Preoperative Hypoalbuminemia is Associated with Increased Mortality in Patients Undergoing Surgery for Gynaecologic Malignancy - A Retrospective Cohort Study.

OBJECTIVE: Our objective was to evaluate the significance of reduced preoperative albumin levels on short-term (90-day and 1-year) mortality in patients undergoing surgery for gynaecologic malignancy in Calgary, Alberta, Canada. METHODS: In this retrospective cohort study, patients with gynaecologic malignancies who had surgery performed at Foothills Medical Centre in Calgary, Alberta, Canada between January 1, 2010, and June 30, 2016, were identified. We performed univariable and multivariable logistic regression analyses to evaluate the association between preoperative serum albumin and 90-day and 1-year mortality. Analysis was conducted with albumin initially as a continuous variable, and subsequently as a categorical variable after clinically relevant threshold levels were identified. RESULTS: A total of 2183 patients were included in our analysis. Of the study population, 51.8% had a preoperative serum albumin level of <35 g/L. Two critical inflection points in mortality rate by serum albumin level were found. Mortality was significantly highest in patients with an albumin level <20 g/L (90-day mortality 17.2%, 1-year mortality 31.9%) and next highest in patients with an albumin level of 20-25 g/L (90-day mortality 2.7%, 1-year mortality 12.0%), compared to patients with a level of >25 g/L (90-day mortality 0.9%, 1-year mortality 3.9%). In both univariable and multivariable analyses, preoperative hypoalbuminemia was significantly and independently associated with increased 90-day and 1-year mortality (P < 0.001). CONCLUSION: Preoperative hypoalbuminemia is independently associated with increased mortality. Patients with gynaecologic malignancies undergoing surgery and who have a preoperative serum albumin level of <20 g/L are at a very high risk of short-term mortality.

FIGO Stage Is the Strongest Prognostic Factor in Adenocarcinoma of the Uterine Cervix.

OBJECTIVE: This study aimed to identify clinical and pathological determinants of invasive adenocarcinoma of the uterine cervix (AC) in a large, single-centre series serving a population of 1.5 million. METHODS: Data on clinical (n = 27) and pathological (n = 23) variables for 166 women with a diagnosis of AC treated between 2000 and 2013 were extracted from their charts and pathology reports. Overall survival (OS) was calculated, and significant determinants were identified using Kaplan-Meier analyses and log-rank tests, respectively (Canadian Task Force Classification II-2). RESULTS: This was a heterogeneous group of women with all stages of disease treated with conization, surgery, radiation, and systemic chemotherapy, alone or in combination. Mean age at diagnosis was 43; 86.7% had stage I disease, 9.6% had stage II, and only 3.6% had stage III and IV disease. Mean follow-up was 108 months. Many histotypes were diagnosed and grouped as mucinous (n = 103), endometrioid (n = 15), rare (n = 9), and adenosquamous (n = 39) types. Twenty-eight women had recurrent cancer and died of the disease; OS at 5 years was 85%. Five-year OS for women with stage I was 92%, compared with 40% for stage II or higher. Univariate analysis revealed that premenopausal status, tumour size, first-line treatment with chemotherapy, lymphovascular invasion, rare histological subtypes, stage, and receipt of second-line treatment were all significantly associated with a lower OS. Using multivariate analysis, only stage remained an independent factor. CONCLUSION: This is the largest single-centre Canadian series of invasive AC. Stage is the strongest prognostic factor in multivariate analysis; in contrast to other studies, lymph node status was not a significant determinant.

Cervical Adenocarcinoma: A Comparison of the Reproducibility of the World Health Organization 2003 and 2014 Classifications.

OBJECTIVE: The aim of the study was to compare the reproducibility of malignant glandular tumors of the uterine cervix classified per World Health Organization (WHO) 2003 and 2014. MATERIALS AND METHODS: Two pathologists reviewed 228 cases composed of adenocarcinoma in situ and 22 adenocarcinoma histotypes and selected 405 representative hematoxylin and eosin slides, which were digitally scanned. Six other pathologists (3 gynecological and 3 anatomical) independently reviewed and classified the images per both WHO classifications. One year later, they classified a random sample of 25 cases. Inter- (inter-OR) and intra-observer (intra-OR) reproducibility of the 6 pathologists and separately for gynecological compared with anatomical pathologists was tested using κ statistics. RESULTS: Both classifications were collapsed into 6 categories as benign, adenocarcinoma in situ, and mucinous, endometrioid, rare, and adenosquamous-miscellaneous carcinomas. WHO 2014 had an additional category: endocervical adenocarcinoma, usual type. Inter-observer κ values were more reliable than the intra-OR results based on 95% CIs. The average inter-OR κ values with both classifications were moderate between the 6 pathologists and between the 3 anatomical pathologists. In contrast, they were substantial between the 3 gynecological pathologists. With both classifications, the average intra-OR κ values of the 6 pathologists and both pathologist groups trended toward substantial. CONCLUSIONS: Reproducibility among 6 pathologists is unaffected by changes in the WHO 2014 classification and averages moderate between different and trends toward substantial between the same pathologist. Reproducibility between different pathologists can improve to substantial when they have expertise in gynecological pathology.

Quantifying Benefit of Autologous Transplantation for Relapsed Follicular Lymphoma Patients via Instrumental Variable Analysis.

The role of autologous stem cell transplantation (ASCT) in patients with relapsed follicular lymphoma (FL) remains controversial because of a lack of proven overall survival (OS) benefit versus nontransplant strategies. We conducted a comparative effectiveness research study involving 3 tertiary Canadian cancer centers to determine whether the ASCT-based approach used at 1 center improved OS relative to non-ASCT approaches used at the other centers. Of 1082 consecutive patients aged 18 to 60 years and diagnosed with FL from 2001 to 2010, the study population included 355 patients who experienced relapse from chemotherapy (center A = 96, center B = 84, center C = 175). Data were analyzed according to the instrumental variable of treatment center to control for confounding factors. The frequency of using ASCT at first or second relapse was significantly different between the centers (A = 58%, B = 7%, C = 5%, P < .001). With a median follow-up of 69.1 months, the actuarial 5-year OS rates after first chemotherapy relapse were 89%, 60%, and 60% for centers A, B, and C respectively (log rank P < .0001). Based on instrumental variable analysis, the use of ASCT at relapse 1 or 2 significantly decreased the risk of death from first relapse (HR .127, P = .004) and from initial diagnosis (HR .116, P = .004). In conclusion, for FL patients who relapse after chemotherapy, these results strongly support more frequent use of ASCT at first or second relapse.

Insulin pump use in pregnancy is associated with lower HbA1c without increasing the rate of severe hypoglycaemia or diabetic ketoacidosis in women with type 1 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to compare glycaemic control and maternal-fetal outcomes in women with type 1 diabetes managed on insulin pumps compared with multiple daily injections of insulin (MDI). METHODS: In a retrospective study, glycaemic control and outcomes of 387 consecutive pregnancies in women with type 1 diabetes who attended specialised clinics at three centres 2006-2010 were assessed. RESULTS: Women using insulin pumps (129/387) were older and had a longer duration of diabetes, more retinopathy, smoked less in pregnancy, and had more preconception care (p < 0.01 for each). Among 113 pregnancies >20 weeks' gestation in women on insulin pumps and 218 in women on MDI, there was a significant difference in HbA1c in the first trimester (mean HbA1c 6.90 ± 0.71% (52 ± 7.8 mmol/mol) vs 7.60 ± 1.38% (60 ± 15.1 mmol/mol), p < 0.001), which persisted until the third trimester (mean HbA1c 6.49 ± 0.52% (47 ± 5.7 mmol/mol) vs 6.81 ± 0.85% (51 ± 9.3 mmol/mol), p = 0.002). Rates of diabetic ketoacidosis were similar in women on insulin pumps vs MDI (1.8% vs 3.0%, p = 0.72). Despite lower HbA1c, women on insulin pumps did not have an increased incidence of severe hypoglycaemia (8.0% vs 7.6%, p = 0.90) or more weight gain (16.3 ± 8.7 vs 15.2 ± 6.2 kg, p = 0.18). More large-for-gestational-age infants in the pump group (55.0% vs 39.2%, p = 0.007) may have resulted from confounding by parity. CONCLUSIONS/INTERPRETATION: In this large multicentre study, women using insulin pumps in pregnancy had lower HbA1c without increased risk of severe hypoglycaemia or diabetic ketoacidosis but no improvement in other pregnancy outcomes. This information can help inform care providers and patients about the glycaemic effectiveness and safety of insulin pumps in pregnancy.

Primary squamous cell carcinoma of the endometrium: clinicopathologic and molecular characteristics.

Molecular alterations leading to cell cycle dysregulation in primary squamous cell carcinoma of the endometrium (PSCCE) and correlation with clinical outcome are incompletely described. Molecular variables of 5 cases of PSCCE were compared with 8 controls of endometrial endometrioid adenocarcinoma and correlated with overall survival. Immunohistochemical expression of pRB, p18, p19, CDK4, CDK6, Cyclin D1, p16, HPVE7, pTEN, ER, PR, and p53 was independently scored (intensity: 0-3 and proportion: 0-5) twice by 2 reviewers. Scores were averaged and expression was categorized as positive or negative. Human papillomavirus (HPV) DNA amplification and Braf and Kras mutations were assessed by polymerase chain reaction. Distribution differences between cases and controls were tested for significance using χ/Fisher exact tests. Differences in overall survival and correlation with variables were calculated using Kaplan-Meier and tested for significance using log rank tests. All cases and controls were mostly positive for pRB, p19, CDK6, and Cyclin D1 and mostly negative for p16, p18, CDK4, HPVE7, pTEN, and p53. Cases were mostly negative for ER and PR, whereas controls were mostly positive. All were negative for HPV DNA amplification and Braf mutations. One case and 2 controls had a Kras mutation. Only the ER and PR distribution difference was significant (P=0.03 and 0.02, respectively) and differences in overall survival did not correlate with any variable. PSCCE has molecular alterations involving the pRB-Cyclin D1-CDK4/6-p16 pathway, and pTEN. In contrast to the type I EACC, PSCCE is not hormonally sensitive, suggesting a unique pathogenesis.

Temporal and Regional Trends in Obstructive Sleep Apnea Using Administrative Health Data in Alberta, Canada.

Rationale: Obstructive sleep apnea (OSA) is a common treatable condition with important health and societal consequences. Objectives: We aimed to assess the annual incidence and prevalence of clinically recognized and geographic clustering of OSA in Alberta, Canada, using administrative health data case definitions. Methods: We used two administrative health databases in Alberta to identify ICD-9 and ICD-10 (International Classification of Diseases, Ninth and 10th Revisions, respectively) diagnostic codes for adults and children at least 2 years old diagnosed with OSA between 2003 and 2020. We defined OSA using an algorithm developed and validated in Alberta: at least three claims or one hospitalization within 2 years. We mapped residential postal codes to 70 subregional health authorities (SRHAs). Crude, age group- and sex-specific incidence and prevalence, and age group- and sex-standardized rates were calculated for Alberta and SRHAs. Spatial scan statistics identified clusters of SRHAs in which OSA cases were higher (hot spots) or lower (cold spots) than expected. Results: Between 2003 and 2020, OSA prevalence increased from 0.14% to 4.59%. The annual incidence of OSA increased after 2013. Incidence and prevalence were higher in older adults and children aged 2-11 years compared with 12-17 years. Cluster analysis revealed regional variation in OSA incidence and prevalence over time with no consistent pattern except for cold spots in one large metropolitan center (Calgary). Conclusions: From 2003 to 2020, the incidence and prevalence of clinically recognized OSA increased but varied by geography. Administrative health data can be used to guide interventions aimed at improving health service delivery and the quality of OSA care.

Interactions and relationships of PTEN, ERG, SPINK1 and AR in castration-resistant prostate cancer.

AIMS: Recently, ETS-related gene (ERG) gene rearrangements, phosphatase tensin homologue (PTEN) deletions and serine protease inhibitor Kazal type 1 (SPINK1) overexpression were investigated as potential markers for molecularly subtyping prostate cancer (PCA). However, their incidence and co-association in castration-resistant PCA (CRPC) has not been characterized fully. METHODS AND RESULTS: A cohort of 59 CRPC patients was investigated for ERG rearrangements, PTEN deletions and androgen receptor (AR) amplification by fluorescence in-situ hybridization. SPINK1 overexpression was assessed by immunohistochemistry. ERG rearrangements and PTEN deletions were detected in 22 of 53 (41.5%) and 35 of 55 (63.6%) of cases, with 15 of 22 (68.1%) of ERG rearrangements occurring through deletions. SPINK1 overexpression occurred in three of 51 (5.8%) of cases exclusively in non-ERG rearranged and AR amplification was detected in 12 of 49 (24.4%) of cases. Only PTEN deletions showed intrafocal heterogeneity occurring in nine of 35 (25.7%) of cases. PTEN deletions were significantly associated with each of ERG rearrangements occurring by deletions only (P = 0.001), AR amplification (P = 0.002) and SPINK1 overexpression (P = 0.002). None of the SPINK1 overexpressing tumours showed AR amplification (P = 0.005) and all occurred in PTEN deleted foci (P = 0.002). CONCLUSION: Te study supports the heterogeneous nature of CRPC and confirms a significant association between PTEN, ERG, AR and SPINK1. Characterizing combined markers will aid in defining PCA subgroups relevant to prognosis contributing to the design of improved therapeutic approaches for CRPC.

Care gaps in achieving cholesterol targets in people with diabetes: A population-based study in a universal health care setting.

AIMS: Statins are first line therapy in people with diabetes. Little is known about real-world statin intensity use and low-density lipoprotein cholesterol (LDL-C) levels achieved. We aimed to describe statin intensity used, achievement of LDL-C targets, and factors associated with achieving targets among adults with diabetes. METHODS: This population based (∼4.3 million), retrospective observational study, used clinical and administrative databases. Statin use by intensity, adherence, and achievement of LDL-C targets in adults with diabetes were described. Multiple logistic regression assessed the factors associated with achieving targets. RESULTS: Out of 331,312 individuals with diabetes, 88% had an index LDL-C test. At follow up, 31% overall did not achieve LDL-C targets and overall adherence was 66%. Failure to achieve targets was 49%, 30%, and 25% in low-, moderate-, and high-intensity statin groups, respectively. Those who were older, males, had a history of myocardial infarction, stroke, congestive heart failure, renal disease, better adherence, and higher intensity statin users were more likely to achieve targets. CONCLUSIONS: One-third of people on statins did not achieve targets. Strategies to fill the gap between ideal and current levels of LDL-C achieved are needed if the benefits of statins demonstrated in trials are to be translated into practice.

Testing Algorithms for the Diagnosis of Malignant Glandular Tumors of the Uterine Cervix Histotyped per the International Endocervical Adenocarcinoma Criteria and Classification (IECC) System.

The International Endocervical adenocarcinoma Criteria and Classification (IECC) categorizes tumors into human papilloma virus (HPV) associated (HPVA), not associated (NHPV), and invasive adenocarcinoma not otherwise specified (IA NOS). HPVA and NHPV encompass 11 histotypes and an algorithm of mucin content, HPV ribonucleic acid (RNA), estrogen receptor and GATA3 is proposed for the diagnosis of most. In this study, the IECC algorithm's diagnoses were compared with hematoxylin and eosin (H&E) based IECC histotyping. Kappa statistics measured performance agreement. With additional markers, hierarchical clustering by random forest (RF) classification identified the most discriminating between tumor types, and investigated other algorithms. Three pathologists independently reviewed digitized H&E images of n=152 primary cervical adenocarcinomas for IECC histotype and mucin content, and tissue microarrays for expression of HPV RNA by in situ hybridization and 16 antibodies by immunohistochemistry. Results were finalized by consensus. There were n=113 HPVA, n=22 NHPV, and n=17 IA NOS. Mucin was obvious in n=36 and limited in n=116. Among n=124 with satisfactory test results, HPV RNA was positive in n=96, estrogen receptor in n=72, and GATA3 in n=15. The IECC algorithm diagnosed n=99 which agreed with H&E histotyping in n=64 for a fair κ of 0.36 (95% confidence interval, 0.21-0.50): n=12 were undiagnosed and n=13 were IA NOS. Small sample sizes restricted RF to HPVA versus NHPV which were discriminated by p16, HPV RNA, and MUC6 with an area under the curve of 0.74 (95% confidence interval, 0.58-0.90). The IECC algorithm for histotyping under-performed. The RF algorithmin for categorization was favorable, but validation in larger studies and investigation of additional algorithms to discriminate between all IECC histotypes are needed.

PTEN genomic deletion is an early event associated with ERG gene rearrangements in prostate cancer.

OBJECTIVE: To investigate the interaction between, and significance of, ERG gene rearrangements and PTEN genomic deletions in relation to the development and progression of prostate cancer (PCA). PATIENTS AND METHODS: We interrogated an initial cohort of 220 men with localized PCA using fluorescence in situ hybridization for ERG rearrangements and PTEN genomic deletions. RESULTS: The incidences of ERG rearrangements and PTEN deletions in PCA were significantly higher than in high-grade prostatic intra-epithelial neoplasia (HGPIN) and benign prostate tissue (P < 0.001). ERG rearrangements and PTEN deletions were detected in 41.9 and 42.6% of patients' tumours, respectively. ERG rearrangements were never detected in benign prostate tissue, while PTEN aberrations were present at a basal level of 4.6%. PTEN hemizygous deletions showed higher frequency than homozygous deletions within each diagnostic category from benign prostate tissue to HGPIN and PCA (P ≤ 0.001). Furthermore, in 29 patients where all three tissues were available, PTEN genomic aberrations in PCA were significantly different from those in benign tissue (P = 0.005) and HGPIN (P = 0.02), reflecting the accumulation of genomic aberrations in the early stages of disease progression. Within this cohort, 71.4% of homozygous and 44.2% of hemizygous PTEN deletions occurred simultaneously with ERG rearrangements (P ≈ 0). Stratified according to Gleason score (GS), hemizygous PTEN deletions across various GS groups were observed at a higher frequency than homozygous deletions. However, PTEN homozygous deletions showed positive trends with higher GS, increasing in poorly differentiated PCA (GS 8-10) in comparison to moderately and well differentiated tumours (GS 6 and 7). CONCLUSION: We show significant association between ERG gene rearrangements and PTEN genomic aberrations in subset of PCA. Our analysis also provides further support for the observation that homozygous PTEN deletions can occur within the subset of HGPIN lesions, and shows accumulating genetic aberrations with disease progression, evidenced by higher detection in PCA than in HGPIN and more PTEN homozygous deletions in GS 8-10 than in 6-7.

Adenocarcinoma of the Uterine Cervix: Immunohistochemical Biomarker Expression and Diagnostic Performance.

Immunohistochemistry (IHC) improves the diagnosis of cervical adenocarcinoma but is not adequately studied. The performance of 16 antibodies previously reported as potentially discriminating between some histotypes was investigated in 184 tumors comprised of 12 histotype groups collapsed into 3 categories [47 adenocarcinomas in situ (AIS), 121 probable human papillomavirus-dependent adenocarcinomas (HPVD), and 16 of probable independence (HPVI)]. IHC sections from 5 tissue microarrays were scanned, and 3 pathologists independently reviewed images to assess staining percentages and intensities. Biomarker expression was based on published positive and negative cutoffs and agreement between any 2 pathologists. Differences between the 3 categories in the hierarchical ranking of biomarker positivity were analyzed by Random Forest classification, and between select groups by Unsupervised Hierarchical Clustering. Important category discriminants were combined in logistic regression models and the area under the curve (AUC) computed. Potential group discriminants were terminal cluster biomarkers with a 50% or more difference in positivity. Strong associations occurred between the lower expression of carcinoembryonic antigen and stromal actin in AIS compared with HPVD [AUC=0.70, 95% confidence interval (CI), 0.59-0.80] and in the higher expression of p16 and estrogen receptor in comparison to HPVI (AUC=0.86, 95% CI, 0.73-0.98), and between the higher expression of p16, carcinoembryonic antigen and estrogen receptor in HPVD compared with HPVI (AUC=0.88, 95% CI, 0.77-0.99). Between select groups, 9 biomarkers emerged as potential discriminants. Select IHC biomarkers can discriminate AIS from invasive adenocarcinomas, and invasive adenocarcinomas stratified by human papillomavirus dependency from each other. Independent replication in larger studies is needed, and to confirm discriminants of histotype groups.

Azithromycin prophylaxis after lung transplantation is associated with improved overall survival.

BACKGROUND: Azithromycin prophylaxis (AP) in lung transplant recipients has been shown to reduce the composite end-point of death or chronic lung allograft dysfunction (CLAD) onset but without a clear effect on overall survival. Our program began using AP in 2010. We sought to evaluate the association between AP and survival and the risk of CLAD and baseline lung allograft dysfunction (BLAD). METHODS: We studied double lung recipients transplanted between 2004 and 2016. We defined AP as chronic use of azithromycin initiated before CLAD onset. We analyzed the association between AP and death or retransplant using Cox regression with adjustment for potential confounders. We further used Cox and logistic models to assess the relationship between AP and post-transplant CLAD onset and BLAD, respectively. RESULTS: A total of 445 patients were included, and 344 (77%) received AP (median time from transplant: 51 days). Patients receiving AP were more likely to receive induction with interleukin-2 receptor antagonists (57% vs 35%; p < 0.001). AP was associated with improved survival (hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.42-0.82; p = 0.0020) in our fully adjusted model, with a reduced adjusted risk of BLAD (odds ratio: 0.53; 95% CI: 0.33-0.85; p = 0.0460) but no clear reduction in the adjusted risk of CLAD (HR: 0.69; 95% CI: 0.47-1.03; p = 0.0697). CONCLUSIONS: AP is associated with improved survival after lung transplantation, potentially through improved baseline function. These findings build on prior trial results and suggest that AP is beneficial for lung transplant recipients.

Transplantation from matched siblings using once-daily intravenous busulfan/fludarabine with thymoglobulin: a myeloablative regimen with low nonrelapse mortality in all but older patients with high-risk disease.

Two hundred patients received hematopoietic stem cell transplantation (HSCT) from matched sibling donors (MSD) after myeloablative conditioning including fludarabine (Flu) and once-daily intravenous busulfan (Bu). Thymoglobulin (TG) was added to methotexate (MTX) and cyclosporine (CsA) as graft-versus-host disease (GVHD) prophylaxis. For low-risk (acute leukemia CR1/CR2, CML CP1) patients projected 5-year nonrelapse mortality (NRM) and overall survival (OS) were 4% and 76% for those 45 (n = 31). For high-risk (HR) patients NRM was 6% versus 27% (18% at 1 year) (P = .04) and OS 64% versus 37% (P = .47) in younger (n = 40) and older (n = 75) patients, respectively. To correct for imbalance in HR diagnoses each of 17 younger HR patients were matched with 2 older HR (OHR) patients by diagnosis and details of stage, and thereafter for other risk factors. For the younger HR and OHR patients, respectively, OS was 70% versus 37% (P = .02) and NRM 0 versus 34% (P = .02). When outcomes of OHR patients were compared with the other 3 groups combined NRM was 27% versus 5%, respectively (P = .002). Incidence of acute graft-versus-host disease (aGVHD) grade II-IV, aGVHD grade III-IV, and chronic GVHD (cGVHD) was 23% versus 10% (P = .02), 4% versus 2% (P = ns), and 66% versus 41% (P = .001), respectively. Nine of 14 nonrelapse deaths in the OHR group were related to GVHD or its treatment compared with 3 of 6 in all others (P value for GVHD related death = .01). Multivariate analysis of OS and DFS correcting for potentially confounding pretransplant factors identified only the OHR patients as having significantly increased risk (relative risk [RR] 3.32, confidence interval [CI] 1.71-6.47, P < .0001, and RR 3.32, CI 1.71-6.43, P < .0001, respectively). The effect of age on NRM is only apparent in HR patients, and is not explained by heterogeneity in diagnoses. Older HR patients experience more GVHD and more GVHD-related death than others, but NRM is no higher than reported with many nonmyeloablative regimens.

Duodenal ulcers are a major cause of gastrointestinal bleeding after cardiac surgery.

OBJECTIVE: To determine the incidence of gastrointestinal (GI) bleeding in patients after cardiac surgery, assess the perioperative risk factors, and determine the type of GI tract pathology associated with bleeding events. METHODS: At a tertiary referral hospital, all cardiac surgery patients having a postoperative GI bleed from April 2002 to March 2012 were identified. To determine bleeding etiology, only patients requiring endoscopy were included in the analysis. By retrospective review of 3 prospectively maintained databases, the incidence and independent predictors of GI bleeding, as well as endoscopic findings, were determined. RESULTS: Ninety-one GI bleeding events that required endoscopy were identified in 9017 patients. Those that bled were aged 71 ± 12 years, and 76% were men. Sixty-three percent of these patients had valve surgery and 37% had an isolated coronary artery bypass grafting. The overall incidence of GI bleeding was 1.01%, with an upper GI source accounting for 78%. Endoscopy data found a duodenal ulcer as the bleeding source in 71%, whereas stress gastritis accounted for 8%. Preoperative risk factors for bleeding included age ≥70 years, ejection fraction <35%, congestive heart failure, cerebrovascular disease, chronic kidney disease, and gastrointestinal disease. A preoperative history of atrial fibrillation and anticoagulation with Coumadin also was associated with bleeding. Patients that bled had a 30-day mortality rate of 8.8%, which was significantly greater than patients who did not bleed (4.3%; P = .03). CONCLUSIONS: Clinical variables can be used to identify patients at high risk for GI bleeding after cardiac surgery. When GI bleeding occurs, the most common cause is duodenal ulceration, which has an association with Helicobacter pylori infection. These findings may provide an opportunity to initiate preoperative preventative strategies.

Accuracy of bronchial brush and wash specimens prepared by the ThinPrep method in the diagnosis of pulmonary small cell carcinoma.

BACKGROUND: ThinPrep bronchial brush and wash accuracy in the diagnosis of pulmonary small cell carcinoma (pSCCa) and measured as sensitivity, specificity, positive and negative predictive values (PPV and NPV) is incompletely studied or unknown. METHODS: Specimens collected over 5 years from 199 pSCCa and 938 negative (Neg) for pulmonary cancer individuals were selected by linking the laboratory file with the cancer registry. Results other than unsatisfactory were classified as true-positive and -negative, and false-positive and -negative tests so as to calculate accuracy estimates. Slides of all false-negative and -positive and randomly selected samples of true-positive and -negative tests were evaluated for 11 abnormal cell features typical of pSCCa in conventional preparations: distribution differences by disease status were tested for significance. RESULTS: There were 129 brush and 170 wash in the pSCCa group and 365 brush and 1153 wash in the Neg group. Of all specimens, 1.2% were unsatisfactory. Brush sensitivity, specificity, PPV, and NPV were 61.9%, 99.4%, 97.5%, and 88%, respectively. Wash frequencies were 53.3%, 98.8%, 86.5%, and 93.5%, respectively. Abnormal cell features occurred in 29.9% of the selected pSCCa and 4.7% of the Neg specimens, and distribution differences were significant for each feature (P < .001). CONCLUSIONS: Unsatisfactory brush and wash specimens are infrequent in the diagnosis of pSCCa, and both have moderate sensitivity and high specificity, PPV, and NPV. pSCCa abnormal cell features resemble those seen in conventional preparations and can distinguish specimens with pSCCa from those negative for pulmonary cancer.

High dose salvage therapy with dose intensive cyclophosphamide, etoposide and cisplatin may increase transplant rates for relapsed/refractory aggressive non-Hodgkin lymphoma.

Only one-quarter to one-third of patients with relapsed/refractory aggressive non-Hodgkin lymphoma (r/r-aNHL) treated with common salvage chemotherapy regimens and autologous stem cell transplant (ASCT) achieve 5-year progression-free survival (PFS). Worse outcomes have been reported after failure of prior rituximab-containing induction, initial time to progression (TTP) < 1 year or age-adjusted International Prognostic Index (aaIPI) = 2-3 at relapse. In Calgary, we have treated patients with r/r-aNHL with dose-intensive cyclophosphamide 5.25 g/m(2), etoposide 1.05 g/m(2) and cisplatin 105 mg/m(2) (DICEP) for both re-induction therapy and autologous blood stem cell mobilization. In this study we retrospectively analyzed 113 consecutive transplant-eligible patients with r/r-aNHL who received one cycle of DICEP (n = 93) or R-DICEP (n = 20) from 1995 to 2009. Patient characteristics included: median age = 49 years (22-69); TTP < 1 year = 85; elevated lactate dehydrogenase (LDH) = 60; Eastern Cooperative Oncology Group performance status (ECOG) 2-4 = 42; aaIPI 2-3 = 59; bulk > 10 cm = 26, prior rituximab = 27. The median number of CD34 + cells collected was 19 × 10(6)/kg (0.3-142), 83.5% responded and 90% (102) proceeded to ASCT. The 5-year PFS rate was 42% for all patients, 32% for those with relapse aaIPI = 2-3, 35% for initial TTP < 1 year and 56% for those who failed initial rituximab induction. In conclusion, (R)DICEP is an effective re-induction regimen for r/r-aNHL, leading to excellent stem cell mobilization, a high chance of proceeding to ASCT and encouraging long-term PFS rates.

Filmcards Used in Radiation Therapy: Are They a Potential Source of Cross-infection?

INTRODUCTION: Industrial radiographic film (exposed to light and then cut into a filmcard) is a tool used by radiation therapists (RTs) in the setup of patients before delivering external beam radiation therapy. At the Tom Baker Cancer Center (TBCC), filmcards are reused throughout the day on multiple patients and multiple body sites; thus the risk of cross-contamination exists. The primary objective of this study was to assess the risk of cross-contamination by determining the potential for bacteria to survive on filmcards, in an effort to reduce the risk of cross-infection. METHODS AND MATERIALS: This control study evaluated the potential of the following to survive on filmcards: coliforms, Pseudomonas, Staphylococcus spp. (specifically S. aureus and methicillin-resistant S. aureus [MRSA]), Enterococcus, and hemolytic streptococcus species. Thirty filmcards used by RTs throughout the day were collected and voluntarily placed in individual collection bags. Thirty control cards (unused filmcards) were also collected. Collection bags were stored at 4°C until cultured. A reference strain of MRSA (38591) was used in the MRSA survival assay, along with methicillin-sensitive S. aureus (MSSA) isolate (pure form). The MRSA survival experiment required eight larger, unused filmcards (four designated as negative controls and four positive control cards) to be cut into 28.5 × 6.5 cm. Microbiological plates were used to identify and select for bacteria. The various selective and differential plates contain growth factors, antimicrobials, and color indicators that can selectively allow some groups of bacteria to grow on the plate while inhibiting other types of bacteria. RESULTS: This study provides evidence to support that filmcards are a source of cross-contamination. 58% (17/29) of the used filmcards tested positive for pathogenic bacteria, compared to only 20% (6/30) of the control cards (P = 0.003). Staphylococcus aureus bacteria were present on 11/29 (38%) of the used filmcards, compared to 2/30 (6.7%) on the control filmcards (P = 0.005). Other colonies found on the used filmcards included strep bacteria (P = 0.24), entero bacteria (P = 0.24), and skin flora (P = 0.36); and although reported as statistically insignificant, these bacteria were viable and thus hold a level of clinical significance. In addition, this experiment provides evidence that certain bacteria (including MRSA found to survive on filmcards for at least 21 days) were viable on filmcards, but an incidental finding reports that fungi is also able to survive on filmcards. CONCLUSION: Filmcards used by RTs can harbor a number of pathogenic bacteria, including MRSA, and are therefore a source of cross-contamination. We recommend that the TBCC external beam radiation treatment program-and any other facilities providing external beam radiation therapy-adopt infection control policies that support discarding filmcards after each use (one-time per patient use) or adopt policies that endorse the elimination of filmcards entirely.

Double high-dose therapy with dose-intensive cyclophosphamide, etoposide, cisplatin (DICEP) followed by high-dose melphalan and autologous stem cell transplantation for relapsed/refractory Hodgkin lymphoma.

The purpose of the present study was to review retrospectively our results of double high-dose therapy with DICEP (dose-intensified cyclophosphamide 5.25 g/m(2), etoposide 1.05 g/m(2), and cisplatin 105 mg/m(2)) re-induction followed by high dose melphalan 200 mg/m(2) (HDM) and autologous stem cell transplantation (ASCT) for 73 consecutive patients with relapsed (n = 43) or refractory (n = 30) classical Hodgkin lymphoma (HL) treated between June 1995 and November 2009. DICEP chemotherapy resulted in successful stem cell mobilization in 71 patients (97%), with a median CD34 (+) cell collection of 15.6 × 10(6)/kg. With a median follow-up of 56 months post-DICEP, the 5-year progression free survival (PFS) and overall survival (OS) rates were 61% [95%CI = 49-72%] and 80% [95%CI = 69-89%], respectively. The 5-year PFS was 65% vs. 30% for DICEP responders vs. nonresponders (logrank p = 0.003) and 89% for International Prognostic Score (IPS) = 0-1, 56% for IPS = 2-3, and 24% for IPS = 4-7 (logrank p < 0.001). Response to DICEP and IPS at relapse were the only two factors that independently predicted PFS and OS in multivariate analyses. Treatment-related mortality was 1%. In conclusion, DICEP-HDM/ASCT is well tolerated double high-dose therapy associated with excellent stem cell mobilization and favorable PFS and OS outcomes for relapsed as well as primary refractory HL.

Durable event-free survival following autologous stem cell transplant for relapsed or refractory follicular lymphoma: positive impact of recent rituximab exposure and low-risk Follicular Lymphoma International Prognostic Index score.

Published studies have provided conflicting results regarding the curative potential of high dose chemotherapy and autologous stem cell transplant (HDT/ASCT) for follicular lymphoma (FL). Our objectives were to evaluate the long-term event-free (EFS) and overall (OS) survival rates following ASCT for FL, and to identify predictors of improved outcome. We conducted a retrospective analysis of the first 100 consecutive patients with relapsed or refractory FL treated with HDT/ASCT in Calgary from 1993 to 2008. With a median follow-up of 65 months (range 16-178) post-ASCT, 5-year EFS and OS rates were 56% (95% confidence interval [CI] 46-66%) and 70% (95% CI 61-79%), respectively. A plateau on the EFS curve is evident starting 6 years post-ASCT. Also, the EFS post-ASCT was markedly longer than the 12-month median EFS from last therapy prior to ASCT (p < 0.0001). Failure of rituximab pre-ASCT was not associated with EFS or OS. Severe toxicities included two early treatment-related deaths, and four late deaths from secondary leukemia. Independent predictors of EFS and OS in multivariate analysis were rituximab therapy within 6 months of ASCT, chemosensitivity and FLIPI (FL International Prognostic Index) score 0-1. In conclusion, our data suggest that over 50% of patients with relapsed/refractory FL who have failed 1-2 prior chemotherapy regimens achieve long-term EFS following HDT/ASCT.