Indications and safety of proton pump inhibitor drug use in patients with cancer.

INTRODUCTION: Although the exact prevalence of proton pump inhibitor (PPI) use in cancer patients is not known, it is generally perceived to be widespread. PPIs are generally well tolerated and carry an excellent safety profile. However, increasing and longer term PPI use has raised concerns about the risk of pneumonia, bone fractures and enteric infections, and a possible interaction with clopidogrel that could increase the risk of cardiovascular events. AREAS COVERED: We conducted a PubMed search of English language articles addressing the safety and adverse events associated with PPI use with particular emphasis in cancer patients. EXPERT OPINION: PPIs, frequently used in cancer patients, are generally well tolerated and carry an excellent safety profile. PPI-induced acid suppression may increase the risk of Clostridium difficile or other enteric infections, nutritional deficiencies and community acquired pneumonia, all particularly important in cancer patients. The indications for PPI use in cancer patients should be carefully reviewed prior to use.

Recurrent hematochezia secondary to gastrointestinal stromal tumors (GISTs) in neurofibromatosis type one.

BACKGROUND: Patients with neurofibromatosis type 1 (NF1) suffer from cutaneous, neurological and intestinal complications due to the mutation of the neurofibromin gene and abnormal protein product. Gastrointestinal stromal tumors (GISTs) are relatively rare primary tumors of the stomach and small intestine. Patients with NF1 are prone to developing GISTs. We present a case of recurrent gastrointestinal (GI) bleeding from multiple GISTs in a patient with NF1. CASE: A 42 year-old male with NF1 presented with significant GI bleeding; endoscopies failed to identify the source. Multiple lesions involving the small bowel were seen on laparotomy; he underwent reparative small bowel resection. Pathology showed a well circumscribed spindle cell proliferation with minimal atypia and rare mitoses; immunostaining was positive for CD117 (KIT) and CD34; KIT mutations in exons 9, 11, 13 and 17 were negative. DISCUSSION: Up to 25% of patients with NF1 develop GISTs with non-specific presentations; however they may be a source of significant GI bleeding. The pathology, course and molecular composition of these tumors are different from sporadic GISTs. In NF1, GISTs are usually multiple, located in the small bowel (as opposed to the stomach as in sporadic cases) and occur at a younger age. Their clinical scenario is not unlike other hereditary tumor syndromes-multiple tumors with a 10-20% malignant potential. NF1-associated GISTs almost uniformly do not exhibit gain-of-function activation of KIT or PDGFA (pathogenesis is suggested to be from the loss of heterozygosity of the NF1 gene) and are not likely to respond to imatinib. Multiple means of localizing GISTs exist and capsule endoscopy should be recommended to all NF1 patients as it provides a non-invasive approach to localizing the tumors for further surgical management.

Algorithmic approach to patients presenting with heartburn and epigastric pain refractory to empiric proton pump inhibitor therapy.

BACKGROUND: Reflux-like dyspepsia (RLD), where predominant epigastric pain is associated with heartburn and/or regurgitation, is a common clinical syndrome in both primary and specialty care. Because symptom frequency and severity vary, overlap among gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), and RLD, is quite common. The chronic and recurrent nature of RLD and its variable response to proton pump inhibitor (PPI) therapy remain problematic. AIMS: To examine the prevalence of GERD, NERD, and RLD in a community setting using an algorithmic approach and to assess the potential, reproducibility, and validity of a multi-factorial scoring system in discriminating patients with RLD from those with GERD or NERD. METHODS: Using a novel algorithmic approach, we evaluated an outpatient, community-based cohort referred to a gastroenterologist because of epigastric pain and heartburn that were only partially relieved by PPI. After an initial symptom evaluation (for epigastric pain, heartburn, regurgitation, dysphagia), an endoscopy and distal esophageal biopsies were performed, followed by esophageal motility and 24-h ambulatory pH monitoring to assess esophageal function and pathological acid exposure. A scoring system based on presence of symptoms and severity of findings was devised. Data was collected in two stages: subjects in the first stage were designated as the derivation cohort; subjects in the second stage were labeled the validation cohort. RESULTS: The total cohort comprised 159 patients (59 males, 100 females; mean age 52). On endoscopy, 30 patients (19%) had complicated esophagitis (CE) and 11 (7%) had Barrett's esophagus (BE) and were classified collectively as patients with GERD. One-hundred and eighteen (74%) patients had normal esophagus. Of these, 94 (59%) had one or more of the following: hiatal hernia, positive biopsy, abnormal pH, and/or abnormal motility studies and were classified as patients with NERD. The remaining 24 patients (15%) had normal functional studies and were classified as patients with RLD. Utilizing the scoring system a total score was calculated for each patient and effectively distinguished patients with GERD (mean score 9), NERD (mean score 6), and RLD (mean score 3). Receiver operating characteristic (ROC) curves confirmed the optimization of the model, particularly in RLD (P = 0.0001, 95% CI: 0.91-0.98). CONCLUSION: In a community cohort of patients presenting with heartburn and epigastric pain partly refractory to empiric PPI therapy, the prevalence of CE was 19%, BE 7%, NERD 59%, and RLD 15%. An algorithmic approach coupled with a novel scoring system, effectively distinguishes GERD from NERD and RLD and facilitates further management decisions. This novel and simple scoring system is both reproducible and validated as a diagnostic aid in evaluating patients presenting with both epigastric pain and heartburn.

Endoscopic approach to capsule endoscope retention.

In recent years, wireless capsule endoscopy has become increasingly indicated and utilized in the diagnosis and management of small bowel disorders. As such, its most common complication, capsule retention, has become a more frequently encountered clinical entity. Historically, when medical management of capsule retention has failed, patients have been sent directly to surgery. However, recent advances in small bowel enteroscopy have demonstrated a high success rate and safety profile in retrieving retained capsules. These approaches appear to be a viable alternative to surgery in many clinical scenarios. This article discusses both standard and advanced endoscopic approaches to capsule retention, and presents an algorithmic approach to their utilization.

Circumferential and focal radiofrequency ablation for the treatment of Barrett's esophagus.

This invited profile summarizes the technical aspects and clinical trial results related to the use of circumferential and focal radiofrequency ablation in the management algorithm for Barrett's esophagus. What makes this relatively new endoscopic intervention unique is its promising safety and efficacy profile reported in published clinical trials. This technology appears to have overcome many of the limitations of prior endoscopic ablative modalities, and is thus garnering a role in the management of this disease state.

Do pH and temperature play a role in gastrostomy tube deterioration?

The effects of pH and temperature over time on percutaneous endoscopic gastrostomy (PEG) tube longevity were examined in an in vitro model. Two sets of tubes were obtained from 7 major US PEG manufacturers. Using scissors, each PEG tube was cut cross-sectionally 8 cm from the bumper end of the tube. Both qualitative (photographs) and quantitative (mass) measurements were taken at baseline. Median physiologic gastric acidity was approximated by completely submerging 1 set of each cut PEG tube in a 250-mL glass jar containing a 0.050-N (pH 1.3) solution of hydrochloric acid. As a control, another set of each PEG tube was completely submerged in a 250-mL glass jar containing a buffer solution of pH 6. Each jar was then submerged in the waterbath so that the water completely covered the tube but did not enter the jar. The waterbath was covered and maintained at a constant temperature of 37 degrees C. Measurements taken at baseline were repeated at 168 days and again at 375 days. On qualitative examination, no dilations, brittleness, obstruction, nodularity, tears, loss of elasticity, color changes, tube fracturing, kinking, loss of resilience, or variation in external diameter was observed. Quantitative examination showed no change in mass. Tubes removed from the pH 1.3 solution appeared identical to the tubes removed from the pH 6 solution. In all cases, there were no apparent changes from baseline. These findings suggest that temperature and pH can be excluded as predominant factors in tube deterioration and lend further support to a microbial hypothesis of PEG tube deterioration.

Ectopic breast cancer: special treatment considerations in the postmenopausal patient.

A 70-year-old woman with congenital bilateral accessory nipples developed a clinical mass and pain in the left accessory breast tissue. Excision revealed a T2 invasive ductal carcinoma with an identifiable in situ component. No masses were present in the normal breast, and 9 years after surgery, radiation therapy, and tamoxifen there has been no recurrence either in the ipsilateral affected accessory or normal breast tissue.