Neoadjuvant Radiotherapy for Rectal Cancer: Meta-analysis of Randomized Controlled Trials

Background

Although neoadjuvant radiotherapy may improve local control of rectal cancer, its clinical value requires further evaluation as a result of potential side effects and advances in surgical technique. A meta-analysis was performed to assess effectiveness and safety of neoadjuvant radiotherapy in the management of rectal cancer.

Methods

The following databases were searched: the Cochrane Library, Biosis, Web of Science, Embase, ASCO Abstracts and WHO International Clinical Trials Registry Platform. Randomized controlled trials on the following comparisons were included: (1) neoadjuvant therapy versus surgery alone and (2) neoadjuvant chemoradiotherapy versus neoadjuvant radiotherapy.

Results

We identified 17 and 5 relevant trials that enrolled 8,568 and 2,393 patients, respectively. Neoadjuvant radiotherapy improved local control (hazard ratio 0.59; 95 % confidence interval 0.48–0.72) compared to surgery alone even after total mesorectal excision, whereas its benefit in overall survival just failed to reach statistical significance (0.93; 0.85–1.00). However, it was associated with increased perioperative mortality (1.48; 1.08–2.03), in particular if a dose of 5 Gy per fraction was administered (1.85; 1.23–2.78). Chemoradiotherapy improved local control as opposed to radiotherapy (0.53; 0.39–0.72), with no impact on perioperative outcome and long-term survival.

Conclusions

Neoadjuvant radiotherapy improves local control in patients with rectal cancer, particularly when chemoradiotherapy is administered. The question if the use of more effective chemotherapy protocols improves overall survival warrants further investigation.     

Expression profile of Toll-like receptor 4 in rat testis and epididymis throughout postnatal development

Toll-like receptors (TLRs) belonging to pattern recognition receptors are involved in maintaining testicular and epididymal immune homeostasis. The purpose of the current study was to investigate TLR4 expression in rat testis and epididymis throughout postnatal development. Weak staining was detected in peritubular myoid cells and immature Sertoli cells while no staining was observed in gonocytes during prepubertal period. However, TLR4 expression began to appear in spermatocytes in pubertal period and gradually increased in spermatids. An intense staining was observed in steps 5–19 spermatids in post pubertal and mature periods. Similarly, TLR4 expression in the testes steadily increased from pubertal period to mature period. Puberty also caused a significant increase in TLR4 expression in epididymis. TLR4 expression in cauda epididymis was lower as compared to those of other epididymal segments. The majority of epididymal epithelial cells exhibited apical TLR4 expression, whereas basal cells showed intense intracytoplasmic immunoreaction. We detected an intense staining in epididymal smooth muscle cells. The expression levels of TLR4 showed dynamic changes in both spermatogenic cells, and entire testicular and epididymal tissues during postnatal development. These results suggest that TLR4 expression contributes not only to inflammation but also to the development of spermatogenic cells.     

Comparison of various surgical approaches for extensive bilateral colorectal liver metastases

Purpose

Tailored operative strategies have been proposed for patients with bilobar colorectal liver metastases (CLM). The aim of the study was to evaluate the long-term outcome, safety and efficacy, including cancer-specific survival, morbidity, and mortality, of three different surgical strategies for extensive bilateral CLM.

Methods

This is a retrospective study of a prospective database of 356 consecutive patients, who underwent hepatic resection due to CLM between January 2003 and January 2009. Fifty-nine patients underwent three different therapeutic approaches: 22 patients with portal vein embolization (PVE) + staged resections, 11 patients with staged resections solely, and 26 patients with an extensive liver resection and simultaneous or subsequent radiofrequency ablation (RFA).

Results

The three groups were comparable regarding their general patient characteristics. The overall morbidity and mortality rates were 27.1 and 1.7 %, respectively. There were no significant differences in morbidity, mortality, or survival between the three groups. The median survival of all patients was 48 months, with a recurrence-free survival of 30 months.

Conclusions

The clearance of bilobar CLM can be achieved by various strategies, all of them providing an acceptable mortality rate and survival for the patients. Therefore, patients with bilobar liver metastases should receive a procedure tailored for their individual extent of disease.     

Protective effect of IGF-1 on experimental liver cirrhosis-induced common bile duct ligation

BACKGROUND/AIMS: The causes of malnutrition in liver cirrhosis are multifactorial. Levels of IGF-1 (insulin like growth factor-1) that is a crucial regulator of intermediary metabolism decreases. The aim of this study was to analyze the effect of IGF-1 supplementation during liver cirrhosis induced by common bile duct ligation. METHODOLOGY: Rats were divided into five different groups: One sham and four experimental groups. Rats in three of four groups were treated with 2 micrograms/day IGF-1 with a different time of experiment in each group. Blood biochemical parameters, tissue malondialdehyde, glutathione levels and the activity of tissue antioxidant enzymes and conventional and immunohistochemical analysis of liver samples were studied for each group. RESULTS: Serum albumin, total protein, fibrinogen levels decreased and prothrombin time was prolonged in the bile duct ligated and transected experimental group but not in the IGF-I treated rats compared with the rats in sham group. Liver malondialdehyde levels significantly increased in control group but not in IGF-1 treated groups. The activities of antioxidant enzymes were decreased compared with the other groups. Histopathology findings of liver biopsy demonstrated intense degree fibrosis and overexpression of fibroblast growth factor and desmin in the control group but a lesser degree of those in the IGF-1 treated groups. CONCLUSIONS: IGF-1 treatment improves liver function and decreases oxidative liver damage and histopathological findings. Further studies are required to delineate the mechanisms of protective effects of IGF-1.     

High prevalence of diabetes in Adana, a southern province of Turkey

OBJECTIVE: To determine the prevalence of diabetes and glucose intolerance and their relationship with risk factors in Adana, a southern province of Turkey, where risk factors are more prominent, probably because of social and economic reasons. RESEARCH DESIGN AND METHODS: The study population included 1637 randomly selected adults aged 20-79 years. Diagnosis of diabetes was based on plasma glucose values using the 1999 diagnostic criteria recommended by the World Health Organization. RESULTS: The crude prevalence of diabetes was 12.9% in men and 10.9% in women (P = 0.207). Total prevalence of diabetes was 11.6%. The screening process identified previously undiagnosed diabetes in 4.2% of individuals and impaired glucose homeostasis (consisting of impaired glucose tolerance and impaired fasting glucose) in an additional 4.3% of subjects. The prevalence of hypertension was 26.4% among men and 36.6% among women (P < 0.0001). Total prevalence of hypertension was 32.9%, and prevalence of obesity was 43.4%. Age, sex, BMI, waist circumference, hypertension, family history of diabetes, and triglycerides were independently associated with diabetes. CONCLUSIONS: The prevalence of diabetes in Adana is higher than expected in both urban and rural areas. Obesity and hypertension also seem to be common metabolic disorders in this area. Age, hypertension, obesity, high triglyceride level, and family history of diabetes are independently associated with diabetes. Therefore, primary prevention through lifestyle modifications may have a critical role in the control of diabetes.     

Expression pattern of galectin-1 and galectin-3 in rat testes and epididymis during postnatal development

Galectins are a family of lectins-binding beta-galactosides involved in a variety of extracellular and intracellular processes, thereby contributing to homeostasis, cell adhesion, cellular turnover, and immunity. This study aimed to determine the localization and expression of galectin-1 (Gal-1) and galectin-3 (Gal-3) in the testis and epididymis of rats at postnatal [(prepubertal (day 5), pubertal (day 20), postpubertal (day 50) and mature (day 70)] periods by using immunohistochemistry and Western blotting. Gal-1 and Gal-3 were differentially expressed in different types of cells in the testis and epididymis during postnatal development. While we detected Gal-1 expression in some spermatogenic cells and Leydig cells in the testis, not in the epididymal epithelium, Gal-3 was expressed in Sertoli cells, peritubular myoid cells, Leydig cells, smooth muscles and interstitial CD68-positive macrophages. Epithelial cells of the corpus and cauda epididymis showed an intense Gal-3 expression. Gal-1 expression was higher in the testis than in the epididymis on days 50 and 70. The expression of Gal-3 in the testis increased from the prepubertal to mature period. While the expression difference of Gal-3 was not statistically significant in the testis and epididymis until puberty, Gal-3 expression in the postpubertal and mature periods was higher in the epididymis. The expression of Gal-3 in the corpus and cauda epididymis was higher than that in the caput epididymis. In conclusion, our findings suggest that puberty has potential regulatory effect on the expression of galectins in testis and epididymis of rats. Gal-1 and 3 may play a role in the development of the reproductive system and the preservation of the immune-privileged environment in the testis, due to their pro-apoptotic and anti-apoptotic functions. The presence of intense expression of Gal-3 in the corpus and cauda epididymis may contribute to the maturation and storage of spermatozoa.     

Meta-Analysis of the Clamp-Crushing Technique for Transection of the Parenchyma in Elective Hepatic Resection: Back to Where We Started?

Background  After introduction of the clamp-crushing technique in the 1970s, various devices have been developed for transection of the liver with the aim of further reducing blood loss and improving the outcome of patients who undergo hepatic resection. We performed a meta-analysis to quantitatively compare the clamp-crushing technique to any subsequently introduced transection technique with respect to patients’ perioperative outcome. Methods  A systematic literature search was conducted to identify randomized controlled trials comparing the clamp-crushing technique to any alternative method of hepatic transection. Relative risks (RR) were calculated for each outcome and reported along with their 95% confidence intervals (95% CI). Meta-analyses were stratified for the various types of transection techniques compared with the clamp-crushing technique and were carried out by a random effects model. Results  Seven randomized controlled trials with a total of 554 patients were included in final analyses. Analyses of overall morbidity (RR .89; 95% CI, .63–1.25), biliary leakage (RR 1.03; 95% CI, .50–2.13), transfusion rates (RR .69; 95% CI, .31–1.51), and mortality RR (.20; 95% CI, .02–1.65) revealed no difference between the clamp-crushing and alternative transection techniques. None of the identified studies demonstrated a clinically important benefit of an alternative transection method in terms of blood loss, parenchymal injury, transection time, and hospital stay. Conclusions  This meta-analysis does not indicate a benefit of any alternative transection technique on patients’ perioperative outcome compared with the clamp-crushing technique. The clamp-crushing technique remains the reference technique for transection of the parenchyma in elective hepatic resection. Nuh N. Rahbari, Moritz Koch authors contributed equally to this article.     

Validation of Prognostic Scoring Systems for Patients Undergoing Resection of Colorectal Cancer Liver Metastases

Background  

Several prognostic scoring systems have been established for patients undergoing resection of colorectal cancer (CRC) liver metastases; however, comparative analyses of their prognostic relevance is still lacking in the literature. The aim of the present study was to assess the predictive value of five published scoring systems in an independent patient cohort for the purpose of external validation.