Background-The influence of gastrin on the colonic mucosa is still uncertain. Some authors have suggested a stimulating eVect on the growth of normal and malignant colonic epithelium, while others have shown no association between gastrin and neoplastic development. Aims-To evaluate the eVect of gastrin on colorectal cell proliferation, patients with chronic endogenous hypergastrinaemia underwent proctoscopy. Biopsy specimens were taken in order to study rectal cell kinetics. Patients and controls-Ten patients with chronic autoimmune gastritis (CAG), six patients with Zollinger-Ellison syndrome (ZES), and 16 hospital controls took part in this study. Patients with CAG and ZES had basal serum gastrin concentrations significantly higher than controls (p<0.001). Methods-Immunohistochemistry was performed on 3 µm sections of rectal biopsy specimens incubated with 5'-bromodeoxyuridine. Results-The percentage of proliferating cells in the entire crypts (overall labelling index) was similar in all the groups. However, the labelling frequency in the upper two fifths of the glands (φh value) was significantly higher in patients with CAG or ZES compared with controls (p<0.01 in both patient groups versus controls). Conclusions-Endogenous hypergastrinaemia is associated with rectal cell proliferation defects, similar to those observed in conditions at high risk for colon cancer. The eVect of the increased serum concentrations of gastrin on the colorectal mucosa after treatment with drugs inhibiting gastric acid secretion should be investigated.

Summary:Late onset haemorrhagic cystitis (HC) occurs in 20-30% of allogeneic bone marrow transplant patients. Human polyomavirus BK (BKV) (or less frequently adenovirus) may be involved in the pathogenesis of viral HC and can represent a serious post-transplant complication. Diagnosis and treatment of viral HC can be difficult and has an uncertain outcome. We report the efficacy of sequential vidarabine in the treatment of a patient with severe BKV-associated HC, despite the delay in implementing therapy. Bone Marrow Transplantation (2000) 25, 319-320. Keywords: BK virus; haemorrhagic cystitis; sequential vidarabine infusion Late-onset haemorrhagic cystitis (HC) occurs in 20-30% of bone marrow transplant (BMT) patients. 1,2 A strong association has been observed between HC and reactivation of the human polyomavirus BK, with viral shedding in the urine. 2,3 Less frequently, involvement of adenovirus infection in HC has also been reported. 4 However, urinary shedding of BKV and of adenoviruses (among others) may frequently be asymptomatic. Urinary shedding of BKV or of adenovirus may be demonstrated by the Papanicolau stain allowing detection of inclusion bodies and by transmission electron microscopy (TEM) allowing observation of viral particles in the urinary sediments, 5 as well as by virus isolation in cell cultures. However, the use of DNA hybridisation assays with labeled probes and especially of PCR has greatly improved the diagnosis of such infections. 2,3 Among the therapeutic approaches that have been adopted against viral HC, vidarabine has been reported to be active against double-stranded DNA viruses including human BKV. 6 Here, we describe the successful use of vidarabine in the treatment of a BKV patient with severe haemorrhagic cystitis. Case reportA 48-year-old man with acute myeloid leukaemia (FAB M6) in complete remission received an allogeneic BMT from his HLA-identical brother. Conditioning was with busulphan 4 mg/kg p.o. in divided doses daily for 4 days (total dose 16 mg/kg) plus cyclophosphamide 50 mg/kg once daily i.v. on days 5-8 (total dose 200 mg/kg). Prophylaxis of acute acrolein-induced haemorrhagic cystitis was with continuous infusion of mesna and hyperhydratation. Graft-versus-host disease (GVHD) prophylaxis comprised cyclosporin and a short course of methotrexate. Bone marrow transplant was carried out without significant complications. Marrow engraftment occurred at day +18 posttransplant. The patient was discharged on day +35 after BMT, with no transfusion requirement.On day +60 he was re-admitted with severe diarrhoea. Cytomegalovirus (CMV) antigenemia was concomitantly detected (47 cells). As routine faecal cultures for bacteria, fungi and viruses were negative, the diarrhoea was thought to be related to GVHD. High doses of steroids and gancyclovir at a dose of 5 mg/kg twice daily i.v. together with total parenteral nutrition (TPN) led to improvement in the clinical situation and an improvement in the CMV antigenemia (0-2 cells). On day +66, the patient started to experience...

Several clinical observations have confirmed that a donor immune-mediated anti-malignancy effect, called graft-versus-leukemia or graft-versus-tumor, occurs following allogeneic hematopoietic stem cell transplantation. While the potential antitumor effect mediated by donor lymphocytes has been established in many hematological malignancies, its efficacy in inducing clinically meaningful responses in solid tumors has been largely unexplored despite evidence of its potential benefit in experimental animal models. Only in recent years has the investigational application of non-myeloablative stem cell transplantation in patients with refractory non-hematological cancers proved that a graft-versus-tumor effect can be generated in patients with metastatic renal cell cancer and possibly with other solid tumors. In the present article we review the biological basis, development and early clinical results of this novel immunotherapeutic approach for solid tumors.