Gravimetric measurements of cerebral edema in a rabbit brain tumor model.

The development of tumor-induced cerebral edema was studied in rabbits to establish a data base for future work using this brain tumor model to correlate the degree of edema with other functional and morphological parameters. The VX-2 carcinoma was implanted into the brains of New Zealand White rabbits. Animals were killed 9 and 13 days later, and gravimetric analysis was used to measure the specific gravity of gray and white matter in both the tumor-bearing implanted and contralateral nonimplanted hemispheres. Studies were conducted in untreated tumor-bearing rabbits as well as in those receiving dexamethasone daily for 4 days before death. Tumor tissue and peritumoral gray and white matter and contralateral gray and white matter were analyzed. In all cases, at both 9 and 13 days after tumor cell implantation, tumor tissue exhibited extremely high specific gravity values exceeding the range detectable by the assay procedure. Compared with controls, specific gravity values in tumor-bearing animals generally increased in gray matter and decreased in white matter as a function of tumor growth. This trend was seen in both peritumoral gray and white matter as well as in contralateral gray and white matter areas. However, in most cases, the changes in specific gravity values as compared with controls were not statistically significantly different. The primary exception to this was in peritumoral white matter, in which mean specific gravity values at both 9 and 13 days after implantation were statistically significantly lower than for the corresponding site in control non-tumor-bearing animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gliomatosis cerebri: quantitative proof of vessel recruitment by cooptation instead of angiogenesis

OBJECT: Gliomas are the most common primary brain tumors, many of which (especially astrocytic and oligodendroglial neoplasms) are characterized by diffuse infiltrative growth in the preexisting brain tissue. Gliomatosis cerebri is a rare glial tumor and represents an extreme example of such diffuse infiltrative growth. This growth pattern not only hampers curative treatment but also allows for vessel cooptation rather than tumor angiogenesis as a way of vessel recruitment by the tumor tissue. The goal of this study was to establish the extent to which tumor angiogenesis occurs in gliomatosis cerebri. METHODS: Computerized image analysis was performed to assess quantitatively two microvascular parameters (vessel density and diameter) in different areas of a brain harboring a gliomatosis cerebri. These regions were the cerebral white and gray matter in which there was a diffuse infiltrative tumor, cerebral white and gray matter in which there was a more compact growth pattern of tumor cells, and normal cerebral white and gray matter. In addition, the authors performed immunohistochemical stainings for blood-brain barrier (BBB) characteristics (Glut-1 and PgP) on samples obtained in these different areas. The results of the quantitative analysis strongly indicated that in gliomatosis cerebri tumor, angiogenesis was completely absent, a finding that is corroborated by the fact that the microvasculature in gliomatosis cerebri persists in exhibiting immunohistochemical characteristics of the BBB. CONCLUSIONS: The results of this study may help resolve the difficulties in radiological detection and delineation of the diffuse infiltrative part of glial brain tumors and put the expectations for antiangiogenic treatment of such tumors into perspective.     

树突状细胞与消化系恶性肿瘤预后的研究进展

目的 了解树突状细胞浸润与消化系恶性肿瘤预后的研究现状。方法 采用文献回顾的方法对树突状细胞浸润与消化系肿瘤的预后加以综述。结果 食道癌、胃癌、大肠癌及胰腺癌肿瘤组织中树突状细胞浸润数目与其预后密切相关。结论 消化系恶性肿瘤组织中树突状细胞浸润数目可作为判断肿瘤预后的独立指标。     

Effect of time interval on residual disease in breast cancer

The histologic responses of breast tissue to injury are limited. Needle core biopsies of the breast are associated with displacement of tumor cells, and the incidence of tumor displacement decreases as the time interval between needle core biopsy and subsequent excision increases. This suggests that displaced tumor cells are destroyed by reparative processes induced by tissue injury. Residual tumor in a lumpectomy site may also be subjected to the same destructive processes associated with tissue repair. A total of 259 consecutive cases of infiltrating ductal carcinoma with margin-positive lumpectomies and their associated reexcision specimens obtained over a 7-year period were analyzed for the presence, type, and quantity of residual disease. The overall incidence of residual disease was 69%. Residual infiltrating ductal carcinoma was present in 35% of cases, and residual ductal carcinoma in situ was present in 50%. An increased time interval between lumpectomy and reexcision was associated with a decreased incidence of residual infiltrating carcinoma (p <0.0043); this decrease was not found associated with ductal carcinoma in situ. These findings suggest that the host response to injury may destroy residual infiltrating carcinoma cells in some margin-positive cases.     

Parasagittal Solitary Fibrous Tumor of the Meninges. Case Report and Review of the Literature

Summary  The clinical, radiologic and pathologic features of a case of parasagittal solitary fibrous tumor of the meninges are reported. The patient was a 44 year-old male who presented with a complex partial seizure and a history of headaches and confusion. Radiological studies showed a large extra-axial dural-based mass in the right parietal region, predominantly isointense with gray matter and hypointense with respect to white matter on T1-weighted images, and hypointense with respect to gray matter on T2-weighted images. At surgery, the mass was very vascular, quite firm and very adherent to the convexity. Histologically the tumor was composed of spindle-shaped cells growing in fascicles within a collagenous matrix. Solitary fibrous tumor of the meninges is a newly described entity, which should be kept in mind in the clinical and radiological differential diagnosis of extra-axial brain tumors.     

Increased expression of activation markers in renal cell carcinoma infiltrating lymphocytes

PURPOSE: As manifested by the presence of immune competent cells, failure to control the progression of renal cell carcinoma by a local immune response attests to impaired local cell mediated immunity. To test this hypothesis we compared the expression of T-cell activation markers in renal cell carcinoma infiltrating lymphocytes with the expression of activation markers of peripheral blood lymphocytes in the same patients. MATERIALS AND METHODS: Tumor infiltrating lymphocytes were harvested from a patient with renal cell carcinoma undergoing radical nephrectomy. Peripheral blood was obtained before surgery. Tumor infiltrating and peripheral blood lymphocytes were incubated with monoclonal antibodies defining specific differentiation and activation markers on the cell surface, and analyzed by flow cytometry. Cell subsets are expressed as a fraction of the total number of mononuclear cells. RESULTS: The T-cell subset level was significantly higher in peripheral blood than in renal cell carcinoma tissue of the same patient. However, the level of activated T-cell subset expressing HLA-DR was significantly higher in renal cell carcinoma tissue than in peripheral blood. The levels of interleukin-2 receptor and transferrin receptors expressing T-cell subsets were also significantly higher in carcinoma tissue than in peripheral blood. Natural killer cells were found in significantly higher proportions in renal cell carcinoma than in peripheral blood. CONCLUSIONS: These results point to significant activation of T, B and natural killer tumor infiltrating lymphocytes. The inability of tumor infiltrating lymphocytes to mount an effective immune response to renal cell carcinoma may be secondary to the presence of suppressive factors in the tumor that prevent tumor infiltrating lymphocytes from transforming into effector cells. These factors may be particularly valuable for the further study of renal cell carcinoma-host interactivity.     

Effects of dexamethasone on tumor-induced brain edema and its distribution in the brain of monkeys.

A human choriocarcinoma was successfully adapted to grow in the brain of monkeys (Macaca mulatta), thus providing a model of tumor-induced brain edema. Four animals were given dexamethasone (3 mg/kg/day) during 3 to 5 days after the onset of clinical signs, and the other five received no treatment for the same period. Tissue water and electrolyte content of treated and untreated animals were compared in cortex and white matter at various distances from the edge of the tumor. In untreated animals, 67.9% and 23.6% swelling was detected in adjacent and remote white matter, respectively, but only 11.8% swelling was noted in adjacent cortex. In animals treated with dexamethasone these percentages of swelling were improved to 32.4% and 11.9% in the corresponding white matter, and to 4.9% in adjacent cortex. The electrolyte changes shown in edematous brain of control animals also demonstrated significant improvement in the dexamethasone-treated group. Tissue radioactivity of 3H-dexamethasone at 60 minutes after intravenous injection was high in the periphery of tumor, adjacent cortex, and white matter, but low in the center of tumor, remote cortex, and white matter. The sites with high concentrations of dexamethasone also showed significant improvement of brain edema after dexamethasone treatment, suggesting that dexamethasone may act directly at these loci.     

Passage of mannitol into the brain around gliomas: a potential cause of rebound phenomenon. A study on 21 patients

AIM: Widespread use of mannitol to reduce brain edema and lower elevated ICP in brain tumor patients continues to be afflicted by the so-called rebound phenomenon. Leakage of mannitol into the brain parenchyma through an altered BBB and secondary reversal of osmotic gradient is considered the major cause of rebound . This has only been demonstrated experimentally in animals. As a contribution to this issue we decided to research the possible passage of mannitol into the brain after administration to 21 brain tumor patients. METHODS: Mannitol (18% solution; 1 g/kg) was administered as a bolus to patients (ten had malignant glioma, seven brain metastases and four meningioma) about 30 minutes before craniotomy. During resection, a sample of the surrounding edematous white matter was taken at the same time as a 10 ml venous blood sample. Mannitol concentrations were measured in plasma and white matter by a modified version of the enzyme assay of Blonquist et al. RESULTS: In most glioma patients, mannitol concentrations in white matter were 2 to 6 times higher than in plasma (mean 3.5 times). In meningioma and metastases patients plasma concentrations of mannitol were higher than white matter concentrations except in three cases with infiltration by neoplastic cells. CONCLUSIONS: The results of our study show that even after a single bolus, mannitol may leak through the altered BBB near gliomas, reversing the initial plasma-to-blood osmotic gradient, aggravating peritumoral edema and promoting rebound of ICP.     

Diffusion-tensor imaging of white matter tracts in patients with cerebral neoplasm

OBJECT: Preserving vital cerebral function while maximizing tumor resection is a principal goal in surgical neurooncology. Although functional magnetic resonance imaging has been useful in the localization of eloquent cerebral cortex, this method does not provide information about the white matter tracts that may be involved in invasive, intrinsic brain tumors. Recently, diffusion-tensor (DT) imaging techniques have been used to map white matter tracts in the normal brain. The aim of this study was to demonstrate the role of DT imaging in preoperative mapping of white matter tracts in relation to cerebral neoplasms. METHODS: Nine patients with brain malignancies (one pilocytic astrocytoma, five oligodendrogliomas, one low-grade oligoastrocytoma, one Grade 4 astrocytoma, and one metastatic adenocarcinoma) underwent DT imaging examinations prior to tumor excision. Anatomical information about white matter tract location, orientation, and projections was obtained in every patient. Depending on the tumor type and location, evidence of white matter tract edema (two patients), infiltration (two patients), displacement (five patients), and disruption (two patients) could be assessed with the aid of DT imaging in each case. CONCLUSIONS: Diffusion-tensor imaging allowed for visualization of white matter tracts and was found to be beneficial in the surgical planning for patients with intrinsic brain tumors. The authors' experience with DT imaging indicates that anatomically intact fibers may be present in abnormal-appearing areas of the brain. Whether resection of these involved fibers results in subtle postoperative neurological deficits requires further systematic study.     

Interferon-alpha can alter the lytic susceptibility of murine bladder transitional cell carcinoma (MBT-2) by their original poor specific cytotoxic tumor infiltrating lymphocytes.

Fresh isolated or short term in vitro cultured tumor infiltrating lymphocytes derived from MBT-2 tumor possess little specific cytotoxicity on MBT-2 cells despite the presence of low (10 units/ml.), moderate (500 units/ml.), or high (1000 units/ml.) dose interleukin-2 and irradiated tumor cells; however the lytic susceptibility of the MBT-2 cells and their expression of MHC class I antigen can be significantly enhanced if the tumor cells are preincubated with interferon-alpha for 24 hours. But the specific antitumor activity of tumor infiltrating lymphocytes cannot be further augmented by coculturing them with irradiated interferon-alpha pretreated MBT-2 tumor cells. In vivo experiments by subcutaneous peritumor injection of interferon-alpha (500 units/ml.) combined with interleukin-2 (500 units/ml.) can suppress the tumor growth of those three-day inoculated MBT-2 cells significantly but not on those already established tiny tumors. We therefore concluded that interferon-alpha can alter the specific antitumor activity of tumor infiltrating lymphocytes chiefly through its modulating effect on the target tumor cells instead of the tumor infiltrating lymphocytes.     

Radiation-induced diffuse brain injury in the neonatal rat model--radiation-induced apoptosis of oligodendrocytes

The mechanism of radiation-induced diffuse brain injury was investigated using a model of delayed myelination in the irradiated neonatal rat brain in which the number of oligodendrocytes decreases without associated necrosis of the cerebral white matter. Immunohistochemical analysis using antibody against the large myelin-associated glycoprotein, a specific marker of oligodendrocytes at an early stage of development, showed that the number of the oligodendrocytes associated with myelination decreased in the irradiated hemisphere 1 day after irradiation and remained low until 5 days after irradiation. In situ terminal deoxynucleotidyl transferase-mediated nick end-labeling assay revealed that apoptosis mainly occurred in the cerebral white matter of the irradiated hemisphere. Three hours after irradiation, apoptotic cells were found in the subcortical white matter and the periventricular white matter. Six hours after irradiation, apoptotic cells were found in the internal capsule, and the numbers of apoptotic cells in the periventricular white matter and subcortical white matter increased. One day after irradiation, the number of apoptotic cells in the periventricular white matter decreased. Three days after irradiation, apoptotic cells were not observed in the cerebral white matter. These results suggest that the oligodendrocytes associated with myelination may be damaged via radiation-induced apoptosis, and depletion of the oligodendrocytes may cause delay of myelination.     

Sequential immunocytological evaluation of murine transitional cell carcinoma during intralesional bacillus Calmette-Guerin and interleukin-2 immunotherapy.

The antitumor effect of intralesionally administered recombinant interleukin-2 was highly effective (90% complete response) in murine bladder cancer. We postulated that interleukin-2 may be integral to the Bacillus Calmette-Guerin-induced antitumor response in human bladder cancer. Flow cytometric evaluation of the tumor infiltrates was compared before and after intralesional treatment of an established, untreated murine bladder tumor model with recombinant interleukin-2, Bacillus Calmette-Guerin or saline. Large increases in the number of tumor infiltrating immune cells occurred between the day of randomization and the second day (one day after the first treatment) in all three groups. However, since tumor volume was reduced by treatment, the ratios of the immune cells to tumor volume was increased. The ratios of T(helper), T(cytotoxic)/suppressor cells, macrophages, and natural killer cells to tumor volume were 1.5 to 3.4 times higher in the interleukin-2 and Bacillus Calmette-Guerin groups in comparison to the saline group. The ratio of T(helper)/T(cytotoxic)/suppressor cells however, remained approximately the same despite treatment. Over the next 22 days all subpopulations of tumor infiltrating immune cells decreased in number and frequency to less than measurable levels. The similar modulation of infiltrating immune cell subpopulations by Bacillus Calmette-Guerin and interleukin-2 may indicate that the production of interleukin-2 is part of the tumor modulating mechanism of Bacillus Calmette-Guerin.     

Peritumoral brain edema associated with meningioma--histological study of the tumor margin and surrounding brain.

Thirty-nine cases of intracranial meningiomas were analyzed to identify factors causing brain edema. Edema was significantly correlated with tumor size and the destruction of the leptomeninges and cortex. Meningotheliomatous meningioma tended to have more peritumoral edema. There was no correlation between the presence of edema and location of the tumor or histological features including lymphocytic infiltration and the presence of glial fibrillary acidic protein-positive cells in the tumor tissue. Larger tumors destroy the leptomeninges and cerebral cortex, allowing direct transmission of humoral edema-promoting factor or edema fluid into the white matter, resulting in vasogenic edema.     

Colonic primary large cell lymphoma with marginal zone growth pattern presenting as multiple polyps.

We report a rare case of primary gastrointestinal lymphoma, stage IE, in a 58-year-old white man who had multiple colonic polyps measuring up to 1 x 1.1 cm. The tumor originated in the marginal zone of the follicles infiltrating the interfollicular spaces. Follicular colonization was frequently seen. The mucosa was spared by the infiltrate. Morphologically, the neoplastic cells were monomorph, intermediate-sized blasts. Rare small to intermediate sized cells, some with centrocyte-like morphology, intermingled the blastic infiltrate. The neoplastic cells expressed CD20 and had a monotypic immunoglobulin of cytoplasmic IgM (kappa) on paraffin sections. Tumor cells stained negative for CD45RO, CD5, CD10, IgD, and CD23. Polymerase chain reaction revealed a clonal V-D-J rearrangement. Bcl-1 and bcl-2 rearrangement were not detected. We therefore suggest the diagnosis of primary large cell lymphoma with marginal zone growth pattern mimicking colonic adenomas.     

Sites of origin of primary intracerebral malignant lymphoma

With the aim of finding characteristics pointing to the primary site, computed tomography examination from 9 patients with primary brain malignant lymphoma (non-Hodgkin's lymphoma originating in the central nervous system, NHL-CNS) (5 single, 4 multiple lesions) were analyzed. The tumors were usually situated in the basal ganglia, corpus callosum, or cerebellum and were always in contact with either the ependyma of the ventricles or the subarachnoid space. Tumors with widespread infiltration of white matter surrounding the ventricles were characteristic of NHL-CNS. Microscopic examination of 3 autopsy cases revealed infiltration of the subependymal layer of the lateral ventricles and the third and fourth ventricles by lymphoma cells. The entire extent of the choroid plexus was invaded by tumor cells. There were multiple foci of similar cells invading the periventricular white matter. The subarachnoid space was filled with lymphoma cells. In many areas the Virchow-Robin spaces and pial-glial membranes were disrupted, and invasion of the underlying gray matter by tumor cells was seen. The ultrastructure of the blood vessels of NHL-CNS was compared with those in glial, nonglial, and metastatic brain tumors. The essential feature in NHL-CNS was fenestrated vessels. They resembled the blood vessels found in nonglial and metastatic brain tumors, but were distinctly different from those seen in glial tumors with nonfenestrated vessels. Although the following scheme in proposed with reservations, it could account for the sites of origin of NHL-CNS: lymphocytes located in the choroid plexus stroma or the subarachnoid space are activated, caused to proliferate, and finally become neoplastic.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of ICAM-1 and CD11b after experimental spinal cord injury in rats

We have performed an immunohistochemical study on the expression of the adhesion molecules ICAM-1 and CD11b 1 h to 1 week following a compression injury to the rat spinal cord. The spinal cord of control animals showed ICAM-1 expression in some vessels and in the leptomeninges. Mechanical compression of the spinal cord induced an endothelial upregulation of ICAM-1 that was maximal in rats surviving 1-2 days after injury. This reaction was seen at the center of the lesion as well as in the perifocal zones. Apart from the endothelial upregulation, increased ICAM-1 expression also was found in leptomeningeal and ependymal cells of traumatized animals. In control animals resting microglial cells were moderately CD11b immunoreactive. Trauma induced a rapid microglial upregulation of CD11b in the white matter that was evident even at 1 h after injury. By 1 day to 1 week posttrauma conformational changes consistent with microglial activation, i.e., transformation into phagocytic microglial cells, were seen in the white matter. In the gray matter, CD11b immunohistochemistry revealed massive infiltration of phagocytic microglial cells and macrophages in animals surviving 1 day to 1 week. Intravascular and infiltrating leukocytes were intensely CD11b immunopositive. As reflected by CD11b immunohistochemistry, the maximal infiltration of polymorphonuclear leukocytes occurred at 2 days after the insult. Endothelial upregulation of ICAM-1 facilitates adhesion and extravasation of leukocytes by binding to the counterreceptor CD11b. Knowledge regarding the expression and cellular distribution of such molecules after central nervous system trauma is important since inflammatory mechanisms have been suggested to be involved in secondary neurological damage and thus constitute potential targets of therapy.     

Race is a fundamental prognostic indicator for 2325 northeastern Ohio women with infiltrating breast cancer

The goal of this research was to determine if race, independent of socioeconomic status, is a prognostic indicator for women diagnosed with infiltrating breast cancer. We hypothesized that black patients would present with breast cancers having less favorable prognostic indicators relative to white patients, regardless of socioeconomic status. Using data collected prospectively in our institutional review board approved breast center patient registry and 2000 Census Tract data for northeastern Ohio, we compared tumor size, node status, hormone receptor status, clinical outcomes, and socioeconomic status for patients who were self-described as either black or white and who had been diagnosed with infiltrating breast cancer. The chi-square test, t-test, log-rank test, and Cox proportional hazards analysis were used to analyze the data. Kaplan-Meier outcome curves were generated. Data were available for 2325 women, including 313 who were black and 2012 who were white. Compared to white patients, black patients were more likely to have positive axillary nodes and to have hormone receptor-negative tumors. Black patients were also more likely to have positive axillary nodes associated with smaller tumors. Independent of socioeconomic status, black patients were more likely to have poorer overall survival and disease-free survival rates for breast cancer relative to white patients. The prognostic significance of race was not dependent on a concomitant relationship with socioeconomic status.     

Metanephric adenofibroma: report of a case and review of the literature.

The recent recognition of a variety of pediatric renal tumors of different biologic behavior places an ever-increasing demand on the surgical pathologist for an accurate diagnosis. Although metanephric adenofibroma is one of the rarest benign renal tumors, the clinical importance of correctly diagnosing it cannot be overemphasized because it can potentially be mistaken as Wilms' tumor. We describe the clinical, radiologic, and pathologic features of a case of metanephric adenofibroma and discuss its differential diagnosis. The neoplasm was composed of two discrete components: a major fibroblastic element and a minor immature epithelial element. The latter formed a small nodule beneath the renal capsule, which could barely be detected by magnetic resonance imaging. This subcapsular nodule, however, was slightly soft and tan and was distinctly different from the white, whorled cut surface of the main tumor. It was formed by closely packed small immature epithelial cells in a slightly edematous background, which was histologically identical to metanephric adenoma and closely resembled epithelial Wilms' tumor. Unlike Wilms' tumor, however, the epithelial cells were very bland with no mitoses. The main bulk of the tumor was formed by spindle fibroblastic cells that were cytologically similar to the spindle cells in congenital mesoblastic nephroma. The tumor, however, was well demarcated without the irregular infiltrating edges of congenital mesoblastic nephroma. In contrast to the randomly distributed epithelial element throughout the stromal component in previous reported cases of metanephric adenofibroma, our finding of the exceedingly small and discrete epithelial component expands the known histologic spectrum of the disease. In addition, the presence of such minute epithelial nodule underscores the importance of diligent pathologic examination and careful sampling of tissue for histologic examination.     

Abrikossof tumor of the cervical esophagus]

The aim of this study was to report one granular cells tumor of the cervical esophagus revealed by dysphagia. X-rays examination showed a paraesophageal tumor and esophagoscopy, a narrow stenosis and a benign ulceration. The tumor was removed through left cervical approach with suture of the esophageal opening. Pathological examination found a granular cells tumor infiltrating musculosa and measuring 4 x 2.5 x 2.5 cm.     

肿瘤压迫脊髓的实验研究

将１０６Ｗａｌｋｅｒ ２５６癌细胞经度注射到８０只Ｗｉｓｔａｒ鼠Ｔ１３椎体的前方， ５～ １０天后出现脊髓压迫损害。应用ＣＴ和ＭＲＩ扫描对椎旁肿瘤进行了测量。电镜检查发现受压段脊髓毛细血管扩张，以后塌瘪，渗透性高，常有红细胞溢出。脊髓微血管造影发现，肿瘤压迫早期为静脉回流障碍，晚期主要是白质和灰质的缺血。脊髓水分测定，证实局部存在脊髓水肿。实验结果表明：脊髓内血循环障碍和轴索破坏是造成截瘫的重要因素。