Primitive neuroectodermal tumor of the central nervous system with glial differentiation: a FISH study of an adult case.

Primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS), a rare occurrence in adults, may show glial differentiation and can be misinterpreted as pure astrocytic neoplasms. Few fluorescence in situ hybridization (FISH) studies have been carried out on these tumors; isochromosome 17q was found to be the major chromosomal abnormality. We present the case of an adult in which we performed a FISH study of both the glial and neuronal components. A complex array of FISH changes, not including an isochromosome 17q were identified.

The 18q21 region in colorectal and pancreatic cancer: independent loss of DCC and DPC4 expression.

UNLABELLED: The 18q21 region is frequently altered in gastrointestinal tumors. Three candidate tumor suppressor genes have been identified in it: DCC, Smad4/DPC4 and Smad2; the mechanisms involving their inactivation have not been completely elucidated. In this study, genetic losses at 18q21 and expression of DCC and DPC4 in colorectal (n=12) and pancreatic (n=16) cell lines and in colorectal tissues (n=10) were analyzed. The status of the 18q21 region was assessed using microsatellite analysis and duplex PCR of exonic sequences; expression was analyzed by RT-PCR; mutational analysis of DPC4 cDNA was performed in selected cases. Homozygous losses of microsatellite markers at 18q21 were not observed in colon or pancreas lines; however, a higher proportion of apparent homozygosity than expected was found. DCC and DPC4 transcripts were detected in 11/12 and 12/12 colorectal cancer lines, respectively. In tumors, homozygous losses at 18q21 were detected in three cases, without affecting DCC. All tumors retained DCC and DPC4 mRNA expression. In pancreatic lines, DPC4 was inactivated through homozygous deletion (n=5), intragenic mutation (n=3), and lack of protein (n=2). IN CONCLUSION: (1) microsatellite analysis does not provide adequate information regarding homozygous losses at 18q21; (2) approximately 65% of pancreas cancer lines show inactivation of DPC4; and (3) loss of DCC and DPC4 occur independently.

Recurrence of IgA nephropathy and Henoch-Schönlein purpura after kidney transplantation: risk factors and graft survival.

BACKGROUND: IgA nephropathy (IgA) is one of the most common glomerulonephritis. Renal transplantation is the treatment of choice for patients with ESRD due to any kind of glomerulopathy, including IgA and Henoch-Schönlein purpura nephritis (H-SP), but original disease recurrence is now the third most frequent cause of allograft loss. METHODS: Eighty-seven cases of glomerulonephritis as the original disease were divided in two groups: group A--37 affected with 31 IgA and 6 H-SP; and group B--50 with other glomerulopathies. We compared patient and graft survivals at 5 years. To assess the presence of IgA or H-SP recurrence in group A patients, we performed an allograft biopsy in the presence of microhematuria, proteinuria, or an increased plasma creatinine. Known risk factors influencing recurrence rate were also analyzed. RESULTS: Five-year patient (97% vs 95%) and graft survivals (81% vs 78%) were not significantly different between groups A and B. Patients with crescentic glomerulonephritis (CGN) at the moment of diagnosis of IgA or H-SP showed a 5-year graft survival of 71% in contrast with 100% graft survival among those with mesangial or focal and segmental glomerulosclerosis pattern (P = .03). Histological recurrence was diagnosed in eight patients: six IgA and two H-SP. Women (P = .013) and a good HLA match (P = .029) were significantly associated with the risk of recurrence. CONCLUSIONS: When compared with other glomerulonephritis patients, with IgA or S-HP showed similar 5-year graft and patient survivals. Nevertheless, graft survival was shorter among patients with crescentic glomerulonephritis at the moment of diagnosis. Thus, the disease prognosis after grafting may be linked to the initial histological aggressiveness. Women and those patients transplanted with a good HLA match were prone to develop disease recurrence with a tendency toward a lower 5-year graft survival.

Role of Helicobacter pylori in stomach cancer after partial gastrectomy for benign ulcer disease.

OBJECTIVE: To determine the prevalence of Helicobacter pylori infection in patients having undergone gastrectomy for non-neoplastic disease who later developed gastric stump cancer. MATERIAL AND METHODS: Retrospective study of all patients with partial gastrectomy for non-malignant peptic disease who were submitted to an endoscopic exploration between 1995 and 2001. A comparison was made of major clinical and histological characteristics, and the presence of Helicobacter pylori among patients with and without gastric cancer in the stomach remnant. RESULTS: A total of 73 patients were studied in this period. Fifteen patients (20.5%) had remnant-stump gastric cancer. All but one were adenocarcinomas (71% intestinal and 29% diffuse, respectively). The average time between diagnosis of gastric cancer and previous gastrectomy was 32 (14-48) years. There was a higher detection rate of Helicobacter pylori in patients with cancer in the gastric remnant (100 vs. 81.5%, respectively, p < 0.07). No relationship was seen between type of gastric reconstruction (Billroth I or II) and rate of Helicobacter pylori detection. CONCLUSIONS: Helicobacter pylori infection is frequent in patients with previous gastrectomy for non-neoplastic disease. The results of the study suggest that Helicobacter pylori infection may play a role in gastric stump cancer.

Mineralization of bone-like extracellular matrix in the absence of functional osteoblasts.

When grown in medium containing ascorbic acid and beta-glycerol phosphate, mouse MC3T3-E1 cells express an osteoblast phenotype and produce a highly mineralized extracellular matrix. The purpose of this study was to independently examine the role of the collagenous matrix and functional osteoblasts on the mineralization process. Cultures with and without an extensive collagenous matrix were prepared by growing MC3T3-E1 cells in the presence and absence of ascorbic acid. Matrix-rich cultures mineralized at much lower calcium phosphate ion products than nonmatrix cultures. At higher ion products, spontaneous precipitation in the medium and cell layers of nonmatrix cultures were observed. In contrast, mineral in matrix-rich cultures was still exclusively associated with collagen fibrils and not with ectopic sites in the cell layer or medium. To examine the effect of cell viability on matrix mineralization, cells were grown 8 or 16 days in the presence of ascorbic acid, then killed and incubated in a mineralizing medium. Significant mineralization was not observed in the collagenous matrix of 8-day killed cultures or age-matched controls. At 16 days mineral was associated with collagen fibrils at specific foci in the matrix of both viable and killed cultures. This observation is consistent with the concept that collagenous matrices must undergo a maturation process before they can support a mineral induction and growth. It further shows that osteoblast-like cells are not required for mineralization of mature matrices, but are required for matrix maturation.

Relationship among densitometry, bone histomorphometry, and histologic stage in idiopathic myelofibrosis.

Idiopathic myelofibrosis (IMF) induces dramatic changes in bone. Bone remodeling and densitometric alterations in a series of nine patients with IMF and their relationship with the histologic stage of the disease were assessed. Patients were included at diagnosis and a bone marrow biopsy, dual-energy X-ray absorptiometry, and transiliac bone biopsy for histomorphometric analysis were performed. Five cases were classified as IMF histologic stage 1, one as stage 2, and three as stage 3. Compared with 40 age- and sex-matched controls, the following histomorphometric parameters were significantly higher in our patients: bone volume (BV/TV), osteoblast surface (Ob.S/BS), eroded surface (ES/BS), osteoclast surface (Oc.S/BS), osteoclast number (N.Oc/TA), mineralizing surface (MS/BS), reversal period (Rv.P), and remodeling period (Rm.P). Mineral apposition rate (MAR) and erosion depth (E.Depth) were significantly decreased (P < 0.05 for all comparisons). Bone mineral density (BMD) measurements showed high values for patient age and sex both at femur neck (Z score range +0.19 to +7) and total femur (Z score range -0.09 to +6.48). When densitometric values were analyzed according to IMF histologic stage, patients in stages 1 and 2 had significantly lower BMD values than to those in stage 3 (P = 0.024). In conclusion, patients with IMF present a characteristic bone histomorphometric pattern with increased bone volume and bone cells but low apposition and decreased erosion depth, suggesting a positive balance in bone remodeling units. This balance would produce the increase in bone mass observed in this disease. Given the increase in BMD observed with more advanced stages of IMF, this noninvasive method could be useful tool for assessing IMF progression.

Multiple "slow" CT scans for incorporating lung tumor mobility in radiotherapy planning.

PURPOSE: The high local recurrence rates after radiotherapy in early-stage lung cancer may be due to geometric errors that arise when target volumes are generated using fast spiral CT scanners. A "slow" CT technique that generates more representative target volumes was evaluated. METHODS AND MATERIALS: Planning CT scans (slice thickness 3 mm, reconstruction index 2.5 mm) were performed during quiet respiration in 10 patients with peripheral lung lesions. Planning CT scans were repeated twice, followed by three slow CT scans (slice thickness 4 mm, index 3 mm, revolution time 4 s/slice). All, except the first scan, were limited to the tumor region. Three-dimensional registration of all scans was performed. The reproducibility of the imaged volumes was evaluated with each technique using (1) the common overlapping volume (COM), the component of the clinical target volume (CTV) covered by all three CT scans, and (2) the encompassing volume (SUM), which is the volume enveloped by all CTVs. RESULTS: In all patients, the target volumes generated using slow CT scans were larger than those derived using planning scans (mean ratio of planning-CTV:slow-CTV of 88.8% +/- 5.6%), and also more reproducible. The mean ratio of the respective COM:SUM volumes was 62.6% +/- 10.8% and 54.9% +/- 12.9%. CONCLUSIONS: Larger, and more reproducible, target volumes are generated for peripheral lung tumors with the use of slow CT scans, thereby indicating that slow scans can better capture tumor movement.

Nuclear beta-catenin in colorectal tumors: to freeze or not to freeze? Colon Cancer Team at IMAS.

beta-Catenin mediates the interaction of E-cadherin with alpha-catenin and the actin cytoskeleton. Recent evidence indicates that when the tumor suppressor gene APC is inactivated, beta-catenin can translocate to the nucleus, where it acts as a transcriptional regulator. Because APC is inactivated in most colorectal cancers, beta-catenin nuclear localization would be expected in these tumors. In a study of adhesion molecule expression in frozen colorectal cancer tissues, we were surprised by failure to detect nuclear beta-catenin. Here we compared the reactivity of an anti-beta-catenin monoclonal antibody with 11 colorectal cancers using immunohistochemistry on sections of frozen or paraffin-embedded samples. beta-Catenin was never detected in the nuclei of normal or tumor cells in frozen tissue sections. By contrast, in 8/11 cases it was detected in the nuclei of tumor cells but not of normal cells in paraffin-embedded tissue sections. These results were confirmed with an independent rabbit polyclonal anti-beta-catenin serum. We also examined beta-catenin distribution in SW480 colon cancer cells, in which its nuclear accumulation has been reported. As in tissues, nuclear beta-catenin was detected in paraffin-embedded but not in frozen samples. These findings are relevant because of the increasing interest in the study of beta-catenin in tumors, based on its dual role in cell adhesion and transcriptional regulation.

Malignant pigmented clear cell epithelioid tumor of the kidney: clear cell ("sugar") tumor versus malignant melanoma.

A 73-year-old woman presented with an hemorrhagic kidney tumor initially interpreted as a renal cell carcinoma (RCC). A retroperitoneal recurrence infiltrating the duodenal wall was made up of clear cells, some of which contained Fontana-Masson positive pigment, immunopositive for HMB-45, S-100 protein, actin, and vimentin. The same immunohistochemical profile was retrospectively reproduced in the kidney tumor, where melanosomes were also found ultrastructurally. Lipomatous differentiation was not observed. There was no history of malignant melanoma (MM), or stigmata of tuberous sclerosis. The patient died of disease 5 years after the initial diagnosis. This neoplasm can be considered as a malignant, pigmented, clear-cell epithelioid variant of angiomyolipoma, or "sugar" tumor of the kidney, with the peculiarity of having a previously unreported component of pigmented cells visible on light microscopy. This finding raises the possibility that the exceptional cases of MM reported in renal parenchyma may be pigmented variants of epithelioid angiomyolipoma rather than true MM.

Renal cell carcinoma with syncytial giant cell component.

We report a case of clear cell renal cell carcinoma in which a prominent multinucleated giant cell component was intermingled with clear, granular, and spindle cells. Histological, ultrastructural, cytometric, and cytogenetic features of giant cells were similar to those of mononucleated cells in the tumor, and therefore they were not from stromal or osteoclast derivation. These giant cells had homogeneous, finely granular, abundant cytoplasm, often with scalloped cell borders, and contained from 5 to more than 50 nuclei, all of them very similar in size and shape, with prominent central nucleoli. Occasionally, surrounding inflammatory cells were also engulfed in the cytoplasm. This syncytial appearance was more similar to that of some giant cell carcinomas from the lung than to the pleomorphic giant cells often encountered in high grade renal cell tumors. Although the patient is alive and free of disease 6 years after diagnosis, a longer follow-up will be required to assess the potential prognostic influence of this peculiar histological appearance.

Aneurysm of the inferior mesenteric artery.

A case of arteriosclerotic aneurysm of the inferior mesenteric artery, in which obliteration of both the coeliac axis and the superior mesenteric artery was found by chance in a patient with chronic ischaemia of the lower extremities and without digestive vascular trouble is reported. The surgical treatment is discussed and the reasons for its applications analysed. A review of world literature revealed only two previously published cases, which are quoted.

[Management of non-functioning renal graft]. / Actitud ante el injerto renal no funcionante.

On a series of 315 consecutive Renal Transplants (RT), the authors analyze the effects from any situation capable of causing the graft's renal failure, whether accompanied or not of oligoanuria. To begin with, the exploratory approach promoted by the ¿non-functioning kidney¿ is established recognizing three typical stages depending on the time of appearance: early, medium-term and long-term. The breakthroughs obtained in the prevention of Acute Tabular Necrosis (A.T.N.) are verified through the use of the receptor's hyperhydration, as well as the good results in the treatment of rejection since the arrival of Cyclosporin and the recent introduction of OKT3. Chronic rejection, is, today, the major cause of our transplantectomies (TX), since our attitude towards the exeresis of all irreversibly non-functioning grafts is well known. Vascular thrombotic problems have a very high percentage of losses among affected kidneys. Little can be done once the problem arises. Prevention is the best weapon available and special attention should be paid to the meticulousness of bank surgery and the suitable final positioning of the organ in the fossa iliaca, having into account the highly close relationship between this problem and the pathological and iatrogenic anomalies displayed by the organs to be transplanted in their arterial tree. The excretory tract problems are repaired in 83% cases, but the rest may even result in the loss of the kidney. In these complications, early surgery is the best way to avoid subsequent amputation surgery.

[Review of 45 cases of renal oncocytomas published in our country, and presentation of 2 new cases]. / Revisión de 45 casos de oncocitomas renales publicados en nuestro país, y aportación de 2 nuevos casos.

A review is made on the characteristics presented by the 45 cases of renal oncocytomas published in the specialized literature in our country, which are compared to major publications on the subject in the international literature in which a recent review reports 200 cases. Also, two new cases are presented. These tumours are included within the 17 benign renal tumours accumulated in our centre (11.7%) accounting for 2.27% of all renal tumours diagnosed by our group. The renal oncocytoma opens a significant controversy with regard to its definitive identity and, therefore, with regard to its possible therapy whether radical or conservative.

Comparability of ecological quality boundaries in the Mediterranean basin using freshwater benthic invertebrates. Statistical options and implications.

Within the Mediterranean region each country has its own assessment method based on aquatic macroinvertebrates. However, independently of the classification system, quality assessments should be comparable across members of the European Commission, which means, among others, that the boundaries between classes should not deviate significantly. Here we check for comparability between High-Good and Good-Moderate classifications, through the use of a common metric. Additionally, we discuss the influence of the conceptual and statistical approaches used to calculate a common boundary within the Mediterranean countries participating in the Intercalibration Exercise (e.g., using individual national type-boundaries, one value for each common type or an average boundary by country; weighted average, median) in the overall outcome. All methods, except for the IBMWP (the Iberian BMWP) when applied to temporary rivers, were highly correlated (0.82

Comparability of river quality assessment using macrophytes: a multi-step procedure to overcome biogeographical differences.

This paper exposes a new methodological approach to solve the problem of intercalibrating river quality national methods when a common metric is lacking and most of the countries share the same Water Framework Directive (WFD) assessment method. We provide recommendations for similar works in future concerning the assessment of ecological accuracy and highlight the importance of a good common ground to make feasible the scientific work beyond the intercalibration. The approach herein presented was applied to highly seasonal rivers of the Mediterranean Geographical Intercalibration Group for the Biological Quality Element Macrophytes. The Mediterranean Group of river macrophytes involved seven countries and two assessment methods with similar acquisition data and assessment concept: the Macrophyte Biological Index for Rivers (IBMR) for Cyprus, France, Greece, Italy, Portugal and Spain, and the River Macrophyte Index (RMI) for Slovenia. Database included 318 sites of which 78 were considered as benchmarks. The boundary harmonization was performed for common WFD-assessment methods (all countries except Slovenia) using the median of the Good/Moderate and High/Good boundaries of all countries. Then, whenever possible, the Slovenian method, RMI was computed for the entire database. The IBMR was also computed for the Slovenian sites and was regressed against RMI in order to check the relatedness of methods (R(2)=0.45; p<0.00001) and to convert RMI boundaries into the IBMR scale. The boundary bias of RMI was computed using direct comparison of classification and the median boundary values following boundary harmonization. The average absolute class differences after harmonization is 26% and the percentage of classifications differing by half of a quality class is also small (16.4%). This multi-step approach to the intercalibration was endorsed by the WFD Regulatory Committee.

Least Disturbed Condition for European Mediterranean rivers.

The present report describes a three-step approach that was used to characterize and define thresholds for the Least Disturbed Condition in Mediterranean streams of four different types, regarding organic pollution and nutrients, hydrological and morphological alterations, and land use. For this purpose, a common database composed of national reference sites (929 records) from seven countries, sampled for invertebrates, diatoms and macrophytes was used. The analyses of reference sites showed that small (catchment <100 km(2)) siliceous and non-siliceous streams were mainly affected by channelization, bank alteration and hydropeaking. Medium-sized siliceous rivers were the most affected by stressors: 25-43% of the samples showed at least slight alterations regarding channelization, connectivity, upstream dam influence, hydropeaking and degradation of riparian vegetation. Temporary streams were the least affected by hydromorphological changes, but they were nevertheless affected by alterations in riparian vegetation. There were no major differences between all permanent stream types regarding water quality, but temporary streams showed lower values for oxygenation (DO) and wider ranges for other variables, such as nitrates. A lower threshold value for DO (60%) was determined for this stream type and can be attributed to the streams' natural characteristics. For all other river types, common limits were found for the remaining variables (ammonium, nitrate, phosphate, total P, % of artificial areas, % of intensive and extensive agriculture, % of semi-natural areas in the catchment). These values were then used to select the list of reference sites. The biological communities were characterized, revealing the existence of nine groups of Mediterranean invertebrate communities, six for diatoms and five for macrophytes: each group was characterized by specific indicator taxa that highlighted the differences between groups.