Cap-assisted endoscopic submucosal resection of a pancreatic rest.
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Biomedical subjects
Publications and source records attributed to D A Weeks.
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The present study was designed to determine whether adult hypertension caused by a reduced number of nephrons from birth is due to preceding glomerular damage. Newborn male Sprague-Dawley rat pups were uninephrectomized during the first 24 hours after birth (UNX rats). At 20 weeks of age, chronically instrumented UNX animals were hypertensive on a normal-sodium (0.20%) diet compared with sham-operated controls (142+/-2 versus 124+/-2 mm Hg in controls). Body weights and the total kidney-to-body weight ratio were not significantly different in adult UNX animals compared with controls. Glomerular filtration rate (GFR) was reduced by 49% in UNX rats (1.85+/-0.24 versus 3.65+/-0.22 mL/min). Urine protein excretions were higher in UNX rats (20+/-2 versus 7+/-1 mg/d in controls). On a high-sodium (3.15%) diet, arterial pressure increased more in UNX than in controls (28+/-9 versus 3+/-1 mm Hg). In contrast, in animals studied at 8 weeks of age, GFR was only reduced by 26% in UNX animals (2.02+/-0.06 versus 2.73+/-0.07 mL/min). Their hypertension (125+/-2 versus 117+/-2 mm Hg) was also salt sensitive (increase on high-sodium diet of 35+/-11 versus 8+/-2 mm Hg in controls) but was not associated with proteinuria or histological signs of glomerular disease. Number of glomeruli per kidney in UNX animals was not different from controls, but individual glomerular volume increased by 41%. Thus, surgical removal of 50% of the nephrons, when done during development, causes reduced renal function and salt-sensitive hypertension in adulthood. Hypertension is present earlier in life than signs of glomerular disease, which suggests that hypertension is a major contributor to rather than primarily resulting from onset of renal disease.
A series of case presentations show unique challenges associated with childhood round cell tumors and the role of ancillary techniques in diagnosis. Electron microscopy is shown to be the most powerful individual technique. Immunohistochemistry is less effective but also essential. Other ancillary techniques may provide needed additional diagnostic information. Because this is an area where it is of great importance to secure the most rapid, accurate, and specific diagnosis possible, an integrated multimodal approach is recommended--incorporating light microscopic, electron microscopic, and immunohistochemical studies as a matter of routine, and providing for cytogenetic and/or molecular diagnostic studies as indicated.
Anaplasia, defined by the presence of extreme nuclear and mitotic atypia, is a potent marker of adverse prognosis in Wilms tumor (WT). Anaplastic WT cells apparently have increased resistance to therapy rather than increased aggressiveness. The distribution of anaplasia should therefore have critical prognostic relevance. The original definitions for focal anaplasia (FA) and diffuse anaplasia (DA) were based on quantitative rather than topographical criteria and lacked prognostic significance. A new definition was developed based on the distribution of anaplastic changes within the tumor: FA applies only to tumors with anaplasia confined to one or a few discrete loci within the primary tumor, with no anaplasia or marked nuclear atypia elsewhere. This revised definition was evaluated in 165 cases with anaplastic WT entered on the third and fourth National Wilms Tumor Study. Only three relapses and one death occurred among 39 cases with FA, regardless of tumor stage, a result comparable to that for nonanaplastic WT. Eight children with metastases at diagnosis and FA in the primary tumor were alive and free of relapse; 22 of 23 children with stage IV DA WT died of tumor. This new definition reinforces the importance of carefully documenting the exact site from which each tumor section is obtained.
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BACKGROUND: External beam radiotherapy in advanced neuroblastoma is limited by the volume of normal radiosensitive tissues included in the radiation field. Limitations to external radiation are the late effects to these tissues. Intraoperative radiotherapy (IORT) delivers a single high-radiation dose to a tumor while displacing normal tissues that would have been included in an external field. Standard external radiotherapy can still be done after "boost" IORT. METHODS: Eight advanced-stage neuroblastoma patients who received IORT as part of their multimodality therapy were reviewed to identify the impact of IORT on operative time, complications, and tumor control in the treatment field. The IORT was accomplished by patient transport from the OR to the radiation therapy suite; these were separated by three floors. RESULTS: IORT added 30-75 min to the operative procedure. Tumors in the resection/IORT fields showed no evidence of disease (one), stable tumor size (six), and tumor recurrence (one). Two complications were identified: a urinary fistula and CO2 retention, which was detected and corrected before the IORT. Neither of these complications was related to the IORT. Two patients who had subsequent tumor resection after IORT demonstrated tumor differentiation to ganglioneuromatous tissue. CONCLUSIONS: IORT usually can be completed in less than an hour. No IORT-associated complications were identified. IORT along with maximal tumor resection, external radiation, and chemotherapy enhances local tumor control.
BACKGROUND: The purpose of this study was to determine the relationship between histologic microsubstaging variables, patient age, and tumor specimen weight in patients with Stage I/favorable histology Wilms' tumors. METHODS: The authors reviewed all randomized patients from the Fourth National Wilms' Tumor Study, who had Stage I/favorable histology Wilms' tumors evaluated for one or more of the microsubstaging variables: (1) the presence of an inflammatory pseudocapsule, (2) renal sinus invasion, (3) tumor in the intrarenal vessels, and (4) tumor capsule invasion. The authors determined the correlation between microsubstaging variables and age at diagnosis or tumor specimen weight. RESULTS: Patients who were younger than 2 years of age at diagnosis were significantly more likely to have all negative microsubstaging variables. Patients who had tumors weighing less than 550 g were more likely to have all negative microsubstaging variables. However, neither renal sinus invasion nor tumor in the intrarenal vessels was more frequent in tumors weighing more than 550 g. CONCLUSIONS: An age at diagnosis of younger than 2 years and a tumor specimen weight of less than 550 g are highly correlated with the absence of adverse microsubstaging variables. The clinical variables of age at diagnosis and tumor specimen weight, compared with the assessment of microsubstaging variables, have the practical advantage of being more objectively determined and not requiring a central pathologic review for confirmation.
The existence of extrarenal rhabdoid tumor (ERRT) as a discrete pathologic entity has been controversial despite frequent reports of its occurrence. We performed immunohistochemistry, electron microscopy, or both on 42 cases with this diagnosis sent in consultation to us. Only 12 of the 42 neoplasms had the histological findings of "classic" malignant rhabdoid tumor of the kidney; the remainder displayed a variety of neural, epithelial, myoid, mesenchymal, or ependymal patterns. Electron microscopy also showed that most possessed neural, epithelial, or ependymal features. Immunohistochemistry generally revealed marked polyphenotypia, with immunoreactivity to a wide array of antibodies against neural, epithelial, glial, and myogenic markers. A specific tissue-based diagnostic category could not be assigned in only 11 of the 42 cases, seven of which lacked material for a comprehensive ultrastructural or immunohistochemical study. We conclude that tumors currently diagnosed as ERRT represent a heterogeneous group of neoplasms that may form unique subsets of known entities within the specific site where they arise or that may defy classification into a specific alternative category. Our findings lead us to believe that the term ERRT is not valid as representing a specific diagnostic entity and to prefer the term "poorly differentiated neoplasm with rhabdoid features" for undifferentiated tumors.
We report a case of a newborn female with a rare tumor, a congenital sarcoma, presenting as an abdominal mass. Laparotomy demonstrated the tumor arising from the wall of the terminal ileum. Histologically, the tumor tissue was indistinguishable from clear cell sarcoma of the kidney and was composed of proliferating cells with poorly stained cytoplasm divided into nests or cords by arborizing vasculature. Immunohistochemical staining revealed that the neoplastic cells had a phenotype similar to metanephric blastemal cells of fetal kidney, ie, positive for vimentin and CD24 but negative for cytokeratin and CD9. The results suggest that this congenital tumor may originate from primitive mesenchymal cells phenotypically related to cells present in the fetal kidney.
Orthotopic concordant xenotransplantation in a juvenile primate model was examined. Eighteen donor rhesus monkeys weighing 2.4 to 3.8 kg (mean 2.9 kg) were matched with juvenile baboons, aged 9 to 19 months (mean 12.7 months) and weighing 3.2 to 4.8 kg (mean 3.9 kg), using ABH blood type and mixed lymphocyte culture. Rhesus monkey hearts were orthotopically transplanted without immunosuppression into six control baboons (group I). In five baboons (group II), 4 mg/kg per day of antilymphocyte globulin was administered for 3 days before the operation and 5 days after the operation. Splenectomy was also performed, and 18 mg/kg per day of FK 506 was administered orally. Intravenous methotrexate, methylprednisolone, or both were used as rescue therapy. Seven baboons (group III) received the same immunosuppression as those in group II, but an intravenous dose of methotrexate (0.1 to 5 mg) was given twice weekly to suppress the proliferative response as monitored by in vitro immunologic assays. Baboons in group I had a mean survival of 8 days; all died as a result of classic cellular rejection. Baboons in group II had a mean survival of 48.4 days (p < 0.05 versus group I). Two died during rescue therapy for rejection, and three died of cytomegalovirus infection. Two group II baboons showed mild rejection at autopsy. Baboons in group III had a mean survival of 127 days, and one baboon was still alive after 286 days. Two died of cytomegalovirus infection, one of toxoplasmosis, one of Klebsiella pneumoniae, one of massive micropulmonary embolism, one of renal failure aggravated by ganciclovir. Only two of the baboons that died showed rejection (estimated as mild) at autopsy. The baboon still alive at 286 days had no rejection on myocardial biopsy on the two hundred forty-fourth postoperative day. FK 506 coupled with low-dose maintenance methotrexate and splenectomy has produced prolonged host survival in this xenotransplantation model. Results suggest that concordant xenotransplantation would be a suitable biologic bridge to allotransplantation.
The purpose of this investigation was to study the effects of a Nd:YAG laser on the cut surface of teeth using scanning electron microscopy (SEM). Eighteen single-rooted teeth were cleaned, shaped, and obturated with gutta-percha and root canal sealer. The apical 3 mm of each tooth were resected with a diamond fissure bur, and the teeth were randomly divided into two groups of nine teeth each. The resected surface of each root in one group was lased twice. The duration of lasing and the number of pulses were recorded for each tooth. The teeth were air dried, mounted on stubs, sputter-coated with gold-palladium and examined under SEM. Application of the Nd:YAG laser caused melting of apical dentine surfaces. The melted material resembled the appearance of glazed interconnected droplets. Resolidification and recrystalization of the melted areas appeared to be incomplete and discontinuous. Some areas between the glazed regions appeared similar to those of non-lased apical dentine resected root surfaces.
Preoperative chemotherapy is being used with increasing frequency in the US for the management of selected children with Wilms' tumor, despite relatively limited knowledge as to the effects of such therapy on tumor histologic features. The authors reviewed pathologic material from all preoperatively treated unilateral Wilms' tumors registered on the third National Wilms' Tumor Study. Preoperative therapy was associated with increased ambiguity of tumor stage. The prevalence of anaplasia in the 83 evaluable specimens was similar to, although slightly increased over, that in comparable high-stage untreated Wilms' tumors (11% versus 5% to 8%), and it appeared to retain its adverse connotations. These data also suggest that alterations of tumor character and distribution by therapy provide useful prognostic information. All 17 children whose residual viable tumor was limited to intrarenal sites at the time of resection were alive and disease-free at last follow-up. Extensive (greater than 90%) tumor necrosis, low mitotic activity, and high degrees of differentiation of residual tumor were also associated with favorable outcomes. Although careful utilization of preoperative chemotherapy can be of value in children with otherwise difficult-to-manage Wilms' tumors, the potential benefits of preoperative tumor bulk reduction must be weighed against the risk of overtreatment or undertreatment as a result of increased ambiguity of tumor stage.
A case of primary small cell carcinoma of the esophagus is presented. The clinical, radiologic, and pathologic findings of our case and 72 other cases were reviewed. The most common presenting symptoms were weight loss and dysphagia. Eighty percent were larger than 4 cm at presentation and 97% were in the mid to distal esophagus. The esophageal tumors were identical histologically to small cell carcinoma of the lung. Esophageal luminal widening on esophagram has been found to be more common in nonsquamous cell carcinomas. While rare, small cell carcinoma should be considered in the differential diagnosis of primary esophageal tumors, particularly in the presence of these findings.
Fifty-six renal neoplasms reviewed by the National Wilms' Tumor Study Pathology Center presented with histologic features that resulted in confusion with rhabdoid tumor of kidney, a usually lethal childhood renal tumor; all were eventually diagnosed as other entities. Conspicuous filamentous cytoplasmic inclusions or large nucleoli, typical findings in rhabdoid renal tumors, were the usual source of diagnostic difficulty. Most, but not all, tumors occurred in pediatric patients. Sixteen were examples of Favorable Histology Wilms' tumor, which invited confusion with rhabdoid tumors either on the basis of filamentous cytoplasmic inclusions (15 cases) or macronucleoli (one case). In most cases, foci of typical Wilms' tumor blastemal aggregation or evidence of definitive nephrogenic differentiation facilitated the correct diagnosis. All 10 patients for whom information about outcome was available were alive at last follow-up. The other 40 renal lesions mimicking rhabdoid tumor of kidney consisted of a clinically and histogenetically diverse group of neoplasms, including anaplastic Wilms' tumor, congenital mesoblastic nephroma, renal cell carcinoma, transitional cell carcinoma, collecting-duct carcinoma, oncocytoma, rhabdomyosarcoma, malignant neuroepithelial tumors, and lymphoma. Most of these lesions could be separated from renal rhabdoid tumors and correctly classified on the basis of careful attention to light microscopic details, but in several cases electron microscopy or immunocytochemical studies were helpful or essential.
Regional lymph node status is a key factor in the staging of pediatric renal tumors on the National Wilms' Tumor Study (NWTS). A review of cases entered on the NWTS has uncovered a number of cases where benign lymph node findings were mistaken for metastases. Most frequently, this was due to the presence of complexes of epithelial cells and Tamm-Horsfall protein within nodal sinuses. The epithelial cells were derived from damaged nephrons, usually resulting from obstruction by tumor. Another epithelial pseudometastic lesion, intranodal squamous epithelial cells, was found to originate from metaplastic calyceal urothelium. Benign mesothelial or coelomic inclusions similar to those previously described in pelvic and periaortic lymph nodes of adult females were found in nodes of four patients, including two boys, who are, to our knowledge, the first to be described with this finding. Other sources of confusion included protrusion of lymphoid follicles or germinal centers into nodal sinuses, thick endothelial cells of postcapillary venules mimicking epithelial tubules, nodal megakaryocytes resembling anaplastic nuclear changes, and histiocytic granulomas. Immunocytochemical methods were useful in evaluating some of these phenomena. Recognition of these pseudometastatic lesions is essential in order to avoid unnecessary and potentially hazardous therapeutic intensification.
Two cases of infectious crystalline keratopathy located in the posterior stroma after penetrating keratoplasty are presented. Topical steroids and suture removal were risk factors in both cases. In the first case, a moderate anterior chamber reaction was present. Crystalline infiltrates persisted on topical and systemic steroid therapy. In the second case, deep corneal ulceration, hypopyon, and vitreitis were noted. A vitreous aspirate showed rare gram-positive cocci in pairs. The corneal ulceration and crystalline keratopathy persisted despite intravitreal and topical antibiotics. Therapeutic penetrating keratoplasty was performed in both cases. Staphylococcus epidermidis sensitive to vancomycin was isolated from corneal tissue. Light microscopy documented aggregates of gram-positive bacteria anterior to Descemet's membrane, with an overlying keratitis. Electron microscopy in the second case showed all bacteria within stromal keratocytes. No clinical recurrence was seen using topical vancomycin. As demonstrated in the cases presented, infectious crystalline keratopathy can occur exclusively in the deeper layers of the cornea. Isolation of S. epidermidis, associated inflammation, and intraocular spread of organisms are rare findings.
Although in three different mouse tumor systems with corn oil as dietary fat we previously found that milk protein decreased tumor development compared with beef, the results were reversed in 1,2-dimethylhydrazine (DMH)-injected mice. The purpose of this study was to determine if the latter result was due to the protein source. BALB/c mice (n = 280) were divided into five diet groups and injected 10 times at weekly intervals with DMH (20 mg/kg wt) or saline. Four diets contained 11% protein (casein, milk, or beef) and 5% fat (corn oil or beef tallow), and the AIN-76A diet was used as a control diet. The source of fat was a significant modulator of tumor development. Corn oil markedly increased total tumor volume and the number of tumors per mouse compared with beef tallow. Its tumor-enhancing effects were evident when it was combined with milk but not with casein. In addition, significantly lower lymphoproliferation and T-cell cytotoxicity against colon tumor cell targets was associated with corn oil consumption, whereas nonfat milk as the protein source was related to normal oxidative burst capacity of phagocytes. These results demonstrate that the source of dietary fat, in addition to the protein source, has a profound effect on both tumor development and immune responsiveness in this animal tumor system.