Jennifer L. Irani

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.

Management and complications of stomas.

Stomas are created for a wide range of indications such as temporary protection of a high-risk anastomosis, diversion of sepsis, or permanent relief of obstructed defecation or incontinence. Yet this seemingly benign procedure is associated with an overall complication rate of up to 70%. Therefore, surgeons caring for patients with gastrointestinal diseases must be proficient not only with stoma creation but also with managing postoperative stoma-related complications. This article reviews the common complications associated with ostomy creation and strategies for their management.

Severe acute gastrointestinal graft-vs-host disease: an emerging surgical dilemma in contemporary cancer care.

OBJECTIVE To determine the natural history of and guidelines for the surgical management of severe acute gastrointestinal (GI) graft-vs-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). DESIGN Case series from a prospective database. SETTING Tertiary care referral center/National Cancer Institute-designated Comprehensive Cancer Center. PATIENTS A total of 63 of 2065 patients (3%) undergoing HSCT for hematologic malignancies from February 1997 to March 2005 diagnosed clinically with severe (stage 3 or 4) acute GI GVHD. Main Outcome Measure Percutaneous or surgical intervention. Perforation, obstruction, ischemia, hemorrhage, and abscess were considered surgically correctable problems. RESULTS Severe acute GI GVHD was diagnosed in 63 patients (median age at HSCT, 47.6 years) at a median of 23 days after HSCT. Clinical diagnosis was confirmed histologically in 84% of patients. On computed tomography and/or magnetic resonance images, 64% had bowel wall thickening, 20% had a normal-appearing bowel, and 16% had nonspecific findings; none had evidence of perforation, obstruction, or abscess. All were initially treated with immunosuppression. Only 1 patient (1.6%) required intervention, undergoing a nontherapeutic laparotomy for worsening abdominal pain. A total of 83% of patients have died (median time to death from HSCT, 119 days; from GI GVHD diagnosis, 85 days). None who underwent an autopsy died of a surgically correctable cause. CONCLUSIONS This series represents a large single-center experience with GI GVHD reviewed from a surgical perspective. Operative intervention was rarely required. Therefore, mature surgical judgment is necessary to confirm the absence of surgically reversible problems, thus avoiding unnecessary operations in this challenging patient population.

Distal Pancreatectomy is Not Associated with Increased Perioperative Morbidity when Performed as Part of a Multivisceral Resection

PurposeTo evaluate the indications for and the outcomes from distal pancreatectomy.MethodsRetrospective chart review of 171 patients who underwent distal pancreatectomy at Brigham and Women’s Hospital between January 1996 and August 2005.ResultsNearly one-third of distal pancreatectomies were performed as part of an en bloc resection for a contiguous or metastatic tumor. Fifty-six percent of the patients underwent a standard distal pancreatectomy +/− splenectomy (group 1), whereas 44% of distal pancreatic resections included additional organs or contiguous intraperitoneal or retroperitoneal tumor (group 2). The overall post-operative complication rate was 37%; the most common complication was pancreatic duct leak (23%). When compared to patients undergoing standard distal pancreatectomy, those with a more extensive resection including multiple viscera and/or metastatic or contiguous tumor resection had no significant difference in overall complication rate (35% v. 39%, p = 0.75), leak rate (25% v. 20%, p = 0.47), new-onset insulin-dependent diabetes mellitus (3% v. 4%, p = 1.0), and mortality (2% v. 4%, p = 0.656).ConclusionThis series includes a large number of patients in whom distal pancreatectomy was performed as part of a multivisceral resection or with en bloc resection of contiguous tumor. Complications were no different in these patients when compared to patients undergoing straightforward distal pancreatectomy.

Educational value of the operating room experience during a core surgical clerkship

BACKGROUND The amount and content of medical student teaching in the operating room and its alignment with clerkship goals was unknown. METHODS A qualitative research design using field observations, followed by qualitative and quantitative data coding and analysis. RESULTS A mean of 9.8% of the total case time (range 1.6%-20.2%) was spent teaching clerkship goals. Teaching strategies based on basic principles of learning were used during a mean of 66% of the total case time (range 30%-99%). The most common teaching strategy was active student participation (28%) followed by command (14%) and lecture (13%). Educational experience in the OR was rated 4.0 (out of 5) by faculty and 3.3 by students. No correlation existed between student satisfaction and time actively participating in the operation or time spent teaching to clerkship goals (P = .66, P = .95, respectively). CONCLUSION Teaching in the OR is more focused on technical aspects of the operation than the goals of a core surgery clerkship.

Participation in Quality Measurement Nationwide

In the interest of improving patient care quality and reducing costs, many hospitals across the nation participate in quality measurements. The three programs most applicable to colon and rectal surgery are the National Surgical Quality Improvement Project, the Surgical Care Improvement Project (SCIP), and the Surgical Care and Outcomes Assessment Program. Participation in each is variable, although many hospitals are eligible and welcome to participate. Currently, SCIP is the only one with a financial incentive to participate. This article will focus on participation; however, the motivation for such is elusive in the literature. It is likely that a combination of resource utilization and faith in the concept that participation results in improvements in patient care actually drive participation.

Perioperative Beta blockade.

The use of preoperative beta (β) blockade has been through several changes, and it is clear that large, randomized controlled trials on the subject are in need. Currently, a judicious approach to perioperative β blockade is supported. Continuation of β blockers is recommended for the patient taking them prior to surgery. Patients undergoing large colorectal procedures, with coronary artery disease or high cardiac risk, should have β blockers titrated to heart rate and blood pressure. Dosages should be titrated to heart rate and blood pressure rather than using fixed, long-acting dosages. When β blockers are indicated, they should be initiated weeks before surgery.