Influence of an increased intracranial pressure on cerebral and systemic haemodynamics during endoscopic neurosurgery: an animal model.

BACKGROUND: During endoscopic neurosurgery, direct mechanical stimulation of the brain by the endoscope and increased intracranial pressure (ICP) caused by the continuous rinsing can induce potentially lethal haemodynamic reflexes, brain ischaemia, and excessive fluid resorption. METHODS: In a newly presented rat model of endoscopic neurosurgery, stereotactic access to the cerebrospinal fluid was secured and the ICP was increased by controlled infusion until complete suppression of the cerebral perfusion pressure (CPP). The haematocrit (Hct) level was determined before and after the procedure. During the whole procedure, invasive arterial pressure, ICP, and heart rate were continuously recorded and evaluated in a subsequent offline analysis. After the procedure, the animals were allowed to recover and 7 days later they were killed for histological examination. RESULTS: Suppression of the CPP resulted in a severe hypertension combined with tachycardia or mild bradycardia. The Hct decreased from 41 to 35 over the minutes of CPP suppression. After cessation of the infusion, the ICP decreased to 37% of the plateau pressure within 2.5 s. In the first few minutes after restoration of normal ICP, five animals died because of pulmonary oedema. CONCLUSIONS: Upon complete suppression of the CPP, an obvious hypertension developed, often together with tachycardia, but no severe bradycardia. At high ICP levels, we observed an important translocation of irrigation fluid to the vascular space. Fatality was not caused by ischaemia or arrhythmia but due to pulmonary oedema.

Telomere biology in giant cell tumour of bone.

Giant cell tumour of bone (GCTB) is a benign bone tumour known for the unpredictable clinical behaviour of recurrences and, in rare instances, distant metastases. It consists of uniformly distributed osteoclastic giant cells in a background of mononuclear rounded and spindle-shaped cells. Cytogenetically, telomeric associations are the most common chromosomal aberrations, which, however, are normally almost exclusively found in high-grade malignancies. GCTB has often been regarded as a polyclonal tumour, but more recently a recurrent specific aberration was reported, which suggests a possible role for disturbed telomere maintenance. Here we further investigate telomere maintenance in GCTB using 19 samples from 19 patients. A combination of immunofluorescence and FISH was performed, applying antibodies directed against promyelocytic leukaemia body-related antigen and hTERT and using telomere peptide nucleic acid probes. The TRAP assay and telomere restriction fragment length analysis were performed for functional detection of telomerase activity and alternative telomere lengthening. Both osteoclastic giant cells and mononuclear cells showed positivity for hTERT and promyelocytic leukaemia body-related antigen. In most mononuclear cells, co-expression was present. The TRAP assay demonstrated heterogeneous telomerase activity, while telomere restriction fragment length analysis showed non-heterogeneous telomere lengths, indicating the absence of alternative telomere lengthening. Confocal microscopy showed stereometric co-localization of nucleolin with promyelocytic leukaemia body-related antigen in association with telomeres in the spindle-shaped cells. hTERT was more diffusely distributed throughout the nucleus. Our results show that GCTB demonstrates remarkable telomere maintenance of activated telomerase and inactivated alternative telomere lengthening in the presence of normal mean telomere restriction fragment lengths. These findings strongly suggest that these aggregates, while activating telomerase, are part of a structural telomere protective-capping mechanism rather than of a telomere-lengthening mechanism. Telomere maintenance could be considered an important key factor in the pathogenesis of GCTB.

A case of recurrent non-small-cell lung carcinoma and paraneoplastic Cushing's syndrome.

Secretion of ectopic adrenocorticotropic hormone (ACTH) with consequently Cushing's syndrome is a rare paraneoplastic phenomenon. It has been described in a variety of malignancies, like bronchial carcinoids, small-cell lung carcinoma, thymoma, pancreatic carcinoma and other. In many cases of suspected ectopic ACTH secretion, it is difficult to histologically or cytochemically confirm the diagnosis. We present a 63-year-old woman with a recurrent poorly differentiated squamous cell lung carcinoma with clinical and biochemical features consistent with ectopic Cushing's syndrome. Immunocytochemical staining confirmed the secretion of ACTH by tumour cells.

Different responses to preoperative chemotherapy for invasive lobular and invasive ductal breast carcinoma.

AIM: Preoperative chemotherapy (PCT) is used in primary breast cancer, to facilitate breast conservative surgery (BCS). Clinical and pathologic responses are important prognostic parameters. Biologic markers are needed to individualize treatment. PATIENTS AND METHODS: One hundred and thirty-five patients with breast carcinoma were treated with PCT, followed by surgery and adjuvant therapy. Clinical response and pathological complete response (pCR), biological markers and type of surgery were compared between invasive ductal (IDC) and invasive lobular carcinoma (ILC). RESULTS: Overall response (OR) for IDC was 75% compared to 50% for ILC (P=0.0151). Pathological CR was 15% for IDC and 0% for ILC (P=0.0066). Fifty-six percent of the responding patients had BCS, in contrast with 16% of the non-responders. BCS was performed in 50% of patients with IDC, in 38% of the patients with ILC. Salvage surgery was more necessary in ILC (19%) compared to IDC (4%) (P=0.0068). Patients with ILC were more frequently ER-positive and HER-2 negative than patients with IDC. CONCLUSIONS: Clinical and pathological responses are lower in ILC compared to IDC. After PCT, patients with large ILC should preferably be offered mastectomy with immediate breast reconstruction. However, PCT still remains valuable to evaluate tumor response and biologic factors in vivo.

The Budd-Chiari syndrome caused by a zygomycete. A new pathogenesis of hepatic vein thrombosis.

The clinical history of a 60-year-old woman suffering from chronic lymphocytic leukemia with sudden deterioration and death is reported. The postmortem macroscopic and microscopic findings included pulmonary aspergillosis and pulmonary zygomycosis (mucormycosis). Hematogenous dissemination of the zygomycete causing cardiac zygomycosis, cerebral infarcts due to vascular occlusion by hyphae, and thrombosis of the major hepatic veins (Budd-Chiari syndrome) with submassive necrosis of the right liver lobe were also observed. To our knowledge, this is the second report dealing with occlusion of the hepatic veins caused by a fungus and the first study reporting the Budd-Chiari syndrome due to a mold of the subclass Zygomycetes.

CEA and HMFG in hyperplastic and malignant lesions of the breast.

In order to evaluate a possible transition from proliferative lesions of the breast to ductal carcinoma in situ (DCIS), an immunohistochemical retrospective analysis was carried out. Twelve patients with hyperplasia without atypia, 11 patients with hyperplastic lesions with atypia, 21 patients with DCIS and 24 patients with invasive carcinoma were studied. The expression of carcino-embryonic antigen (CEA), a dedifferentiation marker, was investigated, applying one monoclonal antibody (Amersham). The expression of human milk fat globulin (HMFG), a differentiation marker, was studied by means of three monoclonal antibodies. The results reveal that no CEA activity can be demonstrated in normal and hyperplastic breast tissue, either with or without atypia. The monoclonal antibody was positive in 48% of DCIS and 50% of the invasive carcinomas. We failed to observe a correlation between the presence of CEA and the differentiation of the tumor. The application of this antiserum adds no substantial information about the phenotypic alterations during the progression from atypical hyperplasia to DCIS. HMFG was present in benign as well as in malignant breast lesions. Therefore, we conclude that HMFG is not useful for the evaluation of the phenotypic change from atypical hyperplasia to malignancy. However, as pointed out by others, it can be used in a diagnostic panel of different antibodies in the distinction between epithelial and non-epithelial lesions.

Feulgen DNA content and mitotic activity in proliferative breast disease. A comparison with ductal carcinoma in situ.

Nuclear Feulgen DNA content was measured by cytophotometry and the number of mitoses per 40 high power fields was determined in hyperplastic and atypical hyperplastic lesions of fibrocystic disease in 18 patients, in ductal carcinoma in situ in 14 patients and in ductal carcinoma in situ associated with infiltrating carcinoma in 11 patients. These parameters were also investigated in the hyperplastic lesions accompanying ductal carcinoma in situ and ductal carcinoma in situ associated with infiltrating carcinoma. The nuclear Feulgen DNA content could not discriminate between atypical hyperplasia and ductal carcinoma in situ. Although differences in the mitotic count between hyperplastic and atypical breast lesions were not statistically significant, there was a statistically significant greater mitotic count in ductal carcinoma in situ alone or associated with infiltrating carcinoma. These findings suggest that the mitotic count is useful for the differential diagnosis between atypical hyperplasia and ductal carcinoma in situ. In addition, hyperplastic lesions associated with ductal carcinoma in situ, with or without infiltrating carcinoma, exhibited a statistically significant higher mitotic count than those in benign fibrocystic disease. Hyperplastic breast lesions exhibiting high mitotic counts may indicate the presence of a neighbouring ductal malignancy and suggest an increased proliferative activity in breast tissue in the neighbourhood of malignancy.

Histogenesis of cholangiomas and cholangiocarcinomas in thioacetamide fed rats.

A sequential, histologic analysis of the livers of male albino rats chronically fed the hepatocarcinogen thioacetamide (TAA) is performed after one, two, three, four, eight and twelve months of treatment. Liver cell alterations present after one, two and three months consist of centrolobular liver cell degeneration and oval cell proliferation. After 8 months of TAA treatment, a variety of benign tumors (cystadenomas, angiomas, cholangiomas) is observed. From the 12th month all experimental animals develop cholangiocarcinomas. Pulmonary metastases are discovered after 15 months. The role of the oval cells in relation to the later appearing cholangiocarcinoma is discussed. A review of literature is given.

Dissociation of glomerular filtration and renal blood flow in HgCl2-induced acute renal failure.

This study evaluates the role of early renal vasoconstriction in the pathogenesis of mercuric chloride (HgCl2)-induced acute renal failure (ARF) in the dog. Within 3 hr after mercury, glomerular filtration rate (GFR), from 45 +/- 4 25 +/- 2 ml/min, and renal blood flow (RBF), from 268 +/- 22 to 161 +/- 19 ml/min, decreased simultaneously. A rise in diuresis and urinary solute excretion occurred. Morphological and functional studies excluded a major role for tubular leakage or obstruction. An attempt was made to prevent the early renal vasoconstriction, by the administration of Haemaccel, a plasma volume expander, alone or in combination with phentolamine. In both settings the fall in RBF after mercury was prevented. Haemaccel volume expansion alone provoked a significant rise in GFR before HgCl2, but the GFR fell by 29% 3 hr after HgCl2. The Haemaccel/phentolamine combination had no influence on pre-mercury GFR values. In this group, a decrease of GFR by 44% was noted 3 hr after mercury. In conclusion, changes in GFR and renal hemodynamics can be dissociated in the early phase of nephrotoxic ARF. The fall in GFR can be attributed either to a decrease in glomerular ultrafiltration capacity and/or changes in glomerular afferent and efferent resistances, leading to a decrease in glomerular hydrostatic pressure.