Blue Arrow Research Articles

Abstract WP70: Artificial Intelligence Based Detection of Large Vessel Occlusion on Non-Contrast Computed Tomography in Stroke

Introduction: Rapid detection of a large vessel occlusion (LVO) in acute ischemic stroke is beneficial as it may accelerate therapeutic management. The hyperdense artery sign (HAS) on non-contrast CT (NCCT) is result of an acute thrombolytic occlusion and is known as the earliest radiological marker to identify LVO. However, HAS is not apparent for all LVOs and detection by a less-trained eye can be sub-optimal. Artificial intelligence (AI) may support the non-trained radiologist in swift and accurate LVO detection. We evaluated the LVO detection accuracy of AI, and compared this to human expert performance. Materials and Methods: We used a convolutional neural network (CNN) developed by Nico.lab (www.nico-lab.com) that automatically detects and segments thrombi on NCCT using a patch-based approach. The CNN was trained using thrombus and non-thrombus patches, combined with the contralateral side. In a retrospective analysis of thin-slice NCCTs, obtained from Amsterdam UMC patients, with (ICA-T, M1, or M2) and without occlusions (stroke mimics), the CNN and two observers (>15y and >4y of experience) assessed LVO-presence and location. Ground truth was established by consensus between two different experts with >5y of experience, using both CTA and NCCT. Thrombus segmentations were considered accurate if segmentations overlapped with the ground truth. Sensitivity and specificity of the LVO detection were assessed. Results: We included 107 patients, of which 59 had proven LVOs. Nico.lab CNN showed a thrombus segmentation accuracy of 81%, vs. 81% and 77% of human experts. Sensitivity of LVO detection by CNN was 0.86, vs. 0.95 and 0.79 for human observers. Specificity was 0.65 for the CNN vs. 0.58 and 0.82 for human experts respectively. Conclusion: AI-based LVO detection on NCCT showed comparable results to expert observers. This supportive tool could lead to earlier detection of LVO in acute stroke situations. Fig 1A. HAS; B. CNN output (red); C. clot on CTA (blue arrow)

Abstract WP526: Molecular Imaging of Carotid Plaques Using a Fibrin-Binding PET Probe

Objectives: We aim to develop molecular fibrin imaging as a tool to stratify high risk atherosclerotic carotid plaques. Here, we describe our results with a fibrin-specific probe [ 68 Ga]CM-246 in two different experimental settings: ex vivo imaging of carotid endarterectomy specimens and in vivo / ex vivo imaging of atherosclerotic plaque rupture in rabbits. Methods: We incubated discarded endarterectomy specimens (n=11) from asymptomatic patients with [ 68 Ga] CM-246 or a scrambled peptide control probe and measured uptake by autoradiography and a tissue binding assay. In a rabbit plaque rupture model of high cholesterol diet followed by abdominal aorta balloon injury (n=13) and subsequent pharmacological plaque rupture, in vivo and ex vivo PET-MR with [ 68 Ga]CM-246 was performed. Tissues were processed for autoradiography and histology to verify presence of fibrin and plaque rupture. Results: Autoradiography (A-B) and tissue binding assays (C) with [ 68 Ga]CM-246 with human carotid plaques show increased tissue binding compared with non-specific control probe. Carstair’s staining (D) verified the presence of fibrin in the specimens (red stained areas). Rabbits with plaque rupture had an increase in [ 68 Ga]CM-246 signal in the abdominal aorta compared with the control group. At 105-120 min post probe injection, there was a clear PET uptake on the aorta in plaque rupture rabbit (E) compared with control rabbit (F). MR images were used to differentiate abdominal aorta (green arrows) and the inferior vena cava (blue arrows). T2-dark blood images confirmed the plaques in rupture (G) and control rabbits (H). ToF images were used to visualize aortic lumen in plaque rupture (I) and control rabbits (J). Ex-vivo PET imaging, autoradiography, and histology confirmed in vivo results. Conclusions: We demonstrated that [ 68 Ga]CM-246 detects high-risk plaque in human and rabbits and can be a useful tool for the stratification of atherosclerotic plaques in patients.

Dermoscopy of Keratoacanthoma Centrifugum Marginatum.

Dermoscopy of Keratoacanthoma Centrifugum Marginatum.

Mounier-Kuhn syndrome.

A 39-year-old man presented with a productive cough, a history of chronic dyspnea and recurrent lower respiratory tract infections. Physical examination and laboratory tests were unremarkable. A chest X-ray (A) showed an enlarged tracheal diameter (white arrows), with multiple cysts in the lower lobes (red arrows). A computed tomography scan of the chest (B) showed the dilatation of both the trachea and the two main bronchi (white arrows) with multiple diverticulae (blue arrows). It also revealed bilateral cystic bronchiectasis involving both lower lung zones (red arrows). A possibility of Mounier-Kuhn syndrome (MKS) was considered. MKS is a rare condition characterized by recurrent lower respiratory tract infections and tracheobronchial dilation that is due to atrophy of the muscular and elastic tissues in the trachea and main bronchial wall. The patient underwent bronchoscopy which demonstrated tracheal dilation with diverticulae and enlargement of both main bronchi confirming the diagnosis of MKS.

Mitral Annulus Calcium Score

Background: The risk of conduction system abnormalities (CSA) after transcatheter aortic valve implantation remains high. We aimed to evaluate the impact of mitral annular calcium (MAC) score on th...

A critique of the alternating access transporter model of uniport glucose transport

The alternating access transporter model (AATM) was initially constructed to rationalize and explain a few readily quantifiable and reproducible experimental findings. The AATM, as originally conceived, consists of single specific binding site centrally situated within the cell membrane. The site alternately faces inwards and outwards. During the inversion process, the site can transport sugar across the membrane, and dissociation into the alternate bathing solution results in net transport. Return of the empty site reinitiates the transport cycle as illustrated in Fig. 1A. Glucose transport, which was demonstrated first in human red cells (Le Fevre and Le Fevre 1952) and sheep placenta (Widdas 1951), has high stereospecificity for D-pyranose sugars, like d-glucose and d-xylose in preference to l-sugars, e.g. l-fructose or non-transported l-glucose. This transport process has similarities to enzyme kinetics: both have saturation kinetics, the Km being the concentration at which half maximal transport velocity, Vmax obtained, is a measure of apparent affinity of ligand for the transporter (Fig. 1B). The process is passive in the human red cell, since at equilibrium the glucose concentrations in the extra and intracellular solutions are the same; i.e. net uphill accumulation does not occur. Open in a separate window Fig. 1 A Conventional representation of the symmetrical carrier model with the KDin = KDout = 3 mmol/L and kCout–in = kCin–out. The thicker arrows represent higher flow rates of liganded carrier than those of the empty carrier. The blue arrows represent the influx pathway and the red arrows the efflux pathway. The symmetrical rates of ligand carrier transit kGCout–in, kGCout–in are 10× faster than the fast rate of empty carrier movement kCout–in, the second-order rates of ligand association with the external and internal carrier forms, Goutkout and Ginkin are assigned to be 1000× faster than kCout–in. B Conventional representation of the asymmetric alternating transporter model with parameters as illustrated in D. The simulation shows that Vm = 1.6 nmol/(L·s) for zero-trans- net influx with the parameters as in D is approximately 33% of the Vm for exchange uptake = 4.8 nmol/(L·s) and the Km for net influx = 1.0 mmol/(L·s) is approximately 20% of the Km for exchange influx = 5.0 mmol/L. The Vm for net efflux = 6.3 nmol/(L·s), i.e. 3.9× faster than net influx. C Jardetzky adaptation of gated asymmetric transporter. D Asymmetric single-cycle alternating carrier model. The lengths of the vertical lines represent the relative rates of association and dissociation. The relative lengths and widths of the horizontal lines represent the relative transit rates of loaded and unloaded carrier forms. The angular displacements of the horizontal rates represent the Gibbs free energy differences between the states. The free energy differences between liganded and unliganded states are not displayed. E Equations showing how asymmetric affinities of a single-cycle carrier enforce asymmetric rates of empty carrier distribution

A Rare Case of Acute Cholangitis in a Young Male with Tropical Chronic Pancreatitis-Induced Pancreatic Adenocarcinoma with Metastasis to the Liver

Tropical chronic pancreatitis (TCP) is a rare and poorly understood variant of chronic pancreatitis. It is typically diagnosed in young, nonalcoholic patients in tropical regions such as southern Asia, often presenting with abdominal pain, and leading to several complications, including diabetes, malnutrition, and pancreatic adenocarcinoma. Though the link between chronic pancreatitis and cancer is established, the risk for malignancy is highest in those with rare causes of chronic pancreatitis. We present a case of TCP-induced pancreatic adenocarcinoma complicated by acute cholangitis. A 34 year-old Bangladeshi male with TCP complicated by diabetes and stage IV pancreatic adenocarcinoma with liver metastasis, s/p whipple procedure, and 3 cycles of adjuvant Gemcitabine and Abraxane presented with acute worsening of chronic abdominal pain. Labs were remarkable for elevated liver enzymes and a marked increase in CA 19-9. CT Abdomen/Pelvis revealed progression of metastatic disease in the liver and upper abdomen, including the peritoneum and anterior abdominal wall. His pain persisted despite EUS-guided celiac plexus block, but became acutely worse on hospital day 15 when he became febrile, jaundiced, and with blood cultures growing E. Coli, Klebsiella, and Aeromonas. Due to concern for acute cholangitis secondary to stenosis of hepaticojejunostomy, he was taken for ERCP. The biliary system was not successfully identified, so he then underwent IR-guided placement of a biliary drain via percutaneous transhepatic cholangiography, which showed central biliary stenosis and severe bilateral ductal dilation. He was subsequently placed in hospice due to his poor prognosis. The etiology of TCP is multifactorial, but also associated with a mutation of the SPINK1 gene, which causes parenchymal damage by lowering the threshold for trypsin activation. Characteristic radiographic findings include a dilated pancreatic duct with large intra-ductal calculi, pancreatic calcifications, and pancreatic atrophy. Data suggests that only 5% of patients with a 20-year history of chronic pancreatitis develop cancer, but 17% of patients with TCP develop malignancy, which is significantly higher than the near 0% risk of malignancy in those with chronic alcoholic pancreatitis. TCP is a rare disease that potentiates many long-term complications that can significantly increase mortality in an otherwise young and healthy population.1273_A.tif Figure 1: Marked dilation of pancreatic duct measuring up to 18 mm (blue arrow) that terminates at the pancreatic head due to a large calcification (red arrow).1273_B.tif Figure 2: Fine needle aspiration of mass at pancreatic head (blue arrow) and dilated CBD measuring up to 13mm (red arrow).1273_C.tif Figure 3: Multiple hepatic metastatic lesions (blue arrows) and invasion of the pancreatic head mass into the anterior abdominal wall (red arrow).

Diffuse Large B-cell Lymphoma - A Rare Cause of Acute Liver Failure

Acute liver failure is a rare but life-threatening illness with an incidence of 2-8 per million populations. Most common causes of ALF include drug-induced liver injury, viral hepatitis, autoimmune disease, metabolic diseases and very rare malignancy. Malignant infiltration of the liver is a rare presentation of acute liver failure associated with poor prognosis. We report a case of a patient with acute liver failure caused by malignant infiltration by diffuse large B-cell lymphoma. A 28-year-old female with no significant past medical history or social history presented with abdominal distention and jaundice for four days associated with increased fatigue. She denied weight loss, fever, or night sweats. On physical examination, the patient had scleral icterus, distended non-tender abdomen with massive hepatosplenomegaly and minimal hepatic encephalopathy. Initial laboratory work was notable for; ALT 53 IU/L, AST 394 IU/L, Alkaline Phosphatase 433IU/L, Direct Bilirubin 7.4mg/dl, total Bilirubin 11.4mg/dl, PT 17.6secs, INR 1.6, PTT 28.2 secs. Abdominal Ultrasound showed an enlarged diffusely, heterogeneous liver concerning for metastasis or primary hepatic malignancy. An abdominal Computed Tomography scan revealed massive hepatosplenomegaly, heterogeneous hepatic involvement, with lymphomatous involvement of abdominal, pelvic and inguinal lymph nodes. Workup for his acute liver failure including viral, autoimmune and metabolic disease was unrevealing. Patient subsequently underwent an inguinal core lymph node biopsy that showed high-grade lymphoma (CD10-, MUM1-), double expression (IHC +, C MYC, BCL6), high replication rate- Ki-67 80-90%, IPI 3, 85% CD5+, CD10+ and CD 20+, as well as weakly positive for CD19 (Figure 1). The patient was started on chemotherapy, which consisted of hyper CVAD (Vincristine, Rituximab, Cyclophosphamide and Dexamethasone. Initial treatment was well tolerated and the patient was discharged for out-patient continuation of chemotherapy. Acute liver failure is characterized by the development of severe liver injury with impaired synthetic capacity and encephalopathy in patients with a previously normal liver. Acute liver failure due to malignant infiltration is very rare, this case highlights a high index of suspicion, particularly if no obvious etiology identified. Malignancy causing acute hepatic failure must be recognized to avoid inappropriate referral for transplantation and delay in initiating treatment.2342_A Figure 1. Inguinal core lymph node biopsy showing high-grade B-cell lymphoma IHC positive for C-MYC and BCL6.2342_B Figure 2. Axial CT abdomen with massive hepatomegaly (red arrow) and splenomegaly (blue arrow)2342_C Figure 3. Coronal CT abdomen with massive hepatomegaly (red arrow) and splenomegaly (blue arrow)

Oropharyngeal Dysphagia With Pyriform Sinus Dilatation Mimicking Zenkerʼs Diverticulum

Dysphagia is a common complaint amongst the elderly, affecting approximately 16 to 22 percent of individuals over the age of 50, with oropharyngeal dysphagia accounting for the majority of cases. Common causes of oropharyngeal dysphagia include stroke, neuromuscular disease, and obstruction (e.g. malignancy). Abnormalities of the upper esophageal sphincter may lead to high hypopharyngeal pressure, causing Zenker's diverticulum. Here we present a case of oropharyngeal dysphagia secondary to lower motor neuron disease, which resulted in pyriform sinus dilatation mimicking Zenker's diverticulum on video fluorescent swallow study. An 82-year-old lady with a history of type 2 diabetes presented with aspiration pneumonia, which was treated with intravenous antibiotics. On review of systems, she reported progressive dysphagia to solids and liquids for 4 years, and workup for dysphagia was initiated. Video fluorescent swallow study showed premature spillage to level of pyriform recesses and delayed pharyngeal response with a large pouch around the level of the pharyngoesophageal segment, suspected to be Zenker's diverticulum. Subsequent EGD was normal. An esophagram with barium contrast was then attempted, however patient aspirated a large volume of contrast during initial phase of the examination, complicated by acute hypoxic respiratory failure requiring intubation and transfer to the intensive care unit. Bronchoscopy was performed with aspiration of about 5 mL of contrast material. The patient was later successfully extubated without complication, however a follow-up CXR showed residual contrast persisting in the hypopharynx. Laryngoscopy was performed, which visualized pooling of material in bilateral pyriform sinuses, which was successfully suctioned. EMG of bilateral genioglossus muscles were done showing chronic bilateral reinnervation, suspicious of possible lower motor neuron disease. Patient recovered on general medical floor with no further hypoxic episodes. PEG tube was placed for long-term feeding and patient was discharged in stable condition with close follow up with neurology for further workup. This patient posed a diagnostic challenge given symptoms of oropharyngeal dysphagia with evidence of hypopharyngeal pooling on video fluorescent swallow study. While hypopharyngeal contrast extravasation would typically elicit a diagnosis of Zenker's diverticulum, in our patient this was a manifestation of dilated pyriform recesses.1749_A Figure 1. Video fluorescent swallow study (left) showing premature contrast spillage to level of pyriforms with delayed pharyngeal response. Large pouch noted around the level of pharyngoesophageal segment, suspected to be Zenker's diverticulum (red arrow). Subsequent barium esophagram (right) showing markedly dilated bilateral symmetric pyriform sinuses (blue arrow) with no evidence of Zenker's diverticulum.1749_B Figure 2. Computed tomography of the neck without contrast (left) delineating retained residual barium within piriform sinuses (red arrows). Chest X-ray (right) showing retained barium within bilateral pyriform sinuses (blue arrows) and bilateral lower lung fields (green arrows).

Mirror Image Technique in Choledocholithiasis: ERCP in Situs Inversus With a Forward Viewing Endoscope

Situs inversus is a congenital disease manifested by complete or partial reversal of anatomy. It occurs during early gestation and typically results in normal function. However, performing procedures on such patients is technically challenging due to their abnormal anatomies. Herein we describe a challenging endoscopic case of choledocholithiasis in a patient with situs inversus. A 45-year-old male with history of abdominal situs inversus from polysplenia syndrome presented for epigastric pain, nausea and vomiting. Vital signs were stable and exam was notable for diffuse tenderness in the epigastrium without jaundice or Murphy's sign. Pertinent labs showed a negative troponin, AST 399 U/L, ALT 385 U/L, alkaline phosphatase 425 U/L, total bilirubin 2.5 mg/dL, direct bilirubin 1.8 mg/dL, and WBC 13.6 K/uL with neutrophilic predominance. CT scan revealed abdominal situs inversus with multiple splenules, gallbladder distention without wall thickening or pericholecystic fluid, and an obstructing stone with common bile duct (CBD) dilatation to 2.1 cm. ERCP was performed by placing the patient in the right lateral decubitus with the endoscopist standing to the right of the patient. A TJF scope was advanced into the duodenum but retracted and was unable to be re-advanced due to the anatomy. The TJF scope was switched out for a forward viewing endoscope which was successfully advanced to the major papilla. The bile duct was then cannulated with the short-nosed traction sphincterotome. Injected contrast showed adequate ductal flow and dilated main bile duct with a 12 mm stone. Biliary sphincterotomy was made with traction sphincterotome using ERBE electrocautery and a plastic double pigtail stent was placed into the CBD allowing free-flow of the bile. Repeat ERCP for mechanical lithotripsy was scheduled and the patient was discharged. Situs inversus is a rare congenital disease that presents with partial to complete reversal of anatomy. Our case utilizes the mirror image technique employed in prior reports. This technique positions the patient in the right lateral decubitus and the endoscopist on the right of the patient. Prior cases were notable for ERCP failure rates of up to 25% in situs inversus. This case was successfully performed by utilizing mirror image technique with a forward viewing 1T scope. Though such cases are rare, we present this case to highlight the difficulties met by changes in anatomy and techniques used to overcome such challenges.2160_A Figure 1. Abdominal CT demonstrating stone obstructing common bile duct (Red Arrow).2160_B Figure 2. Abdominal CT demonstrating intrahepatic ductal dilatation (Red Arrows), contrast filled stomach (Blue Arrow), and liver situated on left side of the body (Green Arrows).2160_C Figure 3. Abdominal CT demonstrating extrahepatic ductal dilatation (Red Arrow), and multiple splenules (Blue Arrows).

Transhiatal Herniation of the Pancreas as a Cause of Acute Pancreatitis

Introduction The two most frequent causes of pancreatitis are gallstones and alcohol, accounting for 80% of cases. Other less common causes include hypertriglyceridemia, trauma, toxins, drugs and other causes. Our case highlights a patient presenting with pancreatitis due to a large hiatal hernia. Case report A 95-year-old woman with history of prior cholecystectomy and known large hiatal hernia presented with severe epigastric pain that radiates to the back. She denied alcohol use, family history of pancreatitis, new medications or trauma. Vital signs were within normal limit. Physical exam was notable for abdominal wall hernia and moderate epigastric tenderness. Lab data revealed normal LFTs, but an elevated serum lipase of 9736 U/L and amylase of 1597U/L. Computed tomography of the abdomen with contrast large hiatus hernia containing most of stomach, portions of pancreas and omentum.1423_A.tif Figure 1: CT abdomen - Coronal view Pancreas indicated by red arrow Pancreatic duct indicated by white arrow Stomach indicated by blue arrowThe patient was managed conservatively with IV fluid and parenteral analgesia. Surgical repair of the herniation was discussed, due to advanced age and resolution of symptoms, a decision to avoid operative management was made. Discussion Transhiatal herniation of the pancreas is rare due to its retroperitoneal location and fixation by the ligament of Treitz. Acute pancreatitis as a complication of this phenomenon is uncommon. Symptoms consist of pain localized to the chest and epigastrium, dyspepsia, nausea, vomiting, and dyspnea. The diagnosis is confirmed by significant serum lipase elevation and imaging evidence of pancreatic herniation with inflammatory changes suggestive of pancreatitis A variety of mechanisms have been proposed to explain hernia-associated pancreatitis. The parenchymal trauma from repetitive transhiatal sliding may itself induce pancreatitis, or it may cause intermittent ischemia. Other possibilities include volvulus formation or intermittent folding of the pancreatic duct leading to pancreatic secretion against a fixed obstruction. Historically, patients were managed with immediate hiatal hernia repair, however recent cases have demonstrated successful supportive management. Severe cases involving incarceration, perforation, or unresponsiveness to medical therapy should be managed surgically Conclusion Pancreatic herniation is a rare entity which may lead rare complications, including pancreatitis. Our case report highlights the importance of maintaining a broad differential diagnosis when approaching patients to include uncommon causes of disease entities1423_B.tif Figure 2: CT Abdomen - Sagittal View Pancreas indicated by red arrow Stomach indicated by blue arrow1423_C.tif Figure 3: CT Abdomen - Coronal View Pancreas indicated by red arrow Pancreatic duct indicated by white Stomach indicated by blue arrow

Septic Panniculitis Due to Fistulizing Crohnʼs Disease Masquerading as Pyoderma Gangrenosum

Pyoderma gangrenosum is an inflammatory and ulcerating dermatosis often associated with autoimmune systemic diseases, including inflammatory bowel disease. Diagnosis can be challenging. We present a patient with Crohn's disease who presented with ulcerating skin lesions mimicking pyoderma gangrenosum. Within 24 hours, feculent drainage from the skin lesions revealed the true nature of the skin lesions - septic panniculitis due to Crohn's fistula to the subcutaneous tissue. The dramatic change in management highlights the importance of recognizing conditions which can initially masquerade as pyoderma gangrenosum, particularly in the setting of inflammatory bowel disease. A 70 year old female with a long history of Crohn's colitis presented to the hospital with erythema to her abdominal wall. She has a history of a Crohn's colo-vaginal fistula treated by resection and colostomy. She was maintained on azathioprine. The abdominal wall around her colostomy was erythematous and warm. She was diagnosed with cellulitis which responded to antibiotics. One week later she presented with a large ulcerating skin lesion adjacent to her colostomy. A dermatology consultant diagnosed her with pyoderma gangrenosum. Corticosteroids were started. Within 24 hours, she developed fevers and leukocytosis. Feculent drainage began oozing from the ulcerating skin lesion (Figure 1). In addition, 2 other ulcerating skin lesions with feculent drainage developed (Figure 1). A CT scan revealed a fistula from the colostomy to the subcutaneous tissue of the abdominal wall with a subcutaneous abscess (Figure 2). She was diagnosed with septic panniculitis due to a Crohn's fistula to the abdominal wall.She was treated with antibiotics, discontinuation of steroids, incision and drainage of the abdominal wall infection, and total colectomy with ileostomy.2056_A Figure 1. Ulcerating skin lesions on abdominal wall resembling pyoderma gangrenosum. However, skin lesions developed a feculent film2056_B Figure 2. CT scan shows fistula from colostomy (yellow arrow) into subcutaneous tissue. Subcutaneous abdominal wall abscess with air bubbles (blue arrows)Pyoderma gangrenosum is a diagnosis of exclusion. As demonstrated by this case, other conditions can mimic pyoderma gangrenosum. This is the first case report, to our knowledge, of a Crohn's fistula to the abdominal wall masquerading as pyoderma gangrenosum. The correct diagnosis is critical, as management is dramatically altered.

A Case of Endoscopic Mucosal Resection of Gastric Metastasis From Renal Cell Carcinoma Without Recurrence

IntroductionRenal cell carcinoma (RCC) with gastric metastasis is extremely rare. The most common intervention is partial gastric resection; however, recently interventions including endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) have been used. We present a case of gastric metastasis from RCC that was completely resected by EMR with pathology showing clear margins. Two year follow up showed no local recurrence or distal metastasis. Case Report A 86-year-old male with history of RCC PT2N0M0 diagnosed 8 years prior s/p partial right nephrectomy presented to the ED with exertional dyspnea. Patient had a hemoglobin of 7mg/dL. Emergent EGD revealed a single 25mm sessile polyp in the gastric fundus with stigmata of recent bleeding treated with epinephrine injection. Subsequently patient underwent repeat EGD and, in view of atypical nature, polyp biopsies were performed. Pathology showed inflammatory changes and no malignancy. Five days later, the patient underwent repeat EGD. The polyp was excised completely by standard EMR technique with methylene blue saline-lift. Pathology of the polyp showed metastatic clear cell renal carcinoma with clear cauterized margin. Follow-up EGDs performed at 10 days, 4, 9 and 22 months and EUS at 9 and 24 months post EMR showed no local recurrence. PET/CT at 15 and 24 months after EMR revealed no evidence of distal metastases. Discussion In a known RCC with gastric metastasis, EUS should be performed to evaluate the involvement of gastric layers. If the fourth layer (muscularis propria) is involved, partial gastrectomy is the preferred choice. Otherwise an ESD with en bloc excision is the best option. In our case, the initial biopsy report was negative for malignancy; therefore, an EMR was done. The polyp could be lifted well with injection of methylene blue saline (lift sign is the best marker that could be used for assessing excision of lesion by EMR) hence the polyp was resected completely with negative cauterized margins. Our close surveillance in the span of 2 years with no recurrence, makes our case of a gastric metastasis resected by EMR an effective endoscopic intervention.2127_A Figure 1. (A) A single 25 mm sessile polyp with stigmata of recent bleeding was found in the gastric fundus. (B) An EGD 5 days later showing 25 mm sessile polyp found on prior endoscopy (C) EGD s/p polypectomy via an EMR with complete resection and retrieval.2127_B Figure 2. (A) This is a H&E slide with 10x magnification. Superficial biopsy showing inflammatory changes, and granulation tissue. (B) H&E slide with 2X magnification showing metastatic RCC with well visualized cauterized resection with clear margins. Cauterized margin (blue arrows) is 1.5 mm away from closest metastatic RCC (asterisks). (C) H&E slide of the RCC with 10x magnification. (D) H&E slide with 40x magnification of RCC.2127_C Figure 3. Two year follow up EUS shows endoclip in the gastric fundus with intact fourth layer (muscularis propria) and no subepithelial lesion.

Itʼs Not Recurrence?

Case presentation A 53-year-old man was evaluated for nausea, fatigue and progressive weakness. He had a history of a 20cm (figure A) stage IIIb gastric high-grade, predominantly epithelioid, GIST (figure B, note the epithelioid appearing GIST within the black arrows, the oxyntic mucosa within the blue arrows and the muscularis separating the two areas) extirpated by partial gastrectomy and Billroth II ˜18 months prior. A 3cm LUQ mass was found on surveillance imaging 12 months later while being treated with adjuvant tyrosine-kinase inhibitors. Repeat imaging demonstrated an enlarging 6.7x7.0cm mass within the abdominal mesentery anterior to the left kidney. He was referred for laparoscopic partial small bowel resection and excision of a 10 cm mesenteric mass at the level of the efferent jejunal limb, a 3cm nodule at the level of the proximal ileum and 6 smaller nodules within the small bowel mesentery. Histopathology of the resected masses demonstrated a vimentin positive, uniform, spindled cell lesion with minimal inflammation and a rare mitotic figure. The lack of inflammation, storiform spindled pattern, mucin and obliterative vasculitis, helped exclude inflammatory myofibroblastic tumor and IgG4 disease. CD117 (c-kit) and CD34 were negative, excluding residual or recurrent GIST. However, the spindled cell did demonstrate nuclear and cytoplasmic positivity for beta-catenin, supporting the diagnosis of intra-abdominal mesenteric fibromatosis (figure C). Discussion Mesenteric fibromatosis or desmoid tumor is group of rare benign tumors that can be locally aggressive but do not metastasize. They develop in ˜20% of patients with FAP but can appear spontaneously, with tissue trauma and radiation exposure as reported risk factors. To date, there are about 30 reported cases of mesenteric fibromatosis following GIST resection. Co-existence of mesenteric fibromatosis with GIST has been reported as well. Distinguishing mesenteric fibromatosis from recurrent GIST may be difficult given common similarities in radiologic appearance and c-kit expression. Accurate diagnosis can only be made after surgical removal and histopathologic examination. Unfortunately, surgery for mesenteric fibromatosis is not always curative and high rates of recurrence are common. Watchful waiting should be considered after resection, especially in patients with minimal symptoms.2701_A Figure 1. CT of the abdomen2701_B Figure 2. Epithelioid GIST, 10X2701_C Figure 3. Jejunal mesenteric mass, desmin stain, 20x

A Strange Connection: Spontaneous Esophageal-Pleural Fistula

Esophageal-pleural fistula (EPF) is a rare clinical entity with a high degree of morbidity and mortality. The unfamiliarity of this condition, along with non-specific clinical presentations and elusive imaging findings makes it a diagnostic challenge. Our goal in presenting this case is to increase the awareness of spontaneous EPF among clinicians. A 64-year-old man who presented with a mechanical fall was found to have a right-sided hydropneumothorax on his chest radiography. A chest tube was placed, after which the patient complained of pain at the site of the tube. He denied any other symptoms and remained afebrile, but was tachycardic and tachypneic. A computed tomographic image of the chest showed small right apical and anterior basal pneumothorax with right-sided chest tube traversing right upper lobe and a small pleural effusion. His chest tube drained approximately 4.5 liters of purulent-appearing fluid overnight and due to concern for empyema, patient was started on broad spectrum antibiotics. Fluid analysis was significant for a pH of 5.56, fluid protein of 0.9 grams/deciliter, glucose of 1088 milligram/deciliter, white blood cell count of 1750 cells/microliter and lactate dehydrogenase >1300 Units/liter. The patient's hospital stay was complicated by melena with a hemoglobin drop from 8.1 to 4.5 grams/deciliter. Urgent endoscopy revealed LA grade D esophagitis and a fistulous tract leading to the right pleural space. Within the tract, retained pills and the patient's chest tube were seen. An esophageal stent was placed. Follow-up barium esophagram showed contrast leakage into the pleural space. The patient was discharged after J-tube placement. Repeat esophagram 14 days later demonstrated improvement in contrast extravasation into the pleural space. Traditionally, cases of EPF have been associated with malignancy, infection or instrumentation, with only a handful of cases occurring spontaneously. Chest imaging is the primary modality in the diagnosis of EPF. Other diagnostic clues include a high output pleural effusion and elevated glucose in the pleural fluid, as seen in our patient. Food particles can also be identified in the pleural space. Management of EPF varies according to the site, size and severity of perforation. Conservative therapy includes drainage of the fluid with gastrostomy or jejunostomy placement for nutrition. Stenting or surgical intervention may be performed, depending on clinical judgment and expertise.1750_A Figure 1. Upper endoscopic view showing LA grade D esophagitis with normal GE junction (left) and opening of fistulous tract approximately 36 cm from entry site (right).1750_B Figure 2. Chest tube and retained pill within fistulous tract leading to right pleural space.1750_C Figure 3. Barium esophagram (left) demonstrating contrast extravasation (blue arrows) from distal esophagus into long narrow fistulous tract projecting over spinal column into right pleural space. Repeat study (right) 14 days later showing narrowing of fistulous tract (red) of contrast extravasation.

On the electron flow sequence driving the hydrometallation of acetylene by lithium hydride.

The sequence of the electronic flow driving the hydrometallation of acetylene by lithium hydride (and that of the opposite β-hydride elimination reaction from the alkenyl metal intermediate), was examined within the perspective provided by the bonding evolution theory (BET). The analysis was based on the application of catastrophe theory to the changes of the electron localization function topology along the intrinsic reaction coordinate. The description of the electronic processes occurring on the process was represented in terms of topological structural stability domains (SSDs) and the associated elementary bifurcation catastrophes. Within such a framework of representation, the "evolution" of the system through the different SSDs reveals the key chemical events driving the transformation, including the large polarization effect as a consequence of Pauli repulsion between ions of the positive cationic metal on the hydride domain, the activation of the CC triple bond to attack the cationic center, and the agostic stabilizing interactions involving the hardest cationic metal, followed by the attack of the hydride center. These results contribute to emphasizing the intrinsic value and usefulness of using topological-based approaches and associated tools to increase our knowledge and understanding of the subtleties underlying the electronic flow as nuclei evolve along the reaction coordinate, providing detailed and complementary insights in comparison to other interpretative tool such those based on orbital-based representations, concerning the intimate nature of the electronic rearrangement of key mechanistic processes in chemistry. Graphical abstract The sequence of the electron flow (indicated by letters a and b) along the intrinsic reaction path for the hydrometallation of acetylene by lithium hydride to yield ethenyl lithium via a four-membered transition structure (TS), as determined within the bonding evolution theory to provide the key chemical events driven the changes in the key bonding patterns. Blue arrow Main event on the side HC ≡ CH + LiH → TS, red arrow the TS → HLiC=CH2 pathway, green arrows relative motion of nuclei along the imaginary frequency at the position of TS on the intrinsic reaction coordinate.

Imaging Pitfalls of the Acutely Traumatized Pediatric Elbow.

A four-year-old otherwise healthy girl presented to our outpatient clinic complaining of left elbow pain and swelling. The child’s parents reported an indoor trauma the previous day. On clinical examination, the left elbow and forearm exhibited diffuse swelling. The gentle passive range of elbow and forearm motion was normal and mostly pain-free. Nevertheless, the radial head was stable but a palpable click was noted. The neurovascular examination was normal. The patient received radiographs of the traumatized left and normal right elbow [Figures 1 and ​and2].2]. Radiographs of her left forearm were unremarkable. Open in a separate window Figure 1 Left elbow radiographs. (a) Two anterior-posterior projections of the left elbow. Note the presence of a well-ossified medial epicondyle epiphysis (red arrow) and simultaneous absence of the radial head epiphysis. Typically, the center of the radial head should ossify before that of the medial epicondyle. Notice the notched radial metaphysis (blue arrow). This notching is undetected in the other projection because of forearm rotation as indicated by radioulnar overlap. (b) Lateral view verifies the presence of well-ossified medial epicondyle epiphysis (red arrow) and simultaneous absence of the radial head epiphysis.

Microbial explanations for field-aged biochar mitigating greenhouse gas emissions during a rice-growing season.

Knowledge about the impacts of fresh and field-aged biochar amendments on greenhouse gas (CH4, N2O) emissions is limited. A field experiment was initiated in 2012 to study the effects of fresh and field-aged biochar additions on CH4 and N2O emissions and the associated microbial activity during the entire rice-growing season in typical rice-wheat rotation system in Southeast China. CH4 and N2O fluxes were monitored, and the abundance of methanogen (mcrA), methanotrophy (pmoA), ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB), nitrite reductase (nirS, nirK), N2O reductase (nosZ), and potential soil enzyme activities related to CH4 and N2O were simultaneously measured throughout different rice developmental stages. There were three treatments: control (urea without biochar), fresh BC (urea with fresh biochar added in 2015), and aged BC (urea with 3-year field-aged biochar added in 2012). Results showed that field-aged biochar significantly decreased seasonal CH4 emissions by 16.8% in relation to the fresh biochar, though no significant differences were detected between biochars and control treatment. The structural equation model indicated that soil pH, microbial biomass carbon (MBC), pmoA, and mcrA were the main factors directly influenced by fresh and aged biochar amendments; aged biochar showed a negative effect while fresh biochar showed positive effects on CH4 fluxes. Both fresh and field-aged biochar obviously increased AOA and AOB abundances and reduced the (nirS+nirK)/nosZ ratio during the entire rice-growing season, although no significant effects were observed on seasonal N2O emissions. Therefore, biochar amendment produced long-term effects on total CH4 and N2O emissions through observed influences of soil pH and functional gene abundance. The figure shows how fresh and field-aged biochar differentially affected CH4 production and oxidation and N2O production and reduction through related functional gene abundances. Blue arrows indicate suppressing while pink arrows indicate promoting effect.

YAP-TEAD signaling promotes basal cell carcinoma development via a c-JUN/AP1 axis.

The mammalian Hippo signaling pathway, through its effectors YAP and TAZ, coerces epithelial progenitor cell expansion for appropriate tissue development or regeneration upon damage. Its ability to drive rapid tissue growth explains why many oncogenic events frequently exploit this pathway to promote cancer phenotypes. Indeed, several tumor types including basal cell carcinoma (BCC) show genetic aberrations in the Hippo (or YAP/TAZ) regulators. Here, we uncover that while YAP is dispensable for homeostatic epidermal regeneration, it is required for BCC development. Our clonal analyses further demonstrate that the few emerging Yap-null dysplasia have lower fitness and thus are diminished as they progress to invasive BCC Mechanistically, YAP depletion in BCC tumors leads to effective impairment of the JNK-JUN signaling, a well-established tumor-driving cascade. Importantly, inthis context, YAP does not influence canonical Wnt or Hedgehog signaling. Overall, we reveal Hippo signaling as an independent promoter of BCCpathogenesis and thereby a viable target for drug-resistant BCC.

Parapapillary Optic Nerve Head Drusen in Leber Congenital Amaurosis

A 20-year-old male who was known to have Leber congenital amaurosis was assessed. Best-corrected visual acuity was counting fingers in both eyes (OU). Anterior segment OU revealed poorly reacting pupils and nystagmoid movements. Dilated fundus examination revealed widespread bone spicule pigmentation with "macular coloboma" OU (Figure a and b). Short-wave autofluorescence showed hyperautofluorescent buried optic nerve head drusen and generalized hypoautofluorescence OU (Figure c and d). Additionally, the left eye showed parapapillary drusen resulting from calcification of swollen and disrupted axons at a remote location in the parapapillary area (blue arrows; Figure b and d). The presence of buried optic nerve head drusen OU gives a clue to the diagnosis of parapapillary drusen, which can be easily mistaken for retinal astrocytoma. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:554.].