Interaction of glutathione-s-transferase genotypes with environmental risk factors in determining susceptibility to head and neck cancer and treatment response and survival outcome

The present case-control study aimed to investigate the role of interaction of glutathione-s-transferase (GST) genotypes with environmental risk factors in determining susceptibility to head and neck squamous cell carcinoma (HNSCC) involving 1,250 cases and equal number of healthy controls. An increase in the risk of HNSCC and its subsites (larynx, pharynx, and oral cavity) was observed among the cases with null genotypes of GSTM1 (odds ratio [OR] = 1.87) or GSTT1 (OR = 1.39) while reduced risk (OR = 0.81) was observed the cases with variant genotype of GSTP1. Tobacco use in the form of smoking or chewing interacted multiplicatively with GSTM1 or GSTT1 to increase the risk several folds (3–10 folds) in HNSCC and its subsites. Alcohol use also increased the risk (2–3 folds) to HNSCC and its subsites in cases with null or variant genotypes of GSTs, though this risk was of lesser magnitude when compared to the tobacco users. A synergistic effect of both, tobacco smoking and alcohol drinking, led to several folds (25-folds) increased risk to HNSCC among the cases with null genotype of GSTM1 and GSTT1 when compared to nonsmokers and nondrinkers with wild genotype of GSTM1 and GSTT1 in controls. Furthermore, cases with variant genotypes of GSTP1 (Val/Val) showed superior treatment response with improved survival rate and lower risk of death when compared to the patients with wild type genotype (Ile/Ile). The data suggest that though polymorphism in GSTs may be a modest risk factor for determining HNSCC risk, gene-environment interactions significantly modify the susceptibility to HNSCC by several folds.     

The double loop mattress suture

An interrupted stitch type with favorable tissue characteristics will reduce local wound complications. We describe a novel high‐strength, low‐tension repair for the interrupted closure of skin, cartilage, and muscle, the double loop mattress stitch, and compare it experimentally with other interrupted closure methods. The performance of the double loop mattress technique in porcine cartilage and skeletal muscle is compared with the simple, mattress, and loop mattress interrupted sutures in both a novel porcine loading chamber and mechanical model. Wound apposition is assessed by electron microscopy. The performance of the double loop mattress in vivo was confirmed using a series of 805 pediatric laparotomies/laparoscopies. The double loop mattress suture is 3.5 times stronger than the loop mattress in muscle and 1.6 times stronger in cartilage (p ≤ 0.001). Additionally, the double loop mattress reduces tissue tension by 66% compared with just 53% for the loop mattress (p ≤ 0.001). Wound gapping is equal, and wound eversion appears significantly improved (p ≤ 0.001) compared with the loop mattress in vitro. In vivo, the double loop mattress performs as well as the loop mattress and significantly better than the mattress stitch in assessments of wound eversion and dehiscence. There were no episodes of stitch extrusion in our series of patients. The mechanical advantage of its intrinsic pulley arrangement gives the double loop mattress its favorable properties. Wound dehiscence is reduced because this stitch type is stronger and exerts less tension on the tissue than the mattress stitch. We advocate the use of this novel stitch wherever a high‐strength, low‐tension repair is required. These properties will enhance wound repair, and its application will be useful to surgeons of all disciplines.