Glucose metabolism: key endogenous regulator of β-cell replication and survival

Recent studies in mice have shown that pancreatic β-cells have a significant potential for regeneration, suggesting that regenerative therapy for diabetes is feasible. Genetic lineage tracing studies indicate that β-cell regeneration is based on the replication of fully differentiated, insulin-positive β-cells. Thus, a major challenge for this field is to identify and enhance the molecular pathways that control β-cell replication and mass. We review evidence, from human genetics and mouse models, that glucose is a major signal for β-cell replication. The mitogenic effect of blood glucose is transmitted via glucose metabolism within β-cells, and through a signalling cascade that resembles the pathway for glucose-stimulated insulin secretion. We introduce the concept that the individual β-cell workload, defined as the amount of insulin that an individual β-cell must secrete to maintain euglycaemia, is the primary determinant of replication, survival and mass. We also propose that a cell-autonomous pathway, similar to that regulating replication, appears to be responsible for at least some of the toxic effects of glucose on β-cells. Understanding and uncoupling the mitogenic and toxic effects of glucose metabolism on β-cells may allow for the development of effective regenerative therapies for diabetes.     

Grading of complications and risk factor evaluation in laparoscopic colorectal surgery

Background

A grading system for postoperative complications is important for quality control and comparison among investigations. The objective of the current study was to evaluate complications associated with laparoscopic colorectal surgery according to a standardized grading system, and to examine risk factors associated with different complication grades.

Methods

Data of all patients who underwent elective laparoscopic colorectal surgery at two medical centers between September 2003 and January 2011 were collected prospectively. Complications were graded retrospectively into five categories based on a previously proposed grading system for colorectal operations. Age, gender, BMI, Charlson comorbidity score, indication for surgery, pathology site, conversion rate, learning curve, operative times, previous abdominal surgery, concurrent surgical procedures performed, and length of hospital stay were evaluated as risk factors and outcome measures for complications.

Results

A total of 501 patients were included in the study. Of them, 30.5 % suffered at least one complication and 6.5 % more than one. Complications that were mainly medical or surgical site infections requiring minor intervention (grades 1 and 2) occurred in 22.9 % of patients. Surgical complications requiring invasive interference (grades 3 and 4) occurred in 7.4 % of patients and mortality (grade 5) occurred in 0.2 % (1 patient). Length of hospital stay was directly related to complication grade. Average hospital stay was 6.8 ± 3.5, 10.5 ± 5.1, and 20.2 ± 12.3 days for patients with no complications, grade 1–2 complications, and grade 3–4 complications, respectively (p < 0.01). Minor complications (grades 1–2) were associated with conversion (p < 0.01), high Charlson score (p = 0.004), and additional surgical procedures (p = 0.04). Major complications (grades 3–4) were associated solely with conversion (p < 0.01) and rectal pathology (p < 0.01).

Conclusion

This study demonstrates the use of a uniform grading system for complications in laparoscopic colorectal surgery. Conversion was found to be associated with all grades of complications.     

Adenoid Cystic Carcinoma of the Nasal Cavity and Paranasal Sinuses: A Meta-Analysis

Objectives To identify independent predictors of outcome in patients with adenoid cystic carcinoma (ACC) of the paranasal sinuses and skull base.Design Meta-analysis of the literature and data from the International ACC Study Group.Setting University-affiliated medical center.Participants The study group consisted of 520 patients, 99 of them from the international cohort. The median follow-up period was 60 months (range, 32 to 100 months).Main Outcome Measures Overall survival (OS) and disease-specific survival (DSS).Results The 5-year OS and DSS of the entire cohort were 62% and 67%, respectively. The local recurrence rate was 36.6%, and the regional recurrence rate was 7%. Distant metastasis, most commonly present in the lung, was recorded in 106 patients (29.1%). In the international cohort, positive margins and ACC of the sphenoid or ethmoidal sinuses were significant predictors of outcome (p < 0.001). Perineural invasion and adjuvant treatment (radiotherapy or chemoradiation) were not associated with prognosis.Conclusion Tumor margin status and tumor site are associated with prognosis in ACC of the paranasal sinuses, whereas perineural invasion is not. Adjuvant treatment apparently has no impact on outcome.