Evidence for the ''paradox'' association between hypertensive lower esophageal sphincter and gastroesophageal reflux disease.

There are several studies suggesting the paradoxical simultaneous presence of hypertensive lower oesophageal sphincter and gastroesophageal reflux disease. We present a case of a 22-year-old male patient who was examined in our outpatient clinic with oesophageal food bolus impaction during a meal, severe chest pain and drooling. Manometry revealed a hypertensive lower esophageal sphincter pressure (resting pressure 35 mmHg) and pHmetry revealed a DeMeester score > 14.72 (43.27). Six months after therapy with lansoprazole, manometry revealed a normal lower oesophageal sphincter (resting pressure 14 mmHg) and the DeMeester score was < 14.72 (5.89). The patient is now asymptomatic. This report is the only published case which exhibits the normalization of lower oesophageal pressure 6 months after gastroesophageal reflux disease management with lansoprazole, thus proving and establishing the above ''paradox''.

A dose escalation study of docetaxel plus capecitabine in combination with gemcitabine in patients with advanced solid tumors.

Capecitabine (CAP), gemcitabine (GEM), and docetaxel (DOC) have shown interesting activity in a wide range of solid tumors. A phase I study was conducted in order to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of their combination in patients with refractory solid tumors. Eighteen patients were enrolled. The patients' median age was 60 years, 15 were male, and 11 were chemo-naive. DOC was administered on day 1 as an 1-h (IV) infusion at escalating doses ranging from 40 to 50 mg/m2. GEM was administered on day 1 as a 30-min (IV) infusion at a standard dose of 1500 mg/m2. CAP was administered orally on days 1 to 7 at escalating doses ranging from 1750 to 2500 mg/m2 given as two daily divided doses. Treatment was repeated every 2 weeks. Five different dose levels were examined. At dose level V two out of three enrolled patients presented DLTs (one patient grade 4 neutropenia and grade 3 stomatitis and another grade 3 diarrhea), and thus the recommended MTD for future phase II studies are CAP 2250 mg/m2, DOC 50 mg/m2, and GEM 1500 mg/m2. A total of 124 treatment cycles were administered. Toxicity was generally mild. Grade 3/4 neutropenia was observed in eight (7%) treatment cycles and grade 3 thrombocytopenia in one (1%). There was no febrile episode. Grade 2/3 asthenia was observed in six (33%) patients, grade 2/3 diarrhea in four (22%), and grade 2/3 hand-foot syndrome in three (17%). Other toxicities were uncommon. There was no treatment-related death. One (6%) CR, four (25%) PRs, and six (38%) SD were observed among 16 evaluable patients. Responses were seen in patients with breast (one CR), gastric (three PRs), and pancreatic (one PR) cancer. These results demonstrate that CAP, DOC, and GEM can be safely combined at clinically relevant doses and this regimen merits further evaluation.