BALB/c and C57BL/6 mouse strains influence gastric function outcomes with administration of cisplatin and dexamethasone

Abstract Our aim was to evaluate the effects of cisplatin and dexamethasone alone and combined on gastric contractility and histomorphometry of BALB/c and C57BL/6 mice. BALB/c and C57BL/6 male mice (8-week-old) were randomly separated into: Control; Cisplatin (7.5 mg/Kg); Dexamethasone (2.0 mg/Kg); and Dexamethasone plus Cisplatin (2.0 mg/Kg of dexamethasone 1-hour prior to 7.5 mg/Kg of cisplatin). Drugs were administered intraperitoneally for three days. Body weight and food intake were evaluated on 2nd day. Alternating Current Biosusceptometry technique was employed to measure gastric contractions on 3rd day. Afterward, mice were killed for gastric histomorphometric analysis. Cisplatin decreased food intake and caused bradygastria in BALB/c mice; however, the amplitude of gastric contractions decreased in both BALB/c and C57BL/6. Dexamethasone and cisplatin combined restored the gastric frequency and food intake only in BALB/c, but drug combination reduced the gastric amplitude of contractions in both strains. Dexamethasone alone increased gastric mucosa thickness in C57BL/6 and decreased muscular thickness in BALB/c. In conclusion, the mouse strains presented differences in acute effects of cisplatin and dexamethasone alone and combined on gastric function. This reinforces the importance of choosing the appropriate mouse strain for studying the acute effects of drugs on the gastrointestinal tract.

Development of microparticles and microparticulated tablets containing piperine

Abstract Piper nigrum (black pepper) is used in Indian traditional medicine and its main alkaloid, Piperine (PIP), presents antioxidant, antitumor and neuroprotective pharmacological properties. This substance is insoluble in aqueous media and can irritate the gastrointestinal tract. Aiming to avoid these inconvenient characteristics and enable PIP oral administration, this study suggested the PIP microencapsulation through the emulsion-solvent evaporation method and the preparation of microparticulated tablets by direct compression. An UV-spectroscopy method was validated to quantify PIP. Microparticles and microparticulated tablets were successfully obtained and the microparticles exhibited excellent flow. The scanning electron microscopy images showed that PIP microparticles were intact after compression. The in vitro release showed a controlled release of PIP from microparticles and PIP microparticles from tablets in comparison to PIP and PIP tablets. The release profiles of PIP microparticles and the microparticulated tablets were similar. Therefore, tablets containing PIP microparticles are promising multiparticulated dosage forms because a tablet allows microparticles administration and the intact ones promote a controlled release, decreasing its irritating potential on the mucosa.

Congenital malformations of the gastrointestinal tract in neonates at aristide le dantec university hospital in Dakar: Concerning 126 cases.

Objective: Congenital malformations of the gastrointestinal tract are one of the major causes of neonatal mortality, especially in developing countries. The aim of this study is to assess the overall management of gastrointestinal malformations. Patients and Methods: The study design is monocentric and retrospective. It includes all newborns aged 1-28 days with malformations of the gastrointestinal tract between 1st January 2014 and 31st December2018, at the Paediatric Surgery Department of Aristide Le Dantec University Hospital in Dakar. Data were collected by studying patient's records and surgical procedures. Results: During the five-year study, 405 newborns with congenital anomalies were admitted to our hospital. A total of 126 newborns were diagnosed with gastrointestinal tract malformations. The incidence was 25.2 cases a year. The sex distribution was 74 boys (58.7%) and 52 girls (41.2%). The mean age at diagnosis was 7.4 ± 3.2 days. Two cases were diagnosed antenatal (1.59%). The mean time to post-natal diagnosis was 6.5 ± 2.1 days. The most common malformation was oesophageal atresia with 43 cases (34.1%). The average time between diagnosis and surgery was 48 h. Out of the 126 cases, 77 (61.1%) received surgery and 49 (38.9%) died before surgery. The main causes of pre-operative death were intricate and dominated by lung infections (42.9%). Among the 77 newborns, who received surgery, 38 (%) had a simple post-operative course, 39 (50.6 %) died. Post-operative deaths were dominated by anaesthetic complications (30.8%), lung infections (46.1%). The overall mortality was 69.8% (n = 88). Conclusion: The low socio-economic status, poor pre-natal diagnosis, prematurity, post-natal diagnostic delay, obsolete medical equipment and the lack of neonatal intensive care units were identified as the major factors for high mortality in neonates with gastrointestinal tract malformations in a developing country.

Effects of reducing postprandial hyperglycemia and metabolism of acetate wheat starch on healthy mice

Abstract Recently, the acetate wheat starch (AWS) has been prepared by acetylation with an acetyl content of 2.42%, containing of rapidly digestible starch (RDS), slowly digestible starch (SDS) and resistant starch (RS) with 25.0%; 22.9% and 34.5%, respectively. In this study, this kind of starch was continuously evaluated with the postprandial blood glucose response and determined short-chain fatty acids (SCFAs) metabolized from AWS in the gastrointestinal tract of healthy mice by HPLC. The result showed that the mice fed with AWS exhibited a very limited increase in blood glucose level and remained stable for 2 hours after meals efficiently comparing with the control group fed with natural wheat starch (NWS). Simultaneously, the content of SCFAs produced in the caecum of the mice fed with AWS was significantly higher than mice fed with NWS, especially with acetic and propionic acids by 28% and 26%, respectively. Thus, AWS has shown to limit the postprandial hyperglycemia in mice effectively through the resistance to amylase hydrolysis in the small intestine. When going into the caecum, it is fermented to form SCFAs providing a part of energy for the body's activities, avoiding rotten fermentation causing digestive disorders which are inherent restrictions of normal high cellulose and fiber food.

Divertículo de Meckel perforado por un cuerpo extraño / Meckel's Diverticulum Perforated by a Foreign Body

Introducción: El divertículo de Meckel es la anomalía congénita más frecuente del tracto gastrointestinal. Por lo general, cursa asintomático, y su diagnóstico es transoperatorio. Cuando presenta síntomas se deben a sus complicaciones, de las cuales la perforación constituye solo el 0,5 por ciento. Objetivo: Describir las características clínico-quirúrgicas de la presentación de un paciente con divertículo de Meckel perforado por cuerpo extraño. Caso clínico: Paciente adulto de 46 años de sexo masculino, piel blanca, que acude con dolor generalizado en el abdomen que se trasladó a Fosa Ilíaca Derecha, con febrícula. Se interviene quirúrgicamente y se halla divertículo de Meckel perforado por cuerpo extraño. Conclusiones: El pronóstico de esta enfermedad depende de la evolución, diagnóstico precoz y tratamiento aplicado en las distintas complicaciones, así como de la decisión de realizar tratamiento quirúrgico en los hallazgos casuales(AU)

Introduction: Meckel's diverticulum is the most frequent congenital anomaly of the gastrointestinal tract. It is generally asymptomatic, with an intraoperative diagnosis. When it presents symptoms, they are due to its complications, of which perforation accounts for only 0.5 percent. Objective: To describe the clinical-surgical characteristics of a patient who presented with a Meckel's diverticulum perforated by a foreign body. Clinical case: 46-year-old adult patient of the male sex and white skin, who presents with generalized pain in the abdomen that moved to the right iliac fossa and low-grade fever. The patient underwent surgery and a Meckel's diverticulum was found, perforated by a foreign body. Conclusions: The prognosis of this disease depends on the evolution, early diagnosis and applied treatment according to the different complications, as well as on the decision to perform surgical treatment in accidental findings(AU)

Combined thoraco-laparoscopic surgery for neonatal alimentary tract duplication.

Transdiaphragmatic duplication of digestive tract in infants is very rare. Open surgery is the main surgical treatment. We report the clinical data of a child with gastrointestinal duplication across the diaphragm who underwent thoraco-laparoscopic surgery at 12 days were retrospectively analyzed, and to explore the experience of thoraco-laparoscopic surgery in the treatment of alimentary tract duplication across the diaphragm in children, we believe minimally invasive surgical resection using thoracolaparoscopy is safe, effective and clinically feasible, focusing on the skilled use of the technique to achieve the ideal surgical effect and appearance.

Peutz-Jeghers syndrome: an unusual autopsy finding in pregnancy

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant polyposis entity that often remains undiagnosed. The major problems associated with PJS are acute complications due to (i) polyp-related intestinal obstruction, (ii) intussusception, and (iii) the risk of cancer in the long-term. We report the case of a 32-year-old female who presented at the emergency room with signs of acute abdomen and died during the clinical workup. She had a one-month history of nausea, vomiting, and diarrhea and was pregnant at about 30 weeks. There was no contributing past history except for undergoing small bowel resection in infancy. The postmortem examination revealed multiple arborizing polyps throughout the gastrointestinal tract, chiefly in the small bowel. Intestinal obstruction was found at the proximal jejunum with necrosis, perforation, and peritonitis. Histologically, the polyps were composed of tree branch-like bundles of smooth muscle covered by normal-appearing glandular epithelium, confirming the diagnosis of hamartomatous polyps. No malignant or premalignant lesions were detected in the gastrointestinal tract or other organs. This case was an opportunity to analyze the natural history and the pathological features of the Peutz-Jeghers syndrome in an adult and to investigate the presence of neoplastic lesions associated with this condition.

Evolution of Resting Energy Expenditure, Respiratory Quotient, and Adiposity in Infants Recovering from Corrective Surgery of Major Congenital Gastrointestinal Tract Anomalies: A Cohort Study.

This cohort study describes the evolution of resting energy expenditure (REE), respiratory quotient (RQ), and adiposity in infants recovering from corrective surgery of major congenital gastrointestinal tract anomalies. Energy and macronutrient intakes were assessed. The REE and RQ were assessed by indirect calorimetry, and fat mass index (FMI) was assessed by air displacement plethysmography. Longitudinal variations over time are described. Explanatory models for REE, RQ, and adiposity were obtained by multiple linear regression analysis. Twenty-nine infants were included, 15 born preterm and 14 at term, with median gestational age of 35.3 and 38.1 weeks and birth weight of 2304 g and 2935 g, respectively. In preterm infants, median REE varied between 55.7 and 67.4 Kcal/kg/d and median RQ increased from 0.70 to 0.86-0.92. In term infants, median REE varied between 57.3 and 67.9 Kcal/kg/d and median RQ increased from 0.63 to 0.84-0.88. Weight gain velocity was slower in term than preterm infants. FMI, assessed in a subset of 15 infants, varied between a median of 1.7 and 1.8 kg/m2 at term age. This low adiposity may be related to poor energy balance, low fat intakes, and low RQ¸ that were frequently recorded in several follow-up periods.

Gastrointestinal pain.

Gastrointestinal (GI) pain - a form of visceral pain - is common in some disorders, such as irritable bowel syndrome, Crohn's disease and pancreatitis. However, identifying the cause of GI pain frequently represents a diagnostic challenge as the clinical presentation is often blurred by concomitant autonomic and somatic symptoms. In addition, GI pain can be nociceptive, neuropathic and associated with cancer, but in many cases multiple aetiologies coexist in an individual patient. Mechanisms of GI pain are complex and include both peripheral and central sensitization and the involvement of the autonomic nervous system, which has a role in generating the symptoms that frequently accompany pain. Treatment of GI pain depends on the precise type of pain and the primary disorder in the patient but can include, for example, pharmacological therapy, cognitive behavioural therapies, invasive surgical procedures, endoscopic procedures and lifestyle alterations. Owing to the major differences between organ involvement, disease mechanisms and individual factors, treatment always needs to be personalized and some data suggest that phenotyping and subsequent individual management of GI pain might be options in the future.

Over-the-scope clip management of non-acute, full-thickness gastrointestinal defects.

BACKGROUND: Endoscopic management of full-thickness gastrointestinal tract defects (FTGID) has become an attractive management strategy, as it avoids the morbidity of surgery. We have previously described the short-term outcomes of over-the-scope clip management of 22 patients with non-acute FTGID. This study updates our prior findings with a larger sample size and longer follow-up period. METHODS: A retrospective analysis of prospectively collected data was conducted. All patients undergoing over-the-scope clip management of FTGID between 2013 and 2019 were identified. Acute perforations immediately managed and FTGID requiring endoscopic suturing were excluded. Patient demographics, endoscopic adjunct therapies, number of endoscopic interventions, and need for operative management were evaluated. Success was strictly defined as complete FTGID closure. RESULTS: We identified 92 patients with 117 FTGID (65 fistulae and 52 leaks); 27.2% had more than one FTGID managed simultaneously. The OTSC device (Ovesco Endoscopy, Tubingen, Germany) was utilized in all cases. Additional closure attempts were required in 22.2% of defects. With a median follow-up period of 5.5 months, overall defect closure success rate was 66.1% (55.0% fistulae vs. 79.6% leaks, p = 0.007). There were four mortalities from causes unrelated to the FTGID. Only 14.9% of patients with FTGID underwent operative management. There were no complications related to endoscopic intervention and no patients required urgent surgical intervention. CONCLUSIONS: Over-the-scope clip management of FTGID represents a safe alternative to potentially morbid operative intervention. When strictly defining success as complete closure of all FTGID, endoscopy was successful in 64.4% of patients with only a small minority of patients ultimately requiring surgery.

Deletion of narfl leads to increased oxidative stress mediated abnormal angiogenesis and digestive organ defects in zebrafish.

Nuclear prelamin A recognition factor-like (NARFL) is a human protein that participates in cytosolic iron-sulfur (Fe-S) protein biogenesis and cellular defense against oxidative stress. Previous studies of Narfl knockout mice did not reveal well the regulatory mechanisms of embryonic development mediated by Narfl because the homozygous mice die in utero. Here, we investigated the function of narfl in an established zebrafish knockout model by taking advantage of zebrafish external fertilization and ease of embryonic development examination. Our experiments showed that narfl deletion resulted in larvae lethality, subintestinal vessel (SIV) malformation and digestive organ defects in the early stages of embryonic development. Biochemical analyses and western blot revealed increased oxidative stress and upregulated hypoxia-inducible factor-1α (HIF-1α) expression in narfl-/- fish. The use of HIF-1α inhibitor 2-methoxyestradiol (2ME2) for the treatment of mutants partially rescued the SIV sprouting. These results suggest that narfl deletion causes increased oxidative stress and subintestinal vessel malformation, which further influence the development of digestive organs and might contribute to the lethality of the narfl knockout fish.

Management and outcomes of gastrointestinal congenital anomalies in low, middle and high income countries: protocol for a multicentre, international, prospective cohort study.

INTRODUCTION: Congenital anomalies are the fifth leading cause of death in children <5 years of age globally, contributing an estimated half a million deaths per year. Very limited literature exists from low and middle income countries (LMICs) where most of these deaths occur. The Global PaedSurg Research Collaboration aims to undertake the first multicentre, international, prospective cohort study of a selection of common congenital anomalies comparing management and outcomes between low, middle and high income countries (HICs) globally. METHODS AND ANALYSIS: The Global PaedSurg Research Collaboration consists of surgeons, paediatricians, anaesthetists and allied healthcare professionals involved in the surgical care of children globally. Collaborators will prospectively collect observational data on consecutive patients presenting for the first time, with one of seven common congenital anomalies (oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation and Hirschsprung's disease).Patient recruitment will be for a minimum of 1 month from October 2018 to April 2019 with a 30-day post-primary intervention follow-up period. Anonymous data will be collected on patient demographics, clinical status, interventions and outcomes using REDCap. Collaborators will complete a survey regarding the resources and facilities for neonatal and paediatric surgery at their centre.The primary outcome is all-cause in-hospital mortality. Secondary outcomes include the occurrence of post-operative complications. Chi-squared analysis will be used to compare mortality between LMICs and HICs. Multilevel, multivariate logistic regression analysis will be undertaken to identify patient-level and hospital-level factors affecting outcomes with adjustment for confounding factors. ETHICS AND DISSEMINATION: At the host centre, this study is classified as an audit not requiring ethical approval. All participating collaborators have gained local approval in accordance with their institutional ethical regulations. Collaborators will be encouraged to present the results locally, nationally and internationally. The results will be submitted for open access publication in a peer reviewed journal. TRIAL REGISTRATION NUMBER: NCT03666767.

Two synchronous congenital neck masses with facial nerve weakness.

OBJECTIVE: To describe a case of a complex neck mass with final pathology significant for two synchronous lesions, a type 1 branchial cleft cyst and an enteric duplication cyst, and to discuss its management given the unique presentation.

Chinese expert consensus on diagnosis and management of acquired respiratory-digestive tract fistulas.

Acquired respiratory-digestive tract fistulas occur with abnormal communication between the airways and digestive tract, causing the interflow of gas and liquid. Despite advances in surgical methods and the development of multimodal therapy in recent years, patients with acquired respiratory-digestive tract fistulas continue to exhibit unfavorable clinical outcomes. Therefore, in order to guide clinical practice in China, the Respiratory and Cancer Intervention Alliance of the Beijing Health Promotion Association organized a group of experienced experts in the field to develop this consensus document. Based on a study of clinical application and expert experience in the diagnosis and management of acquired respiratory-digestive tract fistulas at home and abroad, an Expert Consensus was developed. The panelists recruited comprised experts in pulmonology, oncology, thoracic surgery, interventional radiology, and gastroenterology. PubMed, Chinese Biology Abstract, Chinese Academic Journal, and Wanfang databases were used to identify relevant articles. The guidelines address etiology, classification, pathogenesis, diagnosis and management of acquired respiratory-digestive tract fistulas. The statements on treatment focus on the indications for different procedures, technical aspects, and preprocedural, post-procedural and complication management. The proposed guidelines for the diagnosis and management of acquired respiratory-digestive tract fistulas are the first to be published by Chinese experts. These guidelines provide an in-depth review of the current evidence and standard of diagnosis and management.

Antimesenteric gastrointestinal tract duplication undergoing non-ulcerative perforation.

Duplications of the gastrointestinal tract are rare malformations, most commonly presenting as cystic structures growing within the smooth muscle wall. Very rarely, they are completely detached from the tract. Several theories have been proposed regarding their embryological development, but no single one has been able to account for all of the described variants. The most common type of duplication is related to the small bowel and develops at its mesenteric border, assuming a spherical or tubular shape. Their clinical manifestations vary, depending mainly on their localization and size. Most commonly, they cause subacute abdominal pain and intestinal obstruction in children of less than two years of age. We present a case of an 8.5-year-old girl, investigated for right lower quadrant abdominal pain. On ultrasound scan, a cystic mass indicative of a duplication cyst was discovered and she underwent a laparotomy. A tense cystic spherical mass 2.2 cm in diameter was excised from the terminal ileum, 4 cm from the ileocecal valve. The cyst had the characteristics of a gastrointestinal tract duplication, except from the fact that it was located on the antimesenteric border of the intestine. On the other hand, the lesion did not present the characteristic features of a Meckel's diverticulum. According to our knowledge, this is the first report of an intestinal duplication cyst appearing on the antimesenteric intestinal border.

Endoscopic retrograde cholangiopancreatography with double balloon enteroscope in patients with altered gastrointestinal anatomy: A meta-analysis.

BACKGROUND/AIMS: The aim of this study was to evaluate the effectiveness and safety of endoscopic retrograde cholangiopancreatography with double balloon enteroscope (DBE-ERCP) in patients with altered gastrointestinal anatomy in a meta-analysis. MATERIALS AND METHODS: A comprehensive literature search was conducted on PubMed, EMBASE, and Cochrane library covering the period from January 2001 to December 2015. Data were selected and abstracted from eligible studies and were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. RESULTS: Ten studies involving a total of 301 patients were included in the analysis. The pooled enteroscopy, diagnostic, and therapeutic success rates were 89.75% [95% confidence interval (CI): 79.65-94.30%], 79.92% (95% CI: 68.06-89.59%), and 63.55% (95% CI: 53.70-72.86%), respectively. DBE-ERCP-related complications occurred in 18 patients including perforation (5), pancreatitis (3), cholangitis (9), and bleeding (1). The incidence of DBE-ERCP-related complication was 6.27% (95% CI: 2.61-11.38%). CONCLUSION: Diagnostic and therapeutic DBE-ERCPs are feasible in patients with altered gastrointestinal anatomy. DBE-ERCP may be considered when pancreaticobiliary diseases occur in patients undergoing Roux-en-Y reconstruction or pancreaticoduodenectomy.

Anorectal malformations, associated congenital anomalies and their investigation in a South African setting.

PURPOSE: This study was undertaken to investigate the types of anorectal malformations (ARM), incidence of associated abnormalities and investigative methods used in patients treated at Red Cross War Memorial Children's Hospital and to determine whether these are in keeping with recent literature. Mortality rates were also reviewed. METHODS: A retrospective review of patients with ARM between 1993 and 2016 was undertaken. Clinical notes were reviewed and correlated with radiology and cardiac databases. Abnormalities were grouped according to genitourinary, musculoskeletal, gastrointestinal and cardiovascular systems. The data were separated into three periods to ascertain whether the workup strategy had changed over the years. RESULTS: A total of 282 patients were included. There were 134 (47.5%) high and 116 (41.1%) low lesions and unspecified in 32 (11.3%) patients. There were 59 (20.9%) vestibular fistulae, 46 (16.3%) combined rectourethral fistulae (rectoprostatic, rectobulbar and unspecified rectourethral) and 42 (14.9%) perineal fistulae. Associated abnormalities were detected in 152/221 (69%). Abnormalities were: Genitourinary 88/204 (43.1%), musculoskeletal 80/188 (42.5%), cardiac 44/218 (20.1%) and gastrointestinal 12/216 (5.6%). Twenty patients demised. CONCLUSION: Vestibular fistulae were most common followed by rectourethral and perineal fistulae. Musculoskeletal and genitourinary abnormalities were the most common associated findings. The mortality rate was 7% and cardiac lesions contributed to mortality. As knowledge of ARM improved, so has awareness of associated malformations. This has led to improved, more active workup, in keeping with the latest literature.