The Estimated Cost of Maintenance of Certification.

BACKGROUND: Maintenance of Certification (MOC) is a controversial topic in medicine for many different reasons. Studies have suggested that there may be associations between fewer negative outcomes and participation in MOC. However, MOC still remains controversial because of its cost. We sought to determine the estimated cost of MOC to the average orthopaedic surgeon, including fees and time cost, defined as the market value of the physician's time. METHODS: We calculated the total cost of MOC to be the sum of the fees required for applications, examinations, and other miscellaneous fees as well as the time cost to the physician and staff. Costs were calculated for the oral, written, and American Board of Orthopaedic Surgery Web-based Longitudinal Assessment (ABOS WLA) MOC pathways based on the responses of 33 orthopaedic surgeons to a survey sent to a state orthopaedic society. RESULTS: We calculated the average orthopaedic surgeon's total cost in time and fees over the decade-long period to be $71,440.61 ($7,144.06 per year) for the oral examination MOC pathway and $80,391.55 ($8,039.16 per year) for the written examination pathway. We calculated the cost of the American Board of Orthopaedic Surgery web-based examination pathway to be $69,721.04 ($6,972.10 per year). CONCLUSIONS: The actual cost of MOC is much higher than just the fees paid to organizations providing services. The majority of the cost comes in the form of time cost to the physician. The ABOS WLA was implemented to alleviate the anxiety of a high-stakes examination and to encourage efficient longitudinal learning. We found that the ABOS WLA pathway does save time and money when compared with the written examination pathway when review courses and study periods are taken. We believe that future policy changes should focus on decreasing physician time spent completing MOC requirements, and decreasing the cost of these requirements, while preserving the model of continued evidence-based medical education.

Endoscopic ultrasound-guided biliary access versus precut papillotomy in patients with failed biliary cannulation: a retrospective study.

Background and aims Precut papillotomy is widely used after failed biliary cannulation. Endoscopic ultrasound (EUS)-guided biliary access techniques are newer methods to facilitate access and therapy in failed cannulation. We evaluated the impact of EUS-guided biliary access on endoscopic retrograde cholangiopancreatography (ERCP) success and compared these techniques to precut papillotomy. Patients and methods We retrospectively compared two ERCP cohorts. One cohort consisted of biliary ERCPs (n = 1053) attempted in patients with native papillae and surgically unaltered anatomy in whom precut papillotomy and/or EUS-guided biliary access were routinely performed immediately after failed cannulation. This cohort was compared with a similar ERCP cohort (n = 1062) in which only precut papillotomy was available for failed cannulation. The following outcomes were compared: conventional cannulation success, rates of attempted advanced access techniques (precut or EUS), precut success, EUS-guided biliary access success, and ERCP failure rates. Results Although conventional cannulation success, rates of attempted advanced access technique (precut or EUS), and precut success were similar, the ERCP failure rate was lower when both EUS-guided biliary access and precut were available (1.0 % [95 % confidence interval (CI) 0.4 - 1.6]), compared with when only precut was possible for failed access (3.6 % [95 %CI 2.5 - 4.7]; P < 0.001). Success for EUS-guided biliary access (95.1 % [95 %CI 89.7 - 100]) was significantly higher than for precut (75.3 % [95 %CI 68.2 - 82.4]; P < 0.001), and mainly due to superiority in malignant obstruction (93.5 % vs. 64 %; P < 0.001). Conclusions EUS-guided biliary access decreases the rate of therapeutic biliary ERCP failure. Our results support the use of EUS-guided biliary access to optimize single-session ERCP success. In experienced hands, these techniques appear as effective, if not more so, than precut papillotomy.

Feasibility of nonradiation EUS-based ERCP in patients with uncomplicated choledocholithiasis (with video).

BACKGROUND AND AIMS: ERCP inherently involves radiation exposure. Nonradiation ERCP has been described in pregnancy. Theoretically, the same techniques could be applied to the general population. We prospectively assessed the feasibility of nonradiation, EUS-based ERCP in nonpregnant patients with choledocholithiasis. METHODS: Consecutive patients referred for ERCP for choledocholithiasis were recruited over a 1-year period. Patients providing study consent underwent the following procedural protocol. First, EUS was performed to verify the presence, size, and number of stones. Second, biliary cannulation was attempted without fluoroscopy for a maximum of 10 minutes. Selective cannulation was based on deep insertion with visible bile in the catheter on aspiration. Third, for stone removal, sphincterotomy was performed and stones were removed using a basket or balloon. The number of stones exiting the papilla was matched to the number seen on EUS. Finally, once the duct was deemed clear by the endoscopist, a final occlusion cholangiogram and ductal sweep served as the reference standard for confirmation of stone clearance. RESULTS: Nonradiation ERCP was attempted in 31 patients. Cannulation without fluoroscopy was successful in 26 patients (84%). Complete stone removal without fluoroscopy was achieved in all 26 of these cases. The 5 patients with failed nonfluoroscopic cannulation required double guidewire (n = 2) or precut papillotomy (n = 3) for deep biliary access and subsequent stone clearance. One patient who required precut papillotomy for access developed moderate post-ERCP pancreatitis (3%). CONCLUSIONS: Nonradiation, EUS-based ERCP for uncomplicated choledocholithiasis appears to be successful and safe. (Clinical trial registration number: NCT01678391.).

EUS-guided drainage of peripancreatic fluid collections and necrosis by using a novel lumen-apposing stent: a large retrospective, multicenter U.S. experience (with videos).

BACKGROUND AND AIMS: EUS-guided drainage of peripancreatic fluid collection (PFC) (pancreatic pseudocyst [PP] or walled-off necrosis [WON]) by using a novel lumen-apposing, fully covered, self-expandable metal stent (LAMS) has been promising, but few of these data are from the United States. The aim of this study was to evaluate clinical outcomes and safety of EUS-guided drainage of pancreatic pseudocysts and WON by using the LAMS. METHODS: We conducted a multicenter, retrospective study on 82 patients with symptomatic PFC who underwent EUS-guided drainage by using the LAMS at 4 U.S. tertiary care centers. Outcomes evaluated included successful placement of the LAMS, the number of patients in whom complete resolution of PPs or WON was achieved, the number of procedures performed per patient to achieve PFC resolution, and adverse events. RESULTS: The mean size of the PFC was 11.8 cm. LAMSs were successfully placed in 80 patients (97.5%). Twelve patients had PP and 68 had WON. The median stent in-dwelling time was 2 months (range 1-3 months). Endoscopic debridement with the LAMS in WON was performed in 54 patients. The patency of the stent was maintained in 98.7% of the patients (77/78). There was spontaneous dislodgment of 2 LAMSs. Successful endoscopic therapy by using the LAMS was successful in 12 of 12 patients (100%) with PP compared with 60 of 68 patients (88.2%) with WON. All stents were endoscopically removed from all patients after peripancreatic fluid collection (PFC) resolution. There was 1 PFC recurrence during the 3-month median follow-up period. Procedure-related adverse events occurred in 8 patients (9.8%), and included stent maldeployment (n = 2), and self-limited bleeding (n = 6). In 1 patient with stent maldeployment gastric perforation developed, and the patient underwent surgical repair. CONCLUSION: EUS-guided drainage of PFCs by using the novel LAMS has high technical and long-term success rates. Due to its ease of use, the LAMSs may simplify and streamline EUS-guided management of PFCs, particularly for the endoscopic debridement of WON, and may help in its widespread adoption as an alternative to surgery.

Comparable efficacy with entecavir monotherapy and tenofovir-entecavir combination in chronic hepatitis B patients.

OBJECTIVES: The long-term goal for chronic hepatitis B patients is to maintain viral suppression in order to reduce disease progression risk. Because patients with previous treatment failure may have multiple viral resistance mutations, finding effective therapy is challenging. Because recent studies have shown that the combination of entecavir and tenofovir is effective in achieving virological response in many patients with prior treatment failure and multiple drug resistance mutations, we compared outcomes with this combination versus monotherapy. METHODS: With a retrospective chart review we compared results in 35 patients with previous treatment failure treated with the entecavir-tenofovir combination to results in patients treated with entecavir monotherapy. RESULTS: Although combination therapy resulted in significantly faster achievement of DNA negativity compared to entecavir monotherapy, the modest ten-week advantage is unlikely to be important for most patients since entecavir resistance develops extremely slowly. Significantly more patients on combination therapy experienced viral breakthroughs, most of which were attributed to non-adherence due to difficulties with the combination regimen. CONCLUSIONS: Our findings of reasonably comparable efficacy over time in the combination and monotherapy arms combined with the increased costs and compliance issues related to combination therapy weigh in favor of entecavir monotherapy in patients with previous treatment failure. However, because our study was a retrospective analysis of a small patient population, it will be important to confirm these findings with a randomised, controlled trial that compares these treatment approaches in treatment-experienced patients.

EUS-FNA is superior to ERCP-based tissue sampling in suspected malignant biliary obstruction: results of a prospective, single-blind, comparative study.

BACKGROUND: Both EUS and ERCP sampling techniques may provide tissue diagnoses in suspected malignant biliary obstruction. However, there are scant data comparing these 2 methods. OBJECTIVE: To compare EUS-guided FNA (EUS-FNA) and ERCP tissue sampling for the diagnosis of malignant biliary obstruction. DESIGN: Prospective, comparative, single-blind study. SETTING: Tertiary center. PATIENTS: Fifty-one patients undergoing same-session EUS and ERCP for the evaluation of malignant biliary obstruction over a 1-year period. INTERVENTIONS: EUS-FNA and ERCP tissue sampling with biliary brush cytology and intraductal forceps biopsies. MAIN OUTCOME MEASUREMENTS: Diagnostic sensitivity and accuracy of each sampling method compared with final diagnoses. RESULTS: EUS-FNA was more sensitive and accurate than ERCP tissue sampling (P < .0001) in 51 patients with pancreatic cancers (n = 34), bile duct cancers (n = 14), and benign biliary strictures (n = 3). The overall sensitivity and accuracy were 94% and 94% for EUS-FNA, and 50% and 53% for ERCP sampling, respectively. EUS-FNA was superior to ERCP tissue sampling for pancreatic masses (sensitivity, 100% vs 38%; P < .0001) and seemed comparable for biliary masses (79% sensitivity for both) and indeterminate strictures (sensitivity, 80% vs 67%). LIMITATIONS: Single-center study. CONCLUSION: EUS-FNA is superior to ERCP tissue sampling in evaluating suspected malignant biliary obstruction, particularly for pancreatic masses. EUS-FNA appears similar to ERCP sampling for biliary tumors and indeterminate strictures. Given the superior performance characteristics of EUS-FNA and the higher incidence of pancreatic cancer compared with cholangiocarcinoma, EUS-FNA should be performed before ERCP in all patients with suspected malignant biliary obstruction. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01356030.).

Successful single-session endosonography-based endoscopic retrograde cholangiopancreatography without fluoroscopy in pregnant patients with suspected choledocholithiasis: a case series.

PURPOSE: Same session endosonography (EUS) immediately prior to scheduled endoscopic retrograde cholangiopancreatography (ERCP) may eliminate the need for ERCP and its associated risks in pregnant patients with no evidence of choledocholithiasis on EUS. In patients with choledocholithiasis, EUS provides information regarding the location, size and number of stones present, which helps guide biliary interventions and confirm stone clearance without the use of fluoroscopy. METHODS: We retrospectively identified 10 pregnant patients referred to our tertiary endoscopy center for suspected choledocholithiasis between June 2008 and January 2012. All patients underwent same-session EUS-based ERCP. RESULTS: Of 10 pregnant patients managed with EUS-guided ERCP, six were found to have common bile duct stones and went on to ERCP. Four patients with no evidence of choledocholithiasis on EUS did not undergo ERCP. Patients with confirmed choledocholithiasis underwent ERCP without the use of fluoroscopy using the additional information provided by EUS. CONCLUSIONS: Same-session EUS immediately prior to scheduled ERCP may eliminate the need for ERCP and its risks in pregnant patients with no evidence of choledocholithiasis on EUS. In patients with confirmed choledocholithiasis, EUS provided additional information regarding the location, number and size of bile duct stones, which enabled the successful clearance of the bile duct without the use of fluoroscopy.

Suck-ligate-unroof-biopsy by using a detachable 20-mm loop for the diagnosis and therapy of small subepithelial tumors (with video).

BACKGROUND: The diagnosis and therapy of subepithelial tumors (SETs) can be challenging. OBJECTIVE: Proof-of-concept evaluation of the suck-ligate-unroof-biopsy (SLUB) technique for small (<2 cm), non-pedunculated SETs. DESIGN: Pilot feasibility study. SETTING: Tertiary-care referral center. PATIENTS: Twenty-three patients (median age 60 years) meeting the inclusion criteria after preliminary EUS. INTERVENTION: SET ligation was performed with a detachable 20-mm loop deployed through an 18-mm diameter, soft, oblique, transparent, cap attachment. The SLUB technique comprised (1) suction to draw the SET into the cap; (2) ligation below the SET, confirmation by repeat EUS; (3) unroofing of the overlying mucosa with a needle-knife; and (4) biopsy specimens taken from the exposed tumor. MAIN OUTCOME MEASUREMENTS: Technical success, histology and/or immunohistochemistry yield, adverse events, completeness of resection. RESULTS: SLUB was attempted on 24 SETs and was technically successful in all. Location was the stomach (n = 19), small bowel (n = 1), colon (n = 2), and rectum (n = 2). Median size by EUS was 10 mm (range 6-15 mm). Biopsy specimens provided an immunohistologic diagnosis in all cases: GI stromal tumor (n = 5), leiomyoma (n = 8), carcinoid tumor (n = 5), Vanek's tumor (n = 2), granuloma (n =1), and pancreatic heterotopia (n = 3). Follow-up endoscopy and EUS in 13 patients showed well-healed scars with no residual tumor, including all 9 patients with premalignant neoplastic lesions. The only adverse event was self-limited pain in 2 patients. LIMITATIONS: Single center, single operator, small sample size. CONCLUSIONS: Loop ligation of small, non-pedunculated SETs is feasible by using a cap attachment for suction. Unroofing after ligation is safe and provides sufficient tissue for immunohistochemistry. Ligation combined with unroofing appears to lead to complete ablation by ischemia and tumor enucleation.

"Underwater" EMR of sporadic laterally spreading nonampullary duodenal adenomas (with video).

BACKGROUND: EMR for the treatment of duodenal adenomas is challenging due to a thin wall and rich vascularity. OBJECTIVE: To evaluate a novel technique of "underwater" EMR without prior submucosal injection for the removal of large (≥2 cm) laterally spreading nonampullary duodenal adenomas. DESIGN: Prospective, observational study. SETTING: Tertiary academic referral center. PATIENTS: Twelve patients (median age, 60 years) meeting the inclusion criteria. INTERVENTIONS: Piecemeal EMR technique after sterile water submersion when using a double-channel endoscope. MAIN OUTCOME MEASUREMENTS: Technical success, adverse events, completeness of resection on follow-up endoscopy. RESULTS: Median adenoma size was 35 mm (25% greater than one-half circumference, 50% equal to one-third to one-half circumference, and 25% less than one-third circumference). Median procedure time was 65 minutes (range, 32-151). Final histology was tubular adenoma (7), tubulovillous adenoma (1), villous adenoma (3), and high-grade dysplasia (1). Eleven patients (92%) met the primary endpoint (technical success) and all patients met the secondary endpoint (completeness of resection). Median interval until follow-up endoscopy was 16 weeks (range, 11-56). Adverse events were as follows: delayed bleeding (3 patients, of whom 2 required transfusions), water intoxication syndrome manifested by altered mental status and hyponatremia (1), and stricture formation (1) that responded to balloon dilation. No perforation or postresection abdominal pain was found. LIMITATIONS: Single operator, single center, small sample size, limited follow-up. CONCLUSION: Underwater EMR for large sessile duodenal adenomas has high success rates for complete removal. The risk of delayed bleeding is significant, and precautions are needed when infusing a large volume of fluid into the GI tract.

Coinfection with hepatitis B and D: epidemiology, prevalence and disease in patients in Northern California.

BACKGROUND AND AIMS: With no report on the overall prevalence and ramifications of hepatitis Delta virus (HDV) infection in the United States for more than two decades, the characteristics of chronic hepatitis B virus (CHB) patients coinfected with HDV, including clinical presentation, rate of hepatitis C virus tri-infection, and HDV viral load, were assessed. METHODS: At California Pacific Medical Center, a retrospective chart review was conducted on all CHB patients. RESULTS: Of 1191 CHB patients, 499 had been tested for HDV, with 42 (8%) determined to be coinfected; half of these were also hepatitis C virus-infected. Cirrhosis was present in 73% of the coinfected, 80% of the tri-infected, but only 22% of the monoinfected. Twenty-nine patients (69%) were Caucasian non-Hispanic; 10 (24%) were Asians and Pacific Islanders. Of 39 patients for whom HBV-DNA quantification at time of HDV presentation was available, 22 (56%) had undetectable levels; four (10%) had levels > 100 000 IU/mL. CONCLUSIONS: HDV affects individuals of all ages and various ethnic groups. Although HBV viral loads are lower, rates of cirrhosis are higher in coinfected patients and higher still in the tri-infected. Our data support revising screening guidelines to advocate for all patients with HBV to be screened for HDV in order to both give the individual patient important information related to the possible need for treatment and to support the public health goal of reducing transmission by educating HDV-negative patients about the need for protection against superinfection and HDV-infected patients about the need to protect against transmission to others.

Retract-ligate-unroof-biopsy: a novel approach to the diagnosis and therapy of large nonpedunculated stromal tumors (with video).

BACKGROUND: We report a novel technique of retract-ligate-unroof-biopsy (RLUB) for the diagnosis and treatment of large nonpedunculated upper GI stromal tumors originating from the muscularis propria. OBJECTIVE: Proof-of-concept evaluation of the RLUB technique. DESIGN: Pilot and feasibility study. SETTING: Tertiary care center. PATIENTS: Sixteen patients (median age 71 years) fulfilling the following inclusion criteria: poor surgical candidates with lesions that are broad based with a benign appearance, originating from the muscularis propria, size 2 cm or larger. INTERVENTIONS: A double-channel endoscope was used to simultaneously retract the stromal tumor while advancing an endoloop beyond the tumor for ligation. The overlying tissue was incised ("unroofed") to expose and partially enucleate the tumor, and multiple biopsy samples were obtained. After unroofing, an additional endoloop was placed below the previous one by using the loop-over-loop technique to reinforce enucleation and ischemic ablation. MAIN OUTCOME MEASUREMENTS: Successful ligation, immunohistochemistry and mitotic index yield, therapeutic ablation, adverse events. RESULTS: Technical success was achieved in 13 of 16 patients (81%). Immunohistology of biopsy specimens: GI stromal tumor (n = 10), leiomyoma (n = 3). Twelve of 13 patients (92%) with follow-up (median 22 weeks, range 1-82.5 weeks) had confirmed tumor ablation by endoscopy and EUS. One patient with partial resolution was re-treated, but was subsequently lost to follow-up. Delayed bleeding occurred in 2 patients that required hospitalization and blood transfusions, both successfully controlled with repeat endolooping. One patient reported transient pain. LIMITATIONS: Single center, single operator, small sample size. CONCLUSIONS: The RLUB technique is feasible as a platform for full-thickness treatment of stromal tumors. Limitations encountered included technical challenges and delayed bleeding. Further developmental work is needed.

Endosonography-guided transmural drainage of pancreatic pseudocysts using an exchange-free access device: initial clinical experience.

BACKGROUND: Endosonography (EUS)-guided transmural pseudocyst drainage is a multistep procedure currently performed with different "off-the-shelf" accessories developed for other applications. Multiple device exchanges over-the-wire is time consuming and risks loss of wire access. This report describes the technical feasibility and outcomes for EUS-guided drainage of pancreatic fluid collections using a novel exchange-free device developed for translumenal therapy. METHODS: Between April and November 2010, 14 patients (9 men; mean age, 49.9 years) with pancreatic fluid collection (mean size, 102 mm) underwent 16 EUS-guided drainage procedures using the exchange-free access device at a single tertiary care center. The trocar of the exchange-free device was used to gain pseudocyst access. The dual-balloon catheter then was advanced over the trocar, followed by inflation of the (first) anchor balloon. Cyst contents were sampled, and contrast was injected to define the pseudocyst anatomy. The first guidewire was inserted into the cyst cavity. The cystenterostomy tract was dilated to 10 mm with the (second) dilation balloon, followed by a second guidewire insertion. The exchange-free access device was removed, leaving the two guidewires in place for two double-pigtail stents. RESULTS: The procedure was technically successful for all the patients. No acute procedure-related complications occurred. Late complications included a symptomatic leak in a patient who underwent drainage of a pancreatic uncinate pseudocyst from the second duodenum, a self-limited transfusion-dependent bleed after transbulbar drainage, and symptomatic pseudocyst infection. CONCLUSION: Pseudocyst access, cystenterostomy tract dilation, and placement of two guidewires for dual stent drainage are technically feasible using an exchange-free access device. The device has the potential to standardize, simplify, and streamline EUS-guided pseudocyst drainage with a single instrument. Comparative studies with alternative tools and methods for pseudocyst drainage are warranted.

Macrophage dectin-1 expression is controlled by leukotriene B4 via a GM-CSF/PU.1 axis.

Pattern recognition receptors for fungi include dectin-1 and mannose receptor, and these mediate phagocytosis, as well as production of cytokines, reactive oxygen species, and the lipid mediator leukotriene B(4) (LTB(4)). The influence of G protein-coupled receptor ligands such as LTB(4) on fungal pattern recognition receptor expression is unknown. In this study, we investigated the role of LTB(4) signaling in dectin-1 expression and responsiveness in macrophages. Genetic and pharmacologic approaches showed that LTB(4) production and signaling through its high-affinity G protein-coupled receptor leukotriene B(4) receptor 1 (BLT1) direct dectin-1-dependent binding, ingestion, and cytokine production both in vitro and in vivo. Impaired responses to fungal glucans correlated with lower dectin-1 expression in macrophages from leukotriene (LT)- and BLT1-deficent mice than their wild-type counterparts. LTB(4) increased the expression of the transcription factor responsible for dectin-1 expression, PU.1, and PU.1 small interfering RNA abolished LTB(4)-enhanced dectin-1 expression. GM-CSF controls PU.1 expression, and this cytokine was decreased in LT-deficient macrophages. Addition of GM-CSF to LT-deficient cells restored expression of dectin-1 and PU.1, as well as dectin-1 responsiveness. In addition, LTB(4) effects on dectin-1, PU.1, and cytokine production were blunted in GM-CSF(-/-) macrophages. Our results identify LTB(4)-BLT1 signaling as an unrecognized controller of dectin-1 transcription via GM-CSF and PU.1 that is required for fungi-protective host responses.

Similar risk of renal events among patients treated with tenofovir or entecavir for chronic hepatitis B.

BACKGROUND & AIMS: Tenofovir is a nucleotide reverse-transcriptase inhibitor approved for treatment of human immunodeficiency virus infection, as well as chronic hepatitis B (CHB). We evaluated nephrotoxicity among patients with CHB treated with tenofovir. METHODS: We performed a community-based, retrospective cohort study of 80 patients with CHB who received tenofovir, alone or in a combination regimen; they were matched for age and sex with 80 CHB patients who received only entecavir. Incidences of serum creatinine (SCr) increase ≥0.2 mg/dL and new SCr levels of 1.5, 2.0, or 2.5 mg/dL were assessed. Patients with an estimated glomerular filtration rate (eGFR) <60 mL/min, calculated using the Modification of Diet in Renal Disease or Cockcroft-Gault formula, or who had ≥20% decrease in eGFR were also recorded. RESULTS: More patients given entecavir had increases in SCr ≥2.5 mg/dL (1 vs 6; P = .053), whereas more patients given tenofovir had a new Cockcroft-Gault eGFR of <60 mL/min (15 vs 6; P = .022) and at least 1 dose adjustment (13 vs 4; P = .021). By multivariate analysis, the only significant factors associated with an increase in SCr were a history of organ transplantation (adjusted odds ratio, 6.740; 95% confidence interval, 1.799-28.250; P = .005) and pre-existing renal insufficiency (adjusted odds ratio, 10.960; 95% confidence interval, 2.419-48.850; P = .002). No factors, including therapy assignment, were associated with a new eGFR <60 mL/min. CONCLUSIONS: Markers of renal function indicated that patients who received tenofovir were no more likely to have changes in renal function than patients treated with entecavir. History of transplant and pre-existing renal insufficiency were the only factors independently associated with increases in SCr.

"Underwater" EMR without submucosal injection for large sessile colorectal polyps (with video).

BACKGROUND: Submucosal injection is widely performed before EMR of large sessile colorectal polyps to facilitate resection and decrease perforation risk. We developed a novel method of water immersion ("underwater") EMR (UEMR) that eliminates submucosal injection. OBJECTIVE: To evaluate the feasibility and outcomes of UEMR without submucosal injection for large sessile colorectal polyps. DESIGN: Prospective, observational study. SETTING: Single, tertiary-care referral center. INTERVENTION: The standardized EMR technique involves full water immersion for the entire procedure and piecemeal resection with a 15-mm "duck bill" snare. MAIN OUTCOME MEASUREMENTS: Complete resection, bleeding, perforation, postpolypectomy syndrome, residual or recurrence adenoma. RESULTS: Sixty patients with 62 large sessile colorectal polyps underwent UEMR. The mean/median polyp size was 34/30 mm, and the mean/median resection time was 21/18 minutes. Histology revealed the following: tubular adenoma (n = 22), tubulovillous adenoma (n = 19), villous adenoma (n = 4), serrated adenoma (n = 11), and high-grade dysplasia/carcinoma in situ (n = 6). The mean/median interval until a follow-up colonoscopy in 54 patients (90%) was 20.4/15.2 weeks. One of 54 patients (2%) had an adenoma smaller than 5 mm outside of the postresection scar, consistent with a residual lesion missed on index UEMR. COMPLICATIONS: There was no perforation or postpolypectomy syndrome. Delayed bleeding occurred in 3 patients and was managed conservatively. LIMITATIONS: Limited follow-up; single-center, single-endoscopist, uncontrolled study. CONCLUSIONS: The underwater resection technique enables complete removal of large sessile colorectal polyps without submucosal injection. The technique was safe in a large patient cohort, and the early recurrence rate appears low. Use of a water interface for UEMR has potential advantages that deserve further study.

PTEN directly activates the actin depolymerization factor cofilin-1 during PGE2-mediated inhibition of phagocytosis of fungi.

Macrophage ingestion of the yeast Candida albicans requires its recognition by multiple receptors and the activation of diverse signaling programs. Synthesis of the lipid mediator prostaglandin E(2) (PGE(2)) and generation of cyclic adenosine monophosphate (cAMP) also accompany this process. Here, we characterized the mechanisms underlying PGE(2)-mediated inhibition of phagocytosis and filamentous actin (F-actin) polymerization in response to ingestion of C. albicans by alveolar macrophages. PGE(2) suppressed phagocytosis and F-actin formation through the PGE(2) receptors EP2 and EP4, cAMP, and activation of types I and II protein kinase A. Dephosphorylation and activation of the actin depolymerizing factor cofilin-1 were necessary for these inhibitory effects of PGE(2). PGE(2)-dependent activation of cofilin-1 was mediated by the protein phosphatase activity of PTEN (phosphatase and tensin homolog deleted on chromosome 10), with which it directly associated. Because enhanced production of PGE(2) accompanies many immunosuppressed states, the PTEN-dependent pathway described here may contribute to impaired antifungal defenses.

Leukotrienes target F-actin/cofilin-1 to enhance alveolar macrophage anti-fungal activity.

Candida albicans is the most common opportunistic fungal pathogen and causes local and systemic disease in immunocompromised patients. Alveolar macrophages (AMs) are pivotal for the clearance of C. albicans from the lung. Activated AMs secrete 5-lipoxygenase-derived leukotrienes (LTs), which in turn enhance phagocytosis and microbicidal activity against a diverse array of pathogens. Our aim was to investigate the role of LTB(4) and LTD(4) in AM antimicrobial functions against C. albicans and the signaling pathways involved. Pharmacologic and genetic inhibition of LT biosynthesis as well as receptor antagonism reduced phagocytosis of C. albicans when compared with untreated or WT controls. Conversely, exogenous LTs of both classes augmented base-line C. albicans phagocytosis by AMs. Although LTB(4) enhanced mainly mannose receptor-dependent fungal ingestion, LTD(4) enhanced mainly dectin-1 receptor-mediated phagocytosis. LT enhancement of yeast ingestion was dependent on protein kinase C-δ (PKCδ) and PI3K but not PKCα and MAPK activation. Both LTs reduced activation of cofilin-1, whereas they enhanced total cellular F-actin; however, LTB(4) accomplished this through the activation of LIM kinases (LIMKs) 1 and 2, whereas LTD(4) did so exclusively via LIMK-2. Finally, both exogenous LTB(4) and LTD(4) enhanced AM fungicidal activity in an NADPH oxidase-dependent manner. Our data identify LTB(4) and LTD(4) as key mediators of innate immunity against C. albicans, which act by both distinct and conserved signaling mechanisms to enhance multiple antimicrobial functions of AMs.

A modular approach to the analytic calculation of spectral phase for grisms and other refractive/diffractive structures.

Analytic expressions for spectral phase for optical systems are very important for the design of wide-bandwidth optical systems. We describe a general formalism for analytically calculating the spectral phase for arbitrary optical structure made up of nested pairs of plane-parallel interfaces that can be diffractive or refractive. Our primary application is the calculation of the spectral phase of a grism pair, which is then used to analyze the behavior of higher-order phase terms. The analytic expressions for the grism spectral phase provide insight into the tunability of the third-order phase of grisms as well as the fourth-order limits. Our exact and approximate expressions are compared with a raytracing model.

Quartic-phase-limited grism-based ultrashort pulse shaper.

By replacing the dispersive element in a zero-dispersion pulse shaper with a grism, we have constructed a quartic-phase-limited pulse shaper. We demonstrate compensation of 4500 fs2 without the use of a dynamic element in the pulse shaping line, which is approximately the amount of dispersion induced by a typical multiphoton microscope. We also demonstrate that detuning the pulse shaper to compensate for quadratic phase induces negligible spatial chirp, thereby maintaining a high-quality focal spot for a microscopy setup.