Effect of baseline oestradiol serum concentration on the efficacy of anastrozole for preventing breast cancer in postmenopausal women at high risk: a case-control study of the IBIS-II prevention trial.

BACKGROUND: An increased risk of breast cancer is associated with high serum concentrations of oestradiol and testosterone in postmenopausal women, but little is known about how these hormones affect response to endocrine therapy for breast cancer prevention or treatment. We aimed to assess the effects of serum oestradiol and testosterone concentrations on the efficacy of the aromatase inhibitor anastrozole for the prevention of breast cancer in postmenopausal women at high risk. METHODS: In this case-control study we used data from the IBIS-II prevention trial, a randomised, controlled, double-blind trial in postmenopausal women aged 40-70 years at high risk of breast cancer, conducted in 153 breast cancer treatment centres across 18 countries. In the trial, women were randomly assigned (1:1) to receive anastrozole (1 mg/day, orally) or placebo daily for 5 years. In this pre-planned case-control study, the primary analysis was the effect of the baseline oestradiol to sex hormone binding globulin (SHBG) ratio (oestradiol-SHBG ratio) on the development of all breast cancers, including ductal carcinoma in situ (the primary endpoint in the trial). Cases were participants in whom breast cancer was reported after trial entry and until the cutoff on Oct 22, 2019, and who had valid blood samples and no use of hormone replacement therapy within 3 months of trial entry or during the trial. For each case, two controls without breast cancer were selected at random, matched on treatment group, age (within 2 years), and follow-up time (at least that of the matching case). For each treatment group, we applied a multinominal logistic regression likelihood-ratio trend test to assess what change in the proportion of cases was associated with a one-quartile change in hormone ratio. Controls were used only to determine quartile cutoffs. Profile likelihood 95% CIs were used to indicate the precision of estimates. A secondary analysis also investigated the effect of the baseline testosterone-SHBG ratio on breast cancer development. We also assessed relative benefit of anastrozole versus placebo (calculated as 1 - the ratio of breast cancer cases in the anastrozole group to cases in the placebo group). The trial was registered with ISRCTN (number ISRCTN31488319) and completed recruitment on Jan 31, 2012, but long-term follow-up is ongoing. FINDINGS: 3864 women were recruited into the trial between Feb 2, 2003, and Jan 31, 2012, and randomly assigned to receive anastrozole (n=1920) or placebo (n=1944). Median follow-up time was 131 months (IQR 106-156), during which 85 (4·4%) cases of breast cancer in the anastrozole group and 165 (8·5%) in the placebo group were identified. No data on gender, race, or ethnicity were collected. After exclusions, the case-control study included 212 participants from the anastrozole group (72 cases, 140 controls) and 416 from the placebo group (142 cases, 274 controls). A trend of increasing breast cancer risk with increasing oestradiol-SHBG ratio was found in the placebo group (trend per quartile 1·25 [95% CI 1·08 to 1·45], p=0·0033), but not in the anastrozole group (1·06 [0·86 to 1·30], p=0·60). A weaker effect was seen for the testosterone-SHBG ratio in the placebo group (trend 1·21 [1·05 to 1·41], p=0·011), but again not in the anastrozole group (trend 1·18 [0·96 to 1·46], p=0·11). A relative benefit of anastrozole was seen in quartile 2 (0·55 [95% CI 0·13 to 0·78]), quartile 3 (0·54 [0·22 to 0·74], and quartile 4 (0·56 [0·23 to 0·76]) of oestradiol-SHBG ratio, but not in quartile 1 (0·18 [-0·60 to 0·59]). INTERPRETATION: These results suggest that serum hormones should be measured more routinely and integrated into risk management decisions. Measuring serum hormone concentrations is inexpensive and might help clinicians differentiate which women will benefit most from an aromatase inhibitor. FUNDING: Cancer Research UK, National Health and Medical Research Council (Australia), Breast Cancer Research Foundation, and DaCosta Fund.

Measuring cancer burden in prostatic needle core biopsies: simplified assessments outperform complex measurements in assessing outcome: evidence to assist pathologist efficiency and minimize datasets.

AIMS: The optimal method of measuring cancer extent in prostate cancer (PCa) biopsies is unknown. METHODS AND RESULTS: Nine hundred eighty-one men with clinically localised PCa managed conservatively were reviewed with follow up. The number of positive cores (NPC), the Maximum Cancer Length in a core (MCL), Total Cancer Length (TCL), and percentage of positive cores (%+cores) was calculated and univariate and multivariate analysis performed using prostate-specific antigen (PSA), T-stage, and Gleason score. The presence of stromal gaps (SG) was recorded. Univariate models were run where SG made a difference to the MCL. All variables showed significant association with PCa death in univariate models. In multivariate models, incorporating PSA, T-stage, and Gleason score, only %+cores was a significant predictor of outcome, with a 10% increase in %+cores resulting in a hazard ratio (HR) of 1.07 (likelihood-ratio test P > Χ2  = 0.01). There were 120 patients where SG made a difference to the MCL and a total of 20 events in this group. Including SG, on univariate analysis the median MCL was 10 mm and HR was 1.16 (P = 0.007), not including SG, the median MCL was 6 mm and HR was 1.23 (P = 6.3 × 10-4 ). Inclusion or exclusion of SG made no significant difference to TCL as a predictor of outcome. CONCLUSION: Cancer extent is a strong predictor of PCa death but only %+cores added to the multivariate model. Expressed as a fraction of NPC/total number of cores, this is the simplest method of assessment, which we favour over more complicated methods in nontargeted biopsies.

Comparison of StemPrintER with Oncotype DX Recurrence Score for predicting risk of breast cancer distant recurrence after endocrine therapy.

OBJECTIVE: Molecular tests predicting the risk of distant recurrence (DR) can be used to assist therapy decision-making in oestrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer patients after considerations of standard clinical markers. The Oncotype DX Recurrence Score (RS) is a widespread tool used for this purpose. Here, we compared the RS with the StemPrintER Risk Score (SPRS), a novel genomic predictor with a unique biological basis in its ability to measure the expression of cancer stemness genes. MATERIALS AND METHODS: We benchmarked the SPRS vs. RS, alone or in combination with clinicopathological variables expressed by the Clinical Treatment Score (CTS), for the prognostication of DR in a retrospective cohort of 776 postmenopausal patients with ER+/HER2-breast cancer enrolled in the translational arm of the randomised Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial. Likelihood ratio (LR) with χ2 test and C-index were used to assess prognostic performance for the entire ten-year follow-up period and in early (0-5 years) and late (5-10 years) intervals. RESULTS: In all patients, the SPRS provided significantly more prognostic information than the RS for ten-year DR prognostication (C-index = 0.688, LR-χ2 = 33.4 vs. C-index = 0.641, LR-χ2 = 22.1) and for late (5-10 years) DR prognostication (C-index = 0.689, LR-χ2 = 18.8 vs. C-index = 0.571, LR-χ2 = 4.7). The SPRS also provided more prognostic information than the RS when added to the CTS in all patients (CTS + SPRS: LR-Δχ2 = 14.9; CTS + RS: LR-Δχ2 = 9.7) and in node-negative patients (CTS + SPRS: LR-Δχ2 = 11.7; CTS + RS: LR-Δχ2 = 6.6). CONCLUSIONS: In postmenopausal ER+/HER2- breast cancer patients, SPRS provided more prognostic information than RS for DR when used alone or in combination with the CTS. The SPRS could therefore potentially identify high-risk patients, who might benefit from aggressive treatments, from low-risk patients who might safely avoid adjuvant chemotherapy or prolongation of endocrine therapy.

Establishing Global School Feeding Program Targets: How Many Poor Children Globally Should Be Prioritized, and What Would Be the Cost of Implementation?

The creation of Human Capital is dependent upon good health and education throughout the first 8,000 days of life, but there is currently under-investment in health and nutrition after the first 1,000 days. Working with governments and partners, the UN World Food Program is leading a global scale up of investment in school health, and has undertaken a strategic analysis to explore the scale and cost of meeting the needs of the most disadvantaged school age children and adolescents in low and middle-income countries globally. Of the 663 million school children enrolled in school, 328 million live where the current coverage of school meals is inadequate (<80%), of these, 251 million live in countries where there are significant nutrition deficits (>20% anemia and stunting), and of these an estimated 73 million children in 60 countries are also living in extreme poverty (

The role of Movat pentachrome stain and immunoglobulin G4 immunostaining in the diagnosis of autoimmune pancreatitis.

Autoimmune pancreatitis is highly responsive to steroid therapy, but because it mimics pancreatic cancer, it often precipitates unnecessary surgery. Adequate diagnostic tests are needed to permit appropriate medical therapy. Lymphocytic and obliterative phlebitis are reported in the majority of cases, as are elevated IgG4-positive plasma cells, indicating their high sensitivity. Their specificities, especially when used in conjunction, however, remain largely unknown. Movat pentachrome vascular and IgG4 immunohistochemical stains were performed on a total of 15 autoimmune pancreatitis cases (11 pancreatic resections and 4 biopsies), 39 usual-type alcoholic or idiopathic chronic pancreatitis cases, 35 pancreatic ductal adenocarcinoma-associated chronic pancreatitis cases, and 29 normal pancreata. Marked and diffuse lymphocytic and obliterative venulitis were detected in all 15 cases of autoimmune pancreatitis on Movat staining (100% sensitivity). Only a single carcinoma-associated chronic pancreatitis case among all of the controls showed diffuse benign venulitis that was nonobliterative (99% specificity). Nine of 13, 9 autoimmune pancreatitis cases showed marked IgG4 immunopositivity at >or=10 positive plasma cells per x 400 field (69% sensitivity). No increased IgG4 plasma cells were found in any of 103 controls (100% specificity). In combination, all of the autoimmune pancreatitis cases had at least one (13/13) and most had both markers (9/13), whereas none of the controls had both markers. Overall, these combined stains show very promising diagnostic utility and should be considered in combination with clinical and serologic analyses in the evaluation of chronic pancreatitis suspicious for malignancy. Future validating studies on preoperative biopsies with outcome data following steroid therapy will be essential.

Osteonecrosis of the Hip in Patients with Aplastic Anemia

The incidence and clinical and magnetic resonance imaging features of osteonecrosis of the hip were evaluated in patients with aplastic anemia. Two hundred and forty-one patients with aplastic anemia were examined using MR imaging of bone marrow during the five years from 1994 to 1998. Osteonecrosis of the hip was observed on MR imaging in nineteen (15 males and 4 females, mean age 35 yr) of the 241 patients. It was present in both hips in 14 patients, and there were five cases with unilateral occurrence, with a total of 33 involved hips. All except for five hips with associated bone marrow edema revealed increased fatty marrow conversion in the proximal femoral metaphysis. In nine patients, osteonecrosis was detected without any pain. Five patients already had osteonecrosis before any medication was administered. Twelve patients received antilymphocyte globulin, and seven patients received a low dose of steroids before the MR diagnosis of osteonecrosis. Osteonecrosis of the hip frequently develops in patients with aplastic anemia (7.9%), associated with fatty marrow conversion of the proximal femoral metaphysis.

A Clinical Observation on Leukemia Cutis / 대한피부과학회지

BACKGROUND: Leukemia cutis is readily recognized and documented by biopsy, in contrast. to leukemic involvement in more occult sites. Nine cases of leukemia cutis have been reported in the Korean literatures. However no collective clinical studies have been reported in Korea. OBJECTIVE: We evaluated the differences in patient age and sex, the clinical appearences and distributions of the skin lesions, interval between diagnosis of systemic leukemia and skin involvement, clinical course, and prognosis according to the type of leukemias. METHODS: We carried out a retvospective study of 22 cases of leukemia cutis. Clinical information was obtained from the records of of 22 patients diagnosed at St. Mary's Hospital from 1988 to 1995. All the included cases were well evaluated for their clinical and histopathologic findings. RESULTS: 1. Among 22 patients with leukemia cutis, male patients outnumbered female by 2 to 1 and the mean age was 25.8 years. 2. The clinical appearance of leukemia cutis includes papules, macules, nodules, plaques in all types of leukemia. Ulcerative lesions and vesicles were seen infrequently in leukemia cutis. Leukemia cutis often involved saultiple location of the skin, with no specific predilection of the site. There were no differences in distribution of lesions depending on the types of systemic leukemia. 3. In 68% of the patients with leukemia cutis, the skin lesions developed after the systemic leukemia was diagnosed, and 14% of patients had concomitant, involvement. 18% of patients had skin lesions preceding the diagnosis of systemic leukemia, howevere cytochemical and cytomorphologic studies of bone marrow and peripheral blood smear were not employed at the time of the skin biopsy. 4. Fourteen of 22 patients(64%) did not achieve a complete remission following the diagnosis of leukemia cutis and two of 14 patients without having complete remission could achieve complete remissions with proper anticancer therapy after the diagnosis of leukemia cutis. Total eight patients(36%) achieved a complete remission, then they had a relapse of leukemia in the skin, without having had any skin involvement at the time of the diagnosis of leukemia. 5. Seventeen of 22 patients(77% ) who were being followed up in our series died after leukemia cutis was diagnosed. The mean intervals between diagnosis of leukemia cutis and death was 3.8 months and they died mostly within 1 year. CONCLUSION: The presence of leukemic infiltration in the skin may help the clinician suspect the early diagnosis and relapse of systemic leukemia. It appears that leukemia cutis is associated with a grave prognosis.

Effect of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) on Neutropenia Occuring during Radiotherapy / 대한치료방사선과학회지

PURPOSE: To assess the efficacy of recombinant human granulocyte-macrophage colony-stimulatin g factor(GM-CSF) in the neutropenia by radiotherapy. MATERIALS AND METHODS: Eleven patients with various solid tumor were treated with a daily subcutaneous dose of GM-CSF(3-7 microgram/kg) for 5 days during the radiotherapy. Before and during the course of the study all the patients were monitored by the recording of physical examination, the complete blood count with differential and reticulocyte count and liver function test. Eight patients received patients received prior or concurrent chemotherapy. RESULTS: In 10 patients, the neutrophilic nadir was significantly elevated and the length of time that patients had a neutrophil count below 103/mm3, a threshold known to be critical to acquiring infective complications was shortened following GM-CSF injection. A significant rise (two fold or greater) of neutrophil count was seen in 10 of 11 patients. In most patients, discountinuation of GM-CSF resulted in a prompt return of granulocyte counts toward baseline. However the neutrophil count remained elevated over 103/mm3 during radiation therapy, and radiotherapy delays were avoided. Other peripheral blood components including monocytes and platelets also increased after GM-CSF treatment. No siginificant toxicity was encountered with subcutaneous GM-CSF treatment. CONCLUSION: GM-CSF was well tolerated by subcutaneous route and induced improvement in the neutropenia caused by radiotherapy.

The Arterial Oxygenation Effects of CPAP to the Nonventilated Lung during One Lung Ventilation / 대한마취과학회지

Among patients scheduled for elective thoracic surgery at the Medical Center of Kyung Hee University, 15 patients undergoing lobectomy or pneumonectomy were selected. Three different ventilatory modes were employed and compared to the two-lung ventilation with 50% oxygen (control). First, patients were ventilated with 50% oxygen and left the unventilated lung to deflate during one lung ventilation (test 1). Second, continuous positive airway pressure (CPAP) of 10 cmH2O was applied to the ventilated lung while patients were under one lung ventilation with 50% oxygen (test 2). Lastly, patients were ventilated with 100% oxygen and unventilated lung was left to deflate during one lung ventilation (test 3). PaO2, A-aDO2 and Qsp/QT of three different ventilatory modes were observed and compared to that of control, and that of test 2 to test 1. The results were as followed: 1) Mean PaO2 in test 1 and test 2 were 98+/-24.0 mmHg and 126+/-34.8 mmHg, respectively and were significantly decresed as compared to the PaO2 of control, 234+/-21.4 mmHg. Comparing the PaO2 of test 1 and test 2, there was statistically significant increase in test 2 (P<0.01). 2) Comparing with A-aDO2 of control (68+/-22.5 mmHg), A-aDO2 in both test 1 and test 2 were significantly increased to 210+/-24.3 mmHg and 184+/-33.4 mmHg, respectively. there was significantly decreased in test 2 as compared to test 1 (P<0.01). 3) Shunt percentages (Qsp/QT) were measured as 8.3+/-2.3% in control, 25.4+/- 6.7% in test 1, 19.8+/-3.2% in test 2. Shunt percentages of test 1 and test 2 were increased significantly as compared to the control. Comparing the shunt percentages of test 1 and test 2, there was decreased in test 2 (P<0.01). Based on the above results, the application of appropriate CPAP to the unventilated lung during one lung ventilation is thought to be very effective in preventing hypoxemia. But, vigorous and meticulous monitoring, surveilance of patients and one lung ventilation with 100% oxygen are essential depending on the conditions of ventilated lung and long duration of one lung ventilation.

Richer's Syndrome: Report of a case

Richer's syndrome is a development of a high grade malignant lymphoma in a patient with preexisting chronic 1ymphocytic leukemia, small lymphocytic lymphoma or Waldenstrom's macroglobulinemia. A rare case of Richer's syndrome arising in the spleen of a 35-year-old-man was studied by morphology, immunohistochemistry and gene rearrangement study. He has had weight loss and night sweat for last 6 months. Hepatosplenomegaly and abdominal lymphadenopathy were noted on CT scanning. Especially an ovoid radiolucent mass was found within the image of splenomegaly. Lymph nodes and liver biopsy, bone marrow aspiration and splenectomy were done. In the lymph nodes, liver and bone marrow, well differentiated small lymphocytic infiltrations were found but, in the spleen, pleomorphic, large cells with occasional multinucleated giant cells formed a nodular mass surrounded by diffuse, extensive infiltration of small well differentiated lymphocytes. The two distinctive areas in the spleen had positive staining for B-cell marker (HLA-DR and L26), negative staining for T-cell marker (UCLH1), and positive staining for IgM heavy chain and kappa light chain by immuohistochemical study. so this case was diagnosed as a diffuse large cell 1ymphoma transformed from small lymphocytic lymphoma. We made an another effort to clarify their clonality. Gene rearrangement method usingcomplementarity.determining region 3(CDR3) of immunoglobulin heavy chain (IgH) gene and T-cell receptor gamma (TCRgamma) gene by polymerase chain reaction (PCR) technique was done. The two lymphomas in the spleen demonstrated the same rearrangement pattern in both IgH and TCRgamma gene. We think these findings strongly suggest that the large cell lymphoma has the same clonality with that of the small lymphocytic lymphoma.

A Study for Mechanism of Occlusion of Biliary Stents: A Electron Microscopy Study and Analysis of the Clogging Material / 대한소화기내시경학회지

Endoscopic biliary stents provide effective palliation of malignant obstructive jaundice in patients who are not surgical candidates. Unfortunately the stents in current use have a tendency to block. The clogging phenomenon also severely restricts the value of stents in patients with benign strictures. We studied the mechanism of the occlusion of biliary stents to find ways to prevent it. We have examined 17 blocked stents by electron microscopy(EM), infrared absorption spectrophotometry, and bacteriological cultures. The mean time to stent clogging with 10 french stents was 131 days, and with 12 French stents was 143 days. The differece between the clogging time of the two stents was statistically not sigificant. Scanning EM showed that the internal surfaces of the stent were covered with bacteria embedded in a condensed fibrillar intercellular matrix. The bacteris form a surrounding fibrillar extracellular product which anchors them to the stent. Inorganic crystals were rarely seen, because they presumable dissolved during the fixing for EM. These EM findings are typical of a biofilm. As major components of the occluding material calcium bilirubinate was identified in 15 stents by infrared absorption spectrophotometry. 7 different microorgainsms were isolated from the 17 blocked biliary stents. 6 of the isolates were gram-negative, and 1 was gram-positive. The most frequently isolated genus was Escherichia, which was found in 8 stents, followed by proteus, Pseudomonas, and Morganella, which was found in 2 stents respectvely. We propose that stent colgging is initiated by bacterial adhesion and growth of a biofilm. The bacteria then deconjugate bilirubin in bile and the lumen is progressively occluded by deposition of calcium bilirubinate and further biofilm formation.

A Case of Acute Graft-versus-Host Disease / 대한피부과학회지

We report a case of acute graft-versus-host disease, which developed after bone marrow transplantation because of acute myelocytic leukemia in a 39-year old male, The pruritic, erythematous maculopapular eruptions began to developed on the perioral regions, and spreaded the face, the oral mucosa, both hands, and buttocks at the twenty fourth day after bone marrow transplanta.tion. The eruptions were confluent to form erythematous patches. Iistopathological findings show parakeratosis, lymphoid cell exocytosis, and papillary edema, lymphohistiocytic infiltration, and melanophage in the upper dermis, and basal vacuolation. He was treated systemically by methylprednisolone, and antilymphocytic globulin, and tapically by emollients and steroids.

A Case Report of Rhabdomyosarcoma Originating from the Prostate / 대한비뇨기과학회지

Rhabdomyosarcoma is a very rare case in urological field. We have experienced a case of rbabdomyosarcoma originating from the prostate. So we present this case report with the article review.

Statistical Observation on External Genital Organ Anomaly among Young Male in Korea / 대한비뇨기과학회지

No abstract available.

A Case Repart of Interstitial Cystitis / 대한비뇨기과학회지

No abstract available.

Clinical Observation of Urine Shred / 대한비뇨기과학회지

There have been very rare studies or articles about the shreds of urine. The author had observed microscopically the shreds of urine which were taken from the 624 healthy adult Korean males and obtained the following interesting results: 1) The shreds of urine, in the first urine taken early in the morning, were found in 195 cases (31.3%) among the 624 symptomless adult males. 2) In the above 195 cases, the shreds of urine were found in 45 cases (68.2%) among the 66 cases with a history of previous urethritis. And the shreds of urine were found in 150 cases (26.9%) in 558 cases without a history of previous urethritis. 3) As the result of microscopic examination about the shreds of urine in 624 cases, we found out 57 cases (9.1%) with 5~10 leukocytes/H.P.F. These 57 cases consist of 24 cases (36.4%) in 66 cases with a history of previous urethritis and 33 cases (5.9%) in 558 cases without a history of urethritis.

Penile Horn: A case report / 대한비뇨기과학회지

Penile horn is a peculiar form of penile wart disclosing excessive keratosis with unknown etiology. A case of penile horn arising on the circumcised wound 2 years after circumcision is presented with review of literatures.

Subcotneal Pustular Dermatosis: Report of a Case / 대한피부과학회지

A case of subcorneal pustular dermatosis is reported. This 39 year old woman repeatedly developed the erythematous vesicopustular eruptions on the trunk and the extremeties with scvere tiching sensation for about 7 months. Histological examinstion revealed the subcorneal pustules and the mild inflammatory cell infiltration, so tetracycline 1500mg. And chloramphenicol 1000mg. Were adminiistered without benefit. The second biopsy was obtained and it revealed as the subcorneal pustular dermatosis. Therapy with DDS was instituted and was followed by marked clearing of the lesions.