Spironolactone Depletes the XPB Protein and Inhibits DNA Damage Responses in UVB-Irradiated Human Skin.

UVB wavelengths of light induce the formation of photoproducts in genomic DNA that are potentially mutagenic and detrimental to epidermal cell function. The mineralocorticoid and androgen receptor antagonist spironolactone (SP) was recently identified as an inhibitor of UV photoproduct removal in human cancer cells in vitro via its ability to promote the rapid proteolytic degradation of the DNA repair protein XPB. Using normal human keratinocytes in vitro and skin explants ex vivo, we found that SP rapidly depleted XPB protein in both systems and abrogated two major responses to UVB-induced DNA damage, including the removal of UV photoproducts from genomic DNA and the activation of ATR/ATM DNA damage kinase signaling. These effects were also correlated with both mutagenesis and a predisposition to UVB-induced cell death but were unique to SP, because neither the SP metabolites canrenone and 7α-thiomethylspironolactone nor the more specific mineralocorticoid receptor antagonist eplerenone affected XPB protein levels or the UVB response. Our findings provide an approach for studying XPB and its roles in the UVB DNA damage response in human skin ex vivo and indicate that SP may increase UVB mutagenesis and skin cancer risk in certain individuals.

Effect of elevated hemoglobin A1c in diabetic patients on complication rates after Roux-en-Y gastric bypass.

BACKGROUND: Little is known regarding the effect of chronic hyperglycemia, expressed by glycated hemoglobin, on the healing-related complication rates in Roux-en-Y gastric bypass (RYGB). METHODS: We retrospectively examined the rate of complications in patients with type 2 diabetes mellitus undergoing RYGB according to the preoperative glycated hemoglobin (HbA1c) level, focusing specifically on the complications related to wound healing (i.e., anastomotic leak, stomal stenosis, and wound infection). Two groups were formed separating those with HbA1c values >7 and <7 g/dL. All patients were taking oral antiglycemic medications or insulin to control their blood glucose levels. RESULTS: A total of 342 patients with type 2 diabetes mellitus underwent laparoscopic RYGB during a 3-year period (2008-2011). Of the 342 patients, 170 had elevated HbA1c values >7 g/dL (average 9.0) preoperatively, of which there were 4 superficial surgical site infections and 1 stomal stenosis, but no anastomotic leaks. Of the remaining 172 diabetic patients whose HbA1c level was <7 g/dL preoperatively (average 6.0 g/dL), 2 superficial surgical site infections, 2 stomal stenoses, and, again, no anastomotic leaks. No difference was seen in the combined complication rates between the 2 groups (2.9% versus 2.3%, P = .50). CONCLUSION: In the present study, an elevated HbA1c >7 g/dL in patients with type 2 diabetes mellitus did not convey increased complication rates after RYGB.

Effect of Helicobacter pylori on marginal ulcer and stomal stenosis after Roux-en-Y gastric bypass.

BACKGROUND: Conflicting data have been published regarding whether Helicobacter pylori (HP) positivity is associated with increased complication rates in patients undergoing Roux-en-Y gastric bypass (RYGB). METHODS: We retrospectively examined the rate of complications in patients undergoing RYGB according to preoperative HP positivity and persistent post-treatment positivity to determine whether a correlation exists. RESULTS: A total of 228 patients underwent RYGB during a 2-year period (2009-2011). No patient had evidence of active ulcer disease on preoperative endoscopy. Of the 228 patients, 68 tested positive for HP on serum antigen screening and were treated with omeprazole, clarithromycin, and amoxillin. After treatment, 24 patients were persistently positive on repeat endoscopic biopsy. Of the 228 patients, 12 experienced a total of 13 complications (stomal stenosis in 8, marginal ulcer in 5, and none with anastomotic leak or gastrointestinal bleeding). Of the 68 patients with HP positivity preoperatively, 1 complication (2.3%) developed in the 44 patients who had responded to triple therapy, and no complications occurred in the 24 patients who had remained positive after treatment (P = 1.00), showing no difference. Also, no significant difference was found in the rate of complications (P = .11) between patients who were HP negative preoperatively (11 of 160, 6.9%) and those who were positive preoperatively (1 of 68, 1.5%). CONCLUSION: HP status, whether positive preoperatively or persistently positive after treatment, had no effect on the marginal ulcer or stomal stenosis rates in patients undergoing RYGB in the present study.

Sleeve gastrectomy: 5-year outcomes of a single institution.

BACKGROUND: Laparoscopic sleeve gastrectomy (SG) is the most recent bariatric surgical procedure to gain universal acceptance by providers and payers. Long-term clinical data on outcomes is limited at this time. METHODS: We retrospectively examined 5-year outcomes (weight loss, complications, and resolution of co-morbid conditions) of patients undergoing SG at our institution. RESULTS: Our initial SG was performed in 2005, and we operated on 55 consecutive patients who are 5 years out from surgery. Six patients were excluded from the long-term results. Four patients underwent conversion to a duodenal switch, and 2 patients died in the first year outside the perioperative period. Average starting body mass index was 65 kg/m(2). Five-year average percent excess weight loss was 86% (range 50%-103%). Percentage of co-morbidities resolved: hypertension (95%), type 2 diabetes mellitus (100%), hyperlipidemia (100%), and obstructive sleep apnea (100%). Gastroesophageal reflux disease (GERD) was resolved in 53%, and new GERD symptoms developed in 11% of patients. There was 1 staple line leak (1.9%), no strictures, no gastrointestinal bleeding, and no perioperative deaths. CONCLUSION: In this study, SG is a well-tolerated and effective bariatric surgical procedure with good long-term weight loss and resolution of co-morbid medical conditions.