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Purpose: Distant recurrence is a devastating occurrence after colorectal cancer resection. This study aimed to identify the risk factors for distant recurrence following surgery. Methods: All consecutive colorectal cancer resections with curative intent were included from a prospectively maintained colorectal cancer database. The primary outcome was to identify predictive factors for distant recurrence of colorectal cancer. Results: A total of 670 eligible cases were identified with 88 (13.1%) developing distant recurrence during the follow-up period. The median time to distant recurrence was 1.2 years with the most common sites of distant recurrence being the lung (44.3%) and liver (44.3%). Predictive factors for distant recurrence in colon cancer included a high tumor, nodal, and overall stage of the primary cancer (p < 0.001 for all). Surgical complications (p = 0.007), including anastomotic leak (p = 0.023), were associated with a higher risk of developing distant recurrence in rectal cancer patients. Independent variables associated with distant recurrence included tumor stage (OR 1.61, p = 0.011), nodal stage (OR 2.18, p < 0.001), and both KRAS (OR 11.04, p < 0.001) and MLH/PMS2 (OR 0.20, p = 0.035) genetic mutations. Among patients with distant recurrence, treatment with surgery conferred the best survival, with patients < 50 years of age having the best overall 5-year survival. Conclusion: Predictive factors for distant recurrence include advanced tumor and nodal stages, and the presence of KRAS and MLH/PSM2 mutations. Clinicians should be cognizant of these risk factors, and instate close surveillance plans for patients exhibiting these features. [ABSTRACT FROM AUTHOR]

Introduction: Durability is a key requirement for the broad acceptance of bariatric surgery. We report on durability at and beyond 10 years with a systematic review and meta-analysis of all reports providing data at 10 or more years and a single-centre study of laparoscopic adjustable gastric banding (LAGB) with 20 years of follow-up.Methods: Systematic review with meta-analysis was performed on all eligble reports containing 10 or more years of follow-up data on weight loss after bariatric surgery. In addition, a prospective cohort study of LAGB patients measuring weight loss and reoperation at up to 20 years is presented.Results: Systematic review identified 57 datasets of which 33 were eligible for meta-analysis. Weighted means of the percentage of excess weight loss (%EWL) were calculated for all papers included in the systematic review. Eighteen reports of gastric bypass showed a weighted mean of 56.7%EWL, 17 reports of LAGB showed 45.9%EWL, 9 reports of biliopancreatic bypass +/− duodenal switch showed 74.1%EWL and 2 reports of sleeve gastrectomy showed 58.3%EWL. Meta-analyses of eligible studies demonstrated comparable results. Reoperations were common in all groups. At a single centre, 8378 LAGB patients were followed for up to 20 years with an overall follow-up rate of 54%. No surgical deaths occurred. Weight loss at 20 years (N = 35) was 30.1 kg, 48.9%EWL and 22.2% total weight loss (%TWL). Reoperation rate was initially high but reduced markedly with improved band and surgical and aftercare techniques.Conclusion: All current procedures are associated with substantial and durable weight loss. More long-term data are needed for one-anastomosis gastric bypass and sleeve gastrectomy. Reoperation is likely to remain common across all procedures. [ABSTRACT FROM AUTHOR]

Background: Long-term outcome data are needed to define the role of bariatric surgery in type 2 diabetes (T2D). To address this, we collated diabetes outcomes more than a decade after laparoscopic adjustable gastric band (LAGB) surgery.Method: Clinical and biochemical measures from 113 obese T2D patients who underwent LAGB surgery in 2003 and 2004 were analyzed. Diabetes remission was defined as HbA1c < 6.2% (44 mmol/mol) and fasting glucose < 7.0 mmol/L.Results: Seventy-nine patients had weight data at 10 years and attained a median [Q1, Q3] weight loss of 16 [10, 21] percent. Sixty patients attended a follow-up assessment. Their baseline HbA1c of 7.8 [7.1, 9.3] percentage units (62 [54, 78] mmol/mol) had decreased to 6.6 [6.1, 8.4] (49 [43, 68] mmol/mol) despite no significant change in glucose-lowering therapy. Eleven patients (18%) were in diabetes remission and another 18 had HbA1c ≤ 6.5%. Significant improvements in physical measures of quality of life, blood pressure, and lipid profile were also observed but there was no change in the proportion of patients with albuminuria and a significant decline in estimated glomerular filtration rate. Twelve patients in the follow-up cohort (20%) required anti-reflux medication after surgery and 26 (43%) underwent gastric band revision surgery.Conclusion: Weight loss for over 10 years after LAGB surgery delivers clinically meaningful improvements in HbA1c, blood pressure, lipids, and quality of life at the cost of a high rate of revision surgery and increased use of anti-reflux medication. These findings support the use of bariatric surgery as a long-term treatment for weight loss and wellbeing in patients with T2D.Study Registration: Registered with the Australian Clinical trials registry as ACTRN12615000089538. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Obesity and dysglycaemia are major risk factors for type 2 diabetes. We determined if obese people undergoing laparoscopic adjustable gastric banding (LAGB) had a reduced risk of progressing from impaired fasting glucose (IFG) to diabetes. Methods: This was a retrospective cohort study of obese people with IFG who underwent LAGB. Weight and diabetes outcomes after a minimum follow-up period of 4 years (mean ± SD 6.1 ± 1.7 years) were compared with those of Australian adults with IFG from a population-based study (AusDiab). Results: We identified 281 LAGB patients with baseline IFG. Their mean ± SD age and BMI were 46 ± 9 years and 46 ± 9 kg/m, respectively. The diabetes incidence for patients in the lowest, middle and highest weight loss tertile were 19.1, 3.4 and 1.8 cases/1,000 person-years, respectively. The AusDiab cohort had a lower BMI (28 ± 5 kg/m) and a diabetes incidence of 12.5 cases/1,000 person-years. This increased to 20.5 cases/1,000 person-years when analysis was restricted to the 322 obese AusDiab participants, which was higher than the overall rate of 8.2 cases/1,000 person-years seen in the LAGB group ( p = 0.02). Multivariable analysis of the combined LAGB and AusDiab data suggested that LAGB was associated with ∼75% lower risk of diabetes (OR 0.24 [95% CI 0.10, 0.57], p = 0.004). Conclusions/interpretation: In obese people with IFG, weight loss after LAGB is associated with a substantially reduced risk of progressing to diabetes over ≥4 years. Bariatric surgery may be an effective diabetes prevention strategy in this population. [ABSTRACT FROM AUTHOR]

In a rodent colorectal cancer model, nonsteroidal antiinflammatory drugs reduce tumor mass by increasing the rate of tumor cell apoptosis and decreasing proliferation. We have examined β-catenin as a potential target for these agents in colorectal cancer. Carcinogen-treated rats were treated for 23 weeks with a range of nonsteroidal antiinflammatory drugs. Control animals received vehicle alone. Intracellular β-catenin was examined using immunohistochemistry. In tumors from untreated animals, staining was seen in the cytoplasm and nucleus (median 24% of nucleii). The frequency of nuclear β-catenin staining correlated directly with the volume of tumor and inversely with the rate of apoptosis. In tumors from treatment groups, the cytoplasmic staining for β-catenin was unchanged; however, nuclear staining was absent except in the celecoxib group, where it was reduced to a median of 14%. Colorectal tumors from animals treated with NSAIDs show reduced levels of nuclear β-catenin immunoreactivity. [ABSTRACT FROM AUTHOR]

The ability of 5-aminosalicylic acid and olsalazine to inhibit colonic aberrant crypts and tumors was investigated in 1,2-dimethylhydrazine-treated rats. The effect of these drugs on the rates of tumor apoptosis and proliferation was studied as potential mechanisms for their action. 5-Aminosalicylic acid reduced the number of aberrant crypt foci by over one third, while olsalazine had no effect on this parameter. However, both agents effectively reduced tumor number and load, increased the rate of tumor apoptosis, and reduced the rate of tumor cell proliferation. In conclusion, 5-aminosalicylic acid and olsalazine are both ultimately effective chemopreventive agents in this model; however, only 5-aminosalicylic acid inhibited the formation of aberrant crypt foci. The inhibitory effect of these agents in tumors is related to the inhibition of proliferation and the induction of apoptosis. [ABSTRACT FROM AUTHOR]