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Many patients develop a variety of bowel dysfunction after sphincter preserving surgeries (SPS) for rectal cancer. The bowel dysfunction usually manifests in the form of low anterior resection syndrome (LARS), which has a negative impact on the patients’ quality of life. This study reviewed the LARS after SPS, its mechanism, risk factors, diagnosis, prevention, and treatment based on previously published studies. Adequate history taking, physical examination of the patients, using validated questionnaires and other diagnostic tools are important for assessment of LARS severity. Treatment of LARS should be tailored to each patient. Multimodal therapy is usually needed for patients with major LARS with acceptable results. The treatment includes conservative management in the form of medical, pelvic floor rehabilitation and transanal irrigation and invasive procedures including neuromodulation. If this treatment failed, fecal diversion may be needed. In conclusion, Initial meticulous dissection with preservation of nerves and creation of a neorectal reservoir during anastomosis and proper Kegel exercise of the anal sphincter can minimize the occurrence of LARS. Pre-treatment counseling is an essential step for patients who have risk factors for developing LARS.

Male reproductive toxicity is a well-known adverse effect of cisplatin (CIS), an important antineoplastic agent used to control several types of cancers. Tadalafil (TDF), is a long-acting phosphodiesterase-5 (PDE5) inhibitor commonly used as treatment for erectile dysfunction. The aim of this work was to study the possible protective effect of TDF against CIS-induced testicular toxicity in rats and the possible involvement of Nrf2/HO-1 pathway, which demonstrates antioxidant and inflammatory activities utilizing zinc protoporphyrin-IX (ZnPP) as HO-1 inhibitor. Results revealed that TDF attenuated the CIS-induced disturbances in sperm count and activities, normalized the serum testosterone level, improved the CIS-induced changes in epididymal and testicular weights and restored the normal structure of testicular tissues. In addition, TDF upregulated the gene expression levels of Nrf2 and HO-1 and the activity of HO-1 whereas, it reduced the CIS-induced changes in testicular oxidative stress markers and the levels of inflammatory mediators (TNF-α and iNOS). Furthermore, TDF antagonized the CIS-induced increase in testicular gene expression of apoptotic markers caspase-3 and Bax, and the decrease in Bcl-2. However, ZnPP co-administration significantly attenuated all TDF-mediated improvements in CIS-induced testicular toxicity, biochemical changes, and apoptosis. In conclusion, TDF exerts a protective effect against CIS-induced reproductive toxicity in males, through different mechanisms, besides its inhibitory action to PDE5, possibly mediated by the upregulation of Nrf2/HO-1, along with its antioxidant, anti-inflammatory, and anti-apoptotic effects. Hence, the use of TDF represents a promising therapeutic approach to protect the male reproductive system from the harmful toxic effects of CIS.

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