"Micrometastases": the pathologist's point of view]

The development of cancer screening has led to the discovery of smaller tumours and less frequent dissemination to lymph nodes and organs that requires special techniques for detection. Numerous papers on micrometastases reflect a considerable amount of work devoted to detection methods, technical problems and the prognostic value of these lesions. Apart from cytological techniques, the pathologist can rely on two methods for the detection of micrometastases: serial slicing of paraffin-embedded blocks and immunohistochemistry. When these methods are combined, the detection rate is similar to that of biological methods and can attain levels as high as 60% for the sentinel node with the added vantage of being able to visualise cells. Despite an impressive body of studies, major disparities are found in detection rates and the prognostic value of micrometastases is not firmly established. In order to facilitate comparisons and analyses, it is essential to adopt a common terminology with precise definitions. The UICC advocates the use of the term micrometastasis which denotes a metastasis smaller than or equal to 2 mm in size. The potential aggressiveness of micrometastases is dependent on other poorly explored parameters such as the number of cells detected in the bone marrow or lymph node and the location of micrometastases. The new pTNM classification takes into account this latter parameter and distinguishes two categories of micrometastases: "isolated tumor cells" located in the lumen of vessels or sinuses and "micrometastasis" which has already invaded an organ. This classification warrants further analysis to determine the prognostic value of these categories. The next challenging problem consists in determining the key biological properties that account for distant dissemination.     

Prospects for a better diagnosis and prognosis of NAFLD: a pathologist's view

Despite the development of surrogate non-invasive methods, histological evaluation remains an important tool for reliable classification, grading and staging, a...     

Home infusion therapy system from a resident's point of view

We started a new home infusion therapy system in July 1999. The home infusion therapy system is made up of doctors, nursing stations, and pharmacies in the community. We coordinate these parties before patient discharge from our hospital and support them when the patient needs hospitalization (for example, he or she develops pneumonia). This report discusses past experiences and future issue.     

The pathologist's examination of the "lumpectomy"--the pathologists' view of surgical margins.

Despite the widespread conservative management of breast cancer, the pathologists' examination of these specimens is far from uniform. Pathologists sample margins differently, and even disagree on what constitutes a positive margin. This variability in the pathologic examination of the lumpectomy creates tremendous problems in analyzing the existing literature on the importance of positive margins. Herein is a discussion of the available data on the significance of margin assessment. We furthermore suggest a practical approach to examining margins with an emphasis on a functional orientation of the specimen with respect to the nipple. Only by adopting a uniform system of margin assessment can we begin to critically evaluate the importance of positive margins in segmental resections of the breast.     

Characteristics of radiation-induced neoplastic transformation in vitro

Data are presented to support the hypothesis that the initial step in the morphologic transformation of irradiated rodent cells is a frequent cellular event involving a large fraction of the irradiated population. This process appears to involve DNA damage, but not to represent a targeted mutation in specific structural gene(s). Morphologic transformation and immortalization appear to be distinct steps in the overall process of transformation. In contradistinction to rodent cells, immortalization is a very rare event in human diploid cells which is induced at extremely low frequencies. The hypothesis is presented that immortality develops among clones of cells bearing stable chromosomal rearrangements which emerge during the proliferation of a population of radiation damaged cells.     

The role of nitric oxide in neoplastic transformation of C3H 10T1/2 embryonic fibroblasts

Nitric oxide synthase inhibitors block the neoplastic transformation of C3H 10T1/2 cells in vitro. Evidence presented herein suggests that they mediate their effects early in the carcinogenic process as brief treatment with the NOS inhibitor aminoguanidine (AG) during log phase cell growth (initiation phase) is sufficient to block foci formation. In contrast, treatment initiated after formation of a confluent monolayer was associated with diminished protection, while treatment commencing late in the promotional phase had no protective effect and appeared to enhance the number and stage of foci observed. These findings suggest that while AG treatment can inhibit transformation during the early promotional phase, it most effectively inhibits transformation during the initiation phase. In general AG enhanced growth of both normal and tumor cells, suggesting that effects on growth were unrelated to its anti-transformation properties, however, these effects could be related to the effect on tumor cell stage noted above. Although induction of inducible nitric oxide synthase (iNOS) by treatment with LI during the last 2 weeks of the assay was associated with enhanced transformation, the efficacy of AG in protecting against transformation was not clearly associated with substantial reductions in NO synthesis. The data suggest that AG inhibits transformation early in the transformation process independently of iNOS inhibition and that AG may have deleterious effects late in the process, possibly through stimulation of tumor cell growth.     

The molecular point of view of hepatocellular carcinoma

Carotid blow-out syndrome is the most dreaded complication in head and neck surgical oncology practice This article describes a simple technique of interposition of sternocleidomastoid muscle between pharynx and carotid sheath to isolate the latter from salivary contamination in the event of salivary leak. Authors have used this technique in 83 laryngectomies with excellent results.     

Stepwise neoplastic transformation of a telomerase immortalized fibroblast cell line

We have described recently a human fibroblast cell line immortalized through ectopic telomerase expression (cen3tel), in which the extension of the life span was associated with the appearance of chromosomal aberrations and with the ability to grow in the absence of solid support. As reported in this article, on further propagation in culture, cen3tel cells became neoplastically transformed, being able to form tumors in nude mice. The analysis of the cells, during the gradual transition toward the tumorigenic phenotype, allowed us to trace cellular and molecular changes associated with different phases of transformation. At the stage in which they were able to grow in agar, cen3tel cells had lost contact growth inhibition but still retained the requirement of serum to proliferate and were not tumorigenic in immunocompromised mice. Moreover, they showed a down-regulation of the INK4A locus and were resistant to oncogenic Ras-induced senescence but still retained a functional p53. Subsequently, cen3tel cells became tumorigenic, lost p53 function because of a mutation in the DNA-binding motif, and overexpressed c-myc. Interestingly, tumorigenic cells did not carry activating mutations either in the ras proto-oncogenes (H-ras, N-ras, and K-ras) or in B-raf. Cen3tel cells gradually became hyperdiploid but did not display centrosome abnormalities. To our knowledge, cen3tel is the first telomerase immortalized fibroblast line, which became neoplastically transformed. In this system, we could associate a down-regulation of the INK4A locus with anchorage-independent growth and with resistance to Ras-induced senescence and link p53 mutations and c-myc overexpression with tumorigenicity.     

Brain metastases: a neurosurgical point of view

The question of accessibility to the recent development of diagnostic and therapeutic tools for brain metastasis patients remains a problem. Advances in neurosurgery, new fields in chemotherapy, radiosurgery and different types of radiation therapy are accompanied by the need of dedicated staff time and materials. The limits of what we can offer to our patients regarding access to treatment and costs have to be clarified through a national consensus. Multimodal strategies must take in account the individual patient as well as accessibility to the different treatment tools. The most important problem remain the ongoing need for radiosurgery and various subtype of new radiotherapy methods.