Interferon-Gamma and Tumor Necrosis Factor-Related Weak Inducer of Apoptosis Expression in Neoangiogenesis in Colorectal Polypoid Lesions.

BACKGROUND: Interferon gamma (IFNγ) and tumor necrosis factor-related weak inducer of apoptosis (TWEAK) molecules seem to have a potential effect on angiogenic factors such as vascular endothelial growth factor (VEGF). The aim of this study was to assess a possible interplay between IFNγ and TWEAK cytokines and VEGF machinery in the different steps of colorectal carcinogenesis. METHODS: A total of 92 subjects with colonic adenoma or cancer who underwent screening colonoscopy or surgery were prospectively enrolled. Polypoid lesion tissue samples were collected and frozen. Real-time reverse transcription polymerase chain reaction for IFNγ, TWEAK, and VEGF-A mRNA expression was performed. Immunoassays for VEGF-A, VEGF-C, VEGFR-1, VEGFR-2, and VEGFR-3 were also performed. Nonparametric statistics, receiver operating characteristic curve analysis, and logistic multiple regression analysis were used. RESULTS: IFNγ and TWEAK mRNA expression was higher in patients with T2 or more advanced colorectal cancer than in those with adenomas or T1 cancer (p < 0.001 and p = 0.01, respectively). IFNγ and TWEAK mRNA expression levels directly correlated with VEGF-A mRNA expression levels (rho = 0.44, p < 0.001 and rho = 0.29, p = 0.004, respectively). On the contrary, IFNγ and TWEAK mRNA expression levels inversely correlated with VEGF-C protein levels (rho = -0.29, p = 0.04 and rho = -0.31, p = 0.03, respectively). Similarly, IFNγ and TWEAK mRNA expression levels inversely correlated with VEGFR2 protein levels (rho = -0.38, p = 0.033 and rho = -0.40, p = 0.025, respectively). CONCLUSION: This study showed that in colorectal polypoid lesions, IFNγ and TWEAK expressions are directly correlated to VEGF-A expression but inversely correlated with VEGFR2 levels, suggesting a possible feedback mechanism in the regulation of VEGF-A expression.

Long-term quality of life after esophagectomy with gastric pull-up.

BACKGROUND AND OBJECTIVES: Data on long-term health-related quality of life (HRQL) after esophagectomy for cancer show contradictory results. The aim was to analyze long-term HRQL at 3 or more years after esophagectomy. METHODS: Survivors were identified among patients who had undergone esophagectomy during 2007-2013 using the local clinic database. Quality of life was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 and OG25 questionnaires. Specific aspects were selected a priori and compared with published scores from European healthy subjects (mean difference, MD). RESULTS: Sixty-five long-term survivors (median follow-up 4 years) were identified. All functional scales and most symptom scales were clinically similar between EC long-term survivors and European healthy subjects. Survivors reported more problems concerning eating (MD 13.1, 95% C.I. 10.6-15.6) and reflux (MD 19.7, 95% C.I. 15.9-23.5). HQRL variation from discharge to long term was available in 27 participants who reported improvements in role functioning (MD 40.1, 95%C.I. 24.3-56.0) and dysphagia (MD -41.9, 95% C.I. -51.7 to 32.0). CONCLUSIONS: Long-term HRQL after esophagectomy is similar between EC survivors and European healthy subjects, despite persisting reflux and eating problems. Further research may focus on improvements of postoperative alimentary habits.

Health related quality of life after oesophagectomy: elderly patients refer similar eating and swallowing difficulties than younger patients.

BACKGROUND: Oesophagectomy for cancer could be safe and worthwhile in selected older patients, but less is known about the effect of oesophagectomy on perceived quality of life of such delicate class of cancer patients. The aim of this study was to evaluate the impact of oesophagectomy for cancer in elderly patients in term of health-related quality of life. METHODS: We retrospectively evaluated all consecutive patients who underwent oesophagectomy for cancer at the Surgical Oncology Unit of the Veneto Institute of Oncology between November 2009 and March 2014. Quality of life was evaluated using EORTC C-30 and OES-18 questionnaires at admission, at discharge and 3 months after surgery. Adjusted multivariable linear mixed effect models were estimated to assess mean score differences (MDs) of selected aspects in older (≥70 years) and younger (<70 years) patients. RESULTS: Among 109 participating patients, 23 (21.1 %) were at least 70 years old and 86 (78.9 %) were younger than 70 years. Global quality of life was clinically similar between older and younger patients over time (MD 4.4). Older patients reported clinically and statistically significantly worse swallowing saliva (MD 17.4, 95 % C.I. 3.6 to 31.2), choking when swallowing (MD 13.8, 95 % C.I. 5.8 to 21.8) and eating difficulties (MD 20.1 95 % C.I. 7.4 to 32.8) than younger patients only at admission. CONCLUSIONS: Early health-related quality of life perception after surgery resulted comparable in older and younger patients. This result may also be due to some predisposition of the elderly to adapt to the new status.

Sleep disturbances and quality of life in postoperative management after esophagectomy for esophageal cancer.

BACKGROUND: The aims of this prospective study were to analyze the predictors of postoperative sleep disturbance after esophagectomy for cancer and to identify patients at risk for postoperative hypnotic administration. METHODS: Sixty two consecutive patients who underwent cancer-related esophagectomy were enrolled in this study from May 2011 to February 2012. Data about perioperative management, postoperative complications, ICU stay, and vasopressor, hypnotic, and painkiller administration were retrieved. The EORTC QLQ-C30 was used and global quality of life (QL2 item) and sleep disturbance (SL item) were the primary endpoints. Univariate and multivariate analyses were performed. RESULTS: Postoperative request of hypnotics independently predicted bad quality of life outcome. Sleep disturbance after esophagectomy was independently predicted by the duration of dopamine infusion in the ICU and the daily request of benzodiazepines. Even in this case, only sleep disturbance at diagnosis revealed to be an independent predictor of hypnotic administration need. ROC curve analysis showed that sleep disturbance at diagnosis was a good predictor of benzodiazepine request (AUC = 73%, P = 0.02). CONCLUSIONS: The use of vasopressors in the ICU affects sleep in the following postoperative period and the use of hypnotics is neither completely successful nor lacking in possible consequences. Sleep disturbance at diagnosis can successfully predict patients who can develop sleep disturbance during the postoperative period.

Health-related quality of life in patients with oesophageal cancer: analysis at different steps of the treatment pathway.

BACKGROUND: The main outcome parameters in oesophageal surgery have traditionally been morbidity and mortality, but quality of life (QL) has become an important consideration in view of the severity and persistence of postoperative symptoms. The aim of this study was to analyse QL before and after oesophagectomy for oesophageal cancer and to explore possible association with patient's and disease characteristics. PATIENTS AND METHODS: One hundred twenty-six consecutive patients presenting with oesophageal cancer to the Oncological Surgery Unit of the Veneto Institute of Oncology between 2009 and 2011 were enrolled in this prospective study. The patients were asked to answer three QL questionnaires (the Italian versions of the QLQ-C30, the QLQ-OES18, and the IN-PATSAT32 modules developed by the European Organization for Research and Treatment of Cancer) at the time of disease diagnosis, after neoadjuvant therapy, immediately after surgery and at 1, 3, 6 and 12 months postoperatively. RESULTS: Global quality of life (QL2 item) seemed to improve after neoadjuvant therapy but it dropped markedly after surgery. It then rose to a value in between the one registered after neoadjuvant therapy and the one at diagnosis. Emotional function and dysphagia were associated to QL2 at diagnosis. After neoadjuvant therapy, age, oesophageal stenosis, emotional function and dysphagia were associated to good quality of life at that stage. After surgery, pain was associated to quality of life at that stage. During the early follow-up phase (1-3 months after surgery), role function and postoperative urinary complications were associated to QL2. In the long-term follow-up (6-12 months), adjuvant therapy, eating disorders and postoperative complications were associated to poor quality of life. CONCLUSIONS: Postoperative complications are associated to long-term emotional and physical function impairment which can lead to a significantly impaired global quality of life. Postoperative pain relief plays a key role in achieving a good postoperative quality of life. Finally, HRQL after oesophagectomy seems to be a function of therapeutic efficacy rather than of the specific surgical procedure used.

Overweight patients operated on for cancer of the esophagus survive longer than normal-weight patients.

BACKGROUND: Esophageal adenocarcinoma is often associated with obesity, and a 5 Kg m(-2) increase in body mass index (BMI) has, in fact, been found to be strongly associated with the risk of this type of cancer (RR, 1.52; p < 0.0001). Esophagectomy with lymphoadenectomy is the mainstay of therapy for these patients. The aim of this study was to assess and compare the surgical and oncological outcomes as well as the survival rates of underweight, normal weight, overweight, and obese patients following esophagectomy for esophageal cancer. PATIENTS AND METHODS: Data relative to 1,127 patients with esophageal adenocarcinoma presenting at a specialized tertiary hospital (the Center of Esophageal Diseases for the Veneto Region) between 2000 and 2008 were prospectively collected. The 278 subjects whose BMI values before disease onset were available and underwent esophagectomy were enrolled in the study. Sixty-one of the 278 patients were classified as obese (BMI >30), 121 were classified as overweight (BMI, 25-29.9), 81 were classified as normal weight (BMI <24.9), and 15 ones as underweight (BMI <20). The outcome and survival of the four groups were compared. Frequency and survival analyses were carried out. RESULTS: The rate of R0 esophagectomy and the incidence of toxicity during neoadjuvant chemotherapy were similar in the four groups. Respiratory complications after R0 esophagectomy seemed to be more frequent in the underweight and normal-weight patients group (p < 0.01). Moreover, underweight patients had a significantly higher rate of septic, cardiovascular, and metabolic postoperative complications. The 121 overweight patients had a better overall survival rate compared to normal weight and obese patients (p = 0.05). This difference was not significant if patients were stratified in stages I or II or stages III or IV. CONCLUSION: Overweight patients seem to respond better to esophageal cancer and esophagectomy with respect to normal-weight ones. This data seem to suggest that in spite of several unfavorable features, a moderate increase of weight may be helpful to survive after esophagectomy for cancer.