Mammalian target of rapamycin inhibition induces cell cycle arrest in diffuse large B cell lymphoma (DLBCL) cells and sensitises DLBCL cells to rituximab

Diffuse large B-cell lymphoma (DLBCL) is a common lymphoma entity. Although a significant amount of DLBCL patients can be cured with modern chemotherapeutic regimens, a substantial proportion of patients die because of progressive disease. Therefore, new therapeutic strategies are clearly needed. Inhibitors of mTOR [mammalian target of rapamycin (Rap)] represent a new class of antiproliferative drugs with applications as immunosuppressive and anticancer agents. Extensive safety data exist on the mTOR inhibitor RAD001, which is already approved as an immunosuppressant in organ transplant recipients. Rap and RAD001 inhibited cell cycle progression in DLBCL cells by inducing a G1 arrest without inducing apoptosis. Phosphorylation of the main targets of mTOR, p70 s6 kinase and 4-EBP-1 was reduced in cells cultured in the presence of RAD001. Cell cycle arrest was accompanied by reduced phosphorylation of the retinoblastoma protein (RB) as well as reduced expression of cyclin D3 and A in all cell lines. Although the effect of the chemotherapeutic agent vincristine (vin) was not enhanced by RAD001, rituximab-induced cytotoxicity was augmented in the rituximab-sensitive cell lines. mTOR inhibition is a promising therapeutic strategy in DLBCL by inducing a G1 arrest and augments rituximab-induced cytotoxicity. Therefore, combination of these drugs might be an interesting new therapeutic approach in DLBCL patients.     

Comparison of three patent foramen ovale closure devices in a randomized trial (Amplatzer versus CardioSEAL-STARflex versus Helex occluder)

This randomized trial compared procedural complications and 30-day clinical outcomes of 3 patent foramen ovale (PFO) closure devices (Amplatzer, Helex, and CardioSEAL-STARflex). It examined 660 patients (361 men, 299 women, mean age 49.3+/-1.9 years), with 220 patients per group. All patients had a history of paradoxical embolism. All PFO closures were successful technically. Exchange of devices for others was most frequently required for the Helex occluder (7 of 220) and 2 of 220 in either of the other groups. Three device embolizations in the Helex group were retrieved and replaced successfully. One patient with a Helex occluder developed a transient ischemic attack and recovered without treatment. A hemopericardium in that group was punctured without affecting the device. One tamponade in the Amplatzer group required surgical device explantation. In 8 of 660 patients in the CardioSEAL-STARflex group, thrombi resolved after anticoagulation. Sixteen patients (11 in the CardioSEAL-STARflex group, 3 in the Amplatzer group, and 2 in the Helex group) had episodes of atrial fibrillation. PFOs were closed completely in 143 of 220 patients (65%) in the Amplatzer group, 116 of 220 patients (52.7%) in the Helex group, and 137 of 220 patients (62.3%) in the CardioSEAL-STARflex group at 30 days with significant differences between the Helex and Amplatzer occluders (p=0.0005) and the Helex and CardioSEAL-STARflex occluders (p=0.0003). PFO closure can be performed safely with each device. In conclusion, the Helex occluder embolized more frequently. Device thrombus formation and paroxysmal atrial fibrillation were more common with the CardioSEAL-STARflex occluder.     

Laparoscopic detorsion allows sparing of the twisted ischemic adnexa

STUDY OBJECTIVE: To determine the safety and outcome of laparoscopic detorsion in the management of the twisted ischemic, hemorrhagic adnexa. DESIGN: Retrospective chart review and prospective follow-up (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: Fifty-eight women with twisted black-bluish ischemic adnexa encountered at laparoscopy. INTERVENTION: Laparoscopic detorsion with adnexal sparing. MEASUREMENTS AND MAIN RESULTS: All patients had a benign immediate postoperative course. Transient temperature elevation occurred in seven women (12.1%). No signs of pelvic or systemic thromboembolism were detected in any patient. Long-term follow-up included transvaginal ultrasound, which revealed follicular development in the previously twisted adnexa in 54 women; normal macroscopic appearance at incidental subsequent surgery in 9; and in vitro fertilization with retrieval of oocytes from the previously twisted side in 4. CONCLUSION: Laparoscopic detorsion of the twisted ischemic, hemorrhagic adnexa is a safe procedure with minimal postoperative morbidity and a potential for the ovary to recuperate fully with preservation of normal function. Laparoscopic adnexa-sparing procedures should be performed in place of traditional salpingo-oophorectomy in women with this disorder who desire future fertility. (J Am Assoc Gynecol Laparosc 6(2):139-143, 1999)     

Fertility after nonsurgical treatment of ectopic pregnancy

There is no question that the treatment of choice for ectopic pregnancy is surgery. However, since some ectopic pregnancies terminate in tubal abortion or complete resorption, it is questionable whether surgery is necessary in every case. Some patients can be managed by monitoring rising or falling levels of beta-human chorionic gonadotropin (beta-HCG) until tubal abortion or resorption occurs. This approach, which may be the best means of preserving tubal function and fertility, was used in 14 patients who fulfilled extremely selective criteria. In some of the patients, surgery later proved to be necessary, but in 11 nonsurgical management was followed by a fall in beta-HCG levels, and there were no further untoward effects. Three of these patients subsequently developed intrauterine pregnancies, and one patient had a repeat ectopic.     

Reproductive performance following conservative microsurgical management of tubal pregnancy

Between 1981 and 1986, 58 women underwent conservative surgery for ectopic pregnancy; 30 had both tubes present, and 28 had the operation on their single tube. Twenty-five of the 30 women with both tubes present desired pregnancy; 17 (68%) conceived again, 14 (56%) had at least one intrauterine pregnancy and 3 (12%) had a repeat extrauterine pregnancy. Twenty-six of the women with a solitary tube desired pregnancy, 12 (46%) of them had at least one intrauterine pregnancy, and 10 (38.5%) had a repeat extrauterine pregnancy. It was concluded that the incidence of intrauterine pregnancy after conservative surgery in patients with both tubes present is not lower than after radical surgery, and that the incidence of extrauterine pregnancy is not higher. The intrauterine pregnancy rate in patients with a solitary tube is high and still higher than the best results available with in-vitro fertilization and embryo transfer. Therefore conservative surgery is indicated in these patients despite the high incidence of repeat extrauterine pregnancy. Since most of the patients who conceived did so during the first year following the operation, we recommend that patients try to conceive immediately.