Track topics on Twitter Track topics that are important to you
The study will examine potential biological and genetic mechanisms leading to hiatal and paraesophageal hernia formation in predisposed individuals. It is expected that these patients will have defects in the normal production and maturation of collagen and other connective tissue proteins, thus leading to weakness in the diaphragm that may allow for spontaneous herniation. Comparison of tissue and blood samples from these patients (study group) will be made to those from individuals undergoing lower esophageal surgery who have not developed a concurrent hernia (i.e. esophageal myotomy for achalasia and laparoscopic gastric bypass or laparoscopic adjustable gastric banding for morbid obesity - control group).
Diaphragmatic herniation is a common medical problem characterized by protrusion of the abdominal viscera directly through (95% of cases), or adjacent to (5% of cases), the esophageal hiatus. Individuals suffering from these so-called hiatal and paraesophageal hernias experience symptoms such as regurgitation, heartburn, early satiety, and in extreme cases, respiratory compromise or visceral strangulation and ischemia. Unless the hernia is small, these symptoms are generally refractory to medical management and require surgical correction, with approximately 40,000 antireflux surgeries being performed each year in the United States. The hernia repair procedure, which may be performed in either a laparoscopic or open fashion, involves reduction of the intrathoracic viscera back into the abdominal cavity and closure of the diaphragmatic defect. Generally, this closure of the hernia can be accomplished primarily, using nonabsorbable suture to approximate the edges of the defect. Unfortunately, the recurrence rate for this type of repair is unacceptably high and ranges from 10-40%. Furthermore, in the instance of a particularly large hernia, the edges of the defect may be too far apart to be primarily brought together, necessitating the use of other strategies such as relaxing incisions or patches to bridge the gap. Although the precise recurrence rates of these complex repairs is not clear, it is expected that they are even higher that for those diaphragmatic hernias that can be closed primarily.
The genetic and biologic factors that predispose individuals to forming hernias are not well understood. Several smaller series have suggested that ventral and inguinal hernia formation may be due to weakness of the abdominal wall, possibly secondary to defects in collagen deposition and metabolism. Certain studies have shown higher ratios of Type III collagen (immature) to Type I collagen (mature), at both the protein and mRNA level, in patients with abdominal hernias as compared to those without. Furthermore, other reports indicate that these differences in the levels of mature collagen might be due to underlying differences ion the expression of certain matrix metalloproteinase (MMPs), which are largely responsible for collagen remodeling. MMPs -1, -2, -3, -9, and -13 have been shown to be upregulated in connective tissue injury, and alterations in both MMP-2 and fibrillar collagen can interfere with normal wound healing. Furthermore, Bellon et. al. have shown an overexpression of MMP-2 in fibroblasts in patients with direct inguinal hernias, and Zheng's group detected MMP-13 overexpression in tissue samples from patients with recurrent inguinal hernias. So far, no studies have addressed the role of collagen deposition and MMPs in the formation of hiatal and paraesophageal hernias. Preliminary work at our institution has, however, shown a greater than 50% reduction in the elastin content of the phrenoesophageal and gastrohepatic ligaments ("PEL" and "GHL", respectively) of those patients with a hiatal hernia compared to those without herniation. Additionally, the elastic fibers in the PEL and GHL frequently displayed fragmentation and distortion despite the lack of a visible inflammatory response. (J.A. Curci and N.J. Soper, unpublished results) Nevertheless, neither our early work, nor any of the studies from outside institutions have looked at ways of screening patients (i.e. via blood sampling) to detect those at a higher risk for such hernia occurrence. Currently, new MMP-inhibitory drugs are being studied as methods to potentially block or slow the development of other MMP-dependent conditions such as abdominal aortic aneurysm (AAA). Along these lines, if patients with a genetic/biologic predisposition to hernia formation could be readily identified, then this presents a potential point of medical intervention in preventing future hernia development.
Patients to be enrolled in the study will be standard referrals to our group from primary care physicians or other specialists who feel that surgical correction of a diaphragmatic hernia or achalasia is necessary. Additionally, patients referred to our practice for weight reduction surgery will also be considered eligible for enrollment.
Consent to participate in the study will occur at the time of consent to the surgical procedure and will be obtained by the PI and other attending surgeons within the minimally invasive surgery group. This will occur in the surgeon's office/clinic, or in the hospital if the patient is an in-house consult, several days to weeks prior to the scheduled surgery.
Following the informed consent process, patients will be appropriately placed in either the study or control group. At the time of surgery (hernia repair, bariatric procedure, or esophageal myotomy), a 30 ml venous blood sample will be drawn and stored for later testing and analysis. The appropriate standard surgical procedure will then be performed as per surgical attending judgment, however, during the operation, a small (approximately 1 cm2) piece of tissue will be excised from each of 3 anatomic sites: 1) the left diaphragmatic crus, 2) the PEL, and 3) the GHL. After removal from the abdomen, these tissue samples will be divided into 2 pieces to be set aside for further testing at a later time.
This excised samples represent a minute amount of tissue when compared to the overall size of the diaphragmatic crura and surrounding ligamentous attachments, and their removal is not be expected to cause any foreseeable problem for the patient. In fact, hiatal hernia repair often necessitates dissection of much larger crural and connective tissue pieces than this in order to obtain complete reduction of the abdominal viscera out of the chest and subsequent closure of the hernia defect. Following removal of these small tissue samples, the hernia repair, esophageal myotomy, or gastric bypass/banding will then be completed in a standard fashion.
Inclusion Criteria: Any patient undergoing paraesophageal hernia repair, esophageal myotomy, laparoscopic gastric bypass, or laparoscopic adjustable gastric banding.
Exclusion Criteria: Pregnant females, minors, prisoners
Observational Model: Case Control, Time Perspective: Prospective
Washington University School of Medicine
Enrolling by invitation
Washington University School of Medicine
Published on BioPortfolio: 2014-08-27T03:14:45-0400
Investigator will identify a consecutive cohort of patients who have undergone a hiatal hernia repair and are at least 6 months post index procedure.
One-hundred and fifty-nine patients undergoing Nissen fundoplication for symptomatic gastro-oesophageal reflux disease (GORD), who had a concomitant hiatal hernia of > 2 cm axial length, w...
Background: Obesity and hiatal hernia are both risk factors of gastroesophageal reflux disease (GERD), and the incidence of hiatal hernia is much higher in morbidly obese patients. Many b...
We prospectively studied ninety nine GERD patients following laparoscopic hiatal surgery combined with transoral incisionless fundoplication at two community hospitals. General surgeons an...
This study will collect data on patients undergoing hernia repair using the Bard Ventrio Hernia Patch. The study will evaluate hernia recurrence rates, operating time, quality of life and...
Giant hiatal hernia is characterized by the presence of more than 1/3 of the stomach in the chest, through the diaphragmatic hiatus, with or without other intra-abdominal organs. It is a rare patholog...
Gastrointestinal stromal tumors (GISTs) grow relatively slowly and without specific symptoms; therefore, they are typically incidental findings. We report a rare gastric GIST in the mediastinum associ...
Failure or complications following laparoscopic adjustable gastric banding (LAGB) may necessitate band removal and conversional surgery. Band position and band-induced chronic vomiting create ideal co...
Hiatal hernias (HH) after oesophagectomy are rare, and their surgical management is not well standardized. Our goal was to report on the management of HH after oesophagectomy in high-volume tertiary E...
STOMACH herniation located at or near the diaphragmatic opening for the ESOPHAGUS, esophageal hiatus. When the ESOPHAGOGASTRIC JUNCTION is above the DIAPHRAGM, it is called a SLIDING HIATAL HERNIA. When the ESOPHAGOGASTRIC JUNCTION is below the DIAPHRAGM, it is called a PARAESOPHAGEAL HIATAL HERNIA.
Mobilization of the lower end of the esophagus and plication of the fundus of the stomach around it (fundic wrapping) in the treatment of GASTROESOPHAGEAL REFLUX that may be associated with various disorders, such as hiatal hernia. (From Dorland, 28th ed)
A protrusion of abdominal structures through the retaining ABDOMINAL WALL. It involves two parts: an opening in the abdominal wall, and a hernia sac consisting of PERITONEUM and abdominal contents. Abdominal hernias include groin hernia (HERNIA, FEMORAL; HERNIA, INGUINAL) and VENTRAL HERNIA.
A pelvic hernia through the obturator foramen, a large aperture in the hip bone normally covered by a membrane. Obturator hernia can lead to intestinal incarceration and INTESTINAL OBSTRUCTION.
A groin hernia occurring inferior to the inguinal ligament and medial to the FEMORAL VEIN and FEMORAL ARTERY. The femoral hernia sac has a small neck but may enlarge considerably when it enters the subcutaneous tissue of the thigh. It is caused by defects in the ABDOMINAL WALL.
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...
Surgery is a technology consisting of a physical intervention on tissues. All forms of surgery are considered invasive procedures; so-called "noninvasive surgery" usually refers to an excision that does not penetrate the structure being exci...
Diabetes Diabetes Endocrine Obesity Oxycontin Renal Disease Thyroid Disorders Endocrinology is the study of the endocrine glands and the hormones that they secrete (Oxford Medical Dictionary). There are several groups of h...