Systematic review of team performance in minimally invasive abdominal surgery.

Background: Adverse events in the operating theatre related to non-technical skills and teamwork are still an issue. The influence of minimally invasive techniques on team performance and subsequent impact on patient safety remains unclear. The aim of this review was to assess the methodology used to objectify and rate team performance in minimally invasive abdominal surgery. Methods: A systematic literature search was conducted according to the PRISMA guidelines. Studies on assessment of surgical team performance or non-technical skills of the surgical team in the setting of minimally invasive abdominal surgery were included. Study aim, methodology, results and conclusion were extracted for qualitative synthesis. Results: Sixteen studies involving 677 surgical procedures were included. All studies consisted of observational case series that used heterogeneous methodologies to assess team performance and were of low methodological quality. The most commonly used team performance objectification tools were 'construct'- and 'incident'-based tools. Evidence of validity for the assessed outcome was spread widely across objectification tools, ranging from low to high. Diverse and poorly defined outcomes were reported. Conclusion: Team demands for minimally invasive approaches to abdominal procedures remain unclear. The current literature consists of studies with heterogeneous methodology and poorly defined outcomes.

Subspecialized radiology review at multidisciplinary pancreas conference: impact on patient management.

PURPOSE: At our tertiary medical center, multidisciplinary subspecialists meet twice a week during a CME-accredited conference to discuss oncologic and non-oncologic patients with pancreatic diseases at which time a subspecialized abdominal staff radiologist reinterprets the patient's relevant imaging studies. This study assesses the changes in patient management due to imaging reinterpretation during multidisciplinary pancreas conference (MPC). MATERIALS AND METHODS: In this retrospective, IRB-approved, HIPAA-compliant study, imaging studies of all patients discussed at MPC between July 1 and December 31, 2015 were assessed for technical adequacy, and original reports analyzed for congruency with reinterpretation. Management measures included change in diagnosis, clinical stage, treatment, or workup. Additional data were obtained on referring services affected and their resultant change in practice. Changes in surgical resectability, surgical approach, or delayed operative dates were noted for surgeons. Changes in chemotherapeutic or radiation oncology regimens as well as decisions for additional imaging, laboratory workup, or histologic evaluation were also recorded. RESULTS: A total of 252 patients were included (54.4% males, 45.6% females, mean age 63.71 years). Relevant imaging consisted of 142 abdominal CT scans, 112 abdominal MRI scans, 1 abdominal ultrasound, and 1 nuclear medicine octreotide study of which 69.4% were performed in-house. Image quality was deemed appropriate in 95.2%. Cases presented included solid pancreatic malignancies (n = 140; 55.6%), cystic pancreatic lesions (n = 41; 16.3%), acute and chronic inflammatory conditions (n = 52; 20.6%), and miscellaneous entities (n = 10; 4.0%); 9 (3.6%) cases were normal. Image reinterpretation was congruent with original reports in 56.7%, with minor, moderate, and major discrepancies occurring in 9.5, 26.2%, and 7.5% of cases, respectively. Incongruent reinterpretation was predominantly due to perceptional errors (false-negative reports due to missed findings) and interpretative errors (false-positive results due to over-reporting or misclassification of diagnoses). Services most commonly affected included surgical oncology, radiology, and gastroenterology at 16.7%, 13.1%, and 12.7% of cases, respectively. Management changes included a change in diagnosis in 8.7%, change in clinical stage in 8.7%, change in treatment in 17.9%, and further workup needed in 19.0% of patients, respectively. No change in management occurred in the remaining 61.5% of cases. CONCLUSIONS: Subspecialized abdominal radiologist reinterpretation in the context of more comprehensive patient information heavily impacts the multidisciplinary management of patients with pancreatic disorders. Further efforts are needed to solidify the abdominal radiologist's role in the multidisciplinary clinical setting.

Calmodulin regulation of gallbladder ion transport becomes dysfunctional during gallstone formation in prairie dogs.

Gallbladder absorption is increased prior to gallstone formation in prairie dogs and may promote cholesterol crystallization. Recent studies indicate that Ca2+-calmodulin (CaM) tonically inhibits gallbladder electrolyte absorption in prairie dogs fed a nonlithogenic diet. We hypothesized that dietary cholesterol alters CaM-dependent regulation of gallbladder ion transport, a possible link between increased gallbladder absorption and gallstone formation. Gallbladders from prairie dogs fed control (N = 24) or 1.2% cholesterol-enriched chow (N = 32) were mounted in Ussing chambers. Electrophysiology and ion flux were measured while exposing the epithelia sequentially to trifluoperazine (TFP), a CaM antagonist, followed by the calcium ionophore A23187. Animals fed the high cholesterol diet developed crystals and gallstones in a time-dependent fashion. Mucosal addition of 50 microM TFP decreased short-circuit current (Isc), transepithelial potential, and tissue conductance in control, crystal, and gallstone animals, but the magnitude of its effect was significantly decreased in animals fed cholesterol. TFP stimulated mucosa-to-serosa Na+ flux by 6.9 +/- 0.9 microeq/cm2/hr in control animals but only 3.1 +/- 0.8 microeq/cm2/hr in gallstone animals. Similarly, TFP increased mucosa-to-serosa Cl- flux by 11.9 +/- 1.4 microeq/cm2/hr in controls but only 4.9 +/- 1.4 microeq/cm2/hr in cholesterol-fed animals. TFP effects were not reversed by A23187, which caused differential effects on Isc and ion transport in cholesterol-fed animals. In conclusion, CaM-mediated inhibition of gallbladder Na+ and Cl- transport is diminished in prairie dogs fed cholesterol. We conclude that gallbladder ion transport is partially released from basal inhibition during gallstone formation and propose that dysfunctional CaM regulation may be a stimulus to increased gallbladder absorption.

Endogenous prostaglandins modulate chloride secretion by prairie dog gallbladder.

In addition to concentrating bile, the gallbladder secretes chloride (Cl-) and mucus into its lumen. We recently observed that gallbladder Cl- secretion is increased in prairie dogs during the formation of cholesterol crystals, a period of altered mucosal prostaglandin synthesis. Pathologic Cl- secretion is characteristic of other epithelial disorders such as cystic fibrosis and hypercalciuric nephrolithiasis and may be important in gallstone pathogenesis. We hypothesized that concentrations of endogenous prostaglandin E2 (PGE2) found during experimental gallstone formation may mediate increased Cl- secretion by prairie dog gallbladder. Prairie dog gallbladders were harvested by cholecystectomy and mounted in Ussing chambers. Unidirectional transepithelial Cl-, Na+, and H20 fluxes were measured before and after inhibition of endogenous prostaglandin synthesis with 10 micromol/L indomethacin. Gallbladders were then exposed to increasing concentrations of PGE2 to a maximal dose of 1 micromol/L, as found in animals with gallstones. Standard electrophysiologic parameters were recorded simultaneously. Indomethacin increased mucosal resistance and stimulated gallbladder Na+ and Cl- absorption. These effects were rapidly reversed by PGE2. PGE2 promoted Cl- secretion and decreased mucosal Na+ absorption at concentrations found in the gallbladder bile of animals with gallstones. Endogenous prostaglandin metabolism modulates gallbladder Cl- secretion and may promote changes in Cl- transport associated with cholelithiasis.

CD38/ADP-ribosyl cyclase: A new role in the regulation of osteoclastic bone resorption.

The multifunctional ADP-ribosyl cyclase, CD38, catalyzes the cyclization of NAD(+) to cyclic ADP-ribose (cADPr). The latter gates Ca(2+) release through microsomal membrane-resident ryanodine receptors (RyRs). We first cloned and sequenced full-length CD38 cDNA from a rabbit osteoclast cDNA library. The predicted amino acid sequence displayed 59, 59, and 50% similarity, respectively, to the mouse, rat, and human CD38. In situ RT-PCR revealed intense cytoplasmic staining of osteoclasts, confirming CD38 mRNA expression. Both confocal microscopy and Western blotting confirmed the plasma membrane localization of the CD38 protein. The ADP-ribosyl cyclase activity of osteoclastic CD38 was next demonstrated by its ability to cyclize the NAD(+) surrogate, NGD(+), to its fluorescent derivative cGDP-ribose. We then examined the effects of CD38 on osteoclast function. CD38 activation by an agonist antibody (A10) in the presence of substrate (NAD(+)) triggered a cytosolic Ca(2+) signal. Both ryanodine receptor modulators, ryanodine, and caffeine, markedly attenuated this cytosolic Ca(2+) change. Furthermore, the anti-CD38 agonist antibody expectedly inhibited bone resorption in the pit assay and elevated interleukin-6 (IL-6) secretion. IL-6, in turn, enhanced CD38 mRNA expression. Taken together, the results provide compelling evidence for a new role for CD38/ADP-ribosyl cyclase in the control of bone resorption, most likely exerted via cADPr.

Octreotide stimulates Ca++ secretion by the gallbladder: a risk factor for gallstones.

BACKGROUND: Gallstone formation during octreotide therapy has been linked to elevated levels of gallbladder bile Ca++, a well-known prolithogenic factor. Although the subcutaneous administration of octreotide raises gallbladder bile Ca++ in prairie dogs, the mechanism for this effect is unknown. Octreotide has been shown to increase gallbladder Na+ and water absorption in Ussing chamber studies. Given the known effects of octreotide on gallbladder ion transport, we hypothesized that octreotide may also promote gallstone formation by stimulating gallbladder Ca++ secretion, thereby raising the lumenal concentration of biliary Ca++. METHODS: After cholecystectomy, prairie dog gallbladders were mounted in Ussing chambers, and standard electrophysiologic parameters were recorded. Unidirectional fluxes of Ca++ and Na+ were measured before and after serosal exposure to 50 nmol/L octreotide. RESULTS: Under basal conditions normal prairie dog gallbladder absorbed mucosal Ca++. Serosal octreotide converted the gallbladder from a state of basal Ca++ absorption to one of net Ca++ secretion by stimulating serosa to mucosa Ca++ flux. As anticipated, octreotide increased net Na+ absorption by stimulating mucosa to serosa Na+ flux and decreased tissue conductance and short-circuit current significantly compared with baseline values. CONCLUSION: Fifty nanomoles per liter octreotide stimulated Ca++ secretion by gallbladder epithelium, a possible mechanism for increased biliary Ca++ in prairie dogs receiving subcutaneous injections. Ca++ secretion linked to octreotide therapy may induce gallstones by raising biliary levels of Ca++, a known prolithogenic factor.

Elevated biliary calmodulin during gallstone formation: the role of bile acids.

Hepatic bile synthesis is altered during experimental gallstone formation. In response to cholesterol, there is a hydrophobic shift in hepatic bile acid synthesis and hypersecretion of phospholipids. These changes decrease the vesicular capacity for cholesterol and favor crystallization. The mechanism for these changes in hepatic bile formation is unknown. Calmodulin (CaM), a Ca2+ receptor protein involved in cellular secretion, regulates gallbladder transport and may play an important role in alterations of hepatic bile formation during cholelithiasis. We hypothesized that biliary CaM activity is altered during gallstone formation and may be associated with changes in bile acid and phospholipid synthesis. Prairie dogs were fed either control (N = 22) or 1.2% cholesterol-enriched (N = 26) diets for one to six weeks. Cholecystectomy was performed; the common bile duct was cannulated, and hourly bile samples were collected. CaM was measured in bile and gallbladder tissues by radioimmunoassay. Bile samples were analyzed for cholesterol, phospholipids, total bile acids, total protein, calcium, and individual bile acid composition. Compared to controls, gallstone animals had elevated hepatic bile levels of CaM, phospholipids, and cholesterol. Hydrophobic bile acid synthesis was also stimulated, with increased levels of taurochenodeoxycholic acid (TCDCA) and decreased taurocholic acid (TCA). Gallbladder bile demonstrated similar changes. Although gallbladder bile CaM levels were increased, tissue levels were unchanged, suggesting that increased CaM concentration is a hepatic phenomenon. Hepatic bile CaM activity correlated linearly with TCDCA concentration (r = 0.64, P < 0.004) and phospholipid hypersecretion (r = 0.53, P < 0.03). The relationship between biliary CaM and increased concentrations of TCDCA and phospholipids suggests a role for CaM in alterations of hepatocyte secretion that may promote gallstone formation.

Converting gallbladder absorption to secretion: the role of intracellular calcium.

BACKGROUND: Experimental cholelithiasis is associated with elevated biliary calcium concentration and altered gallbladder absorption. Recent studies showed that extracellular calcium ([Ca2+]ec) plays a role in regulating gallbladder ion transport. The extent to which intracellular calcium ([Ca2+]ic) mediates the changes in gallbladder ion transport is not clear. We hypothesize that [Ca2+]ic is an important regulator of gallbladder ion transport. METHODS: Prairie dog gallbladders were mounted in Ussing chambers, standard electrophysiologic parameters were recorded, and unidirectional Na+, Cl- and H2O fluxes were measured before and after mucosal exposure of 10-5 mol/L calcium ionophore A23187 was performed. RESULTS: A23187 caused an increase in transepithelial short-circuit current and potential difference and a decrease in transepithelial resistance. A23187 inhibited mucosa to serosa Cl- flux and stimulated serosa to mucosa Na+ flux, resulting in increased net Cl- secretion and decreased net Na+ absorption. A23187 converted H2O from absorption to secretion. Transepithelial short-circuit current effect of A23187 was delayed by indomethacin pretreatment and was completely blunted by low bathing Ca2+. CONCLUSIONS: This is the first demonstration that increased [Ca2+]ic converts the gallbladder from its normal absorptive state to a secretory one. Furthermore [Ca2+]ic appears to regulate ion transport through mechanisms that are partially prostaglandin-dependent. Studies are necessitated to define possible links between gallbladder secretion of Cl- and H2O and mucus hypersecretion, a well-described phenomenon associated with cholesterol gallstone formation.

Octreotide promotes gallbladder absorption in prairie dogs: a potential cause of gallstones.

BACKGROUND/AIMS: Gallstone formation during octreotide administration has been causally linked to increased biliary concentrations of calcium, protein, and total lipids, all purported prolithogenic factors. These changes may be caused by octreotide-induced gallbladder stasis or a direct effect of octreotide on gallbladder absorption. We tested the hypothesis that octreotide stimulates gallbladder ion and water transport. METHODS: Prairie dog gallbladders were mounted in Ussing chambers and bathed in oxygenated Ringer's solution. Electrophysiological parameters were recorded, and unidirectional Na+, Cl-, and H2O fluxes were measured before and after serosal exposure to 50 nmol/L octreotide. RESULTS: Octreotide exposure caused a significant decrease in transepithelial short-circuit current and potential difference and an increase in tissue resistance compared with baseline. These alterations in electrophysiological parameters coincided with changes in ion transport. Octreotide stimulated net Na+ and H2O absorption and converted the gallbladder from a state of Cl- secretion to one of Cl- absorption by increasing mucosal to serosal fluxes. Octreotide effects on ion transport were blocked by 4,4'-diisothiocynostilbene-2,2'-disulfonic acid and amiloride and reversed by theophylline. CONCLUSIONS: Octreotide may promote gallstone formation by inducing gallbladder stasis and by directly increasing gallbladder absorption, which may act synergistically to increase the concentration of prolithogenic factors in bile and to facilitate nucleation and stone growth.

Protein kinase C regulates prairie dog gallbladder ion transport.

BACKGROUND: Gallstone formation is characterized by increased biliary calcium (Ca2+) level and altered gallbladder absorption. Recent studies suggest that luminal Ca2+ regulates gallbladder ion transport via intracellular calcium ([Ca2+]ic). Ca2+-calmodulin and protein kinase C (PKC) are two major systems through which [Ca2+]ic carries out second-messenger functions in many cell types. We have previously shown that Ca2+-calmodulin regulates basal gallbladder ion transport in prairie dog. The present study tests the hypothesis that PKC is also essential in regulation of gallbladder ion transport in this model. METHODS: The role of PKC in regulation of gallbladder ion transport was determined by studying the effects of phorbol esters, synthetic analogues of diacylglycerol, which directly activates PKC. Gallbladders were mounted in Ussing chambers, and standard electrophysiologic parameters were recorded after exposing tissues to either 10(-5) mol/L of 4-alpha-phorbol 12,13-didecanoate (PDD), 4-beta-phorbol 12-myristate 13-acetate, 4-beta-phorbol 12,13-dibutyrate (PDB), or 10(-4) mol/L serotonin. Unidirectional Na+, Cl-, and H2O fluxes were measured before and after treatment with only inactive PDD and most active PDB. RESULTS: Mucosal and serosal exposure of tissues to either 4-beta-phorbol 12-myristate 13-acetate or PDB resulted in a decrease in short-circuit current and transepithelial potential difference without any change in tissue resistance. Serotonin induced similar changes in gallbladder electrical properties. PDB caused an inhibition of mucosal to serosal fluxes of Na+, Cl-, and H2O, with a decrease in net Na+ absorption, an increase in net Cl- secretion, and a conversion of net H2O absorption to net H2O secretion. Serosal-to-mucosal fluxes of Na+, Cl-, and H2O did not change. Inactive PDD had no effect on either electrophysiologic parameters or ion and water fluxes. Pretreatment of tissues with PKC antagonist 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine blocked the phorbol ester-induced inhibition of ion transport. CONCLUSION: PKC regulates gallbladder ion transport in the prairie dog by inhibiting Na+ absorption and stimulating Cl- secretion.

Adaptation of the Na+/glucose cotransporter following intestinal resection.

Following massive small bowel resection, the remaining intestine adapts to compensate for lost absorptive capacity. Although the Na+/glucose cotransporter plays a critical role in nutrient, fluid, and electrolyte transport in the small intestine, its role in adaptation following resection has not been defined. To examine this, we sought to determine whether there were changes in the expression of the Na+/glucose cotransporter, SGTL1, at the messenger RNA level. Lewis rats underwent either transection or 70% small bowel resection and reanastomosis. The animals were sacrificed at intervals following operation. Jejunum proximal to the anastomosis and ileum and colon distal to the anastomosis were harvested and analyzed for Na+/glucose mRNA by reverse transcriptase-polymerase chain reaction and Southern blot. Blots were semiquantitated by 32P labeling and standardized to beta-actin. Histologic sections and analysis of DNA, RNA, and protein content revealed hyperplastic changes. Following resection, mRNA for the Na+/glucose cotransporter in the jejunum increased significantly (P < 0.05) by 1 week and remained elevated. In the ileum, an almost fivefold increase occurred at 6 hr and persisted throughout the study (P < 0.05). The early response was greater in the ileum, distal to the reanastomosis, than that in the jejunum (P < 0.05). In contrast, there was no change in the small amount of transporter mRNA detected in the colon. These results suggest that, in addition to mucosal hyperplasia, the intestinal response to resection involves upregulation of transporter mRNA by the individual enterocyte. This transcriptional increase in the Na+/glucose cotransporter appears to be an early response by the intestine and may be important in maintaining overall intestinal transport capacity following resection.

Increased biliary protein precedes gallstone formation.

Although nucleation is critical to the pathogenesis of cholesterol gallstones, the factors responsible for this process are poorly defined. Numerous potential nucleating agents have been identified in the bile of humans and animals with cholelithiasis, including mucus, calcium, and bilirubin. Recent studies have shown that patients with cholesterol crystals and gallstones have increased biliary total protein, suggesting that protein may be a previously unrecognized nucleating factor. We tested the hypothesis that biliary total protein is increased prior to cholesterol gallstone formation. Prairie dogs were maintained on either control (N = 22) or 0.4% cholesterol-enriched chow (N = 18) for up to 18 weeks. Cholesterol-fed animals were classified as pregallstone (N = 12) or gallstone (N = 6) based on gross examination of the gallbladder bile. Both hepatic and gallbladder biles were then analyzed for lipid, bile acid, calcium, and protein content. Cholesterol feeding was associated with increased gallbladder concentrations of cholesterol, phospholipids, and calcium in the pregallstone and gallstone groups. Biliary total protein was significantly elevated in the pregallstone (5.8 +/- 0.4 mg/ml, P < 0.001) and gallstone animals (6.0 +/- 0.6 mg/ml, P < 0.001) as computed to controls (3.8 +/- 0.3 mg/ml). Regression analysis showed positive correlations between gallbladder bile total protein and the gallbladder bile cholesterol saturation index (CSI) (P < 0.001), as well as between gallbladder total protein and calcium (P < 0.001). Although the hepatic bile CSI was elevated in cholesterol-fed animals, total protein remained unchanged, suggesting that the alteration in biliary protein is a gallbladder phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)

Peripheral arterial thrombosis in the nephrotic syndrome.

Peripheral arterial thrombosis is a rare complication of nephrotic syndrome that occurs in conjunction with a hypercoagulable state and results in a high rate of limb loss and death. We report a case of brachial artery thrombosis in a pediatric patient with nephrotic syndrome, antithrombin III deficiency, and antecedent vessel trauma. An extensive review of the literature is presented. We conclude that management of arterial thrombosis requires aggressive replenishment of antithrombin III and adequate heparinization in addition to the traditional surgical management. Moreover, arterial puncture should be avoided because of the high risk of thrombosis in these patients.

Ca2+ calmodulin regulates basal gallbladder absorption.

BACKGROUND: Gallbladder absorption is altered during gallstone formation, a phenomenon that may be partly the result of elevated biliary Ca2+ levels. Recent studies suggest that changes in gallbladder absorption are mediated by intracellular Ca2+ ([Ca2+]ic). However, the mechanisms by which [Ca2+]ic regulates gallbladder ion transport are not known. Calmodulin is a Ca2+ receptor protein in the Ca2+ messenger system that modulates ion transport in the small intestine. We hypothesized that Ca(2+)-calmodulin mediates the effects of [Ca2+]ic on gallbladder absorption. METHODS: Prairie dog gallbladders were mounted in Ussing chambers, and standard electrophysiologic parameters were recorded. Unidirectional Na+, Cl-, and water fluxes were measured before and after mucosal exposure to 5 x 10(-5) mol/L trifluoperazine, a potent calmodulin antagonist. In addition, the ion transport effects of increased extracellular calcium and theophylline were determined in the presence of calmodulin inhibition. RESULTS: Inhibition of calmodulin resulted in an increase in net Na+ and water absorption and converted the gallbladder from a Cl- absorptive state. Similar results were obtained during exposure to two other calmodulin antagonists that differ only in their affinity for calmodulin but not in their hydrophobicity, suggesting that the observed changes were caused by specific calmodulin inhibition. Effects of trifluoperazine were reversed by increasing luminal [Ca2+] or theophylline exposure. CONCLUSIONS: The effects of calmodulin inhibition are directly opposite of the effects of the Ca2+ ionophore. We conclude that Ca(2+)-calmodulin regulates gallbladder absorption at basal [Ca2+]ic. Further studies are needed to determine whether altered calmodulin activity is responsible for increased gallbladder absorption during gallstone formation.