Current Opinion on Optimal Treatment Choices in First-line Therapy for Advanced or Metastatic Colorectal Cancer: Report From the Adelaide Colorectal Tumour Group Meeting; Stockholm,Sweden; September 2008

The medical treatment of patients with metastatic colorectal cancer (mCRC) has evolved greatly in the past 10 years, involving complex combined chemotherapy protocols and, in more recent times, new biologic agents. Clinical benefit from the use of the targeted monoclonal antibodies bevacizumab, cetuximab, and panitumumab in the treatment of patients with mCRC is now well-established, but the optimal timing of their use requires careful consideration in order to derive the maximal benefit. Evidence to date suggests potentially distinct roles for bevacizumab and epidermal growth factor receptor–targeted biologic agents (cetuximab and panitumumab) in the treatment of patients with mCRC. This article reviews the evidence in support of modern treatments for mCRC and the decision making behind the treatment choices as well as their benefits and toxicities. An evidence-based algorithm is proposed that incorporates the use of these biologic agents early in the treatment of patients with initially nonresectable mCRC based on clearly defined tumor-related factors dependent on the immediate treatment goal. Real-world application of this algorithm is dependent on an individual countries' approval of access to new biologic agents.     

Cetuximab is associated with excessive toxicity when combined with bevacizumab Plus mFOLFOX6 in metastatic colorectal carcinoma

BackgroundThe bevacizumab-cetuximab combination has shown promising activity in chemotherapy-refractory metastatic colorectal cancer (mCRC). We sought to determine the safety and efficacy of cetuximab added to bevacizumab plus standard mFOLFOX6 (modified 5-fluorouracil [5-FU]/leucovorin/oxaliplatin) as first-line therapy for mCRC.Patients and MethodsSixty-six patients received cetuximab (400 mg/m² loading dose, then 250 mg/m² weekly intravenously [I.V.]) plus bevacizumab 5 mg/kg and mFOLFOX6 chemotherapy every 2 weeks. The primary endpoint was toxicity.ResultsThe most common grade 3-4 events included diarrhea (14%), fatigue (14%), neuropathy (12%), venous thrombosis (9%), acneiform rash (8%), and desquamation (8%). A protocol-defined prohibitive adverse event occurred in 4 patients (6%), including 2 treatment-associated deaths. Thirty-seven patients (56%) discontinued therapy before disease progression because of either toxicity (n = 19; 29%) or patient withdrawal (n = 18; 27%). Twenty-eight of 37 patients (76%) who discontinued therapy before disease progression did so because of cetuximab-associated toxicity.ConclusionAlthough the addition of cetuximab to bevacizumab plus mFOLFOX6 was not associated with excessive life-threatening toxicity, many patients discontinued therapy because of cetuximab-associated toxicity. Taken together with the results of recently reported phase III trials, cetuximab should not be used concurrently with bevacizumab and infusional 5-FU, leucovorin, and oxaliplatin chemotherapy for the treatment of mCRC.     

Primary prevention of bleeding from esophageal varices in patients with liver cirrhosis

Variceal bleeding is a life threatening situation with mortality rates of at least 20%. Prophylactic treatment with non-selective beta blockers(NSBBs) is recommended for patients with small varices that have not bled but with increased risk for bleeding. The recommended treatment strategies on primary prevention of variceal bleeding in patients with medium and largesized varices are NSBBs or endoscopic band ligation. Nitrates, shunt surgery and sclerotherapy are not recommended in this setting. In this review, the most recent data on prevention of esophageal variceal bleeding are presented. Available data derived from randomized-controlled trials suggest both treatment strategies, and according to Baveno V consensus in portal hypertension "the choice of treatment should be based on local resources and expertise, patient preference and characteristics, side-effects and contra-indications".     

Neuroticism personality trait is associated with Quality of Life in patients with Chronic Heart Failure

AIM: To evaluate Quality of life(QoL) in chronic heart failure(CHF) in relation to Neuroticism personality trait and CHF severity.METHODS: Thirty six consecutive, outpatients with Chronic Heart Failure(6 females and 30 males, mean age: 54 ± 12 years), with a left ventricular ejection fraction ≤ 45% at optimal medical treatment at the time of inclusion, were asked to answer the Kansas City Cardiomyopathy Questionnaire(KCCQ) for Quality ofLife assessment and the NEO Five-Factor Personality Inventory for personality assessment. All patients un-derwent a symptom limited cardiopulmonary exercise testing on a cycle-ergometer, in order to access CHF severity. A multivariate linear regression analysis us-ing simultaneous entry of predictors was performed to examine which of the CHF variables and of the person-ality variables were correlated independently to QoL scores in the two summary scales of the KCCQ, namely the Overall Summary Scale and the Clinical Summary Scale.RESULTS: The Neuroticism personality trait score had a significant inverse correlation with the Clinical Sum-mary Score and Overall Summary Score of the KCCQ(r =-0.621, P 0.05 and r =-0.543, P 0.001, respec-tively). KCCQ summary scales did not show significant correlations with the personality traits of Extraversion, Openness, Conscientiousness and Agreeableness. Mul-tivariate linear regression analysis using simultaneous entry of predictors was also conducted to determine the best linear combination of statistically significant univari-ate predictors such as Neuroticism, VE/VCO2 slope and VO2 peak, for predicting KCCQ Clinical Summary Score. The results show Neuroticism(β =-0.37, P 0.05), VE/VCO2 slope(β =-0.31, P 0.05) and VO2 peak(β = 0.37, P 0.05) to be independent predictors of QoL. In multivariate regression analysis Neuroticism(b =-0.37, P 0.05), the slope of ventilatory equivalent for carbon dioxide output during exercise,(VE/VCO2 slope)(b =-0.31, P 0.05) and peak oxygen uptake(VO2 peak),(b = 0.37, P 0.05) were independent predictors of QoL(adjusted R2 = 0.64; F = 18.89, P 0.001).CONCLUSION: Neuroticism is independently associat-ed with QoL in CHF. QoL in CHF is not only determined by disease severity but also by the Neuroticism person-ality trait.     

Robotic technology for pelvic exenteration in cases of cervical cancer

Background

Cervical cancer represents one of the most common types of neoplasia among women; the use of minimally invasive techniques in the treatment of cervical cancer is a challenge.

Objectives

To present evidence regarding robotic technology in the performance of pelvic exenteration in cases of cervical cancer.

Search strategy

PubMed and Scopus databases were searched.

Selection criteria

Articles examining the use of robotic technology for pelvic exenteration in cases of cervical cancer were included.

Data collection and analysis

Four studies were included.

Main results

Most cancers treated with robotic-assisted pelvic exenteration were squamous cell carcinomas of the cervix. The stage of primary cancer ranged from IB2 to IVA. In 7 of the 8 patients, anterior pelvic exenteration was performed; the other patient underwent total pelvic exenteration. Procedure duration ranged from 375 to 600 minutes; blood loss was 200–550 mL. Postoperative complications occurred in 2 of the 8 patients and included perineal abscess, Miami pouch fistula, and ureteral stenosis. Postoperative hospital stay ranged from 3 to 53 days, and postoperative follow-up ranged from 2 to 31 months.

Conclusions

The gold standard for pelvic exenteration remains the open surgical approach; however, the application of robotic technology could be an alternate choice associated with excellent results.     

Single-site port robotic-assisted hysterectomy: a systematic review

Introduction

Robotic single-port hysterectomy is a rather new technique.

Materials and Methods

We performed a systematic literature review to evaluate the till-now evidence regarding the use of robotic single-port hysterectomy technique as a method of management in gynecological pathologies.

Results

The till-now used port systems are discussed. The advantages and disadvantages of such a technique, as well as the indications and contraindications of it are also presented. Such a technically challenging operation seems to have similar results regarding blood loss and surgical time while the cosmetic outcome is better compared to the classic robotic hysterectomy. The technical difficulties include loss of instrumental triangulation, reduced operative working place, reduced visualization, instrumental crowding and clashing. The ways to overcome such difficulties are also described.

Conclusion

The need of technique standardization is the future aim.     

Breastfeeding in Byzantine icon art

Introduction

The Mary Galaktotrophousa is a representation of the Virgin breastfeeding the infant Jesus.

Materials

The origin of this theme goes back to Antiquity when images of gods feeding humans were considered as an example that should be imitated by human. In the early days of Christianity, the Fathers of the Church recognized on the feature of Mary the ideal exemplary of maternity.

Conclusion

The image of the Virgin breastfeeding the Holy Child, except the theological interpretation of the gesture, underline the fact that breastfeeding represents one of the most substantial gestures in the woman nature.     

Five-year incidence of type 2 diabetes mellitus among cardiovascular disease-free Greek adults: findings from the ATTICA study

Objective

We evaluated the 5-year incidence of diabetes in an adult population from Greece.

Research design and methods

3042 individuals (>18 years), free of cardiovascular disease, participated in the baseline examination (during 2001–2002). Of this sample, 1012 men and 1035 women were found alive at the time of follow-up, while 32 (2.1%) men and 22 (1.4%) women died during this period. The rest were lost to follow-up. Incidence of type 2 diabetes mellitus was evaluated in 1806 participants who did not have diabetes at baseline.

Results

The age-adjusted 5-year incidence of diabetes was 5.5% (men, 5.8%; women, 5.2%). A linear trend was observed between diabetes incidence and age (5.6% increases in incidence per 1-year difference in age, p < 0.001). Multiple logistic regression analysis revealed that age (OR per 1 yr = 1.04, 95% CI 1.02–1.06), waist (OR per 1 cm = 1.02, 95% CI 1.01–1.003), physical activity (OR = 0.62, 95% CI 0.35–1.02) and family history of diabetes (OR = 2.65, 95% CI 1.58–4.53), as well as fasting glucose levels (OR per 1 mg/dl = 1.05, 95% CI 1.03–1.07), were the most significant baseline predictors for diabetes, after adjusting for various potential confounders. Additionally, presence of metabolic syndrome at baseline evaluation 2.95-fold the risk of diabetes (95% CI 1.89–4.61), and showed better classification ability than the model that contained the components of the syndrome (ie, correct classification rate: 94.5% vs. 92.3%).

Conclusion

Our findings show that a 5.5% incidence rate of diabetes within a 5-year period, which suggests that the prevalence of this disorder in Greece is rising. Aging, heredity, and metabolic syndrome were the most significant determinants of diabetes.