Expression of neutrophil gelatinase-associated lipocalin in colorectal neoplastic progression: a marker of malignant potential?

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) has a diverse functional repertoire, involved in the innate immune response as well as cell growth and differentiation. Expression has been linked to malignant disease development and progression. METHODS: Neutrophil gelatinase-associated lipocalin expression was assessed immunohistochemically in 98 colorectal neoplastic lesions (52 cancer polyps (CaPs) and 46 sporadic adenoma/adjacent normal mucosa paired specimens) to investigate association with adenoma progression and early colorectal carcinogenesis. RESULTS: Within CaPs, all adenomatous and carcinomatous epithelium expressed NGAL, with 92% (43 out of 47) and 58% (19 out of 33) epithelial positivity, respectively, as well as positive stromal cell expression. This was significantly increased compared with normal mucosal epithelium (P=0.0001). Neutrophil gelatinase-associated lipocalin positivity was also identified in sporadic low-grade adenomas, in both the epithelial and stromal compartments as compared with adjacent normal mucosa (P=0.0001 and 0.0002), and this increased along with adenoma size >1 cm (P=0.03). CONCLUSION: Neutrophil gelatinase-associated lipocalin is expressed by the majority of human neoplastic colorectal lesions. This phenotypic switch occurs at an early stage in neoplastic progression with clear differential expression between normal mucosa and adenomatous polyps, rather than further downstream in disease progression at the adenoma-carcinoma transformation. Thus, NGAL expression is not a useful biomarker for determining disease progression from adenomatous to malignant colorectal neoplasia.

COX-2 expression in sporadic colorectal adenomatous polyps is linked to adenoma characteristics.

AIMS: To assess cyclooxygenase-2 (COX-2) expression in sporadic colonic adenomas and to explore the association of COX-2 positivity with adenoma characteristics linked to increased risk of malignant transformation. METHODS AND RESULTS: COX-2 expression and localization were assessed in 64 colorectal adenomas and 35 paired adjacent normal colonic mucosal biopsy specimens. The number of adenoma specimens was then extended to include polyps exhibiting an increasing degree of epithelial dysplasia. Forty colonic hyperplastic polyps were also identified from the pathology diagnostic database and included in the analysis. Immunohistochemistry was performed with the Envision+ peroxidase-linked biotin-free system incorporating a signal amplification step. There was a statistically significant increase in COX-2 expression in colonic polyps compared with paired adjacent normal mucosa, chi(2) = 40.1, P = 0.001. The probability of COX-2 expression increased along with increasing adenoma size and increasing degree of epithelial dysplasia. Fifty-five per cent of the hyperplastic polyp specimens expressed COX-2. CONCLUSIONS: This study associates COX-2 epithelial expression with a number of adenoma characteristics that convey an increased risk of malignant transformation. This is in keeping with a positive role for COX-2 in early colorectal carcinogenesis.

Thyroid transcription factor 1 in pulmonary adenocarcinoma.

AIMS: To discover whether variations in thyroid transcription factor 1 (TTF-1) staining in different subtypes and patterns of pulmonary adenocarcinoma are related to the putative origin of the tumour. In addition, to confirm the specificity of TTF-1 for pulmonary (as opposed to other sites) adenocarcinoma, to examine the possible prognostic relevance of TTF-1 positivity in lung cancer, and to review this laboratory's experience of TTF-1 in diagnostic practice. MATERIALS/METHODS: In total, 128 primary lung adenocarcinomas, 106 primary non-pulmonary adenocarcinomas, and 37 pulmonary non-adenocarcinoma tumours were studied. In addition, 100 cases where TTF-1 was used in routine surgical pathology practice were investigated. Immunoperoxidase staining was performed on formalin fixed, paraffin wax embedded sections using anti-TTF-1 antibody. Staining was evaluated semiquantitatively using the frequency and intensity of nuclear positivity. RESULTS: None of the 106 non-pulmonary adenocarcinomas expressed TTF-1 and only three of the 37 non-adenocarcinoma lung cancers, all neuroendocrine carcinomas, were positive. Of the pulmonary adenocarcinomas, 75% were strongly positive for TTF-1. Mucinous (two of six) and poorly differentiated adenocarcinomas (four of 10) were less likely to stain. Of the peripheral adenocarcinomas, 33 of 37 were positive, whereas only seven of 14 of those of bronchial origin stained strongly. Atypical adenomatous hyperplasia strongly expressed TTF-1. No "false positives" were encountered in the 100 routine diagnostic cases. CONCLUSION: Positive TTF-1 staining is useful in the differential diagnosis of pulmonary adenocarcinomas. TTF-1 may be a lineage marker for tumours arising from the peripheral airway or alveolar epithelium and has no prognostic relevance.

Prosthetic rehabilitation of amputees aged over 90 is usually successful.

Prosthetic rehabilitation and prosthetic limb use in patients over 90 years of age have not been studied in detail. This study reports two concurrent successful cases and a review of registered patients aged over 90. Satisfactory outcomes often occur in this population and such patients should be referred for prosthetic rehabilitation, regardless of advanced age.

Effectiveness of rehabilitation following amputation.

For many patients, the outcome of rehabilitation following amputation depends substantially on comorbidity. This is particularly so where amputation is performed because of peripheral vascular disease which may involve other end-organs, but also applies in trauma where loss of limb may not be the only injury. In evaluating outcome, measures must take account of the very different goals for rehabilitation. These may range from cosmesis or the simple ability to transfer from bed to chair, to successful competition in the Para-Olympics. Rehabilitation programmes for amputees are not simply prosthetic services, but must take account of the whole patient, their goals and ambitions. Research to date has made a contribution in identifying prognostic factors for prosthetic rehabilitation, thus helping to target limited resources. Controlled studies are still required, however, to establish the optimum services to offer to different groups of patients.

Follicular keratoses at amputation sites.

We describe two patients with painful follicular keratoses at lower limb amputation sites. Subsequent examination of 31 amputees revealed evidence of keratoses in four of 28 patients with lower limb stumps. Two of the four affected subjects experienced stump pain exacerbated by weight-bearing. This problem is not well documented. Local treatment measures may be ineffective. Painful stump follicular keratoses may be a cause of significant morbidity in lower limb amputees, and may be the result of an ill-fitting prosthesis.

Ranges of movement at the shoulder complex using an electromagnetic movement sensor.

There are few published data on the ranges of available motion at the shoulder and no clinical technique for the assessment of three dimensional movement. An electromagnetic movement sensor (Isotrak), which makes three dimensional measurements of shoulder movement and measures the ranges of flexion, extension, abduction in the neutral position, abduction preceded by external rotation, and internal rotation achieved by placing the hand as far up the back as possible, was used to study 16 normal subjects. Intraobserver repeatability was good, and a study of five subjects by two observers showed no significant difference between single measurements made by each. The measured ranges were in broad agreement with published data, though they tended to be smaller. This was attributed to either the bulk of the mounting for the movement sensor or to the immobilisation of the elbow and hence the biceps muscle. Women had greater ranges, except for externally rotated abduction.

An audit of amputation levels in patients referred for prosthetic rehabilitation.

Most lower limb amputations in the United Kingdom (UK) are carried out within general surgical, orthopaedic and plastic surgical units of district hospitals. This study of patients referred for rehabilitation was undertaken to determine the number and specialty interests of surgeons referring amputees, the numbers referred by each and, as one of several possible measures of appropriateness for rehabilitation, the amputation levels in patients referred for the first time to one sub-regional Disablement Services (limb fitting) Centre (DSC) over a 14 month period. Thirty nine surgeons, referred 263 amputees. The majority (61%) of surgeons referred 5 or fewer: a nucleus of 11 vascular surgeons (28%) referred 64% of the patients. The underlying pathology, specialty interest of the surgeon or numbers referred by individual surgeons had no relation to final healed level which was below the knee in 55% of cases compared to national figures for all other DSC's ranging between 39% and 48% below-knee between 1981 and 1988. Since current practice in the UK is to refer all but the frailest patients for consideration of prosthetic rehabilitation, this study suggests that, nationally, more patients could be suited for the functionally superior below-knee level of amputation than are currently benefiting from it.

Bile peritonitis after removal of T-tubes from the common bile duct.

Bile peritonitis can occur when a T-tube is electively removed from the common bile duct, but this is regarded as a rare complication. Plastic T-tubes are known to increase the risk and should not be used. Latex rubber T-tubes are preferred but the complication can still occur. We present three patients with this complication despite the use of a latex T-tube. A questionnaire was sent to 107 surgeons in the South East Thames Region. The replies showed that the complication is far more common than generally realized. Based on these replies the risk of bile peritonitis each time a latex T-tube is electively removed from the common bile duct is calculated to be 0.84 per cent or 1 in every 119 explorations.

The effects of silica on lymph nodes and vessels--a possible mechanism in the pathogenesis of non-filarial endemic elephantiasis.

Non-filarial tropical elephantiasis, which occurs in certain volcanic areas of the world, has been postulated to be an obstructive lymphopathy due to the fibrogenic effects of silica absorbed through the plantar skin of bare-footed people. Animal experiments involving the direct intralymphatic injection of fine silica particles have been carried out in order to assess the extent to which this substance can engender lymphatic obstruction and to determine its main site of action. Intralymphatic silica provoked an immediate and intense macrophage reaction with later fibrosis both within lymph vessels and to a lesser extent within lymph nodes. Lymphography indicated that the consequent obstruction resulted more from the effects of silica on vessels than on nodes.

The distribution of an oil-based corticosteroid following intralymphatic infusion.

Following infusion of tritium labeled clobetasol propionate in Ultrafluid Lipidol (UFL) into a right hind limb lymphatic of rabbits, the radioactivity levels in various tissues at intervals up to 28 days were determined by liquid scintillation counting. There was a rapid decline in activity in the right popliteal node over the first three days due to early bloodstream absorption. From three to 28 days radioactivity levels were consistently higher in the right popliteal node and lung than in other tissues sampled. This distribution suggests that there is an affinity between clobetasol and the lipidol vehicle which retards (but does not prevent) free diffusion of this agent out of lymphatic tissues. Thus, while permitting generalized perfusion of tissues by clobetasol propionate, intralymphatic infusion maximizes its initial concentration and duration of activity within specific node groups and, therefore, may be useful in certain patients with primary lymphedema where lymph nodes affected by fibrosis constitute a major site of obstruction.

"Die-back" in primary lymphedema -- lymphographic and clinical correlations.

Both obliteration and dilatation of distal lymphatics are seen in primary lymphedema but it is only in secondary lymphedema that the lymphographic progression of the disease has been documented. In this retrospective study the same progression was found in 13 out of 20 patients had initial evidence of proximal lymphatic obstruction. In ten patients the lymphangiographic changes were associated with a clinical deterioration of the leg. These findings suggest some urgency in diagnosing those patients that may benefit from a lymph bypass procedure.

Intralymphatic steroid therapy for lymphoedema: preliminary studies.

Lymph node fibrosis is a significant feature in patients with primary lymphoedema. Its importance in causing obstruction to the flow of lymph has lead to this study which is an attempt to reduce the effect of fibrosis by treatment with a corticosteroid preparation administered by direct intralymphatic infusion. In a pilot study, twenty patients received an intralymphatic infusion of Clobetasol propionate in Ultra-fluid Lipiodol (18 lower limb, 2 face). Clinical improvement occurred in eight of the patients with leg oedema over a period of up to nine months. Both face-affected patients were helped by this form of therapy. In patients with lymphoedema of the lower limb with lymph node abnormalities, it was advantageous if the lymph vessels leading up to the nodes were patent.