Clinical outcomes in patients with a diagnosis of "indefinite for dysplasia" in Barrett's esophagus: a multicenter cohort study.

BACKGROUND AND STUDY AIM: Data are limited on the natural history of patients with Barrett's esophagus with a diagnosis of "indefinite for dysplasia" (IND). The aims of this study were to: (i) determine rates of progression to high grade dysplasia (HGD) or esophageal adenocarcinoma, and compare these with rates for low grade dysplasia (LGD); and (ii) determine the proportion of patients whose histological IND diagnosis changed on follow-up endoscopy. PATIENTS AND METHODS: Demographic, endoscopic, and histologic information of patients with diagnoses of IND and LGD and at least 12 months of follow-up were extracted from the database of a multicenter Barrett's esophagus study. Rates and times for progression to HGD and esophageal adenocarcinoma and regression to nondysplastic epithelium were calculated. Proportions of diagnoses upgraded to HGD/esophageal adenocarcinoma or downgraded to nondysplastic epithelium at first follow-up endoscopy were evaluated. RESULTS: Amongst 2264 patients, 83 with a diagnosis of IND (mean age 60 years, 95 % men, 95 % white; mean follow-up 5.6 years) and 79 with diagnosis of LGD were identified. In the IND group, annual incidences of esophageal adenocarcinoma and HGD were 0.21 % and 0.64 %, respectively, representing a combined incidence of 0.8 %. Mean time to progression was 4.72 years. Within the IND group 55 % patients showed regression to nondysplastic epithelium at first follow-up endoscopy and the overall regression rate was 80 %. Corresponding rates in LGD patients were similar. CONCLUSIONS: Lesions diagnosed as IND and LGD show similar biological behavior and can be treated as a single category with respect to surveillance and follow-up.

Association between length of Barrett's esophagus and risk of high-grade dysplasia or adenocarcinoma in patients without dysplasia.

BACKGROUND & AIMS: It is not clear whether length of Barrett's esophagus (BE) is a risk factor for high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in patients with nondysplastic BE. We studied the risk of progression to HGD or EAC in patients with nondysplastic BE, based on segment length. METHODS: We analyzed data from a large cohort of patients participating in the BE Study-a multicenter outcomes project comprising 5 US tertiary care referral centers. Histologic changes were graded as low-grade dysplasia, HGD, or EAC. The study included patients with BE of documented length without dysplasia and at least 1 year of follow-up evaluation (n = 1175; 88% male), and excluded patients who developed HGD or EAC within 1 year of their BE diagnosis. The mean follow-up period was 5.5 y (6463 patient-years). The annual risk of HGD and EAC was plotted in 3-cm increments (≤3 cm, 4-6 cm, 7-9 cm, 10-12 cm, and ≥13 cm). We calculated the association between time to progression and length of BE. RESULTS: The mean BE length was 3.6 cm; 44 patients developed HGD or EAC, with an annual incidence rate of 0.67%/y. Compared with nonprogressors, patients who developed HGD or EAC had longer BE segments (6.1 vs 3.5 cm; P < .001). Logistic regression analysis showed a 28% increase in risk of HGD or EAC for every 1-cm increase in BE length (P = .01). Patients with BE segment lengths of 3 cm or shorter took longer to develop HGD or EAC than those with lengths longer than 4 cm (6 vs 4 y; P = nonsignificant). CONCLUSIONS: In patients with BE without dysplasia, length of BE was associated with progression to HGD or EAC. The results support the development of a risk stratification scheme for these patients based on length of BE segment.

Gastroparesis and gastroparesis-like syndrome: response to therapy and its predictors.

PURPOSE: The natural history and outcome of patients with gastroparesis is not well known. The aim of this study was to identify the clinical or pathophysiological characteristics, if any, that may be helpful in predicting therapeutic response in this condition. METHODS: This is a retrospective study of a cohort of patients who presented to a tertiary referral center with symptoms suggestive of gastroparesis. All patients were evaluated by scintigraphic measurement of gastric emptying and symptoms were scored using a modification of the Gastroparesis Cardinal Symptom Index (GCSI). Treatment generally included conservative measures such as antiemetics, prokinetics, tricyclic antidepressants, and analgesics as well as various more invasive interventions in selected patients. Response to treatment was defined as a change in the overall GCSI score of two-thirds or more as compared with baseline. RESULTS: Out of a total of 93 patients, 69 patients met the eligibility criteria. Of these, 29 patients had diabetes mellitus and 40 patients had gastroparesis of nondiabetic etiology. Out of 69 patients, 49 were responders (71%) and 20 were nonresponders (29%). The cause (diabetic versus nondiabetic) of gastroparesis or the presence of delayed emptying did not correlate with response. However, the severity of stomach distension, bloating subscale score, and the global GCSI score at baseline presentation were predictive of response by multivariate analysis. CONCLUSION: Higher global GCSI score, bloating subscale score, and severity of stomach distension at baseline presentation correlated with an unfavorable response in gastroparetic patients. On the other hand, neither the etiology of gastroparesis nor associated delay in gastric emptying appeared to be important in the clinical response. Patients with symptoms of typical gastroparesis but without delays in gastric emptying may have a distinct syndrome with a greater proportion of males than classical gastroparesis.

A case of malignant abdominal pain.

BACKGROUND: Testicular cancer is a common neoplasm in young and middle-aged men. Although the most common presentation is a palpable testicular mass, it can present with atypical symptoms. There is a lack of awareness among primary-care physicians about the less common presentations of testicular tumors. Early detection is a key prognostic variable. This case demonstrates an unusual first presentation of testicular cancer with chylous ascites and abdominal pain. CASE REPORT: We report a case of a 19-year-old man who presented with severe atypical abdominal pain, which was initially diagnosed as acute appendicitis. He underwent laparoscopic appendectomy and was found to have chylous ascites and a normal-appearing appendix. As part of his work-up for chylous ascites, he was found to have mesenteric lymphadenopathy. These nodes were sampled and revealed a mixed germ cell tumor. The primary tumor was later traced to his right testis. CONCLUSIONS: The differential diagnosis of atypical abdominal pain in young men should include testicular tumors. A thorough testicular exam should be part of the routine physical exam in such situations.

Pain and chronic pancreatitis: is it the plumbing or the wiring?

Our progress in understanding the biology of chronic pancreatitis has been slow, particularly with respect to the pathogenesis of pain, the cardinal symptom. Although traditional theories have focused on anatomic changes, with interstitial and ductal hypertension as the main inciting factors for pain generation, subsequent studies have not confirmed a correlation between ductal pressure and the severity of pain or its relief after ductal decompression. Empirical approaches directed at anatomic causes are at best of marginal value. Although these phenomena are clearly associated with the disease, they are not likely the root cause of the pain. Instead, they probably are inciting factors on a background of neuronal sensitization induced by damage to the perineurium and subsequent exposure of the nerves to mediators and products of inflammation. In this review, we discuss the inherent limitations in our current therapies and try to identify new targets and approaches for the future, such as TRPV1, nerve growth factor-TrkA signaling, and perhaps protease activator receptor-2.

Progression of Barrett oesophagus: role of endoscopic and histological predictors.

Barrett oesophagus is an important precursor lesion for the development of oesophageal adenocarcinoma (OAC). Upper gastrointestinal endoscopy is the modality most widely used to visualize and biopsy the oesophagus to establish a diagnosis. Additional clues are available at the time of endoscopy that can identify high-risk features known to increase the risk of progression to OAC, such as the length of the Barrett oesophagus segment, length of hiatal hernia and the presence of nodularity or visible endoscopic lesions in this segment. Until molecular biomarkers are identified and validated as adjunctive tools for risk stratification, knowledge of endoscopic features could complement dysplasia grading for risk stratification of patients with Barrett oesophagus and identify subgroups at risk of progression to OAC. This approach would, in turn, facilitate more rational tailoring of endoscopic surveillance. This Review summarizes the current role of endoscopic and histological factors involved in neoplastic progression of Barrett oesophagus to OAC, and provides an overview of the risk-prediction models that have utilized endoscopic and histological factors for risk stratification in patients with Barrett oesophagus.

Drug interaction presenting as acute abdomen.

Warfarin is the most common oral anticoagulant prescribed around the world. Adverse drug interactions with warfarin are a huge problem especially in the elderly and in patients who take multiple medications. Most adverse drug interactions involve concomitantly prescribed oral or intravenous medications. Occasionally, topical or mucosally absorbed drugs can interact, leading to fluctuations in warfarin levels with adverse consequences. In this case report, we describe a case of intestinal intramural hematoma, a rare but known consequence of a supra therapeutic international normalized ratio (INR). The supra therapeutic INR was a consequence of mucosally absorbed miconazole, prescribed for vaginal candidiasis. We wish to highlight this rare and potentially fatal drug interaction, along with the need for frequent INR monitoring when new drugs are added or removed in patients taking warfarin.