Long-term safety of monthly zoledronic acid therapy beyond 1 year in patients with advanced cancer involving bone (LoTESS): A multicentre prospective phase 4 study.

Malignant bone disease can cause significant morbidity. Monthly zoledronic acid (ZOL) reduces skeletal complications; however, limited data are available regarding long-term safety. We aimed to assess efficacy and safety of ZOL beyond 1 year of treatment. We prospectively evaluated 73 patients; breast cancer (n = 29), castrate-resistant prostate cancer (n = 13), multiple myeloma (n = 31) from 2006 to 2008 in 19 cancer centres. All patients were diagnosed with bone disease and had completed 1-2 years of monthly ZOL (4 mg) and received a further 1-2 years of therapy following contemporary guidelines for managing risks of osteonecrosis of the jaw (ONJ) and renal toxicity. Overall rates of skeletal-related events (SREs), renal impairment and ONJ were assessed. Over the additional 1 year of treatment, only 5.5% (n = 4) of patients developed a new SRE. The overall Kaplan-Meier estimate for SRE incidence after 48 weeks on study was 6.75% (95 CI: 2.5-17.3). Although 51% of patients reported serious adverse events, only two cases were suspected as ZOL related. No patients had confirmed ONJ. The observed incidence of new renal impairment was 11% (none due to ZOL). Our study confirms the benefit over risk of continuing monthly ZOL for at least 2 years in patients with advanced cancer involving bone.

Use of total parenteral nutrition in children with cancer: a review and some recommendations.

Total parenteral nutrition (TPN) is now a standard component of supportive treatment in many pediatric oncology units for patients undergoing intensive therapy. TPN incurs many risks and significant costs, however, that may not always be balanced by major benefits. Infection rates are reported to be high in patients receiving TPN, and TPN use is associated with a range of metabolic problems. With standard TPN regimens, the catabolic state of many intensively treated patients may not be adequately reversed. Because TPN may enhance tumor cell growth, there is justifiable concern about giving TPN when a cancer patient is not also receiving cytotoxic therapy. Recommendations for TPN use in pediatric oncology patients include using TPN formulas containing glutamine to stimulate anabolism and timing TPN cycles to be given just before cytotoxic chemotherapy, when stimulation of tumor growth might actually improve the effectiveness of antimitotic chemotherapy.

Pneumomediastinum complicating childhood acute lymphoblastic leukaemia.

A case of pneumomediastinum that developed in a 10 year old girl receiving induction chemotherapy for acute lymphoblastic leukemia is reported. Three factors were identified that may have been associated with this complication: the patient suffered recurrent vomiting during her induction chemotherapy; she had travelled by air the day before the pneumo mediastinum was diagnosed; and was septic with Enterobacter at time of diagnosis. The pneumomediastinum resolved over 2 weeks without specific treatment and without further complications.

The putative melanoma tumor-suppressor gene on human chromosome 6q.

The tumorigenicity of malignant melanoma cells may be suppressed experimentally by the introduction into these cells of human chromosome 6 or mouse chromosome 4. These chromosomes share a homologous region, contained in human chromosome 6q12-21. Abnormalities of this human chromosomal region have been found frequently not only in cutaneous and uveal malignant melanomas, but also in a range of other tumors. In all these, mutations of tumor-suppressor genes on human chromosome 6q may be involved. Identification of this putative tumor-suppressor gene may give new insights into the biology of malignant melanomas, and could pave the way for new treatment for such tumors, based upon the tumor-suppressor protein which this gene is likely to encode.

The extracellular matrix of hybrids between melanoma cells and normal fibroblasts.

It has been shown that when malignant tumour cells are fused with normal fibroblasts the suppression of malignancy in the hybrids is linked to their ability to produce a collagenous extracellular matrix in vivo. When, as a consequence of chromosome loss, segregants arise that reacquire malignancy, these do not produce any detectable matrix. In this paper we examine the main components of the extracellular matrix produced in vitro by hybrids between malignant mouse melanoma cells and normal mouse fibroblasts. Hybrids in which malignancy is suppressed synthesize about ten times as much type 1 procollagen as the malignant segregants derived from them; they also retain more fibronectin in the cell layer and release less protease activity into the medium. Malignant segregants more closely resemble the parental melanoma cells in producing fibronectin and mainly types IV and V procollagen. When hybrid cells in which malignancy is initially suppressed are grown continuously in vitro, the production of type I procollagen declines, and the production of type V procollagen and the release of protease activity into the medium increase. These changes, which are associated with the loss from the hybrid cells of both copies of the chromosome 4 derived from the parental fibroblast, predict the reacquisition of malignancy when the cells are inoculated into mice. It is possible that one gene or set of genes located on chromosome 4 determines both the execution of the fibroblast differentiation programme and the suppression of malignancy.

Presenting symptoms of neoplastic spinal cord compression.

The cases of 28 patients with neoplastic spinal cord compression were reviewed. The most common presenting symptoms were: back pain (68%), bilateral leg weakness (61%), urinary retention (36%), and bilateral leg numbness (32%). Twelve patients (43%) had known neoplastic disease prior to diagnosis of spinal cord compression. Only two patients (7%) were diagnosed within one week of the onset of major spinal symptoms. The commonest symptoms associated with delay in diagnosis were again back pain (50%) and bilateral leg weakness (38%). However, when certain symptoms were present, diagnosis was almost always delayed, particularly with unilateral leg weakness or pain (100%), ataxic gait (80%), and back pain (68%). Symptoms in the neck, chest, and arms were also always associated with delayed diagnosis.

Desensitization to DNFB in hairless mice.

Naive hairless mice may be rendered partly tolerant to dinitrofluorobenzene (DNFB) by painting DNFB on skin irradiated with 30 mJ.cm-2 ultraviolet B light (UVB) over 4 days. However, DNFB-sensitized hairless mice show no decrease in sensitivity when repainted with DNFB on skin irradiated with the same dose of UVB. Hence, established hypersensitivity appears not to be reduced by this method of inducing tolerance in naive mice.

Arterial Brown-Séquard's syndrome after a penetrating injury of the spinal cord at the cervicomedullary junction.

A case of a 12-year-old boy, in whom a partial Brown-Séquard's syndrome developed after a gunshot injury to the back of the neck, is reported. The bullet, which was removed at operation, penetrated the left side of the spinal cord at the cervicomedullary junction. The patient recovered useful function in his left leg within a month after the injury, and was able to walk with the aid of a crutch on discharge from hospital. The case is unusual, because of the survival and subsequent good recovery of the patient after a high, penetrating injury of the spinal cord.