D. Alderson

Health-related quality of life among patients cured by surgery for esophageal cancer

Little is known regarding the long‐term, health‐related quality of life (HRQL) of survivors of esophagectomy for cancer.

c-erbB-2 overexpression in the dysplasia/carcinoma sequence of Barrett's oesophagus.

AIMS--To investigate overexpression of the oncoprotein c-erbB-2 in the dysplasia/carcinoma sequence of Barretts columnar-lined oesophagus (CLO). METHODS--Immunohistochemical staining was performed using the monoclonal antibody NCL-CB-11 on formalin fixed tissue from 31 cases of Barretts carcinoma, 20 cases of cancer associated dysplastic CLO, seven cases of dysplastic CLO without cancer, and 20 cases of non-dysplastic CLO. Membranous staining was regarded as positive for c-erbB-2 overexpression; cytoplasmic staining was recorded separately as its significance is uncertain. RESULTS--Membranous c-erbB-2 overexpression was observed in eight of 31 (26%) carcinomas and in none of the cases of dysplastic CLO. Variable cytoplasmic staining was seen in four of 31 (13%) tumours and seven of 27 (26%) cases of dysplastic CLO. No staining was observed in non-dysplastic CLO. CONCLUSIONS--C-erbB-2 overexpression is a relatively late event in the development of some Barretts carcinomas and is unlikely to be involved in the early stages of neoplastic transformation of CLO.

Health‐related quality of life during neoadjuvant treatment and surgery for localized esophageal carcinoma

Esophagectomy has a negative influence on health‐related quality of life (HRQL) during the first postoperative year, but it is not known how chemotherapy or chemoradiotherapy treatment before surgery affects HRQL. The current study examined HRQL during preoperative chemotherapy/chemoradiotherapy treatment and compared postoperative recovery of HRQL in patients undergoing combined treatment with patients undergoing surgery alone.

IGFBP-3 PROLONGS THE p53 RESPONSE AND ENHANCES APOPTOSIS FOLLOWING UV IRRADIATION

Neoplastic transformation is characterised by an imbalance in favour of cell growth over programmed cell death (apoptosis). The tumour‐suppressor gene p53, responsible for maintaining cell‐cycle control, is mutated in the majority of human cancers. Loss of function of the target genes of p53 are therefore important in tumourigenesis. One such target gene is the insulin‐like growth factor binding protein‐3 (IGFBP‐3), an extracellular protein responsible for the carriage of IGF‐I but which can act independently of IGF‐I, inhibiting cell growth and enhancing apoptosis. Using the KYSE190 oesophageal carcinoma cell line, we have demonstrated that IGFBP‐3 alone has no effect on cell growth or cell survival. However, it significantly enhanced apoptosis, with a 67% increase in the pre‐G1 peak on flow cytometry following UV irradiation. The increase in p53 was enhanced and prolonged when cells are stressed in the presence of IGFBP‐3. These data suggest an autocrine/paracrine feedback loop exists between IGFBP‐3 and p53, which may provide the social control necessary to maintain normal tissue homeostasis. Int. J. Cancer 88:336–341, 2000.

Influence of specialization on the management and outcome of patients with pancreatic cancer

Cancer care is increasingly specialized. Relationships between pancreatic cancer care, mortality and patterns of clinical practice among the full spectrum of patients, including those with irresectable tumours, are not well understood.

Quality of life during potentially curative treatment for locally advanced oesophageal cancer

Combination chemoradiotherapy with or without surgery are internationally applied alternative strategies for potential cure of oesophageal cancer. This study compared health‐related quality of life (HRQL) between patients selected for chemoradiation and those who had combination treatment including oesophagectomy.

Satisfaction with care: An independent outcome measure in surgical oncology

BackgroundOutcomes for treatment for upper gastrointestinal cancer traditionally include procedure-related morbidity and mortality and long-term survival. Patient-reported outcomes, such as quality of life (QOL) and satisfaction measures, add to standard end points, but associations between these factors are not fully understood. This study examined how patient satisfaction related to surgical morbidity, treatment type, and QOL outcomes after inpatient treatment for upper gastrointestinal cancer.MethodsConsecutive patients who had completed treatment in one unit were invited to participate in this study and complete the European Organization for Research and Treatment of Cancer QLQ-PATSAT32 and QLQ-C30 questionnaires within 2 months of discharge. Regression analyses examined relationships between satisfaction and surgical morbidity (major complications and type of treatment) and between satisfaction and QOL variables, adjusting for age and sex.ResultsDuring the study, 181 patients were treated, 162 were eligible, and 139 returned both questionnaires (response rate, 86%). Of the study sample, the treatment outcome was potential cure in 105 (67 esophagectomy and 38 D2 gastrectomy), and 34 received palliative treatment. Thirty-seven patients (27%) had major complications. Patients who received palliative treatment reported satisfaction and QOL scores similar to those of patients who received curative treatment. However, patients who experienced major morbidity reported significantly worse QOL than those without morbidity (P < .01). Satisfaction scores were the same in patients with or without complications. There were no associations between satisfaction and QOL scores (r < .34).ConclusionsPatient satisfaction with hospital care is independent of morbidity, treatment type, and QOL outcomes. It may be used to feed back information to providers of health care to improve patients’ experiences of treatment.

Health-related quality of life and survival in the 2 years after surgery for gastric cancer

BACKGROUND This prospective study examined health-related quality of life (HRQL) and survival in patients with potentially curable gastric cancer. METHODS Consecutive patients (n=58) selected for curative surgery completed a validated questionnaire (EORTC QLQ-C30) and site-specific module (QLQ-STO22) before surgery and regularly for 2 years afterwards. Changes of 10 or more points on a 0-100 scale were considered clinically significant. RESULTS Some 30 patients were alive after 2 years (52%). In the first 3 months after surgery, HRQL was significantly reduced across all dimensions except emotional and cognitive functioning (mean reduction of 10 or more points). Functional aspects of HRQL recovered by 6 months in patients who subsequently were alive at 2 years, although at least a third of patients experienced specific symptoms, even 6 months after surgery, especially diarrhoea. For those dying within 2 years, some postoperative functional HRQL recovery occurred, but many symptoms were common. CONCLUSIONS Potentially curative gastrectomy for cancer has a detrimental impact on HRQL that mostly recovers in patients surviving some 2 years. Patients who die within 2 years may experience limited postoperative recovery. It is recommended that patients receive HRQL information about the outcomes of surgery for gastric cancer.

Human papillomavirus and oesophageal squamous cell carcinoma in the UK

Human papillomavirus (HPV) has previously been identified in up to 67% of squamous cell carcinomas of the oesophagus. In particular, HPV types of 16 and 18 are believed to play an important role in neoplastic transformation, by means of their oncoproteins E6 and E7. Most of these studies, however, pertain to areas of high incidence of squamous cell carcinoma of the oesophagus (the Far East and South Africa). It is not known if HPV plays any role in the development of oesophageal squamous cell carcinoma in the UK, where the tumour is relatively uncommon. The polymerase chain reaction was used to examine frozen tissue from 22 oesophageal squamous cell carcinomas for the presence of specific DNA sequences from oncogenic strains of HPV. PCR products were further analysed by Southern blot hybridization. No HPV sequences were detected in any tumours. These results suggest that these types of HPV are not associated with oesophageal squamous cell carcinoma in this country. It is unlikely, therefore, that HPV plays a significant role in the pathogenesis of squamous cell carcinoma of the oesophagus in the UK.

Prognostic value of TP53 codon 72 polymorphism in advanced gastric adenocarcinoma

Purpose: A common polymorphism of the tumor suppressor gene TP53 at codon 72 has been associated with human cancer susceptibility. The prognostic role of the polymorphism was assessed in 102 patients with advanced gastric adenocarcinoma. Experimental Design: We followed up 102 consecutive Caucasian patients with advanced gastric adenocarcinoma for >5 years and determined the status of the TP53 codon 72 polymorphism in DNA samples extracted from archived gastric tissues. Results: The frequency of the arginine homozygous allele was positively correlated to patient age at baseline (P = 0.002). However, the age-related increase in the percentage of codon 72 arginine p53 was not correlated to the prognosis for gastric cancer patients. Multivariable analysis in patients who had surgery showed that baseline age may be inversely associated with patient survival (odds ratio, 1.1; 95% confidence interval, 1.0–1.2; P = 0.02). Furthermore, alcohol consumption may be associated with reduced survival (P = 0.06). Conclusions: These findings indicate that codon 72 arginine p53 may not be associated with a prolonged survival in patients with advanced gastric adenocarcinoma, but further study is needed to assess whether this polymorphism is associated with a late onset or slow progress of early gastric adenocarcinoma.