Associations differ by sex for catechol-O-methyltransferase genotypes and bladder cancer risk in South Egypt

ObjectivesTo examine associations between urinary bladder cancer risk and polymorphisms of the gene encoding the catechol estrogen-metabolizing enzyme, catechol-O-methyltransferase (COMT), among Egyptian women and men.Materials and methodsWe used questionnaire and genotype data from a case-control study in Egypt. This analysis focused on South Egypt cases with confirmed urothelial (UC) or squamous cell (SCC) carcinoma of the bladder, and controls frequency-matched on sex, 5-year age-group, and residence governorate. Real-time PCR on blood specimen DNA was used to determine COMT genotypes encoding for Val/Val, Val/Met, and Met/Met, the enzyme forms associated with high, intermediate, or low activity, respectively.ResultsThe study sample, which included 255 women and 666 men, consisted of 394 cases with histologically confirmed UC (225) or SCC (n = 169), and 527 controls. The odds of having either type of bladder cancer were lower among men with genotypes encoding Val/Met or Met/Met than among those with the genotype encoding Val/Val, even after adjustment for other factors, such as smoking and schistosomiasis history [adjusted odds ratio (AOR): 0.64; 95% confidence interval (CI): 0.43, 0.96]; however, the association was statistically significant for SCC (AOR 0.57; 95% CI: 0.34, 0.96) but marginal for UC (AOR: 0.64; 95% CI: 0.39, 1.02). No significant associations were detected between bladder cancer risk and COMT genotypes among postmenopausal women.ConclusionsThese findings suggest that even after controlling for established risk factors, the involvement of COMT genotypes in bladder cancer risk differs among men compared with women in South Egypt.     

Tracheal inujry due to blunt chest trauma: a rare surgical emergency

Tracheal injury is a rare complication of blunt chest trauma. The patients usually present with signs of respiratory distress. Primary repair is the treatment of choice in case of large defects, while small tears can be managed conservatively. Immediate operation is recommended to improve deteriorating pulmonary function. The decrease in mortality and long-term morbidity depends on early diagnosis. We report a case of tracheal injury due to non-penetrating thoracic trauma which was successfully managed with surgery.     

Significance of Diaphragmatic Resections and Thoracic Chemoperfusion on Outcomes of Peritoneal Surface Disease Treated with Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Background

Diaphragmatic resection (DR) during CRS/HIPEC exposes the thoracic cavity to direct contamination from the peritoneal cavity. The effect of thoracic chemoperfusion in combination with HIPEC in these patients is unknown.

Methods

A prospective database of 1,077 procedures was analyzed. Type of malignancy, thoracic perfusion, resection status, comorbidities, morbidity, mortality, and overall survival were reviewed.

Results

DR was a component of 102 CRS/HIPEC procedures performed for 57 (55.9 %) appendiceal and 22 (21.6 %) colon primary lesions. DR was associated with higher volume of disease as evidenced by more organ resections (3.7 vs. 2.8, p < 0.001) and increased rates of incomplete cytoreduction (67 vs. 52 %, p = 0.004). Patients with and without DR had similar 30-day major morbidity (23.5 vs. 16.8 %, p = 0.1) and worse 90-day mortality (12.8 % vs. 6.12 %, p = 0.03), respectively. Multivariate analysis showed DR (p = 0.01) and diabetes (p = 0.005) to be associated with worse mortality. Nineteen (20 %) DR patients underwent synchronous abdominal and thoracic chemoperfusion. Intrathoracic recurrence following DR with thoracic perfusion was 17 % (3/18) vs. 2.3 % (2/85) without perfusion (p = 0.04). Median survival following complete cytoreduction was similar for patients with low-grade appendiceal (LGA) (not reached with DR and 175 months without DR, p = 0.17) and colorectal cancer (23 months with and 31 months without DR, p = 0.76).

Conclusions

Diaphragmatic resection during CRS/HIPEC is an independent predictor of surgical mortality. Intrapleural perfusion was associated with more thoracic recurrence; however, complete cytoreduction with or without DR can achieve similar survival for patients with LGA and colorectal primary lesions. DR should be performed only if careful inspection deems all peritoneal disease resectable.     

Cathepsin D protein levels in colorectal tumors: divergent expression patterns suggest complex regulation and function

Cathepsin D protein patterns were analyzed in 59 colorectal tumors by Western blotting, glycosylation and immunohistochemical assays. Measurement of protein content by laser densitometry of tumor/normal pairs on Western blots revealed loss of cathepsin D protein in more than 50% of colorectal tumors. Independent loading controls and statistical estimates of reproducibility on duplicate assays confirmed frequent decreases in cathepsin D. For cases having a tumor/normal ratio (T/N) <1, the average T/N was 0.50+/-0.19, equivalent to the loss of one cathepsin D allele. However, 2-fold increases in cathepsin D protein levels were also observed in approximately 1/3 of tumors, supporting the concept that colorectal cancers develop via divergent molecular pathways and that cathepsin D may function differently in different cancers. Although normal cathepsin D expression was detected in some earlier stage tumors, protein levels became increasingly bimodal with progression such that cathepsin D levels were increased in 1/3 but decreased in 2/3 of stage III and IV cancers. Other laboratories have reported both significant loss and gain of chromosome 11 (site of the cathepsin D gene) in different colorectal tumors, providing a possible mechanism for our observations on cathepsin D. However, differential regulation of cathepsin D expression by mutant versus wild-type p53 may also contribute to variable cathepsin D levels in colorectal cancers. Immunohistochemical studies demonstrated a shift from a predominantly punctate distribution of cathepsin D protein in normal mucosa to a more diffuse cytoplasmic distribution in tumor tissues. Mutant forms of cathepsin D were not detected in tumors either as changes in electrophoretic mobility or altered glycosylation but minor changes in protein sequence could not be ruled out. Loss of cathepsin D protein may provide an advantage to colorectal tumors related to a loss of cathepsin D function in proapototic or antiangiogenic pathways while increased cathepsin D may promote cancer cell proliferation or invasion.     

Tobacco control – An integral component of the national action plan on non communicable diseases in Pakistan

Pakistan is currently implementing a national programme for the prevention and control of non-communicable diseases (NCD) – the NAP-NCD program. As an integrated approach to addressing the multidisciplinary range of issues across the broad range of NCDs, this strategy has been modeled to impact a set of indicators through the combination of a range of actions capitalizing on the strengths of a public-private partnership, which is led by the NGO Heartfile and constituted additionally by the Ministry of Health, Government of Pakistan and WHO. Focused on institutional, community and public policy level change, this strategy factors integration through its Integrated Framework for Action at four levels: grouping NCDs so that they can be targeted through a set of actions, harmonizing actions, integrating actions with existing public health systems and incorporating contemporary evidence-based concepts with this approach. A range of policy and environmental strategies are part of the tobacco control component of the plan. These involve regulating access and limiting demand through restrictions on advertising, marketing, promotion and through price control and taxation; community and school interventions; cessation programmes; mass media counter-marketing campaigns for both prevention and cessation; surveillance and evaluation of efforts and operational research around tobacco and building capacity in the health system in support of tobacco control. NAP-NCD also stresses the need to develop and enforce legislation on smuggling contrabands and counterfeiting along with legislation to subject tobacco to stringent regulations as those governing pharmaceutical products. The adoption of measures to discourage tobacco cultivation and assist with crop diversification; integration of guidance on tobacco use cessation into health services and ensuing the availability and access to nicotine replacement therapy are also part of NAP-NCD.