Gastric perforation secondary to incarcerated para-esophageal hiatal hernia in a French bulldog.

A 6-month-old, intact female, French bulldog was presented to the Emergency Department for evaluation of vomiting and diarrhea over the preceding week which had not responded to supportive medical therapy. Imaging studies identified an incarcerated para-esophageal hernia with peritoneal effusion and gas consistent with gastrointestinal perforation. Following stabilization, the dog underwent an exploratory laparotomy which confirmed an incarcerated hiatal hernia and gastric perforation. A gastrectomy was performed to repair the defect, and to prevent recurrence both a herniorrhaphy and esophagopexy were performed. Post-operative care required treatment for septic shock including vasopressor and hydrocortisone infusions and plasma transfusions for colloidal support. The patient was successfully discharged 4 days after surgery. The histopathology results identified spiral bacteria consistent with Helicobacter spp. which was subsequently treated with oral antibiotics and a proton pump inhibitor. The dog has had no further gastrointestinal signs in the 90 days since surgery. Gastric perforation and peritonitis can occur secondary to an incarcerated esophageal hiatal hernia, and if treated promptly can result in a successful outcome. This case demonstrates a novel etiology of gastric perforation which may be associated with brachycephalic breeds.

Une femelle bouledogue français intacte de 6 mois a été présentée au service des urgences pour une évaluation des vomissements et de la diarrhée au cours de la semaine précédente qui n'avaient pas répondu à un traitement médical de soutien. Les études par imagerie ont identifié une hernie para-œsophagienne incarcérée avec un épanchement péritonéal et des gaz compatibles avec une perforation gastro-intestinale. Après stabilisation, la chienne a subi une laparotomie exploratoire qui a confirmé une hernie hiatale incarcérée et une perforation gastrique. Une gastrectomie a été réalisée pour réparer le défaut et pour prévenir les récidives, une herniorraphie et une œsophagopexie ont été réalisées. Les soins postopératoires ont nécessité un traitement pour choc septique comprenant des perfusions de vasopresseurs et d'hydrocortisone et des transfusions de plasma pour le soutien colloïdal. La patiente a obtenu son congé avec succès 4 jours après la chirurgie. Les résultats d'histopathologie ont identifié des bactéries en spirale compatibles avec Helicobacter spp. qui a ensuite été traité avec des antibiotiques oraux et un inhibiteur de la pompe à protons. La chienne n'a plus eu de signes gastro-intestinaux dans les 90 jours qui ont suivi la chirurgie.Une perforation gastrique et une péritonite peuvent survenir à la suite d'une hernie hiatale oesophagienne incarcérée et, si elles sont traitées rapidement, peuvent donner un résultat positif. Ce cas démontre une nouvelle étiologie de perforation gastrique qui peut être associée aux races brachycéphales.(Traduit par Docteur Serge Messier).

Pancreatic herniation: a large pancreatic mass concealed within the intrathoracic cavity.

Cancer of unknown primary is a challenging entity. We present an elderly woman with metastatic cancer of unknown primary despite comprehensive imaging and immunohistochemical analysis. Based on a thorough history, a gastrointestinal source was suspected and a diagnosis of pancreatic cancer concealed within a type IV hiatal hernia was made using multimodal imaging. On review of prior imaging, due to the highly complex anatomy within our patient's hiatal hernia, the pancreatic mass was retroactively noted. While initial imaging may detect metastatic disease, identifying the primary malignancy requires a thorough history and physical examination, multimodal imaging where malignancy is suspected, and immunohistochemical analysis of metastatic deposits. Herniation of pancreatic cancer has not been previously described in the literature and serves as an important reminder of the importance of multimodal imaging in patients with significantly complex anatomy.

The structural and functional workings of KEOPS.

KEOPS (Kinase, Endopeptidase and Other Proteins of Small size) is a five-subunit protein complex that is highly conserved in eukaryotes and archaea and is essential for the fitness of cells and for animal development. In humans, mutations in KEOPS genes underlie Galloway-Mowat syndrome, which manifests in severe microcephaly and renal dysfunction that lead to childhood death. The Kae1 subunit of KEOPS catalyzes the universal and essential tRNA modification N6-threonylcarbamoyl adenosine (t6A), while the auxiliary subunits Cgi121, the kinase/ATPase Bud32, Pcc1 and Gon7 play a supporting role. Kae1 orthologs are also present in bacteria and mitochondria but function in distinct complexes with proteins that are not related in structure or function to the auxiliary subunits of KEOPS. Over the past 15 years since its discovery, extensive study in the KEOPS field has provided many answers towards understanding the roles that KEOPS plays in cells and in human disease and how KEOPS carries out these functions. In this review, we provide an overview into recent advances in the study of KEOPS and illuminate exciting future directions.

Estudio comparativo de precisión diagnóstica preoperatoria y la confirmación laparoscópica de hernia hiatal / Comparative study of preoperative diagnostic precision and laparoscopic confirmation of hiatal hernia

Resumen Introducción: La hernia hiatal (HH) de tipo I por deslizamiento es el tipo más frecuente, siendo difícil de definir objetivamente, por lo que el principal foco de controversia es su diagnóstico. El objetivo del presente trabajo es reportar los resultados respecto de la precisión diagnóstica del estudio preoperatorio y confirmarlo con el diagnóstico laparoscópico de este tipo de HH. Materiales y Método: Estudio prospectivo descriptivo de serie que incluyen pacientes con síntomas típicos de enfermedad por reflujo gastroesofágico, los cuales se sometieron a estudio con esófago-gastro-duodenoscopía, estudio manométrico y radiológico de esófago, estómago y duodeno con bario. Se incluyen sólo los pacientes en los cuales la endoscopía revela la existencia de HH por deslizamiento ≪ 5 cm. Estos pacientes se sometieron a tratamiento quirúrgico confirmándose o no la existencia de HH al momento de la exploración laparoscópica. Resultados: El valor predictivo positivo y sensibilidad para manometría fue de un 51,2% y 70%, para la radiología 91,7% y 80,5% y para endoscopia 80,3% y 70,7% respectivamente. Conclusión: Para el diagnóstico confiable de HH antes del tratamiento, las tres investigaciones mencionadas deben ser obligatorias antes de la cirugía.

Introduction: Being type I hiatal hernia (HH) the most frequent, is difficult to define objectively and therefore, the main focus of controversy is the diagnosis. The aim of this paper is to report the results regarding the diagnostic accuracy of the preoperative study and to confirm it with the laparoscopic diagnosis of hiatal hernia. Materials and Method: This descriptive and prospective study includes patients with typical symptoms of gastroesophageal reflux disease who underwent esophageal-gastro-duodenoscopy, manometry and radiological study of esophagus with barium swallow. Only patients in whom endoscopy reveals the existence of HH by sliding ≪ 5 cm are included. These patients underwent surgical treatment confirming or not the existence of HH at the time of laparoscopic exploration. Results: The positive pre- dictive value and sensibility for manometry was 51.2% and 70%, for radiology 91.7% and 80.5%, and for endoscopy 85.3% and 70.7% respectively. Conclusion: For the reliable diagnosis of HH before treatment, the three mentioned investigations must be mandatory before the surgery.

Congenital hiatal hernia segregating with a duplication in 9q22.31q22.32 in two families.

Congenital hiatal hernia (HH) is a rare congenital defect and is often described on a sporadic basis, but familial cases have also been reported. The mechanism of development is not well understood, and to our knowledge no specific genetic factors have been implicated to date. We report on seven individuals from two families with 9q22 duplication, who have variably associated features including congenital HH in four individuals. One family had an 1.09 Mb 9q22 duplication, and the other family had an overlapping 2.73 Mb 9q22 duplication. We review the genes in this region and discuss BARX1 (BarH-like homeobox gene 1) as a gene of interest.

[A rare cause of type 2 non-ST-elevation myocardial infarction: Cardiac compression and left ventricular obstruction by a giant hiatal hernia]. / Une cause rare d'infarctus du myocarde sans sus-décalage du segment ST de type 2 : compression cardiaque et obstruction intraventriculaire gauche par une volumineuse hernie hiatale.

We report the case of a 89 year-old woman admitted to the emergency department for epigastric pain, nausea, vomiting. Because of a circulatory failure with electrocardiographic ST changes and a slight elevation of ultra-sensible troponin, a coronary angiography was performed and found normal coronary arteries. Thoraco-abdominal CT scan revealed a large hiatal hernia causing a cardiac compression, and a left intraventricular obstruction showed by Doppler echocardiography. All signs resolved after fasting and gastric drainage.

Endoscopic Prediction for Acid Reflux in Patients without Hiatus Hernia.

Background/Aims: A diagnosis of gastroesophageal reflux disease is challenging in patients who have reflux symptoms but do not respond to proton pump inhibitors nor have reflux esophagitis and hiatal hernia (HH) on endoscopy. This study examined the predictive role of the endoscopic findings, including the flap valve grade for pathologic acid exposure (PAE) to establish an endoscopic prediction model in patients with neither reflux esophagitis nor HH. Methods: Five hundred seventy-eight patients who underwent upper endoscopy and 24 hours pH monitoring for reflux esophageal symptoms without evidence of reflux esophagitis and HH were analyzed. The gastroesophageal flap valve (GEFV), esophageal metaplasia, and chronic atrophic gastritis were assessed. The association between the endoscopic parameters and PAE was evaluated. Results: Four hundred ninety-four patients were enrolled. The most common complaint was chest discomfort (42.3%) followed by globus (31.8%), dysphagia (7.9%), and heartburn (7.7%). PAE was present in 43 patients (8.7%). Multivariable analysis revealed PAE to be associated with the GEFV grade (p<0.001) and inversely associated with the chronic atrophic gastritis grade (p=0.005). Using these features, a predictive model was established and showed an area under the receiver operating characteristic curve of 0.705 (95% CI 0.619-0.790). The cutoff value of 12.0 had a sensitivity and specificity of 44.0% and 84.0%, respectively. Conclusions: A loosened GEFV is associated with a risk of PAE in patients with neither reflux esophagitis nor HH, while atrophic gastritis is preventive. On the other hand, the endoscopic predictive model revealed a low sensitivity for detecting PAE. Thus, reflux testing needs to be performed further when gastroesophageal reflux disease is suspected, even without endoscopic evidence.

GERD for the nongastroenterologist: successful evaluation, management, and lifestyle-based symptom control.

Gastroesophageal reflux disease (GERD) is a complex disorder. Symptoms of heartburn can help find the disorder of GERD. pH testing is the mainstay of evaluation of symptoms, including 24-h and longer pH studies to detect pathologic acid exposure. The use of proton pump inhibitor (PPI) therapy for approved indications is helpful for both symptomatic relief and esophagitis healing in the majority of patients with abnormal acid exposure. PPI medications are safe in short- or long-term use. It is recommended not to maintain cirrhotic patients on PPI therapy without a meaningful indication. Dietary adjustment can provide benefit to some patients, but the data are mixed on how much benefit has been demonstrated from specific food avoidance. Reduction in weight improves reflux. Obesity has measurable effects on the esophageal acid exposure but fewer effects on the motility of the esophagus itself. Controlling weight and changing lifestyle can be helpful for improving GERD symptoms. For some patients in whom either the control of reflux with medications and lifestyle change is not sufficient or a hernia is contributing to symptom generation, surgical and endosurgical interventions can be considered to help manage reflux after a thorough workup with pH testing and manometry.

Anatomic Observation of Recurrent Hiatal Hernia: Recurrence or Disease Progression?

BACKGROUND: Recurrence after hiatal hernia repair is common. The causes are uncertain. Our observation is the site of recurrence is primarily the nonsutured or nonreinforced anterior-left lateral portion of the hiatus. Our aim was to assess the distribution of hiatal hernia recurrence location as a basis for developing a theory of recurrence. METHODS: Consecutive patients who underwent repair of recurrent hiatal hernias from March 2012 to December 2019 were reviewed. Data collected included age, sex, date of operation, location of hiatal hernia recurrence, operative approach, method of hiatal hernia repair, fundoplication performed, need for gastrectomy, and additional procedures. RESULTS: One hundred and eight consecutive patients were studied. The distribution of recurrence locations was as follows: anterior 67%, posterior 12%, and circumferential 21%. Foreshortened esophagus was a contributing factor in 12%. Median time from the original repair to recurrence was 1.5 years (interquartile range 0.9 to 3.75 years) for posterior recurrences, 2.75 years (interquartile range 1.15 to 8.5 years) for circumferential recurrences, and 3.25 years (interquartile range 1.38 to 10 years) for anterior recurrences. Recurrences were repaired in a variety of techniques, depending on the clinical circumstances. CONCLUSIONS: Hiatal hernia recurrences due to failure of the crural closure were less common, but early, recurrences. The majority of recurrences were due to stretching of the hiatus anterior and to the left of the esophagus. We theorize that the pathophysiology of late hiatal hernia recurrence is widening of the anterior and left lateral portion of the hiatus secondary to repeated stress from differential pressures that eventually overcomes the tensile strength of the hiatus.

Hernia hiatal mixta congénita gigante en lactante de cuatro meses / Congenital mixed giant hiatal hernia in a four-month-old infant

Introducción: La hernia hiatal congénita es poco frecuente, con una edad media de presentación a los 28 meses de vida. Las hernias paraesofágicas/mixtas provocan más frecuentemente infecciones respiratorias repetitivas, vómitos, anemia y fallo de medro. Caso clínico: Nos encontramos ante un lactante de 4 meses que presenta irritabilidad desde el nacimiento y rechazo parcial de las tomas en las últimas 24 horas. En el tránsito esófago-gastro-duodenal se evidencia un estómago parcialmente intratorácico. Tras realizarse una tomografía computarizada toraco-abdominal, se plantean como diagnósticos hernia hiatal mixta gigante vs. hernia diafragmática posterolateral derecha vs. esófago corto congénito. Intraoperatoriamente se visualiza hernia hiatal mixta gigante, realizándose herniorrafia laparoscópica y funduplicatura de Nissen. Comentarios: Las hernias con afectación diafragmática más frecuentes en Pediatría son la hernia de Bochdalek y de Morgagni. La hernia hiatal produce más frecuentemente síntomas gastrointestinales; así, el tratamiento es quirúrgico, con el objetivo de evitar o minimizar dichos síntomas y prevenir las consecuencias de la volvulación gástrica

Introduction: Congenital hiatal hernia is a rare pathology, presenting at 28 months of age on average. Paraesophageal/mixed hernias cause recurrent respiratory infections, vomiting, anemia, and growth failure. Clinical case: Four-month-old infant, with irritability since birth and partial feeding intolerance in the last 24 hours. A partial intratho-racic stomach was evidenced in the esophago-gastro-duodenal contrast study. A thoraco-abdominal CT scan was carried out, with giant mixed hiatal hernia, right posterolateral diaphragmatic hernia, and congenital short esophagus being considered as potential diagnoses. A giant mixed hiatal hernia was noted during surgery. Laparoscopic herniorrhaphy and Nissen fundoplication were performed. Discussion: In the pediatric population, Bochdalek's hernia and Morgagni's hernia are the most frequent congenital diaphragmatic hernias. Hiatal hernia is rare and causes gastrointestinal symptoms more frequently. Surgery is the treatment of choice, with the objective of preventing or minimizing these symptoms as well as gastric volvulus

Modern era surgical outcomes of elective and emergency giant paraesophageal hernia repair at a high-volume referral center.

INTRODUCTION: Repair of giant paraesophageal hernia (PEH) has historically been associated with significant morbidity and mortality such that elective repair is only offered to symptomatic patients. Recent reports suggest modern era outcomes have improved such that elective repair may now be safer than historically thought. Furthermore, the morbidity of emergency surgery may still be significant. These changes may have important implications for patient selection for elective repair. The objectives of this study were to determine and compare modern era surgical outcomes after elective and emergency repair of giant PEHs at a high-volume tertiary care center. METHODS: A retrospective review was conducted for all Type II-IV giant PEH repairs performed between 1 January 2012 and 31 December 2017. Type 1 hiatal hernias, fundoplication for reflux, and any co-surgery other than cholecystectomy were excluded from the final analysis. Baseline patient demographics, operative details, postoperative complications within 30 days and in-hospital or 30-day mortality were tabulated from the electronic medical record. Data were reported as median (interquartile range) unless otherwise specified. RESULTS: A total of 352 cases were reviewed, of which 204 met inclusion criteria (18 emergency, 186 elective). Eight had Type II PEH, 146 had Type III, and 50 had Type IV. Median length of stay was shorter in the elective group [1 (1) day elective vs. 5 (7) days emergency, p < 0.0001], and emergency patients were less likely to return directly to their original residence at discharge (13, 72% emergency vs 185, 99.4% elective, p < 0.0001). There were significantly more major complications (Clavien-Dindo score ≥ 3) in the emergency group (5, 28% emergency vs. 10, 5% elective, p = 0.005). There were no perioperative deaths in either group. Morbidity and mortality in both groups were less than historically reported. CONCLUSIONS: Informed consent discussions and patient selection for repair of giant PEHs should reflect modern era and institution-specific outcomes.

Asymmetrical elevation of esophagogastric junction pressure suggests hiatal repair contributes to antireflux surgery dysphagia.

The radial distribution of esophago-gastric junction (EGJ) pressures with regard to troublesome dysphagia (TDysph) after antireflux surgery is poorly understood. Before and after antireflux surgery, end-expiratory and peak-inspiratory EGJ pressures were measured at eight angles of 45° radial separation in patients with reflux disease. All 34 patients underwent posterior crural repair, then either 90° anterior (N = 13) or 360° fundoplication (N = 21). Dysphagia was assessed prospectively using a validated questionnaire (score range 0-45) and TDysph defined as a dysphagia score that was ≥5 above pre-op baseline. Compared with before surgery, for 90° fundoplication, end-expiratory EGJ pressures were highest in the left-anterolateral sectors, the position of the partial fundoplication. In other sectors, pressures were uniformly elevated. Compared with 90° fundoplication, radial pressures after 360° fundoplication were higher circumferentially (P = 0.004), with a posterior peak. Nine patients developed TDysph after surgery with a greater increase in end-expiratory and peak-inspiratory EGJ pressures (P = 0.03 and 0.03, respectively) and significantly higher inspiratory pressure at the point of maximal radial pressure asymmetry (P = 0.048), compared with 25 patients without TDysph. Circumferential elevation of end-expiratory EGJ pressure after 90° and 360° fundoplication suggests hiatal repair elevates EGJ pressure by extrinsic compression. The highly localized focal point of elevated EGJ pressure upon inspiration in patients with TDysph after surgery is indicative of a restrictive diaphragmatic hiatus in the presence of a fundoplication.

[Anatomical features and biomechanical properties of the diaphragm in pathogenesis of hiatal hernia]. / Anatomicheskie osobennosti i biomekhanicheskie svoistva diafragmy v patogeneze razvitiia gryzh pishchevodnogo otverstiia diafragmy.

OBJECTIVE: To study changes of diaphragm and esophageal-diaphragmatic junction depending on age and constitutional features. MATERIAL AND METHODS: We studied changes of diaphragm and esophageal-diaphragmatic junction depending on age and constitutional features by using of 40 cadaveric specimens (people aged 19-75 years). RESULTS: Esophageal-aortic ligament is observed rarer with age. This ligament is poorly developed in brachiomorphic body type while diaphragmatic-cardiac ligament is generally absent as a rule. This is a predisposing factor for weakening this area. It was revealed that reduced strength and elasticity (especially esophageal-aortic and esophageal-diaphragmatic ligaments) is one of the key factors in the development of hiatal hernia. It is especially relevant for brachiomorphic body type, the 2nd mature and elderly age. The 2nd mature period is associated with reduced diameter and kinking of great arteries, that leads to 1.5-2 times decrease of arterial capacity of the diaphragm. Therefore, hiatal hernia repair using own tissues may be insufficient and accompanied by recurrence in persons with brachiomorphic body type in the 2nd mature period. CONCLUSION: Analysis of biomechanical data and anatomical features of the diaphragm may be useful to predict recurrent hiatal hernia.

The other explanation for dyspnea: giant paraesophageal hiatal hernia repair routinely improves pulmonary function.

Paraesophageal hiatal hernias (PEHs) are most commonly associated with gastrointestinal symptoms; less widely appreciated is their potentially important influence on respiratory function. We hypothesize that surgical repair of PEH will significantly improve not only gastrointestinal symptoms, but also preoperative dyspnea and spirometry scores. A prospective Institutional Review Board-approved database was used to review all patients undergoing PEH repair from 2000 to 2016. Patients with pre- and postoperative pulmonary function tests assessed by spirometry were included. Postoperative changes in spirometry measurements were compared to PEH size as reflected by the percentage of intrathoracic stomach observed on preoperative contrast studies. Patients were stratified according to improvement in forced expiratory volume in 1 second (FEV1). Patients with >12% ('significant') improvement in FEV1 after surgery were compared to the remaining patient population. In total, 299 patients met the inclusion criteria. Symptomatic improvement in respiratory function was noted in all patients after PEH repair. Age, gender, BMI, presenting symptoms, Charlson comorbidity index as well as preoperative comorbidities did not significantly impact the functional outcome. Spirometry results improved in 80% of the patients, 21% of whom showed an improvement of >20% compared to the preoperative level. 'Significant' improvement in respiratory function was seen in 122 of 299 (41%) patients. Patients presenting with moderate and severe preoperative pulmonary obstruction demonstrated 'significant' improvement in FEV1 in 48% and 40% of cases, respectively. Large PEHs, characterized by a percentage of intrathoracic stomach >75%, was strongly associated with 'significant' improvement in FEV1 (P = 0.001). PEHs can impact subjective and objective respiratory status and surgical repair can result in a significant improvement in dyspnea and pulmonary function score that is independent of preoperative pulmonary disease. Gastric herniation of more than 75% was associated with higher possibility for improvement of pulmonary function tests. Patients with persistent and unexplained dyspnea and coexistent PEH should be assessed by an experienced surgeon for consideration of elective repair.

Gender Specific Differences in Prevalence and Risk Factors for Gastro-Esophageal Reflux Disease.

BACKGROUND: Gender-related factors might play an important role in the development of reflux esophagitis (RE) and symptomatic gastro-esophageal reflux disease (GERD). We aimed to evaluate the prevalence and risk factors for RE and symptomatic GERD and determine whether gender specific differences exist. METHODS: This study was conducted on a health cohort consisting of 10,158 participants who underwent comprehensive health screening. Lifestyles and gastrointestinal symptoms were investigated using a self-reported structured questionnaire. Questionnaires about menstrual status were added for the women. RESULTS: The prevalence of RE in men was significantly higher than that in women (10.6% vs. 2.0%, P < 0.001); however, symptomatic GERD showed predominance in women (6.2% vs. 2.5%, P < 0.001). Although the prevalence of RE gradually increased with the duration of menopause stratified by decade (P = 0.007), that of symptomatic GERD rapidly increased across the menopausal transit in women. Apart from common risk factors of obesity and current smoking for RE, over 70 years of age in women and hiatal hernia and hypertriglyceridemia in men were significant risk factors. In symptomatic GERD, high somatization was a common risk factor. Excessive alcohol drinking was a significant risk factor in men, but not in women. CONCLUSION: This study showed a predominance of RE in men, but a predominance of symptomatic GERD in women. In women, dynamic increase in the prevalence of GERD is closely related to the menopause conditions and its duration. There are specific risk factors for RE and symptomatic GERD according to gender differences.

Giant hiatal hernias.

Dyspnoea is most often caused by disorders of the respiratory and/or cardiovascular systems. Much less often it is brought about by the displacement of abdominal organs into the thoracic cage. Hiatal hernias may give rise to diagnostic difficulties, as both clinical and radiological symptoms suggest different disorders. Computed tomography is the method of choice when making a diagnosis. We have presented a series of 7 cases of giant hiatal hernias, each with a varying course of the disease, clinical symptoms, radiological features and prognoses. In two of the cases, the hernias were of a post-traumatic nature. Four cases of large diaphragmatic hernias were found in elderly patients (over 90 years old). An advanced age and numerous coexisting chronic diseases disqualified most of the patients from surgical treatment despite the hernias' large sizes. In only one case was fundoplication performed with a good end result. Two patients died, and an extensive hernia was the cause of one of the deaths. Upper gastrointestinal symptoms were present only in a few of the patients. An early diagnosis of giant hiatal hernia is crucial for the patients to undergo prompt corrective surgeries.

WDR73-related galloway mowat syndrome with collapsing glomerulopathy.

Galloway-Mowat syndrome (GAMOS [MIM 251300]) is a rare autosomal recessive disorder that manifests as a combination of nephrotic syndrome, brain abnormalities and developmental delay. It is a clinically and genetically heterogeneous disease. The WDR73 variations are associated with GAMOS1. Here we report two consanguineous families affected by GAMOS1. In the first family, three sisters are affected and in the second family, only one index case is identified. They all show a nephrotic syndrome, a neurological involvement and a collapsing glomerulopathy. The analysis of mutations of WDR73 revealed a new homozygous missense mutation NM_032856.3 c.293T > C; p.(Leu98Pro) in two patients from the first family, and a new homozygous missense mutation NM_032856.3: c.767G > A; p.(Arg256Gln) in the second one. This study extended the clinical and molecular spectrum of GAMOS1 with other cases associated with collapsing glomerulopathy and two novel WDR73 variations that are most likely pathogenic.

Life-threatening bleeding for a large cameron ulcer. A novel description of a tailored-surgical strategy: report of a case and literature overview.

Hiatal hernias (HHs) are usually divided into two main groups: sliding and para-esophageal (torsional) ones. Sometimes patients presenting HHs experience progressive anemia, whereas rarely an acute anemia with melena or hematemesis can occur. In such cases a Cameron ulcer should be suspected and a careful esophago-gastro-duodenoscopy (EGDS) with a meticulous inspection of the mucosal folds along the neck of the hernia is the best examination in order to find out the ulcer itself. In front of massive hemorrhage due to a Cameron erosion, the first aim should be the control of the bleeding itself, in order to ree1Romastablish hemodynamic stability. The Authors report the case of a 72-year-old man presenting a severe bleeding secondary to a large Cameron ulcer in a para-esophageal hiatal hernia. Firstly, a combined medical-endoscopic therapy was tried; the patient underwent transfusions of pooled red blood cells and endovenous anti-acid therapy combined with an operative endoscopic treatment; unfortunately this initial approach failed, therefore the patient was referred to surgery. The surgeons realized a minimally invasive atypical gastric resection associated with the HH repair; the post-operative course was uneventful and no other rebleeding episodes occurred. The urgency treatment of a life-threatening bleeding for Cameron ulcers remains a very challenging problem as no univocal and standardized recommendation has been described in literature since now. In this case-report the Authors make an overview of the current literature on the treatment of Cameron ulcers, describing a novel surgical technique for massive upper gastro-intestinal bleeding secondary to these lesions.

Homozygous splicing mutation in NUP133 causes Galloway-Mowat syndrome.

OBJECTIVE: Galloway-Mowat syndrome (GAMOS) is a neural and renal disorder, characterized by microcephaly, brain anomalies, and early onset nephrotic syndrome. Biallelic mutations in WDR73 and the 4 subunit genes of the KEOPS complex are reported to cause GAMOS. Furthermore, an identical homozygous NUP107 (nucleoporin 107kDa) mutation was identified in 4 GAMOS-like families, although biallelic NUP107 mutations were originally identified in steroid-resistant nephrotic syndrome. NUP107 and NUP133 (nucleoporin 133kDa) are interacting subunits of the nuclear pore complex in the nuclear envelope during interphase, and these proteins are also involved in centrosome positioning and spindle assembly during mitosis. METHODS: Linkage analysis and whole exome sequencing were performed in a previously reported GAMOS family with brain atrophy and steroid-resistant nephrotic syndrome. RESULTS: We identified a homozygous NUP133 mutation, c.3335-11T>A, which results in the insertion of 9bp of intronic sequence between exons 25 and 26 in the mutant transcript. NUP133 and NUP107 interaction was impaired by the NUP133 mutation based on an immunoprecipitation assay. Importantly, focal cortical dysplasia type IIa was recognized in the brain of an autopsied patient and focal segmental glomerulosclerosis was confirmed in the kidneys of the 3 examined patients. A nup133-knockdown zebrafish model exhibited microcephaly, fewer neuronal cells, underdeveloped glomeruli, and fusion of the foot processes of the podocytes, which mimicked human GAMOS features. nup133 morphants could be rescued by human wild-type NUP133 mRNA but not by mutant mRNA. INTERPRETATION: These data indicate that the biallelic NUP133 loss-of-function mutation causes GAMOS. Ann Neurol 2018;84:814-828.

GERD: Presence and Size of Hiatal Hernia Influence Clinical Presentation, Esophageal Function, Reflux Profile, and Degree of Mucosal Injury.

A hiatal hernia (HH) is a frequent finding in patients with gastroesophageal reflux disease (GERD). We examined a consecutive series of patients with GERD diagnosed by a 24-hour pH monitoring. Based on the presence and size of HH on barium swallow, patients were divided into the following groups: no HH, HH <3 cm, HH 3-5 cm and HH >5 cm. A total of 175 patients were included: 43 with no HH, 86 with HH <3 cm, 34 with HH 3-5 cm, and 12 with HH >5 cm. Patients with larger HH had more frequent episodes of coughing and wheezing associated with episodes of reflux. High-resolution manometry showed that the increasing size of the HH was associated with decreasing pressure of the lower esophageal sphincter and weaker peristalsis. Ambulatory pH monitoring revealed that patients with larger HH had more acid reflux, in both the distal and proximal esophagus. Endoscopy showed that patients with larger HH had more severe esophagitis. Fifty per cent of patients with HH >5.0 cm had Barrett's esophagus. These findings should guide gastroenterologists and surgeons in choosing the appropriate therapy in patients with GERD and large HH.