US Referral Center Research Articles

Efficacy of axitinib in a US cohort of patients with programmed cell death protein 1-resistant mucosal melanoma.

Mucosal melanoma is a rare melanoma subtype, accounting for about 1% of all diagnosed melanomas. It is characterized by an aggressive phenotype with a poor prognosis and a low response rate to approved treatments. We retrospectively analyzed the clinical features, treatments, and outcomes of patients diagnosed with mucosal melanoma treated with axitinib ± anti-programmed cell death protein 1 (PD-1) therapy at a single US referral center between 2018 and 2021. Radiologic response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST), v1.1. Twenty-three patients were included in this study. In all, 78% were females with a median age of 62 years. The originating site of mucosal melanoma was the sinonasal (35%), genitourinary (35%), and gastrointestinal (30%) tracts. Sixty-five percent of patients had M1c or M1d disease and 0% had BRAF V600 mutations detected. The majority (96%) had prior treatment inclusive of anti-PD-1, with a median of 2 prior lines, and 78% of patients received a combination of axitinib and PD-1 and the median duration of treatment was 3.2 months. The overall response rate was 13% and the disease control rate was 26%. The median progression-free survival was 3.2 months, and the median overall survival was 8.2 months. Overall, the regimen was well tolerated with 39% of patients requiring dose reduction and 9% requiring treatment cessation. Axitinib with anti-PD-1 therapy has modest clinical activity in heavily pretreated patients with mucosal melanoma outside of Asia, including some with long-term benefits. This data supports the worldwide clinical trials evaluating this combination and the role of incorporating vascular endothelial growth factor-based therapy in the therapeutic paradigm for patients with mucosal melanoma.

Association Between Mobilization and Composite Postoperative Complications Following Major Elective Surgery

Mobilization after surgery is a key component of Enhanced Recovery after Surgery (ERAS) pathways. To evaluate the association between mobilization and a collapsed composite of postoperative complications in patients recovering from major elective surgery as well as hospital length of stay, cumulative pain scores, and 30-day readmission rates. This retrospective observational study conducted at a single quaternary US referral center included patients who had elective surgery between February 2017 and October 2020. Mobilization was assessed over the first 48 postoperative hours with wearable accelerometers, and outcomes were assessed throughout hospitalization. Patients who had elective surgery lasting at least 2 hours followed by at least 48 hours of hospitalization were included. A minimum of 12 hours of continuous accelerometer monitoring was required without missing confounding variables or key data. Among 16 203 potential participants, 8653 who met inclusion criteria were included in the final analysis. Data were analyzed from February 2017 to October 2020. Amount of mobilization per hour for 48 postoperative hours. The primary outcome was a composite of myocardial injury, ileus, stroke, venous thromboembolism, pulmonary complications, and all-cause in-hospital mortality. Secondary outcomes included hospital length of stay, cumulative pain scores, and 30-day readmission. Of 8653 included patients (mean [SD] age, 57.6 [16.0] years; 4535 [52.4%] female), 633 (7.3%) experienced the primary outcome. Mobilization time was a median (IQR) of 3.9 (1.7-7.8) minutes per monitored hour overall, 3.2 (0.9-7.4) in patients who experienced the primary outcome, and 4.1 (1.8-7.9) in those who did not. There was a significant association between postoperative mobilization and the composite outcome (hazard ratio [HR], 0.75; 95% CI, 0.67-0.84; P < .001) for each 4-minute increase in mobilization. Mobilization was associated with an estimated median reduction in the duration of hospitalization by 0.12 days (95% CI, 0.09-0.15; P < .001) for each 4-minute increase in mobilization. The were no associations between mobilization and pain score or 30-day readmission. In this study, mobilization measured by wearable accelerometers was associated with fewer postoperative complications and shorter hospital length of stay.

Clinical Features and Management of Small Bowel Masses Detected During Device-Assisted Enteroscopy: A Multi-Center Experience.

Small bowel mass lesions (SBMLs) are rare, span a range of different histologies and phenotypes, and our understanding of them is limited. Some lesions occur in patients with recognized polyposis syndromes and others arise sporadically. The current literature regarding SBMLs is limited to small retrospective studies, case reports, and small case series. This large multi-center study aims to understand the various clinical presentations, histologies and management options for SBMLs. After obtaining Institutional Review Board (IRB) approval, electronic records were used to identify all device-assisted enteroscopy (DAE) performed for luminal small bowel evaluation in adult patients at three US referral centers (Duke, LSU and UMass) from January 1, 2014, to October 1, 2020. We identified all patients within this cohort in whom a SBML was detected. Using a focused electronic medical record chart review, we collected patient, procedure, and lesion-related data and used descriptive statistics to explore relationships between these data and outcomes. A total of 218 patients (49 at Duke, 148 at LSU, and 21 at UMass) in this cohort had at least one SBML found on DAE. The most common presenting symptoms were iron-deficiency anemia/bleeding (73.3%) and abnormal imaging (33.6%). Thirty-five percent of patients had symptoms for more than a year prior to their diagnosis. Most patients (71.6%) underwent video capsule endoscopy (VCE) prior to DAE and 84% of these exams showed the lesion. The lesion was seen less frequently (48.9%) on computed tomography (CT) scan performed prior to DAE. The majority of lesions were found on antegrade (56%) or retrograde (29.8%) double-balloon enteroscopy (DBE). The most common lesion phenotypes were submucosal (41.3%) and pedunculated (33%) with a much smaller number being sessile (14.7%) or obstructing/invasive (11%). They were found equally as commonly in the jejunum (46.3%) and ileum (49.5%). Most lesions were 10 - 20 mm in size (47%) but 22.1% were larger than 20 mm. The most common histologies were neuroendocrine tumors (NETs, 20.6%) and hamartomas (20.6%). Primary adenocarcinoma of the small bowel was rare, constituting only 5% of lesions. The majority of polyps (78.4%) were sporadic, compared to 21.7% associated with a polyposis or hereditary cancer syndrome, most commonly Peutz-Jeghers syndrome (18.3%). After DAE, 37.6% were advised to undergo surgical resection and 48% were advised to undergo endoscopic surveillance or no further management because of benign histology or successful endoscopic resection. In this multi-center retrospective study we found that SBMLs are more likely to be sporadic than syndromic, medium in size and either pedunculated or submucosal. NETs and hamartomas predominated and symptoms, most commonly anemia, can be present for more than a year prior to diagnosis. Close to one half of lesions required either no further intervention or only endoscopic surveillance.

S1571 Device-Assisted Enteroscopy (DAE) in the Surveillance of Intestinal Polyposis in Peutz-Jeghers Syndrome

Introduction: Peutz-Jeghers Syndrome (PJS) is an autosomal dominant, genetic disorder characterized by the formation of hamartomatous polyps in the gastrointestinal tract. These polyps are a source of significant morbidity and mortality in this population due to associated complications of intestinal obstruction, bleeding, and malignant transformation. Surveillance of intestinal polyposis in patients with PJS has not been extensively studied, although centers which perform a significant volume of device-assisted enteroscopies (DAEs) encounter multiple cases each year. With the progressive adoption of DAE, examination of the deep small bowel for monitoring and prophylactic polypectomy has the potential to prevent complications of PJS and minimize the need for repeated laparotomy. Methods: After obtaining IRB approval, electronic health records were used to identify all DAEs performed on patients with PJS at 3 US referral centers (LSU, Duke, and UMass) between January 1, 2007 and January 1, 2020. Electronic medical records were reviewed to collect and analyze multiple data points. Primary endpoints included the complications associated with DAE performed for removal of intestinal hamartomas and the rate of laparotomy in PJS patients prior to and after index DAE. Secondary data points included patient characteristics, procedural details, and size/location/distribution of small bowel hamartomas. Results: Twenty-four patients met our inclusion criteria. Of these, 18 (75%) had previously undergone small bowel surgery for complications related to small bowel hamartomas. Between 2007 - 2020, a total of 46 DAEs were performed in these patients with an average of one surveillance exam every 2.5 years. A total of 131 polypectomies were performed during our study period with an observed complication rate of 1.5%, including one bowel perforation requiring surgery. Only one patient underwent surgery related to small bowel hamartomas following initial DAE surveillance exam over a total of 366 years of aggregated follow-up (Figure). Conclusion: Endoscopic management of small bowel polyps in patients with PJS using DAE is an effective strategy for prophylactic removal of hamartomas. DAE surveillance and endoscopic polypectomy is safe and may decrease the need for repeated laparotomy due to complications from intestinal hamartomas in patients with PJS.Figure 1.: Hamartomatous polyp in the ileum removed with saline injection-lift technique and hot snare polypectomy

A Descriptive Analysis of Immune Thrombotic Thrombocytopenic Purpura (iTTP) Patients with Fatal Outcomes in the U.S. Thrombotic Microangiopathy (USTMA) TTP Registry

Background:Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy (TMA) occurring due to an acquired deficiency in ADAMTS13. Mortality due to iTTP is estimated at 10% with current standard treatment that consists of plasma exchange (PLEX) and corticosteroids. The United States TMA (USTMA) registry incorporates 15 large US referral centers across the nation, and includes patients diagnosed with iTTP between 1985 and 2019. We sought to perform a descriptive analysis on the patients with fatal outcomes attributable to acute iTTP episodes in the registry.Methods:We utilized the USTMA registry (n=771) and analyzed twenty-two baseline patient demographics, presenting symptoms, and laboratory findings. The study cohort included participants with iTTP diagnosis based on the presence of thrombocytopenia (platelet count <100 /µL), microangiopathic hemolyic anemia (hemoglobin less than the lower limit of normal with schistocytes on the peripheral blood smear), and either ADAMTS13 activity <10% or ADAMTS13 activity <20% with an anti-ADAMTS13 inhibitor or antibody. For participants diagnosed before the ADAMTS13 assay was developed (2006), the iTTP diagnosis was based on the clinical course and absence of alternative causes. iTTP exacerbation was defined as clinical disease recurrence within 30 days of PLEX discontinuation, and clinical relapse was defined as disease recurrence after 30 days of last PLEX, as per the international working group definitions 1.Results:A total of 33 patients (4.28%) in the USTMA cohort died during acute iTTP episodes. The patient demographics and initial presenting lab values are summarized in Table 1.Time of death (Figure 1):22 patients (66.7%) died during the initial iTTP episode, and within 30 days of presentation.3 patients (9.0%) died during disease exacerbation of the initial episode.8 patients (24.2%) died due to disease relapse.Median time to death at initial presentation/exacerbation (n=25) = 8 days [IQR: 4-19]Median time to death due to relapse = 1.6 years [IQR: 1.1-5.7]Patient demographics and presenting features (Table 1):Median age = 51 years [IQR: 27.8-60]Sex = 54.5% female, 45.5% malePresence of neurologic symptoms on presentation: 22 (66.7%)Presence of any symptoms on presentation: 32 (97%)Conclusion:Patients with fatal outcomes due to acute iTTP episodes presented with variable symptoms and baseline characteristics. While the vast majority of deaths occurred during the initial acute episode, death also occurred during exacerbation of the initial episode or subsequent disease relapse. Vigilant laboratory and clinical monitoring both after achieving initial remission and during long-term follow-up are necessary, to allow detection of disease exacerbation and relapse, and potentially prevent iTTP-related deaths.1. Cuker A, Cataland SR, Coppo P, et al. Redefining outcomes in immune TTP: an international working group consensus report. Blood. 2021;137(14):1855-1861. [Display omitted] DisclosuresMazepa: Answering TTP Foundation: Research Funding; Sanofi Aventis: Other. Lim: Hema Biologics: Honoraria; Sanofi Genzyme: Honoraria; Dova Pharmaceuticals: Honoraria.

US referral center experience removing nonpalpable and difficult contraceptive implants with in-office ultrasonography: A case series

ObjectivesTo assess referral center outcomes with removal of difficult or nonpalpable contraceptive implants using high-frequency point-of-care ultrasonography. Study DesignWe present a case series examining patients referred to our specialty center from January 2019 through September 2020 for difficult or nonpalpable implant removal. ResultsOf the 54 referrals, 6 had palpable implants and 48 required ultrasonography. We localized 46 (96%) implants in-office, including 13 located subfascially; 2 Implanon implants could not be localized. We successfully completed 50 (96%) of 52 attempted in-office removals, including 12 (92%) subfascial implants. ConclusionHigh-frequency point-of-care ultrasonography can effectively localize nonpalpable contraceptive implants leading to successful in-office removal. ImplicationsSpecialists can use high-frequency point-of-care ultrasonography to localize nonpalpable implants without formal radiology scans and skilled technologists, optimizing patient time and convenience. However, the probe is expensive, and providers may need to consider this cost in the context of reimbursement for these highly specialized procedures.

Use, Yield, and Risk of Device-assisted Enteroscopy in the United States: Results From a Large Retrospective Multicenter Cohort.

Since 2001, device-assisted enteroscopy (DAE) has revolutionized the diagnostic and therapeutic capabilities for managing small bowel pathology. Though commonly performed, there have been no recent large studies to assess the use, yield, and risks of DAE and none that include all 3 DAE modalities. We hypothesized that DAE is safe with high diagnostic and therapeutic yields achieved within reasonable procedure duration and here we present a large retrospective multicenter US study evaluating the use, yield, and complications of DAE. After obtaining institutional review board approval, electronic records were used to identify all DAE's performed for luminal small bowel evaluation in adult patients at 4 US referral centers (Duke University Medical Center, New York University Langone Medical Center, Louisiana State University Health Sciences Center, and University of Massachusetts Medical Center) from January 1, 2014 to January 1, 2019. Electronic medical records were reviewed to collect and analyze a variety of procedure-related outcomes. Using the data pooled across centers, descriptive statistics were generated for the patient and procedure-related characteristics and outcomes; relationships between characteristics and outcomes were explored. A total of 1787 DAE's were performed over this 5-year period (392 at Duke University Medical Center, 887 at Louisiana State University Health Sciences Center, 312 at New York University Langone Medical Center, and 195 at University of Massachusetts Medical Center). Of these, there were 1017 (57%) double-balloon, 391 (29%) single-balloon, and 378 (21%) spiral enteroscopies. The mean age of patients undergoing DAE was 66 years and 53% of examinations were performed on women; 18% of patients in the cohort underwent >1 DAE over this time span. A total of 53% of examinations were performed for suspected small bowel bleeding, 31% were directly guided by video capsule endoscopy findings and 8% were performed for abnormal imaging. A total of 85% of examinations used an antegrade approach and DAE took a mean of 45 minutes to complete; 76% of examinations revealed abnormal findings, with vascular, inflammatory, and neoplastic findings seen in 49%, 17%, and 15% of the cohort, respectively. Older age was significantly associated with any abnormal finding, including arteriovenous malformations (P<0.0001); 50% of examinations included a therapeutic maneuver, most commonly argon plasma coagulation/cautery (43%). There were complications in 16 examinations (0.9%) including 2 perforations (0.1%), 6 cases with bleeding (0.3%) and 1 episode of pancreatitis (0.1%). DAE is most commonly performed to evaluate suspected small bowel bleeding and is commonly directed by video capsule findings. DAE is safe, has a high diagnostic yield, with 76% of examinations showing abnormal findings, and frequently features therapeutic maneuvers. Advancing age is associated with abnormal findings on DAE.

Matched retrospective study of infective endocarditis among solid organ transplant recipients compared to non-transplant: Seven-year experience in a US Referral Center.

Infective endocarditis (IE) is a rare complication following solid organ transplant (SOT); data on the clinical features and outcomes of IE in SOT recipients in the modern era are limited. We conducted a single-center retrospective cohort study of IE diagnosed from 1/2008-12/2014 in SOT recipients, who were matched by age and microorganism to cases of IE in non-SOT, to describe the clinical features and outcomes. There were 14 cases of IE identified in SOT recipients matched to 56 non-SOT controls. Median time from transplant to IE was 1017days (IQR 379-1830). Compared to non-SOT patients, SOT patients were more likely to be undergoing current hemodialysis (16% vs 36%) and to possess indwelling central venous catheters within the 30days prior to diagnosis of IE (27% vs 50%). No SOT patients had documented drug use as a risk factor for IE whereas 6 (11%) non-SOT did. Enterococcus was the most common etiologic agent and was isolated in 50% of cases; only one fungal infection was identified, a mixed infection with Candida. Thirty-day mortality was 14% in SOT patients, significantly higher versus no deaths in non-SOT (P=.037). The present study illustrates a change in epidemiology of IE in SOT patients characterized by IE that generally occurs more than one-year post-transplant, is due to bacterial infection rather than fungus, and appears to be health care associated. Multicenter studies are merited to explore transplant-specific risk factors for IE in the special population of SOT patients.

Differential Effect of Rituximab on Relapse-Free Survival in De Novo and Relapsed Immune Thrombotic Thrombocytopenic Purpura in African-American and Caucasian Populations

Differential Effect of Rituximab on Relapse-Free Survival in De Novo and Relapsed Immune Thrombotic Thrombocytopenic Purpura in African-American and Caucasian Populations

Lower endoscopic ultrasound in preoperative evaluation of rectosigmoid endometriosis.

Background and study aims Endometriosis affects a significant proportion of reproductive-aged women and involves the bowel in up to one-third of patients with the condition. Lower endoscopic ultrasound (LEUS) in assessment of endometriosis of the rectosigmoid colon was first described 20 years ago in European populations. The current study aimed to describe the diagnostic characteristics of this imaging modality at a tertiary US referral center in a large cohort and its impact on surgical planning. Patients and methods This was a retrospective cohort study of adult women evaluated for rectosigmoid endometriosis by LEUS at an American tertiary referral center between January 2003 through June 2017. The reference standard for rectosigmoid endometriosis was surgical evaluation regardless of whether tissue was obtained for histologic evaluation. Two separate analyses were run; one comparing EUS to laparoscopic findings and another comparing EUS to histologic findings. Results LEUS demonstrated a positive predictive value (PPV) of 93.8 % (CI:68.1,99.1) and negative predictive value (NPV) of 96.4 % (CI:87.8,99.0) in the diagnosis of rectosigmoid endometriosis. Test sensitivity was 88.2 % (CI:63.6,98.5) and specificity was 98.2 % (CI:90.1,99.9). Overall diagnostic accuracy of the test was 95.8 % (CI:88.1,99.1). Conclusions In this large cohort of women at an American tertiary referral center undergoing evaluation for rectosigmoid endometriosis, LEUS demonstrated high PPV and NPV as well as excellent diagnostic accuracy. In addition, the LEUS findings provided important information to the referring gynecologic surgeon. This minimally-invasive imaging modality should be utilized in preoperative evaluation of women undergoing surgery for suspected or known endometriosis.

Practice Patterns and Utilization of Tube Feedings in Acute Pancreatitis Patients at a Large US Referral Center.

Clinical trials on tube feedings (TFs) have not been sufficiently powered to change practice patterns in acute pancreatitis (AP). We aimed to describe the use, duration, and resource utilization of TF in AP patients at an expert US center. Of 423 AP patients prospectively enrolled at the University of Pittsburgh Medical Center from 2004 to 2014, 139 (33%) received TF. Data on TF were assessed in 100 (72%) of 139 patients with complete data available. Patients on TF were more likely to be male, be obese, have alcohol etiology, and have moderately severe (34% vs 19%) or severe AP (62% vs. 3%) (P < 0.05). Tube feedings were started after a median of 5 days (interquartile range, 3-8 days) from admission and were administered for a median of 39 days (interquartile range, 19-58 days). A nasojejunal route (95%) with an oligomeric formula (92%) was the preferred TF strategy. Feeding tube complications led to at least 1 endoscopic tube replacement in 42% of patients and to an unexpected health care visit in 29% of those discharged on TF (16/55 patients). Tube feedings form an important component in the management of patients with moderately severe and severe AP. Further studies should define the optimal utilization of TF and ways to reduce TF-related complications.

601 - Natural History of Crohn's Disease Postoperative Recurrence in a US Referral Center in the Era of Biologics and Therapeutic Intensification Based on Early Endoscopic Findings

601 - Natural History of Crohn's Disease Postoperative Recurrence in a US Referral Center in the Era of Biologics and Therapeutic Intensification Based on Early Endoscopic Findings

Tropheryma whipplei Infection (Whipple Disease) in the USA.

Whipple disease (WD) is an infection caused by the bacterium Tropheryma whipplei (TW). Few cases have been reported in the USA. To report on the demographics, clinical manifestations, diagnostic findings, treatment, and outcomes of TW infection. Cases of TW infection diagnosed from 1995 to 2010 were identified in three US referral centers and from 1995 to 2015 in one. Definite classic WD was defined by positive periodic acid-Schiff (PAS) staining and probable WD by specific positive TW polymerase chain reaction (PCR) of intestinal specimens. Localized infections were defined by a positive TW PCR result from samples of other tissues/body fluids. Among the 33 cases of TW infections, 27 (82%) were male. Median age at diagnosis was 53years (range 11-75). Diagnosis was supported by a positive TW PCR in 29 (88%) and/or a positive PAS in 16 (48%) patients. Classic WD was the most frequent presentation (n = 18, 55%), with 14 definite and 4 probable cases. Localized infections (n = 15, 45%) affected the central nervous system (n = 7), joints (n = 4), heart (n = 2), eye (n = 1), and skeletal muscle (n = 1). Blood PCR was negative in 9 of 17 (53%) cases at diagnosis. Ceftriaxone intravenously followed by trimethoprim and sulfamethoxazole orally was the most common regimen (n = 23, 70%). Antibiotic therapy resulted in clinical response in 24 (73%). TW infection can present as intestinal or localized disease. Negative small bowel PAS and PCR do not exclude the diagnosis of TW infection, and blood PCR is insensitive for active infection.

The End–of-Life Experience for International Patients: Review from a Destination Medical Center (S763)

•Recognize the unique nature of the population of seriously ill international patients.•Review the end-of-life experience of seriously ill international patients at a major US referral center. Patients from all over the world travel to the United States to receive medical care. Seriously ill international patients and their families may face barriers to goal concordant end-of-life (EOL) care, especially those whose illness severity prevents a return to their home country. Little is known about the EOL experiences of this diverse group. This review was designed to characterize the EOL experiences of all international patients that died at Mayo Clinic Rochester, a tertiary care academic medical center with a large international referral base, from 2005-2015. After institutional review board approval, charts in the electronic medical record were reviewed for patients that died from 01/01/2005-12/31/2015 with a primary address outside of the United States. Data were abstracted and analyzed with standard statistical methods. Eighty-two (n = 82) international patients meeting the inclusion criteria died at Mayo Clinic between 2005-2015 with a median age at death of 59.5 years (range 21-88). Forty-eight patients (59%) were male, and the top three countries of origin were Saudi Arabia (n = 20), Kuwait (n = 16), and Canada (n = 9). The median length of the terminal hospital stay was 13 days (range 1-231 days). Nine patients (11%) had completed an advanced directive and 74% of patients had a DNR status at time of death. Thirty-four patients (42%) received palliative medicine consultation during terminal admission at a median of 8.5 days before death. Most changes to resuscitation preferences occurred during terminal hospitalization; three patients (4%) had do not resuscitate (DNR) status on admission and 61 patients (74%) were DNR at time of death. Compared to other published datasets of American patients, our cohort demonstrated a much lower completion of advance directives (11%).

Identifying patients at risk of inhospital death or hospice transfer for early goals of care discussions in a US referral center: the HELPS model derived from retrospective data

ObjectiveCreate a score to identify patients at risk of death or hospice placement who may benefit from goals of care discussion earlier in the hospitalisation.DesignRetrospective cohort study to develop a...

Percutaneous debridement and washout of walled-off abdominal abscess and necrosis using flexible endoscopy: a large single-center experience.

Background and study aims: Direct percutaneous endoscopic necrosectomy has been described as a minimally invasive intervention for the debridement of walled-off pancreatic necrosis (WOPN). In this retrospective cohort study, we aimed to confirm these findings in a US referral center and evaluate the clinical value of this modality in the treatment of pancreatic necrosis as well as other types of intra-abdominal fluid collections and necrosis. Patients and methods: Twelve consecutive patients with WOPN or other abdominal abscess requiring debridement and washout underwent computed tomography (CT)-guided drainage catheter placement. Each patient then underwent direct percutaneous endoscopic necrosectomy and washout with repeat debridement performed until complete. Drains were then removed once output fell below 30 mL/day and imaging confirmed resolution. The primary endpoints were time to clinical resolution and sustained resolution at 1-year follow up. Results: Ten patients were treated for WOPN, one for necrotic hepatic abscesses, and one for omental necrosis. The median time to intervention was 85 days with an average of 2.3 necrosectomies performed. Complete removal of drains was accomplished in 11 patients (92 %). The median time to resolution was 57 days. No serious adverse events occurred; however, one patient developed pancreaticocutaneous fistulas. Ten patients completed 1-year surveillance of which none required drain replacement. No patients required surgery or repeat endoscopy. Conclusions: This series supports the premise that direct percutaneous endoscopic necrosectomy is a safe and effective intervention for intra-abdominal fluid collections and necrosis in appropriately selected patients. Our study demonstrates a high clinical success rate with minimal adverse events. This modality offers several potential advantages over surgical and transgastric approaches including use of improved accessibility, an excellent safety profile, and requirement for only deep or moderate sedation.

Covering the Cover

Covering the Cover

Mutation Spectrum and Risk of Colorectal Cancer in African American Families with Lynch Syndrome

African Americans (AAs) have the highest incidence of and mortality resulting from colorectal cancer (CRC) in the United States. Few data are available on genetic and nongenetic risk factors for CRC among AAs. Little is known about cancer risks and mutations in mismatch repair (MMR) genes in AAs with the most common inherited CRC condition, Lynch syndrome. We aimed to characterize phenotype, mutation spectrum, and risk of CRC in AAs with Lynch syndrome. We performed a retrospective study of AAs with mutations in MMR genes (MLH1, MSH2, MSH6, and PMS2) using databases from 13 US referral centers. We analyzed data on personal and family histories of cancer. Modified segregation analysis conditioned on ascertainment criteria was used to estimate age- and sex-specific CRC cumulative risk, studying members of the mutation-carrying families. We identified 51 AA families with deleterious mutations that disrupt function of the MMR gene product: 31 in MLH1 (61%), 11 in MSH2 (21%), 3 in MSH6 (6%), and 6 in PMS2 (12%); 8 mutations were detected in more than 1 individual, and 11 have not been previously reported. In the 920 members of the 51 families with deleterious mutations, the cumulative risks of CRC at 80 years of age were estimated to be 36.2% (95% confidence interval [CI], 10.5%-83.9%) for men and 29.7% (95% CI, 8.31%-76.1%) for women. CRC risk was significantly higher among individuals with mutations in MLH1or MSH2 (hazard ratio, 13.9; 95% CI, 3.44-56.5). We estimate the cumulative risk for CRC in AAs with MMR gene mutations to be similar to that of individuals of European descent with Lynch syndrome. Two-thirds of mutations were found in MLH1, some of which were found in multiple individuals and some that have not been previously reported. Differences in mutation spectrum are likely to reflect the genetic diversity of this population.

Use of pulmonary arterial hypertension-approved therapy in the treatment of non-group 1 pulmonary hypertension at US referral centers.

Pulmonary hypertension (PH) is a frequent complication of left heart disease and parenchymal lung disease, and it portends increased mortality. A growing number of medications are approved for the treatment of World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH). However, they are not well studied in PH of other etiologies (WHO groups 2-5). We sought to assess treatment approaches used by PAH referral centers in this diverse group of patients. We developed a semiquantitative online survey designed to evaluate the use of PAH-approved therapy by pulmonary vascular disease centers in the United States for management of non-group 1 PH. Thirty of 50 centers completed the survey. Almost all centers (93%) reported using PAH therapy for patients with non-group 1 PH, including 77% with group 2 PH and 80% with group 3 PH. Elevated transpulmonary gradient or pulmonary vascular resistance and the presence of right ventricular (RV) dysfunction were commonly cited as supporting use of PAH therapy in patients with PH secondary to left heart disease. For patients with PH and concomitant parenchymal lung disease, degree of pulmonary function impairment and RV dysfunction were most important in influencing use of PAH therapy. In conclusion, pulmonary vascular disease treatment centers use PAH-approved therapy for patients with WHO group 2-5 PH, mostly relying on hemodynamics and assessment of RV function to identify candidates for therapy. Clinical trials designed to test the efficacy of PAH therapy in PH due to left heart and lung disease are needed, as clinical practice has extended beyond the evidence for these etiologies of PH.

710 Use and Perceived Effectiveness of Endoscopic Therapies in Recurrent Acute Pancreatitis (RAP) Patients Treated At US Referral Centers

710 Use and Perceived Effectiveness of Endoscopic Therapies in Recurrent Acute Pancreatitis (RAP) Patients Treated At US Referral Centers