Cancer-specific mortality of high-risk prostate cancer after carbon-ion radiotherapy plus long-term androgen deprivation therapy.

The treatment outcomes of patients with high-risk localized prostate cancer (PC) after carbon-ion radiotherapy (CIRT) combined with long-term androgen deprivation therapy (LTADT) were analyzed, and compared with those of other treatment modalities, focusing on PC-specific mortality (PCSM). A total of 1247 patients were enrolled in three phase II clinical trials of fixed-dose CIRT between 2000 and 2013. Excluding patients with T4 disease, 608 patients with high-risk or very-high-risk PC, according to the National Comprehensive Cancer Network classification system, who received CIRT with LTADT were evaluated. The median follow-up time was 88.4 months, and the 5-/10-year PCSM rates were 1.5%/4.3%, respectively. T3b disease, Gleason score of 9-10 and percentage of positive biopsy cores >75% were associated with significantly higher PCSM on univariate and multivariate analyses. The 10-year PCSM rates of patients having all three (n = 16), two (n = 74) or one of these risk factors (n = 217) were 27.1, 11.6 and 5.7%, respectively. Of the 301 patients with none of these factors, only 1 PCSM occurred over the 10-year follow-up (10-year PCSM rate, 0.3%), and significant differences were observed among the four stratified groups (P <0.001). CIRT combined with LTADT yielded relatively favorable treatment outcomes in patients with high-risk PC and very favorable results in patients without any of the three abovementioned factors for PCSM. Because a significant difference in PCSM among the high-risk PC patient groups was observed, new categorization and treatment intensity adjustment may be required for high-risk PC patients treated with CIRT.

Clinical treatment of dry eye using 0.03% tacrolimus eye drops.

PURPOSE: To report the clinical outcome of the treatment of dry eyes using 0.03% tacrolimus eye drops (olive oil + tacrolimus 0.03%) (Ophthalmos, Sao Paulo, Brazil). METHODS: Sixteen eyes of 8 patients with Sjögren syndrome dry eyes (age, 51.13 ± 9.45 years) were enrolled in this study (prospective noncontrolled interventional case series). Patients were instructed to use topical 0.03% tacrolimus eye drops twice a day (every 12 hours) in the lower conjunctival sac. Schirmer I test, break-up time, corneal fluorescein, and rose bengal staining score were performed in all patients 1 day before, and 14, 28, and 90 days after treatment with 0.03% tacrolimus eye drops. RESULTS: The average fluorescein staining and rose bengal staining scores improved statistically significantly after 14 days of treatment and improved even more after 28 and 90 days. The average Schirmer I test did not improve statistically significantly after 28 days of treatment, although we did observe a significant improvement after 90 days of treatment with 0.03% tacrolimus eye drops. The average break-up time did not improve statistically after 14 days of treatment, although we observed a significant improvement after 28 and 90 days of treatment with 0.03% tacrolimus eye drops. CONCLUSIONS: Topical 0.03% tacrolimus eye drops successfully improved tear stability and ocular surface status in patients with dry eyes.

Tear film with "Orgahexa EyeMasks" in patients with meibomian gland dysfunction.

PURPOSE: To evaluate the efficacy of a new Orgahexa eye warmer mask for patients with simple meibomian gland dysfunction (MGD) in a prospective comparative study. METHODS: Twenty right eyes of 20 patients with simple MGD, and 22 right eyes of 22 healthy controls were studied. Subjects were allocated to Orgahexa or conventional eye mask wear for 10 min (short-term study), and for 2 weeks (long-term study). Eyelid temperature measurements, slit lamp examination, tear film break-up time, Schirmer test, vital staining, tear film lipid layer interferometry, and dry eye symptomatology scoring with visual analog scales were performed. RESULTS: The Orgahexa eye warmer improved both tear function and ocular surface status, and decreased symptoms significantly without any complications. CONCLUSIONS: The Orgahexa eye warmer is a simple, safe, and convenient method, which seems to improve the ocular surface status and tear functions in patients with simple MGD.

Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.

PURPOSE: To evaluate the safety and efficacy of an original warm moist air device on tear functions and ocular surface of patients with simple meibomian gland dysfunction (MGD). METHODS: Fifteen patients with simple MGD and 20 healthy volunteers were recruited in an initial prospective interventional clinical trial to evaluate the safety and short-term effects of the warm moist air device. The device was applied to the eyes of the subjects for 10 minutes. Temperatures of the eye lids and corneas were measured with an infrared thermometer. Symptoms of ocular fatigue were scored using visual analog scales (VASs). Schirmer test, tear film break-up time (BUT), DR-1 tear film lipid layer interferometry, fluorescein staining, and rose bengal staining were also performed before and after the application of the eye steamer. After the initial study, another 2-week prospective clinical trial was carried out in 10 patients with MGD who received the warm moist air treatment. Ten other patients were also recruited and received warm compress treatment with hot towels for 2 weeks to evaluate the long-term effects of the warm moist air device and the warm compresses on tear film lipid layer thickness and ocular surface health. The warm moist air device and the warm compresses were applied for 10 minutes twice a day. The changes in VAS scores for symptoms, BUT values, fluorescein, and rose bengal staining scores were examined before and after each treatment during the second trial. RESULTS: VAS scores of ocular fatigue improved significantly with short- and long-term applications of the warm moist air device in both studies. The mean corneal surface and eye lid temperatures showed significant elevation within safe limits 10 minutes after the moist air application. The mean BUT prolonged significantly in the patients receiving warm moist air applications but did not change significantly in those treated with warm compresses. DR-1 tear film lipid layer interference showed evidence of lipid expression in the patients and controls, with thickening of the tear film lipid layer after 10 minutes of warm moist air device use. In the 2-week trial, tear film lipid layer thickness increased in both warm moist air device and warm compress groups, with a greater extent of increase in the warm moist air device group. CONCLUSION: Warm moist air device use provided symptomatic relief of ocular fatigue and improvement of tear stability in patients with MGD. The new warm moist air device seems to be a safe and promising alternative in the treatment of MGD.

[Stage A prostate cancer: comparison of subclassification between Japanese rule and TNM, and outcome].

Between 1980 and June, 2002, transurethral resection of prostate was performed against 3294 cases of benign prostatic hyperplasia, and 144 cases of stage A cancer were detected (4.4%). Among these cases, 136 cases which had complete records of examination were studied. Annual number of stage A and A1:A2 ratio were not influenced by introducing PSA determination from 1991, although the number of T1c has been increasing gradually. Since subclassification of stage A is different between Japanese rules (A1; 3 chips of cancer with well-differentiated adenocarcinoma, A2; others) and TNM (T1a; 5% of less number of chips with cancer, T1b; others), two criteria were compared. Coincidence was found with 93.7%, and disagreement was due to ratio of number of chips with cancer to whole number resected, or different grade. The former difference was caused by a larger or smaller prostate. Most cases of A1 and A2 were subjected to watchful waiting or subsequent therapy. PSA was elevated in 10 cases (7%), two of which died from progression of cancer. Other cases were disease-free. Individual pathological findings are important for subclassification of stage A.

Disposable eyelid-warming device for the treatment of meibomian gland dysfunction.

PURPOSE: To assess the clinical efficacy of a newly developed disposable eyelid-warming device (Eye Warmer) for the treatment of meibomian gland dysfunction (MGD). METHODS: The Eye Warmer was applied for 5 minutes to 44 eyes of 22 patients who exhibited decreased tear break-up time (BUT) and dry-eye symptoms. Its efficacy was assessed on the basis of BUT and dry-eye symptoms in the short-term study. In the therapeutic study, the Eye Warmer was applied to 34 eyes of 17 MGD patients with decreased BUT and dry-eye symptoms for 5 minutes once a day for 2 weeks. The 16 eyes of 8 patients served as untreated controls. We examined tear film lipid layer interference patterns, BUT, meibomian gland secretion, and dry-eye symptoms in both groups before and after the treatment. RESULTS: BUT and dry-eye symptoms significantly improved after the treatment in both the short-term and the therapeutic study (P<.01). The incidence of normal tear lipid layer in the treated group was significantly higher after treatment (28 eyes [82.4%]) than before (19 eyes [55.9%]) (P=.036). The incidence of meibomian gland obstruction was significantly decreased after treatment (14 eyes [41.2%]) compared to before treatment (26 eyes [76.5%]) (P=.006). CONCLUSIONS: Warming the eyelids with the Eye Warmer improved the stability and uniformity of the tear lipid layer in MGD patients by melting the meibomian gland lipid. Our study demonstrates the usefulness of the Eye Warmer for the treatment of MGD.

Tear function and ocular surface changes with topical mitomycin (MMC) treatment for primary corneal intraepithelial neoplasia.

PURPOSE: To evaluate the tear function and ocular surface alterations in patients with primary CIN before and after treatment with topical mitomycin (MMC). PATIENTS AND METHODS: We describe seven patients with unilateral CIN treated with 0.04% topical MMC three times daily until full eradication of the lesion. The patients underwent tear and ocular surface examinations including Cochet-Bonnet corneal sensitivity measurements, tear film break-up time (BUT), Schirmer test, and Rose-Bengal staining before, at the time of resolution of the CIN, and at the final follow-up. Conjunctival impression cytology was performed before treatment and at the last visit. RESULTS: The mean pretreatment corneal sensitivity was 30.3 +/- 7.4 mm and improved to 55 +/- 5 mm at the final visit (P < 0.05). There were no aqueous-deficient eyes. The BUT values and Rose-Bengal staining scores also showed significant improvement at the last follow-up compared with the pretreatment values (P < 0.05). Initial impression cytology specimens showed goblet cell loss, higher grades of squamous metaplasia, areas of isolated keratinized, binucleated, and actively mitotic disfigured epithelial cells in all patients. The mean goblet cell density and squamous metaplasia grade were observed to improve significantly at the last visit (P < 0.05). MMC-induced cytologic changes were seen to persist long after cessation of treatment in some patients. All eyes remained free of recurrence and complications during the follow-up period. CONCLUSION: We found 0.04% topical MMC treatment tid until full eradication to be effective in the management of CIN. The ocular surface disease of CIN was characterized by disturbance of tear film stability, goblet cell loss, and increased squamous metaplasia in all patients. Impression cytology proved useful in attaining the diagnosis of CIN, evaluating the effect of treatment, and showing MMC-related long-term changes on the ocular surface.

Low-concentration homogenized castor oil eye drops for noninflamed obstructive meibomian gland dysfunction.

OBJECTIVE: We developed low-concentration homogenized castor oil eye drops for the treatment of patients with noninflamed obstructive meibomian gland dysfunction (MGD), a major cause of lipid-deficiency dry eye, and assessed the safety, stability, and efficacy of the eye drops. DESIGN: Randomized, double-masked, placebo-controlled crossover clinical trial. PARTICIPANTS: Forty eyes of 20 patients with noninflamed MGD. METHODS: After a preliminary study of eye drops containing castor oil, 2% castor oil and 5% polyoxyethylene castor oil (emulsifier) were mixed to formulate homogenized oil eye drops. The patients were assigned randomly to receive oil eye drops or placebo six times daily for 2 periods of 2 weeks each. MAIN OUTCOME MEASURES: At the end of each treatment period, we assessed symptoms, tear interference grade, tear evaporation, fluorescein and rose bengal scores, tear break-up time (BUT), and meibomian gland orifice obstruction. Safety and stability tests were also performed. RESULTS: Symptom scores, tear interference grade, tear evaporation test results, rose bengal scores, tear BUT, and orifice obstruction scores after the oil eye drop period showed significant improvement compared with the results after the placebo period. No complications attributable to the eye drops were observed. The oil eye drops were stable when stored at 4 degrees C. CONCLUSIONS: The results indicate that castor oil eye drops are effective and safe in the treatment of MGD. The possible mechanisms of this treatment are improvement of tear stability as a result of lipid spreading, ease of meibum expression, prevention of tear evaporation, and the lubricating effect of the oil eye drops.

Clinical application of living-related conjunctival-limbal allograft.

PURPOSE: To report one successful case of conjunctival-limbal allograft for the treatment of a severe ocular surface disorder. METHODS: Interventional case report. A 9-year-old patient suffering from Stevens-Johnson syndrome with total keratinization of the ocular surface of both eyes was treated in the left eye by corneal and conjunctival stem cell transplantation. Oral cyclosporin A and topical autologous serum and corticosteroids were administered. RESULTS: Mucosal epithelial phenotype was maintained in the left eye at most recent examination for more than 3 years after ocular surface reconstruction. CONCLUSION: A total keratinized ocular surface may be treated with the combination of conjunctival and corneal stem cell transplantation.