Developmental basis of trachea-esophageal birth defects.

Trachea-esophageal defects (TEDs), including esophageal atresia (EA), tracheoesophageal fistula (TEF), and laryngeal-tracheoesophageal clefts (LTEC), are a spectrum of life-threatening congenital anomalies in which the trachea and esophagus do not form properly. Up until recently, the developmental basis of these conditions and how the trachea and esophagus arise from a common fetal foregut was poorly understood. However, with significant advances in human genetics, organoids, and animal models, and integrating single cell genomics with high resolution imaging, we are revealing the molecular and cellular mechanisms that orchestrate tracheoesophageal morphogenesis and how disruption in these processes leads to birth defects. Here we review the current understanding of the genetic and developmental basis of TEDs. We suggest future opportunities for integrating developmental mechanisms elucidated from animals and organoids with human genetics and clinical data to gain insight into the genotype-phenotype basis of these heterogeneous birth defects. Finally, we envision how this will enhance diagnosis, improve treatment, and perhaps one day, lead to new tissue replacement therapy.

Primary midgut volvulus without intestinal malrotation in a young adult: a case report.

BACKGROUND: Midgut volvulus is a rare cause of acute abdomen characterized by a twisting of the entire small intestine around its mesenteric pedicle. It is a well-known complication of intestinal malrotation usually occurring in infants and young children. We report a rare case of a midgut volvulus without any underlying condition occurring in a young adult. CASE PRESENTATION: A 24-year-old male was admitted to our surgical department with symptoms and signs of small bowel obstruction. The abdominal computed tomography (CT) scan showed dilatation of the entire small intestine and a rotation of the mesentery. The patient underwent an urgent explorative laparoscopy with conversion to median laparotomy, revealing a midgut volvulus with marked intestinal ischemia. Mesenteric fixation was normal but the mesenteric pedicle was described as relatively narrow. The midgut volvulus was untwisted with subsequent recovery of the intestinal ischemia. RESULTS: The postoperative period was marked by prolonged ileus requiring nasogastric tube decompression that gradually resolved after 1 week. The patient was discharged on the tenth postoperative day. He had fully resumed his daily activities 1 month after surgery and had experienced no recurrent symptoms 6 months later. CONCLUSION: Primary midgut volvulus is an extremely rare condition that must be considered in all young adults presenting with intestinal obstruction without previous abdominal surgery. Early diagnosis and immediate surgical intervention are the key factors to a successful outcome.

[The 'missing' of the duodenum]. / Sluchai 'otsutstviia' dvenadtsatiperstnoi kishki.

The article presents the outcome in patient with duodenal congenital abnormality caused by defective intrauterine rotation of the intestinal tube with premature turn of back intestine.

Esophageal Atresia with or without Tracheoesophageal Fistula (EA/TEF): Association of Different EA/TEF Subtypes with Specific Co-occurring Congenital Anomalies and Implications for Diagnostic Workup.

BACKGROUND: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) represents the most common developmental malformation of the upper digestive tract. It is classified into six subtypes according to the classification of Vogt, depending on anatomical variation of this malformation. Around 50% of the patients with EA/TEF present additional anomalies, which often influence, next to the EA/TEF subtype, the overall prognosis of EA/TEF newborns. Here, we investigated the association of the different EA/TEF subtypes with co-occurring congenital anomalies in EA/TEF patients and demonstrate their implications for postnatal diagnostic workup. MATERIALS AND METHODS: We investigated 333 patients of a large German multicenter study born between 1980 and 2012. After evaluation of all available clinical records, 235 patients were included in our analysis. We compared our results with existing data. RESULTS: The highest risk for co-occurring anomalies was seen in patients with most common Vogt 3b (p = 0.024), especially for additional gastrointestinal anomalies (p = 0.04). Co-occurring anomalies of the skin were significantly more common in patients with subtype Vogt 2 (p = 0.024). A significant correlation was observed for an impaired neurodevelopmental outcome and EA/TEF Vogt 3a (p = 0.041). Patients with EA/TEF showed a higher risk to present with any additional congenital anomaly compared with the general population (p < 0.001). CONCLUSION: Our results warrant thorough clinical workup for gastrointestinal anomalies especially in patients with Vogt 3b. Moreover, it might be necessary to focus on a thorough aftercare for neurocognitive development in patients with Vogt 3a. The here presented observations need to be confirmed by future studies.

Preemptive Ladd Procedure in congenital diaphragmatic hernia and Abdominal Wall defects does not reduce the risk of future volvulus.

INTRODUCTION: Patients with congenital diaphragmatic hernia (CDH), gastroschisis, and omphalocele are prone to abnormalities of intestinal rotation and thus future midgut volvulus. Controversy exists whether routine preemptive Ladd procedure in this subgroup of asymptomatic patients is of value to reduce future volvulus. METHODS: The Pediatric Health Information System (PHIS) database was queried for neonates with CDH, gastroschisis, and omphalocele between January 2009 and September 2015. Standard univariate and multivariate analysis was completed to compare risk of volvulus between patients treated with a preemptive Ladd versus no Ladd (p<0.05). RESULTS: Seven thousand seven hundred forty-nine neonates with CDH (40%), gastroschisis (38%), omphalocele (14%), and abdominal wall malformation (NOS) (9%) were identified. Overall, 3.6% (n=279) had a preemptive. Thirty-two patients had subsequent volvulus. Ladd procedure did not reduce volvulus readmissions for any diagnosis and was associated with a significantly increased risk of volvulus for omphalocele patients (9.1% vs 0.1%, p<0.001). Overall, a Ladd procedure during the index admission was associated with a higher risk for volvulus (1.4% vs. 0.4%, p=0.021) and was associated with a 3.28 increased odds ratio of future volvulus (95% CI 1.12-9.68). CONCLUSION: Ladd procedure performed prophylactically in patients with CDH, gastroschisis, and omphalocele did not reduce subsequent volvulus. LEVEL OF EVIDENCE: III, Retrospective Comparative Study.

Neonatal intestinal obstruction associated with situs inversus totalis: two case reports and a review of the literature.

BACKGROUND: The association of neonatal intestinal obstruction with situs inversus totalis is extremely rare with only few cases reported in the literature to date. This association poses dilemmas in management. We present two such cases (of Indian origin), and briefly discuss the pertinent literature and measures to prevent unfavorable outcome. CASE PRESENTATION: Case 1: a 1-month-old preterm (1300 g) male neonate belonging to Hindu (Indian) ethnicity presented with recurrent bile-stained vomiting, non-passage of stools and epigastric fullness. A babygram and upper gastrointestinal contrast studies revealed situs inversus and suggested proximal jejunal obstruction with midgut volvulus. Exploration confirmed situs inversus totalis along with reverse rotation and midgut volvulus. There was a small gangrenous area in the proximal jejunal loop. A Ladd's procedure, resection of the gangrenous jejunal loop, and jejunojejunal anastomosis was performed. Note was made of the unusual appearance of the intestines suggestive either of fibrous or fatty infiltration. Postoperatively, our patient developed septicemia and died. Case 2: a 4-day-old female neonate belonging to Hindu (Indian) ethnicity, small (1320 g) for gestation, presented with history of non-passage of meconium since birth, refusal to accept feeds, and episodes of recurrent bilious vomiting with abdominal distension. A plain radiogram revealed situs inversus and proximal jejunal obstruction. Ultrasonography of her abdomen revealed renal dysplastic changes in both her kidneys. Laparotomy confirmed multiple jejunoileal atresias with situs inversus totalis. Resection anastomoses was performed for multiple atresias. Our patient passed a few pellets of meconium stools postoperatively; feeds were started gradually on the sixth day. Our patient gradually developed oliguria and renal failure, followed by respiratory distress and generalized edema requiring ventilatory support. She died later due to multiorgan failure. CONCLUSIONS: Clinicians should have high index of suspicion for malrotation with midgut volvulus or intestinal atresias in neonates of situs inversus presenting with bilious vomiting. The surgical treatment should follow the same surgical principles. In situs inversus, because of transposition of viscera, midgut volvulus may occur in an anticlockwise direction, hence derotation is performed clockwise. Prognosis was poor in our series because of low birth weight, late presentation, presence of gangrenous locus in the small bowel and development of septicemia in our first case and multiorgan fibrosis/dysplasia in our second case. Early diagnosis and timely referral is paramount for favorable outcome.

Impact of a Newly Developed Short Double-Balloon Enteroscope on Stent Placement in Patients with Surgically Altered Anatomies.

A newly developed short double-balloon enteroscope with a working channel enlarged to a diameter of 3.2 mm is a novel innovation in stent placement for patients with surgically altered anatomies. Herein, we report three patients in whom this new scope contributed to an efficient technique and ideal treatment. In the first case, the double guidewire technique was efficient and effective for multiple stent placements. In the second case, covered self-expandable metal stent (SEMS) placement, which is the standard treatment for malignant biliary obstruction, could be performed in a technologically sound and safe manner. In the third case, SEMS placement was performed as palliative treatment for malignant afferent-loop obstruction; this procedure could be performed soundly and safely using the through-the-scope technique. The wider working channel of this new scope also facilitates a smoother accessory insertion and high suction performance, which reduces procedure time and stress on endoscopists. Furthermore, this new scope, which has advanced force transmission, adaptive bending, and a smaller turning radius, is expected to be highly successful in both diagnosis and therapy for various digestive diseases in patients with surgically altered anatomies.

The risk of midgut volvulus in patients with abdominal wall defects: A multi-institutional study.

BACKGROUND: The management of malrotation in patients with congenital abdominal wall defects has varied among surgeons. We were interested in investigating the risk of midgut volvulus in patients with gastroschisis and omphalocele to help determine if these patients may benefit from undergoing a Ladd procedure. METHODS: A retrospective chart review was performed for all patients managed at three institutions born between 1/1/2000 and 12/31/2008 with a diagnosis of gastroschisis or omphalocele. Patient charts were reviewed through 12/31/2012 for occurrence of midgut volvulus or need for second laparotomy. RESULTS: Of the 414 patients identified with abdominal wall defects, 299 patients (72%) had gastroschisis, and 115 patients (28%) had omphalocele. The mean gestational age at birth was 36.1±2.3weeks, and the mean birth weight was 2.57±0.7kg. There were a total of 8 (1.9%) cases of midgut volvulus: 3 (1.0%) patients with gastroschisis compared to 5 patients (4.4%) with omphalocele (p=0.04). CONCLUSIONS: Patients with omphalocele have a greater risk of developing midgut volvulus, and a Ladd procedure should be considered during definitive repair to mitigate these risks. LEVEL OF EVIDENCE: III; retrospective comparative study.

Total midgut volvulus in adults with intestinal malrotation. Report of eleven patients.

OBJECTIVE: Total small-intestinal volvulus with malrotation (TSIVM) classically presents in the neonatal period; it occurs much less frequently in the adult and is often misdiagnosed. Prognosis is directly related to the degree and duration of intestinal ischemia. Our goal is to describe our experience with TSIVM in the adult, to identify any specific findings and to discuss its management. METHOD: Eleven patients who had undergone surgery for TSIVM at three centers between 1992 and 2012 were included. Surgery was performed as an emergency for five patients and surgery was elective for six. RESULTS: Mean follow-up was 63 months (range: 12-270). Six patients had had previous abdominal surgery. In nine cases, the diagnosis of TSIVM was made preoperatively, mainly by CT scan in eight cases. Seven patients had associated congenital failure of retroperitoneal fixation of the right colon and all of these underwent a Ladd procedure. The mortality rate was zero. Of the five patients who underwent emergency surgery, three required intestinal resections, one of whom developed a short bowel syndrome. The six patients who underwent surgery electively had no surgical complications. CONCLUSION: TSIVM is a very unusual finding in adult patients. The diagnosis can be made by CT scan with IV and oral contrast, but it often comes to light only at the time of surgery, even though the patients have often had recurrent episodes of abdominal symptomatology that dated back to childhood. The Ladd procedure, consisting of division of Ladd's bands, widening of the mesentery, and incidental appendectomy, remains the standard surgical repair. Digestive surgeons who care for adults should be familiar with this procedure, and it should be performed, as often as possible, with the assistance of a pediatric surgeon.

[Mesenteric volvulus associated with mesenteric lipoma: about a case]. / Volvulus du mesentere sur lipome mesenterique: à propos d'un cas.

We report the case of a 7-year old patient presenting for acute paroxysmal abdominal pain at the level of epigastrium associated with vomiting without involving blockage of materials and gas. Clinical examination and laboratory tests were unremarkable. Abdominal ultrasound was requested as a first line investigationa and showed a right echogenic homogeneous flank and iliac fossa mass with regular contours without vascular Doppler signal and associated with "whirl sign" of mesenteric vessels. On CT scan this mass was seen as a well-defined lipoma formation, exerting a mass effect on the cecum, which was in direct contact with mesenteric volvulus. Arrangement of the mesenteric vessels at their origin was normal. The diagnosis of mesenteric volvulus associated with lipoma was retained. Surgical management and histological analysis of the surgical specimen confirmed the diagnosis. This clinical case aims to highlight the contribution of ultrasound and CT scan in the diagnosis of midgut volvulus.

The risk of volvulus in abdominal wall defects.

BACKGROUND: Congenital abdominal wall defects are associated with abnormal intestinal rotation and fixation. A Ladd's procedure is not routinely performed in these patients; it is believed intestinal fixation is provided by adhesions that develop post-repair of the defects. However, patients with omphalocele may not have adequately protective postoperative adhesions because of difference in the inflammatory state of the bowel wall and in repair strategy. The aim of this study is to describe the occurrence of midgut volvulus in patients with gastroschisis or omphalocele. METHODS: A retrospective chart review was performed for all patients managed in a single institution born between 1/1/2000 and 12/31/2008 with a diagnosis of gastroschisis or omphalocele. Patient charts were reviewed through 12/31/2012 for occurrence of midgut volvulus or need for second laparotomy. RESULTS: Of the 206 patients identified with abdominal wall defects, 142 patients (69%) had gastroschisis and 64 patients (31%) had omphalocele. Patients' follow up ranged from 4 years to 13 years. The median gestational age was 36 weeks (26-41 weeks) and the median birth weight was 2.42 kg (0.8-4.87 kg). None of the patients with gastroschisis developed midgut volvulus, however two patients (3%) with omphalocele developed midgut volvulus. CONCLUSIONS: No patients with gastroschisis developed midgut volvulus. Therefore, the current practice of not routinely performing a Ladd's procedure is a safe approach during surgical repair of gastroschisis. The two cases of volvulus in patients with omphalocele may be related to less bowel fixation. It is necessary to examine current practice in regards to the need for assessing the risk of volvulus during omphalocele closure and counseling of these patients. This assessment may be achieved via routine examination of the width of the small bowel mesenteric base, whenever feasible; however, the sample size is relatively small to draw any definitive conclusions.

The heterogeneity of non-motor symptoms of Parkinson's disease.

In addition to motor symptoms, patients with Parkinson's disease (PD) may experience non-motor symptoms (NMS), more often with more advanced disease stage. However, the clinical feature of the NMS and potential risk factors that affect NMS in idiopathic PD patients remain unclear. 493 PD patients diagnosed with PD via the UK. Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria and 93 healthy control subjects (CN) were recruited in the current study. Questionnaires were used to assess the NMS, motor symptoms, cognitive function, and disease severity in both groups. Levodopa daily dose was calculated in PD patients. Multivariate linear regression analysis was used to identify the risk factors that potentially affect NMS in PD patients. The results showed that, the NMS occurrence and positive endorsement rate of PD patients were significantly higher compared to CN subjects. Multiple stepwise regression analysis found the motor symptom was the only factor that affected NMS in PD patients within five years of the disease course, whereas motor symptoms, cognitive function, disease severity and Levodopa daily dose significantly affected NMS if the disease course was more than five years. These findings demonstrated that NMS are affected by several risk factors at different stages of PD. The distribution of difference NMS is associated with the severity of motor symptoms and the dosage of anti-PD medications in Chinese PD patients.

Novel MNX1 mutations and clinical analysis of familial and sporadic Currarino cases.

Currarino Syndrome (CS) is a rare congenital malformation characterized by three major clinical aspects: sacral anomalies, anorectal malformation and presacral mass. In familial settings the disorder is transmitted as autosomal dominant trait, with a wide phenotype variability and low penetrance. The causative gene of CS is the motor neuron and pancreas homeobox-1 (MNX1), mapped at 7q36, and coding for a transcription factor. Mutations in the MNX1 have been implicated in almost all familial but only in 30% of sporadic cases. In our cohort of 28 CS cases, 8 were familiar, 18 were sporadic and 2 were not determined cases. We performed mutational analysis of MNX1 in all cases by DNA sequencing as well as by Multiplex Ligation-dependent Probe Amplification (MLPA) in those CS cases where no MNX1 mutations were found, to exclude a MNX1 heterozygous loss. We identified 10 novel and 4 recurrent mutations. Among the novel mutations, 2 were frameshift variants (p.Ser4IlefsX52, p.Phe248SerfsX35), 6 were missense variants (p.Pro27Leu, p.Gly103Arg, p.Leu254Pro, p.Leu278Pro, p.Glu282Lys, p.Arg292Gly), one was a non-sense variant (p.Lys297X), and the last one was a synonymous variant (p.Gln290Gln). Mutated patients showed a variability of phenotypes but all share at least the association of sacral agenesis and presacral mass, and this co-occurrence can constitute a pathognomonic sign to perform MNX1 analysis. Genetic heterogeneity could be a possible explanation for some of the sporadic not mutated patients even if a mis-diagnosis could not be excluded. Finally, we provide an up-date of the more recent literature, reporting a total number of 82 MNX1-CS related mutations.

A rare complication of small bowel intussusception: report of a case and review of literature.

Volvulus and intussusception are rare conditions in children. We describe an unusual case of intussusception due to a solitary Peutz-Jeghers type hamartomatous polyp complicated by volvulus, which occurred in an 11-year-old girl. A laparotomy allows to successfully treat the pathology. The postoperative course was favourable. We discuss the clinical findings and the values of the preoperative instrumental diagnosis. The literature is reviewed. Identifying a midgut volvulus, as complication of a small bowel intussusception, during the diagnostic phase could help in choosing the most appropriate surgical approach.