PubMed Health⌕ Search

Biomedical subjects

D Hollywood

Publications and source records attributed to D Hollywood.

8 recordsLinked to original sources
PubMed2006

(18)FDG uptake during induction chemoradiation for oesophageal cancer fails to predict histomorphological tumour response.

To determine whether [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) could predict the pathological response in oesophageal cancer after only the first week of neoadjuvant chemoradiation. Thirty-two patients with localised oesophageal cancer had a pretreatment PET scan and a repeat after the first week of chemoradiation. The change in mean maximum standardised uptake value (SUV) and volume of metabolically active tissue (MTV) was compared with the tumour regression grade (TRG) in the final histology. Those who achieved a TRG of 1 and 2 were deemed responders and 3-5 nonresponders. In the responders (28%), the SUV fell from 12.6 (+/-6.3) to 8.1 (+/-2.9) after 1 week of chemoradiation (P=0.070). In nonresponders (72%), the results were 9.7 (+/-5.4) and 7.1 (+/-3.8), respectively (P=0.003). The MTV in responders fell from 36.6 (+/-22.7) to 22.3 (+/-10.4) cm(3) (P=0.180), while in nonresponders, this fell from 35.9 (+/-36.7) to 31.9 (+/-52.7) cm(3) (P=0.405). There were no significant differences between responders and nonresponders. The hypothesis that early repeat FDG-PET scanning may predict histomorphologic response was not proven. This may reflect an inflammatory effect of radiation that obscures tumour-specific metabolic changes at this time. This assessment may have limited application in predicting response to multimodal regimens for oesophageal cancer.

Adult↗
PubMed2006

Primary thromboprophylaxis for cancer patients with central venous catheters--a reappraisal of the evidence.

Venous thromboembolism (VTE) is responsible for an estimated 25 000 deaths per annum in UK hospital practice. It is well established that many of these deaths could be prevented through the use of appropriate thromboprophylaxis. This issue is of particular relevance in oncology practice, where the risks of VTE and bleeding are both significantly higher than those observed in general medical patients. Cancer patients with in-dwelling central venous catheters (CVCs) are at particularly high risk of developing thrombotic complications. However, the literature has produced conflicting conclusions regarding the efficacy of using routine primary thromboprophylaxis in these patients. Indeed such is the level of confusion around this topic, that the most recent version of the American College of Chest Physicians (ACCP) guidelines published in 2004 actually reversed their previous recommendation (published in 2001). Nevertheless, minidose warfarin continues to be routinely used in many oncology centres in the UK. In this article, we have performed a systematic review of the published literature regarding the efficacy and the risks, associated with using thromboprophylaxis (either minidose warfarin or low-dose LMWH) in cancer patients with CVC. On the basis of this evidence, we conclude that there is no proven role for using such thromboprophylaxis. However, asymptomatic CVC-related venous thrombosis remains common, and further more highly powered studies of better design are needed in order to define whether specific subgroups of cancer patients might benefit from receiving thromboprophylaxis.

Anticoagulants↗
PubMed2006

Clinicopathologic factors predicting complete pathological response to neoadjuvant chemoradiotherapy in esophageal cancer.

Multimodal therapy comprising neoadjuvant chemotherapy and radiation therapy prior to radical resection is increasingly utilized in gastroesophageal cancer. The achievement of a complete pathological response (pCR) or a major response is associated with an improved survival. However, up to 70% of patients show an incomplete or no response to the neoadjuvant regimen, and the identification of factors which predict a response would be of considerable clinical benefit. A retrospective analysis of a prospectively updated esophageal cancer database was performed. The predictive values of the following clinicopathological factors were investigated: age, sex, tobacco, alcohol, weight, clinical history, tumor type, site, length, width, morphology and differentiation. Statistical analysis was performed using Chi-square test with Pearson's test or Kruskal-Wallis test. One hundred and seventy-six patients were identified who had undergone neo-adjuvant chemoradiotherapy at St James's Hospital Dublin, between January 1990 and June 2003. A complete pathological response was seen in 40 cases (23%). There was a significant (P < 0.05) relationship between response to chemoradiotherapy and pretreatment tumor length. The median tumor length in the pCR group was 2 cm (1-5 cm) compared with 3 cm (2-7 cm) in non-responders (P < 0.05). Body weight, sex, tobacco or alcohol usage, tumor site, or differentiation were not predictive of response, although a trend (P = 0.08) was observed for squamous cell cancer compared with adenocarcinoma. Smaller tumor length was predictive of a greater response to chemotherapy and radiation therapy. This may reflect different tumor biology, perhaps with acquired resistance to treatment-induced apoptosis in the larger tumors. A simpler explanation is that the existing dose and treatment schedule for combination chemoradiotherapy is suboptimal in patients with larger tumors.

Adenocarcinoma↗
PubMed2005

Achieving hypoxia-inducible gene expression in tumors.

Hypoxia is an inevitable feature of solid tumors and a common cause of treatment failure. Hypoxia acts as a trigger to genetic instability, apoptosis and possibly metastases. The adaptive response to cellular hypoxia involves the modulation of the synthesis of multiple proteins controlling processes such as glucose homeostasis, angiogenesis, vascular permeability and inflammation. The hypoxia responsive element (HRE) sequences isolated from oxygen-responsive genes have been shown to selectively induce gene expression in response to hypoxia when placed upstream of a promoter. The levels of induced gene expression were dependent on the number of HRE copies and the oxygen tension. Hypoxia-mediated cancer gene therapy strategies may represent a promising mean to significantly improve the efficacy of standard radiation therapy and chemotherapy approaches.

Animals↗
PubMed1996

A comparison of multimodal therapy and surgery for esophageal adenocarcinoma.

BACKGROUND: Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma. We conducted a prospective, randomized trial comparing surgery alone with combined chemotherapy, radiotherapy, and surgery. METHODS: Patients assigned to multimodal therapy received two courses of chemotherapy in weeks 1 and 6 (fluorouracil, 15 mg per kilogram of body weight daily for five days, and cisplatin, 75 mg per square meter of body-surface area on day 7) and a course of radiotherapy (40 Gy, administered in 15 fractions over a three-week period, beginning concurrently with the first course of chemotherapy), followed by surgery. The patients assigned to surgery had no preoperative therapy. RESULTS: Of the 58 patients assigned to multimodal therapy and the 55 assigned to surgery, 10 and 1, respectively, were withdrawn for protocol violations. At the time of surgery, 23 of 55 patients (42 percent) treated with preoperative multimodal therapy who could be evaluated had positive nodes or metastases, as compared with 45 of the 55 patients (82 percent) who underwent surgery alone (P<0.001). Thirteen of the 52 patients (25 percent) who underwent surgery after multimodal therapy had complete responses as determined pathologically. The median survival of patients assigned to multimodal therapy was 16 months, as compared with 11 months for those assigned to surgery alone (P=0.01). At one, two, and three years, 52, 37, and 32 percent, respectively, of patients assigned to multimodal therapy were alive, as compared with 44, 26, and 6 percent of those assigned to surgery, with the survival advantage favoring multimodal therapy reaching significance at three years (P=0.01). CONCLUSIONS: Multimodal treatment is superior to surgery alone for patients with resectable adenocarcinoma of the esophagus.

Adenocarcinoma↗
PubMed1991

Signal transduction.

Ordered cell proliferation relies on a complex interplay between diverse cell types, interstitial stroma and organ vasculature. At a cellular level the response to growth stimuli is dependent on the bidirectional exchange of information between the cell membrane and nucleus. Specific regulatory molecules enable the transfer of growth signals and constitute the signal transduction pathways. In malignant disease deregulation of growth regulatory pathways is believed to contribute to the characteristic features of neoplasia, unrestricted cell proliferation, direct invasion of surrounding tissues and the formation of distant metastases. Many proto-oncogenes and oncogenes encode proteins that are strongly suspected to function in aberrant signal transduction (Table 1).

Cell Division↗