Failure of radiotherapy in acromegaly

BACKGROUND: Recent data has raised skepticism regarding the long-term effectiveness of radiotherapy (RxT) in acromegaly and its role as an ancillary tool to neurosurgery (Tx). PATIENTS: We evaluated 72 acromegalic patients previously submitted to RxT. Data were discarded in 23 patients, who were lost to follow-up, operated on after RxT or irradiated with techniques different from external conventional fractionated RxT. Among the remaining 49 (five with mixed GH-prolactin adenoma), 34 were irradiated after surgical failure and 15 as primary treatment. A second cycle of RxT was administered in two. RESULTS: (i) GH/IGF-I. After a median follow-up of 14 years (range 3-41), normal age-matched IGF-I levels were reached in eight patients (16%) after 10 years, and GH levels <2.5 microg/l in six (12%) after 9 years. The rate of persistently pathological hormonal levels was still 90% at 25 years. All patients with GH/IGF-I normalization had undergone irradiation without any antisecretory drug. Neither basal GH nor tumor size affected the outcome of RxT. In three patients (6%) a relapse/worsening occurred. (ii) Tumor size. Tumor shrank after 8.5 years in 24 patients (49%), in nine of whom during GH-suppressive treatment. Tumor shrinkage was not predictive of hormonal normalization. (iii) Side-effects. Hypopituitarism was diagnosed in four patients (selective in three and global in one) and GH deficiency in one. Three patients had neurological side-effects and meningioma was shown in two patients. CONCLUSION: RxT is unable to cure acromegaly, because it seldom achieves hormonal normalization even after a very prolonged follow-up. Concomitant antisecretory treatment seems to counteract its effects. RxT can still play a role in those patients with large tumor remnants, because of its capacity to shrink tumor size.

La Gastroprotezione Nel Paziente Oncologico: Approccio Razionale, Ruolo Dei Farmaci Antisecretori Ed Eventuali Ulteriori Prospettive in Oncologia

In view of the large number of cancer patients treated with FANS and/or corticosteroids for long periods of time, Authors discuss how the use of antisecretory drugs for gastroprotection has become common practice in spite of the lack of clear scientific evidence. The paper analyses the principal mechanisms of gastrotoxicity of FANS, essentially associated with the inhibition of prostaglandins and consequent reduction of the secretion of mucous and bicarbonate. It also discusses the numerous controlled trials evaluating the efficacy of ranitidine for gastroprotection versus placebo and versus the analogous synthetic substance, misoprostole, derived from prostaglandin E1. This analysis shows that misoprostole provides significant protection against both gastric and duodenal ulcers, whilst the antisecretory drug protects only against localised duodenal ulcer. The conclusion is that optimum protection against FANS is provided by misoprostole. In any case more than 30% of patients are destined to develop ulcerous or minor lesions for which treatment with antisecretory drugs is correct. After analysis of the available literature on the gastrotoxicity of corticosteroids, it is clear that this risk is real only for a small sub-population of patients (treated in dual therapy with FANS, for long periods, with high doses or in presence of ulcer anamnesis). It is not known in these cases whether prophylactic treatment is suitable, nor which would be the best prophylactic treatment. In other cases the problem does not arise since the number of patients developing ulcers is similar with corticosteroids treatment or with placebo. Some further interesting features of ranitidine compared to cimetidine (its better pharmacological profile due to the lack of side effects, lack of medullary depression, lack of interference with the immunological system, lack of antiandrogen effects) are also discussed. Particularly interesting is the lack of interference with cyclophosphamide metabolism, such interference having shown for cimetidine. Studies involving ranitidine treatment in association with Interleukin-2 for renal carcinoma and metastatic melanoma are also of interest although no statistically significant results are available as yet.

Improving the detection rate of early gastric cancer requires more than open access gastroscopy: a five year study

Background/aims—To explore the reasons why patients with gastric cancer continue to present with advanced disease despite open access gastroscopy.Patients—All patients diagnosed with gastric cancer between 1 August 1989 and 31 July 1994.Methods—A retrospective study of the presentation of gastric cancer in South Tees; patients were diagnosed at open access gastroscopy or referred through conventional channels. Primary care records of 81 patients dying between 1991 and 1995 were analysed for previous symptoms, investigations, and antisecretory drug therapy. Findings were compared with 200 age and sex matched controls.Results—The overall incidence of earlier stage gastric cancer remains low at 13%. Diagnostic delay occurs in both primary and secondary care due to a high incidence of previous dyspepsia and investigation. One in six patients had been previously investigated in the three years prior to diagnosis, the majority of whom were on antisecretory drugs.Conclusions—Early gastric cancer remains rare in South Tees health district. Advantages of open access gastroscopy appear to be compromised by delayed referral to hospital and failure of endoscopists to recognise the early disease; either they are unaware of its appearance or prior treatment with an H2receptor antagonist masks the disease by allowing mucosal healing.