Phase II study of cisplatin, etoposide and paclitaxel in locally advanced or metastatic adenocarcinoma of gastric/gastroesophageal junction.

BACKGROUND: Unresectable and metastatic gastric cancers carry a poor and dismal prognosis. Several phase II studies have identified effective anticancer drugs. AIMS: To evaluate safety and efficacy of low-dose cisplatin, etoposide and paclitaxel (CEP) based combination chemotherapy in locally advanced or metastatic adenocarcinoma of gastric/gastroesophageal junction. SETTING AND DESIGN: Prospective single-arm phase II study. MATERIALS AND METHODS: Thirty-three patients were enrolled onto this study, out of which, all but one received cisplatin 15 mg/m 2, etoposide 40 mg/m 2 and paclitaxel 50 mg/m 2, given on day 1 and 4 every week for three weeks in a 28-day cycle. Survival analysis was done using SPSS program. RESULTS: Median age of group was 56 years. Twenty-five were males. Twenty-nine had metastatic/inoperable disease and four patients had recurrent disease. Liver was the commonest metastatic site seen in 15 patients. With a median of 2 cycles per patient, a total of 76 cycles was administered. Grade III or IV toxicity were seen in 11 (35%) patients; diarrhea, 5 patients; vomiting, 3 patients; and neutropenia, 7 patients, 5 of whom also had fever). One patient died of neutropenic fever. Best responses, seen in 32 evaluable patients, were 2 CR (6.1%), 21 PR (63%) and 3 SD (9.2%). Four patients were considered operable after chemotherapy. With median follow-up of 11 months in surviving patients, median OS was 10 months and PFS was 8 months. Median OS was 13 months in responders versus 8 months in nonresponders (P =0.04). Seven patients survived> 12 months. CONCLUSION: Combination of low-dose CEP shows good clinical response and an acceptable toxicity profile in advanced or metastatic adenocarcinoma of gastric/gastroesophageal cancers. Whether addition of 5 FU or capecitabine adds to the benefit should be explored. This may be tested with other standard/conventional protocols in a randomized fashion.

Pneumatic dilation versus intrasphincteric botulinum toxin injection in the treatment of achalasia cardia in India: an economic analysis.

BACKGROUND: Pneumatic dilation (PD) is an established therapeutic option for achalasia cardia. Recently, intrasphincteric botulinum toxin (BT) has been used to treat achalasia cardia in view of its simplicity and safety. However, it is likely to be a costly treatment as repeated injections are often needed due to its short-lasting effect. No economic analysis of PD and BT strategies has been done in India. METHODS: A decision tree was constructed using decision analysis software (DATA 4.0; TreeAge Software, Williamstown, MA, USA). Probability estimates for BT injection and PD (and, in case of failure, surgery) were obtained from published literature, preferably from India. Direct "out-of-pocket" costs (in Indian rupees; currently US$ 1 = 49 rupees approximately) for baseline analysis were obtained from our hospital and from some private hospitals. Sensitivity analysis was done using a wide range of probability and cost estimates. RESULTS: Intrasphincteric BT injection strategy was more costly at 18,520 rupees per patient than PD strategy (4,568 rupees), yielding an incremental cost of 13,952 rupees per patient successfully treated. Sensitivity analysis supported the conclusions of the baseline analysis. CONCLUSION: Primary intrasphincteric BT injection strategy was costlier than primary PD strategy in the treatment of achalasia cardia in India, and therefore cannot be justified despite its efficacy, relative ease of administration and safety.

Characterization of nerve-induced relaxation of gastrointestinal sphincteric smooth muscle in a South American opossum (Didelphis albiventris)

The presence of inhibitory nonadrenergic noncholinergic (NANC) intrinsic innervation of the circular muscle of the gastrointestinal sphincters of the South American (SA) opossum was investigated in vitro. Isolated circular muscle strips from the esophagogastric and ileocolonic junctions but not from the gastroduodenal (pylorus) region developed spontaneous tension. Tetrodotoxin (TTX, 1 muM) augmented the spontaneous tension only in the ileocolonic junction strips. Electrical field stimulation of esophagogastric and ileocolonic junction strips caused frequency-dependent responses consisting of a relaxation at lower frequencies (<1 Hz) and a biphasic response or contraction at higher frequencies. In the strips from the pyloric region electrical field stimulation abolished the spontaneous activity at lower frequencies and induced contractions at higher frequencies. The responses elicited by electrical field stimulation in the three sphincters were abolished by TTX (1 muM). Electrical field-induced contractions were reduced while relaxations were enhanced by atropine (1 muM). In the presence of atropine (1 muM) and guanethidine (3 muM), electrical field stimulation, nicotine and ATP induced frequency-or concentration-dependent relaxations of the three sphincters that were abolished by TTX (1 muM). Isoproterenol and sodium nitroprusside caused concentration-dependent relaxations which were TTX-resistant. These findings indicate that the sphincteric circular muscle of the SA opossum gastrointestinal tract is relaxed by the activation of intrinsic NANC nerves and therefore can be used as a model for the study of the mechanisms involved in these responses.

Efeito de antiácido e bloqueadores H2 sobre a zona de alta pressao esofagogástrica do cäo / Effect of antiacido and H2 blockers on high pressure zone of esophagogastric funciton in dog

Em dez cäes machos, foi estudado o efeito da administraçäo oral de antiácido (hidróxido de alumínio) e bloqueadores H2 (cimetidina e ranitidina) sobre a zona de alta pressäo esofagogástrica (amplitude de pressäo e comprimento). Näo foram observadas modificaçöes na pressäo e comprimento na zona de alta pressäo esofagogástrica após a administraçäo das três drogas

Açäo da pentagastrina no esfíncter inferior do esôfago de pacientes com megaesôfago chagásico / Effect of pentagastrin on the lower esophageal sphincter in patients with chagasic megaesophagus

Com o objetivo de estudar o comportamento do esfíncter inferior do esôfago (E.I.E.) em pacientes com doenças de Chagas, foram analisados os valores da pressäo esfincteriana basal e o padräo de resposta do esfíncter a doses crescentes de Pentagastrina (PG) administrada em infusäo I.V. constante. Os resultados de pacientes com a Forma Indeterminada (12 casos) e com Megaesôfago chagásico (12 casos) foram comparados aos obtidos em um Grupo Controle (12 casos). Para a análise do comportamento do E.I.E. foi empregado o método manométrico com tubos abertos e infusäo constante de água (1,6 cm*3/min). O registro das pressöes intraluminares foi realizado através do sistema de retirada rápida. Inicialmente era administrada soluçäo fisiológica e, a seguir, PG nas doses de 0,5-1,0-2,0-4,0 microng/Kg/h, respectivamente, diluída em água destilada equivalendo a um volume de 20 cm*3/h. Cada uma das soluçöes era infundida por aproximadamente 15 minutos, intercaladas com a administraçäo de soluçäo fisiológica. Os seguintes resultados (média aritmética, x, ñ erro padräo da média, e.p.m.), expressos em cm H20, foram obtidos: 1) durante a infusäo de soro fisiológico I.V., a pressäo do E.I.E. apresentou valores médios de 27,4ñ1,8 no Grupo Controle; 33,0+2,3 no grupo portador de Forma Indeterminada e 36,2ñ2,5 no Grupo Megaesôfago; 2) durante a infusäo de PG, a pressäo ao nível do E.I.E. apresentou os seguintes valores, respectivamente, para as doses de 0,5-1,0-2,0-4,0 microng/kg/h: 37,7ñ3,0; 40,5ñ2,9ñ40,4ñ3,3; 43,