Long-term safety and efficacy of bimatoprost solution 0·03% application to the eyelid margin for the treatment of idiopathic and chemotherapy-induced eyelash hypotrichosis: a randomized controlled trial.

BACKGROUND: Bimatoprost ophthalmic solution 0·03% is approved in several countries for the treatment of eyelash hypotrichosis. Previous trials were limited to 4 months of treatment and primarily idiopathic hypotrichosis. OBJECTIVES: To evaluate the long-term safety and efficacy of bimatoprost in patients with idiopathic or chemotherapy-induced hypotrichosis. METHODS: This multicentre, double-masked, randomized, parallel-group study included two 6-month treatment periods [treatment period 1 (TP1) and treatment period 2 (TP2)]. Patients with idiopathic hypotrichosis were randomized to three treatment groups: (i) bimatoprost (TP1 and TP2); (ii) bimatoprost (TP1) and vehicle (TP2); and (iii) vehicle (TP1) and bimatoprost (TP2). Patients with chemotherapy-induced hypotrichosis were randomized to two treatment groups: (i) bimatoprost or vehicle (TP1) and (ii) bimatoprost (TP2). Primary end point was a composite of at least a one-grade improvement in investigator-assessed Global Eyelash Assessment and at least a three-point improvement in patient-reported Eyelash Satisfaction Questionnaire Domain 2 at month 4. Secondary measures included digitally assessed eyelash characteristics. RESULTS: The primary efficacy end point was met in both populations (idiopathic responder rate was 40·2% for bimatoprost vs. 6·8% for vehicle; postchemotherapy responder rate was 37·5% for bimatoprost vs. 18·2% for vehicle). Efficacy by month 6 was maintained (idiopathic) or enhanced (postchemotherapy) at 12 months. Treatment effects were maintained for approximately 2 months but markedly diminished 4-6 months following treatment cessation in patients with idiopathic hypotrichosis. No drug-related serious adverse events were reported. CONCLUSIONS: Daily treatment with bimatoprost ophthalmic solution 0·03% for 1 year was effective and well tolerated in patients with idiopathic and chemotherapy-induced hypotrichosis.

Bimatoprost for eyelash growth in Japanese subjects: two multicenter controlled studies.

BACKGROUND: Bimatoprost 0.03% has enhanced eyelash prominence in clinical trials enrolling mostly Caucasian subjects. The studies described in this report evaluated the efficacy and safety of bimatoprost in Japanese subjects with idiopathic and chemotherapy-induced eyelash hypotrichosis. METHODS: In two multicenter, double-masked, randomized, parallel-group studies (study 1: n=173 [idiopathic]; study 2: n=36 [chemotherapy-induced]), subjects received bimatoprost 0.03% or vehicle applied once daily to the upper eyelid margins. The primary efficacy measure was eyelash prominence measured by Global Eyelash Assessment (GEA) scores. Additional measures were eyelash length, thickness, and darkness, assessed by digital image analysis, and patient satisfaction (Eyelash Satisfaction Questionnaire-9). Safety assessments included adverse-event monitoring and ophthalmic examinations. RESULTS: Significantly more bimatoprost-treated subjects had at least a one-grade improvement in GEA score from baseline to month 4 compared with vehicle in study 1 (77.3 vs 17.6%; P<0.001) and study 2 (88.9 vs 27.8%; P<0.001). Bimatoprost-treated subjects had significantly greater increases in eyelash length, thickness, and darkness at the primary time point (month 4 in both studies; all P<0.001, study 1; P≤0.04, study 2). The bimatoprost group showed greater subject satisfaction in both studies. The incidence of adverse events was similar in the two groups. Ophthalmic examination showed slightly greater mean reductions in intraocular pressure (IOP) with bimatoprost than with vehicle, and the reductions were within the normal range for daily IOP fluctuations. CONCLUSION: Bimatoprost 0.03% was shown to be effective and safe in these studies of Japanese subjects with eyelash hypotrichosis. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Intracranial germ cell tumors: a single institution experience and review of the literature.

There is little literature to guide therapy in children and young adults with intracranial germ cell tumors. We present 17 consecutively diagnosed intracranial germ cell tumors at The Children's Hospital, Denver, from 1995 to 2001. Of 17 patients, 3 had considerable delay in diagnosis. Two with suprasellar tumors presented with dementia, blindness and pan-hypopituitarism and another with recurrent subarachnoid hemorrhage. Seven had germinoma, three were metastatic at diagnosis. Ten had non-germinomatous germ cell tumors (NGGCT), 5/10 were alpha feto-protein (AFP) positive only, one beta-human chorionic growth (betaHCG) factor positive only, 3 positive for AFP and betaHCG, and 1 malignant teratoma. Therapy for metastatic patients consisted of chemotherapy followed by craniospinal radiation (CSI). Patients with localized disease received chemotherapy followed by focal radiation. Two patients received chemotherapy only, one because she died of sepsis while receiving chemotherapy and one because of neurologic injury incurred during surgery parents elected for no therapy. Three patients have died, one of tumor recurrence, one from a remote complication of surgery and one of sepsis. Twelve patients are alive without evidence of disease from 10 to 68 months (median 31.5 months). All five children with only AFP positivity, treated with chemotherapy and focal radiation are alive without evidence of disease at 10, 16, 22, 41 and 41 months. Thus, there is little evidence that CSI is necessary in non-metastatic germinomas and AFP positive NGGCTs when combined chemotherapy and radiation therapy is used. However, complications of delayed diagnosis, surgery and chemotherapy are important causes of mortality, with only one patient dying of tumor.

Outcomes and factors impacting local recurrence of ductal carcinoma in situ.

BACKGROUND: The optimal management of ductal carcinoma in situ (DCIS) remains controversial. Investigators have focused on identifying patients who are eligible for treatment by excision alone. A retrospective analysis of patients with DCIS treated by various modalities was conducted to compare outcomes and determine factors significant for local recurrence (LR). METHODS: Between 1985-1992, 88 consecutive diagnoses of DCIS were identified in 85 patients. Seventy-four percent were detected mammographically. The most common histologic subtypes were comedo (54%) and cribriform (23%). Tumor sizes were < 2.5 cm (49%), > 2.5-5 cm (26%), > 5 cm (23%), and unknown (2%). Final resection margins were tumor free (75%), close/positive (23%), and unknown (2%). Treatment methods included mastectomy (30%), localized surgery and radiation therapy (LSR) (43%), or wide localized surgery alone (LS) (27%). Radiation therapy (RT) was comprised of 50 grays to the breast, and 53% of treated patients received local "boost" irradiation. RESULTS: The median follow up was 8.3 years. The overall recurrence rate was 13. 6%, whereas the median time to LR was 27.8 months. Recurrence rates according to treatment modality were: LS: 25%; LSR: 13%; and mastectomy: 4%. However, if surgical margins were tumor free, LSR had a LR rate of 3.4%. After RT, no LR occurred prior to 15 months, and 4 of 5 tumors were noninvasive. Nine patients treated by excision alone conformed to the criteria of Lagios et al. criteria and LR occurred in three of nine tumors. Of the factors analyzed, margin status was found to be the best predictor for LR (P = 0.05). CONCLUSIONS: If surgical margins are tumor free, the LSR regimen is equivalent to mastectomy for local tumor control. Annual mammograms may be adequate for the follow-up of patients with irradiated breasts, but biannual studies still are recommended for patients treated with excision alone.

Accuracy and clinical impact of mediastinal lymph node staging with FDG-PET imaging in potentially resectable lung cancer.

To determine the sensitivity, specificity, and accuracy of staging mediastinal nodal disease in potentially resectable lung cancer using fluorodeoxyglucose-positron emission tomography (FDG-PET), computed tomography (CT), or both and compare these results to surgical staging. We also assessed whether PET scanning results changed clinical management. From 1992 to 1997, 50 patients underwent CT, and PET scanning before or close to the time of surgical staging. Sensitivity, specificity, accuracy, and predictive values were then calculated based on pathology results. A retrospective review of the records was performed to determine how PET results affected clinical treatment decisions. Forty-seven of 50 patients had non-small-cell lung cancer. The prevalence of pathologically confirmed mediastinal and hilar involvement was 38%. The sensitivity, specificity, and accuracy of mediastinal disease staging were as follows: CT alone = 73%, 77%, 76%; PET alone = 73%, 94%, 87%; PET + CT = 82%, 96%, 91%, respectively. PET was more specific and accurate than CT (p = 0.025). The results of PET changed management decisions in 12 of 50 cases (24%). Using FDG-PET in conjunction with CT scanning provides the most accurate staging of mediastinal disease in lung cancer by contributing complementary information. Furthermore, PET can affect clinical decision-making and allow some patients considered unresectable a chance for resection.

Longitudinal observations on 15 children with Wiedemann-Beckwith syndrome.

We conducted a follow-up study on 15 patients with Wiedemann-Beckwith syndrome (WBS) to further clarify major and minor diagnostic clinical characteristics and longterm expectations for growth and development. We found patients with WBS tended to have polyhydramnios with large placentas which were almost twice normal placental weight. The large fetal size and polyhydramnios often resulted in early delivery with occasional perinatal mortality (three cases). Increased placental size, with associated polyhydramnios resulting in excessive umbilical cord length, may be useful in suspecting WBS prior to delivery, thereby facilitating perinatal management. The presence of abdominal wall defects and/or macroglossia may help to confirm the diagnosis. At birth, patients were almost 2 standard deviations above the expected mean for gestational age, length, and weight. This trend continued through early childhood and then excessive size became less dramatic with increasing age. We detected no cytogenetic variations in nine patients who had studies done and, to date, no tumors have been detected other than a gastric teratoma that was evident in one infant at birth. Longitudinally, the children have not had an unusual incidence of medical problems, and long-term ultrasound monitoring was not burdensome to the families. In comparison, mental and social development to unaffected siblings and cousins appeared normal.

[Influences of acupuncture on gastroduodenal mucosal lesion and electrical changing induced by stress in rats].

Experiments were performed in 57 SD rats. The stress was induced by binding plus revolving (5.5 xg, 170 c/min, 10 min) or cold (0-4 degrees C, 30-60 min). Selected acupuncture points were "Zusanli" and "Weishu". Bipolar Ag-AgCl recording electrodes were respectively implanted on the serous membrane surface of the antrum, duodenum and on the abdominal skin corresponding to above areas. The results were as follows: (1) There are 63.2% individuals in the stress group which showed a large quantity of bleeding points spreading over the gastroduodenal mucosal membrane. The area density of lesion was 15.8-27.7%. Under microscope the signs emerged including mucosal blood vessel dilatation and hyperaemia, gland cell swelling, virlus broken and peeling off and lymph cell accumulating, etc. 84% individuals showed obvious inhibition of gastroduodenal electroactivities including that the amplitude of slow wave was lower, the frequency decreased even the rhythm was disordered, the number of fast wave reduced and the IDMEC III cycle was prolonged. (2) In the group of acupuncture plus stress only 16.7% individuals showed bleeding or hyperaemia, and the lesion area density was only 1.7%. Also the pathohistological changes were obviously decreased. Gastroduodenal electrical changes were hardly seen (27.2%) or the inhibitory state above were significantly reduced (54.5%) when compared with the stress group. There is strong reason to consider that acupuncture could effectively reduce the mucosal lesion and the electrical inhibition of stomach and duodenum induced by stress in rats.