Current concepts of tumour metastasis

Background: Tumour metastasis remains the principal cause of treatment failure and poor prognosis in patients with cancer. Recent advances in our understanding of the biology of metastasis are providing novel potential targets for anti-cancer therapies. Aim: This paper reviews the current concepts in tumour metastasis. Methods: A review of Medline publications relating to the molecular biology and therapy of human tumour metastasis was conducted. Results and Discussion: Early metastasis models were based upon the premise of uninterrupted tumour growth, with the inevitable formation of distant metastases and eventual death of the patient. However, current research suggests that metastasis is an inefficient process governed by several rate-limiting steps, and that failure to negotiate these steps can lead to tumour dormancy. Successful metastatic tumour growth depends upon appropriate tumour-host microenvironment interactions and, ultimately, the development of vascularised metastases post-extravasation in the target organ. An understanding of the molecular mechanisms involved in this dynamic process will aid in the identification of therapeutic targets that may allow earlier diagnosis and more specific therapies for patients with metastasis.

Assessing the effectiveness of a mammography screening service

Background: Trials have shown that mammography screening reduces mortality and probably decreases morbidity related to breast cancer. Methods: We assessed whether the major mammography service in Western Australia (BreastScreen WA) is likely to reduce mortality by comparing prognostic variables between screen-detected and other cases of breast cancer diagnosed in 1999. We assessed likely reductions in morbidity by comparing treatments received by these two groups. To confirm mortality and morbidity reduction, we also compared prognostic variables and treatments with targets. Information on demographic variables, tumour characteristics at presentation and treatments were collected from medical records for all incident cases of breast cancer in Western Australia in 1999. We matched cases with the Western Australian Cancer Registry records to determine which cases had been detected by BreastScreen WA. Results: BreastScreen WA achieved the targets for mortality reduction. Tumours detected by BreastScreen WA were smaller in size, less likely to have vascular invasion, of lower histological grade and were more likely to be ductal carcinoma in situ alone without invasive carcinoma. Oestrogen receptor status was more likely to be positive, the difference in progesterone status was not significant, and lymph node involvement tended to be lower. BreastScreen WA patients were treated more often with local therapy and less often with systemic therapy, and the proportion of patients treated with breast-conserving surgery was close to the target for minimizing morbidity in breast cancer. Conclusion: Mammographic detection of breast cancer by BreastScreen WA is associated with reduced breast cancer morbidity and a more favourable prognosis.

Genetics and genomics of osteoclast differentiation: Integrating cell signaling pathways and gene networks

The regulation of osteoclast differentiation in the bone microenvironment is critical for normal bone remodeling, as well as for various human bone diseases. Over the last decade, our knowledge of how osteoclast differentiation occurs has progressed rapidly. We highlight some of the major advances in understanding how cell signaling and transcription are integrated to direct the differentiation of this cell type. These studies used genetic, molecular, and biochemical approaches. Additionally, we summarize data obtained from studies of osteoclast differentiation that used the functional genomic approach of global gene profiling applied to osteoclast differentiation. This genomic data confirms results from studies using the classical experimental approaches and also may suggest new modes by which osteoclast differentiation and function can be modulated. Two conclusions that emerge are that osteoclast differentiation depends on a combination of fairly ubiquitously expressed transcription factors rather than unique osteoclast factors, and that the overlay of cell signaling pathways on this set of transcription factors provides a powerful mechanism to fine tune the differentiation program in response to the local bone microenvironment.

Characterisation of the signalment, clinical and survival characteristics of 41 cats with mast cell neoplasia

Mast cell tumours (MCTs) are relatively common tumours of cats, and are the second most common cutaneous tumours in cats in the USA. While the primary splenic form of the disease is far less common, it is usually associated with more severe clinical signs. Signalment, clinical and survival characteristics of mast cell neoplasia were characterised in 41 cats. The most common tumour location was cutaneous/ subcutaneous head and trunk. Stage la was the most common tumour stage at first diagnosis (n = 20), followed by stage 4 (both stage 4a and stage 4b; n = 10). Of 22 cats that underwent excisional biopsy, mast cell neoplasia recurred in four cats during the study period. Three of the 41 cats presented with simultaneous cutaneous and either splenic or lymph node tumours. A comparison between cats with only cutaneous tumours (n = 30) and those with tumours involving the spleen or lymph nodes (n = 11) showed longer survival times for the cutaneous-only group (P = 0.031). Twelve of the 41 cats died of mast cell neoplasia during the study period. When a subgroup of cats with only cutaneous tumours (no lymph node or visceral involvement) were divided according to whether there were multiple (five or more) tumours (n = 6) or a single tumour (n = 19), cats with single tumours survived longer than those with multiple tumours (P = 0.001). Solitary cutaneous feline MCTs without spread to the lymph nodes usually manifest as benign disease with a relatively protracted course. However, multiple cutaneous tumours, recurrent tumours and primary splenic disease should receive a guarded prognosis due to the relatively short median survival times associated with these forms of the disease. (C) 2006 ESFM and AAFR Published by Elsevier Ltd. All rights reserved.

Correlation of T-cell immune response with spontaneous resolution and subsequent relapse of Hodgkin's lymphoma

To our knowledge, there has been no report of spontaneous regression in a non-immunocompromised adult with classical Hodgkin's lymphoma (HL) in the absence of chemotherapy. We describe spontaneous regression and subsequent relapse of Epstein - Barr virus (EBV)-positive HL in an otherwise healthy male adult. The clinical course was associated with an increase in regulatory T-cell markers within the peripheral blood and diseased lymph node at the time of relapse and with a concomitant reduction in cellular immunity against relevant EBV latent membrane protein tumor-associated antigens. Our findings are in keeping with previous observations that implicate impaired cellular immunity in the immunopathogenesis of EBV-positive HL.

Probability of axillary node involvement in patients with tubular carcinoma of the breast

The aim of this study was to investigate the frequency of axillary metastasis in women with tubular carcinoma (TC) of the breast. Women who underwent axillary dissection for TC in the Western Sydney area (1984-1995) were identified retrospectively through a search of computerized records. A centralized pathology review was performed and tumours were classified as pure tubular (22) or mixed tubular (nine), on the basis of the invasive component containing 90 per cent or more, or 75-90 per cent tubule formation respectively. A Medline search of the literature was undertaken to compile a collective series (20 studies with a total of 680 patients) to address the frequency of nodal involvement in TC. A quantitative meta-analysis was used to combine the results of these studies. The overall frequency of nodal metastasis was five of 31 (16 per cent); one of 22 pure tubular and four of nine mixed tumours (P = 0.019). None of the tumours with a diameter of 10 mm or less (n = 16) had nodal metastasis compared with five of 15 larger tumours (P = 0.018). The meta-analysis of 680 women showed an overall frequency of nodal metastasis in TC of 13.8 (95 per cent confidence interval 9.3-18.3) per cent. The frequency of nodal involvement was 6.6 (1.7-11.4) per cent in pure TC (n = 244) and 25.0 (12.5-37.6) per cent in mixed TC (n = 149). A case may be made for observing the clinically negative axilla in women with a small TC (10 mm or less in diameter).

Sentinel node biopsy for breast cancer: Using local results for estimation of risk to the patient

Background: Sentinel node biopsy (SNB) is being increasingly used but its place outside randomized trials has not yet been established. Methods: The first 114 sentinel node (SN) biopsies performed for breast cancer at the Princess Alexandra Hospital from March 1999 to June 2001 are presented. In 111 cases axillary dissection was also performed, allowing the accuracy of the technique to be assessed. A standard combination of preoperative lymphoscintigraphy, intraoperative gamma probe and injection of blue dye was used in most cases. Results are discussed in relation to the risk and potential consequences of understaging. Results: Where both probe and dye were used, the SN was identified in 90% of patients. A significant number of patients were treated in two stages and the technique was no less effective in patients who had SNB performed at a second operation after the primary tumour had already been removed. The interval from radioisotope injection to operation was very wide (between 2 and 22 h) and did not affect the outcome. Nodal metastases were present in 42 patients in whom an SN was found, and in 40 of these the SN was positive, giving a false negative rate of 4.8% (2/42), with the overall percentage of patients understaged being 2%. For this particular group as a whole, the increased risk of death due to systemic therapy being withheld as a consequence of understaging (if SNB alone had been employed) is estimated at less than 1/500. The risk for individuals will vary depending on other features of the particular primary tumour. Conclusion: For patients who elect to have the axilla staged using SNB alone, the risk and consequences of understaging need to be discussed. These risks can be estimated by allowing for the specific surgeon's false negative rate for the technique, and considering the likelihood of nodal metastases for a given tumour. There appears to be no disadvantage with performing SNB at a second operation after the primary tumour has already been removed. Clearly, for a large number of patients, SNB alone will be safe, but ideally participation in randomized trials should continue to be encouraged.

Participation in the RACS sentinel node biopsy versus axillary clearance trial

Background: The Royal Australasian College of Surgeons (RACS) SNAC trial is a randomized controlled trial of sentinel node biopsy (SNB) versus axillary clearance (AC). It opened in May 2001 and is recruiting rapidly with good acceptance by consumers. Methods: A study of eligibility and treatment choices was conducted between November 2001 and September 2002 for women presenting with early breast cancer to 10 centres participating in the trial. Results: More than half of the 622 women (54%) were ineligible for trial entry because they had large (> 3 cm) or multicentric cancers. Participation was offered to 92% of eligible women and was taken up by 63%. The commonest reason for not participating was the desire to choose treatment rather than have it randomly allocated. Despite this there is a great acceptance of clinical trials because very few women (4% of those eligible) gave 'lack of interest in clinical trials' as the reason for non-participation. Few women who declined trial participation chose to have SNB alone (4.5% of those eligible). Conclusion: Sentinel node biopsy may become the standard of care for managing small breast cancers, but a significant number of patients will still require or choose axillary dissection. Results from large randomized trials are needed to determine the relative benefits and harms of SNB compared with AC. Surgeons must carefully discuss options for management with their patients.

A consistent point-searching algorithm for solution interpolation in unstructured meshes consisting of 4-node bilinear quadrilateral elements

To translate and transfer solution data between two totally different meshes (i.e. mesh 1 and mesh 2), a consistent point-searching algorithm for solution interpolation in unstructured meshes consisting of 4-node bilinear quadrilateral elements is presented in this paper. The proposed algorithm has the following significant advantages: (1) The use of a point-searching strategy allows a point in one mesh to be accurately related to an element (containing this point) in another mesh. Thus, to translate/transfer the solution of any particular point from mesh 2 td mesh 1, only one element in mesh 2 needs to be inversely mapped. This certainly minimizes the number of elements, to which the inverse mapping is applied. In this regard, the present algorithm is very effective and efficient. (2) Analytical solutions to the local co ordinates of any point in a four-node quadrilateral element, which are derived in a rigorous mathematical manner in the context of this paper, make it possible to carry out an inverse mapping process very effectively and efficiently. (3) The use of consistent interpolation enables the interpolated solution to be compatible with an original solution and, therefore guarantees the interpolated solution of extremely high accuracy. After the mathematical formulations of the algorithm are presented, the algorithm is tested and validated through a challenging problem. The related results from the test problem have demonstrated the generality, accuracy, effectiveness, efficiency and robustness of the proposed consistent point-searching algorithm. Copyright (C) 1999 John Wiley & Sons, Ltd.

A Century of Change in Coral Reef Status in Southeast and Central Pacific: Polynesia Mana Node, Cook Islands, French Polynesia, Kiribati, Niue, Tokelau, Tonga, Wallis and Futuna

The Polynesia Mana Node of the southeast and central Pacific contains 7 independent or autonomous countries or territories with only 6,000 km2 of land on 347 islands, but surrounded by 12 million km2 of EEZ. These seas contain 13,000 km2 of coral reefs as the main natural ecosystem providing food resources and opportunities for development, especially for tourism and pearl culture for 500,000 inhabitants. During the 19th and first half of the 20th centuries, there was major exploitation by the colonial powers of mother-of-pearl oysters for the button industry, as well as guano, sandalwood and trepang. The Polynesian people were largely involved in a subsistence economy and all coral reefs and lagoons were healthy. During the last two decades of the 20th, all countries experienced rapid development and urbanization, rising populations, and some increased agriculture. These developments were limited to a few islands of each country (i.e. 15 islands amongst the 347) with resulting degradation of the coral reefs around these sites. The other islands remained mostly uninhabited and pristine, and continued with a subsistence economy. Generally, there was more damage to the coral reefs through natural events such as cyclones and coral bleaching, than by human activities. There is however, an urgent need to combat the threats on some islands from increased sedimentation, over-fishing, dredging and nutrient pollution.

Applying statistical approaches in the dissection of genes versus environment for asthma and allergic disease

Now that some of the genes involved in asthma and allergy have been identified, interest is turning to how genetic predisposition interacts with exposure to environmental risk factors. These questions are best answered by studies in which both genotypes and other risk factors are measured, but even simpler studies, in which family history is used as a proxy for genotype, have made suggestive findings. For example, early breast feeding may increase the risk of allergic disease in genetically susceptible children, and decrease the risk of 'sporadic' allergy. This review also addresses the overall importance of genetic causes of allergic disease in the general population.

Postoperative vaginal vault brachytherapy for node-negative Stage II (occult) endometrial carcinoma

Objective. The aim of this study is to look at the efficacy of extended surgical staging and postoperative vaginal vault brachytherapy in patients with Stage II (occult) endometrial carcinoma. Methods. Between January 1989 and December 1997, there were 30 patients with Stage II (occult) endometrial carcinoma who received postoperative vaginal vault brachytherapy as the only adjuvant treatment. The study group consisted of 15 of these patients who had extended surgical staging (including lymphadenectomy). Results. At a median follow-up of 36 months (range 17 to 113 months), there has been no recurrence. There were no major complications from surgery. Only 1 patient had mild rectal bleeding following vaginal vault brachytherapy and there were no grade 3 or 4 bowel toxicities. Conclusions. Extended surgical staging and postoperative vaginal vault brachytherapy for Stage II (occult) endometrial carcinoma is associated with minimal morbidity and excellent survival. (C) 2001 Academic Press.