Translational gastroenterology and hepatology最新文献

There are several esophageal disorders that can occur in the pediatric population. Eosinophilic esophagitis (EoE) is an eosinophil predominant inflammatory disease of the esophagus that was first characterized in the early 1900's. EoE is the most common pediatric esophageal inflammatory condition after gastroesophageal reflux disease (GERD). Longstanding GERD is a known risk factor for the development of Barrett's esophagus (BE) in both children and adults. BE is associated with the development of dysplasia and, if left undiagnosed, may progress to the development of esophageal adenocarcinoma (EAC). EAC and esophageal squamous cell carcinoma (ESCC) comprise the majority of childhood esophageal malignant neoplasms. The prevalence of EoE continues to rise within the pediatric population. On the other hand, both BE and esophageal neoplasms remain extremely rare in children. The relationship between a chronic inflammatory condition like EoE to BE and/or esophageal neoplasms remains unclear. The current research of these disease entities is prioritized to further understanding the disease pathogenesis and disease progression, exploring new diagnostic modalities, and developing novel treatments or less invasive therapeutic options. The focus of the following narrative review is to provide a summary of the current clinical practices, future research and their implications on these various esophageal disorders.

Achalasia is a rare condition affecting esophageal motility in children. In a manner similar to the disease found in the adult population, children experience symptoms of dysphagia, regurgitation, and chest pain due to a failure of relaxation of the lower esophageal sphincter. Standard diagnostic approaches include upper endoscopy and esophageal manometry. New developments in diagnosis include high-resolution esophageal manometry and the endoscopic functional lumen imaging probe. Therapies available include endoscopic balloon dilations and botulinum toxin injections into the lower esophageal sphincter, as well as surgical interventions. The Heller myotomy was first described in 1913; since then, there have been many modifications to the procedure to improve outcomes and lower morbidity. Currently, the most commonly performed surgical procedure is the laparoscopic Heller myotomy, in which the sphincter muscle is divided using longitudinal incisions with or without a partial fundoplication procedure. In recent years, per oral endoscopic myotomy (POEM) is gaining support as a viable natural orifice therapy for achalasia. Complications of POEM occur at a relatively low rate, and outcomes following the procedure have been promising. The treatment of end-stage achalasia however, may include partial or total esophagectomy with reconstruction if possible. Future research is focused primarily on increasing the efficacy, and lowering complications, of existing therapeutic modalities.

Background: Biliary dyskinesia generally refers to a hypofunctioning gallbladder with an ejection fraction (EF) of <35% on hepatobiliary iminodiacetic acid scan with cholecystokinin stimulation (CCK-HIDA testing). In adults, biliary hyperkinesia has a defined association with biliary colic symptoms and can be relieved with surgical intervention. This clinical entity has not been well described in children or adolescents. In fact, only recently have we seen biliary hyperkinesia on HIDA at our centers. To that end, we reviewed our recent experience with adolescents who have presented and been treated for this unusual clinical entity.

Methods: With IRB approval, we retrospectively reviewed the records of all patients with abnormally high HIDA EFs (>80%) cared for by the pediatric surgery services at two tertiary care centers over the span of a three-year period. Age, sex, BMI, CCK-HIDA results, and preoperative testing and post-operative pathology were noted. Resolution of symptoms was determined by subjective patient self-reporting at postoperative visit.

Results: Eighteen patients met inclusion criteria. Average age 15.7 (range, 10-17 years), median BMI 27.3 (±8.2). Fifteen patients were female and 3 were male. Average CCK-HIDA EF was 91.6% (±5.2), 82.4% of the patients had evidence of chronic cholecystitis and/or cholesterolosis on pathology. Postoperatively, 82.4% of the patients available for follow up (n=17) reported complete or near complete resolution of symptoms.

Conclusions: Biliary hyperkinesia is an emerging clinical entity in children and adolescents and has a similar presentation to biliary hypokinesia. While the pathophysiologic mechanism of pain is not fully elucidated, laparoscopic cholecystectomy appears to provide a surgical cure for these patients and should be considered in the differential for the patient with an unremarkable workup and history suggestive of biliary colic.

Choledochal cysts (CC) ae rare congenital dilations of the biliary tract that harbor lifelong malignancy risk. CC are treated with surgical excision and bilioenteric reconstruction. In the modern era, the surgical approach to pediatric patients has enjoyed significant innovation with regards to minimally invasive techniques. In this review, we discuss these advances, including laparoscopic, single-incision laparoscopic, and robotic strategies, with a focus on the clinical outcomes of patients undergoing these procedures. By presenting an overview of the technical pearls emphasized by pioneers of these procedures, we examine the benefits and limitations of various minimally invasive techniques and analyze the utility and effectiveness of laparoscopy and robotics in comparison to each other and open techniques. Additionally, we highlight the importance of surgeon experience and skill in the management of this rare pediatric disease and explore the significance of the surgical learning curve in minimally invasive approaches in the excision of CC. We discuss the challenge of achieving surgical competency along this learning curve, and present proposed strategies to improve skill sets in the face of low case volumes. Finally, the relative dearth of data discussing long-term follow-up in these patients is discussed, and additional research regarding outcomes, malignancy risk and surveillance, and quality of life is necessary to better understand this disease and the implications of its surgical management.

Appendicitis is a common condition in childhood and adolescence that frequently requires urgent surgical intervention. For almost two centuries appendicitis has been recognized as a medical problem with a surgical solution. Currently the appendix can be removed with a minimally invasive approach, low anesthetic and surgical risk, and swift hospital discharge. Despite these advances, surgery and anesthesia have associated risks including postoperative infection, bleeding, hernia and organ injury among others. In addition, surgery requires time off of school and work to recover and associated healthcare costs can be significant. In both adult and pediatric populations, quality data suggesting a nonoperative approach is suggesting a change to the traditional surgical paradigm. Adults studies have demonstrated both safety and efficacy in the nonoperative management of acute appendicitis. In selected children with uncomplicated appendicitis, initial nonoperative management has been shown to be safe with fewer complications, fewer disability days and less healthcare costs while avoiding the risks inherent to surgery. Ongoing randomized controlled clinical trials in both the United States and Europe seek to further demonstrate the safety of nonoperative management and assist physicians with educating patients about the risk profile of their treatment decision. In complicated appendicitis presenting with abscess or acute appendiceal phlegmon, an initial nonoperative strategy with or without abscess drainage followed by interval appendectomy is the current state of the art though the utility of interval appendectomy is questioned.

Background: Laparoscopic approach for the surgical management of familial adenomatous polyposis (FAP) has become increasingly common for pediatric patients. The purpose of this study was to compare short-term outcomes and resource utilization between open and laparoscopic surgery for prophylactic colectomy in children with FAP.

Methods: The Kids' Inpatient Database (2009 and 2012) was analyzed for children (age ≤20 years) with FAP that underwent prophylactic total colectomy or proctocolectomy. Patient demographics, treating hospital characteristics, hospital charges, and short-term outcomes were compared according to the surgical technique utilized (open versus laparoscopic).

Results: Overall, we identified 216 patients with FAP that underwent elective total colectomy, of which 95 cases were performed by open surgery and 121 were done laparoscopically. The majority of patients were treated at large, not-for-profit, urban teaching hospitals, and the median age was equal (16 years) in both groups. Complications that were more common for open procedures included accidental perforation or hemorrhage (4% vs. 0%, P=0.023), reopening of surgical site (3% vs. 0%, P=0.049), and pneumonia (3% vs. 0%, P=0.049). Simultaneous proctectomy was performed more commonly in the open cohort (91% vs. 71%, P<0.001) as well as ileostomy creation (74% vs. 49%, P<0.001). The median length of stay was similar in the open and laparoscopic groups (7 vs. 6 days, P=0.712). Median total hospital charges were also similar ($67,334 vs. $68,717, P=0.080).

Conclusions: A laparoscopic approach for prophylactic colectomy can be safely performed in children with FAP, and total hospital charges are equivalent compared to open surgery. However, simultaneous proctectomy was performed less often with laparoscopic surgery.

Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease characterized by inflammatory destruction of the intrahepatic and/or extrahepatic bile ducts, leading to bile stasis, fibrosis, and ultimately to cirrhosis, and often requires liver transplantation (LT). PSC occurs more commonly in men, and is typically diagnosed between the ages of 30 and 40. Most cases occur in association with inflammatory bowel disease (IBD), which often precedes the development of PSC. PSC is usually diagnosed after detection of cholestasis during health evaluation or screening of patients with IBD. When symptomatic, the most common presenting symptoms are abdominal pain, pruritus, jaundice or fatigue. The etiology of PSC is poorly understood, but an increasing body of evidence supports the concept of cholangiocyte injury as a result of environmental exposure and an abnormal immune response in genetically susceptible individuals. PSC is a progressive disease, yet no effective medical therapy for halting disease progression has been identified. Management of PSC is mainly focused on treatment of symptoms and addressing complications. PSC can be complicated by bacterial cholangitis, dominant strictures (DSs), gallbladder polyps and adenocarcinoma, cholangiocarcinoma (CCA) and, in patients with IBD, colorectal malignancy. CCA is the most common malignancy in PSC with a cumulative lifetime risk of 10-20%, and accounts for a large proportion of mortality in PSC. LT is currently the only life-extending therapeutic approach for eligible patients with end-stage PSC, ultimately required in approximately 40% of patients. LT secondary to PSC has an excellent outcome compared to other LT indications, although the disease can recur and result in morbidity post-transplant.

The observation of bile duct paucity is an important diagnostic finding in children, occurring in roughly 11% of pediatric liver biopsies. Alagille syndrome (ALGS) is a well-defined syndromic form of intrahepatic bile duct paucity that is accompanied by a number of other key features, including cardiac, facial, ocular, and vertebral abnormalities. In the absence of these additional clinical characteristics, intrahepatic bile duct paucity results in a broad differential diagnosis that requires supplementary testing and characterization. Nearly 30 years after ALGS was first described, genetic studies identified a causative gene, JAGGED1, which spearheaded over two decades of research aimed to meticulously delineate the molecular underpinnings of ALGS. These advancements have characterized ALGS as a genetic disease and led to testing strategies that offer the ability to detect a pathogenic genetic variant in almost 97% of individuals with ALGS. Having a molecular understanding of ALGS has allowed for the development of numerous in vitro and in vivo disease models, which have provided hope and promise for the future generation of gene-based and protein-based therapies. Generation of these disease models has offered scientists a mechanism to study the dynamics of bile duct development and regeneration, and in doing so, produced tools that are applicable to the understanding of other congenital and acquired liver diseases.

Giant cell hepatitis associated with autoimmune hemolytic anemia (GCH-AHA) is a rare and severe disease characterized by autoimmune hemolysis associated with acute liver injury, histologically defined by widespread giant cell transformation. It occurs after the neonatal period, most commonly in the first year of life and uniquely affects pediatric patients. It is still poorly understood and likely underdiagnosed, although in recent years there have been advances in the understanding of its pathogenesis and the liver injury is now hypothesized to be secondary to a humoral immune mechanism. Although no laboratory test specific for the diagnosis currently exists, given its severity, it is fundamental to rule out GCH-AHA when evaluating a patient in the first year of life presenting with AHA and/or with acute liver disease of unknown etiology. While GCH-AHA is progressive in nature as other autoimmune liver disorders, it differs significantly from juvenile autoimmune hepatitis (JAIH) in that a cure can be achieved after several years of intensive treatment in a portion of patients. Conventional first line therapy consist of prednisone/prednisolone combined with azathioprine, however, several immunosuppressive drugs, commonly used in the treatment of JAIH have been tried as second line therapy, including cyclosporine, cyclophosphamide, mycophenolate mofetil, 6-mercaptopurine, calcineurin inhibitors, and sirolimus. Intravenous immunoglobulins have also been used in cases of severe liver dysfunction and/or severe anemia allowing for transitory remission. More recently treatment with B-cell depletion has been attempted in some patients and encouraging results have been reported in refractory cases. Although what constitutes optimal treatment has yet to be determined, the recent progress in the understanding of the pathogenetic mechanisms of GCH-AHA have made positive strides, cautiously pointing toward a hopeful prognosis for some of these patients.