Addressing Gender Disparity: Increase in Female Leadership Increases Gender Equality in Program Director and Fellow Ranks.

INTRODUCTION: Women make up 15% of the total number of practicing gastroenterology (GI) physicians in the US. Despite this disparity, only 33% of the current GI fellows are female. Increasing female GIs is a major goal of all four GI societies. It is known that gender disparity exists in the field of gastroenterology, and women are underrepresented in the leadership ranks and trainee level at academic programs. Whether an increase in female leadership in academic medicine is associated with an increase in female program directors and trainees is unknown. The aim of this study was to assess this relationship in GI. MATERIALS AND METHODS: Data were collected via a standardized protocol from all 173 US gastroenterology fellowship programs up until October 2018 from program websites and supplemented by online surveys completed by program coordinators. Any missing information was collected by calling the program coordinators. Data were collected on gender and academic rank of the program director, associate program director, division chief, chair of medicine, program size, academic center affiliation, number, and academic rank of female faculty and geographic region. The association was assessed using a Chi-square test or independent samples t test. RESULTS: In leadership positions, men were listed as comprising 86% of chairs, 82% of division chiefs, 76% of program directors and 63% of associate program directors. Forty-three percent of programs did not have female representation at any leadership level. The presence of a female program director or female associate program director was associated with an increase in the number of female fellows (4.03 vs 3.20; p = 0.076; 4.26 vs 3.36; p = 0.041), respectively. Overall, the presence of a female in any leadership position led to an increase in the number of female fellows (4.04 females vs 2.87 females; p = 0.007) enrolled in a program. If a GI division chief was male, the program director was more likely to be male as well (81% male vs. 18.8% female). Conversely, having a female division chief was likely to lead to a more equitable program director representation, 54% female to 48% male (p value < 0.0001, OR 5.03 95% CI 2.04-12.3). Furthermore, if either the internal medicine department chair or GI chief was female, the proportion of female program directors increased to 41% as compared to 19% if both were male (p value < 0.0001, OR 2.99 95% CI 1.34-6.6). CONCLUSION: Women are significantly underrepresented in the number of practicing gastroenterologists, at all levels of leadership in GI fellowship programs, and at the fellow level. Increasing the number of women in fellowship leadership positions is associated with an increase in female program directors and trainees. Per our knowledge, this is the first study to examine the relationship between female leadership in fellowship programs and the gender of trainees. Increasing female representation in leadership positions would not only address current gender disparity, but it may also increase the number of female future GI trainees.

Achalasia subtypes can be identified with functional luminal imaging probe (FLIP) panometry using a supervised machine learning process.

BACKGROUND: Achalasia subtypes on high-resolution manometry (HRM) prognosticate treatment response and help direct management plan. We aimed to utilize parameters of distension-induced contractility and pressurization on functional luminal imaging probe (FLIP) panometry and machine learning to predict HRM achalasia subtypes. METHODS: One hundred eighty adult patients with treatment-naïve achalasia defined by HRM per Chicago Classification (40 type I, 99 type II, 41 type III achalasia) who underwent FLIP panometry were included: 140 patients were used as the training cohort and 40 patients as the test cohort. FLIP panometry studies performed with 16-cm FLIP assemblies were retrospectively analyzed to assess distensive pressure and distension-induced esophageal contractility. Correlation analysis, single tree, and random forest were adopted to develop classification trees to identify achalasia subtypes. KEY RESULTS: Intra-balloon pressure at 60 mL fill volume, and proportions of patients with absent contractile response, repetitive retrograde contractile pattern, occluding contractions, sustained occluding contractions (SOC), contraction-associated pressure changes >10 mm Hg all differed between HRM achalasia subtypes and were used to build the decision tree-based classification model. The model identified spastic (type III) vs non-spastic (types I and II) achalasia with 90% and 78% accuracy in the train and test cohorts, respectively. Achalasia subtypes I, II, and III were identified with 71% and 55% accuracy in the train and test cohorts, respectively. CONCLUSIONS AND INFERENCES: Using a supervised machine learning process, a preliminary model was developed that distinguished type III achalasia from non-spastic achalasia with FLIP panometry. Further refinement of the measurements and more experience (data) may improve its ability for clinically relevant application.

Predictors of postendoscopic retrograde cholangiopancreatography pancreatitis, analysis of more than half a million procedures performed nationwide over the last 15 years.

BACKGROUND AND AIM: Post-ERCP pancreatitis (PEP) is the most common complication following endoscopic retrograde cholangiopancreatography (ERCP). It is still controversial whether the presence of a trainee would increase the risk of PEP. Additionally, the effects of demographic factors and comorbidities on the risk and severity of PEP are not fully understood. Our aim was to evaluate these factors using national database. METHODS: Nationwide Inpatient Sample 2000-2014 was used to identify adult patients admitted with biliary obstruction without acute pancreatitis and had an inpatient ERCP. PEP was defined as having a subsequent diagnosis of acute pancreatitis. The presence of major organs failure marked moderate-severe PEP. Demographic information, hospital characteristics, and ERCP intervention types were collected. RESULTS: We included 654 394 patients. Overall PEP rate was 5.4%. The PEP rate was lower in teaching (4.8%) compared with nonteaching (6.2%, P < 0.001) hospitals. The highest PEP rate was observed among patients undergoing Sphincter of Oddi Manometry (15.1%, odds ratio [OR] = 2.5, P < 0.001) as compared to diagnostic cholangiography (4.4%). Asians and Hispanics had higher rate of PEP (10% and 7.9%, respectively) compared with Caucasians and African Americans (4.9% and 5%, respectively, P < 0.001). Multivariate analysis showed that after controlling for the ERCP intervention types, Asians and Hispanics continued to have higher odds of PEP (OR = 1.3, P < 0.001). Seventeen percent of patients were classified as moderate-severe PEP. Older patients (OR = 3.2, P < 0.001), males (OR = 1.4, P < 0.001), and high comorbidities (1.3, P < 0.001) were major predictors of moderate-severe PEP. CONCLUSION: No evidence of higher PEP rates in teaching hospitals. Asians and Hispanics had higher PEP rates. Although ERCP intervention type is the major PEP predictor, its severity is dependent on patient characteristics.

Endoscopic management of postcholecystectomy biliary leak: When and how? A nationwide study.

BACKGROUND AND AIMS: ERCP is considered the first-line therapy for biliary duct leaks (BDLs). However, the optimal ERCP timing and endotherapy methods remain controversial. Our aim was to evaluate these factors as predictors of poor clinical outcomes after BDLs. METHODS: Adults who underwent ERCP for BDLs after cholecystectomy were identified from the Nationwide Inpatient Sample from 2000 to 2014. ERCP was classified as emergent, urgent, and expectant if it was done within 1 day, after 2 to 3 days, or >3 days after BDLs, respectively. Endotherapy was classified into sphincterotomy, stent, or combination. Post-ERCP adverse events (AEs) were defined as requiring pressor infusion, endotracheal intubation, invasive monitoring, or hemodialysis. Early endotherapy failure was defined as the need for salvage surgical or radiology-percutaneous biliary intervention after ERCP. RESULTS: A total of 1028 patients with a median age of 56 years were included. ERCP was done emergently (19%), urgently (30%), and expectantly (51%). Endotherapy procedures were sphincterotomy (24%), biliary stent (24%), and combination (52%). Post-ERCP AEs were 11%, 10%, and 9% for emergent, urgent, and expectant ERCP, respectively (P = .577). In-hospital mortality showed a U-shape trend of 5%, 0%, and 2% for emergent, urgent, and expectant ERCP, respectively (P < .001). Combination and stent monotherapy had lower failure rates of 3% and 4%, respectively as compared with sphincterotomy monotherapy with failure rate of 11% (P < .001). When multivariate analysis was used, both combination (odds ratio, .2; 95% confidence interval, .1-.5) and stent monotherapy (odds ratio, .4; 95% confidence interval, .2-.9) were less likely to fail as compared with sphincterotomy monotherapy. There were no statistically significant differences between combination therapy and stent monotherapy in the univariate and the multivariate analyses. CONCLUSIONS: Although limited by retrospective design and the possibility of selection bias, this analysis suggests that the timing of ERCP is not a significant predictor of post-ERCP AEs after BDLs. Furthermore, combination or stent monotherapy had lower failure rates as compared with sphincterotomy monotherapy.

Clinical Implication of MicroRNAs in Molecular Pathology: An Update for 2018.

MicroRNAs (miRNAs) are poised to provide diagnostic, prognostic, and therapeutic targets for several diseases including malignancies for precision medicine applications. The miRNAs have immense potential in the clinical arena because they can be detected in the blood, serum, tissues (fresh and formalin-fixed paraffin-embedded), and fine-needle aspirate specimens. The most attractive feature of miRNA-based therapy is that a single miRNA could be useful for targeting multiple genes that are deregulated in cancers, which can be further investigated through systems biology and network analysis that may provide cancer-specific personalized therapy.

Role of Esophageal Metal Stents Placement and Combination Therapy in Inoperable Esophageal Carcinoma: A Systematic Review and Meta-analysis.

INTRODUCTION: More than 50% of patients with esophageal cancer already have inoperable disease at the time of diagnosis. Controversy surrounds the outcomes of patients with advanced esophageal cancer who receive palliative care by either stent alone or stent plus an additional modality. We set out to perform a systematic review and meta-analysis of studies assessing the use of metal stents as treatment options for symptomatic improvement, survival, and adverse events. METHODS: We searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception until January 14, 2016, as well as other databases for randomized controlled trials (RCTs) comparing esophageal stent versus either esophageal stent plus brachytherapy, radiotherapy, or chemotherapy. For quality assurance purposes throughout the systematic review, multiple independent extractions were performed, and the process was executed as per the standards of the Cochrane collaboration. Primary outcomes were mean change in dysphagia score, overall survival, and quality of life. Secondary outcomes were adverse events including fever, severe pain, aspiration, fistula, stent migration, perforation, and restenosis. RESULTS: Eight RCTs enrolling 732 patients were included with three distinct comparisons: stents combination therapy vs stents alone (5 studies, n = 417), stents alone versus brachytherapy alone (2 studies, n = 274), and stents + brachytherapy vs brachytherapy alone (1 study, n = 41). Stents combination therapy was defined as stents plus radiotherapy, chemotherapy, or both. Mean change in dysphagia scores favored stents combination therapy versus stents alone, and the effect was seen in patients surviving longer than 3 months. Stents combination therapy was also associated with a more favorable overall survival. The risks of stent migration, aspiration pneumonia, and restenosis were lower in the stents combination group compared to stents alone, while the risks of severe pain, hemorrhage, and fistula formation were higher. Changes in dysphagia scores and overall survival did not differ significantly in the brachytherapy-alone vs stents-alone comparison. The risk of fistula formation and hemorrhage were higher in the stents-alone group, while the risk of perforation was lower, compared to brachytherapy alone. Quality of life improvements were seen in all treatment groups, but were not pooled in analysis due to differing methods of measurement. DISCUSSION: While there appears to be no immediate short-term differences, those who live longer than 3 months experience a significant improvement in dysphagia score using a stents combination therapy approach vs stents alone. The combination therapy significantly improves the overall survival as well as showed improvements in quality of life scores. Larger randomized controlled trials are needed to assess improvements in dysphagia score, overall survival, quality of life, and adverse events.

Diet and gastroesophageal reflux disease: role in pathogenesis and management.

PURPOSE OF REVIEW: Gastroesophageal reflux disease (GERD) is a common disease that presents with a variety of symptoms including heartburn and acid regurgitation. Although dietary modification is currently regarded as first-line therapy for the disease, the role of diet in the pathogenesis and management of GERD is still poorly understood. The present article aims to review recent literature that examines the relationship of diet and GERD. RECENT FINDINGS: Increased awareness of medications side effects and widespread overuse has brought nonpharmacological therapies to the forefront for the management of GERD. Recent findings have established the important role of nutrition for the managements of symptoms of GERD. Increasing scientific evidence has produced objective data on the role of certain trigger foods, whereas population studies endorse decreased reflux symptoms by following certain diets. Obesity has been linked with increased symptoms of GERD as well. Furthermore, the importance of lifestyle techniques such as head of bed elevation and increased meal to sleep time may provide nonpharmacologic methods for effective symptom control in GERD. SUMMARY: We provide a comprehensive review on the association between diet and its role in the development and management of GERD.

A rare case of a primary hepatic neuroendocrine tumor.

Neuroendocrine tumors are well-differentiated low grade malignant neoplasms. Their pathogenesis is thought to be secondary to the unrestricted proliferation of neuroendocrine cells. They most commonly arise in the bronchopulmonary or gastrointestinal tract but can originate from almost any organ. While the liver is a common site of metastases, primary hepatic neuroendocrine tumors are an exceedingly rare pathology, of which fewer than 100 cases have been described in world literature. Thus, there exists a paucity of data regarding the clinical presentation, diagnosis and management of this disease. We present a case of a 35-year-old patient who presented to our facility for evaluation of a cough and cervical lymphadenopathy. Two biopsies of the lymph nodes were negative, however on workup for an occult malignancy a hypodense heterogeneous hypervascular lesion measuring 3.7 cm × 2.7 cm in segment IVb of the liver was noted on computer tomography (CT) scan. The levels of laboratory studies such as liver enzymes, alkaline phospatase, chromogranin A, 24-hour 5 hydroxyindoleacetic acid (5-HIAA) and tumor markers including alpha fetoprotein were not elevated. An MRI confirmed the mass, and the patient underwent CT guided biopsy of the hepatic lesion. Staining from the biopsy resulted in cells reactive for synaptophysin, chromogranin, anti-Cytokeratin (CAM 5.2), MOC31, CD 56 and mucin glycoprotein (MUC) confirming a nonsecretory neuroendocrine tumor. Patient underwent octreotide scan, PET scan, CT chest, MRI head along with EUS, EGD and colonoscopy to evaluate for a primary source, however, none was found. The well localized presentation without extensive hepatic invasion made the patient a candidate for surgical resection which was successfully performed. The patient remains disease free over 36 months after initial presentation. Primary hepatic neuroendocrine tumors are an exceedingly rare entity whose variable presentation necessitates provider familiarity with this condition. Once identified, excluding other primary locations with thorough investigation and treatment with surgical resection has been shown to provide the most patient benefit.

Civilian gunshot injuries of the humerus.

An institutional review board-approved retrospective study was performed at a level 1 trauma center to evaluate the adequacy of current treatment guidelines in the management of humerus fractures following civilian gunshot injuries. Fifty-four patients with a humerus shaft fracture from a low-velocity gunshot wound were included in the study. Twenty-nine patients were treated nonoperatively, while 25 patients had operative treatment, with 14 undergoing plate fixation, 6 having application of an external fixator, 3 receiving an intramedullary rod, and 2 having irrigation and debridement with fracture immobilization provided by a brace. Patient demographics and injury data, radiographic analyses, and treatment complications were recorded. Healing of soft tissue and bony injuries, including fracture alignment in patients treated nonoperatively, was also evaluated. Fifty-two of 54 patients had minor soft tissue damage and were treated successfully with minimal local wound care. Two patients with larger wounds required extended wound care with repeated irrigation and debridement. Overall, 47 of 54 fractures healed with the primary mode of treatment, and 7 patients went on to nonunion requiring further intervention. Of the patients treated nonoperatively, the average deformity was 16.5°±7.4° in the coronal plane and 4.4°±4.0° in the sagittal plane. This study supports the view that the majority of humerus fractures following civilian gunshot wounds may be treated nonoperatively, with a select group of patients requiring surgical stabilization.

Regulating miRNA by natural agents as a new strategy for cancer treatment.

MicroRNAs (miRNAs) are small single-strand non-coding endogenous RNAs that regulate gene expression by multiple mechanisms. Recent evidence suggests that miRNAs are critically involved in the pathogenesis, evolution, and progression of cancer. The miRNAs are also crucial for the regulation of cancer stem cells (CSCs). In addition, miRNAs are known to control the processes of Epithelial-to-Mesenchymal Transition (EMT) of cancer cells. This evidence suggests that miRNAs could serve as targets in cancer treatment, and as such manipulating miRNAs could be useful for the killing CSCs or reversal of EMT phenotype of cancer cells. Hence, targeting miRNAs, which are deregulated in cancer, could be a promising strategy for cancer therapy. Recently, the regulation of miRNAs by natural, nontoxic chemopreventive agents including curcumin, resveratrol, isoflavones, (-)-epigallocatechin-3-gallate (EGCG), lycopene, 3,3'- diindolylmethane (DIM), and indole-3-carbinol (I3C) has been described. Therefore, natural agents could inhibit cancer progression, increase drug sensitivity, reverse EMT, and prevent metastasis though modulation of miRNAs, which will provide a newer therapeutic approach for cancer treatment especially when combined with conventional therapeutics.

Retrograde versus antegrade intramedullary nailing of gunshot diaphyseal femur fractures.

BACKGROUND: The use of retrograde nailing for gunshot wound femur fractures is controversial due to concerns of knee sepsis after this procedure since the knee is entered to introduce the nail into the canal. QUESTIONS/PURPOSES: We compared retrograde and antegrade nailing for gunshot femur fractures to determine whether (1) knee sepsis or other adverse events were more likely to complicate procedures using retrograde nails, (2) there were differences in surgical time or blood loss, and (3) there were differences in radiographic union. METHODS: We retrospectively reviewed our prospective trauma database from 1999 to 2012 for patients with a diagnosis of gunshot and femur fracture. We performed a detailed review of medical records and radiographs for those patients with OTA Classification Type 32 femur fractures secondary to gunshot injury treated with either retrograde or antegrade femoral nailing. Eighty-one patients were treated with intramedullary nailing (53 retrograde and 28 antegrade). We reviewed elements of the operative treatment (procedure, anesthesia time, operative time, and estimated blood loss) for all 81 patients. For clinical and radiographic review, followup was adequate for 43 and 25 patients with retrograde and antegrade nailing, respectively. Minimum followup was 3 months for both groups (retrograde: mean, 41 months; range, 3-148 months; antegrade: 26 months: range, 3-112 months). RESULTS: No patients in either group developed knee sepsis. No significant differences were found between groups with regard to operative time, blood loss, or radiographic union. CONCLUSIONS: With the numbers available, immediate retrograde nailing appears as safe and effective as antegrade nailing for gunshot femur fractures. Immediate retrograde nailing is as safe as antegrade nailing for gunshot femur fractures.

Knee pain in patients with cancer after chemotherapy, radiotherapy, and bone marrow transplantation.

The causes of knee pain in patients with cancer with are different from those without cancer, and the purpose of this study was to evaluate these differences. Thirty-six patients with cancer who had knee pain who had undergone 1 or more modalities of treatment, including chemotherapy, radiotherapy, and bone marrow transplant, for a primary diagnosis of cancer were compared with a cohort of 40 patients without cancer who had knee pain. All patients were evaluated clinically and underwent radiographic examination, and some underwent computed tomography or magnetic resonance imaging examination. Among patients with a primary diagnosis of cancer, the most common diagnosis was lymphoma (n=10), and the most common causes of knee pain were avascular necrosis of bone, osteoarthritis, insufficiency fractures, and septic arthritis. In 5 patients, the classical signs of a septic knee were not present. Other causes of knee pain included meniscus tear and anterior cruciate ligament rupture with instability. The most common diagnosis in patients without cancer was osteoarthritis of the knee. No patient without cancer was diagnosed with avascular necrosis, metastatic lesion, or insufficiency fracture. Two patients without cancer were diagnosed with septic arthritis of the knee. This study showed that the causes of knee pain in patients with cancer are different from those without cancer. Septic arthritis may present without the classical clinical signs in patients with cancer, and a high index of suspicion should be maintained for it.