Paul J. Jenkins

Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002)

The British Society of Gastroenterology (BSG) and the Association of Coloproctology for Great Britain and Ireland (ACPGBI) commissioned this update of the 2002 guidance. The aim, as before, is to provide guidance on the appropriateness, method and frequency of screening for people at moderate and high risk from colorectal cancer. This guidance provides some new recommendations for those with inflammatory bowel disease and for those at moderate risk resulting from a family history of colorectal cancer. In other areas guidance is relatively unchanged, but the recent literature was reviewed and is included where appropriate.

Acromegaly, colonic polyps and carcinoma

It has been suggested that patients with acromegaly may be at risk of developing colorectal carcinoma. In order to clarify this issue, we have evaluated the prevalence of carcinoma, premalignant tubulovillous adenomas and hyperplastic colonic polyps in a large cohort of patients with acromegaly.

Outcome of transsphenoidal surgery for acromegaly using strict criteria for surgical cure

OBJECTIVE Previous studies of surgical treatment for acromegaly have used varied criteria for ‘cure’, but elevated GH levels are considered to be associated with continuing disease activity. We wished to analyse the results of transsphenoidal pituitary surgery for acromegaly and assess the longer‐term outcome for patients not offered further treatment when post‐operative levels of GH < 5 mU/l were achieved.

Does growth hormone cause cancer

The ability of GH, via its mediator peptide IGF‐1, to influence regulation of cellular growth has been the focus of much interest in recent years. In this review, we will explore the association between GH and cancer. Available experimental data support the suggestion that GH/IGF‐1 status may influence neoplastic tissue growth. Extensive epidemiological data exist that also support a link between GH/IGF‐1 status and cancer risk. Epidemiological studies of patients with acromegaly indicate an increased risk of colorectal cancer, although risk of other cancers is unproven, and a long‐term follow‐up study of children deficient in GH treated with pituitary‐derived GH has indicated an increased risk of colorectal cancer. Conversely, extensive studies of the outcome of GH replacement in childhood cancer survivors show no evidence of an excess of de novo cancers, and more recent surveillance of children and adults treated with GH has revealed no increase in observed cancer risk. However, given the experimental evidence that indicates GH/IGF‐1 provides an antiapoptotic environment that may favour survival of genetically damaged cells, longer‐term surveillance is necessary; over many years, even a subtle alteration in the environmental milieu in this direction, although not inducing cancer, could result in acceleration of carcinogenesis. Finally, even if GH/IGF‐1 therapy does result in a small increase in cancer risk compared to untreated patients with GH deficiency, it is likely that the eventual risk will be the same as the general population. Such a restoration to normality will need to be balanced against the known morbidity of untreated GH deficiency.

Treatment of metastatic carcinoid tumours, phaeochromocytoma, paraganglioma and medullary carcinoma of the thyroid with 131I-meta-iodobenzylguanidine (131I-mIBG)

OBJECTIVE Meta‐iodo‐benzyl‐guanidine labelled with 131‐iodine (131I‐mIBG) has been used extensively for imaging tumours originating from the neural crest but experience with its therapeutic use is limited, particularly for non‐catecholamine secreting tumours. In order to assess the therapeutic response and potential adverse effects of the therapeutic administration of 131I‐mIBG, we have reviewed all patients who had received this form of treatment in our department.

The GH–IGF-I axis and breast cancer

The growth hormone-insulin-like growth factor-I (GH-IGF-I) axis plays a fundamental role in the development of the breast. The maintenance of breast tissue architecture is aided by its effect on proliferation, differentiation and apoptosis. There has been increasing recognition of its role as a major determinant of breast cancer and, more recently, its involvement in the development of resistance to both tamoxifen and an important novel therapy for advanced disease, trastuzumab (Herceptin). Here, we discuss the influence of the GH-IGF-I axis in normal mammary development and homeostasis, its putative role in breast tumorigenesis and its interactions with estrogen signalling.

The mRNA expression of cyclo-oxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in human breast cancer.

Summary Aims: There is a growing body of evidence that cyclo-oxygenase 2 (COX-2) plays an important role in carcinogenesis and angiogenesis of human tumours. The present study aims to compare COX-2 expression in human breast cancer and adjacent non-cancerous tissue (ANCT), and to identify any correlation between COX-2 and VEGF expression. Methods: Total cellular RNA was extracted from frozen breast tissue samples according to standard methodology. The mRNA copy numbers for COX-2 and vascular endothelial growth factor 189 (VEGF-189) were determined 40 infiltrating carcinomas and 40 matched ANCT specimens using quantitative RT-PCR and TaqMan methodology. Results: The COX-2 mRNA copy number per ixg of RNA was two-fold higher in ANCT compared with the cancerous tissue (p = 0.01). Median mRNA copy number was 5.44 x 106 for ANCT and 2.30 x 106for tumour, (ANCT range: 1 x 106to4.12x 107) (tumour range: 1.29 x 105to1.07x 107). There was a significant correlation between COX-2 and VEGF-189 mRNA copy numbers in the cancer specimens (correlation coefficient = 0.5528, p = 0.0076). Conclusions: COX-2 mRNA is overexpressed in both human breast cancer and ANCT. We found higher levels in the matched ANCT which suggests that paracrine effects may be important in the role of COX-2 in mammary carcinogenesis. Furthermore, our results indicate that in human breast cancers COX-2 overexpression is linked to VEGF-189 overexpression and therefore tumour angiogenesis.

Growth hormone and exercise

This review summarizes the interactions between GH and exercise. Not only does exercise have profound effects upon the GH/IGF‐I axis per se, but there is increasing evidence that such physiological perturbations might be influential in the performance responses to repeated training. However, the effects of systemic administration of rGH in restoring exercise capability and muscle strength in GH deficient adults and the ergogenic benefits of GH doping amongst athletes remain unproven. What is certain is that these issues will be of increasing relevance to clinical endocrinologists.

Unmasking of central hypothyroidism following growth hormone replacement in adult hypopituitary patients

Background  The effect of GH replacement on thyroid function in hypopituitary patients has hitherto been studied in small groups of children and adults with conflicting results.

Sustained reduction in circulating cholesterol in adult hypopituitary patients given low dose titrated growth hormone replacement therapy: a two year study

To study the effects of short (6 months) and longer‐term (up to 24 months) growth hormone (GH) replacement therapy using a dose titration regimen, on lipid and glucose metabolism in GH‐deficient, hypopituitary adults.