Adjuvant aromatase inhibitor therapy in patients with stage I breast cancer at a regional oncology center in Israel: implementation of a 'switching' policy in postmenopausal patients after initial tamoxifen.

OBJECTIVE: To analyze the implementation of a switching policy of adjuvant aromatase inhibitor (AI) therapy sequentially after tamoxifen in consecutively treated stage I (T1N0M0) hormone receptor (HR)-positive breast cancer (BC) patients. METHODS: The records of 279 consecutive HR-positive BC patients diagnosed between 2002 and 2006 and followed at the Soroka Medical Center were reviewed. RESULTS: Two-hundred-seventeen patients who initially received tamoxifen were suitable for switching and 28 received an AI as initial adjuvant treatment. The switch was accomplished in 82.5% of the 217 patients. Those who switched to an AI had a higher proportion of T1c stage than patients eligible who were not switched, but did not differ in age, histologic grade, or having received chemotherapy. Of the 179 patients who switched, 155 (86.6%) completed at least 4.5-5 years of adjuvant tamoxifen/AI therapy. Eighteen patients discontinued AI therapy prematurely because of toxicity. CONCLUSIONS: In this stage I BC population, despite the toxicities of AI therapy, >84% of eligible patients received an AI as adjuvant therapy. Measures to improve the management of AI toxicity, such as changing to a different AI, may reduce early stopping.

Gastrointestinal colonization with ESBL-producing Klebsiella in preterm babies--is vancomycin to blame?

In this study, we examine the possible association between treatment with vancomycin and colonization with extended-spectrum beta-lactamase (ESBL)-producing Klebsiella in our neonatal intensive care unit (NICU). Variables compared between newborns which developed rectal colonization and those who did not include: gestational age, birth weight, gender, and total length of hospital stay until positive stool culture or discharge, treatment with vancomycin, and positive blood culture for coagulase-negative Staphylococcus. We found that lower birth weight, younger gestational age, and treatment with vancomycin were statistically significant risk factors for gastrointestinal colonization with ESBL-producing Klebsiella. When applying a multivariate model, treatment with vancomycin, both for a full 10-day course and for a short 3-day empirical treatment, remained statistically significant. Treatment with vancomycin is a risk factor for gastrointestinal colonization with ESBL-producing Klebsiella in premature babies.

The impact of the 21-gene recurrence score assay on decision making about adjuvant chemotherapy in early-stage estrogen-receptor-positive breast cancer in an oncology practice with a unified treatment policy.

BACKGROUND: The 21-gene recurrence score (RS) assay has been validated in retrospective studies as prognostic of distant disease recurrence and predictive of the benefit of adjuvant chemotherapy in estrogen-receptor-positive breast cancer (BC). There is limited published data on the impact of the assay on clinical practice, particularly in the context of a single practice with a unified treatment policy. PATIENTS AND METHODS: Between 2006 and 2009, RS was obtained on 135 patients in a single practice with a uniform treatment policy. Treatment recommendations before and after RS result were analyzed retrospectively. Pre-RS treatment recommendations were based on clinicopathological features and Adjuvant! Online (AO) calculated survival advantage. RS and AO survival advantage for adding chemotherapy were compared for each patient. RESULTS: The distribution by risk group of RS was low- 49.6%, intermediate-37.8%, and high-12.6%. In 34 patients (25.2%, 95% confidence interval 17.9% to 32.5%), recommendation for chemotherapy was changed after obtaining assay result. Most changes (70.6%) were from chemotherapy to no chemotherapy. The RS correlated poorly with AO predictions. CONCLUSION: The 21-gene assay, when applied in a consistent manner in early-stage BC, changes treatment recommendations in one-quarter of patients tested.

[Giant condyloma of the penis with malignant transformation associated with lichen sclerosus et atrophicus]. / Riesenkondylom des Penis mit maligner Transformation bei vorbestehendem Lichen sclerosus et atrophicus.

A 72-year old patient presented with a 6 months history of a rapidly growing tumor of the glans and foreskin. He had a long history of phimosis with lichen sclerosus et atrophicus-like lesions on the foreskin which had not been treated. The rest of the personal, family and sexual history was unremarkable. Treatment consists of circumcision and tumor excision. Histopathology confirmed a squamous cell carcinoma within a giant condyloma with a concomitant lichen sclerosus et atrophicus. CT- and ultrasound scans showed no metastases. Giant condylomas are a rare sexually transmitted disease usually caused by human papilloma virus subtypes 6, 11, but also by 16 and 18 among others. They are expansive, cauliflower-like destructive lesions that most frequently affect the anogenital region. In about 30 percent a giant condyloma progresses into a squamous cell carcinoma. Therapy of choice is the histopathologically controlled excision. Recurrences are often seen, so the patients should be monitored frequently after therapy.

Breast reconstruction: complication rate and tissue expander type.

BACKGROUND: Limited literature exists regarding complication rates among women undergoing breast reconstruction and the association of these rates with tissue expander types (anatomic, round and Becker). METHODS: A historical cohort study investigated all breast reconstructions performed at Hadassah Medical Center for 140 consecutive women. Analyses were performed using both logistic and Poisson regression multivariate methods. RESULTS: At least one major complication occurred in each of the following groups: anatomic (41%), round (20%), and Becker (11.7%) (p = 0.015). Women reconstructed with anatomic expanders were at increased risk for at least one complication (odds ratio [OR], 3.96; 95% confidence interval [CI], 1.18-13.3; p = 0.026) and an average increase of 331% (95% CI, 102-817%; p = 0.0002) in the number of major complications. CONCLUSION: The results of this study suggest that integrated-valve expanders are associated with more complications than the distant inflation port. The benefits of an anatomic shape may perhaps be better exploited using devices with a distant port.

Routine use of bilateral skeletonized internal thoracic artery grafting: long-term results.

BACKGROUND: Skeletonized harvesting of the internal thoracic artery (ITA) decreases the severity of sternal devascularization, thus reducing the risk of postoperative sternal complications in patients undergoing bilateral ITA grafting. METHODS AND RESULTS: Between 1996 and 2001, 1515 consecutive patients underwent skeletonized bilateral ITA grafting. Of the 1179 male and 336 female patients, 641 (42.3%) were >70 years of age, and 519 (34.2%) had diabetes mellitus. Operative mortality was 2.8%. Early postoperative morbidity included sternal infection (1.6%), cerebrovascular accident (3%), and perioperative myocardial infarction (1%). Multiple regression analysis showed chronic obstructive pulmonary disease (odds ratio, 11.3; 95% confidence interval [CI], 4.45 to 28.55), repeat operation (odds ratio, 12.7; 95% CI, 3.25 to 49.56), and diabetes mellitus (non-insulin dependent: odds ratio, 4.64; 95% CI, 1.85 to 11.59; insulin dependent: odds ratio, 6.9; 95% CI, 1.35 to 35.27) to be associated with increased risk of sternal infection. Follow-up (between 5 and 12 years) revealed 305 late deaths. Kaplan-Meier 10-year survival rates for patients <65, 65 to 74, and >75 years of age were 87%, 75%, and 52%, respectively. Cox regression analysis revealed increased overall mortality (early and late) in patients with peripheral vascular disease (hazard ratio [HR], 1.8; 95% CI, 1.39 to 2.33), patients >75 years of age (HR, 7.23; 95% CI, 4.16 to 12.55), those undergoing repeat operations (HR, 2.22; 95% CI, 1.27 to 3.89), patients with preoperative congestive heart failure (HR, 1.64; 95% CI, 1.29 to 3.75), and those with chronic renal failure (HR, 1.52; 95% CI, 1.11 to 2.01). Operations performed without cardiopulmonary bypass were associated with better postoperative survival (HR, 0.66; 95% CI, 0.49 to 0.87). CONCLUSIONS: Bilateral ITA grafting is associated with low morbidity and good long-term results. Use of skeletonized bilateral ITA is appropriate for the elderly and most patients with diabetes; however, it is not recommended for repeat operations or for patients with chronic obstructive pulmonary disease.

Parental religious affiliation and survival of premature infants with severe intraventricular hemorrhage.

OBJECTIVE: To evaluate the association between parents' ethnic/religious affiliation (secular Jewish, religious Jewish, ultra-orthodox Jewish, Muslim Arabs) and survival of premature infants with severe intraventricular hemorrhage (IVH). STUDY DESIGN: Survival of 102 infants (birth weight

A comparison of the potential acuity meter (PAM) and the illuminated near card (INC) in patients undergoing phacoemulsification.

PURPOSE: To compare the accuracy of the potential acuity meter (PAM) and the illuminated near card (INC) in patients undergoing phacoemulsification. METHODS: During presurgical evaluations, both PAM and INC were tested on each study patient following dilation. Patients then rated the subjective ease of use of each test. Best spectacle-corrected visual acuity (BSCVA) was recorded at 4 and 12 weeks postoperatively. McNemar's chi(2) test for paired associations was used to analyse categorical data; paired t-tests were used for continuous variables. RESULTS: Overall, the INC was more likely than the PAM to predict BSCVA within one Snellen line (P=0.002), but this difference decreased for accuracy within two lines. The PAM predicted BSCVA within one line in 87 (70.7%) eyes, as compared to 102 (82.9%) eyes by the INC. The PAM was accurate within two lines in 109 (88.6%) eyes; the INC was accurate in 115 (93.5%) eyes. The PAM was more likely to underpredict potential acuity (P<0.001), while the INC was more likely to overpredict (P=0.004) or give exact predictions of BSCVA (P<0.001). Accuracy of the INC declined in eyes with macular comorbidity. The PAM and INC were rated as 'easy' tests by 54 (45.4%) and 93 (78.2%) patients, respectively. CONCLUSIONS: Both the PAM and the INC were useful for predicting BSCVA after phacoemulsification, but the PAM was more likely to underestimate potential acuity. The INC was easier for patients to use, and had better accuracy than the PAM in patients without macular comorbidity, but was more likely to overestimate potential acuity.

Midterm results of routine bilateral internal thoracic artery grafting.

BACKGROUND: Skeletonized dissection of the internal thoracic artery (ITA) decreases the occurrence of sternal devascularization, thus decreasing the risk of postoperative sternal complications in patients undergoing bilateral ITA grafting. METHODS: From April 1996 to July 1999, 1000 consecutive patients underwent bilateral skeletonized ITA grafting. Of the 770 male and 230 female patients, 420 were older than 70 years, and 312 had diabetes. RESULTS: Operative mortality was 3.3%. Follow-up (40-78 months) revealed 79 late deaths, and the Kaplan-Meier 6-year survival rate was 88%. Cox regression analysis revealed increased overall mortality (early and late) in patients with preoperative congestive heart failure (risk ratio [RR], 2.13; 95% confidence interval [CI], 1.31-3.45), in patients with peripheral vascular disease (RR, 5.52; 95% CI, 3.31-9.19), and in patients older than 70 years (RR, 2.18; 95% CI, 1.37-3.47). Early postoperative morbidity included sternal infection (2.2%), cerebrovascular accident (1.6%), and perioperative myocardial infarction (1%). Multiple regression analysis showed repeat operation (odds ratio [OR], 7.5; 95% CI, 1.77-31.6) and chronic obstructive pulmonary disease (OR, 3.6; 95% CI, 1.27-10.75) to be independent predictors of sternal infection. During follow-up, angina returned in 95 patients, 24 of whom required reintervention (20 cases of percutaneous balloon angioplasty and 4 reoperations). Postoperative coronary angiography performed in 87 patients revealed an ITA patency rate of 91%. CONCLUSIONS: Bilateral skeletonized ITA grafting is associated with satisfactory early and midterm results. We do not recommend the use of this surgical technique in patients with chronic obstructive pulmonary disease.

Confounding and effect modification in the short-term effects of ambient particles on total mortality: results from 29 European cities within the APHEA2 project.

We present the results of the Air Pollution and Health: A European Approach 2 (APHEA2) project on short-term effects of ambient particles on mortality with emphasis on effect modification. We used daily measurements for particulate matter less than 10 microm in aerodynamic diameter (PM10) and/or black smoke from 29 European cities. We considered confounding from other pollutants as well as meteorologic and chronologic variables. We investigated several variables describing the cities' pollution, climate, population, and geography as potential effect modifiers. For the individual city analysis, generalized additive models extending Poisson regression, using a smoother to control for seasonal patterns, were applied. To provide quantitative summaries of the results and explain remaining heterogeneity, we applied second-stage regression models. The estimated increase in the daily number of deaths for all ages for a 10 microg/m3 increase in daily PM10 or black smoke concentrations was 0.6% [95% confidence interval (CI) = 0.4-0.8%], whereas for the elderly it was slightly higher. We found important effect modification for several of the variables studied. Thus, in a city with low average NO2, the estimated increase in daily mortality for an increase of 10 microg/m3 in PM10 was 0.19 (95% CI = 0.00-0.41), whereas in a city with high average NO2 it was 0.80% (95% CI = 0.67-0.93%); in a relatively cold climate the corresponding effect was 0.29% (95% CI = 0.16-0.42), whereas in a warm climate it was 0.82% (95% CI = 0.69-0.96); in a city with low standardized mortality rate it was 0.80% (95% CI = 0.65-0.95%), and in one with a high rate it was 0.43% (95% CI = 0.24-0.62). Our results confirm those previously reported on the effects of ambient particles on mortality. Furthermore, they show that the heterogeneity found in the effect parameters among cities reflects real effect modification, which is explained by specific city characteristics.

MAG3-F0 scintigraphy in decision making for emergency intervention in renal colic after helical CT positive for a urolith.

UNLABELLED: Patients with renal colic are evaluated with clinical, laboratory, and imaging methods for stratification for emergency decompression, medical treatment, or discharge and follow up. The current standard practice is heavily based on unenhanced helical CT for detecting uroliths. However, the presence of a urolith does not necessarily mean that the kidney is obstructed and requires emergency decompression. In this study, technetium-mercaptoacetyltriglycine (MAG3) diuretic scintirenography was used to detect obstruction in patients with renal colic. The contribution of this test to patient management after positive findings from helical CT was also studied. METHODS: Diagnostic criteria were established on the basis of previous experience with 60 patients who had renal colic and had undergone radiography of the kidneys, ureters, and urinary bladder (KUB) and diuretic Tc-MAG3 scintirenography and were followed up to correlate scintigraphic findings with clinical outcome. Subsequently, 80 patients with renal colic underwent scintigraphy within 12 h of presentation in the emergency room, after abdominal helical CT showed findings positive for calculus and suggestive of obstruction. After therapeutic oral or intravenous hydration and analgesics, diuretic dynamic renal scintigraphy (flow, function, delayed imaging) was performed after intravenous injections of 10 mCi (370 MBq) 99mTc-MAG3 and 40 mg furosemide (at zero time, or F0). Results were available soon after completion of the study and were considered in patient management. Four characteristic patterns of scintirenography, essential in patient stratification and treatment, had been standardized and were used for interpretation of the studies: the unobstructed kidney; the partially obstructed kidney, proximally or distally obstructed, with mild to severe obstruction and impairment of function; the totally obstructed kidney, with arrested renal function; and the unobstructed but dysfunctioning kidney after decompression, or stunned kidney. RESULTS: Among the 80 patients with positive helical CT findings, 56.5% were found to have obstruction by scintigraphy (32.5% partially, 24% completely); the remaining 43.5% did not have obstruction (21% without an indication of recent obstruction and 22.5% with stunned kidneys after spontaneous decompression). Occasionally, findings of preexistent urine extravasation or infection were present. Patients who, by scintigraphy, never had obstruction or had experienced spontaneous decompression did not require admission or emergency intervention; those with complete or severe obstruction required admission and decompression for relief of pain or restoration of function, whereas those with mild obstruction were treated variably with forced fluids, analgesics, or, less frequently, elective surgery. Outcome information from clinical examination, imaging, and interventional findings indicated that this stratification was successful. The test caused no side effects. CONCLUSION: For renal colic, clinical selection, KUB radiography, and even positive helical CT findings were all found to have a low positive predictive value for obstruction (in this study, 35%, 32%, and 56% respectively). Anatomic studies, including helical CT, should be followed by diuretic MAG3-F0 scintirenography to diagnose and quantify or exclude obstruction, detect spontaneous decompression, and appropriately stratify patients for emergency intervention, observation and medical therapy, or further work-up and discharge with referral to the clinic.

Propionibacterium acnes as a cause of visually significant corneal ulcers.

PURPOSE: To report Propionibacterium acnes as a cause of vision-threatening infectious keratitis and to discuss culture isolation and antibiotic treatment. METHODS: Retrospective case series presentation collected from three academic medical centers. RESULTS: Six cases of P. acnes infectious keratitis are presented, all of which were associated with a compromised corneal barrier or environment. All cases were culture-positive on thioglycolate broth; none became positive before 7 days of growth. No other organisms were isolated from any culture, and the growth of P. acnes occurred in some cases despite negative gram stains. CONCLUSION: P. acnes can produce vision-debilitating keratitis when the cornea is compromised. Growth in culture should be monitored for at least 10 days to ensure isolation of this fastidious organism. P. acnes may respond to several different antibiotics that have gram-positive coverage, but it should be treated with vancomycin to enhance clearance of the organism.

Mutation hot spots in 5q31-linked corneal dystrophies.

Mutations in the BIGH3 gene on chromosome 5q31 cause four distinct autosomal dominant diseases of the human cornea: granular (Groenouw type I), Reis-Bücklers, lattice type I, and Avellino corneal dystrophies. All four diseases are characterized by both progressive accumulation of corneal deposits and eventual loss of vision. We have identified a specific recurrent missense mutation for each type of dystrophy, in 10 independently ascertained families. Genotype analysis with microsatellite markers surrounding the BIGH3 locus was performed in these 10 families and in 5 families reported previously. The affected haplotype could be determined in 10 of the 15 families and was different in each family. These data indicate that R555W, R124C, and R124H mutations occurred independently in several ethnic groups and that these mutations do not reflect a putative founder effect. Furthermore, this study confirms the specific importance of the R124 and R555 amino acids in the pathogenesis of autosomal dominant corneal dystrophies linked to 5q.

Intraocular metallic-appearing foreign bodies after phacoemulsification.

Intraocular metallic-appearing foreign bodies in the anterior segment were seen in six eyes after cataract extraction by two-handed phacoemulsification. These fragments produced no symptoms and had no clinically significant effect on visual function. Similar-appearing foreign bodies were experimentally produced by applying ultrasound power with a phacoemulsification handpiece to the surface of a cyclodialysis spatula in vitro. Microscopic examination of the phaco handpiece tip and cyclodialysis spatulas revealed numerous surface irregularities, suggesting a possible source of these fragments. These results suggest that instrument touch during phacoemulsification may be the cause of the fragments. Long-term follow-up of these patients is required to determine the overall effect of the fragments.

Objective measurement of corneal light scattering after excimer laser keratectomy.

PURPOSE: To obtain objective measurements of corneal light scattering after excimer laser keratectomy, and to evaluate the relation of light scattering to clinical haze grading and visual acuity. METHODS: The authors measured best-corrected visual acuity, subjective clinical haze grade, and corneal light-scattering index in patients undergoing photorefractive keratectomy (PRK) (n=26), and phototherapeutic keratectomy (n=8), preoperatively and postoperatively at 1,3,6,9, and 12 months or later. Corneal light scattering was correlated with visual acuity and clinical haze grade. RESULTS: Corneal light scattering increased after PRK and was reduced after phototherapeutic keratectomy. Corneal light scattering index showed a stronger positive correlation with logMAR visual acuity (r=0.57) than clinical haze grading (r=0.34). Corneal light-scattering index (P<0.05 at 1 and 3 months) and clinical haze grading (P<0.05 at 6, 9, and 12 months) were significantly higher in eyes undergoing PRK with ablation depths of more than 80 microns. CONCLUSIONS: Excimer laser surgery affects corneal light scattering. Ablations with depths greater than 80 microns produce significantly higher levels of haze than those less than 80 microns. Objective measurement of corneal light scattering may be useful in monitoring the outcome of excimer keratectomy.

Endoscopy and biopsy of the orbit.

Flexible endoscopes produce high-quality images, are small in size, and can deliver microsurgical instruments or laser probes. Early attempts at orbital endoscopy were limited by the relatively large size and poor visualization of rigid endoscopes. We performed endoscopic orbital exploration using the Olympus HYF flexible endoscope in four live dog orbits. We achieved excellent visualization of orbital structures including the globe, blood vessels, extraocular muscles, intermuscular septa, optic nerve, and fat. Visualization, hemostasis, and dissection were aided by the use of hyaluronic acid infused through the endoscope. We biopsied fat and extraocular muscle without complication using Olympus endoscopic cup biopsy forceps (confirmed by histopathologic examination). Our experience indicates that orbital endoscopy aided by viscoelastic hydrodissection may permit a less invasive approach to optic nerve sheath fenestration, tumor biopsy and treatment, and the removal of foreign bodies.

Sudden visual loss associated with sexual activity.

OBJECTIVE: To characterize the ocular fundus findings of patients who suffered sudden visual loss associated with sexual activity. DESIGN: Case series. SETTING: Outpatient ophthalmic practice. PATIENTS: Six patients presented with a precipitous decrease in vision in one eye with no apparent predisposing factors. After obtaining a careful history, each patient revealed that he or she had been engaging in rigorous sexual activity immediately before experiencing the visual loss. INTERVENTION: Five of the six patients were followed up without intervention. One patient required prophylactic laser photocoagulation of a retinal tear to decrease the risk of retinal detachment. RESULTS: Six patients aged 24 to 53 years suffered sudden loss of vision secondary to intraretinal, preretinal, or vitreous hemorrhaging. Visual acuity in the affected eyes ranged from a mild decrease (20/40) to profound visual loss (counting fingers at 6 in). Five of the six patients were followed up for at least 1 month and showed spontaneous improvement in vision as the blood cleared. Those who returned for long-term follow-up enjoyed complete visual recovery without any sequelae. CONCLUSIONS: Sudden debilitating visual loss may occur during sexual activity from the rupture of retinal blood vessels in the macular region or from the development of vitreous bleeding from an induced retinal tear. The long-term prognosis after such hemorrhaging appears to be excellent, with good visual recovery occurring as the blood resorbs spontaneously.

Ocular findings in cutaneous T-cell lymphoma.

Seventeen patients with cutaneous T-cell lymphoma undergoing an investigative treatment regimen using extracorporeal photochemotherapy underwent ophthalmologic examinations to investigate the ocular findings in this disease. The most frequent finding was seborrheic blepharoconjunctivitis, which was noted in 13 of 17 patients. Other common lid findings included cicatricial ectropion, meibomianitis, chalazia, and madarosis. Corneal and conjunctival disease was also increased in this group of patients. The syndrome of cutaneous T-cell lymphoma has recently been redefined, and a discussion of the revised concept of this disease is included. Previous studies used the old definition of this disease and were limited to the subgroups of mycosis fungoides and Sezary syndrome, which comprise only one third of the cutaneous T-cell lymphoma population.