Biomedical subjects
Publications and source records attributed to D Carter.
A survey of 50 health visitors revealed a wide range of views on the frequency of certain behaviour patterns associated with feeding, sleeping and crying in babies. The implications of this for health visitor training and client contact are discussed.
A fifth case of adenocarcinoma arising at an ileostomy site many years after total colectomy for ulcerative colitis is reported with a review of the literature. The patient is a 79-year-old white man who presented with a bleeding, locally invasive exophytic mass at his ileostomy site 36 years after total colectomy for ulcerative colitis; he is the oldest patient, with the longest interval from creation of his ileostomy to diagnosis of adenocarcinoma. Careful gross and histopathologic examination of any mass arising at an ileostomy site is recommended. Early detection of such a slowly growing malignancy arising in a long-standing ileostomy may result in cure.
Six micron paraffin sections of paraformaldehyde-fixed endometrial currettings of 21 benign and neoplastic endometrial specimens were assayed for tumor cell-specific oncogene expression by in situ hybridization with probes for six oncogenes, beta-actin, and the E. coli plasmid pBR322. In the benign hyperplasias and invasive adenocarcinomas, multiple oncogenes, including erbB, fms, c-myc, and Ki-ras were expressed at significant levels. For the adenocarcinomas, statistical analysis demonstrated that high levels of expression of fms-complementary mRNA correlated strongly with clinicopathologic features (high FIGO histologic grade, high FIGO clinical stage, deep myometrial penetration) predictive of aggressive clinical behavior and poor outcome. The authors discuss the role which M-CSF receptor (the fms gene product) and locally-produced M-CSF may play in the development of the observed aggressively-malignant phenotypes. They also propose that pre-hysterectomy assay of fms gene expression in endometrial currettings in FIGO Stage I patients might be clinically useful to help identify preoperatively those patients with deep myometrial penetration or other locoregional spread.
Cryptorchidism is associated with impaired spermatogenesis and, at times, sterility. Early orchiopexy has been advocated as a possible means to prevent spermatogenic impairment and infertility in patients with cryptorchidism. This retrospective study is derived from data obtained from 74 cases that were observed during a period of approximately 10 years at our hospital. Particular attention was devoted to epididymal and vas deferens histological status. Of the 47 epididymides and vas deferens examined only 2 epididymides and 2 vas deferens showed histological maturity. The remainder showed varying degrees of immaturity that additionally correlated, when testicular tissue was available, with the presence of unfavorable testicular histological findings. Cryptorchidism is associated with changes in the gonads and spermatic duct system.
Carcinosarcoma of the uterine cervix is a rare tumor. A case of carcinosarcoma of uterine cervix initially interpreted as sarcoma, NOS, is presented along with immunohistochemical findings.
A case of a 55-year-old man with known Fabry's disease, complicated by entero-vesical fistula and associated with enlarged mesenteric lymph nodes, is reported. Histopathologic and ultrastructural findings of the involved lymph nodes are described, and pathogenesis of the entero-vesical fistula is briefly discussed. This is the first case, to the authors' knowledge, of urologic complication in Fabry's disease.
The clinicopathologic features of 17 fibrous tumors of the pleura are presented. Eight were benign localized fibrous tumors; all of these were negative when stained with antibodies to keratin. Eight were diffuse malignant tumors that demonstrated intense immunohistochemical staining of the spindle cells with antibodies to keratin. One case presented as a histologically malignant spindle cell tumor that was initially localized but recurred subpleurally three times in 12 years. This spindle cell tumor was consistently negative when stained for keratin. We conclude that there are three types of fibrous tumors of the pleura: (a) a localized, histologically benign, keratin-negative spindle cell tumor that might be termed "fibroma," (b) a diffuse, histologically malignant, keratin-positive neoplasm that might appropriately be termed a "sarcomatoid mesothelioma," and (c) a histologically malignant, keratin-negative, spindle cell tumor with the potential to spread under the pleura that might appropriately be termed a "sarcoma." Immunohistochemistry proved to be useful in distinguishing the sarcomatoid mesothelioma from the sarcoma.
Abnormal Doppler ultrasound signals were detected in 44 of 47 patients with primary malignant tumors of the liver, kidney, adrenal gland, or pancreas (94%). Two different signal types were noted: a high-velocity signal (n = 38) with Doppler shifts exceeding 3 kHz (at an insonating frequency of 3 MHz) and a very low-impedance signal (n = 9) demonstrating little systolic-diastolic variation. In three patients, both types were present. In 19 patients, histologic (n = 12) and/or angiographic (n = 16) correlation was available. Among 13 patients with angiographic studies and signals over 3 kHz, arteriovenous shunting was demonstrated in six. The ratio of the systolic to diastolic Doppler shift is a function of vascular impedance. This systolic/diastolic index was less than 3 in eight patients with histologic correlation. All eight had prominent vascular spaces, and the flow in such thin-walled, endothelium-lined spaces would account for the low-impedance signals. Of nine patients with systolic/diastolic indexes of 3 or less and angiographic correlation, three had marked and four had moderate tumor staining.
The vascularity of 49 renal masses (26 malignant and 23 benign lesions) was investigated with duplex Doppler ultrasound. Doppler signals obtained at the margins of renal masses were defined as "tumor signals" when the Doppler-shifted frequency of the lesion exceeded the frequency shift in the ipsilateral main renal artery. These exceeded 2.5 kHz with a 3-MHz insonating frequency. Among the 26 renal masses that subsequently proved to be malignant, tumor signals were obtained in 15 of 18 (83%) untreated renal cell carcinomas, in three of four Wilms tumors, and in two patients with metastases to the kidney, but not in the one patient with lymphoma. None of the 23 benign renal masses demonstrated tumor signals. Tumor vascularity in malignant lesions gives rise to abnormal, high-velocity, Doppler-shifted signals that can help in the differential diagnosis of renal masses.
This paper describes the immunohistochemical staining properties of four monoclonal antibodies (MAbs) (CF, EB, AD, and KB) which had been previously shown to be specific for purified neuron-specific enolase (NSE) by a solid-phase radioimmunoassay. In this study, the authors immunostained a spectrum of normal and neoplastic neuronal, "neuroendocrine," and nonneuronal tissues fixed in formalin and embedded in paraffin. Positivity was generally restricted to normal neuronal structures and neuronal tumors, including adrenal neuroblastoma, ganglioneuroblastoma, olfactory neuroblastoma, pheochromocytoma, carotid body paraganglioma, duodenal gangliocytic paraganglioma, and teratoma with neuroepithelial components. Three staining patterns of the normal or neoplastic neuronal structures were observed: two MAbs (CF and EB) stained predominantly the nerve fibers (axoplasm); one (AD) stained predominantly the cell bodies (perikaryon); and one (KB) stained both the axoplasm and the perikaryon. "Neuroendocrine" tumors such as pulmonary small cell carcinoma, pancreatic islet cell tumor, thyroid medullary carcinoma, and carcinoid tumors from various locations showed a variable staining pattern. Tumor cells undergoing mitotic division were usually positive regardless of type. Normal structures other than neuronal or "neuroendocrine," including normal glial cells, were negative. The authors also studied a range of glial cell tumors with MAbs CF and AD as well as with Dako polyclonal antiserum to NSE. The results showed that CF stained the axonal fibers in the normal white matter surrounding these tumors; it did not stain the tumor cells or the perikarya of neurons in the surrounding normal gray matter. AD stained the glioma cells as well as the perikarya and dendrites of neurons in the surrounding normal gray matter; it did not stain the axonal fibers in the surrounding normal white matter. By contrast, the polyclonal antiserum stained all of these structures. The high degree of staining specificity of the MAbs should prove them to be valuable in immunohistochemical diagnosis of tumors as well as in further understanding the role of NSE in neuronal differentiation.
Patterns of cartilage invasion by squamous carcinoma were examined in 40 laryngectomy specimens with particular reference to selective involvement of ossified cartilage. The study determines whether external radiation administered at therapeutic levels to the human larynx has selective effects on the osteoclast cell population and subsequent bone resorption. Radiated and nonirradiated tissues were compared as were cases with and without laryngeal framework involvement by cancer. Morphologic changes in ossified laryngeal cartilage showed that invasion is a largely indirect process dominated by local bone destruction with osteoclasts operating in front of the advancing tumor. Morphometric studies indicate that framework invasion correlates significantly with both increased numbers of osteoclasts and increased bone resorption. An original finding here was that radiation therapy resulted in similarly increased osteoclast activity among cases without framework involvement by cancer. In these cases radiation appeared to act independently of tumor in producing osteoclast activation.
Pleural mesotheliomas and peripheral pulmonary adenocarcinomas were evaluated by immunohistochemistry at two institutions (Yale University School of Medicine and the City of Hope National Medical Center). Twenty-three mesotheliomas, 11 with ultrastructural verification, and 24 pulmonary adenocarcinomas were studied. Antikeratin, anticarcinoembryonic antigen, anti-human milk fat globule related antigen, MC-1, B72.3, and Leu M-1 antibodies were employed. The immunohistochemistry of each case prepared at one institution was reviewed at the other. As groups, the two tumor types were distinguishable using this antibody panel. Essentially, mesotheliomas were keratin positive only. The adenocarcinomas were positive for CEA, MFG, B72.3, and Leu M-1. However, there were some ambiguities presented by the immunohistochemistry. The higher molecular weight keratins were found in most but not all mesotheliomas and in only a few adenocarcinomas. Lower molecular weight keratins were positive not only in all the mesotheliomas, but also in nearly all the adenocarcinomas, but also in a tumor determined by electron microscopy to be mesothelioma. Preabsorption of CEA decreased the sensitivity for adenocarcinoma, but did not change the positivity of the putative mesothelioma. B72.3 and Leu M-1 were specific for adenocarcinoma, but were found in only half of them. The MFG was apparently specific for adenocarcinoma, but the findings were difficult to interpret. At the level of individual cases, greater sensitivity of separation can be achieved by combining the results of two or more antibodies, but the lack of a detectable specific antigen in mesothelioma continues to make some cases difficult to evaluate by immunohistochemistry alone.
One hundred eighty women with clinical Stage I or II operable breast carcinoma were treated by radiotherapy following local tumor excision at Yale-New Haven Hospital through 1980. With a median follow-up time of 6.9 years, the actuarial 5-year overall and disease-free survival rates were 82% and 78%, respectively. The 5-year actuarial breast-recurrence-free survival rate was 92%. Several clinical-histopathologic features and treatment parameters were assessed for their significance as predictors of local breast failure or distant relapse. Cox lifetable regression analysis showed that patients with clinical Stage II carcinomas had significantly worse overall and relapse-free survival rates, but clinical stage alone had no effect on the rate of breast recurrence. Furthermore, a decrease in overall and disease-free survival was evident when necrosis was present in the tumor or when patients had an infiltrating lobular carcinoma. Breast recurrence-free survival was also influenced adversely by the presence of these two tumor features, especially when either tumor necrosis or infiltrating lobular carcinoma was found in conjunction with clinical Stage II lesions. Other histologic features such as grade, vascular invasion, perineural invasion, or the presence of an intraductal component of carcinoma did not affect outcome, nor did the treatment techniques employed appear to have a differential effect.
With the use of hybridization in situ, c-myc and c-ras oncogene expression has been identified in the cytotrophoblast of hydatidiform mole and in the malignant trophoblast cell line BeWo. Expression was also found in early villous placenta. No expression of these two oncogenes was found in the cytotrophoblast of an 11-week conceptus, nor was it found in term placenta. The significance of these findings is discussed.
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The occurrence of visual loss in substantial numbers of adult patients with pseudotumor cerebri is well recognized. In children, the disease has been said to spare the visual system. We evaluated the ophthalmologic features of 36 children with pseudotumor cerebri followed up for one to 12 years. Four patients had rapid, severe loss of visual acuity and visual field changes while receiving medical therapy. Six others had less-severe but prominent abnormalities of visual acuity and/or visual fields at some point during the disease process. Only one patient had a permanent, severe visual impairment, but five had moderate permanent visual abnormalities. A severe degree of papilledema was seen only in the group with visual loss, but some patients in this group had only moderate papilledema. More patients with dural sinus thrombosis had serious visual loss than did those with other associated diseases or idiopathic pseudotumor cerebri. Quantitative perimetry of some sort can be performed in most children and is the preferred sequential test for planning treatment.
The cure rate in childhood cancer has improved markedly during the past 20 years. In the 1960s the cure rate was about 20 to 30 per cent, but today more than 50 per cent of children and adolescents with cancer are being cured. This improvement is principally due to multidisciplinary teamwork in diagnosing, staging, and treating children with cancer; newer and more chemotherapeutic agents; and a recognition that combination therapy consisting of surgery, radiotherapy, and chemotherapy is frequently indicated.