Black Arrow Research Articles

Fabry cardiomyopathy: myocardial fibrosis, inflammation and reduced mannose6phosphate receptors cause low accessibility to enzyme therapy

Abstract Background Clinical impact of enzyme replacement therapy (ERT) on advanced Fabry disease cardiomyopathy (FDCM) appears limited. Purpose Clarify the pathologic mechanisms responsible of ERT inefficacy in the advanced FDCM. Methods Ten male patients with advanced FDCM (echocardiographic maximal wall thickness 19.3 ± 2.1 mm) underwent left ventricular endomyocardial biopsy before and 4 hours after beta-agalsidase infusion. Comparative studies between pre and post infusion samples included: histology and electron microscopy; assessment of myocardial alpha-galactosidase A activity; immunohistochemistry for alpha-galactosidase A and semiquantitative evaluation (from 0 to 3) of its cardiomyocyte content; Ultrastructural immunogold analysis with anti-alpha-galactosidase A ab. Western Blot (WB) quantification of mannose-6-phosphate receptors (M6Pr). Controls were surgical left ventricular biopsies from patients with mitral stenosis. Results Histologic and Ultrastructural evaluation showed no removal of storage material while myocardial fibrosis was 9.8 ± 6.8 vs 3.8 ± 2.0 of controls and virus-negative lymphocytic inflammation was observed in 7 out of 10 patients. At Ultrastructural immunogold analysis, Myocardial alpha-galactosidase A activity increased in post infusion samples by overall 1.89-fold. Alpha-galactosidase A immunostaining in cardiomyocytes was absent at baseline in all patients and did not significantly improve in post-infusion samples. Immunogold particles increased by 1.33-fold remaining far from normal controls (86.9 ± 6.6). Protein analysis showed M6Pr in advanced FDCM to be 81% lower than in normal heart. Conclusions Our study shows a low accessibility to ERT of cardiomyocytes affected by advanced FDCM. It is sustained by myocardial fibrosis, inflammation and severe down-regulation of M6Pr. Figure Legend Histologic and ultrastructural and mannose6phosphate receptors characteristics of patients with severe Fabry Disease Cardiomyopathy. Panel A shows severe cellular glycolipid infiltration associated with diffuse interstitial fibrosis (Masson trichrome, 100x). Panel B reveals an overlapping lymphocytic CD45Ro+ myocardial inflammation with focal necrosis of adjacent cardiomyocytes. Insert(i), Ultrastructural detail showing vacuoles (black arrows) to consist of myelin bodies,( scale bar=3μm). Panel C (upper) Western blot analysis of all 10 patients of Mannose-6-phosphate Receptor, molecular weight 275 Kd. Alpha sarcomeric actin (43 kDa) was used as a loading control. (Panel C -lower) Panel D: Graphs document western blot of Mannose-6-phosphate Receptor, in all 10 patients with severe FDCM showing 3-fold lower of Mannose-6-phosphate Receptor values in patients versus normal heart (4.830 ± 1116,724 vs 14.737± 1145,386; p < 0.001).

N-ethylmaleimide-sensitive factor elicits a neuroprotection against ischemic neuronal injury by restoring autophagic/lysosomal dysfunction

Autophagosome-lysosome fusion defects play a critical role in driving autolysosomal dysfunction, leading to autophagic/lysosomal impairment in neurons following ischemic stroke. However, the mechanisms hindering autophagosome-lysosome fusion remain unclear. Soluble N-ethylmaleimide-sensitive factor (NSF) is an essential ATPase to reactivate STX17 and VAMP8, which are the paired molecules to mediate fusion between autophagosomes and lysosomes. However, NSF is frequently inactivated to inhibit the reactivation of STX17 and VAMP8 in ischemic neurons. Herein, we investigated whether autophagosome-lysosome fusion could be facilitated to alleviate autophagic/lysosomal impairment in ischemic neurons by over-expressing NSF. Rat model of middle cerebral artery occlusion (MCAO) and HT22 neuron ischemia model of oxygen-glucose deprivation (OGD) were prepared, respectively. The results demonstrated that NSF activity was significantly suppressed, accompanied by reduced expressions of STX17 and VAMP8 in penumbral neurons 48 h post-MCAO and in HT22 neurons 2 h post-OGD. Moreover, the attenuated autolysosome formation accompanied by autophagic/lysosomal dysfunction was observed. Thereafter, NSF activity in HT22 neurons was altered by over-expression and siRNA knockdown, respectively. After transfection with recombinant NSF-overexpressing lentiviruses, both STX17 and VAMP8 expressions were concurrently elevated to boost autophagosome-lysosome fusion, as shown by enhanced immunofluorescence intensity co-staining with LC3 and LAMP-1. Consequently, the OGD-created autophagic/lysosomal dysfunction was prominently ameliorated, as reflected by augmented autolysosomal functions and decreased autophagic substrates. By contrast, NSF knockdown conversely aggravated the autophagic/lysosomal impairment, and thereby exacerbated neurological damage. Our study indicates that NSF over-expression induces neuroprotection against ischemic neuronal injury by restoring autophagic/lysosomal dysfunction via the facilitation of autophagosome-lysosome fusion.Over-expression of NSF promotes fusion by reactivating STX17 and VAMP8. Black arrows represent the pathological process after cerebral ischemia, green arrows represent the mechanism of remission after NSF over-expression, and red arrows represent the effect on the pathological process after NSF knockdown.

Two-stage orchiopexy for intra-abdominal testis with short spermatic vessels wrapped in anti-adhesion conduit. 25 years of experience

Treatment of high cryptorchidism can be challenging, often with frustrating results. We report 25 years of experience in the treatment of the cryptorchidism with very short spermatic vessels using an original two-stage orchiopexy that preserves the spermatic vessels. We reviewed the clinical charts of children affected by cryptorchidism with very short spermatic vessels treated through our original surgical approach in tree Institutes of Pediatric Surgery. The first stage of the procedure started with an inguinal incision and a standard orchiopexy with a deep mobilization in the retroperitoneum to straighten the spermatic vessels that are entirely preserved. After realizing intraoperatively that such maximal retroperitoneal mobilization cannot ensure a satisfactory scrotal position of the testis, the spermatic cord is wrapped in a thin sheet of polytetrafluoroethylene (PTFE) shaped as a conduit. The testis is fixed to the bottom of the scrotum which remains invaginated due to the tension. [Fig.A - scheme of the operation]. This first stage can also be performed in laparoscopy, with a video-assisted positioning of the PTFE conduit [Fig.B - laparoscopic view with vessels and vas respectively marked by black and white arrows]. The second surgical stage is scheduled after 6-12 months to remove the PTFE conduit. A group of 100 children affected by cryptorchidism and very short spermatic vessels (9 bilateral, 86 intra-abdominal, 23 "peeping" at the internal ring) for a total of 109 testes underwent surgery with a two-stage procedure. From the first to the second stage, a progressive lowering of each testis towards the scrotum was observed. During the second stage, after removal of the PTFE sheet, the preserved cord was loose in the inguinal canal and all the testes were located in the scrotum: 68 testes were found correctly located with no further care needed, while 41 were still in a high scrotal position. However, the latter were easily detached from the scrotal bottom and re-fixed in a more satisfactory location. At 1-9 years follow-up all the testes but one (99%) were in the correct scrotal position with stable or increased testicular volume [Fig.C], while 1 testis vanished. No complications were observed all along the follow-up. This long term 25-year review indicates that our original surgical technique guarantees a high rate of success with neither evident contraindications nor drawbacks for patients affected by undescended testes with spermatic vessels so short to be untreatable through a standard orchiopexy.

A313 DISCONNECTED PANCREATIC DUCT SYNDROME: A RETROSPECTIVE OBSERVATIONAL STUDY REVIEWING AN IMPORTANT BUT OVERLOOKED COMPLICATION OF NECROTIZING PANCREATITIS

Abstract Background Disconnected pancreatic duct syndrome (DPDS) is a complication of acute necrotizing pancreatitis (ANP) characterized by a complete disruption of the main pancreatic duct, leading to the loss of continuity between the pancreatic duct and the gastrointestinal tract (figure 1). Due to unopposed leakage of residual pancreatic fluid, patients with DPDS often experience a prolonged disease course with significant morbidity, including complications such as pancreatic fistulas. However, information about the epidemiology, clinical characteristics, and outcomes of DPDS remains scarce. Aims To assess clinical outcomes, diagnostic delay, burden of endoscopic and surgical interventions, and complications related to DPDS. Methods A retrospective review was conducted for all patients diagnosed with DPDS who underwent either endoscopic ultrasound (EUS) or endoscopic retrograde cholangiopancreatography (ERCP) at our tertiary center between January 2010 and December 2022. Results Fifteen patients with DPDS following ANP were identified. The median age of patients at DPDS diagnosis was 56 years (range 33-86 years), with 47% being female. The most common etiology of ANP was biliary (40%), followed by idiopathic (33%) and alcoholic (27%). The median time between ANP diagnosis and DPDS diagnosis was 265 days (range 86-2023 days). Patients underwent a median of 3 (1-9) endoscopic interventions and 1 (0-5) surgical intervention between the initial ANP episode and DPDS diagnosis. 40% of patients experienced intra-abdominal sepsis secondary to infected pancreatic fluid collections. 20% developed pancreatic fistulas (two small bowel fistulas and one cutaneous fistula). 20% developed new-onset diabetes, and 13% had significant worsening of pre-existing diabetes. No mortalities were reported. Conclusions There is a significant delay in diagnosing DPDS following ANP, and a substantial burden of endoscopic interventions is required. Frequent complications of DPDS were pancreatic fistulas, recurrent pancreatic fluid collections, and pancreatogenic diabetes. Developing a predictive model for assessing the risk of DPDS development following ANP could aid in earlier diagnosis and potentially reduce morbidity and complications associated with DPDS. Figure 1. Contrast enhanced CT demonstrating typical finding in DPDS in coronal (A) and axial (B) views. CT demonstrates 3cm area of necrosis involving pancreatic neck/body (asterisk) with viable upstream parenchyma in the remainder of the body and tail (white arrow). Pancreatic head/uncinate parenchyma and main duct appear intact (black arrow). B, the distal pancreatic duct is not dilated. DPDS, disconnected pancreatic duct syndrome. Funding Agencies None

Sudden Sensorineural Hearing Loss from a Jugular Bulb Diverticulum

A 19-year-old woman presented with an 11-month history of sudden-onset left sided hearing loss accompanied by vertigo and headache. Audiometric testing revealed profound left- sided hearing loss. A contrast-enhanced MRI of the internal auditory canal performed 5 months after symptom onset was interpreted as showing a vascular loop, probably the anterior inferior cerebellar artery, abutting and indenting on the left vestibulocochlear nerve; and a prominent and high-riding left jugular bulb. In this study, the internal auditory canals were assessed to be of normal width, with walls that were smooth and sharply defined. A cerebral CT angiogram subsequently performed did not show any abnormal findings related to the previously identified vascular loop. On the basis of these radiologic findings, the patient was advised surgery by physicians at a tertiary- care institution, presumably to address the identified vascular loop. A second opinion was sought by the patient.
 Review of the MRI initially focused on the axial high-resolution T2-weighted sequence (T2-DRIVE), as the fast spin-echo T2-weighted sequence has been recommended as a reliable and cost-effective MR screening protocol for the detection of masses in the IAC.1 In contrast to the official radiology report, stenosis of the left internal auditory canal by a protrusion (Figure 1, white asterisk) originating from the posteromedial wall of the internal auditory canal was noted. This protrusion, which had no MR signal intensity, appeared to abut and compress the cranial nerves within the IAC. Reconstruction of the images in non-orthogonal planes aligned with the orientation and direction of the left 8th cranial nerve showed the protrusion causing upward compression on and distortion of the nerve. (Figure 2, white arrows)
 Attention was directed to the axial high-resolution T1-weighted sequence (T1W-3D FFE), which revealed that the protrusion contained an isointense soft tissue structure (Figure 3, white asterisk) located within the petrous bone medial to the posterior semicircular canal. This structure appeared to be an upward extension of the jugular bulb.
 The axial high-resolution contrast-enhanced T1-weighted sequence (T1W-3D TFE Gd) showed smooth, vivid enhancement of the identified structure (Figure 4, black asterisk), which connected with the sigmoid sinus in lower cuts. This confirmed the presence of a high-riding jugular bulb that encroached on the internal auditory canal.
 Any doubt as to its true nature was dispelled by a review of the temporal bone structures on high-resolution CT which was fortunately available in the cerebral CT angiogram. This revealed a protrusion of the high-riding jugular bulb with a waist-like margin (Figure 5A and B, black arrows), allowing further characterization of the lesion as a jugular bulb diverticulum.2
 A high-riding jugular bulb that projects into the middle ear is not an uncommon anatomic variation. On the other hand, a jugular bulb diverticulum, which is an outpouching of the jugular bulb that can extend superiorly, medially, and posteriorly in the petrous bone, is a true venous anomaly that has been described rarely in the medical literature.3,4 When symptomatic, patients with this anomaly can present with sensorineural hearing loss, tinnitus, vertigo and auricular pain.3-5 Proper identification of a jugular bulb diverticulum in the evaluation of a patient with neurotologic symptoms is necessary to avoid inappropriate medical and surgical intervention.
 As demonstrated in this patient, a jugular bulb diverticulum may not be identified by a screening MRI that utilizes only a T2-weighted sequence. T1-weighted MRI sequences with and without contrast are necessary to demonstrate its soft tissue imaging characteristics. Although not the initial imaging study of choice for sudden sensorineural hearing loss, high-resolution bone-window CT may be necessary to delineate the bony anatomy of the jugular foramen and confirm the presence of this anomaly.

Dynamic response of the cell traction force to osmotic shock

Osmotic pressure is vital to many physiological activities, such as cell proliferation, wound healing and disease treatment. However, how cells interact with the extracellular matrix (ECM) when subjected to osmotic shock remains unclear. Here, we visualize the mechanical interactions between cells and the ECM during osmotic shock by quantifying the dynamic evolution of the cell traction force. We show that both hypertonic and hypotonic shocks induce continuous and large changes in cell traction force. Moreover, the traction force varies with cell volume: the traction force increases as cells shrink and decreases as cells swell. However, the direction of the traction force is independent of cell volume changes and is always toward the center of the cell-substrate interface. Furthermore, we reveal a mechanical mechanism in which the change in cortical tension caused by osmotic shock leads to the variation in traction force, which suggests a simple method for measuring changes in cell cortical tension. These findings provide new insights into the mechanical force response of cells to the external environment and may provide a deeper understanding of how the ECM regulates cell structure and function.Traction force exerted by cells under hypertonic and hypotonic shocks. Scale bar, 200 Pa. Color bar, Pa. The black arrows represent the tangential traction forces.

Cholangioscopy-guided tunneling and coaxial stenting of a large choledocholithiasis: a novel approach to mechanical lithotripsy

Video 1Cholangioscopy-guided tunneling and coaxial stenting of a large choledocholithiasis: a novel approach to mechanical lithotripsy. Fluoroscopy image of initial ERCP shows large filling defect (blue circle) and guidewire passing toward the common hepatic duct (black arrow).

PO-04-015 BIVENTRICULAR ARRHYTHMOGENIC CARDIOMYOPATHY ASSOCIATED WITH A NOVEL HETEROZYGOUS PLAKOPHILIN-2 EARLY TRUNCATING VARIANT

N/A N/A N/A A 31-year-old male patient suffered from palpitations, which occurred particularly during and shortly after physical activity. The patient was very athletic and took part in marathons. His family history was unremarkable. The electrocardiogram showed T wave inversions in V1-V3 (Figure 1A). During bicycle ergometry monomorphic premature ventricular complexes (PVC) and non-sustained ventricular tachycardia episodes (left-bundle branch block morphology, inferior axis) evolved (Figure 1B, black arrow). Of note, under maximal physical stress a second PVC with a right-bundle branch block morphology occurred (Figure 1B, red arrow) suggesting left ventricular (LV) involvement. Echocardiographic evaluation showed a dilated right ventricle (RV) with reduced systolic function, a subtricuspid aneurysm and multiple sacculations of the RV free wall (Figure 1C-D, white markers). Cardiac magnetic resonance imaging (MRI) confirmed the right ventricular findings (Figure 1E, red arrows). In addition, late gadolinium enhancement and fatty deposits were visible in the LV lateral wall (Figure 1F-G, yellow arrows and blue asterix). Genetic testing was performed using a panel covering 173 genes (Agilent, SureSelectQXTTarget Enrichment) and next generation sequencing (NGS) (Illumina MiSeq). It revealed a novel heterozygous nonsense variant in the plakophilin-2 (PKP2) gene (808C>T p. (Gln270Ter) in exon 3) that causes an early truncation, which was confirmed by Sanger sequencing. It was classified as pathogenic (class V). Cascade screening of the asymptomatic patient’s mother (64-y-old), father (70-y-old) and sister (33-y-old) showed that the patient's father and sister harbored the same PKP-2 variant. Both did not report a history of participating in competitive sports, and thorough cardiac evaluation of these two genotype positive family members showed normal findings. Previous studies have indicated that early truncation of the PKP2 C-terminus likely causes arrhythmogenic right ventricular cardiomyopathy (ARVC) irrespective of transcript position. Although desmosomal and non-desmosomal variants create certain genetic potential for the development of ARVC, exercise has an important role in determining the development, severity, and pattern of phenotypic expression. The fact that the only index patient, as a marathon runner, developed ARVC, suggests that the novel PKP2 variant poses a genetic risk, but is not sufficient for inducing an ARVC phenotype by itself.

PO-02-122 TRACKING AND ABLATING THE MUSCLE SLEEVE/FASCICLE FOR PULMONARY VEIN ISOLATION

Pulmonary vein isolation (PVI) remains the cornerstone for atrial fibrillation (AF) ablation. However, it yields unsatisfactory outcomes requiring repeat procedures especially in persistent AF. Additional linear ablation, or of complex fractionated atrial electrograms, atrial rotors or ganglionated plexi prolongs procedure time and increases complications with small additional benefits. We evaluated the efficacy of a new method of tracking and ablating pulmonary vein (PV) muscle sleeve/fascicle followed by wide area circumferential ablation (WACA) as a method of treatment of AF. To track a muscle sleeve/fascicle, a Lasso catheter was placed into one PV and based on the electrograms pattern on the catheter, sites of exit of muscle sleeves/fascicles were determined along the wide area circumferential ablation (WACA) line. (Panel A of figure shows the electrogram pattern, which suggests two muscle fascicles [red and blue arrows]). Focal ablation at sites on the planned WACA line was then performed to interrupt the muscle sleeve/fascicle connection with atrium (Panel B and C of figure shows point ablation resulting in partial and complete isolation; black arrow marks the location of ablation catheter). The same method was repeated to the ipsilateral PV before full WACA of both PVs was commenced. The strategy was repeated on the contralateral PVs. Ablation of these fascicle-atrium connections resulted in PVI isolation before WACA was completed in all 18 patients. Intravenous adenosine was used at the end to elicit dormant PV connections. We schematically labeled the areas around the PVs into zones and summarized the location of these muscle fascicles in each patient. (Panel D; each dot represents a fascicle and color matches with the PV with which it is associated). Eighteen patients (61±11 years old, 56% male) with AF (12 persistent {67%}) were analyzed in this study. Fascicles were identified in all patients and focal ablation of fascicles resulted in isolation of the PVs. In addition to PVI, 8 had Cavotricuspid isthmus ablation, 1 for right focal atrial tachycardia (AT), one left focal AT, and 1 for biatrial reentrant AT. With a follow-up of 155 ±120 days, 83% of paroxysmal and 75% of persistent AF remained in sinus rhythm. Left atrial dwell time for PVI alone was less than 2 hrs and no complications were seen. The tracking and ablating muscle sleeve/fascicle before performing WACA is a strategy with outcomes superior to previously reported in literature.

血胸を伴う出血性ショックを来した左胃動脈瘤破裂の1例(A ruptured aneurysm of left gastric artery that progressed to right hemothorax: a case report)

症例は50歳代女性，心窩部痛と呼吸苦で発症し，近医にて胸水を指摘されて前医を受診した。前医では，単純CT検査で血性胸腹水，食道壁肥厚，膵周囲の脂肪織濃度の上昇を認め，2日間加療したが改善を認めないため精査目的に当院へ紹介された。来院時，四肢末梢に湿潤を認め，脈拍110/分，血圧80/50mmHg（ドパミン9μg/kg/min）であった。造影CT検査で右血性胸水と食道裂孔ヘルニア，胸部中部以下の食道から胃噴門部小弯側にかけての血腫を認めたが，食道や肺野など胸部には出血源を認めなかった。腹腔内には血性腹水とともに，胸部中部食道周囲から胃小彎側に連続する血腫を認め，内部に直径1.5cmの左胃動脈瘤を認めた。左胃動脈瘤破裂による出血が，食道裂孔を介して縦隔へ進展し，胸腔内に穿破して血胸に至ったものと推測した。血胸に対して単回の胸腔穿刺，左胃動脈瘤破裂に対して血管造影による塞栓術を施行した。翌日から経口摂取を開始し，血胸が再燃することもなく経過は良好で，第22病日に自宅退院した。腹部内臓動脈瘤破裂による出血が食道裂孔を介して胸腔内に穿破し，血胸を契機に診断された稀な症例を経験したので報告する。 A 59–year–old woman visited her local hospital with dyspnea and epigastric pain. A chest X–ray showed a right pleural effusion. The patient consulted a second hospital where she was treated for two days, but due to her unstable vital signs, she was transferred to our hospital. A contrast–enhanced CT scan revealed a right hemothorax and esophageal hiatal hernia. While there was no source of bleeding in the thoracic cavity, there was an intra–abdominal hemorrhage from a ruptured aneurysm of the left gastric artery. The suspected cause of the hemothorax was bleeding from a ruptured aneurysm that entered the thoracic cavity through the esophageal hiatus. We performed a transcatheter arterial embolization for the ruptured aneurysm. After treatment, the patient recovered without significant incidents and was discharged on the 22nd day of hospitalization. We speculated that the hemorrhage from the rupture of the gastric aneurysm extended through the esophageal hiatus into the mediastinum and perforated into the thoracic cavity, resulting in a hemothorax. Since such conditions are rare, we will report this case with a review of the literature. 腹部内臓動脈瘤は破裂すれば出血性ショックにより致死的状況に至ることもある重篤な疾患である。本邦の腹部内臓動脈瘤破裂として報告されている症例の多くは腹腔内出血による出血性ショックを呈している 1, 2。しかし，今回我々は左胃動脈瘤破裂による出血が食道裂孔ヘルニアを介して縦隔，胸腔内へ進展し，出血性ショックを来した症例を経験したので，文献的考察を加えて報告する。 本論文は，個人情報保護法に基づいて匿名化がなされており，本人から論文報告に関する同意を得ている。また，本論文は倫理委員会の承諾を要する事項として該当しない。 症 例：50歳代の女性 主 訴：心窩部痛 現病歴：搬送6日前に突然の心窩部痛，呼吸困難感が出現し，食事摂取ができなくなった。搬送2日前に近医を受診したところ，胸水を指摘され前医を紹介された。前医受診時より血圧が低下しており，単純CT検査で血性胸腹水，食道壁肥厚，膵周囲の脂肪織濃度の上昇を認め急性膵炎などが疑われた。2日間の入院加療後も改善に乏しく，循環動態の維持にカテコラミン投与を要する状態となったため，当院救命救急センターへ搬送された。 既往歴：特記事項なし 生活歴：ビール１本/日，喫煙なし 来院時現症：意識清明。軽度の呼吸困難感の訴えを認めるが呼吸促拍はなく，呼吸数22/分，酸素飽和度97%（3L/min），顔面蒼白，四肢末梢に冷感湿潤を認め，脈拍110/分，血圧80/50mmHg（ドパミン 9µg/kg/min）。左背部痛の訴えがあるものの圧痛は認めなかった。 血液検査：RBC 213×104 /μL，Hb 6.7g/dL（前医受診時 Hb 9.8g/dL）と著明な貧血を認めた。血小板数や凝固検査には異常を認めなかった。 画像検査：胸腹部造影CT検査；胸部CTでは右血胸，滑脱型食道裂孔ヘルニアを認め，周囲に縦隔血腫，左少量胸水を認めた。腹部CTでは直径1.5cmの左胃動脈瘤を認め（Fig. 1a），周囲の血腫は胸部中部食道周囲から胃小弯側へ連続していた（Fig. 1b）。左肝動脈は左胃動脈から分岐しており，肝左葉外側区に微小動脈瘤を認めた。食道や肺野には出血源を認めなかった。 An enhanced CT scan of the abdomen revealed a pseudoaneurysm of the left gastric artery. Computed tomography (CT) of the chest showed a right massive hemothorax，a slipped esophageal hiatal hernia, and a mediastinal fluid collection (black arrow). 搬入後経過：乳酸リンゲル液の急速輸液を行うとともに輸血を開始した。搬入後より呼吸困難感が増悪し，仰臥位の維持が困難となったため，右血胸に対し慎重に胸腔穿刺を施行したところ，約830mLの血性排液を認めた。穿刺後，呼吸困難感の改善を認め，輸血投与後よりバイタルサインの安定を得た。左胃動脈瘤からの出血が食道裂孔ヘルニアを介して血胸に進展したものと推測し，動脈瘤に対して緊急interventional radiology（IVR）による止血術を行う方針とした。 腹部血管造影：腹腔動脈からの造影では，直径1.5cmの左胃動脈瘤を認め（Fig. 2a），瘤よりも近位より分岐する左胃動脈分枝，瘤末梢から分岐する左肝動脈を金属コイルでisolationし，瘤内をNBCA（n–butyl–2–cyanoacrylate）により塞栓した（Fig. 2b）。 Celiac artery angiography showed a pseudoaneurysm of the left gastric artery and left hepatic artery. Transcatheter arterial embolization (TAE) was done successfully. Arterial flow for the aneurysm was shut out. 入院後経過：後日判明したmyeloperoxidase–anti–neutrophil cytoplasmic antibodies（MPO–ANCA）や，proteinase–3–anti–neutrophil cytoplasmic antibodies （PR3–ANCA）などの血管炎マーカーはいずれも陰性であり，微小動脈瘤形成の所見から，臨床的に節性動脈中膜壊死（segmental arterial mediolysis: SAM）と診断した。濃厚赤血球4単位の輸血投与と緊急IVR後は循環動態の安定が得られた。呼吸器症状も改善し第2病日から経口摂取を開始した。胸水の再貯留は認めず，その後も血胸が再燃することはなかった。IVR後大きな合併症なく経過は良好で，第22病日に独歩で退院した。その後発症から1年までの時点では，新たな動脈瘤の形成もなく経過している。 腹部内臓動脈瘤は比較的稀な疾患であり，その発生頻度は0.01～2%とされている。Stanleyらの腹部内臓動脈瘤1,118例の集計によると，脾動脈が最も多く656例（58.7%），次いで肝動脈が227例（20.2%），上腸間膜動脈瘤89例（7.9%）と続くのに対し，胃動脈瘤は53例（4.7%）であると報告されている 3。 腹部内臓動脈瘤の成因としては，動脈硬化，神経線維種症I型やEhlers–Danlos症候群などの先天性疾患，腹部外傷，ベーチェット病や高安病，多発血管炎などの膠原病，正中弓状靭帯圧迫症候群，慢性膵炎などの炎症性疾患などがあるが，近年画像診断の進歩に伴って，SAMが注目されている 4。SAMは1976年にSlavinらにより提唱された疾患概念 5で，腹部内臓動脈の中膜が分節性に融解し動脈瘤を呈する病態である。稲田らの報告によると，SAMと診断された患者の35.7%に多発動脈瘤を認めており，一般的には異所性，異時性に動脈瘤を形成することが多いとされている 6。 SAMの確定診断は切除標本からの病理学的診断によってなされていたが，近年，画像診断の進歩や開腹手術と比較して低侵襲であるIVRが動脈瘤治療の第一選択となってきており，病理学的確診が得られる機会が少なくなってきた。内山ら 7は腹部内臓動脈瘤の中で，①中高年の患者，②炎症性変化や動脈硬化性病変などの基礎疾患がない患者，③突然の腹腔内出血で発症，④血管造影で血管の数珠状の不正な拡張と狭小化を認める，の4項目をSAMの特徴とし，これに合致するものをSAMと診断する臨床的診断基準を提唱している。本症例においては，中年女性であること，非動脈硬化性，非炎症性であること，血管造影検査で左胃動脈だけでなく左肝動脈外側区領域にも動脈瘤を形成し，特徴的な数珠状変化も認めていたことから臨床的にSAMと診断した。 また，胃動脈瘤の中では左胃動脈瘤破裂が最も多く報告されている。医学中央雑誌による検索では，左胃動脈瘤破裂の本邦報告例は25例であり，いずれも腹腔内出血あるいは消化管出血によるショック症状で搬送されていた。海外においては，腹部内臓動脈瘤破裂に伴い胸水貯留を呈した症例についての報告 8, 9, 10が散見される。一般に，腹部内臓動脈瘤破裂は血性腹水の貯留を認めるが，本症例の場合は血胸を呈していた。横隔膜を隔てた液体成分の移動に関して，腹腔内圧の上昇に伴い，横隔膜小孔を通じて胸腔内へ液体成分が漏出した症例報告がみられる。本症例では，滑脱型食道裂孔ヘルニアが存在し，腹腔内における血腫が食道裂孔を介して腹腔から縦隔へ連続していた。食道裂孔は伸縮性を持つ約3cmの筋性管で，左右の横隔膜脚内側縁により境界される。食道裂孔を形成する筋束は右脚の内側部から送られ，これが食道を包むようにめぐっており，下部食道～胃噴門部は横隔食道膜という靭帯に固定されている。食道裂孔ヘルニアとは，加齢によりこの横隔食道膜が弛緩することにより胃の一部が胸腔側に逸脱した状態である。食道は漿膜を持たず，周囲は疎な結合組織と脂肪組織に覆われているため，食道胃接合部手術における剥離は容易である。また，右胸腔とは薄い食道臓器鞘で接していることから，剥離操作時には右胸腔開放に注意を要する。腹部内臓動脈瘤破裂症例で，合併する食道裂孔ヘルニアを通じて胸腔穿破，胸水貯留を来した報告は少数にみられ 11, 12，食道裂孔ヘルニア内の胃穿孔から縦隔気腫や膿瘍を形成した報告例 13もある。また，慢性膵炎における仮性膵嚢胞で，嚢胞が後腹膜を頭側へ進展することで食道裂孔を貫き，胸腔へ穿破，内瘻を形成したことで膵性胸水貯留を来した症例も報告されている 14。食道裂孔部が弛緩した状態では，食道周囲の結合組織が疎であることによる血腫の下縦隔への進展，そこに接する胸膜穿破が起こりうると考える。本症例は，画像診断では血胸の原因となる病変を肺，胸膜，食道に認めず，単回の胸腔穿刺ドレナージとIVRによる止血術で血胸の再燃を認めなかった。左胃動脈瘤破裂による出血が，腹腔内の圧が上昇したことで，最も抵抗の少ない食道裂孔ヘルニア部から疎な結合組織を通じて縦隔へ進展し，壁側胸膜を穿破して血胸に至ったものと推測した。 右血胸を伴い出血性ショックを呈した左胃動脈瘤破裂の症例を経験した。腹腔内を出血源とする血液が，食道裂孔ヘルニアを介して主に胸腔内へと進展した可能性が考えられた。 共著者全員が利益相反はない。

急性膵炎後の被包化壊死増大に伴い脾梗塞・胃壁虚血に陥り外科手術を要した1例(Acute pancreatitis and enlarged area of walled–off necrosis followed by infarction of the spleen and ischemia of the gastric wall requiring surgery: case report)

症例は40歳の男性。基礎疾患に高トリグリセリド血症があり，急性膵炎を繰り返していた。約9か月前に壊死性膵炎を発症して膵尾部と胃脾間，結腸間膜に被包化壊死を合併，以降定期的にCT画像検査による経過観察を行っていた。今回左側腹部痛を主訴に来院し，腹部CT検査において胃脾間，膵尾部に各々44mm，43mmの被包化壊死を認め，いずれも2か月前の検査時より被包化壊死の増大を認めた。またそれぞれの被包化壊死に隣接して胃穹窿部の浮腫性変化と脾動脈閉塞，脾梗塞を認めた。ヘパリン・抗菌薬・鎮痛薬による保存的治療から開始したが，発熱が継続し，炎症反応の改善も得られず，入院第4病日のCT検査では脾梗塞の状況に改善がなく，一方で被包化壊死に接する胃壁全層の虚血所見が明らかとなったため，保存的治療を断念し，緊急開腹術での膵尾部切除・脾摘出・胃部分切除術を施行した。病理所見では被包化壊死と脾動脈との間には炎症性細胞の浸潤を認め，脾動脈内腔には白色血栓を認めた。胃壁漿膜側は被包化壊死に伴う炎症所見や周囲血管内の血栓形成を認めた。被包化壊死の自然史は明確ではなく，保存的治療においては，症状や画像所見を丁寧に評価して外科的治療介入の時期を見逃さないことが重要である。 A 40–year–old male with hypertriglyceridemia and recurrent acute pancreatitis was undergoing regular imaging to monitor walled–off necrosis (WON) that had developed 9 months earlier secondary to necrotic pancreatitis. The patient presented with acute left abdominal pain. Abdominal CT showed WON by the gastrosplenic ligament (44mm) and in the pancreatic tail (43mm). Both areas grew since the last imaging 2 months earlier. Edematous changes in the fornix, splenic artery occlusion, and splenic infarction were observed adjacent to areas of WON. Despite conservative management, fever and elevated inflammatory biomarkers persisted. CT after admission showed no change in the splenic infarction. It also detected ischemia in all layers of the gastric wall adjacent to areas of WON. Emergency laparotomy was performed for pancreatic tail resection, splenectomy, and partial gastric resection. Pathologic examination showed infiltration of inflammatory cells between the areas of WON and the splenic artery and a white thrombus in the splenic artery lumen. There was inflammation and thrombus in the blood vessels surrounding areas of WON on the serosal side of the gastric wall. Although the natural history of WON is not well studied, careful evaluation of clinical findings and imaging for timely surgical intervention is required. 2012年の改訂アトランタ分類 1により膵炎の局所合併症としてみられる膵あるいは膵周囲の液体貯留は，壊死の有無と発症からの経過時間により，間質性浮腫性膵炎後に発症する急性膵周囲液体貯留（acute peripancreatic fluid collection: APFC）と壊死性膵炎後に発症する急性壊死性貯留（acute necrotic collection: ANC），それぞれが4週以上経過した膵仮性嚢胞（pancreatic pseudocyst: PPC）と被包化壊死（walled–off necrosis: WON）の4つのカテゴリーに分類された。ガイドライン 2, 3, 4ではこれら膵局所合併症に関して無症候性，非感染性のものについては保存的加療を推奨し，症候性，感染合併症例を治療適応としている。今回我々は，繰り返す急性膵炎後にWONを発症し，その経過観察中に合併した脾動脈本幹閉塞による脾梗塞と，胃後壁への炎症波及に伴う胃壁虚血に対して外科的治療を施行した1例を経験した。これまでに急性膵炎に伴う脾梗塞の発生率は約7%と報告され 5，また急性膵炎に伴い胃壁梗塞および脾梗塞を合併した報告例はある 6が，WONの自然経過における同合併症の発生に関しては明確にされていない。我々は自験例におけるWONの経時的画像所見と術中所見および切除標本の病理学的所見からその機序と治療方針について考察した。 本論文は倫理委員会の承諾を必要としない症例報告である。また，個人情報保護法に基づいて匿名化がなされており，患者本人から論文出版に関する同意を取得している。 患 者：40歳の男性 主 訴：左側腹部痛 基礎疾患：高トリグリセリド血症（LPL遺伝子異常症疑い） 生活歴：喫煙歴なし，飲酒習慣なし 現病歴：以前より急性膵炎を繰り返していた。9か月前に壊死性膵炎を罹患以降，膵尾部と胃脾間，結腸間膜にWONが形成されていた（Fig. 1a–c）。6か月前，4か月前には浮腫性膵炎を罹患し絶食，輸液，ガベキサートメシル酸塩点滴，抗菌薬，経管栄養による保存的治療を受けていた。今回来院約12時間前に突然左側腹部痛を自覚，改善を認めないため，ウォークインで救急外来を受診した。 Abdominal computed tomography (CT) with contrast (a–e: contrast–enhanced CT, delayed phase, f: contrast–enhanced CT, arterial phase). a: 9 months before admission, at the onset of WON, a solitary lesion was found in the pancreatic tail. b: 6 months before admission, cystic lesions were found in the pancreatic tail and by the gastrosplenic ligament. There was no abnormal contrast effect on the spleen. c: 4 months before admission, cystic lesions were found in the pancreatic tail and by the gastrosplenic ligament. There was no abnormal contrast effect on the spleen. d: Edematous changes in the fornix of the stomach adjacent to WON on arrival (white arrow). e: All layers of the gastric wall were poorly enhanced on day 4 of admission (black arrow). f: On CT scan at the time of admission, the splenic artery next to WON in the pancreatic tail had a contrast defect (white and black arrowheads). d–f: There was poor contrast enhancement of the spleen. 経 過：来院時のバイタルサインは意識清明，心拍数91/分，血圧169/109mmHg，呼吸数24/分，酸素飽和度97%（室内気），体温37.1℃であった。身体診察では，腹部は平坦，左側を中心に腹部全体の圧痛，筋性防御を認めた。血液検査では，白血球18,100/µL，CRP 12.15mg/dLと非特異的炎症反応上昇を認め，Fib 536mg/dL，D–dimer 1.29µg/mLと軽度の線溶系亢進を認めた。膵酵素の上昇は認めなかった（Table 1）。腹部造影CT検査（Fig. 1d）では，胃脾間に最大径44mm（前回2か月前撮影時41mm），膵尾部に最大径43mm（前回2か月前撮影時38mm）のWONを認め，膵尾部以遠の脾動脈造影欠損，脾全体の造影不良を認めた（Fig. 1f）。またWONに接した胃穹窿部壁の造影不良を認めたが（Fig. 1d白矢印），胃周囲の血管には造影欠損を認めず，胃壁の浮腫性変化と考えた。脾梗塞の診断で入院加療とし，抗菌薬，ヘパリン15,000単位/日点滴静注，疼痛管理を開始した。入院後痛みは軽減したが，発熱の持続と第3病日の血液検査では白血球17,900/µL，CRP 31.40mg/dLと炎症反応の改善を得られず，入院第4病日に腹部造影CT検査を再検したところ，胃穹隆部の壁全層に及ぶ造影欠損が明確となった（Fig. 1e黒矢印）。上部消化管内視鏡検査を施行したところ，噴門部大弯から後壁にかけて胃粘膜の虚血性変化を認めた（Fig. 2）。比較的広範囲で胃壁全層の虚血壊死が生じていると疑われたため治療方針を改め，同日，緊急開腹手術を行った。腹腔内には漿液性腹水を少量認め，大網切開し網嚢腔を開放すると胃脾間・膵尾部のWONは胃後壁・膵尾部と強固に癒着一塊となっていた。脾動脈への前面からのアプローチは炎症波及により剥離困難であったため膵脾脱転したうえで脾動脈を根部から約1cmの部位で結紮し，膵臓も同部位で切離，合わせて梗塞に陥った脾を摘出した。胃後壁はWON癒着部から1cmほど離れた部位で胃壁を貫通し，壊死した胃粘膜を視認しつつWONを含めた胃部分切除を行った。結果的に胃穹窿部から体部後壁までを切除した（手術時間3時間39分，術中出血量470mL）。病理所見では胃後壁・WON・膵尾部・脾臓は一塊となり（Fig. 3a），線維性肉芽組織からなるWONの嚢胞壁には好中球浸潤を伴う中等度の急性炎症がみられ，内部は壊死物質で満たされていた。胃壁は固有筋層に及ぶ潰瘍形成を認め，一部で胃壁全層に及ぶ凝固壊死，浮腫，高度の急性炎症を認めた。漿膜側にはWONに伴う炎症所見とともに周囲の動脈内に血栓形成を認めた（Fig. 3b）。胃壁の明らかな穿孔は認めなかった。WONと隣接する動脈との間には炎症性細胞の浸潤を認め，脾動脈内腔は白色血栓で閉塞（Fig. 3c），脾臓は凝固壊死に陥っていた。術後経過は良好で，術後4日目に経口摂取を開始，同11日目に退院した。 Upper gastrointestinal endoscopy findings. There was ischemia of the gastric mucosa from the cardia and greater curvature to the posterior wall. Macroscopic and microscopic (×20) surgical pathology findings. a: Macroscopic cystic lesions were partially solid. (b, c) Histologically, the wall of the cystic lesion consists of fibrous granulation tissue with no epithelium, acute inflammation with infiltration by neutrophils, and contained internal necrotic tissue. b: The gastric wall had ulcer formation extending to the muscularis propria, coagulative necrosis throughout all layers, edema, and severe acute inflammation. Inflammatory infiltrates and thrombus were observed in the blood vessels surrounding WON on the serosal side of the gastric wall. c: In the pancreas, there was severe fibrosis, edema, and moderate to severe acute and chronic inflammation. A white thrombus was observed in the lumen of the splenic artery. W: walled–off necrosis (WON), P: pancreas, St: stomach, Sp: spleen 急性膵炎における壊死性膵炎の発症率は10～20%とされ 7，WONは壊死性膵炎の晩期合併症として生じる。WONは膵実質および膵周囲脂肪組織の壊死部が時間とともに当初の固形から融解壊死により液状化し，周囲を肉芽性・繊維性皮膜で覆う状態になったものである。近年までWONと間質性浮腫性膵炎の晩期合併症であるPPCは明確には区別されておらず，両者を含めた検討において，経過観察症例の30～50%で重大な偶発症・合併症が発生したと報告され 8, 9，発生6週以降では自然消退は期待できず偶発症・合併症率が高いとする報告 10や，嚢胞径が6cmを超えるものでは自然消退の可能性が低下し偶発症・合併症率が高くなるとする報告 9がある。一方でManraiら 11は壊死性膵炎153名の観察研究において，143名がANCを合併し，そのうちの84名がWONに移行したが，84名のWON症例中，保存的治療を受けた23名（約27%）において局所病変の自然消失もしくは軽快が得られたと報告した。また酒井ら 12は10cmを超える巨大WONの保存的治療例を報告している。このようにWONに関する保存的治療経過の詳細は未だ不明な点もあるが，現在のガイドライン 2, 3, 4においては，膵局所合併症の種数やサイズは問わず，無症候性，非感染性の症例に対しては保存的に経過観察することが推奨され，症候性の症例では感染合併が疑われるか否か，全身状態が安定か否かにより抗菌薬投与やインターベンション治療が選択される。インターベンション治療に際しては，経皮的或いは内視鏡的経消化管的ドレナージなどの非侵襲的処置から開始し，治療効果が不十分な場合には外科的手術を行うというstep–up approach法の有用性が確認されている。 本症例はこれまでに急性膵炎を繰り返していたが，今回9か月前に発症した壊死性膵炎の際に膵尾部に造影不良域を認めたほか，結腸間膜および胃脾間に不整形脂肪織濃度上昇を認めていた。膵尾部不染領域は8か月前には最大径40mmの境界明瞭な多房性病変となり，7か月前には膵尾部病変は同サイズ，胃脾間に径50mmの嚢胞性病変，結腸間膜に径67mmの不整形脂肪織濃度上昇域を認めていた。いずれも壊死性膵炎を契機に発生しており，WONと診断し1か月ごとのCT検査を行い経過観察していた。経過中の6か月前と4か月前にはそれぞれ間質性浮腫性膵炎を発症し保存的治療を行っているが，その際はいずれの局所合併症も大きさに著変はなく，その後は2か月前のCT検査において膵尾部病変は径38mm，胃脾間病変は径41mm，結腸間膜病変は径23mmとそれぞれ縮小傾向であり，脾動脈，脾臓，胃壁の造影効果にも異常は認めなかった。したがって本症例において，脾梗塞と胃壁虚血を同時に発症したのは，膵局所合併症出現から約9か月が経過したところであった。局所合併症のサイズは続発症が増加するとされる60mmより小さい40mm前後であり，この間腹部自覚症状も認めなかったため，外来経過観察中であった。 膵局所合併症の経過中にみられる病態として，感染，消化管・胆管閉塞，腹腔内・隣接消化管や臓器への破裂・穿通，出血がある 13。本症例では胃壁虚血と脾動脈閉塞に伴う脾梗塞を発症した。膵局所合併症の消化管瘻・穿破は嚢胞性病変が消化管に癒着して線維化が進行することにより，癒着臓器の伸展が強制されて生ずると考えられる。本症例では病理所見として胃壁漿膜側にWONによる炎症波及を認め，周囲動脈内の血栓形成が散見された。炎症所見は一部固有筋層に及び，比較的広範囲の胃粘膜虚血が起き，潰瘍形成を生じたと考えられた。脾梗塞に関しては，WONによる脾動脈の物理的圧排のほか，経過中に繰り返された膵炎の炎症波及による脾動脈周囲の線維化から脾動脈狭窄を生ずる機序，血管炎に伴う血栓形成機序などの関与が考えられる。本症例は短胃動脈や胃大網動脈からの十分な側副血行路が発達する前に脾全体の梗塞を来しており，動脈周囲に好中球浸潤を伴う急性炎症所見を認めることから，徐々に進行する物理的圧迫よりも，炎症に伴って急速に進行する血栓形成の要素が大きいと考えられた。脾動脈閉塞の結果として生じた脾梗塞は，発熱，疼痛などの自覚症状が改善しない場合や，膿瘍形成，破裂，敗血症性ショック，出血などの合併症を来した場合には脾摘術の適応がある 14。梗塞範囲が増えるほど合併症のリスクが高まると考えられるが，脾機能亢進症に対して行われる部分的脾塞栓術のように，無菌性脾梗塞と適切な梗塞率が保たれていれば外科的治療を必要としないという報告 15や，胃癌術後に発症した全脾梗塞の保存的治療例の報告 16がある。本症例は当初，胃壁造影不良域を浮腫性変化と捉えていた。脾梗塞に対しては出血・感染合併による病態悪化時の手術適応を念頭に置きつつ，ヘパリン・抗菌薬・鎮痛薬による内科的治療から開始したが，発熱が続き炎症反応の改善も得られなかった。入院第4病日の再評価において脾動脈閉塞および脾梗塞の状況に変化はなく，一方で胃壁の虚血所見が明確となったため，保存的治療を断念して手術治療を行った。本症例は来院時点で左側を中心とした腹部全体の圧痛・筋性防御や非特異的炎症反応上昇という腹膜炎を疑う所見を認めており，当初からstep–up approach法に則った治療介入を検討すべきであった。本症例の術中所見においてWONは胃壁と強固に癒着していたためWONを含め一塊切除とする膵尾部切除・脾摘出・胃部分切除術を施行した。 WONの合併症治療においては，常に外科的治療に移行する選択肢を念頭に置き，症状や画像所見から臨床経過を継続的に評価することが致死的合併症を防ぐために重要である。 本症例は，繰り返す急性膵炎に生じたWONの経過観察中に脾動脈本幹閉塞からの脾梗塞および胃壁虚血を合併した。自然消退しない膵局所合併症の治療方針を検討するうえで教訓的な1例と思われ報告した。 本論文の要旨は，第49回日本救急医学会総会・学術集会において発表した。 著者全員において本症例報告に関する利益相反はない。

Teaching Neuro Images : Obstructive sleep apnea triggered by vagus nerve stimulation

A 47-year-old man with drug-resistant cryptogenic epilepsy, treated with vagus nerve stimulation (VNS), underwent polysomnography (PSG) for suspected obstructive sleep apnea (OSA). A previous PSG study, performed 1 year before VNS, had showed an apnea-hypopnea index (AHI) = 4 events/hour, but the patient reported that the activation of the VNS was associated with increase of apneas witnessed by his bed partner. PSG was consistent with mild OSA; the AHI was 14.0 events/hour. During PSG, the stimulator was active for periods of 30 seconds, generating a peculiar artifact (figure, black arrows), separated by a 3-minute interval. In 67% of the obstructive events (9.5 events/hour), the onset of the event was simultaneous or immediately followed the start of VNS activation, suggesting that VNS might trigger obstructive apneas/hypopneas1,2 (figure, white arrows).

Erratum: Utilizing In Vivo Postnatal Electroporation to Study Cerebellar Granule Neuron Morphology and Synapse Development.

An erratum was issued for:Utilizing In Vivo Postnatal Electroporation to Study Cerebellar Granule Neuron Morphology and Synapse Development. A figure was updated. Figure 2 was updated from: Figure 2: In vivo cerebellar electroporation of granule neuron progenitors in P7 wildtype mouse pups. (A) Pups are anesthetized with 4% isoflurane delivered at a rate of 0.8L/minto ensure anesthesia throughout the injection of the DNA solution. Isoflurane is delivered at a rate of 0.8 L/min. (B) After sterilizing the mouse 3 times with betadine and 70% ethanol, an incision is made that spans the distance of the ears, revealing the hindbrain. (C) A magnified image of a white demarcation on the cranium, a landmark for the injection site. DNA construct should be injected within 1 mm above the mark; dotted lines outline the demarcation, and black arrow denotes the injection site. The ridges of the cerebellar vermis may be visible and can be useful for finding the injection site. (D) Tweezer-type electrode orientation for efficient electroporation. Plus (+) end must be oriented downwards to pull negatively charged DNA into the cerebellar parenchyma prior to administration of electrical pulses. (E) Test injection of 1 µL of a 0.02% Fast Green dye shows injection is localized to the middle of the cerebellar vermis between lobules 5-7. Please click here to view a larger version of this figure. to: Figure 2: In vivo cerebellar electroporation of granule neuron progenitors in P7 wildtype mouse pups. (A) Pups are anesthetized with 4% isoflurane delivered at a rate of 0.8L/minto ensure anesthesia throughout the injection of the DNA solution. Isoflurane is delivered at a rate of 0.8 L/min. (B) After sterilizing the mouse 3 times with betadine and 70% ethanol, an incision is made that spans the distance of the ears, revealing the hindbrain. (C) A magnified image of a white demarcation on the cranium, a landmark for the injection site. DNA construct should be injected within 1 mm above the mark; dotted lines outline the demarcation, and black arrow denotes the injection site. The ridges of the cerebellar vermis may be visible and can be useful for finding the injection site. (D) Tweezer-type electrode orientation for efficient electroporation. Plus (+) end must be oriented downwards to pull negatively charged DNA into the cerebellar parenchyma prior to administration of electrical pulses. (E) Test injection of 1 µL of a 0.02% Fast Green dye shows injection is localized to the middle of the cerebellar vermis between lobules 5-7. Please click here to view a larger version of this figure.

Lichen Planus

HomeRadioGraphicsVol. 43, No. 4 PreviousNext Cases from the Cooky JarFree AccessLichen PlanusEdward McDermott , Nadia Solomon, Annelise M. Silva, Parisa KhoshpouriEdward McDermott , Nadia Solomon, Annelise M. Silva, Parisa KhoshpouriAuthor AffiliationsFrom the Department of Radiology, Mater Misericordiae University Hospital, Eccles Street, Dublin D07 R2WY, Ireland (E.M.); Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Conn (N.S.); Department of Education, Wright State University Boonshoft School of Medicine, Dayton, Ohio (A.M.S.); and Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institution, Baltimore, Md (P.K.).Address correspondence to E.M. (email: [email protected], @edwardmcd).Edward McDermott Nadia SolomonAnnelise M. SilvaParisa KhoshpouriPublished Online:Mar 16 2023https://doi.org/10.1148/rg.220200MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Lichen planus is a chronic condition that predominantly affects middle-aged and older women and represents an autoimmune T-cell–mediated inflammatory disorder (Fig 1) that affects the skin, oral and genital mucosa, esophagus, hair, and nails (1). Cutaneous involvement manifests with flat violaceous papules, and mucosal manifestations typically manifest with white lacelike lesions, papules, erythematous lesions, and erosions (Fig 2) (2). Esophageal lichen planus has been reported in more than 50% of patients with mucocutaneous lichen planus and is underrecognized and underreported (2).Figure 1. Esophageal lichen planus. There are limited studies of the pathogenesis of esophageal lichen planus, but it appears to be mediated by cytotoxic CD8-positive T cells. Biopsy of affected esophageal tissue shows keratinization with inflammatory cell infiltration of the epithelium with activated T lymphocytes (6).Figure 1.Download as PowerPointOpen in Image Viewer Figure 2. Mucosal manifestations of lichen planus in a 73-year-old woman who presented with solid food dysphagia. (A) Photograph shows white plaquelike lesions on the tongue. (B) Endoscopic image demonstrates erythema and white papules (arrows).Figure 2.Download as PowerPointOpen in Image Viewer Barium esophagography is the most relevant imaging study to evaluate esophageal lichen planus. Imaging features include a smooth small-caliber esophagus with cervical esophageal webs, strictures, and pseudodiverticula (Fig 3) (3,4). Strictures most commonly occur in the proximal esophagus, and their presence correlates with a longer duration of disease (5). Squamous cell carcinoma of the esophagus has been rarely reported in patients with esophageal lichen planus; for this reason, early diagnosis is key.Figure 3. Esophageal lichen planus in a 73-year-old woman (same patient as in Fig 2). Barium esophograms show smooth long stricturing of the entire course of the esophagus with tapered margins (white arrow in A) and esophageal webs (black arrows in A). There are focal weblike strictures in an overall small-caliber lumen of the cervical esophagus (black arrow in B). Overall thin smooth luminal narrowing of the entire course of the esophagus is seen in C.Figure 3.Download as PowerPointOpen in Image Viewer Patients with esophageal lichen planus often present with dysphagia related to the strictures, with reflux-type symptoms, and weight loss. Strictures can be treated with balloon dilation, although this often requires regular repeat treatments (5). Endoscopic findings include superficial white papules, pseudomembranes, webs, and strictures.Disclosures of conflicts of interest.—All authors have disclosed no relevant relationships.AcknowledgmentWe thank Ciléin Kearns, MD, MBChB, for feedback and advice on the medical illustration in Figure 1.All authors have disclosed no relevant relationships.

膵十二指腸全摘術により救命し得た急性輸入脚症候群の1症例(Acute afferent loop syndrome complicated with severe necrotizing acute pancreatitis: a case successfully salvaged by total pancreatectomy)

輸入脚症候群は胃切除術Billroth–IIまたはRoux–en–Y（以下R–Y）再建後の稀な合併症であるが，急性に輸入脚が完全閉塞した急性輸入脚症候群（acute afferent loop syndrome: AALS）は膵炎を併発し致死的な病態となることがある。症例は胃癌に対し幽門側胃切除，D–2郭清，R–Y再建術の既往のある81歳の男性。腹痛を主訴に当院へ救急搬送されCTで絞扼性腸閉塞と診断された。緊急手術を施行したところ，Y脚が内ヘルニアとなってclosed loop obstructionを形成しており，Y脚を引き抜き，絞扼を解除した。術後は集中治療室で全身管理を行ったが，重症急性膵炎に進展し，CTで膵周囲壊死が疑われ，膵液瘻も認めた。術後19時間後に再開腹したところ膵十二指腸壊死を疑う所見を認め，膵十二指腸全摘術（total pancreatectomy: TP）を施行した。術後より全身状態は改善し，インスリン導入，膵消化酵素補充剤を開始した。SSIを併発したが，第45病日に独歩退院した。本症例ではAALSから重症壊死性膵炎に進展したが，緊急TPにより救命し得た。十二指腸壊死を伴うAALSに対してはTPも選択肢となると考えられた。 Acute afferent loop syndrome (AALS) is a rare complication that the afferent loop is acutely closed and obstructed after distal gastrectomy with Billroth–II or Roux–en–Y reconstruction, complicated with acute pancreatitis and sometimes critical. An 81–year–old man with past history of distal gastrectomy and Roux–en–Y reconstruction was admitted to our hospital presenting abdominal pain. Computed tomography (CT) revealed closed loop obstruction of the afferent loop incarcerated in a mesentery and the internal hernia was reduced by emergent surgery. After the initial surgery, the patient glowed a pancreatic fistula and severe pancreatitis. CT showed necrotizing in the pancreas and duodenum. Re–operation was considered to be necessary and total pancreatectomy (TP) was carried out. After the TP, the patient started to recover, insulin and pancreatic enzyme replacement therapy has been introduced, and was discharged on day 45. He has been followed on the outpatient and stable. AALS should be in a differential diagnosis in patients presenting small bowel obstruction with a history of gastrectomy. Urgent intervention is indispensable for AALS, and although it is a high–risk and invasive procedure, TP is an option for the most severe cases complicated with necrotizing acute pancreatitis. 輸入脚症候群は胃切除術Billroth–II法（以下B–II）/ Roux–en–Y（以下R–Y）再建後の稀な合併症であるが，急性に輸入脚が完全閉塞しclosed loopとなった場合は膵炎を併発し致死的となることがある。今回我々は，膵十二指腸全摘術により救命し得た急性輸入脚症候群の1症例を経験したため報告する。 なお，本症例の掲載にあたっては，患者の了承を得ている。また倫理委員会の承諾の必要がない論文であり，個人情報保護法に基づいて匿名化している。 患 者：81歳の男性 手術歴：73歳；胃癌（pT4aM1M0 pStage IIIa）に対し幽門側胃切除+D–2郭清，R–Y再建術，79歳；胆嚢結石症に対し腹腔鏡下胆嚢摘出術 既往歴：高血圧 内服薬：テルミサルタン 主 訴：腹痛 現病歴：1時間前に発症した上腹痛のため当院救命救急センターへ救急搬送された。嘔吐なし。 入院時現症：意識清明，血圧162/92mmHg，心拍数77/min，呼吸数24/min，SpO2 98%（室内気），体温36.5℃。心音整，呼吸音清。腹部板状硬，心窩部に圧痛あり。 入院時血液検査所見をTable 1に示す。 入院時造影CT検査：Y脚がTreitz靭帯直後で狭窄し，その直遠位部で拡張し，さらにその遠位でまた狭窄しており，両狭窄部は互いに近接してbeak signを認め，Y脚が横行結腸間膜をヘルニア門として左頭側に脱出した内ヘルニアとなってclosed loop obstructionを形成していると考えられた。膵臓は正常大で，膵管拡張，腫瘤影，周囲液貯留はいずれも認めなかった（Fig. 1）。 a: Computed tomography showed dilated duodenum (black arrows) and closed loop obstruction of the Y–limb (white arrow). b: Dilated duodenum (black arrows) and beak sign (white arrow). 経 過：絞扼性腸閉塞の診断で緊急手術を施行した。 全身麻酔，仰臥位で，胃切除時の上腹部正中切開創から開腹した。腹壁への癒着は認めなかった。腹水は黄色混濁していた。Treitz靭帯から吻合部までのY脚空腸が，上腸間膜動脈の背側を通り，右側に脱出していた。ヘルニア門を拡大し，空腸を引き抜いた。空腸は肉眼的には壊死に至っていないと判断し，腸管切除は行わなかった。後腹膜に暗赤色の液貯留が透見された。後腹膜を開放し，結腸肝湾曲，十二指腸下行脚を授動し，十二指腸に穿孔部がないか検索したが，明らかな穿孔部は認めなかった。横行結腸間膜のヘルニア門を縫合閉鎖し，左右横隔膜下，骨盤腔，開放した後腹膜腔にドレーンを留置し，閉腹して手術を終了した。手術時間は2時間54分，出血量100mL，輸血は施行しなかった。 ＜術後経過＞ 術後は抜管して集中治療室へ帰室した。腹痛は経時的に増悪してきた。左横隔膜下，骨盤腔のドレーン排液は淡血性から漿液性へ変化していったが，右横隔膜下，後腹膜ドレーンの排液は術後より一貫して暗赤色であり，術後4時間時点でドレーン排液中のアミラーゼ値を測定したところ後腹膜は11,485IU/L，右横隔膜下は5,115IU/Lと高値であり，同時刻の血清アミラーゼ値は855IU/Lであり，膵液瘻を疑った。輸液にも関わらず，経時的に代謝性アシドーシスが進行しBEは−6.3mEq/Lまで低下した。LDH >基準値の2倍，年齢>70歳，SIRS3項目陽性（脈拍>90/分，呼吸数>20/分，幼若白血球>10%）で重症急性膵炎の診断基準を満たした。術後16時間後に再度造影CTを撮影したところ，十二指腸下行脚内側の壁内および膵周囲，後腹膜に連続するガス像を認め，十二指腸壊死とそれによる穿孔が疑われた（Fig. 2）。末梢冷感や冷汗はなく，輸液により収縮期血圧>90mmHgは保たれたが，血清クレアチニン値は1.83mg/dLまで上昇し，純酸素投与下でP/F=321で，modified Marshal scoreは3点であった。以上より，膵液瘻，十二指腸壊死・穿孔，臓器不全を伴う急性壊死性膵炎と診断し，再手術を施行する方針とした。術式としては十二指腸切除術または，膵壊死が認められれば膵頭十二指腸切除術（pancreaticoduodenectomy: PD）または膵十二指腸全摘術（total pancreatectomy: TP）を考慮した。 a, b: Sixteen hours after initial surgery. CT showed free air accumulation around duodenum and pancreas (white arrows). 初回手術終了の約19時間後に再手術を開始した。全身麻酔，仰臥位で手術を開始した。前日の正中創を抜糸して開腹した。肝外側区域を横隔膜から授動し，左三角靭帯は結紮切離した。膵臓は固縮しており，膵周囲は胃切除術後の影響と炎症の影響で癒着していた。小腸全体に浮腫，壁肥厚，組織の脆弱性を認めた。十二指腸背側にはドレーン排液と同様の暗赤色液の貯留がみられた。十二指腸下行脚背側の膵頭部との境界付近が黒色調であるのを認め，同部位の壊死を疑った。十二指腸に明らかな穿孔部位は同定できなかった。術中カテコラミンを要する血圧低下を伴っており，腸管の状態も不良であることから，膵頭十二指腸切除術は膵管空腸吻合の縫合不全リスクが高く，術後に膵液瘻が生じれば致死的になると考えられたため，TPを施行する方針とした。 膵頭部頭側に総肝動脈を触知し膵上縁の剥離を行い胃十二指腸動脈，門脈を確認した。Y脚吻合部を一旦切離し，Treitz靭帯に向かって小腸間膜を腸管に沿って処理し，上腸間膜動脈（superior mesenteric artery: SMA），上腸間膜静脈（superior mesenteric vein: SMV）の背側を通り右側に引き抜いた。前面で膵頭部に流入する血管を結紮切離しSMVと膵頭部を剥離した。SMVの直上で膵臓を離断し，膵頭部とSMAの間を下膵十二指腸動脈や神経叢を処理しながら剥離した。総胆管は十二指腸上縁で切離し，膵頭部と十二指腸の標本を摘出した。次に膵下縁から脾下極を回る後腹膜を切開し，膵尾部，脾臓を脱転した。膵体部断端を腹側に挙上しつつ脾動静脈との間を剥離し，脾動静脈および脾臓は温存して膵体尾部の標本を摘出した。Y脚吻合部で小腸を切離し，肛門側断端を後結腸経路で挙上し胆管空腸吻合を行った。胆道減圧目的に5Frステントチューブを吻合部に留置し，挙上空腸断端から引き出し外瘻とした。胆管空腸吻合から45cm肛門側の小腸と，残胃と連続していた空腸を側々吻合した（Fig. 3）。左右横隔膜下，骨盤腔，胆管空腸吻合近傍にドレーンを留置し，閉創して手術を終了した。手術時間は8時間59分，出血量は2,300mL，輸血は赤血球4単位，新鮮凍結血漿8単位であった。 The schema of the surgery and reconstruction. 術後病理所見では十二指腸と膵臓の広範な壊死や膿瘍形成が認められ，急性出血性壊疽性膵炎と診断された（Fig. 4）。 Pathological findings showed hemorrhagic necrosis of the duodenum and pancreas with gangrenous inflammation. a: Pancreas showed focal necrosis and abscess with phlegmonous peritonitis. b: Duodenum with hemorrhagic erosion. ＜術後経過＞ 術後よりアシドーシス，循環動態は経時的に改善し始めた。第3病日にカテコラミンを離脱，第5病日から経口摂取を開始し，第6病日にICUから一般病棟へ転棟した。正中創のSSI，創離開，腹腔内遺残膿瘍を合併し，陰圧閉鎖療法，膿瘍穿刺ドレナージを併用し加療した。膵内外分泌障害に対しインスリンおよび消化酵素補充薬パンクレリパーゼを導入した。第45病日に独歩退院した。退院後も1年以上外来通院しており，経口摂取状況や血糖コントロールは概ね良好に経過している。 輸入脚とはB–II法または胃空腸吻合術後の胃空腸吻合部より近位の十二指腸空腸ループのことであり，輸入脚症候群とは一般的に輸入脚の一部閉塞により膵臓および肝胆膵の分泌物が腸管内に貯留し，腸管が拡張して発生する病態であるとされている。慢性輸入脚症候群ではblind loop syndromeによるVitB12欠乏，巨赤芽球貧血，脂肪吸収不良などが問題になるが，不完全閉塞であれば内圧上昇に伴い内容物が排出されるため最終的に輸入脚内容物が排出され症状は緩和される 1。 一方，輸入脚が急性に完全閉塞した急性輸入脚症候群（acute afferent loop syndrome: AALS）は，急性膵炎を併発し重篤と成りうる 2。輸入脚閉塞の原因としては悪性疾患，狭窄，癒着，捻転，内ヘルニア，腸石 3，胆石 4など多岐に渡る。膵炎に至る機序としては，膵液のトリプシンが，輸入脚閉塞により膵管内に逆流するため 5, 6, 7，または輸入脚圧の上昇により膵実質の循環不全が生じ，free radicalが発生するため 8と考えられている。症候としては，胃の手術歴がある患者で，画像上腸閉塞の一形態ではあるが，嘔吐は出現し難い点に留意が必要である。胃の術後早期の報告が多いが，最長で37年経過後に発症した報告 3もあり，病歴聴取，CTなど画像検査による術後再建方法の検索が重要である。 AALSはB–II再建に限らずR–Y再建後にも生じ得 2，（R–Y後は0.2～0.68%，B–II後は0.3～1.0% 3），Braun吻合や器械吻合でも防ぎ得ない 3。本症例は幽門側胃切除，R–Y再建後で，輸入脚が横行結腸間膜をヘルニア門とする内ヘルニアとなってclosed loopを形成し，絞扼性腸閉塞が生じて輸入脚内圧が上昇しAALSに至ったと考えられた。AALSの死亡率は11～60% 2, 3ともいわれ，迅速な診断と対応が必要である。 本症例では来院時点では膵炎の所見を呈していなかったことから，AALSによる膵炎は急速に発症・増悪しうると考えられた。また初回手術時の後腹膜に認めた暗赤色貯留液はAALSによる膵炎の発症や重症化を予期していた可能性があったと考えられた。急性膵炎の死亡率は全体で2.1%，重症では10.1%であり，70歳以上の急性膵炎は死亡率が3倍とも報告されている 9。さらに本症例ではCTで膵周囲十二指腸壊死が疑われ，壊死性膵炎を併発したと考えられた。壊死性膵炎は膵実質または膵周囲組織の両者またはいずれか一方が壊死に陥ったもので，急性膵炎の10～20%を占め，死亡率は15～20%と言われる 9。膵壊死を伴う重症膵炎の死亡率は23% 10と言われ，壊死性膵炎に臓器不全を伴う場合の死亡率は約50%，急性膵炎の発症早期に臓器不全がある場合や48時間以上続く臓器不全がある場合は死亡率70%とされている 9。また初回手術後にドレーンアミラーゼ値が高値となったため，膵液瘻も生じてきたものと考えられ，CTで十二指腸壊死・穿孔を疑われた。初回手術により腸閉塞は解除されて輸入脚内圧は減圧されており，ドレーンも留置されていたにも関わらず病状が増悪してきており，発症24時間時点でmodified Marshal score 3点 11であった。術後病理診断では十二指腸と膵臓の広範な壊死や膿瘍形成が認められる急性出血性壊疽性膵炎を呈していた。以上より，膵液瘻，十二指腸壊死，発症早期に臓器不全を伴う重症壊死性膵炎に該当する致死的な病態であり，救命のための介入が必要であったと考えられた。 AALSに対する手術術式としては，輸入脚の絞扼や内ヘルニアであれば解除，輸入脚の穿孔や壊死を伴っていれば切除・吻合（バイパス），吻合部狭窄では吻合部を切除して新たなRoux–en–Y再建，B–II後で元々Braun吻合がなかった症例では減圧のためBraun吻合追加，などがよく行われる 2。手術以外の治療選択肢として経皮的腸管ドレナージ 2, 3，経皮経肝輸入脚ドレナージ 2，経皮経肝胆道ドレナージ 2，経皮経肝胆嚢ドレナージ 2，内視鏡的ドレナージ 2, 3，内視鏡的ステント留置 2，狭窄部の内視鏡的バルーン拡張術 12などがあるが，内視鏡的減圧後の死亡の報告 4もあり，AALS急性期の治療について統一見解は得られていない。本症例では初回手術後のCTで十二指腸穿孔が疑われたため再開腹した。術中所見では十二指腸穿孔部位は同定できなかったものの十二指腸下行脚背側および膵頭部の壊死が疑われたため，PDまたはTPが必要であると考えられた。 TP後には膵内外分泌能が欠落するため，糖代謝障害，消化吸収障害などの代謝栄養障害を来す 13というデメリットもあるが，TPは膵管空腸吻合を要さず，膵自体を全摘するため，膵液瘻のリスクはない。TPの手術死亡率は2.6～9%，術後合併症発生率31～74%で，PDの術後合併症発生率と差がないと報告されている 14ものの，これは癌の定時手術の場合であり，本症例では腹腔内および全身状態から術後膵液瘻のリスクが高く，かつ生じれば致死的になると考えられたため，PDは選択しなかった。また若年者であれば膵機能温存を試みて，一期的再建を断念して膵外瘻のみとするか，あるいは一旦再建を省略した膵頭部切除＋膵外瘻とし，全身状態安定後に膵管空腸吻合を含む二期的再建を狙う戦略も考えられたが，本症例では全身状態不良かつ高齢で再々手術が施行可能となるかも不透明であり，初回の保存的な輸入脚減圧手術後に状態が悪化したなかでの再手術であったため，救命，短期予後および早期社会復帰を最優先とし，TPを選択した。 医学中央雑誌を用いて「輸入脚症候群」，「輸入脚閉塞」をキーワードに会議録を除いて本邦報告例を検索したところ，AALSに対して膵切除を施行した報告は4例あるが，TPの報告はない 15, 16, 17, 18（Table 2）。急性膵炎の急性期手術については，1970年代から1980年代にかけて膵全摘術を含む膵広範囲切除術が行われた時期もあった 19が，現行のガイドラインでは推奨されていない 9。しかし，臓器不全を伴う重症急性膵炎に対するTP術後死亡率が60%に対し，75%以上の壊死を伴う膵炎の死亡率が90%であることを踏まえると壊死性急性膵炎に対しTPは救命率を改善させうるという報告もある 20。SSIなどの術後合併症のため入院期間は延長したが，TP後の膵内外分泌障害に対しては投薬により退院後も良好に経過している。以上より，本症例においてTPは妥当であったと考えられ，膵周囲壊死および臓器不全を伴う重症急性膵炎を呈したAALSに対しては，高侵襲な手技ではあるが，TPにより救命しうる可能性が示唆された。 year (published) past history interval (years) wide resection for GU wide resection for GU AALSに併発した重症壊死性急性膵炎に対しTPにより救命し得た1症例を報告した。 本論文のすべての著者に利益相反はない。

Diffusion Tensor Imaging of Ulnar Neuropathy Caused by an Accessory Anconeus Muscle.

HomeRadiologyRecently Published PreviousNext Reviews and CommentaryFree AccessImages in RadiologyDiffusion Tensor Imaging of Ulnar Neuropathy Caused by an Accessory Anconeus MuscleTeodoro Martín-Noguerol , Antonio LunaTeodoro Martín-Noguerol , Antonio LunaAuthor AffiliationsFrom the Department of Radiology, MRI Unit, HT Médica, Clínica Las Nieves, Calle Carmelo Torres 2, 23007 Jaén, Spain.Address correspondence to T.M.N. (email: [email protected]).Teodoro Martín-Noguerol Antonio LunaPublished Online:Mar 21 2023https://doi.org/10.1148/radiol.221854MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In A 29-year-old woman presented with complaints of progressive numbness in the left ulnar nerve territory. Physical examination demonstrated left ring and little finger weakness and hypoesthesia with positive flexion elbow test. MRI of the elbow with diffusion tensor imaging (DTI) neurography was performed and revealed extrinsic compression of the ulnar nerve by an accessory anconeus epitrochlearis muscle (Figure). DTI neurography scan showed deformity of the ulnar nerve with corresponding focal decrease in fractional anisotropy (FA) values at the compression site (0.3). FA values were also slightly decreased distally to the compression level (0.41), with normal appearance of the rest of the ulnar nerve (1).MRI scans show the left elbow in a 29-year-old woman with progressive numbness in the left ulnar nerve distribution. (A, B) Axial proton density–weighted images with spectral fat suppression show an accessory anconeus epitrochlearis muscle (arrow) with entrapment of the ulnar nerve (arrowhead). (C) Three-dimensional neurography reconstruction of diffusion tensor imaging with use of directional encoding color fused with proton density with spectral fat suppression shows deformity of the ulnar nerve at the site of extrinsic compression (arrowhead). A focal decrease in the fractional anisotropy values of the ulnar nerve (black arrow) is seen below the level of compression by the anconeus epitrochlearis muscle (white arrow).Download as PowerPointOpen in Image Viewer The anconeus epitrochlearis muscle is an accessory muscle located at the medial aspect of the elbow, originated at the inferior surface of medial epicondyle, and inserted at the medial cortex of the olecranon (2). The relationship between the accessory anconeus muscle and prevalence of ulnar neuropathy remains unknown (3). By providing quantitative information, DTI neurography allows detection of subtle changes in ulnar nerve morphologic conditions (4) and may prove helpful in diagnosis and treatment monitoring in ulnar neuropathy caused by accessory anconeus muscle. In the presented case, the patient was treated conservatively with a favorable clinical outcome.Disclosures of conflicts of interest: T.M.N. No relevant relationships. A.L. Royalties or licenses from Springer; fee to institution as lecturer from GE; Digital Oncology board member for Siemens Healthineers.

COVID-19 infection and extensive subdural empyema: cause or consequence?

Adolescent, female, 12 years old, with a history of headache and vomiting, without fever, with progressive worsening and coma. Laboratory tests showed positive SARS-CoV-2 PCR RNA. She has not had the vaccine for COVID-19. A non-contrast-enhanced cranial tomography(Figure 1a) showed a right fronto-temporo-parietal cortical hypodense area with significant midline shift. A decompressive craniectomy was performed with drainage of extensive subdural empyema(Figure 1c). Subdural empyema is most often a consequence of paranasal sinus infections. With the COVID-19 virus also located in the paranasal sinuses, it is not possible to determine whether it is a consequence or cause of subdural empyema (1). Although the pathophysiology is unclear, it is possible that upper respiratory infection by COVID-19 creates a favorable environment for bacterial sinusitis coinfection(Figure 1b), intracranial extension, and formation of subdural empyema (2). Another possible explanation is that the SARS-CoV-2 virus infection affects the immune system and makes the individual more susceptible to infection (3). Therefore, more studies are needed to clarify the relationship between SARS-CoV-2 infection and other infections. Figure Caption Figure 1 (a) Computed tomography of the skull, with the axial section showing a right fronto-temporo-parietal hypodense area(black arrows) with significant midline shift(black arrowheads). (b) Computed tomography of the skull, with the coronal section showing signs of sinusitis with opacification of the right ethmoid sinus(black arrow). (c) Intraoperative view after opening the dura mater showing exposure of the right fronto-temporo-parietal cortex covered by viscous purulent secretion(black arrow). (d) Computed tomography of the skull, with the coronal section showing after treatment without ethmoid opacification(black arrow) and small postoperative CSF collection(black arrowhead).

A case of multiple myeloma with AL amyloidosis showing giant Russel bodies.

A 67-year-old male patient presented to our hospital with streptococcus pneumonia and a neck phlegmon. As part of an initial workup, a review of an intravenous immunoglobulin order for a possible secondary hypogammaglobinaemia and pneumosepsis showed low IgA and IgM subsets but overall increased IgG class proteins (0.08, 0.3, and 22.8 g/L respectively). The IgG class subset analysis showed decreased IgG class 2–4 but elevated IgG class 1 levels (28.7 g/L). For lack of bona fide hypogammaglobinemia, intravenous immunoglobulin therapy was denied, and further workup including a bone marrow biopsy was undertaken. Patient also presented with secondary erythrocytosis (Haemoglobin 195, janus kinase 2 [Jak2] negative, with increasing erythropoietin [EPO] level), attributed to severe sleep apnea and asthma. A serum electrophoresis (SPEP) showed an IgG lambda monoclonal protein (19 g/L) with elevated serum lambda free light chain (588.5 mg/L) with a marked concomitnat background gamma globulin suppression. A bone marrow biopsy showed scanty background residual trilinear hematopoiesis with an increase in lambda clonal plasma cells (90% of cellularity). Specifically the bone marrow aspirate showed frequent inclusions overlaying the nucleus (Dutcher bodies) and cytoplasm (Russel bodies) of the plasma cells (Figure 1, panel A, white and black arrows respectively, stained by May-Grünwald- Giemsa x 40 objective). Many of the inclusions seen were smaller leaving the cellular morphology intact. Having said this, within the aspirate particles, large/giant inclusions were seen (panel B, aspirate granule x40 magnification). Moreover, a trephine biopsy showed many large spherical bodies which showed cytoplasmic ballooning and resulted in complete cellular effacement and displacement of the nucleus (Figure 1, panels C–E Hematoxylin and Eosin stain x40 (C) and x50 (D,E) magnification respectively; black arrows point to overstuffed plasma cells with eccentric nuclei). CD138/lambda stains confirmed that these were not cell-free but were inclusions within the plasma cell cytoplasm (Figure 1, panels F and G, CD138 and lambda stains respectively, x20 magnification). Lastly a Congo red stain for amyloid showed salmon pink deposits with apple green birefringence under polarized light (panels H&I showing a bone marrow blood vessel, Congo red ×20 magnification). With a confirmed diagnosis of plasma cell myeloma the patient was treated with cyclophosphamide, bortezomib and dexamethasone therapy, forgoing any intravenous immunoglobulin. The first description of intracytoplasmic inclusion in multiple myeloma were provided by Russel (1890) and subsequently termed Russel bodies. Mott cells refer to plasma cells with multiple inclusions such as Russel bodies. Dutcher bodies refer to cytoplasmic inclusions that overlay the nucleus. These cytoplasmic inclusions have been observed in both reactive and malignant plasma cells. They represent accumulations of mucopolysaccarides and immunoglobulin, which highlights the common nature of these inclusions. There is no established prognostic significance of such inclusions. One study by Jiang et al. reveals a correlation between the presence of Dutcher bodies and t(4;14), which is an adverse prognostic marker in multiple myeloma. Both authors were involved with taking photos, and writing and editing the manuscript. The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported The authors received no specific funding for this work. There are no patient identifiers in this study. Verbal consent has been obtained at the time of bone marrow biopsy. All data have been presented and are available for review.

Adult-Onset Asthma With Periocular Xanthogranuloma: Clinical-Histological Correlation.

A 48-year-old male presented with 10 years of gradually enlarging yellow eyelid lesions. Past medical history was notable for adult-onset asthma diagnosed 5 years ago. He denied pain, diplopia, bone/joint pain, or systemic findings such as weight loss or fatigue. His father had similar eyelid lesions. Preoperative photograph demonstrated bilateral upper eyelid yellowish lesions with prominent edema and tissue expansion inducing bilateral ptosis (Fig. 1A). MRI demonstrated eyelid inflammation, enlargement of the extraocular muscles, especially the right lateral rectus (Fig. 1B, white arrow), and enlargement and enhancement of lacrimal gland (Fig. 1C, black arrow). He desired debulking excisional biopsies with bilateral blepharoplasty. Intraoperative photos show significant soft tissue inflammatory infiltration, particularly the lacrimal gland (Fig. 1D, red arrows).FIG. 1.Histopathologically, xanthogranulomatous inflammation is characterized by diffuse inflammatory infiltrate composed of histiocytes and lymphocytes (Fig. 2A, H&E, 100×). Specifically, the presence of foamy macrophages (Fig. 2B, H&E, 400×, red arrows) and Touton Giant cells (Fig. 2C, H&E, 400×, black arrow) are the histological hallmarks of the disease. The differential diagnosis of xanthogranulomatous inflammation includes adult-onset xanthogranuloma, adult-onset asthma with periocular xanthogranuloma (AAPOX), Erdheim-Chester disease (ECD), necrobiotic xanthogranuloma (NBX), and juvenile xanthogranuloma.FIG. 2.The patient was diagnosed with AAPOX given the association with adult-onset asthma. While the vast majority of yellow eyelid lesions are clinically benign, ECD and NBX are must-not-miss diagnoses, given their potential life-threatening systemic manifestations. These include vital organ (heart/kidney/lung) involvement in ECD, and association with serum protein abnormalities and hematological malignancies in NBX.

Hodgkin lymphoma in the bone marrow aspirate of a young patient with human immunodeficiency virus.

Hodgkin lymphoma in the bone marrow aspirate of a young patient with human immunodeficiency virus.