Search Results - (Author, Cooperation:P. J. O'Dwyer)

2011-03-26

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Adult ; Aged ; Animals ; Antibodies, Monoclonal/administration & dosage/adverse ; effects/metabolism/*therapeutic use ; Antigens, CD40/*agonists/*immunology ; Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carcinoma, Pancreatic Ductal/*drug therapy/immunology/pathology/secondary ; Deoxycytidine/analogs & derivatives/therapeutic use ; Disease Models, Animal ; Disease-Free Survival ; Female ; Humans ; Immunologic Surveillance ; Macrophage Activation ; Macrophages/immunology ; Male ; Mice ; Middle Aged ; Pancreatic Neoplasms/*drug therapy/immunology/pathology ; T-Lymphocytes/immunology ; Tumor Microenvironment ; Young Adult

1530-0358

Intraluminal tumor cells ; Perianastomotic tumor growth ; Fibrin tissue sealant

Springer Online Journal Archives 1860-2000

Medicine

Abstract Viable intraluminal tumor cells can penetrate a clinically intact rodent colonic anastomosis and give rise to perianastomotic tumor growth. The aim of this study was to determine whether transanastomotic cell migration can be prevented by fibrin-based tissue sealant. Following distal colonic transection and reanastomosis with 5/0 silk sutures, Fischer F344 rats were randomly allocated to three experimental groups. In Group A, a circumferential ring of tissue sealant was placed around the serosal surface of the anastomosis; in Group B, sealant was limited to 50 percent of the anastomotic circumference; and, in Group C, no sealant was applied. All rats then had 10 5 Mtln 3 carcinoma cells injected into the proximal colonic lumen via a rectal catheter. The incidence of perianastomotic tumor at 21 days was significantly lower in Group A (3 of 14 animals) than in Group B (11 of 16 rats) (P =0.012; Fisher's exact test) or Group C (10 of 14 rats;P=0.011). A further experiment demonstrated that sealant did not protect the anastomosis when tumor cells were instilled directly into the peritoneal cavity. A topical carcinocidal action therefore appears unlikely, but our results suggest that a circumferential anastomotic ring of fibrin sealant forms an effective mechanical barrier preventing intraluminal tumor cells from reaching the peritoneal cavity.

Electronic Resource

1432-2323

Springer Online Journal Archives 1860-2000

Medicine

Résumé Afin d'évaluer le CA 15-3, un nouvel antigène associé au cancer du sein, et de le comparer a l'ACE, toutes les femmes ayant un cancer du sein ont eu des dosages pré-opératoires et postopératoires réguliers (tous les 3 mois) de ces deux antigènes. Parmi les 124 femmes avec un cancer primitif du sein, 23% avaient une élèvation du CA 15-3 (supérieure à 25 unités/ml) alors que 11% avaient une élévation de l'ACE (supérieure à 5 ng/ml) (p=NS). Aucun de ces marqueurs n'était corrélé avec un envahissement lymphatique régional. Dans 45 cas de premières récidives, le taux de CA 15-3 était élevé dans 58% des cas alors que le taux d'ACE était élevé dans 47% (p=NS). Chez 17 femmes ayant une récidive loco-régionale seule, le taux de CA 15-3 n'était jamais supérieur à 40 unités/ml alors que 11 des 12 femmes, ayant à la fois récidive loco-régionale et récidive à distance, avaient un taux de CA 15-3 supérieur à 40 unités/ml (χ2∶ 21.36,p〈0.0001). Cette étude montre que le CA 15-3, tout comme l'ACE, ne présente que peu de valeur clinique seule dans le cancer primitif du sein. Le CA 15-3 est un marqueur précis (précision globale, 97%) des métastases à distance chez la patiente avec cancer du sein et récidive loco-régionale. Ce fait présente une grande importance dans la démarche diagnostique et thérapeutique chez ces patientes.

Resumen Con el objeto de evaluar y comparar el CA 15-3, un nuevo antígeno asociado con cáncer mamario, y de compararlo con el antígeno carcinoembriónico (CEA), se hizo la determinación preoperatoria y postoperatoria seriada (trimestral), en todos los pacientes que se presentaron con cáncer mamario a partir de octubre de 1986. De 124 pacientes con cáncer mamario, 23% presentaban un CA 15-3 elevado (〉25 unidades/ml), mientras el 11% exhibía un CEA elevado (〉5 ng/ml) (p=NS). Ninguno de los dos marcadores sirvió como indicador de la extensión del cáncer primario a los ganglios regionales. En 45 recurrencias de cancer mamario el CA 15-3 apareció elevado en el momento de la aparición de la primera recurrencia en el 58% de los casos, en tanto que el CA 15-3 apareció elevado en 47% (p=NS). De 17 pacientes con recurrencia local-regional solamente, ninguno mostró un CA 15-3 por encima de 40 unidades/ml, mientras 11 de 12 con recurrencias local-regional y distante sincrónicas mostraron niveles de CA 15-3 mayores de 40 unidades/ml (χ2∶ 21.36,p 〈 0.0001). Este estudio demuestra que el CA 15-3, al igual que el CEA, es de escaso valor clínico en la valorización del cáncer mamario primario. Sin embargo, el CA 15-3 es un indicador certero (certeza global de 97%) de metástasis distantes sincrónicas en pacientes con recurrencia local-regional de un cáncer mamario. La presente información tiene importantes implicaciones para el desarrollo de futuras investigaciones y para el manejo de tales pacientes.

Abstract To evaluate CA 15-3, a new breast cancer associated antigen, and to compare it with carcinoembryonic antigen (CEA), all patients presenting with breast cancer had preoperative and serial (3-monthly) postoperative levels measured. Of 124 patients with primary breast cancer, 23% had an elevated CA 15-3 (〉25 units/ml) while 11% had an elevated CEA (〉5 ng/ml) (p=not significant). Neither marker was an indicator of spread to regional lymph nodes in primary breast cancer. In 45 recurrences of breast cancer, CA 15-3 was elevated at the time of first recurrence in 58% while CEA was elevated in 47% (p=not significant). Of 17 patients with locoregional recurrence alone, none had a CA 15-3 above 40 units/ml while 11 of 12 with synchronous locoregional and distant recurrence had a CA 15-3 level greater than 40 units/ml (χ2∶ 21.36,p 〈 0.0001). This study shows that CA 15-3, like CEA, is of little clinical value in primary breast cancer. CA 15-3, however, is an accurate indicator (overall accuracy, 97%) of synchronous distant metastases in patients with locoregional recurrence from breast cancer. This information has important implications for further investigation and management of such patients.

Electronic Resource

1248-9204

Inguinal hernia ; Randomised controlled trial ; Health status measures

Springer Online Journal Archives 1860-2000

Medicine

Summary The objective was to compare laparoscopic with open groin hernia repair in respect of patient-assessed outcome up to three months post-operatively. As part of a multicentre pragmatic trial 716 patients were recruited in 13 UK hospitals and randomly assigned to receive laparoscopic or open repair. Most participants were men (95%) with unilateral hernias (92.5%) which were inguinal (98.5%). Questionnaires were completed one week, one month, and three months after surgery. The principal endpoints were groin pain and return to usual social activities. The other outcomes were herniaspecific questions and the SF-36, EQ-5D and HADS measures. All analyses were by intention to treat. At one week and one month, respectively 10.3% and 13.9% fewer people in the laparoscopic group had groin pain and 27.7% and 37.2% fewer had numbness (all P 〈 0.001). Return to usual social activities was quicker in the laparoscopic group (P = 0.01). The laparoscopic group also had significantly more favourable scores at one week in five SF-36 subscales (physical functioning (P 〈 0.001), social functioning (P = 0.004), role physical (P 〈 0.001), role mental (P = 0.003) and pain (P 〈 0.001)), the EQ-5D utility score (P = 0.003) and the depression subscale of HADS (P = 0.001), and at one month in two SF-36 subscales (physical functioning (P = 0.01) and role physical (P = 0.01)). There was no detectable advantage by three months. Our findings that short-term outcome was better for patients allocated laparoscopic repair are consistent with other trials.

Electronic Resource

1432-2218

Carbon dioxide ; Pneumoperitoneum ; Extraperitoneal insufflation

Springer Online Journal Archives 1860-2000

Medicine

Abstract Carbon dioxide pneumoperitoneum has been shown to produce respiratory and hemodynamic changes due to both CO2 absorption and the effects of increased intraperitoneal pressure. We have measured the blood gas, end-tidal CO2, and hemodynamic changes produced during extraperitoneal CO2 insufflation (n=22). These have been compared with the changes occurring during CO2 pneumoperitoneum (n=11) under standardized anesthetic conditions. The changes observed during pneumoperitoneum were consistent with previous descriptions. There was a median rise in arterial pCO2 of 1 kPa over the first 15–20 min, followed by a second phase of only gradual change. There was also an increase in mean arterial pressure of 18 mmHg during the insufflation period. We have found a similar magnitude of rise in arterial pCO2 during extraperitoneal insufflation (median 0.83 kPa), but the rate of rise was significantly slower (P〈0.05). In addition, there was no change in the mean arterial pressure during extraperitoneal insufflation. Our results suggest that extraperitoneal CO2 insufflation may be safer than CO2 pneumoperitoneum in patients with preexisting cardiorespiratory disease.

Electronic Resource

1569-8041

camptothecin analogues ; GG211 ; continuous infusion ; phase I trial ; topoisomerase I inhibitors

Springer Online Journal Archives 1860-2000

Medicine

Abstract Background: Preclinical results support a prolonged schedule of administration for topoisomerase I inhibitors, and we have previously demonstrated the safety and activity of the novel water-soluble topoisomerase I inhibitor GG211 when given as a 72-hour continuous infusion to cancer patients. Patients and methods: In a three-center international phase I trial, 38 patients received GG211 doses from 0.3 to 0.5 mg/m2/day by continuous intravenous infusions for seven, 14, and 21 days. Patients' median performance status was 1; nearly half had colorectal cancer, and 35 patients had prior chemotherapy. Results: The first patient cohort received 0.3 mg/m2/day for seven days with no significant toxicities. Subsequent cohorts received continuous infusions for 14 and 21 days at this dose level with only mild myelosuppression noted. Dose-escalation on the 21-day schedule was then performed. No dose-limiting toxicity occurred at the 0.4 mg/m2/day dose level. Thrombocytopenia was dose-limiting with 0.5 mg/m2/day dosing but was not cumulative. Other grade 3–4 toxicities included neutropenia, nausea, vomiting, diarrhea, and fatigue. Partial responses occurred with 21-day infusion in two patients with breast and ovarian cancer at the 0.3 and 0.4 mg/m2/day dose levels, respectively. Mean GG211 lactone Css ranged from 0.17 to 0.64 ng/ml. Conclusion: The maximum tolerated dose of GG211 administered as a 21-day continuous infusion is 0.4 mg/m2/day with antitumor activity noted at tolerable doses.

Electronic Resource

1432-2218

Key words: Driver reaction times — Inguinal hernia repair

Springer Online Journal Archives 1860-2000

Medicine

Abstract Background: The aim of this study was to assess whether prosthetic tension-free inguinal hernia repair would cause less impairment of reaction times, thus allowing an earlier return to driving than previously recommended after conventional hernia repair. Methods: Driver reaction times were measured in 64 patients randomized to open tension-free repair or totally extraperitoneal endoscopic inguinal hernia repair. Measurements were made preoperatively and on postoperation days 1, 3, and 6. Results: In the endoscopic group, there was a gradual improvement in hand and foot reaction times over the days tested. In the open group, there was a slowing in both hand and foot reaction times on postoperation days 1 and 3. The difference in foot reaction times between the open and endoscopic groups was significant on these days (p= 0.01 and 0.003, respectively). By day 6, the foot reaction times in the open group were slightly faster than before surgery. Conclusions: After prosthetic tension-free inguinal hernia repair, patients can return to driving 1 week after the operation.

Electronic Resource

1573-0646

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Abstract Ilmofosine, an ether lipid derivative of lysophosphatidylcholine has antineoplastic activityin vitro andin vivo. Maximum efficacy in preclinical models is associated with prolonged exposure to the drug. In a Phase I trial of a weekly 2 hour infusion schedule of ilmofosine, a syndrome of lethargy, diminished performance status, and mild hepatotoxicity was dose-limiting at 550 mg/m2. To avoid the higher drug concentrations associated with a brief infusion, a Phase I study of a weekly 24 hour infusional schedule was undertaken in an attempt to maximize dose-intensity. Doses were escalated from 550 to 800 mg/m2. Toxicities included nausea, anorexia, fatigue, and minor elevations of liver function tests. The dose limiting toxicity at 800 mg/ m2 was a syndrome of severe abdominal pain. No neutropenia or thrombocytopenia was observed except in one patient who was found to have a myelodysplastic syndrome, thought not to be related to drug therapy. The more prolonged infusion schedule of ilmofosine did not result in a substantial increase in the tolerable dose.

Electronic Resource

1573-0646

5-fluorouracil ; infusion ; infusional therapy ; colorectal cancer

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Abstract A novel schedule of 5-fluorouracil administration has been developed for biochemical modulation studies. In combination with the pyrimidine synthesis inhibitor PALA, 5-fluorouracil has been given as a 24-hour infusion, repeated weekly: a dose of 2600 mg/m2 is well tolerated. To identify a suitable dose of 5-fluorouracil as a single agent on this schedule, we treated 26 patients at doses ranging from 2800 to 3400 mg/m2 per week. Two-thirds of the patients had failed previous therapy, and most were symptomatic from their disease. Over half of the patients had metastatic colorectal cancer. The dose-limiting toxicity was diarrhea: Grade 3 or 4 toxicity occurred at every level tested. Twenty-two of the 26 patients required therapy interruption because of toxicity. The severity of this toxicity indicated that escalation of 5-fluorouracil on this schedule beyond the 2600 mg/m2 known to be tolerated in the PALA-containing regimen, would be impractical. Two patients, both with previously untreated colorectal cancer, had partial remissions lasting three and five months respectively. This dose-intense schedule of 5-fluorouracil administration will be explored further in large-scale randomized trials.

Electronic Resource