Safety and efficacy of lenalidomide (Revlimid) in recurrent ovarian and primary peritoneal carcinoma

OBJECTIVES: To conduct a phase I trial to determine the safety and toxicity profile of a novel immunomodulatory drug, lenalidomide, in recurrent ovarian and primary peritoneal cancer. The secondary objective is to evaluate the efficacy profile and quality of life (QOL) parameters in patients receiving this treatment. METHODS: Patients with recurrent ovarian or peritoneal cancer who received standard staging surgery and at least one prior platinum-based chemotherapy regimen were treated with single-agent oral lenalidomide 25 mg daily for 21 days of a 28-day cycle. Toxicities were monitored by patient report, physical exam, and laboratories. Response was assessed by imaging, physical exam, and CA-125. Therapy was discontinued with disease progression and/or unacceptable toxicity. RESULTS: 20 patients with recurrent ovarian or peritoneal cancer were enrolled and received 70 completed 28-day cycles and 10 partial cycles of lenalidomide therapy. The majority of adverse events were grades 1-2, including fatigue (25/80 cycles), nausea/vomiting (23/80), constipation (13/80), abdominal pain (17/80), rash (12/80), neutropenia (12/80), and anemia (12/80). Grade 3 toxicities occurred in 12 of 80 cycles (14%) and no grade IV toxicities were observed. Eleven patients completed > or = 2 cycles and were evaluable for response. Nine achieved stable disease (SD) of at least 3 months, with four patients maintaining SD for > 6 months. The mean time to progression was 5.8 months (range 2-12 months). CONCLUSION: Overall, oral lenalidomide was well tolerated and may have some activity as a single agent in this heavily pre-treated population. Further studies combining lenalidomide with cytotoxic treatments may be warranted in this disease setting.     

Detection of pelvic lymph node micrometastasis in stage IA2-IB2 cervical cancer by immunohistochemical analysis

OBJECTIVES: The objectives of this study were to (1) determine the incidence of lymph node micrometastasis in cervical cancer by immunohistochemical analysis and (2) determine if the presence of micrometastasis is a poor prognostic feature in early cervical cancer. METHODS: We retrospectively reviewed the medical records of 62 patients who underwent radical hysterectomy and lymphadenectomy for FIGO stage IA2-IB2 cervical cancer at Stanford University Hospital from 1990 to 2000. Forty-nine patients with negative lymph nodes were identified. A total of 976 formalin-fixed paraffin-embedded pelvic lymphadenectomy specimens were serially sectioned and stained with anti-cytokeratin antibodies AE1 and AE1/CAM5.2. RESULTS: Six patients had stage IA2 disease, 37 had stage IB1, and 6 had IB2. The mean age of the patients was 44 years (range, 24-76). Seventy-one percent had squamous cell carcinomas, 22% had adenocarcinomas, and 6% had other types. Lymph node micrometastases were immunohistochemically detected in 4 of the 49 (8.1%) patients, comprising 4 of 976 (0.41%) pelvic lymph nodes examined. Twelve of 45 (15.6%) patients with negative nodes had lymph-vascular space invasion (LVSI) whereas 3 of 4 (75%) patients with micrometastases had LVSI. At a mean follow-up time of 39.4 months, 2 of 4 (50%) patients with micrometastasis had recurrent disease, while 3 of 45 (6.7%) patients without micrometastasis developed recurrent disease. CONCLUSIONS: These preliminary data suggest that immunohistochemical detection of pelvic lymph nodes is more frequent in patients with LVSI and may identify patients needing adjuvant chemoradiation.     

Experience with a low-pressure colonic pouch (Mainz II) urinary diversion for irreparable vesicovaginal fistula and bladder extrophy in East Africa

Introduction and hypothesis  

We report our experience with a low-pressure colonic pouch for urinary diversion in women with irreparable vesicovaginal fistulas and bladder extrophy.     

Vertical Strut Ossiculoplasty: A Versatile Alternate to Conventional Techniques—A Randomized study

IntroductionVarious ossicular reconstruction materials and techniques have been described in literature using autologous ossicle, cortical bone, autologous cartilage, synthetic materials and implants like total/partial ossicular replacement prosthesis (TORP/PORP) etc., but it has always been a topic of controversy in terms of the efficacy, longevity and complications of the material or method used.Material and MethodsThis is a prospective, interventional, comparative, double-blind randomized control study which was done at a tertiary care center to compare outcomes of conventional and carved conchal cartilage (vertical strut) type III Tympanoplasty in terms of graft uptake and hearing gain. A total number of 52 cases were enrolled, randomized and allocated to 2 groups (26 each) i.e. group A (conventional type III) and group B (vertical strut technique).ResultsGraft uptake was seen in 25 (96.16%) patients in group B while it was observed in 23 (88.5%) cases in group A. Hearing gains were also better in group B.ConclusionThis study suggests that Vertical Strut technique can be studied further as it gives better gains in Air Conduction threshold and A-B Gap along with graft uptake as it provides better middle ear space and ossicular / tympanic membrane interface resulting in better hearing.     

Long-term survivors using intraoperative radiotherapy for recurrent gynecologic malignancies

PURPOSE: To analyze the outcomes of therapy and identify prognostic factors for patients treated with surgery followed by intraoperative radiotherapy (IORT) for gynecologic malignancies at a single institution. METHODS AND MATERIALS: We performed a retrospective review of 36 consecutive patients treated with IORT to 44 sites with mean follow-up of 50 months. The primary site was the cervix in 47%, endometrium in 31%, vulva in 14%, vagina in 6%, and fallopian tubes in 3%. Previous RT had failed in 72% of patients, and 89% had recurrent disease. Of 38 IORT sessions, 84% included maximal cytoreductive surgery, including 18% exenterations. The mean age was 52 years (range, 30-74), mean tumor size was 5 cm (range, 0.5-12), previous disease-free interval was 32 months (range, 0-177), and mean IORT dose was 1,152 cGy (range, 600-1,750). RT and systemic therapy after IORT were given to 53% and 24% of the cohort, respectively. The outcomes measured were locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and treatment-related complications. RESULTS: The Kaplan-Meier 5-year LRC, DMFS, and DSS probability for the whole group was 44%, 51%, and 47%, respectively. For cervical cancer patients, the Kaplan-Meier 5-year LRC, DMFS, and DSS estimate was 45%, 60%, and 46%, respectively. The prognostic factors found on multivariate analysis (p 相似文献   

An update on Ayurvedic herb Convolvulus pluricaulis Choisy

Convolvulus pluricaulis Choisy (C. pluricaulis) is a perennial herb that seems like morning glory. All parts of the herb are known to possess therapeutic benefits. The plant is used locally in Indian and Chinese medicine to cure various diseases. It is used in Ayurvedic formulation for chronic cough, sleeplessness, epilepsy, hallucinations, anxiety etc. Based on the comprehensive review of plant profile, pharmacognosy, phytochemistry, pharmacological and toxicological data on the C. pluricaulis, there will be more opportunities for the future research and development on the herb C. pluricaulis. Information on the C. pluricaulis was collected via electronic search (using Pub Med, SciFinder, Google Scholar and Web of Science) and library search for articles published in peer-reviewed journals. Furthermore, information also was obtained from some local books on ethnopharmacology. This paper covers the literature, primarily pharmacological, from 1985 to the end of 2012. The C. pluricaulis is an important indigenous medicine, which has a long medicinal application for liver disease, epileptic disease, microbial disease, cytotoxic and viral diseases, central nervous system (CNS) disease in Ayurvedic medicine, traditional Chinese medicine and other indigenous medical systems. The isolated metabolites and crude extract have exhibited a wide of in vitro and in vivo pharmacological effect, including CNS depression, anxiolytic, tranquillizing, antidepressant, antistress, neurodegenerative, antiamnesic, antioxidant, hypolipidemic, immunomodulatory, analgesic, antifungal, antibacterial, antidiabetic, antiulcer, anticatatonic, and cardiovascular activity. A chemical study of this plant was then initiated, which led to the isolation of carbohydrats, proteins, alkaloids, fatty acids, steroids, coumarins, flavanoids, and glycosides as active chemicals that bring about its biological effects. A series of pharmacognostical studies of this plant show that it is a herb, its stem and leaves are hairy, more over it has two types of stomata, anisocytic and paracytic. A herb, C. pluricaulis has emerged as a good source of the traditional medicine for the treatment of liver disease, epileptic disease, microbial disease, cytotoxic and viral diseases, and CNS disease. Pharmacological results have validated the use of this species in traditional medicine. All the parts of the herb are known to possess therapeutic benefits. Expansion of research materials would provide more opportunities for the discovery of new bioactive principles from C. pluricaulis.     

Contribution of arginase activation to vascular dysfunction in cigarette smoking

Background

Cigarette smoke increases the risk of several cardiovascular diseases and has synergistic detrimental effects when present with other risks that contribute to its pathogenesis. Oxidative injury to the endothelium via reactive oxygen species (ROS) and nitric oxide (NO) dysregulation is a common denominator of smoking-induced alterations in vascular function. However, the mechanisms underlying ROS and NO dysregulation due to smoking remain unclear. We tested if arginase (Arg) activation/upregulation contributes to this phenomenon by constraining nitric oxide synthase (NOS) activity.

Methods

Arg2 knockout (Arg2^−/−) and control C57BL/6J mice were either exposed to cigarette smoke, 6 h/day/2 weeks (Second Hand Smoking; SHS) or housed in normal environment (Non Smoking; NS). Arg activity, NO and ROS levels were determined by measuring urea production, fluorescent dye (DAF), and dihydroethedium (DHE) respectively in isolated mouse aorta.

Results

Arg activity and ROS levels were higher NO lower in SHS compared to NS mice. SHS failed to lower NO levels in Arg2^−/− mice. Endothelial dependent vasodilation (EDV) was attenuated in SHS mice as compared to controls (78.80% ± 8 vs 46.58% ± 5). This impaired EDV was abolished in Arg2^−/− mice (67.48% ± 7 in SHS vs. 78.80% ± 8 in NS). Vascular stiffness was increased in SHS mice as compared to NS controls but remained unchanged in Arg2^−/− mice.

Conclusion

Endothelial NOS is uncoupled by smoking exposure, leading to endothelial dysfunction and vascular stiffness, a process that is prevented by Arg2 deletion. Hence, we identify Arg2 upregulation as a critical pathogenic factor and target for therapy in oxidative injury following smoking exposure through reciprocal regulation of endothelial NOS.