NF-κB/p65 expression before and after treatment in rectal cancer patients undergoing neoadjuvant (chemo)radiotherapy and surgery: prognostic marker for disease progression and survival.

Nuclear factor-kappaB (NF-κB), especially p65 subunit, has been associated with origin and progression of cancer as well as with the resistance to radiotherapy and chemotherapy in experimental models. The aim of the present study was to determine expression of NF-κB/p65 in tumor specimens before and after treatment of rectal cancer patients and to evaluate possible relationship between expression of NF-κB/p65 before and after (chemo)radiotherapy, other tumor characteristics and the clinical outcome. Furthermore, NF-κB/p65 was studied in relationship to pathologic response to preoperative (chemo)radiotherapy. Fifty patients with rectal cancer undergoing neoadjuvant (chemo)radiotherapy and surgery were included in the study. Pre-treatment rectal cancer specimens were obtained from diagnostic colonoscopy. Post-treatment rectal cancer specimens were obtained from surgically removed part of the rectum with the tumor. NF-κB/p65 expression was determined by immunohistochemistry and analysis was performed both in biopsies and in post-treatment tumor samples. Cytoplasmic positivity in tumor cells and nuclear positivity in lymphocytes were detected. High NF-κB/p65 positivity in pre-treatment tumor samples was significantly associated with shortened overall survival (OS). Disease-free survival (DFS) tends to be shortened as well. In post-treatment tumor samples, high NF-κB/p65 positivity was neither associated with shortened OS nor with shortened DFS. In post-treatment samples residual tumor cells deeply infiltrating the wall of the rectum with high NF-κB/p65 expression were found. The cells were linked to significantly worse clinical outcome in terms of shortened OS and DFS. NF-κB/p65 positivity did not correlate with pathologic response to preoperative (chemo)radiotherapy. In conclusion, our data suggest that high level of NF-κB/p65 subunit may be associated with more aggressive features of the tumor, higher metastatic potential, and shortened overall survival, but it does not correlate with resistance to (chemo)radiotherapy. Consequently, the level of NF-κB/p65 may help to select those patients who have poor prognosis and are candidates for more intensive anticancer therapy. For these purposes both pre-treatment and post-treatment tumor samples may be used.

[NF-kappaB, colorectal carcinoma and radiotherapy: results of a clinical and experimental study]. / NF-kappaB, kolorektální karcinom a radioterapie: výsledky klinické a experimentální studie.

Resistance to radiotherapy often seen in rectal cancer patients requires intensive study of mechanisms taking part in this process. It seems that nuclear factor-kappaB (NF-kappaB), especially its subunit p65, could play an important role in radioresistance. The aims of this study were: 1. to assess expression of p65 in rectal cancer patients and to evaluate its possible predictive role; 2. to determine in in vitro experiments possibilities of p65 modulation and to evaluate, whether this modulation can result in enhacement of efficiency of radiation therapy. We found that the level of NF-kappaB expression may serve as a predictive marker of overall survival. Further we found that inhibition of NF-kappaB activity caused by radiation improves impact of radiation therapy.

Protracted infection of pacemaker leads with development of large vegetations: three years follow up. Case report.

A case history of a patient with permanent pacemaker reports inaccurate diagnosis of inflammation at the site of operation wound and a protracted infection of pacemaker leads. Inadequate therapy led to protracted inflammation with the leads fixed in the superior vena cava and the development of large vegetations in the right heart. Finally, the condition was resolved by surgical explantation and long-term antibiotic therapy. This case history describes infectious complications related to the implantation of a permanent pacemaker and the role of echocardiography in diagnosis of vegetations and points out the surgical treatment as a method of choice.

Marjolin's ulcer.

In 1828 John Nicolas Marjolini characterized ulcer with malignant degeneration which developed in scars after burns, but it occurs under varying clinical conditions. Typical feature is the latent period (on average 30 years). It is encountered in 2 forms: a shallow ulcer or exophytic tumour, most frequently on the lower extremities. At the Prague Burn Centre 11 patients were treated since 1978 till 1998. A unique case was a man suffering from congenital form of epidermolysis bullosa who developed Marjolin's ulcer on his foot (histological examination confirmed well differentiated squamous cell carcinoma). After 4 years he died with extreme cachexia and metastatic spread of the tumour, because he refused repeatedly amputation and lymph nodes dissection. To prevent Marjolin's ulcer several recommendations are presented.

Remodeling of chick embryonic ventricular myoarchitecture under experimentally changed loading conditions.

Adult myocardium adapts to changing functional demands by hyper- or hypotrophy while the developing heart reacts by hyper- or hypoplasia. How embryonic myocardial architecture adjusts to experimentally altered loading is not known. We subjected the chick embryonic hearts to mechanically altered loading to study its influence upon ventricular myoarchitecture. Chick embryonic hearts were subjected to conotruncal banding (increased afterload model), or left atrial ligation or clipping, creating a combined model of increased preload in right ventricle and decreased preload in left ventricle. Modifications of myocardial architecture were studied by scanning electron microscopy and histology with morphometry. In the conotruncal banded group, there was a mild to moderate ventricular dilatation, thickening of the compact myocardium and trabeculae, and spiraling of trabecular course in the left ventricle. Right atrioventricular valve morphology was altered from normal muscular flap towards a bicuspid structure. Left atrial ligation or clipping resulted in hypoplasia of the left heart structures with compensatory overdevelopment on the right side. Hypoplastic left ventricle had decreased myocardial volume and showed accelerated trabecular compaction. Increased volume load in the right ventricle was compensated primarily by chamber dilatation with altered trabecular pattern, and by trabecular proliferation and thickening of the compact myocardium at the later stages. A ventricular septal defect was noted in all conotruncal banded, and 25% of left atrial ligated hearts. Increasing pressure load is a main stimulus for embryonic myocardial growth, while increased volume load is compensated primarily by dilatation. Adequate loading is important for normal cardiac morphogenesis and the development of typical myocardial patterns.

Clear cell malignant myoepithelioma of the salivary glands.

Previous reports of monomorphic clear cell carcinoma of the salivary glands have shown inconsistent results with immunohistochemistry, especially for S-100 protein, and this has led to uncertainty about the nature of these tumours. We believe that much can be explained by considering this group as comprising not one but two separate neoplasms, one epithelial and the other myoepithelial. The former has been described as hyalinizing clear cell carcinoma--it generally occurs in the minor salivary glands, and strongly expresses cytokeratins but not S-100 protein or alpha smooth muscle actin. In contrast, this study presents five primary malignant tumours of the major salivary glands also composed largely of a single population of clear cells, but displaying histological and immunohistochemical features of myoepithelial differentiation, such as the formation of collagenous spherules and expression of S-100 protein and actin. A small number of similar tumours have been reported previously. We, therefore, believe that these neoplasms represent a clear cell variant of malignant myoepithelioma (myoepithelial carcinoma).

Parietal cell carcinoma of the stomach.

Two cases of parietal cell carcinoma are reported and compared with seven cases previously described. Eight of nine patients have been male. The tumours grow mainly outside the mucosa and can macro- and microscopically be misinterpreted as leiomyoblastomas or lymphomas. The survival, also with metastases, is long. The proper diagnosis requires ultrastructural investigation.

Bilateral and multifocal breast carcinoma. A clinical and autopsy study with special emphasis on carcinoma in situ.

Bilateral clinical breast carcinoma has been reported to appear in up to approximately 10% of patients with breast carcinoma. Increasing diagnostic activity has raised figures of bilaterality, mainly due to detection of lesions of the in situ type. Knowledge of the natural history of carcinoma in situ is incomplete and clinical implications are uncertain. In the present study bilateral lesions were analysed by extensive histological examination in the following groups of patients: (1) Forty-six women (median age 44 years) with clinical and mammographical unilateral invasive breast carcinoma, where the contralateral breast was removed at subcutaneous mastectomy (SCM) during the course of breast reconstruction, 24/46 (52%) had bilateral malignant lesions, four invasive carcinomas and 20 in situ carcinomas (two ductal carcinomas in situ /DCIS/, 15 lobular carcinomas in situ (LCIS), three both DCIS and LCIS). (2) Fifty-two women (median age 50 years) with a unilateral diagnosis of in situ carcinoma (32 DCIS, 16 LCIS, four both DCIS and LCIS), in whom both breasts were removed at SCM. 25/52 (48%) had bilateral malignant lesions, one invasive carcinoma, 24 in situ carcinomas (three DCIS, 18 LCIS, three both DCIS and LCIS). Twelve of 20 cases with LCIS (60%) were bilateral. Of 36 cases with DCIS, seven (19%) were bilateral. (3) The contralateral breast was removed at autopsy in 64 women previously unilaterally mastectomized (at median age 65) for invasive breast carcinoma. Fifteen of 64 (23%) had contralateral primary carcinoma at autopsy, four invasive carcinomas, 11 in situ carcinomas (six DCIS, five LCIS) and 8/64 (13%) had metastases in the breast. Multifocal malignant findings were also analysed in 47 SCM specimens after excisional biopsy for in situ carcinoma. In 35/47 (75%) further malignant lesions were present in spite of normal mammographic and clinical findings. Four were invasive and 31 had in situ lesions (16 DCIS, 10 LCIS, five both DCIS and LCIS): These findings may favour the hypothesis that some carcinomas in situ may remain silent or even regress. It is thus important to embark upon randomized trials to clarify the natural history of breast carcinoma in situ. Such a trial has been started in the southern region of Sweden.

Formation of the heart loop and proliferation structure of its wall as a base for ventricular septation.

Controversial criteria for definition and classification of univentricular hearts are discussed from the point of view of proliferation pattern in the wall of heart tube and heart loop stage. The persistence of the primitive diffuse proliferation structure is the condition for the development of univentricular heart in which the morphogenetic mechanism forming the ventricular septum does not operate. Pseudouniventricular heart, i.e. the heart with the large main chamber accompanied by a small accessory cavity, is the result of total or partial right or left hypoplasia in which the extent of operation of the above mentioned mechanism is determined by the degree of ventricular hypoplasy. The morphogenesis of the heart wall structure and relief including the atrioventricular and arterial valves is a secondary feature, mostly dependent on the changed hemodynamic conditions.

Experimental cardiac necrosis in hypobaric and anemic hypoxia.

Resistance to isoproterenol-induced cardiac necrosis (IPRO) was compared in rats exposed to two types of hypoxia (i.e., hypobaric and anemic). IPRO was induced by two consecutive, subcutaneous injections of isoproterenol (80 mg/kg) at 24-h intervals. The animals were killed on the third day and the severity of the lesion was evaluated on a 0 (no damage) to 4 (severely damaged) scale. White male rats (HA) were exposed in a barometric chamber to a simulated altitude of 7,000 m (307 mmHg) for 4 h/day for 24 days. Two groups of control rats were kept at sea level; one group (SLA) was the same age and one group (SLW) was the same weight as the altitude-exposed rats. The HA rats were significantly more resistant to IPRO with a mean necrogenic rating of 1.8 compared to 3.3 for the SLA and SLW rats. Infant rats (AA) were made anemic by feeding full-cream milk and glucose for 100 days after weaning. Two groups of control animals were fed a standard laboratory diet; one group (AC) was the same age and one group (AW) was the same weight as the AA rats. There was no significant difference in the necrogenic ratings of the AA (3.3), AC (3.5), or WC (3.7) hearts. Thus, hypobaric hypoxia affords some protection against IPRO which is not afforded by anemic hypoxia. Similarities and differences in the two hypoxias are discussed.

Inhalatory infection of mice with influenza A0/PR8 virus. II. Detection of the virus in the blood and extrapulmonary organs.

In the course of experimental aerosol infection of mice with influenza A virus, the latter was regularly detected in the blood, liver, salivary glands, spleen, pancreas, kidneys, heart and irregularly in cervical and mediastinal lymph nodes. The findings of extrapulmonary virus were in direct quantitative relationship to the rate of lung involvement.