A template for reducing ophthalmology outpatient waiting times: community ophthalmic care.

BACKGROUND: Through an Irish Health Service Executive (HSE) initiative to tackle excessive hospital outpatient waiting times, 996 patients referred to the Ophthalmology Outpatient Department (OPD) of the Mater Misericordiae University Hospital (MMUH), Eccles Street, Dublin 7, Ireland, were outsourced to a community medical eye clinic (CMEC) for consultation with specialist-registered ophthalmologists. AIMS: The study aims to determine if patients referred as routine to the OPD department could be managed in a community setting. METHODS: 996 patients were reviewed in the CMEC, and their data was collected and placed into a spreadsheet for analysis. RESULTS: 61.2% of patients referred to the OPD were fully managed in the community clinic, and 34.9% required ophthalmic surgery in hospital. CONCLUSIONS: By facilitating direct listing of some of the surgical patients to the hospital theatre list, 89.8% of the 996 referrals received treatment without needing to attend the hospital outpatients department.

Stimulation of the human RAD51 nucleofilament restricts HIV-1 integration in vitro and in infected cells.

Stable HIV-1 replication requires the DNA repair of the integration locus catalyzed by cellular factors. The human RAD51 (hRAD51) protein plays a major role in homologous recombination (HR) DNA repair and was previously shown to interact with HIV-1 integrase (IN) and inhibit its activity. Here we determined the molecular mechanism of inhibition of IN. Our standard in vitro integration assays performed under various conditions promoting or inhibiting hRAD51 activity demonstrated that the formation of an active hRAD51 nucleofilament is required for optimal inhibition involving an IN-DNA complex dissociation mechanism. Furthermore we show that this inhibition mechanism can be promoted in HIV-1-infected cells by chemical stimulation of the endogenous hRAD51 protein. This hRAD51 stimulation induced both an enhancement of the endogenous DNA repair process and the inhibition of the integration step. Elucidation of this molecular mechanism leading to the restriction of viral proliferation paves the way to a new concept of antiretroviral therapy based on the enhancement of endogenous hRAD51 recombination activity and highlights the functional interaction between HIV-1 IN and hRAD51.

Pathologic response rates following definitive dose image-guided chemoradiotherapy and resection for locally advanced non-small cell lung cancer.

INTRODUCTION: Treatment of technically operable, medically fit locoregionally advanced non-small cell lung cancer (NSCLC) patients is a controversial therapeutic challenge. Our group routinely uses a trimodality approach. Recent advances in radiotherapy allow for improved tumor targeting and daily patient positioning. We hypothesized that these technologies would improve pathologic response rates. We analyzed consecutively treated stage IIIA/IIIB NSCLC patients undergoing chemoradiotherapy before major lung resection, with particular attention paid to the impact of advanced technologies. METHODS: Locoregionally advanced NSCLC patients (N2) staged in a multidisciplinary forum with mediastinoscopy were planned to receive platinum-based chemotherapy and 60Gy and major lung resection. Four-dimensional CT (4DCT) and image-guided radiotherapy (IGRT) were used as available. Survival endpoints were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using Cox proportional hazards models. RESULTS: We identified 53 patients from 2/1999 to 2/2010. Median RT dose was 59Gy. 68% underwent lobectomy. Forty-three patients were downstaged pathologically (81%), 38 experienced mediastinal sterilization (72%), and 21 (40%) had complete pathologic response (pCR). 1 and 2 year OS were 85.5% and 61.6%. Superior OS and DFS were associated with nodal downstaging and mediastinal sterilization (pN0). Treatment with IGRT/4DCT in 10 patients resulted in high rates of nodal downstaging (100% vs 77%, p=0.0452), mediastinal sterilization (90% vs 67%, p=0.0769), and pCR (60% vs 35%, p=0.0728). CONCLUSIONS: In selected patients, definitive dose CRT followed by major lung resection results in promising DFS and OS. The use of advanced radiotherapy techniques (4DCT and IGRT) appears to result in promising pathologic response rates.

Endogenous endophthalmitis: 10-year experience at a tertiary referral centre.

PURPOSE: Endogenous endophthalmitis (EE) is a sight-threatening emergency and the aetiology is often multifactorial. Delayed diagnosis may exacerbate the poor visual prognosis. We describe the management and visual outcomes of EE presenting to a tertiary referral centre. PATIENTS AND METHODS: A prospective consecutive case series of 64 patients presenting with presumed EE from 1997 to 2007 to the Royal Victorian Eye and Ear Hospital were included. All data were collected in a standardized manner. Outcome measures included: visual acuity, microbial profiles, and vitrectomy rate. RESULTS: In total, 64 cases of EE were identified over the study period with a mean age of 57.5 years, and 53.5% were male. Presenting acuities ranged from Snellen 6/6 to no perception of light (NPL). Identifiable risk factors were present in 78.1%, with the majority related to intravenous drug abuse. A 64.1% culture positivity rate was recorded. A vitrectomy rate of 57, 56, and 21% was recorded in documented bacterial, fungal, and no growth cases, respectively. Final Snellen acuities ranged from 6/6 to NPL. A total of 5 out of 64 eyes were enucleated, of which 3 identified Klebsiella species. Better visual outcome was documented in fungal cases. CONCLUSION: EE is a serious ocular condition and has a varied aetiology. Visual outcomes are often poor, irrespective of the method of management. Fungal aetiology often confers a better prognosis, and vitrectomy is advocated for bacterial proven cases.

Acute sixth nerve palsy in a young man, beware of the 'red herring'.

BACKGROUND: Cranial nerve palsies has several etiologies including vascular insufficiency, neoplasm, trauma and inflammation. Isolated sixth nerve palsy is an extremely rare presenting feature of leukemia. AIM: We describe an unusual ocular presentation of a bilateral progressive sixth nerve palsy in a young male with a preceding head injury. CONCLUSION: Acquired sixth nerve palsies in young adults may be due to trauma but in the absence of a definitive history other systemic processes must be outruled. We describe a case of bilateral sixth nerve palsy in a patient with ALL with no obvious CNS involvement. Potential etiological mechanisms are discussed.

Construction-related eye injuries in Irish nationals and non-nationals: attitudes and strategies for prevention.

BACKGROUND: Construction-related ocular injuries are an important cause of vision loss but few studies on the incidence, epidemiology and nature of these injuries exist. AIMS: Due to the perceived increase in occupation-related eye injuries in non-nationals we aimed to investigate the nature of such injuries presenting to a single eye unit over a two-month period. METHODS: One hundred and fifty-five patients presenting to the accident and emergency department with construction related ocular injury were examined. RESULTS: Of 155 patients, 80 were Irish and 75 nonnational, of whom 60, 21.3 and 6.7% were Polish, Lithuanian and Romanian, respectively. Common causative factors included hammering, grinding, drilling and splash injury. Average rate of eyewear protection usage was 35%, with attendance at safety courses highest in Irish nationals. A penetrating eye injury rate of 4.9% overall was observed, all in non-nationals. CONCLUSION: Construction related ocular injury is a serious cause of visual loss in non-nationals. Greater adherence to safety regulations and training is required.

Long term follow up of nasolacrimal intubation in adults.

BACKGROUND/AIMS: The authors have previously reported a short term mean 15 month follow up of nasolacrimal intubation in adults. The effectiveness of this procedure for long term (mean 78 months) control of epiphoria is assessed here. METHODS: 65 eyes from 40 patients who underwent nasolacrimal intubation were followed. Mean age at intubation was 59.2 years. The mean follow up period was 6.2 years. The results were based on long term symptomatic improvement. RESULTS: Complete long term resolution of symptoms was reported in 50.7%. A partial improvement was reported in 38.5%, and no improvement in 10.7%. A better outcome was associated with a canalicular than nasolacrimal duct obstruction. On long term follow up 16.9% required dacrocysto-rhinostomy (DCR). CONCLUSION: Nasolacrimal intubation, a minimally invasive procedure is successful in the long term control of epiphora. Selection of patients with canalicular duct obstruction gives higher success rates with fewer patients subsequently requiring the DCR procedure.

Outcome of endometrial carcinoma patients with involvement of the uterine serosa.

OBJECTIVE: The goal of this work was to evaluate the outcome of endometrial carcinoma patients undergoing primary surgery who have serosal involvement (SI). METHODS: Between 1980 and 1998, 562 women underwent primary surgery for endometrial cancer at the University of Chicago. Thirty-nine were noted to have SI. FIGO stages were IIIA (19), IIIB (1), IIIC (7), and IV (12). Of the 19 IIIA patients, 15 had solitary SI. Twenty-six patients received pelvic radiation therapy (RT) with or without vaginal brachytherapy (VB). One patient received whole-abdomen radiation therapy, and 13, adjuvant chemotherapy. Solitary SI patients received pelvic RT with or without VB as their sole adjuvant therapy. Disease-free survivals (DFSs) were estimated using the method of Kaplan and Meier and prognostic factors were analyzed by the log-rank test. RESULTS: With a median follow-up of 30.3 months, the 5-year actuarial DFS of the entire group was 28.9%. Factors correlated with disease recurrence included tumor stage (P = 0.003) and lymph node involvement (P = 0.04). In addition, patients with solitary SI had a better 5-year DFS (41.5% vs 20%, P = 0.04) than patients with SI plus other extrauterine sites. Relapse occurred in 23 women overall and in 7 of 15 solitary SI patients. The most common site of disease recurrence was distant both in the entire group and in the solitary SI patients. While abdominal recurrences were common in the entire group, they were infrequent in solitary SI patients. CONCLUSION: Endometrial carcinoma patients with SI have a high rate of relapse and a poor outcome. Even when patients have extrauterine disease limited to SI, the outcome is relatively unfavorable. Nonetheless, our results demonstrate the need to distinguish patients with solitary SI and those with SI plus other extrauterine disease sites.

Significant pelvic recurrence in high-risk pathologic stage I--IV endometrial carcinoma patients after adjuvant chemotherapy alone: implications for adjuvant radiation therapy.

OBJECTIVE: To evaluate the risk of pelvic recurrence (PVR) in high-risk pathologic Stage I--IV endometrial carcinoma patients after adjuvant chemotherapy alone. METHODS: Between 1992 and 1998, 43 high-risk endometrial cancer patients received adjuvant chemotherapy. All patients underwent primary surgery consisting of total abdominal hysterectomy and bilateral salpingo-oophorectomy. No patients received preoperative radiation therapy (RT). Regional lymph nodes and peritoneal cytology were sampled in 62.8% and 83.7% of cases, respectively. Most patients had Stage III--IV disease (83.7%) or unfavorable histology tumors (74.4%). None had evidence of extra-abdominal disease. All patients received 4-6 cycles of chemotherapy as the sole adjuvant therapy, consisting primarily of cisplatin and doxorubicin. Recurrent disease sites were divided into pelvic (vaginal, nonvaginal) and extrapelvic (para-aortic, upper abdomen, liver, and extra-abdominal). Median follow-up was 27 months (range, 2--96 months). RESULTS: Twenty-nine women (67.4%) relapsed. Seventeen (39.5%) recurred in the pelvis and 23 (55.5%) in extrapelvic sites. The 3-year actuarial PVR rate was 46.5%. The most significant factors correlated with PVR were cervical involvement (CI) (p = 0.01) and adnexal (p = 0.05) involvement. Of the 17 women who developed a PVR, 8 relapsed in the vagina, 3 in the nonvaginal pelvis, and 6 in both. The 3-year vaginal and nonvaginal PVR rates were 37.8% and 26%, respectively. The most significant factor correlated with vaginal PVR was CI (p = 0.0007). Deep myometrial invasion (p = 0.02) and lymph nodal involvement (p = 0.03) were both correlated with nonvaginal PVR. Nine of the 29 relapsed patients (31%) developed PVR as their only (6) or first site (3) of recurrence. Factors associated with a higher rate of PVR (as the first or only site) were CI and Stage I--II disease. CONCLUSIONS: PVR is common in high-risk pathologic Stage I-IV endometrial cancer patients after adjuvant chemotherapy alone. These results support the continued use of locoregional RT in patients undergoing adjuvant chemotherapy. Further studies are needed to test the addition of chemotherapy to locoregional RT.

Surgery and postoperative radiation therapy in FIGO Stage IIIC endometrial carcinoma.

OBJECTIVE: To determine the outcome, pattern(s) of failure, and optimal treatment volume in Stage IIIC endometrial carcinoma patients treated with surgery and postoperative radiation therapy (RT). METHODS: Between 1983 and 1998, 30 Stage IIIC endometrial carcinoma patients were treated with primary surgery and postoperative RT at the University of Chicago. All underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, sampling of pelvic lymph nodes (PLN), and peritoneal cytology. All were noted to have PLN involvement. Para-aortic lymph nodes (PALN) were sampled in 26 cases, and were positive in 14 cases (54%). Twenty women received whole-pelvic RT (WPRT) and 10 (WPRT), plus paraortic RT (extended-field RT, EFRT). One EFRT patient also underwent concomitant whole-abdominal RT (WART). Adjuvant vaginal brachytherapy (VB) was delivered in 10, chemotherapy in 5, and hormonal therapy in 7 patients. RESULTS: At a median follow-up of 32 months, the actuarial 5-year disease-free and cause-specific survivals of the entire group were 33.9% and 55.8%, respectively. Overall, 16 women (53%) relapsed. Sites of failure included the pelvis (23%), abdomen (13%), PALN (13%), and distant (40%). Of the 7 pelvic failures, 4 were vaginal (3 vaginal only). Patients treated with VB had a trend to a lower vaginal recurrence rate (0/10 vs. 4/20, p = 0.12) than those not receiving VB. All 4 PALN failures were in women treated with WPRT (2 negative, 1 unsampled, and 1 positive PALN). None of the 10 EFRT patients (2 negative, 8 positive PALN) recurred in the PALN. No patient developed an isolated abdominal recurrence. Two patients developed significant RT sequelae: chronic diarrhea in 1 patient treated with WPRT and VB, and small bowel obstruction in 1 patient treated with EFRT. CONCLUSION: FIGO Stage IIIC disease comprises a small percentage of endometrial carcinoma patients but carries a poor prognosis. Our failure pattern suggests that the optimal adjuvant RT volume is EFRT, even in women with negative PALN sampling. VB should also be administered to improve local control. The low rate of abdominal recurrence does not support the routine use of WART in these women. Given the predominance of failure in distant sites, attention should be focused on the development of systemic chemotherapy protocols.

Equivalent racial outcome after conformal radiotherapy for prostate cancer: a single departmental experience.

PURPOSE: African-American (AA) men with prostate cancer present with advanced disease, relative to white (W) men. This report summarizes our clinical and biochemical control (bNED) rates after conformal radiotherapy (RT). In particular, we aim to characterize any race-based outcome differences seen after comparable treatment. PATIENTS AND METHODS: We reviewed 893 patients (418 AA and 475 W) with clinically localized prostate cancer treated between 1988 and 1997. Neoadjuvant hormonal blockade was used in 22.5% of cases, and all patients received conformal RT to a median dose of 68 Gy (range, 60 to 74.8 Gy). Biochemical failure was defined according to the American Society of Therapeutic Radiology and Oncology consensus definition. Median follow-up was 24 months (range, 1 to 114 months). RESULTS: The 5-year actuarial survival, disease-free survival, and bNED rates for the entire population were 80.5%, 70.0%, and 57.6%, respectively. When classified by prognostic risk category, the 5-year actuarial bNED rates were 78.7% for favorable, 57.7% for intermediate, and 39.8% for unfavorable category patients. AA men presented at younger ages and with more advanced disease. Controlled for prognostic risk category, AA and W men had similar 5-year actuarial bNED rates in favorable (78% v 79%, P: = .91), intermediate (52% v 62%, P: =.44), and unfavorable categories (36% v 45%, P: = .09). Race was not an independent prognostic factor (P: = .36). CONCLUSION: Conformal RT is equally effective for AA and W patients. More research is needed in order to understand and correct the advanced presentations in AA men. These data suggest a need for early screening in AA populations.

Characteristics and outcome of endometrial carcinoma patients age 45 years and younger.

Recent reports have suggested that the pathologic features of young patients with endometrial cancer are less favorable than previously thought. We retrospectively reviewed the characteristics and outcome of young patients with endometrial cancer at our institution. A total of 457 surgically staged patients were divided in 2 groups: Group A (age < or =45 years, n = 41) and B (age >45, n = 416). Groups A and B had a similar distribution of tumor stage, grade, histology, lymphovascular invasion, synchronous ovarian primaries, and positive cytology. Although group A tumors had less myometrial invasion (MI) (p = 0.004) and were lower grade (p = 0.06), a trend to more frequent nodal involvement was seen in group A women (p = 0.09). Adverse pathologic features, in particular deep MI, were more common in group A patients older than age 40. Group A patients had a disease-free (p = 0.56) and cause-specific (p = (0.26) survival that was similar to that of group B patients. Young patients with endometrial cancer have a distribution of most pathologic features and equivalent outcome similar to that of older women. However, adverse features are not equally distributed in young women. A discordance may also exist between MI, grade, and nodal involvement.

Synchronous ovarian and endometrial malignancies.

Synchronous ovarian primaries are infrequently found in patients with endometrial cancer. Although numerous investigators have examined the characteristics of these women, most include patients with tumors of similar histology, which may simply represent ovarian metastases. To overcome this problem, we present here patients found to have tumors of dissimilar histology. Of 499 patients with endometrial cancer undergoing primary surgery between 1980 and 1997, 18 (3.6%) were found to have endometrial and ovarian primaries of dissimilar histology. The median age was 64.2 years. Most had stage I, grades I and II, minimally invasive endometrial adenocarcinomas and stage IA mucinous or serous ovarian cystadenocarcinomas. Most ovarian tumors were either borderline or grades I and II. The 5-year actuarial disease-free (DFS) and cause-specific survivals of the entire group were 81.2% and 89.5%, respectively. Those with both stage I ovarian and endometrial primaries had a trend to a better DFS (100 versus 68.6%, p = 0.07) than did women with higher stage disease. Our data demonstrate that synchronous ovarian primaries of dissimilar histology are infrequently found in women undergoing surgery for endometrial cancer. These women seek treatment at a relatively advanced age, and have early-stage, low grade disease in both sites. Their outcome is favorable, particularly those with stage I disease in both sites.

Do conventional pathologic features lose their prognostic significance following postoperative radiation therapy in pathologic stage I-II endometrial adenocarcinoma?

Recent data have suggested that conventional pathologic features (myometrial invasion (MI), grade, stage) lose their prognostic significance following postoperative radiation therapy (RT) in Stage I-II endometrial carcinoma. Our goal was to test this finding in a large cohort of women treated at our institution. Between 1980 and 1997, 188 Stage I (140) and II (48) endometrial adenocarcinoma patients received postoperative RT. RT consisted of pelvic RT (112), vaginal brachytherapy (36), or both (40). Clinicopathologic factors were evaluated as prognostic factors on both univariate and multivariate analyses. Factors correlated with recurrence on univariate analysis included MI (P = 0.05), grade (P = 0.07), lymphovascular invasion (LVI) (P = 0.001) and stage (P = 0.03). Multivariate analysis confirmed the significance of grade (P = 0.02), LVI (P = 0.001), and stage (P = 0.02). Conventional pathologic features do not lose their prognostic significance in pathologic Stage I-II endometrial adenocarcinoma patients following postoperative RT. These factors should continue to be used to identify women at risk for recurrence despite adjuvant RT. New prognostic markers are needed to better identify high-risk patients. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 224-230 (2000).

Age as a prognostic factor for recurrence in patients with endometrial carcinoma.

PURPOSE: The aim of this study was to evaluate age as a prognostic factor for recurrence in endometrial cancer patients treated with primary surgery. METHODS: Between 1983 and 1998, 455 endometrial cancer patients underwent primary surgery at our institution. Patients were divided into three age groups based on age at diagnosis: Group A (age <60, n = 156), B (age 60-69, n = 147), and C (age >/=70, n = 152). Clinicopathologic, treatment factors, and outcome were compared among the three groups. Prognostic factors were evaluated by univariate and multivariate analysis. RESULTS: The three age groups had a similar distribution of most pathologic features including stage, histology, cervical involvement, positive cytology, adnexal involvement, nodal metastases, serosal involvement, and lymphovascular invasion (LVI). Older women had a higher rate, however, of deep (>1/2) myometrial invasion (P < 0.0001) and grade 3 tumors (P < 0.0001). The extent of surgical staging and use of adjuvant radiation therapy were similar. Five-year disease-free survivals (DFS) of Groups A, B, and C were 74.3, 70.2, and 60.3%, respectively (P = 0.08). A significant difference in DFS was seen when Groups A and B were combined and compared with Group C (72.0 vs 60.3%, P = 0.03). Multivariate analysis confirmed the significance of race, stage, grade, and LVI. Age was not found to be associated with recurrence (HR 1.1, 95% C.I. 0.91-1.5, P = 0.21). CONCLUSION: Our results reveal that, in a large cohort of comparably staged and treated endometrial carcinoma patients, age is not a prognostic factor for recurrence.

One versus two intracavitary brachytherapy applications in early-stage cervical cancer patients undergoing definitive radiation therapy.

PURPOSE: The purpose of this study was to compare the outcomes of early stage cervical cancer patients undergoing definitive radiation therapy (RT) with one versus two low-dose-rate intracavitary brachytherapy (ICB) applications. METHODS AND MATERIALS: Between 1983 and 1993, 140 stage IB-IIA patients underwent whole-pelvis RT (WPRT) and ICB. Prior to 1988, 56 patients (40%) received two ICB applications. After 1988, our policy was modified and subsequently 84 (60%) patients underwent one application. Patient, tumor, and treatment characteristics, outcome, and complications of the two groups were compared. RESULTS: The groups were balanced in terms of race, hemoglobin level, histology, grade, treatment duration, chemotherapy, and follow-up. The single-application group, however, had more stage IB disease, had small (< or =4 cm) tumors, and received higher WPRT and lower point A doses. Overall, the two groups had similar 5-year local control (P = 0.83) and disease-free (P = 0.23) and cause-specific (P = 0.29) survival rates. Moreover, no differences were seen when analyzed by tumor size or stage. On multivariate analysis, the number of applications was not correlated with recurrence (P = 0.59, hazard rate = 1.1, 95% confidence interval = 0.6-2.2). Chronic complications were similar in the two groups. CONCLUSION: Our nonselected comparison of one versus two ICB applications in early-stage cervical cancer patients reveals comparable outcomes and complication rates for the two approaches. These results support the use of a single application in early-stage patients undergoing definitive RT.

Acute problems during low-dose-rate intracavitary brachytherapy for cervical carcinoma.

OBJECTIVE: To estimate the incidence and severity of problems arising during the hospitalization of cervical carcinoma patients undergoing low-dose-rate intracavitary brachytherapy (ICB). METHODS: One hundred seventy ICB implants in 128 cervical carcinoma patients undergoing curative radiation therapy were reviewed. All events during the hospitalization requiring physician evaluation and/or intervention were scored as a "problem" and divided into 10 categories (fever/infection, pain, gastrointestinal, renal, pulmonary, cardiac, dermatologic, gynecologic, endocrinologic, psychiatric). Problems were scored as mild (no significant morbidity, therapy not discontinued), moderate (therapy discontinued but no significant morbidity), or severe (significant morbidity or mortality). Patient and treatment factors were correlated with acute problems. RESULTS: Forty-two implants (24.7%) were associated with acute problems (95% minor, 5% moderate, 0% severe). The most common types were fever/infection (14.1%) and gastrointestinal problems (5. 9%). Other problem types occurred in <3% of implants. No patient or treatment factor including age, comorbid disease, weight, implant duration, or anesthesia type was significantly correlated with acute problems. Patients who developed acute problems had a survival (P = 0.21) and risk of late sequelae (P = 0.74) similar to those of patients without acute problems. CONCLUSION: Problems occur during the hospitalization in approximately one-quarter of cervical carcinoma patients undergoing low-dose-rate ICB. However, most are minor and do not result in morbidity, require discontinuation of therapy, or adversely impact on outcome.