Specific Cohort Of Patients Research Articles

Major abdominal cancer resections in cirrhotic patients: How frequent is postoperative hepatocellular decompensation?

The reported incidence of postoperative liver failure in cirrhotic patients is highly varied with diverse risk factors identified to predict risk, mainly drawn from organ or disease-specific studies. We aimed to assess risk factors for the development of postoperative liver failure in a specific cohort of patients with cirrhosis undergoing abdominal cancer resection. From November 2007 to October 2012, 30 cirrhotic patients who underwent curative resection for abdominal cancer were analyzed. The postoperative trends in liver function were followed and the incidence of postoperative liver failure was demonstrated. Among the 30 patients, the tumors were located in the stomach (n = 5), pancreas (n = 5), colon/rectum (6), liver (n = 11), gallbladder (n = 1), and retroperitoneum (n = 2). Eighteen (60 %) patients experienced postoperative liver failure of which 7 (23 %) patients required deviation from the clinical course or management. There was one mortality due to grade C liver failure and hepatorenal syndrome. On multivariate analysis, only age (>55 years) was found to be statistically significant to predict postoperative liver failure (p = 0.024). Liver dysfunction remains a major problem during the postoperative phase of major gastrointestinal cancer resections. However, less than one fourth of well-selected patients will develop significant postoperative liver failure. This incidence may be further reduced if the selection is restricted to younger patients.

The pre-treatment prevalence and types of sexual dysfunction among patients diagnosed with prostate cancer

Erectile dysfunction (ED) following prostate cancer therapy is a common condition that is well documented in literature. Despite the significant focus placed on ED and prostate cancer, very little is known regarding the baseline prevalence of other aspects of sexual dysfunction (SD) in this specific cohort of patients. The objective of the current manuscript was to assess the prevalence of subtypes of SD, including ED, ejaculatory dysfunction (EjD) and decreased libido among men with newly diagnosed prostate cancer. To achieve this objective, patients presenting to our clinic with a new diagnosis of prostate cancer from July 2011 and May 2012 completed the Male Sexual Health Questionnaire (MSHQ) to assess baseline sexual function. A total of 60 patients completed an MSHQ, with a mean age of 60.28±6.25 (range 44-73years). Of patients surveyed, 14% reported no sexual activity within the previous month, while 53% had sex at least once weekly. The percentage of patients reporting ED, EjD and decreased sexual desire ≥50% of the time was 37, 26 and 48% respectively. Eleven to 18% of patients reported that these symptoms were 'very' or 'extremely' bothersome. Patients noted dissatisfaction with the quality of their sexual relationship, frequency of sexual activity and quality of sex in 18, 31 and 20%, respectively. Overall findings suggest that patients with newly diagnosed prostate cancer experience a high rate of SD at baseline. Knowledge of these prevalence rates may assist physicians managing patient's expectations with planned therapies.

Gait Asymmetries Persist 1 Year After Anterior Cruciate Ligament Reconstruction.

Background:After anterior cruciate ligament reconstruction (ACLR), motivation to return to previous levels of activity is high. Very few studies have used return-to-activity criteria to determine when to permit athletic play. Return-to-activity measures objectively evaluate functional limb symmetry; however, previous biomechanical studies have found gait deviations in these individuals that persist up to 2 years after surgery.Purpose:To evaluate gait biomechanics in a specific cohort of ACL patients 1 year after surgery and retrospectively compare individuals who pass return-to-activity criteria 6 months after surgery with those who fail.Study Design:Prospective analysis.Methods:A total of 40 athletes who participated regularly (>50 h/y) in cutting, jumping, and pivoting activities and who sustained an isolated, unilateral ACL rupture were included in this study. All participants underwent reconstruction by the same surgeon and received individualized postoperative rehabilitation. Performance-based and self-report data were measured 6 months after surgery to assess readiness to return to activity (90% outcome required to pass); 20 subjects passed return-to-activity criteria and 20 subjects did not. Motion analysis was performed 1 year after surgery, and knee flexion angles, moments, and excursions were measured during gait and evaluated for all subjects.Results:There was no limb × group interaction or effect of group for all measures. Decreased knee measures were seen on the involved limb compared with the uninvolved limb for all subjects, and failed subjects demonstrated larger differences between limbs.Conclusion:Patients continued to demonstrate biomechanical limb asymmetries 1 year after ACLR, regardless of performance-based measures at 6 months. Early return to activity did not ensure limb symmetry at 1 year.Clinical Relevance:Gait asymmetries were seen in all subjects 1 year after surgery regardless of status at 6 months. Potentially prolonging athlete’s timelines for returning to activity may prove beneficial for a successful return to activity as well as for long-term knee function.

SU‐E‐T‐245: A Physics Database for a Multi‐Institutional Quality Consortium

Purpose: A collaborative quality initiative (CQI) has been developed in the state of Michigan to assess physician and patient reported outcomes to compare conformal and IMRT techniques for a specific cohort of breast and lung cancer patients. Here, we present a web‐based database that was designed to collect planning and delivery information to facilitate analysis of outcomes for the CQI. Methods: A web‐based database was built to capture key physics information, including dose that may be related to acute toxicities. An annual institutional questionnaire captures the technology available for these patients. A patient‐specific survey collects simulation, planning, and delivery information. To overcome differences in DVH file formats, a simple interface was developed where the user selects from a structure list, submits numeric data, and reviews the data summary. To analyze the delivery type, DICOM‐RT plan files are uploaded via a web interface. The data are anonymized and displayed for the user to verify that no protected health information is submitted. Results: Initial partner institutions tested and provided feedback on all aspects of the physics data collection. Institutions have shared customized programs for extracting DVH and DICOM‐RT data and documents for electronic workflow. Data submission began via the web portal in April 2012. There are 4 planning systems represented among the 14 institutions. Delivery techniques include static, dynamic and segmental MLC, Tomotherapy, and VMAT. As of February, data have been submitted for approximately 80% of the 815 eligible cases. Centers will be audited for data quality once per year. Conclusion: A system has been designed to capture high integrity simulation, plan, and delivery data for a CQI focused on breast and lung cancer. This information will be used to quantitatively evaluate the use of IMRT techniques in the state of Michigan and to permit dose‐based correlations to physician and patient‐rated toxicities. This work was funded by Blue Cross Blue Shield of Michigan.

CLINICAL BIOCHEMISTRY DATABASE ANALYSIS: A RESTRICTED DIALYSIS COHORT /

Summary Background: A retrospective study was undertaken to inves- tigate the biochemistry data of a restricted cohort of dialysis- related arthropathy patients. The aim of our study was to characterize this specific cohort of dialysis patients using a clinical chemistry database analysis. Methods: An elaboration of more than 160,000 items of biochemical data, collected from 2001 to 20|11, was made of 50 patients, 25 with dialysis-related arthropathy and 25 patients asymptomatic for arthropathy. A Student's t-test was applied, considering a P-value less than 0.05 as statistically significant. Results: Significant and relevant unexpected biochemical dif- ferences were found between the two groups of patients. The serum level of p2-microglobulin was similar, while fer- ritin values were significantly higher in symptomatic patients. We excluded the possibility that the ferritin difference between the two groups was due to different iron storage and to an inflammatory profile. Conclusions: The correct use of a biochemical database could permit to identify significant values which must be cor- related with clinical data, but which could be the first step to a wider research.

Reply to Dayan et al.

I would like to thank Dayan et al. for their insightful comments [1] on our recently published manuscript [2]. Moreover, Dayan et al. should be congratulated for their own contributions in the field of BAV-associated aortopathy [3, 4]. The above-discussed manuscript does not give definite answer to the question of predictors for proximal aortic dilatation after AVR surgery in BAV patients [2]. Our multivariate analysis was based on eight (5%) clinically relevant adverse aortic events, which inherently limit the number of variables, which may be reasonably included in the regression analysis. We did not include the variable ‘BAV configuration’ in our statistical analysis, as this morphological information was available retrospectively in only 55% of our study population (i.e. 84 of 152 patients). In contrast to the findings of Dayan et al. [4], we did not find any significant correlation between the body surface area (BSA), family history of BAV and the increased risk of adverse aortic events in our study. One possible explanation for this discrepancy may be the inclusion of BAV patients with an isolated/predominant aortic valve insufficiency (i.e. 17% of the study cohort) in the series of Dayan et al. [3]. This specific subgroup of BAV patients, which may be also defined as a ‘root phenotype’, is predominantly male (i.e. larger BSA) and have often a strong family history of BAV/aortopathy [5]. Recent data from the literature indicate significantly increased risk of late adverse aortic events in this specific cohort of BAV patients after isolated AVR [6]. There is emerging evidence that this phenotype of BAV disease may represent a predominantly congenital/ genetic form of BAV/aortopathy [5]. The inclusion of BAV patients with a ‘root phenotype’ in the study of Dayan et al. [4] may reasonably explain the progression of aortic root dimensions late after AVR surgery and the observed correlations with the BSA as well as with the family history of BAV/aortopathy. In contrast to that, we included only BAV patients with an isolated/predominant aortic valve stenosis [2]. Unfortunately, our study was not designed to specifically analyse the protective effects of long-term pharmacological treatment (i.e. effects of beta-blockers and statins). The vast majority of our patients (i.e. 95% of the study cohort) underwent long-term beta-blocker therapy after AVR, whereas only very few of them received statins. Therefore, we were not able to reasonably include these variables in our Cox regression model. Dayan et al. [4] found recently some positive effects of betablocker/statin use in the BAV patients in preventing aortic root dilatation between 6 and 8 years after an isolated AVR. However, such data should be interpreted with a caution. Only a small proportion of the initial study cohort received pharmacological treatment postoperatively (i.e. 11 (18%) patients with betablockers and 8 (13%) patients with statins postoperatively) [3]. Moreover, only 23 of 60 (38%) patients of the initial study cohort underwent an echocardiographical follow-up examination at 8 years post-AVR [4]. This would result in a very limited number of pharmacologically treated BAV patients at 8 years post-AVR. In summary, the protective effect of long-term betablocker/statin therapy in BAV-associated aortopathy is still unclear and should be addressed in future by means of largescale prospective studies.

Is the routine screening for significant atherosclerotic renal artery stenosis during coronary angiography/intervention indispensable?

We read the article “Screening for significant atherosclerotic renal artery stenosis with a regression model in patients undergoing transradial coronary angiography/intervention” by Pu et al. (2012), published in Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), with great interest. Of particular interest to us was the part considering the logistic regression model in this specific cohort of patients for future screening for significant atherosclerotic renal artery stenosis (ARAS). Although arteriography represents the gold standard for evaluation of ARAS, this exam is invasive and requires nephrotoxic iodinated contrast media which makes it less suitable as a first option for diagnosis or screening. Several non-invasive assessment tools, such as Doppler ultrasound and non-enhanced magnetic resonance angiography, have high sensitivity and specificity rates, but also have certain shortcomings. It seems that the invasive approach presented is too aggressive, considering the results of the regression analysis in this paper (Pu et al., 2012); clearly, patients with these variables can be suspected of having significant ARAS. Also, the study design indicates that the primary indication for angiography was coronary artery disease, and that renal angiography was also performed after the completion of coronarography. The results from Table 1 of Pu et al. (2012) seem puzzling as more than half of the patients (n=805, 54.2%) had normal coronary angiograms. Although several authors (Alpert, 1994; da Costa et al., 2001; Bugiardini and Bairey Merz, 2005) have described a small series of myocardial infarctions occurring in patients with normal coronary arteries, the incidence of such events is considered to be low, varying from 1% to 12%. Based on this finding, our question is: what was the indication for coronarography in these patients, or how did the authors define the term “normal” in relation to coronary arteries?

P-0248 Bevacizumab after Cetuximab Failure in Kras Wild-Type Metastatic Colorectal Carcinoma

ABSTRACT Introduction Bevacizumab and cetuximab both improve treatment efficacy when given with chemotherapy for metastatic colorectal carcinoma (mCRC) in both first- and second-line setting. Cetuximab has enhanced efficacy in Kras wild-type tumor. However, inferior outcomes were reported in two phase III randomised controlled trials for the concurrent use of bevacizumab and cetuximab with chemotherapy. There is an urgent need to define the optimal sequence of use of these two agents. With regard to the pre-clinical data that increased VEGF expression is associated with acquired resistance to anti-EGFR antibody, we performed a retrospective analysis on the outcomes of patients who received bevacizumab-containing regimens after cetuximab failure in Kras wild-type mCRC. Methods From January 2006 to December 2011, patients who received bevacizumab-containing regimens for mCRC in our institution were reviewed. Patients were eligible for further analysis if all the following criteria were met: [1] Kras wild-type mCRC, [2] received chemotherapy and cetuximab as immediate prior treatment, [3] received chemotherapy and bevacizumab as the index line of treatment and [4] had imaging for response evaluation. Outcome measures included median progression-free survival (mPFS) and objective response rate (ORR). Targeted adverse events were recorded in accordance with the two prospective observational cohort studies, the BRiTE and BEAT study. Adverse events include gastrointestinal perforation [perforation, intra-abdominal abscess, and fistula], arterial thromboembolic events (ATE) [myocardial infarction, cerebrovascular accident, transient ischemic attack, and unstable angina], postoperative bleeding or wound-healing complications (POWHC), grade 3/4 bleeding, and hypertension requiring additional anti-hypertensive. Results Fifty patients received bevacizumab-containing regimens were reviewed and 18 of them met all the criteria for further analysis. The median age was 56.5 and 10 patients had metastasis in multiple organs. After a median follow up of 12.1 months, the mPFS for the whole group of patients was 26.3 weeks (95% CI 19.5 – 33.0 weeks) with an ORR of 38.9%. For the 8 patients who received bevacizumab-containing regimens at second line, 1 complete response and 3 partial responses were observed, giving an ORR of 50%. The mPFS was 27.4 weeks (95% CI 2.0-52.8 weeks). For the 10 patients treated at third line, 3 PRs were observed, giving an ORR of 30%. The mPFS was 23.9 weeks (95% CI 19.7 – 28.1 weeks). Regarding previous exposure to oxaliplatin, irinotecan and 5FU, patients who exposed to only two of these agents, compared with those who exposed to all three agents, were more likely to respond to bevacizumab-containing regimen after cetuximab failure (Odds ratio 5.0, 95% CI 0.44-56.6). 2 patients (11.1%) had hypertension that required additional anti-hypertensive and 1 patient died of bowel perforation. The event of bowel perforation was unlikely attributed to bevacizumab since the event occurred 78 days after the last dose of bevacizumab while the patient was receiving hypofractionated palliative radiotherapy to the pelvis. There was no case of ATE, POWHC and grade 3/4 bleeding. Conclusion In patients with Kras wild-type mCRC, bevacizumab-containing regimens after cetuximab failure have promising activity and manageable toxicity. Further study is needed to compare switching to bevacizumab versus cetuximab beyond progression in this specific cohort of patients.

The Immunology of Glaucoma.

The presence of specific antibodies and T cells that are specific in patients with glaucoma supports the idea that the immune system may play an important role in the initiation and/or sustainment of glaucomatous optic neuropathy, at least in some patients. At present, our understanding regarding immunological mechanisms associated with glaucomatous optic neuropathy is far from satisfactory. In this review, we examined evidence suggesting involvement of autoimmune responses in the pathogenesis of glaucoma. These include detection of autoantibodies and T cells and expression of cytokines and stress proteins in patients with glaucoma. Although immune responses are thought to be detrimental, some responses may exert a protective effect against neurodegenerative damage. Likely, the balance between positive and negative regulators determines the survival or demise of cells. It is vital that research continues to elucidate the roles of the immune system in glaucomatous neurodegeneration and the possibility of alternative modalities of treatment. These studies may also provide valuable molecular biomarkers for the diagnosis and identification of a specific cohort of patients with glaucoma, that is, those with normal-tension glaucoma.

Preoperative Brain Natriuretic Peptide (BNP) Is a Better Predictor of Adverse Cardiac Events Compared to Preoperative Scoring System in Patients Who Underwent Abdominal Surgery

Cardiovascular disease is the leading cause of perioperative death in surgical patients. A variety of clinical scoring systems have been developed to predict adverse cardiovascular events. B-type natriuretic peptide (BNP) is a sensitive and specific predictor of left ventricular systolic dysfunction and predicts first cardiovascular event and death in the general population. We present a prospective, single-center, observational cohort study of patients undergoing major abdominal surgery and evaluate the role of BNP in predicting adverse cardiac events. A total of 205 patients were included in the study. All patients were assessed by a cardiological clinical evaluation, a 12-lead ECG report, and a preoperative and postoperative blood sample for plasmatic BNP assessment. The primary end point was the predictive power of preoperative BNP levels for adverse cardiac events until 30 days after discharge. Thirty-one of 205 (15%) patients had adverse cardiac events in the postoperative period up to 30 days after discharge. Five patients (2.4%) of these died of cardiac events. Preoperative BNP values were significantly increased in the 31 patients compared to the other patients in the postoperative period [mean = 112.93 pg/ml (range = 5-2,080) vs. 178.99 pg/ml (range = 5-3,980); median = 117 vs. 23 pg/ml; 95% CI = 49-181; p < 0.0001]. At logistic regression, a preoperative BNP value of >36 pg/ml was the only effective predictor of adverse cardiac events. We have demonstrated that elevated preoperative BNP levels are independent predictors of adverse cardiac events in a cohort of patients undergoing major abdominal surgery in a general surgery department, and this is the first study about this specific cohort of patients.

Principles and Recommendations for the Provision of Healthcare in Canada to Adolescent and Young Adult-Aged Cancer Patients and Survivors.

Adolescents and young adults (AYA) with cancer and survivors of cancer in childhood, adolescence, and young adulthood are a constituency facing disparities of care affecting quality of life and other outcomes in many parts of the world. In Canada, this situation occurs in a nation with population-based cancer control programs and a government-funded healthcare system. The Canadian Task Force on Adolescents and Young Adults with Cancer was established in 2008 with a mission to ensure that AYA-aged Canadians with cancer and AYA survivors of cancer have prompt, equitable access to the best care, and to establish and support research to identify how their health outcomes and quality of life can be optimized. Following a survey of existing services, and in consultation with survivors, healthcare professionals, and policy makers, the Task Force identified principles of care, priority issues for research and the establishment of outcome metrics, and strategies for implementing change that are designed to improve the outcomes and quality of life of this specific cohort of patients and survivors with unique developmental needs. The six broad recommendations highlight the need for age-appropriate psychosocial, survivorship, palliative, and medical care as well as research to redress inequities in the care provided to this group relative to both younger and older cancer patients. Improved care for this group will enable individuals to reach their full potential as productive, functioning members of society, and will provide economic and other societal benefits.

Commentary on an article by Brett P. Wiater, MD, et al.: “Risk Factors for Chondrolysis of the Glenohumeral Joint. A Study of Three Hundred and Seventy-five Shoulder Arthroscopic Procedures in the Practice of an Individual Community Surgeon”

Chondrolysis remains a catastrophic and devastating condition of the shoulder that has had many associated but not well-proven causes. Numerous published case reports and small case series have led to difficulty in extrapolating any meaningful data with respect to the true etiology of this condition1-6. Wiater et al. were presented with a unique opportunity to review a specific cohort of patients from a single community orthopaedic surgeon as a result of a medicolegal action related to chondrolysis. They were provided complete access to the medical records on 375 intra-articular shoulder arthroscopic procedures performed by the surgeon from 1999 to 2008. A number of factors were assessed, including patient age at the time of surgery, side of surgery, date of surgery, preoperative diagnosis, type of anesthesia, procedure performed, use and type of suture anchors, use of radiofrequency, and use and location of a postoperative local anesthetic infusion catheter. They also were able to ascertain the type and concentration of local anesthetic used for postoperative analgesia and whether epinephrine was used in the infusate. Forty-nine surgical procedures (13%) were complicated by chondrolysis. Each of these forty-nine procedures was associated with intra-articular infusion of either Marcaine (bupivacaine) or lidocaine. Furthermore, none of the patients who had an arthroscopic procedure without infusion of anesthetics developed postoperative chondrolysis. Additional significant factors associated with the development of chondrolysis were arthroscopic Bankart repair, arthroscopic debridement, one or more suture anchors in the glenoid, and surgery duration. Only six shoulders had 0.25% Marcaine, but none had chondrolysis in that group. A recent systematic review of studies from peer-reviewed journals identified 100 cases of chondrolysis7. Fifty-nine percent of the cases involved post-arthroscopic use of anesthetic infusate (usually bupivacaine, with lidocaine used in only two cases). Finally, the authors of a recent study reported eighteen cases of chondrolysis related to the intra-articular infusion of bupivacaine with epinephrine through an intra-articular pain pump catheter8. Forty-five pain pumps were used in the 113 arthroscopic procedures during the same time period. Chondrolysis developed in sixteen of thirty-two patients with a high-flow intra-articular pain pump catheter and in just two of twelve patients with a low-flow intra-articular pain pump catheter. (The pump type was not determined for the forty-fifth patient.) This information, in conjunction with the finding by Wiater et al. that the duration of surgery was correlated with the development of chondrolysis, provides a possible link between the newer, higher-flow pain pumps and the development of this condition. Given the literature to date, in conjunction with this unique article by Wiater et al., it appears reasonable to caution against the use of intra-articular infusion of anesthetics, specifically bupivacaine or higher concentrations of lidocaine. Basic science studies by Chu et al.9 and Gomoll et al.10 further highlight the potential chondrotoxic effects of bupivacaine, and these negative correlations far outweigh any possible analgesic benefits. Furthermore, the issue of the association of high-flow intra-articular pain pumps with higher rates of chondrolysis and their continued use should be carefully examined as well. The authors did not specifically analyze or hypothesize about the association between chondrolysis and suture anchors in the glenoid, and it is not intuitively clear why this association would exist, given that hundreds of thousands of these implants have been placed since their introduction in the early 1990s. In summary, Wiater et al. were provided with a unique opportunity to explore the possible causes of chondrolysis, a rare but devastating condition in the shoulder. While many unanswered questions remain, their paper, combined with the recent peer-reviewed literature, has further illuminated the role of local anesthetics and high-flow pain pumps in causing chondrolysis, and the intra-articular use of these techniques in association with shoulder arthroscopy should be avoided.

Outcomes for those with or without physical comorbidity for a specific cohort of chronic low back pain patients in an active rehabilitation approach

AbstractThe objective of the study was to determine the relationship between physical comorbidity and outcomes in a cohort of chronic low back pain (LBP) patients (n = 2777). Patients were treated at one of 48 physiotherapy clinics between January 1, 2005 and September 30, 2006. All patients were categorized into either: (i) physical Comorbidity Group (n = 898), or (ii) only Back Pain Group (n = 1879). There were no baseline statistical differences in symptom duration, visual analogue scale, function and medication use between groups. The Comorbidity Group was significantly older by 5 years and more females (p < 0.0001); odds ratios were adjusted for age and sex. Logistic regression analysis revealed no statistically significant differences for change in functional score (OR = 0.996), change in pain rating (OR = 1.013) and total treatment sessions (OR = 0.997), between groups. Those with LBP and a physical comorbidity (coronary artery disease, hypertension, rheumatoid arthritis, diabetes, non-spinal malig...

The novel nomogram of Gleason sum upgrade: Possible application for the eligible criteria of low dose rate brachytherapy

To examine the rate of Gleason sum upgrading (GSU) from a sum of 6 to a Gleason sum of ≥7 in patients undergoing radical prostatectomy (RP), who fulfilled the recommendations for low dose rate brachytherapy (Gleason sum 6, prostate-specific antigen ≤10 ng/mL, clinical stage ≤T2a and prostate volume ≤50 mL), and to test the performance of an existing nomogram for prediction of GSU in this specific cohort of patients. The analysis focused on 414 patients, who fulfilled the European Society for Therapeutic Radiation and Oncology and American Brachytherapy Society criteria for low dose rate brachytherapy (LD-BT) and underwent a 10-core prostate biopsy followed by RP. The rate of GSU was tabulated and the ability of available clinical and pathological parameters for predicting GSU was tested. Finally, the performance of an existing GSU nomogram was explored. The overall rate of GSU was 35.5%. When applied to LD-BT candidates, the existing nomogram was 65.8% accurate versus 70.8% for the new nomogram. In decision curve analysis tests, the new nomogram fared substantially better than the assumption that no patient is upgraded and better than the existing nomogram. GSU represents an important issue in LD-BT candidates. The new nomogram might improve patient selection for LD-BT and cancer control outcome by excluding patients with an elevated probability of GSU.

Pre-operative assessment enables early diagnosis and recovery of shoulder function in patients with breast cancer

In order to determine the extent and time course of upper limb impairment and dysfunction in women being treated for breast cancer (BC), and followed prospectively, a novel physical therapy surveillance model post-treatment was used. Subjects included adult women with newly diagnosed, untreated, unilateral, Stage I to III BC, and normal physiological and biomechanical shoulder function. Subjects were excluded if they had a previous history of BC, or prior injury or surgery of the affected upper limb. Measurements included body weight, shoulder ranges of motion (ROM), manual muscle tests, pain levels, upper limb volume, and an upper limb disability questionnaire (ULDQ). Measurements were taken at baseline (pre-surgery), and 1, 3-6, and 12 months post-surgery. All subjects received pre-operative education and exercise instruction and specific physical therapy (PT) protocol after surgery including ROM and strengthening exercises. All measures of function were significantly reduced 1 month post-surgery, but most recovered to baseline levels by 1-year post-surgery. Some subjects developed signs of lymphedema 3-12 months post-surgery, but this did not compromise function. Shoulder abduction, flexion, and external rotation, but not internal rotation ROM, were associated with the ULDQ. Most women in this cohort undergoing surgery for BC who receive PT intervention may expect a return to baseline ROM and strength by 3 months. Those who do not reach baseline, often continue to improve and reach their pre-operative levels by 1-year post-surgery. Lymphedema develops independently of shoulder function 3-12 months post-surgery, necessitating continued monitoring. A prospective physical therapy model of surveillance allows for detection of early and later onset of impairment following surgery for BC in this specific cohort of patients.

Progression and treatment of HER2-positive breast cancer

Approximately 20-30% of breast cancer tumors overexpress or amplify human epidermal growth factor receptor 2 (HER2). The role of this receptor in the progression of HER2+ breast cancer and resistance to certain anticancer monotherapies was investigated. The results of several pre-clinical and clinical trials, with the aim of determining the most safe and effective course of treatment for HER2+ breast cancer, were also thoroughly examined. A thorough search of databases including Pubmed, Springer, and The American Society of Clinical Oncology was performed, and pertinent studies were identified. The most relevant studies were preclinical, phase II, and III clinical trials identifying the function of the HER2 receptor in HER2+ breast cancer progression, as well as studies assessing the efficacy of monotherapy and combination therapy in the treatment of this aggressive form of cancer. The HER2 receptor belongs to a family of receptors that consists of four cell-surface receptors (HER1-4) that share strong homology with the epidermal growth factor receptor (EGFR). All HER receptors interact with specific types of ligands to induce receptor activation, except for HER2, for which no known ligand has yet been identified. HER2 is activated by forming dimers with other HER receptors, and this results in a stronger and more prolonged signal transduction event. When expressed at normal levels, HER2 regulates cell growth, differentiation, and survival. However, under pathological conditions of HER2 overexpression, numerous HER2 heterodimers are formed resulting in aggressive tumor growth. Therefore, the prognosis associated with HER2-positive breast cancer is usually poor. A specific cohort of patients with breast cancer whose tumors test both hormone receptor (estrogen receptor [ER] and progesterone receptor [PR]) and HER2 positive have been found to be resistant to targeted hormone therapy. Studies investigating the etiology of this resistance have found that the cell membrane estrogen receptor communicates with HER2 in promoting the release of ER coactivators that cause the endocrine drug and selective estrogen receptor modulator, tamoxifen, to act as an agonist rather than an antagonist of the hormone estrogen. Thus, research has directed its inquiry toward the development of therapies specifically targeting HER2. The development of trastuzumab, a recombinant monoclonal antibody against HER2, initially proved to be a well-tolerated first line of treatment. However, in the long-term patients, trastuzumab was shown to develop resistance to this monotherapy. Therefore, research on HER2 positive breast cancer has focused on the study of different anti-HER2 combination therapies over the past decade. While the development and approval of the HER2-targeted recombinant monoclonal antibody trastuzumab (Herceptin) has been efficacious in slowing HER2 cancer progression, combining this and other anti-HER2 therapy with either chemotherapy or endocrine therapy has proven more effective in improving overall and progression free survival.

Grade 3 Status Dominates Prognosis in Breast Cancer.

Abstract Background: Histological grading (HG) is probably the most important clinico-pathological parameter that will provide information about tumour intrinsic characteristics and aggressiveness. HG is included in prognostic guidelines for treatment decision making such as St Gallen, Nottingham Prognostic Index and Adjuvant!Online. Grade 3 (G3) Breast cancer (BC) is associated with poor prognosis in terms of survival and recurrence. G3 BC reflects independent biological entities rather than being the end of the spectrum of cancer progression. Our aim is to establish the clinical relevance of HG as prognostic factor in a specific cohort of BC patients and define its relation with survival and recurrence endpoints.Method: This is a retrospective cohort analysis from 1489 operable Breast Cancer patients attending the Oncology Service at Singleton Hospital, Wales, UK between 1996 and 2002.HG was recorded for 1339 cases and outcome data were available on 1213 cases. Correlation of clinical variables with Overall Survival (OS), Distant Disease Free Survival (DDFS) and Disease Free Survival (DFS) was performed using Cox regression model.Results:The median follow-up for the cohort was 5.43 years (range 0.09 to 10.14 years) Patients were characterised according to age, HG, tumour size (TNM-T), nodal status, ER status and systemic treatment received (polychemotherapy/tamoxifen). Independent Cox regression models for each endpoint were developed based on univariate analyses. Multivariate analysis results are presented in Figure 1.Subgroup analysis of G3 cases showed a younger population: median age G3 59.4y vs G1/G2 62.9 y p:&amp;lt; 0.001); 47.5% of G3 cases were ER positive against 94.5% of Grade 1/2 (p &amp;lt; 0.001). Patients with G3 tumours died more rapidly from all causes (median time to death 2.22 vs 3.42 y, p &amp;lt;0.001) and from BC (median time to death from BC 2.22 y vs 3.82 y in G1/G2, p &amp;lt;0.001) than other HG. Similarly, G3 also relapsed quicker both distantly, (median time 1.64 vs 2.54 y G1/G2 (p&amp;lt;0.04) and locally, median time to relapse 1.6 vs 2.35 y for G1/G2 (p&amp;lt;0.036). There was also a significant association between grade and tumour size (median G1/G2 1.7cm vs G3 2.2cm(p&amp;lt; 0.001); and nodal involvement and tumour size, median 1.5cm N-ve, 2.2 cm N+ve (p&amp;lt; 0.001).Conclusion: Patients with G3 tumours tended to be younger, had a more advanced TNM staging at diagnosis and relapsed and died more rapidly than other histological grades. In our cohort, G3 tumours were adversely associated with OS, DDFS and DFS with a stronger association with these endpoints than node positivity. It is perhaps time to reconsider the HG as a prognostic factor as important as nodal status for the selection of adjuvant chemotherapy regimens. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6005.

Outcome of Antibiotic Prophylaxis Cessation in Patients With Persistent Vesico-Ureteral Reflux Who Initially Presented With a Febrile Urinary Tract Infection

Purpose Growing evidence suggests that antibiotic prophylaxis (ABP) may not prevent urinary tract infections (UTI). We report on the outcome of a specific cohort of patients assembled based on initial VUR diagnosis after a febrile UTI. Material and Methods We retrospectively reviewed a prospectively collected database of patients with persistent VUR who discontinued ABP once toilet trained and with no evidence of dysfunctional voiding. End points included febrile UTIs, abnormalities on follow-up renal ultrasound and need for further interventions. Results 72 girls and 24 boys were evaluated. Mean patient age at ABP cessation was 5.4 years (range 2.3-11.8), and mean subsequent follow-up was 28months (range 5-101). Reflux grade at presentation was I in 3%, II in 37%, III in 46%, IV in 8% and V in 4%; VUR was bilateral in 51 patients (53%). Febrile urinary tract infection developed in 9 girls and 1 boy (10% of the cohort, mean age=6 years), an average of 17.2 months (range 5 to 44 months) after ABP discontinuation. Findings consistent with new renal scarring on ultrasound were identified in one patient who developed a febrile UTI and in one without infection. Upon comparison of the group who developed febrile UTI against those that did not a significant difference was found in number of high grade VUR (p 0.007) and the development of dysfunctional voiding (p=0.002). Conclusions This data supports ABP discontinuation in the majority of patients with VUR who present with a febrile UTI. Development of dysfunctional elimination symptoms seems to be a preventable risk factor amenable to treatment. Growing evidence suggests that antibiotic prophylaxis (ABP) may not prevent urinary tract infections (UTI). We report on the outcome of a specific cohort of patients assembled based on initial VUR diagnosis after a febrile UTI. We retrospectively reviewed a prospectively collected database of patients with persistent VUR who discontinued ABP once toilet trained and with no evidence of dysfunctional voiding. End points included febrile UTIs, abnormalities on follow-up renal ultrasound and need for further interventions. 72 girls and 24 boys were evaluated. Mean patient age at ABP cessation was 5.4 years (range 2.3-11.8), and mean subsequent follow-up was 28months (range 5-101). Reflux grade at presentation was I in 3%, II in 37%, III in 46%, IV in 8% and V in 4%; VUR was bilateral in 51 patients (53%). Febrile urinary tract infection developed in 9 girls and 1 boy (10% of the cohort, mean age=6 years), an average of 17.2 months (range 5 to 44 months) after ABP discontinuation. Findings consistent with new renal scarring on ultrasound were identified in one patient who developed a febrile UTI and in one without infection. Upon comparison of the group who developed febrile UTI against those that did not a significant difference was found in number of high grade VUR (p 0.007) and the development of dysfunctional voiding (p=0.002). This data supports ABP discontinuation in the majority of patients with VUR who present with a febrile UTI. Development of dysfunctional elimination symptoms seems to be a preventable risk factor amenable to treatment.

OUTCOME OF ANTIBIOTIC PROPHYLAXIS CESSATION IN PATIENTS WITH PERSISTENT VESICO-URETERAL REFLUX WHO INITIALLY PRESENTED WITH A FEBRILE URINARY TRACT INFECTION

Purpose Growing evidence suggests that antibiotic prophylaxis (ABP) may not prevent urinary tract infections (UTI). We report on the outcome of a specific cohort of patients assembled based on initial VUR diagnosis after a febrile UTI. Material and Methods We retrospectively reviewed a prospectively collected database of patients with persistent VUR who discontinued ABP once toilet trained and with no evidence of dysfunctional voiding. End points included febrile UTIs, abnormalities on follow-up renal ultrasound and need for further interventions. Results 72 girls and 24 boys were evaluated. Mean patient age at ABP cessation was 5.4 years (range 2.3-11.8), and mean subsequent follow-up was 28months (range 5-101). Reflux grade at presentation was I in 3%, II in 37%, III in 46%, IV in 8% and V in 4%; VUR was bilateral in 51 patients (53%). Febrile urinary tract infection developed in 9 girls and 1 boy (10% of the cohort, mean age = 6 years), an average of 17.2 months (range 5 to 44 months) after ABP discontinuation. Findings consistent with new renal scarring on ultrasound were identified in one patient who developed a febrile UTI and in one without infection. Upon comparison of the group who developed febrile UTI against those that did not a significant difference was found in number of high grade VUR (p 0.007) and the development of dysfunctional voiding (p = 0.002). Conclusions This data supports ABP discontinuation in the majority of patients with VUR who present with a febrile UTI. Development of dysfunctional elimination symptoms seems to be a preventable risk factor amenable to treatment.

Gram-negative organisms predominate in Hickman line-related infections in non-neutropenic patients with hematological malignancies

Catheter-related blood stream infections (CRBSI) cause significant morbidity and mortality in patients with hematological malignancies. Previous studies have identified a predominance of gram-positive organisms causing CRBSI but they included both neutropenic and non-neutropenic patients with solid organ and hematological malignancies. The aim of our study was to evaluate the incidence and microbiological profile of CRBSIs in a specific cohort of patients with hematological malignancies in their non-neutropenic phase of illness. A detailed retrospective review was done from January 2003 to December 2005 on all patients with hematological malignancies who had double-lumen non-antibiotic impregnated tunneled CVCs (Hickman catheters) inserted in our hospital to identify those fulfilling our criteria for CRBSI episodes. Amongst 273 evaluable patients, 61 developed CRBSI on 70 occasions. In contrast to previous studies, there was a predominance of gram-negative infections (68%). The majority (73%) of initial CRBSI episodes required catheter removal within 7 days of onset. Vancomycin and cefepime was the most common initial antibiotic regimen used. This study highlights the predominance of gram-negative infections in our cohort of non-neutropenic patients with underlying hematological malignancies who had Hickman catheters whose lines were not salvageable in the majority of cases. Empiric monotherapy with an antimicrobial agent with broad spectrum gram-negative cover needs to be given upfront pending results of the nature and sensitivity of organisms identified.