Total pancreatectomy with islet cell transplantation vs intrathecal narcotic pump infusion for pain control in chronic pancreatitis

AIM: To evaluate pain control in chronic pancreatitis patients who underwent total pancreatectomy with islet cell transplantation or intrathecal narcotic pump infusion. METHODS: We recognized 13 patients who underwent intrathecal narcotic pump (ITNP) infusion and 57 patients who underwent total pancreatectomy with autologous islet cell transplantation (TP + ICT) for chronic pancreatitis (CP) pain control between 1998 and 2008 at Indiana University Hospital. All patients had already failed multiple other modalities for pain control and the decision to proceed with either intervention was made at the discretion of the patients and their treating physicians. All patients were evaluated retrospectively using a questionnaire inquiring about their pain control (using a 0-10 pain scale), daily narcotic dose usage, and hospital admission days for pain control before each intervention and during their last follow-up. RESULTS: All 13 ITNP patients and 30 available TP + ICT patients were evaluated. The mean age was approximately 40 years in both groups. The median duration of pain before intervention was 6 years and 7 years in the ITNP and TP + ICT groups, respectively. The median pain score dropped from 8 to 2.5 (on a scale of 0-10) in both groups on their last follow up. The median daily dose of narcotics also decreased from 393 mg equivalent of morphine sulfate to 8 mg in the ITNP group and from 300 mg to 40 mg in the TP + ICT group. No patient had diabetes mellitus (DM) before either procedure whereas 85% of those who underwent pancreatectomy were insulin dependent on their last evaluation despite ICT. CONCLUSION: ITNP and TP + ICT are comparable for pain control in patients with CP however with high incidence of DM among those who underwent TP + ICT. Prospective comparative studies and longer follow up are needed to better define treatment outcomes

Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice.

Leptin, the protein product of the ob gene, increases energy expenditure and reduces food intake, thereby promoting weight reduction. Leptin also regulates glucose homeostasis and hepatic insulin sensitivity via hypothalamic proopiomelanocortin neurons in mice. Roux-en-Y gastric bypass (RYGB) induces weight loss that is substantial and sustained despite reducing plasma leptin levels. In addition, patients who fail to undergo diabetes remission after RYGB are hypoletinemic compared to those who do and to lean controls. We have previously demonstrated that the beneficial effects of RYGB in mice require the melanocortin-4 receptor, a downstream effector of leptin action. Based on these observations, we hypothesized that leptin is required for sustained weight reduction and improved glucose homeostasis observed after RYGB.To investigate this hypothesis, we performed RYGB or sham operations on leptin-deficient ob/ob mice maintained on regular chow. To investigate whether leptin is involved in post-RYGB weight maintenance, we challenged post-surgical mice with high fat diet.RYGB reduced total body weight, fat and lean mass and caused reduction in calorie intake in ob/ob mice. However, it failed to improve glucose tolerance, glucose-stimulated plasma insulin, insulin tolerance, and fasting plasma insulin. High fat diet eliminated the reduction in calorie intake observed after RYGB in ob/ob mice and promoted weight regain, although not to the same extent as in sham-operated mice. We conclude that leptin is required for the effects of RYGB on glucose homeostasis but not body weight or composition in mice. Our data also suggest that leptin may play a role in post-RYGB weight maintenance

Celiac disease in Middle Eastern and North African countries: A new burden?

Celiac disease (CD) is now recognized as a common disorder among Middle Eastern (ME) and North African (NA) populations. The aim of this review is to assess the available data regarding CD in the ME and NA and to compare this information with that of Western countries. A literature review was performed using the electronic databases PubMed and Medline (1950-2008) as search engines, and “celiac disease” was used as a Mesh term. The search was limited to ME and NA countries. The prevalence of CD in ME and NA countries among low risk populations is similar to that of Western countries, but is higher in high risk populations such as those with type 1 diabetes. It is underestimated because of lack of clinical suspicion and lack of patient awareness. Clinical presentations in term of gastrointestinal, hematologic, skeletal, and liver manifestations are similar between both populations except for a high prevalence of short stature in some ME and NA countries. Few studies have addressed atypical or silent CD. As in the West, diagnosis is initially made by serological tests and is confirmed by small intestinal biopsies. Gluten-free diet is the main mode of treatment with a higher apparent adherence rate than in the West. Most disease complications result from malabsorption. The disease is strongly associated with HLA DQ2 and to a lesser extent with HLA DQ8 alleles. In conclusion, CD prevalence is underestimated, with little data available about its malignant complications. Disease parameters in the ME and NA are otherwise similar to those in Western countries

High fat diet promotes positive energy balance and weight gain in RYGB-treated <i>ob/ob</i> mice.

<p>(A) Daily weight gain during challenge of sham and RYGB-treated <i>ob/ob</i> mice with high fat diet (HFD), expressed as a percentage of pre-challenge body weight. (B) Average daily energy intake on regular chow (RC) and during challenge with HFD in sham and RYGB mice. (C) Feeding efficiency and (D) energy expenditure in sham and RYGB mice on RC and HFD. (n = 15, sham; n = 8, RYGB). Results are presented as mean ± SEM. ^@<i>P <</i> .05 vs day 0 within surgical group of panel (A), and $ <i>P <</i> .05 vs RC within surgical group or *<i>P <</i> .05 vs sham within diet group for panels (A, B, C) were assessed using Student’s t-test.</p

RYGB reduces fasting glucose in <i>ob/ob</i> mice.

<p>(A, left) Fasting blood glucose and (B, Left) fasting blood insulin in sham, PF-sham, and RYGB-treated <i>ob/ob</i> mice. Non-operated, age-matched, lean C57BL/6 mice (Lean WT) are presented as control for insulin sensitivity. Data from sham and RYGB-treated DIO mice are shown in panels (A, Right) and (B, Right) as controls for comparison. (<i>ob/ob</i>: n = 21, sham; n = 7, PF-sham, n = 13–15, RYGB | Lean WT: n = 6–12 | DIO: n = 5–7 sham, n = 6–8, RYGB). Results are presented as mean ± SEM. * p < .05 vs sham, ^# p < .05 vs PF-sham, ⁺ p < .05 lean vs RYGB were assessed using 1-Way ANOVA or Student’s t-test, where appropriate.</p

RYGB induces weight loss in <i>ob/ob</i> mice.

<p>(A, Left) Body weight curves expressed as a percentage of body weight at post-operative week 2 (upon resumption of ad libitum diet after post-operative recovery) for sham, PF-sham, and RYGB-treated <i>ob/ob</i> mice from post-operative week 2 through 6. (A, Right) Average daily change in body weight during this same period. (B) Total body weight as measured during week 6. (C) Total body weight during week 6, expressed as a percentage of pre-operative weight in <i>ob/ob</i> mice. DIO mice are presented as a control for the effects of surgery on body weight. (D) Fat and lean mass in sham, PF-sham, and RYGB-treated <i>ob/ob</i> mice as measured during week 5. (E) Change in body composition (fat and lean mass) in sham, PF-sham, and RYGB-treated <i>ob/ob</i> mice from week 2 to week 5. Non-operated, age-matched C57BL/6 mice (Lean WT) maintained on regular chow are presented in panels (B) and (D) as controls for the expected body weight, fat mass, and lean mass of age-matched lean mice. (<i>ob/ob</i>: n = 21–25, sham; n = 7, PF-sham; n = 17, RYGB |Lean WT: n = 5 | DIO WT: n = 7, sham; n = 8, RYGB). Results are presented as mean ± SEM. * <i>P <</i> .05 vs sham, # <i>P <</i> .05 vs PF-sham, + <i>P <</i> .05 lean vs RYGB. Curves of Panel (A) were assessed using 2-Way ANOVA with repeated measures. All other comparisons were assessed using 1-Way ANOVA or Student’s t-test, where appropriate.</p

Leptin is not required for effects of RYGB on fasting hepatic triglyceride.

<p>Total triglyceride content in liver of sham, PF-sham, RYGB, and WM-sham <i>ob/ob</i> mice. (n = 7, sham; n = 7, PF-sham, n = 3, RYGB, n = 7, WM-sham). Results are presented as mean ± SEM. * p < .05 vs sham, ^# p < .05 vs PF-sham were assessed using 1-Way ANOVA.</p