Comparative post-operative study of prostheses, with and without an anti-reflux valve system, in the palliative treatment of esophageal carcinoma

BACKGROUND/AIMS: Palliative treatment of advanced esophageal carcinoma by esophageal tunnelization with a prosthesis allows immediate relief of dysphagia. However, the procedure is subject to a high rate of morbidity, including gastroesophageal reflux (GER) present in all patients with a prosthesis positioned through the gastroesophageal junction, resulting in complications (pyrosis, aspiration pneumonias, sleep disorders) and reduced quality of life in these patients who already have a lower rate of survival. In an attempt to reduce GER and its complications, the authors created a surgical prosthesis coupled to an anti-reflux valve system, comparing it to the use of an esophageal prosthesis without an anti-reflux valve mechanism. METHODOLOGY: Twenty-two patients were allocated to 2 tunnelization groups: esophageal prosthesis without an anti-reflux valve mechanism (group 1) and surgical prosthesis coupled to an anti-reflux valve system (group 2). The GER was quantified measuring esophageal-gastric pH, and using fluoroscopy, contrast radiographs and esophageal emptying scintigraphy. Initially, the pH of secretions in S1 (esophagus) and S2 (stomach) was determined using reagent strips after aspirating their contents with different syringes. First with the patient seated at rest in bed, later performing a Valsalva maneuver, deep breathing and forced coughing. The same procedure was performed with the patient in left lateral decubitus, right lateral decubitus, and dorsal decubitus with the head of the bed lowered to 20 degrees. After finishing these maneuvers, 15 ml of 1 molar acetic acid were infused through the catheter positioned in the antrum, and, after 5 min, S1 and S2 material sampling was repeated in the same positions as mentioned above. RESULTS: The pH values between the various positions and maneuvers performed in each group separately were not significantly different, but, if we compare the 2 groups, and the secretions obtained in S1 and S2, there was a significant difference in pH measures in all positions. In the patients in group 1, S1 presented a mean pH ranging from 2.87-3.62 in the initial measures, and between 2.17 and 3.5 after the infusion of 15 ml of 1 molar acetic acid. On the other hand, in group 2, the mean pH of S1 remained between 6.34 and 8.32 in the initial measures and between 4.99 and 7.33 in the presence of acid infusion. At the level of S2, the pH remained unchanged between 2 and 2.7, in both groups. CONCLUSIONS: The authors conclude that the association of an esophageal prosthesis with a valve system significantly reduces GER, as compared with its use alone. Furthermore, it allows marked reduction of the symptoms and resulting complications, and does not interfere clinically with esophageal emptying. It thus significantly improves the quality of life of these patients.     

Gastrointestinal complications of immunosuppression

The gastrointestinal manifestations of drug-induced immunosuppression may result from direct drug effects, from infectious complications, or both. Graft-versus-host disease (GVHD) is a third mechanism whereby immunosuppressive agents are linked with gastrointestinal injury. This article reviews individual immuno-suppressive medications, first concentrating on their reported gastrointestinal side effects, then reviewing other gastrointestinal phenomena, which may represent side effects of immunosuppressive agents but have not been reported yet.     

Three new active cisplatin-containing combinations in the neoadjuvant treatment of locally advanced and locally recurrent breast carcinoma: a randomized phase II trial

We designed three new four-drug cisplatin-containing combinations and evaluated their activity in a randomized phase II study including patients with locally advanced (stage III) and locally recurrent breast carcinoma. All combinations included methotrexate (M) on day 1 and cisplatin (P) on day 2 (MVAC-like combinations) and differed from one another by the addition of Epirubicin (Epi), Vincristine (V), Etoposide (E), Mitomycin (Mi). Based on the administered agents, they were named MPEMi, MPEpiE, MPEpiV. The combinations were randomly assigned to 101 patients, 57 with locally advanced and 44 with locally recurrent breast carcinoma. Response was evaluated after 4 cycles. The complete response (CR) rates were 7% and 43% and the CR plus partial response (PR) rates were 84% and 89% in locally advanced and in locally recurrent disease, respectively. In locally advanced disease, a pathologic CR (pCR) was assessed in seven of 57 patients (12%). There were no significant differences among the three combinations. The toxicities were at times severe, but generally tolerable, as demonstrated by the high cumulative doses of the drugs received by the patients. In conclusion, these three innovative chemotherapy regimens induced high CR plus PR rates in the neoadjuvant treatment of stage III and of locally recurrent breast carcinoma, and a high rate of pCR in stage III disease. These regimens warrant testing in phase III trials.     

Glutamatergic control of food intake in pigeons: effects of central injections of glutamate, NMDA, and AMPA receptor agonists and antagonists

The possible involvement of glutamatergic mechanisms in the control of food intake was studied in free-feeding and in 24-h food-deprived (FD24) pigeons for 1 h after intracerebroventricular (i.c.v.) treatment with glutamate (Glu, 0, 50, 150, 300, and 600 nmol). Glu injections dose dependently induced decreases (30-65%) in food intake (FI) and feeding duration (FD), and increases in latency to start feeding (LSF) in FD24 animals, but not in free-feeding ones. None of these treatments affected noningestive behaviors (locomotion, sleep, and preening). In FD24 pigeons, i.c.v. treatments with N-methyl-D-aspartic acid (NMDA, 0.1, 1, 4, 8, or 16 nmol) or D,L-alpha-amino-3-hydroxy-isoxazole proprionic acid (AMPA, 0.1, 1, 4, or 8 nmol) decreased FI and FD, but left LSF unchanged compared to vehicle-treated FD24 controls. Kainic acid (0.1, 0.5, and 1 nmol), or [trans-(1S,3R)-ACPD-(5NH4OH)] (ACPD, 0.1, 1, 4, 8, and 16 nmol) left unchanged the ingestive profile of FD24 pigeons. Pretreatment with the NMDA receptor antagonist MK-801 (15 nmol) and the AMPA-kainate receptor antagonist CNQX (390 nmol), 20 min before an i.c.v. injection of Glu (300 nmol) induced a partial blockade of the Glu-induced decreases in FI and FD and completely inhibited the Glu-induced increase in LSF in FD24 pigeons. I.c.v. injections of MK-801 (30 nmol) and of CNQX (780 nmol) increased FI and FD and reduced LSF in free-feeding pigeons. A lower dose of MK-801 (15 nmol) increased FI and FD, but not LSF. Conversely, a lower dose of CNQX (390 nmol) reduced LSF without changing FI or FD. These findings indicate the involvement of Glu as a chemical mediator in the regulation of food intake in the pigeon, possibly acting on multiple central mechanisms in this species through NMDA- and AMPA-sensitive Glu receptors.     

Coeliac disease in identical twins.

Coeliac disease occurred at the same age in MZ twins. The diagnosis was confirmed by histology of the small intestine, rapid response to a gluten-free diet, and relapse after reintroduction of gluten.     

Antinociceptive properties of N-aryl-glutaramic acids and N-aryl-glutarimides

This study describes the antinociceptive activity of some N-aryl-glutaramic acids and N-aryl-glutarimides in writhing and formalin tests, two classical models of pain in mice. These compounds show high activity, being more active than acetyl salycilic acid, acetaminophen and indomethacin, used as standard drugs for comparison. The introduction of different substituent groups in the aromatic ring caused a significant change in activity. The results obtained here are promising from a pharmacological point of view, since these simple compounds might be used as models to obtain new and potent analgesic drugs.