Induction of final follicle maturation with a gonadotropin-releasing hormone agonist in women at risk of ovarian hyperstimulation syndrome undergoing gonadotropin stimulation and intrauterine insemination: proof-of-concept study.

OBJECTIVE: To evaluate the reproductive performance and safety of gonadotropin-stimulated intrauterine insemination (IUI) cycles in women at risk for ovarian hyperstimulation syndrome (OHSS) when final follicle maturation was induced using a gonadotropin-releasing hormone (GnRH) agonist. MATERIALS AND METHODS: Thirty-three women presenting with a history of cancelled ovarian stimulation for fear of OHSS, underwent repeat gonadotropin ovarian stimulation for IUI. They were all found to be at high-risk for OHSS once more, and were counseled to receive a GnRH agonist to trigger final follicle maturation before insemination. GnRH agonist trigger of ovulation (triptorelin) was given subcutaneously every 12 hours in three repeated doses: 0.3, 0.2, 0.2 mg, respectively. RESULTS: Induction with the agonist was associated with a 30.3% take-home pregnancy rate and 20% miscarriage rate. Multiple pregnancy rates were 26.7%. There were no reported cases of clinically significant moderate/severe ovarian hyperstimulation syndrome. CONCLUSIONS: The use of a GnRH agonist to trigger final follicle maturation in stimulated cycles of hyper responders was associated with a favorable reproductive outcome and no incidence of OHSS. The rate of multiple pregnancies nevertheless was found to be uncontrollably elevated, raising serious concerns regarding the safety of this protocol in standard clinical practice in the context of IUI.

Evidence of androgen receptor expression in squamous and adenocarcinoma of the esophagus.

Androgen receptors (AR) are known to stimulate cellular proliferation in certain tumors. We have assessed the androgen receptor status of esophageal carcinoma in surgically resected specimens as well as in established human esophageal carcinoma cells lines. In these initial studies we sought to characterize the frequency of expression of androgen receptors in squamous versus adenocarcinoma and in male versus female patients, and to assess the possible influence of AR expression on survivaL We analyzed androgen receptor expression utilizing immunohistochemistry in adenocarcinoma and squamous cell carcinoma of the esophagus in surgical specimens from 25 patients treated at Johns Hopkins Bayview Medical Center. Tumors in 7 of 21 males (33%) and 1 of 4 females (25%) showed positive androgen receptor staining with the monoclonal body antibody AR 441. There was no suggestion of a difference in expression of AR between males and females. Five of 11 adenocarcinomas (45%) and 3 of 14 squamous carcinomas were positive. Survival was similar in AR+ and AR- patients. Studies with established tissue culture cell lines showed AR expression by RT-PCR, with stronger expression of AR in adenocarcinoma lines than in squamous carcinoma lines. The presence of AR in human esophageal cancer is an impetus for further studies to assess anti-androgen therapy for treatment and or prevention of these tumors.

Anasarca and small bowel obstruction secondary to endometriosis.

Intestinal involvement by endometriotic tissue occurs in up to 37% of patients with endometriosis. The vast majority of patients do not experience symptoms related to the gastrointestinal tract. In particular, the complications of intestinal obstruction and malabsorption secondary to endometriosis are exceedingly uncommon. We present a 42-year-old woman with intestinal obstruction, protein-losing enteropathy, and anasarca secondary to endometriosis. She had a 1-year history of watery diarrhea, bloating, and abdominal pain with a 30-lb weight-loss over 3 months. She had no previous history of endometriosis, and laboratory investigations showed severe hypoalbuminemia, hypokalemia, and metabolic acidosis. Abdominal x-rays revealed air-fluid levels and dilated loops of small bowel. She underwent surgical resection with primary anastomosis. Pathologic evaluation showed extensive endometriosis of the small bowel and appendix, which resulted in complete obstruction. Segments of ileum also demonstrated moderate-to-marked blunting of the villi. Postoperatively, the patient had a slow recovery with resolution of anasarca and a gradual increase in her weight. This report illuminates the rare, yet significant, complications of intestinal endometriosis, including small bowel obstruction, the development of a protein-losing enteropathy, and anasarca. One should consider the possibility of intestinal endometriosis in the differential diagnosis of bowel obstruction in women of childbearing age.

Management of Barrett's esophagus.

There have been major recent advances in the understanding of the pathogenesis and epidemiology of Barrett's esophagus and adenocarcinoma of the esophagus. The advent of potent acid suppression with proton pump inhibitors and safe, minimally invasive antireflux procedures has made alleviating symptoms and eliminating peptic complications achievable goals for the vast majority of patients. Endoscopic surveillance of Barrett's esophagus is considered the standard of care and is widely used in clinical practice. Neither medical nor surgical antireflux procedures, however, result in the regression of Barrett's esophagus in any consistent manner. Thermal and chemical endoscopic ablation techniques show promise in both the management of high grade dysplasia and the reversal of Barrett's esophagus, but these techniques are still of unproven benefit, and can be costly and risky. Therefore, prospective and controlled studies with long term follow-up are needed before incorporating ablative techniques into routine clinical practice. Management of high grade dysplasia remains controversial. Alternative management strategies include surveillance, resection or ablation, tailored to the individual patient and the available expertise. Targets for future research include defining appropriate surveillance intervals; finding biological markers that identify patients at higher risk of progressing to cancer; defining the cancer risk and the appropriate management of patients with short segment Barrett's esophagus; understanding the natural history of dysplasia and comparing alternatives for the management of high grade dysplasia; and studying whether surgical management can delay or prevent the progression to dysplasia and adenocarcinoma.

New developments and concepts in antimicrobial therapy for intra-abdominal infections.

Antimicrobial therapy plays an integral role in the management of intra-abdominal infections. Recent developments include increased prevalence of antimicrobial resistance (eg, Streptococcus pneumoniae and Enterococcus species) coupled with general decline in the antimicrobial susceptibility of anaerobes and gram-negative organisms, new antibiotics and dosing regimens, and better understanding of the role of various microbial pathogens and of prophylactic antimicrobial agents. Therapeutic approaches to intra-abdominal infections, such as the various forms of peritonitis, cholecystitis, cholangitis, and diverticulitis, are reviewed here. Specific recommendations for antimicrobial therapy in various clinical settings are provided, with special emphasis on recent trends and developments that reflect changes in understanding or therapy.

The spectrum of spontaneous and iatrogenic esophageal injury: perforations, Mallory-Weiss tears, and hematomas.

Esophageal perforations, Mallory-Weiss tears, and esophageal hematoma involve traumatic injury to the esophagus. These can be iatrogenic, in particular due to esophageal instrumentation, but can also occur spontaneously. The remarkable increase in diagnostic and therapeutic endoscopy as well as esophageal surgery has made instrumentation the most common cause of esophageal perforation. In many instances, spontaneous perforations are associated with retching and vomiting, which causes a sudden increase in intraesophageal pressure. A high index of suspicion leading to rapid diagnosis and appropriate therapy are needed to optimize clinical outcomes. This article focuses on esophageal perforations, Mallory-Weiss tears, and esophageal hematomas, with emphasis on etiology, pathogenesis, clinical presentation, diagnosis, management, and prevention.

Diagnostic evaluation in gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) describes the clinical manifestations of reflux of gastric contents and the associated symptoms and patterns of tissue injury. Although its exact prevalence is difficult to determine, there is no doubt the GERD is the most common esophageal disease and probably among the most prevalent conditions seen in the primary care setting. GERD has a wide clinical spectrum, making the diagnostic evaluation challenging and complicated at times. Confirmatory test are rarely needed in patients with typical symptoms of heartburn or regurgitation who have a good clinical response to GERD therapy. This article describes the diagnostic tests necessary for some cases of GERD.

Congenital esophageal stenosis: clinical and endoscopic features in adults.

BACKGROUND: Congenital esophageal stenosis (CES) is an uncommon anomaly that reportedly rarely goes undiagnosed until adulthood. One variant of CES includes patients with multiple cartilaginous rings described usually in the mid-distal esophagus. METHODS: Ten patients with CES seen over the past 7 years were interviewed and their clinical and endoscopic records reviewed. RESULTS: Eight patients were male and age at time of diagnosis ranged from 21 to 75 years. Meat impaction was the presenting symptom in 8 patients and 3 patients reported a relapsing history. Intermittent solid food dysphagia over extended duration (10-40 years) was reported in all patients with an estimated onset of symptoms at a mean age of 27 years (11-52 years). Endoscopically, all patients had segmental esophageal stenosis (length 2-8 cm, mean = 4.7 cm) due to 'trachea-like' multiple submucosal rings. Pseudodiverticulosis and distal reflux esophagitis were evident in 1 patient. Nine of 10 patients had no macroscopic esophagitis. Dilatation was performed by balloon insufflation (18 mm in 5 patients, 15 mm in 3 patients, 12 mm followed by 15 mm in a patient with a tight stricture) and by Savary dilators in 1 patient, without any complications. No patient had recurrent meat impaction on follow-up (1-7 years, mean = 3 years) after education about the condition. CONCLUSION: (1) We suspect CES is an under-recognized cause for intermittent, long-standing dysphagia in adults. (2) Food impaction is a frequent initial presentation. Recognition of CES is critical for appropriate patient education and planning.

Antimicrobial treatment of intra-abdominal infections.

There have been several recent changes that influence the management of intra-abdominal infections. These changes include important developments in antibiotic resistance such as increases in pneumococcal resistance, emergence of multi-drug-resistant enterococcal isolates, and decreasing sensitivity of anaerobes and gram-negative rods. In addition there are new antibiotics such as piperacillin/tazobactam, and new antibiotic dosing regimens such as single daily dosing of aminoglycosides. In this article, we will review the therapeutic approach to intra-abdominal infections with special emphasis on the various forms of peritonitis, cholecystitis, cholangitis, and diverticulitis. Several new concepts about the treatment of enterococcus, the management of bacterial and fungal peritonitis, and the prevention of spontaneous bacterial peritonitis will also be reviewed. Specific recommendations for the management of the different infections including antibiotic doses and costs will be provided. Finally the role of invasive procedures in the management of some of the infections will be explored.

Molecular and genetic advances in gastrointestinal cancer: state of the art.

There have been major advances in the understanding of the molecular and genetic basis of gastrointestinal malignancies. The introduction of new genetic techniques has generated considerable insight into the understanding of familial cancer as is the case with hereditary nonpolyposis colon cancer and familial adenomatous polyposis syndrome and in the understanding of premalignant conditions such as the various dysplasias and adenomas. This new information will be of tremendous help in the early detection, the prognostication, and hopefully the therapy of premalignant and malignant gastrointestinal diseases. This article will attempt to review all these advances with added emphasis on the clinically relevant issues.