (21.9%, 95% CI = 9.3% to 40.0%) and positive predictive value (23.3%, 95% CI = 9.9% to 42.3%) were noted for large-cell carcinoma, probably because other more specific features of adenocarcinoma or squamous carcinoma were absent. Adenocarcinoma had the lowest specificity (84.4%, 95% CI = 79.0% to 88.9%), negative predictive value (85.2%, 95% CI = 79.9% to 89.6%), and percent exact agreement (82.9%, 95% CI = 79.2% to 86.6%). Samples collected by cytologic examination (odds ratio [OR] = 2.4, 95% CI = 1.1 to 5.2) or biopsy examination (OR = 2.2, 95% CI = 1.1 to 4.2) were more likely to be misclassified than samples obtained via resection. Thus, the histologic type obtained by the Iowa Cancer Registry is reasonably reliable, but independent slide review is needed for precise histologic typing of lung cancer.

In vitro maintenance, cooling and cryopreservation of red wolf (Canis rufus) spermatozoa.

A current priority for the preservation of the endangered red wolf (Canis rufus) is the development of a sperm-based genome resource bank. The aims of this study were to examine the effects of (i) holding temperature on the motility of spermatozoa over time, and (ii) cooling methods on the characteristics of spermatozoa after cooling and cryopreservation. Electroejaculates (n = 11; fresh) were evaluated for the percentage of motile spermatozoa, cell and acrosome morphology (Spermac (Meditech 1st Canada Inc, Montreal, Ontario) and fluorescein isothiocyanate-labelled Pisum sativum agglutinin lectin (PSA/FITC; Sigma Diagnostics, Oakville, Ontario) staining), and zona penetration. Semen samples were then divided into two equal samples and centrifuged to remove seminal plasma. One half of the ejaculate sample was re-suspended in sperm-Tyrode's albumin lactate pyruvate (TALP), divided into three aliquots and maintained either at room temperature (approximately 21-23 degrees C), 0 degree C or 37 degrees C. Sperm motility was examined at 0.5 and 1.0 h, and subsequently every hour for 10 h. Motility of spermatozoa decreased after 2 h, but was consistently greater at room temperature than at 37 degrees C or 0 degree C. The other half of the ejaculate sample was re-suspended in an egg yolk-based extender and divided into two aliquots. One aliquot was cooled in a refrigerator (5 degrees C) for 30 min, whereas the second aliquot was put into a beaker containing water at 37 degrees C, which was then placed into an ice bath until the sample reached 0 degree C (approximately 120 min). Spermatozoa were evaluated after cooling and after freezing and thawing treatments. No differences were observed between cooling treatments either after cooling or freezing and thawing. However, marked decreases in intact acrosomes, post-thaw motility and normal morphology of spermatozoa after treatment demonstrate that further investigations are necessary to improve cryopreservation methods in this species.

Use of permanent interstitial temperature self-regulating rods for ablation of prostate cancer.

BACKGROUND AND PURPOSE: We have examined a new technique for the thermal treatment of prostate cancer involving the percutaneous placement of small magnetic alloy rods into the gland in a procedure analogous to the placement of permanent brachytherapy seeds. When the patient and the implanted rods are placed in an extracorporeal alternating magnetic field, the rods heat and can produce tissue necrosis. The rods are temperature self-regulating and produce temperatures no higher than their preprogrammed regulation value. The rods are biocompatable permanent implants, comprised of cobalt and palladium. MATERIALS AND METHODS: We examined rods that heat to 55 degrees, 60 degrees, and 70 degrees C. Patients are treated for 1-hour sessions and easily have multiple sessions. RESULTS: Isolated rods produced little or asymmetrical necrosis. However, arrays of 70 degrees C rods placed within 1 cm of each other caused consistent necrosis between the rods. The temperature at the edge of the array dropped off quickly, and therefore, the rods can be placed within 2 mm of the capsule even posteriorly near the rectum. CONCLUSIONS: Arrays of high-temperature rods can be employed for tissue ablation, while lower-temperature arrays could be used to produce hyperthermia in order to achieve synergism with adjuvant radiation therapy. The technique is applicable in an outpatient setting.

Residential radon gas exposure and lung cancer: the Iowa Radon Lung Cancer Study.

Exposure to high concentrations of radon progeny (radon) produces lung cancer in both underground miners and experimentally exposed laboratory animals. To determine the risk posed by residential radon exposure, the authors performed a population-based, case-control epidemiologic study in Iowa from 1993 to 1997. Subjects were female Iowa residents who had occupied their current home for at least 20 years. A total of 413 lung cancer cases and 614 age-frequency-matched controls were included in the final analysis. Excess odds were calculated per 11 working-level months for exposures that occurred 5-19 years (WLM(5-19)) prior to diagnosis for cases or prior to time of interview for controls. Eleven WLM(5-19) is approximately equal to an average residential radon exposure of 4 pCl/liter (148 Bq/m3) during this period. After adjustment for age, smoking, and education, the authors found excess odds of 0.50 (95% confidence interval: 0.004, 1.81) and 0.83 (95% percent confidence interval: 0.11, 3.34) using categorical radon exposure estimates for all cases and for live cases, respectively. Slightly lower excess odds of 0.24 (95 percent confidence interval: -0.05, 0.92) and 0.49 (95 percent confidence interval: 0.03, 1.84) per 11 WLM(5-19) were noted for continuous radon exposure estimates for all subjects and live subjects only. The observed risk estimates suggest that cumulative ambient radon exposure presents an important environmental health hazard.

Procurement of population-based cancer tissue in Iowa.

We describe the first systematic survey of pathology laboratories serving Iowans to assess attitudes concerning assistance with cancer research efforts. Previous reports suggested that pathologists are reluctant to loan slides and/or paraffin tissue blocks for research purposes because of potential loss or damage, medicolegal concerns, or lack of compensation for time and effort spent in retrieving materials. In this study, we obtained survey responses from laboratory directors of 54 of the 56 pathology laboratories serving Iowans. The survey covered issues related to the availability of research materials, reimbursement for the retrieval of materials, and turnaround time for returning borrowed materials. Contrary to previous reports, we found that the laboratory directors surveyed were willing to loan slides and blocks for research purposes, provided that confidentiality is maintained, that the materials are handled properly and returned in a timely manner, and that compensation is provided.

Characteristics of fresh and frozen-thawed red wolf (Canis rufus) spermatozoa.

Ejaculates of the red wolf (Canis rufus) were evaluated immediately after collection and freeze-thawing to initiate a reproductive database for this endangered species. Electroejaculates from 13 adult red wolves collected during the breeding season (February-March; n=25; 1-3 collections/male) had a mean volume of 4.7+/-0.7 ml, 146.5+/-25.7 x 10(6) spermatozoa/ml and 71.2% motile spermatozoa. The mean proportion of cells with normal morphology was 73.6+/-3.2% (range, 20.3-93.7%), with 64% of ejaculates (16/25) containing 70-90% normal spermatozoa. The four most predominant abnormalities were a coiled flagellum (8.1%), a bent flagellum (4.7%), a bent midpiece with no cytoplasmic droplet (3.3%;), and a detached head defect (6.4%). After cooling in glycerolated extender, semen was frozen using a pelleting method on dry ice before plunging into liquid nitrogen. Pellets were thawed in phosphate buffered saline and examined for % sperm motility, normal morphology, viability and intact acrosomes. There was a decline (P < 0.05) in sperm motility (approximately 40%) and percentage of normal sperm (11.9%) after freezing, but no change in the proportion of viable cells. After freezing, there was a marked decline (P < 0.05) in the proportion of intact acrosomes from 74.5% to 55.5% which was accompanied by an increased proportion (P < 0.05) of partial acrosomes from 11.9% to 35.8%. These data demonstrate that, although red wolf spermatozoa can survive freeze-thawing using a technique common for domestic dog sperm, the finding of significant acrosome damage reveals (1) likely species specificity in the Canis genus and (2) the need for refining sperm cryopreservation technology for the red wolf.

Marked granulocytic proliferation induced by granulocyte colony-stimulating factor in the spleen simulating a myeloid leukemic infiltrate.

The authors describe a patient with a long-standing history of systemic lupus erythematosus and leukopenia who received multiple intermittent doses of recombinant granulocyte colony-stimulating factor (G-CSF) and who underwent splenectomy because of a clinical impression of sequestration of granulocytes by the spleen. Histologic evaluation of the spleen revealed marked granulocytic hyperplasia with an increase in immature myeloid precursors, morphologically indistinguishable from a myeloid leukemic infiltrate. A postsplenectomy bone marrow aspirate and biopsy revealed a normocellular bone marrow with active hematopoiesis and trilineage maturation. The bone marrow aspirate cultured cells showed no numeric or structural chromosomal abnormality. Extramedullary hematopoiesis after receipt of G-CSF was previously reported, but, to our knowledge, ours is the first report of morphologic changes virtually identical to a leukemic infiltrate in spleen after G-CSF treatment. We describe the histologic and immunohistochemical findings in the spleen, compare our observations with those of others reported in the literature, and postulate a possible mechanism for this phenomenon.

Semen parameters and electron microscope observations of spermatozoa of the red wolf, Canis rufus.

Semen parameters were evaluated on ejaculates of a captive population of red wolves (Canis rufus) sampled over two consecutive mating seasons. A total of 31 samples from 15 animals yielded mean sperm motility of 69.6 +/- 19.4%, mean sperm density of 131 +/- 124 x 10(6) ml-1, mean total number of spermatozoa of 470 +/- 465 x 10(6) and mean percentage morphologically abnormal spermatozoa of 35 +/- 11.8%. Restricting the data to animals sampled three times or more or limiting the samples to proven breeders resulted in statistically non-significant differences in these numbers (P < 0.05). When compared with data from other canines the seminal parameters of red wolves are at the lower extremes of the range. In particular the proportion of morphologically abnormal spermatozoa (35%) is approximately twice that seen in other canine species. Light microscopic analysis of abnormal forms revealed that almost half (45%) were bent defects, another 40% were secondary defects (coiled, detached and immature) and 15% were primary defects. Electron microscopy confirmed the presence of substantial numbers of morphologically abnormal forms including double-headed and double-flagellar cells, bent or kinked forms especially in the neck region, acrosomal abnormalities and bizarre spermatids. Approximately one-third of the samples also showed the presence of white blood cells, in some cases demonstrating sperm phagocytosis (spermophagy). These results are consistent with the concept of declining sperm parameters associated with restricted gene pools in numerically limited populations. However, alternative explanations are also explored.

Histologic characteristics of electrosurgical injuries.

STUDY OBJECTIVE: To describe the wide variation of histologic characteristics produced by electrosurgical burns. DESIGN: Retrospective analysis. SETTING: University-associated teaching hospital. SUBJECTS: Pigs and dogs. INTERVENTIONS: Various power settings were employed with both monopolar and bipolar electrodes to incur electrosurgical damage. Animals were followed for up to 96 hours after injury. MEASUREMENTS AND MAIN RESULTS: Histologic analysis yielded characteristics of electrosurgical damage including areas of complete necrosis and coagulation, perivascular changes, endothelial damage, and hyperchromic pyknotic nuclei. White cell infiltration was seen only at the margin of necrotic zones of coagulation. CONCLUSION: The wide spectrum of histology from electrosurgical burns is primarily a result of the area that is sampled. Surgeons should actively investigate any postsurgical complications involving electrosurgery to obtain a definitive cause.

Is microstaging of early invasive cancer of the urinary bladder possible or useful?

Reports suggest that it is possible and useful to classify T1 (Stage A) carcinomas of the urinary bladder into subgroups dependent on the depth of invasion as defined by the muscularis mucosae (MM). In an attempt to evaluate the reproducibility of these findings, we reviewed the slides from 77 cases of T1 bladder cancer diagnosed in 1983 in Iowa residents. The cases were identified through a statewide cancer registry. Slides and pathology reports were obtained from the original laboratories. Two pathologists independently evaluated each case, most (74 cases) of which were transurethral resections, for the presence or absence of MM and three levels of invasion (lamina propria, MM, and submucosa). Disagreements were resolved by simultaneous review resulting in a consensus diagnosis. Because of the population-based source, tissue had been obtained by multiple urologists and processed in multiple laboratories, resulting in noticeable variation in quality of material. Interobserver agreement for the level of invasion was poor between the two pathologists (kappa = 0.22; 95% C.I. = 0.08-0.36). Consensus resulted in 34 cases (44.2%) invasive to the lamina propria, 23 (29.9%) to the MM, and 11 (14.3%) to the submucosa. The level was indeterminate in nine (11.7%). All of the 77 cases were followed until death or 1993-95, with 57 patients dying during this interval. There were no significant differences in survival for each level of invasion (lamina propria, MM, submucosa) and the indeterminate cases, as determined by either consensus or individual observer evaluation. Our findings suggest that microstaging of early invasive bladder cancer is technically difficult and, at least in cases derived from various urologists and laboratories, does not yield a prognostically significant separation.

Second malignant neoplasms among long-term survivors of ovarian cancer.

Second malignant neoplasms were evaluated among 32,251 women with ovarian cancer, including 4,402 10-year survivors, within the nine population-based registries of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute (1973-1992) and the Connecticut Tumor Registry (1935-1972). Overall, 1,296 second cancers occurred against 1,014 expected [observed/expected (O/E), 1.28; 95% confidence interval (CI), 1.21-1.35]. Sites contributing 25 or more excess cancers included leukemia (O/E, 4.17; O, 111; 95% CI, 3.43-5.03) and malignancies of colon (O/E, 1.33; O, 188; 95% CI, 1.15-1.54), rectum (O/E, 1.43; O, 76; 95% CI, 1.13-1.79), breast (O/E, 1.18; O, 404; 95%, CI 1.07-1.30), and bladder (O/E, 2.07; O, 65; 95% CI, 1.59-2.63). Ocular melanoma (O/E, 4.45; O, 8; 95% CI, 1.92-8.77) was also significantly increased. Second cancer risk was high during all follow-up intervals, and cumulative risk at 20 years was 18.2%, compared with a population expected risk of 11.5%. Statistically significant relationships existed between serous adenocarcinoma of the ovary and breast cancer (O/E, 1.29; 95% CI, 1.06-1.56) and mucinous ovarian adenocarcinoma and rectal cancer (OE/E, 1.95; 95% CI, 1.09-3.22). Secondary leukemia appeared linked with antecedent chemotherapy, whereas radiotherapy was associated with cancers of connective tissue, bladder, and possibly pancreas. Genetic and reproductive factors predisposing to ovarian cancer may have contributed to the elevated risk of breast and colorectal neoplasms and possibly ocular melanoma. Thus, excess malignancies following ovarian cancer represent complications of curative therapies and/or underlying susceptibility states that have etiological and clinical ramifications.

Clinical and pathological features of pediatric dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon malignant mesenchymal tumor characterized by local invasion and recurrence. Fewer than 50 cases have been reported in the pediatric population. We reviewed our experience in the treatment of children with DFSP to define clinical and pathological characteristics. Seven pediatric patients were included in the study (mean age, 11.7 yr). Clinically, the tumors were described as firm nodules fixed to the skin but mobile over the deep fascia, with slow, progressive growth. Diagnosis was made by excisional biopsy in 6 patients and punch biopsy in 1 patient. Six of 7 patients had positive margins after the diagnostic procedure. Pathologically, diagnosis was based on histology, with confirmation by CD34 staining. Definitive surgical therapy consisted of wide local excision (1-3 cm margins) in 5 patients and Moh's micrographic resection in 2 patients. There have been no local recurrences or distant metastases, with a mean follow-up of 15.1 months. Pathological and clinical diagnostic criteria for the pediatric population are reviewed, and treatment options are discussed.

Clinical survey of a psychiatric mother and baby unit: characteristics of 100 consecutive admissions.

Demographic, obstetric, clinical features and clinical outcome of 100 consecutive admissions to a psychiatric mother and baby unit are presented. Referral patterns by health services involved are also examined. 56% of admissions occurred within 2 weeks of delivery and the mean duration of admission was 2 months. Patients were categorized as having schizophrenia (n = 20), affective psychosis (n = 56) or non-psychotic disorders (n = 24) and these three groups were compared. There were few demographic and obstetric differences between diagnostic categories. The affective psychosis group were more likely to have acute illnesses with an onset and admission occurring within 2 weeks of delivery. Women with non-psychotic disorders were also most likely to become ill within 2 weeks of delivery but tended to be admitted later. Only 7% of the affective psychotic and non-psychotic women were discharged separated from their infants. Women with schizophrenia were less likely to have acute admissions and required greater input of nursing and service resources than mothers with other illnesses but 50% were discharged without their infants. More research is needed into matching models of care to the needs of mothers with different kinds of chronic, recurrent and new episodes of mental illness that present after childbirth. There are few guidelines to aid clinical staff in assessing the risk, current or future, of significant harm to an infant as a consequence of maternal mental illness, particularly of schizophrenia.

Female genital tract cancer.

BACKGROUND: Site-specific cancer frequencies and incidence rates are reported regularly by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, but not by histologic type within site. This report reviews data for 160,977 histologically or cytologically confirmed invasive and in situ cancers of the female genital tract. METHODS: Data were supplied by the SEER program for histologically confirmed cases of uterine corpus, uterine cervix, ovary, vulva, vagina, fallopian tube, and placental cancers diagnosed between 1973 and 1987. Histologic types were reviewed for race, age at diagnosis, incidence, stage, and survival. RESULTS: There were 89,943 invasive and 71,034 in situ neoplasms. Squamous carcinoma was the most common invasive malignancy of the cervix (77.1%), vulva (74.4%), and vagina (70.8%). Adenocarcinoma was the most frequent malignancy in the uterine corpus (81.5%) and ovary (86.6%), with these percentages reaching 91.6% for corpus and 86.9% for ovary if adenosquamous carcinoma and adenocarcinoma with squamous metaplasia are included. Cervical carcinoma in situ accounted for 91.0% of all in situ cancers. In situ cancers made up 78.5% of all cervical cancers, 35.1% of vaginal cancers, and 50.4% of vulvar cancers. CONCLUSIONS: There are dominant histologic groups in each female genital tract site that are largely responsible for incidence and survival statistics. Within the groups, however, there are subtypes with differing features. Epidemiologic studies may provide more definite information by considering the effect of these subtypes in examining risk factors.

Primary germinoma of the spinal cord: a case report with 28-year follow-up and review of the literature.

Germ cell neoplasms occur in extra-gonadal midline locations of the retroperitoneum, mediastinum, pineal gland, areas of the suprasellar cistern, and rarely in the spinal cord. We recently reviewed a case of an unresectable lumbar spinal cord tumor in a 16-year-old female previously diagnosed as "metastatic poorly differentiated carcinoma." An extensive evaluation for a primary neoplasm at that time was unsuccessful and the patient was treated with local radiation therapy. Recently, additional histochemical and immunocytochemical studies were performed on the archival formalin-fixed paraffin-embedded material and the clinical history was reviewed. These ancillary studies (including positive immunohistochemical staining for placental alkaline phosphatase) support a diagnosis of intramedullary germinoma of the conus medullaris. This patient has enjoyed 28 years of disease free survival which reflects the radiosensitive nature of this neoplasm. These data lend support to the existence of a primary germinoma in the spinal cord and illustrate the utility of using histochemical stains and immunohistochemistry to assist in diagnosing this treatable neoplasm.

A laparoscopic complication? A medical legal case analysis. Part I.

This article describes a case of a laparoscopic injury and the ensuing litigation. Data from the hospital report and the testimony of witnesses are presented. In the next issue of this Journal, the results of the jury finding will be presented as Part II.

Screening women for high risk of postnatal depression.

A ten-item screening questionnaire was constructed from previous reports on risk factors for postnatal depression, and its ability to predict antenatally the development of postnatal depression was tested. Women attending an antenatal clinic at 36 wk gestation completed the questionnaire and, at 8 wk postpartum, were assessed for the presence of depression using the Edinburgh Postnatal Depression Scale (EPDS). Although antenatal questionnaire scores correlated significantly with postnatal EPDS scores, this was largely because the questionnaire was able to identify correctly those who would not become depressed. Neither the questionnaire as a whole, nor groups of items, was able to discriminate well between women who later did or did not become depressed. However, women who reported previous or current treatment for depression were at a threefold greater risk of becoming or remaining depressed postnatally. Possible reasons for the negative results are discussed, including the heterogeneity of depression occurring in the postnatal period.

Conception by use of postmortem epididymal semen extraction in a dog.

A 9-year-old sexually intact male Boxer was euthanatized because of progressive, generalized seizures that were refractory to medical treatment. To try to preserve the breeding line, postmortem epididymal semen extraction was attempted. The testes were excised after the dog was euthanatized, and semen was extracted, frozen, and stored in liquid nitrogen. Approximately 3.5 months later, a suitable recipient was identified, and surgical intrauterine insemination was performed. Fifty-seven days after insemination, a viable pup was born.

Spermophagy in semen in the red wolf, Canis rufus.

The red wolf (Canis rufus) is an endangered species with 194 individuals remaining in the wild and in various captive facilities. Breeding efforts at the Graham, WA site (Point Defiance Zoo and Aquarium) have involved artificial insemination with fresh or frozen semen in an effort to increase population and maximize the genetic potential of the stock. Electron microscopic observations were made in semen specimens obtained by electro-ejaculation from mature males prior to their use in an effort to determine semen parameters that might be useful in guiding breeding procedures. Sperm samples were either fixed immediately or treated with capacitating media and fixed after 4 to 7 hr of incubation. Many of the specimens examined were pyospermic (white cell in semen) and showed evidence of spermophagy, primarily by neutrophils. Of the six animals surveyed, only one showed little evidence of spermophagy, and three had extensive pyospermia and spermophagy but this finding was not correlated with fertility. Samples fixed immediately as well as those incubated for several hours showed evidence of spermophagy, indicating that the phagocytosis was not the result of culture. Gene pool restriction and/or captive stress may be contributing factors of reduced semen quality.