The influence of low fat, low lactose diet on diarrhoea during pelvic radiotherapy

In a prospective clinical trial 143 women undergoing pelvic radiotherapy for gynaecological malignancies, were randomized to receive either a low-fat, low-lactose diet (intervention group) or a regular diet (control group) in order to evaluate the possible impact of diet therapy on radiation induced diarrhoea, nausea and vomiting. The daily number and consistency of stools, use of antidiarrhoeal agents, nausea and vomiting were recorded before radiotherapy was begun (week 0), in the last week of therapy (week 6) and 6 weeks after the end of therapy (week 12). The intervention group used half the amount of antidiarrhoeal agents in week 6, than used by the control group (mean 0.6 tablets per day versus 1.1, p < 0.01). 14 patients (23%) in the intervention group reported diarrhoea, versus 32 (48%) in the control group (p < 0.01). In week 12 there were no differences in the use of antidiarrhoeal agents and the prevalence of diarrhoea between the groups.     

Effect of intermittent versus continuous energy restriction on weight loss,maintenance and cardiometabolic risk: A randomized 1-year trial

Background & aims

Long-term adherence to conventional weight-loss diets is limited while intermittent fasting has risen in popularity. We compared the effects of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk factors in adults with abdominal obesity and ≥1 additional component of metabolic syndrome.

Cisplatin/5-Fluorouracil Treatment of Recurrent Cervical Carcinoma: A Phase II Study with Long-Term Follow-up

Objective: To evaluate the response rate and corrected survival in patients with recurrent cervical carcinoma (RCC) treated with 100 mg/m²cisplatin (CDDP) iv on Day 1 and 1000 mg/m²5-fluorouracil (5-FU) iv on Days 1 to 5. Methods: A phase II study of CDDP/5-FU in RCC was initiated in 1986. Up to December 1991, a total of 72 patients were enrolled. Of these, 65 were evaluable for response. Results: The overall response rate was 49%. For 9 patients with complete remission, the median duration of response was 16 months, range 6 to 79+. The corresponding figures for 26 patients with partial remission were 10 months, range 3 to 80 months. By multivariate analysis, FIGO stage, disease-free interval, WHO performance status, and number of lesions at recurrence were independent prognostic variables. Twenty-two percent of the patients survived for more than 2 years and 9% for more than 5 years. Toxicity was tolerable. Leucopenia, ototoxicity, and neurotoxicity were the main problems. Conclusion: A high response rate (49%) was observed with CDDP/5-FU treatment in patients with RCC with 9% of the patients surviving for more than 5 years.     

Normobaric oxygen treatment during radiotherapy for carcinoma of the uterine cervix. Results from a prospective controlled randomized trial.

BACKGROUND AND PURPOSE: Hypoxia, a frequent characteristic of cervical cancer, is associated with reduced sensitivity to irradiation and thus may be a source of radiotherapy failure. This study was planned to test the hypothesis, that inhalation of oxygen during radiotherapy may increase the radiation effect on the tumor and improve loco-regional control and overall survival. MATERIAL AND METHODS: From 1963 to 1965, a consecutive series of 208 patients with cervical cancer stage II/III who were to be treated by external irradiation plus radium inserts, were included in this study. They were randomly assigned to either receive oxygen inhalations during the radiotherapy sessions or just breathing air. Due to technical reasons the oxygen group was divided. For the first 10 months, they did receive oxygen during the radium inserts only, the last 13 months during all radiotherapy sessions. RESULTS: After median 33 years follow-up, there are no differences in overall survival, cancer-specific survival or loco-regional control. Subgroup analysis shows significantly improved loco-regional control in the stage IIB patients, with squamous cell carcinoma who received oxygen during all radiotherapy sessions. This improvement was especially pronounced among the patients who also received blood transfusions. CONCLUSIONS: There was no influence of normobaric oxygen treatment on the overall outcome to radiotherapy in patients with stage II cervical cancer, but subgroup analyses support the hypothesis that there is tumor areas of hypoxia-based radioresistance that may be counteracted by oxygen administration.     

Effect of lifestyle changes on atherogenic lipids and endothelial cell adhesion molecules in young adults with familial premature coronary heart disease

Guidelines have recommended that a family history of premature coronary heart disease (CHD) warrants screening and preventive efforts, including lifestyle change. The objective of this study was to evaluate the effects of a lifestyle modification program on lipids and novel risk markers in young relatives of patients with premature CHD. In a parallel, randomized, intervention trial, intensified support to quit smoking and dietary modification was compared with general lifestyle advice in 172 men and women aged 18 to 39 years with a total cholesterol of 5 to 8 mmol/L and >or=1 lipid abnormality (high low-density lipoprotein [LDL] cholesterol, triglycerides or lipoprotein(a), or low high-density lipoprotein cholesterol). All had a first-degree relative with premature CHD or with hyperlipidemia and other relative(s) with premature CHD, and 40% were daily smokers. After a mean of 8 months, the intervention group reduced the dietary intake of saturated fat and cholesterol compared with controls (p = <0.01). Ten smokers in the intervention group quit, whereas 2 subjects in the control group started and none quit. LDL cholesterol (p = 0.007), oxidized LDL (p = 0.03), and E-selectin (p = 0.02) concentrations were reduced in the intervention group compared with controls. In subjects who quit smoking, concentrations of intercellular adhesion molecule-1 decreased (261 +/- 66 to 228 +/- 30 ng/ml) compared with that in continuing smokers (308 +/- 106 ng/ml to 304 +/- 109 ng/ml) (p = 0.05 between groups). These findings indicate that dietary modification and smoking cessation are feasible in young adults with familial premature CHD and document novel mechanisms by which lifestyle modification may reduce CHD risk.     

Phosphorylation of EGFR measured with in situ proximity ligation assay: Relationship to EGFR protein level and gene dosage in cervical cancer

Purpose

We have applied the sensitive and specific in situ proximity ligation assay (PLA) to characterize Tyr1068 phosphorylation of the epidermal growth factor receptor (EGFR) in cervical cancer in relation to the protein level and gene dosage.

Materials and methods

Pretreatment tumor biopsies from 178 patients were analyzed. EGFR protein level was determined by immunohistochemistry, and Tyr1068 phosphorylation was detected with PLA in 97 EGFR positive tumors. EGFR gene dosage was derived from array comparative genomic hybridization of 86 cases.

Results

EGFR was expressed in most tumors, whereas phosphorylation was seen in about half of the EGFR positive ones. A correlation was found between the expression of EGFR and phosphorylated EGFR (p = 0.016, membrane; p = 0.012, cytoplasm). However, tumor regions with high protein level without phosphorylation were occasionally seen and the percentage of EGFR positive cells was higher than the phosphorylated percentage (p < 0.001). Moreover, an increase in the phosphorylation in both the membrane (p = 0.014) and cytoplasm (p = 0.002) was seen in 11 tumors with gain of EGFR. The protein level was not correlated with gene dosage.

Conclusion

In contrast to gain of the EGFR chromosomal region, high EGFR protein level may not necessarily indicate Tyr1068 phosphorylation and thereby receptor activation in cervical cancer.     

Improved sensitivity to fluorescence for cancer detection in wide-field image-guided neurosurgery

In glioma surgery, Protoporphyrin IX (PpIX) fluorescence may identify residual tumor that could be resected while minimizing damage to normal brain. We demonstrate that improved sensitivity for wide-field spectroscopic fluorescence imaging is achieved with minimal disruption to the neurosurgical workflow using an electron-multiplying charge-coupled device (EMCCD) relative to a state-of-the-art CMOS system. In phantom experiments the EMCCD system can detect at least two orders-of-magnitude lower PpIX. Ex vivo tissue imaging on a rat glioma model demonstrates improved fluorescence contrast compared with neurosurgical fluorescence microscope technology, and the fluorescence detection is confirmed with measurements from a clinically-validated spectroscopic probe. Greater PpIX sensitivity in wide-field fluorescence imaging may improve the residual tumor detection during surgery with consequent impact on survival.OCIS codes: (170.3890) Medical optics instrumentation, (170.6280) Spectroscopy, fluorescence and luminescence     

Hypoxia-induced treatment failure in advanced squamous cell carcinoma of the uterine cervix is primarily due to hypoxia-induced radiation resistance rather than hypoxia-induced metastasis

Poor outcome of treatment in advanced cervix carcinoma has been shown to be associated with poor oxygenation of the primary tumour. Hypoxia may cause radiation resistance and promote lymph-node metastasis. The purpose of the study reported here was to investigate whether hypoxia-induced treatment failure in advanced cervix carcinoma is primarily a result of hypoxia-induced radiation resistance or the presence of hypoxia-induced lymph-node metastases at the start of treatment. Thirty-two patients with squamous cell carcinoma of the uterine cervix were included in the study. Radiation therapy was given with curative intent as combined external irradiation and endocavitary brachytherapy. The oxygenation status of the primary tumour was measured prior to treatment using the Eppendorf PO2 Histograph. Pelvic and para-aortal lymph-node metastases were detected by magnetic resonance imaging at the time of initial diagnosis. The primary tumours of the patients with metastases (n = 18) were significantly more poorly oxygenated than those of the patients without metastases (n = 14). Multivariate Cox regression analyses involving biological and clinical parameters identified the tumour subvolume having PO2 values below 5 mmHg (HSV (pO2 < 5 mmHg) as the only significant, independent prognostic factor for locoregional control, disease-free survival and overall survival. The probabilities of locoregional control, disease-free survival and overall survival were significantly lower for the patients with HSV (PO2 < 5 mmHg) above the median value than for those with HSV (PO2 < 5 mmHg) below the median value. On the other hand, the outcome of treatment was not significantly different for the patients with metastases and the patients without metastases at the start of treatment, irrespective of clinical end-point. Consequently, treatment failure was primarily a result of hypoxia-induced radiation resistance rather than hypoxia-induced lymph-node metastasis, suggesting that novel treatment strategies aiming at improving tumour oxygenation or enhancing the radiation sensitivity of hypoxic tumour cells may prove beneficial in attempts to improve the radiation therapy of advanced cervix carcinoma.     

Tumour hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix.

Some clinical studies involving several histological types of cancer have suggested that high vascular density in the primary tumour promotes metastasis. Other studies have suggested that a high incidence of metastases is associated with low oxygen tension in the primary tumour. The purpose of the study reported here was to search for correlations between incidence of metastases and oxygen tension or vascular density in the same population of patients. Thirty-eight consecutive patients with squamous cell carcinoma of the uterine cervix were included in a prospective study. Pelvic, iliac and retroperitoneal lymph node metastases were detected by magnetic resonance imaging at the time of initial diagnosis. Oxygen tension was measured polarographically using the Eppendorf pO2 Histograph 6650. Vascular density was determined by histological examination of tumour biopsies. The primary tumours of the patients with metastases (n = 19) were more poorly oxygenated than those of the patients without metastases (n = 19). Thus, the fractions of the pO2 readings resulting in values below 5 mmHg and 10 mmHg were significantly higher for the former group of patients than for the latter (P = 0.03 and 0.02 respectively). In contrast, the vascular density of the primary tumour was not significantly different for the two groups of patients. The present study suggests that a high incidence of metastases in squamous cell carcinoma of the uterine cervix is associated with poor oxygenation of the primary tumour and not with a high vascular density.     

Treatment outcome in advanced squamous cell carcinoma of the uterine cervix: relationships to pretreatment tumor oxygenation and vascularization.

Poor outcome of treatment was found to be associated with low oxygen tension in the primary tumor and not with high intratumor microvessel density in 40 patients with advanced squamous cell carcinoma of the uterine cervix. Multivariate Cox regression analysis identified the total volume of the hypoxic tumor regions, i. e. the tumor subvolume having pO(2) values below 5 mmHg, as a significant prognostic factor for locoregional control, disease-free survival, and overall survival. Other important prognostic factors, identified by univariate Cox regression analysis, were tumor volume, the fraction of pO(2) readings giving pO(2) values below 5 mmHg, and tumor stage.