Ali Tavakkolizadeh

Acute Pancreatitis and Pregnancy: A 10-Year Single Center Experience

BackgroundAcute pancreatitis in pregnancy is rare. We report our institutional therapeutic approaches to this disease and its effect on maternal and fetal outcomes.MethodsA retrospective review of medical records of pregnant women admitted to Brigham and Women’s Hospital between 1996 and 2006.ResultsTwenty-one patients, presenting with 34 episodes of acute pancreatitis were identified. Most attacks (56%) occurred in the second trimester. Twelve patients had biliary pancreatitis. Three had pancreatitis secondary to other causes and six had “undetermined” etiologies. Of those with biliary pancreatitis, six underwent cholecystectomy; in a third of these cases, initial conservative therapy had failed. The other six patients underwent endoscopic sphincterotomy (n = 2) or conservative therapy (n = 4). Fifty percent of the patients with biliary pancreatitis managed conservatively had a recurrent episode of pancreatitis vs none in the cholecystectomy group. There was no significant difference in length of hospital stay between the three treatment groups (cholecystectomy, sphincterotomy, and conservative therapy). No maternal deaths were observed; there were four preterm labors and one fetal loss.ConclusionIf treated conservatively, pregnant patients with biliary pancreatitis appear to have a high recurrence rate. Early surgical intervention is appropriate, safe, and does not increase the length of hospital stay.

Rapid upregulation of sodium-glucose transporter SGLT1 in response to intestinal sweet taste stimulation.

Objective:We set out to examine the short-term regulation of the intestinal sodium/glucose cotransporter SGLT1 by its substrate glucose and sweet taste analogs. Summary Background Data:Intestinal SGLT1 is a putative target for antidiabetic therapy; however, its physiological regulation is incompletely understood, limiting its application as a pharmacological target. While it is clearly regulated by dietary composition over a period of days, its short-term regulation by nutrients is unknown. Methods:Sprague-Dawley rats were anesthetized, and the duodenum cannulated. d-glucose, d-fructose, saccharin, d-mannitol, and water were infused for 3 hours, before harvest of proximal jejunum for SGLT1 analysis with Western blotting and quantitative polymerase chain reaction. In further experiments, the receptor region was identified by d-glucose infusion of isolated regions. Lastly, the vagus was de-afferented with capsaicin, and 5HT3-receptor activation of vagal afferents inhibited using ondansetron, before repeating experiments using water or d-glucose infusion. Results:Infusion of d-glucose led to 2.9-fold up-regulation in SGLT1 compared with water or iso-osmotic d-mannitol; this effect was replicated by d-fructose or saccharin. This response was strongest following isolated infusions of duodenum and proximal jejunum, with a blunted effect distally; topography matched the expression profile of sweet taste receptor T1R2/T1R3. The reflex was abolished by capsaicin pretreatment, and blunted by ondansetron. Conclusions:The agonist response implicates the luminal-based sweet-taste receptor T1R2/T1R3, with the reflex apparently involving vagal afferents. The proximal nature of the sensor coincides with the excluded biliopancreatic limb in Roux-en-Y gastric bypass, and this may provide a novel explanation for the antidiabetic effect of this procedure.

Band revision versus Roux-en-Y gastric bypass conversion as salvage operation after laparoscopic adjustable gastric banding

BACKGROUND With the increasing popularity of laparoscopic adjustable banding (LAGB), reoperations to treat band complications have become increasingly more common. Few studies, however, have documented the outcomes of such revisional procedures. The purpose of the present study was to compare the different reoperative approaches after LAGB placement. The present study was conducted at a tertiary referral academic medical center in the United States. METHODS We reviewed our bariatric database to identify patients who had undergone LAGB from 2004 to 2007 and had undergone either revision of their original band or conversion to Roux-en-Y gastric bypass. RESULTS Of the 66 patients who met our inclusion criteria, 47 (71.2%) had undergone revision and 19 (28.8%) conversion. The patient demographics were similar between the 2 groups. The interval to revision or conversion was 22 and 28 months, respectively. Band slippage was the most common surgical indication in the revision group, and inadequate weight loss was the most common in the conversion group. Although patients in the revision group had experienced good weight loss before their reoperation, the conversion group had not. However, the conversion group experienced good weight loss after their reoperation, with an average excess body weight loss of 48%. CONCLUSION Patients who have experienced successful weight loss with LAGB and experience band complications will have satisfactory outcomes with band revision, maintaining their excess body weight loss. These data suggest that patients with inadequate weight loss after LAGB can do well after conversion to Roux-en-Y gastric bypass.

Influence of Imaging on the Negative Appendectomy Rate in Pregnancy

Appendectomy is the most common non-gynecologic surgery performed during pregnancy. Little data exist on the accuracy of imaging studies in the diagnosis of appendicitis in pregnancy. The objective of this study was to evaluate the probability of ultrasound and computed tomography (CT) scan in diagnosing appendicitis in pregnancy, as reflected in the negative appendectomy rate. We retrospectively reviewed the charts of 86 pregnant women who underwent an appendectomy between January 1, 1997 and January 1, 2006. Patients were divided into three groups: clinical evaluation, ultrasound, and ultrasound followed by a CT scan. The clinical evaluation group had 13 patients, with a negative appendectomy rate of 54% (7/13). Fifty-five patients underwent an ultrasound alone, with a negative appendectomy rate 36% (20/55). In the ultrasound/CT group (n = 13), the negative appendectomy rate was 8% (1/13). There was a significant reduction in the negative appendectomy rate in the ultrasound/CT scan group compared to clinical evaluation group (54 vs 8%, p < 0.05). This reduction was not achieved in the ultrasound group when compared to the clinical evaluation group or the ultrasound/CT group (p = 0.05). A significant reduction was achieved when the ultrasound/CT group was compared to the patients in the ultrasound only group who had a normal or inconclusive ultrasound (p < 0.05). Our data documents a very high negative appendectomy rate in the pregnant patient. We recommend an ultrasound followed by a CT scan in patients with a normal or inconclusive ultrasound.

Tissue-engineered neomucosa: morphology, enterocyte dynamics, and SGLT1 expression topography.

Background. The standard therapy for short bowel syndrome is total parenteral nutrition, which is expensive and associated with significant morbidity and mortality. New therapeutic approaches for this disorder are needed. We have applied the techniques of tissue engineering to develop a prototype neointestine. We hypothesized that anastomosis of this neointestine to the native bowel would result in regeneration of mucosal morphology and enterocyte dynamics. Methods. Biodegradable polymers seeded with neonatal rat intestinal organoid units were implanted into the omenta of adult rats to form neointestinal cysts. Five weeks after implantation, side-to-side cyst-jejunal anastomoses were fashioned in one cohort of rats. Tissues were harvested from all rats at 5 months after implantation. Native jejunal (J) and non-anastomosed (N-N) and anastomosed (A-N) neointestinal tissues were assessed for morphology, epithelial cell proliferation (5-bromo-2-deoxyuridine immunohistochemistry), apoptotic rates (terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay), and SGLT1 in situ hybridization. Results. Mucosal morphology, rates and topography of enterocyte proliferation, and transporter expression in A-N neointestine recapitulated those of native jejunum. Each of these features was rudimentary in N-N neointestine. Conclusions. These results suggest that the tissue-engineered neomucosa can develop structural and dynamic features of the normal jejunum. Anastomosis to the native intestine is an essential step for neomucosal development. Tissue engineering offers promise as a novel approach to the treatment of patients suffering from short bowel syndrome.

Diurnal rhythmicity in glucose uptake is mediated by temporal periodicity in the expression of the sodium-glucose cotransporter (SGLT1)

BACKGROUND Intestinal transport exhibits distinct diurnal rhythmicity. Understanding the mechanisms behind this may reveal new therapeutic strategies to modulate intestinal function in disease states such as diabetes and obesity, as well as short bowel syndrome. Although diurnal rhythms have been amply documented for several intestinal transporters, the complexity of transepithelial transport has precluded definitive attribution of rhythmicity in glucose uptake to a single transporter. To address this gap, we assessed temporal changes in glucose transport mediated by the Na(+)/glucose cotransporter SGLT1. METHODS SGLT1 expression was assessed at 4 times during the day: ZT3, ZT9, ZT15, and ZT21 (ZT, Zeitgeber time; lights on at ZT0; n = 8/ time). SGLT1 activity, which is defined as glucose uptake sensitive to the specific SGLT1 inhibitor phloridzin, was measured in everted intestinal sleeves. Changes in Sglt1 expression were assessed by real-time polymerase chain reaction (PCR) and immunoblotting. RESULTS Glucose uptake was significantly higher at ZT15 in jejunum (P < 0.05 vs ZT3). Phloridzin significantly reduced glucose uptake and completely abolished its rhythmicity. Sglt1 mRNA levels were significantly greater at ZT9 and ZT15 in jejunum and ileum, respectively (P < 0.05 vs ZT3), whereas SGLT1 protein levels were significantly greater at ZT15 in jejunum (P < 0.05 vs ZT3). CONCLUSIONS Our results definitively link diurnal changes in intestinal glucose uptake capacity to changes in both SGLT1 mRNA and protein. These findings suggest that modulation of transporter expression would enhance intestinal function and provide an impetus to elucidate the mechanisms that underlie diurnal rhythmicity in transcription. Modulation of intestinal function would benefit the management of malnutrition as well as diabetes and obesity.

Understanding and augmenting human intestinal adaptation: a call for more clinical research

Since its description in the early 20th century, the phenomenon of intestinal adaptation has been the focus of considerable interest. However, there is a paucity of evidence documenting the significance of this phenomenon in man. Indeed, our understanding of intestinal adaptation is based almost exclusively on extrapolations from studies of laboratory rodents. Given the possibility of pharmacologically modifying select components of adaptation as a therapeutic strategy for patients with intestinal insufficiency, a clear understanding of human intestinal adaptation is of paramount importance.

Appendectomy in pregnancy: evaluation of the risks of a negative appendectomy.

BACKGROUND In pregnant women, a high negative appendectomy (NA) rate often is reported; however, the outcome of pregnancy after a NA is not well studied. METHODS Among 1,696 consecutive patients (728 men and 968 women) who underwent an appendectomy at our institution (1996-2005), 87 pregnant women were identified. Postoperative surgical and obstetric outcomes were analyzed based on the final pathologic report of the appendix (normal appendix, inflamed, or perforated). RESULTS The NA rate was significantly higher in pregnant women compared with nonpregnant women (36% vs 14%; P < .05). The fetal demise rate was similar between the NA group and the inflamed group (3% vs 2%; P = NS), and highest (14%) in the perforated group, although this difference did not reach statistical significance (P = .3). Wound infections were most frequent in the perforated group (P < .05). CONCLUSIONS NA during pregnancy is not free of risk to the fetus. We recommend careful assessment to avoid unnecessary exploration when appendicitis is suspected in pregnant women.

Impact of Mesh Use on Morbidity Following Ventral Hernia Repair With a Simultaneous Bowel Resection

OBJECTIVE To evaluate the impact of mesh use on outcomes following ventral hernia repairs and simultaneous bowel resection. DESIGN Retrospective review. SETTING Teaching academic hospital. PATIENTS We studied 177 patients who underwent a ventral hernia repair with a bowel resection between May 1, 1992, and May 30, 2007. A prosthesis was used in 51 repairs (mesh group), while 126 repairs were primary (mesh-free group). MAIN OUTCOME MEASURES Demographic characteristics, comorbidities, mesh type, bowel resection type (colon vs small bowel), defect size, drain use, and length of hospital stay were compared between groups with Fisher exact test and multivariate analysis. RESULTS There were no statistically significant differences between patient characteristics and relevant comorbidities. The incidence of postoperative infection (superficial or deep) was 22% in the mesh group vs 5% in the mesh-free group (P = .001). Other complications (fistula, seroma, hematoma, bowel obstruction) occurred in 24% of patients in the mesh group vs 8% of patients in the mesh-free group (P = .009). Focusing on the patients who developed an infection, prosthetic mesh use was the only significant risk factor on multivariate regression analysis, irrespective of drain use, defect size, and type of bowel resection. CONCLUSIONS We recommend caution in using mesh when performing a ventral hernia repair with a simultaneous bowel resection because of significantly increased postoperative infectious complications. Drain use, defect size, and bowel resection type did not influence outcomes.

MicroRNA mir-16 is anti-proliferative in enterocytes and exhibits diurnal rhythmicity in intestinal crypts

BACKGROUND AND AIMS The intestine exhibits profound diurnal rhythms in function and morphology, in part due to changes in enterocyte proliferation. The regulatory mechanisms behind these rhythms remain largely unknown. We hypothesized that microRNAs are involved in mediating these rhythms, and studied the role of microRNAs specifically in modulating intestinal proliferation. METHODS Diurnal rhythmicity of microRNAs in rat jejunum was analyzed by microarrays and validated by qPCR. Temporal expression of diurnally rhythmic mir-16 was further quantified in intestinal crypts, villi, and smooth muscle using laser capture microdissection and qPCR. Morphological changes in rat jejunum were assessed by histology and proliferation by immunostaining for bromodeoxyuridine. In IEC-6 cells stably overexpressing mir-16, proliferation was assessed by cell counting and MTS assay, cell cycle progression and apoptosis by flow cytometry, and cell cycle gene expression by qPCR and immunoblotting. RESULTS mir-16 peaked 6 hours after light onset (HALO 6) with diurnal changes restricted to crypts. Crypt depth and villus height peaked at HALO 13-14 in antiphase to mir-16. Overexpression of mir-16 in IEC-6 cells suppressed specific G1/S regulators (cyclins D1-3, cyclin E1 and cyclin-dependent kinase 6) and produced G1 arrest. Protein expression of these genes exhibited diurnal rhythmicity in rat jejunum, peaking between HALO 11 and 17 in antiphase to mir-16. CONCLUSIONS This is the first report of circadian rhythmicity of specific microRNAs in rat jejunum. Our data provide a link between anti-proliferative mir-16 and the intestinal proliferation rhythm and point to mir-16 as an important regulator of proliferation in jejunal crypts. This function may be essential to match proliferation and absorptive capacity with nutrient availability.