The association of new-onset diabetes with subsequent diagnosis of pancreatic cancer-novel use of a large administrative database.

BACKGROUND: Screening options for pancreatic ductal adenocarcinoma (PDAC) are limited. New-onset type 2 diabetes (NoD) is associated with subsequent diagnosis of PDAC in observational studies and may afford an opportunity for PDAC screening. We evaluated this association using a large administrative database. METHODS: Patients were identified using claims data from the OptumLabs® Data Warehouse. Adult patients with NoD diagnosis were matched 1:3 with patients without NoD using age, sex and chronic obstructive pulmonary disease (COPD) status. The event of PDAC diagnosis was compared between cohorts using the Kaplan-Meier method. Factors associated with PDAC diagnosis were evaluated with Cox's proportional hazards modeling. RESULTS: We identified 640 421 patients with NoD and included 1 921 263 controls. At 3 years, significantly more PDAC events were identified in the NoD group vs control group (579 vs 505; P < 0.001). When controlling for patient factors, NoD was significantly associated with elevated risk of PDAC (HR 3.474, 95% CI 3.082-3.920, P < 0.001). Other factors significantly associated with PDAC diagnosis were increasing age, increasing age among Black patients, and COPD diagnosis (P ≤ 0.05). CONCLUSIONS: NoD was independently associated with subsequent diagnosis of PDAC within 3 years. Future studies should evaluate the feasibility and benefit of PDAC screening in patients with NoD.

Patient-specific risk factors for infection in arthroplasty procedure.

All patients are not equally at risk when it comes to postoperative infections, whether the risks are related to the environment or the patient. Patient-specific infection risk factors for arthroplasty should be a focal point during the preoperative consultation as they impact the treatment decision. Eighty percent of patients have at least one modifiable infection risk factor. These risk factors must be corrected preoperatively whenever possible so that the patient is operated under the best possible conditions, with the lowest possible infection risk. The screenings and preoperative preparations are multidisciplinary but must also involve the patient. The information provided to the patient must match the patient's infectious risk profile. This lecture will review every infection risk factor, whether it is modifiable or not, and then suggest how the treatment decision should be adapted to each patient's infection risk.

Chronic infection of unicompartmental knee arthroplasty: one-stage conversion to total knee arthroplasty.

BACKGROUND: The main reasons for revision of unicompartmental knee arthroplasty (UKA) are loosening, wear, extension of osteoarthritis to another compartment, and infection. There have been no studies of the management of infected UKA, whose incidence varies from 0.2% to 1%. Our objective was to describe infection-related and mechanical outcomes of chronic UKA infection managed by one-stage conversion to total knee arthroplasty (TKA). PATIENTS AND METHODS: Consecutive patients with chronic UKA infection managed by one-stage conversion to TKA between January 2003 and December 2010 were included in a retrospective single-center study. All patients also received appropriate dual antibiotic therapy intravenously for 6 weeks then orally for 6 additional weeks. RESULTS: During the study period, among 233 cases of infected knee arthroplasty managed at our center, 9 met the study inclusion criteria. The UKA was medial in 6 patients, lateral in 2, and patellofemoral in 1. Median age was 67 years (range, 36-83 years) and median infection duration was 9months. In 5 patients, previous treatment with synovectomy, joint lavage, and antibiotics had failed. The following bacteria were identified: oxacillin-susceptible Staphylococci, n=6 (S. epidermidis, n=4; S. capitis, n=1; and S. lugdunensis, n=1); nutritionally deficient Streptococcus, n=1; Enterococcus durans, n=1; and Escherichia coli, n=1. Median follow-up was 60 months (range, 36-96 months). No patient experienced recurrent infection or required revision surgery for infection. No medical complications limiting the use of appropriate antibiotic therapy were recorded. The mean preoperative knee and function scores were 60 and 50, respectively; corresponding mean postoperative values were 75 and 65, respectively. DISCUSSION: UKA infection involves both the prosthesis and the native cartilage, neither of which can be treated conservatively in chronic forms. After identification of the causative organism, synovectomy and joint excision followed by same-stage TKA and combined with appropriate antibiotic therapy for 3 months is effective. LEVEL OF EVIDENCE: IV, retrospective cohort study.

The impact of center accreditation on hematopoietic cell transplantation (HCT).

There are two voluntary center-accrediting organizations in the USA, the Foundation for the Accreditation of Cellular Therapy (FACT) and core Clinical Trial Network (CTN) certification, that are thought to improve and ensure hematopoietic cell transplantation (HCT) center quality care and certify clinical excellence. We sought to observe whether there are differences in outcomes between HLA-matched and -mismatched HCT by CTN and FACT status. Using the 2008-2010 Center for International Blood & Marrow Transplant Research data we created three center categories: non-FACT centers (24 centers), FACT-only certified centers (106 centers) and FACT and core clinical trial network (FACT/CTN) certified centers (32 centers). We identified patient characteristics within these centers and the relationship between FACT certification and survival. Our cohort consisted of 12 993 transplants conducted in 162 centers. After adjusting for patient and center characteristics we found that FACT/CTN centers had consistently superior results relative to non-FACT and FACT-only centers (P<0.05) especially for more complex HCT. However, non-FACT centers were comparable to FACT-only centers for matched related and unrelated patients. Although FACT status is an important standard of quality control that begins to define improved OS, our results indicate that FACT status alone is not an indicator for superior outcomes.

Aligning US health and immigration policy to reduce the incidence of tuberculosis.

OBJECTIVES: Tuberculosis (TB) is a significant public health issue, claiming 1.4 million lives worldwide in 2011. Using data from the 2009-2010 National Health Interview Survey, we examine variation in 'having heard of TB' (HTB) by global region of birth and health insurance status. METHODS: Cross-sectional analysis with bivariate comparisons and multivariate logistic regression to evaluate how adults differed in reported HTB, controlling for global region of birth. RESULTS: HTB rates ranged from 63.4% of adults born in Asia to 88.6% born in Europe. Uninsured immigrants had the lowest rate of HTB, ranging from a low of 50.1% of uninsured adults born in Asia to 77.6% born in Europe and 90.8% of US-born uninsured adults. Longer length of time in the United States (>5 years) was significantly associated with increased likelihood of HTB, as did being of Asian race/ethnicity and being male. Those with private health insurance coverage had the highest rates of HTB. CONCLUSIONS: To reduce persistent TB, public health program directors and policy makers must 1) recognize the variation in HTB by global region of birth and prioritize areas with the lowest HTB rates, and 2) reduce barriers to health insurance coverage by eliminating the 5-year ban for public program coverage for new immigrants.

Value of EUS-FNA cytological preparations compared with cell block sections in the diagnosis of pancreatic solid tumours.

OBJECTIVE: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is performed in order to achieve a definite tissue diagnosis of pancreatic lesions. This in turn is a guide to the appropriate treatment for the patient. Tissue samples collected by the same needle for cytological preparations and cell block histological sections (often referred to as FNA-cytology and FNA-biopsy, respectively) are handled differently. The specific contribution of each of these tests was evaluated. METHODS: One hundred and two consecutive patients underwent EUS-FNA while being investigated for pancreatic solid lesions. Diagnosis was made by cytology, cell block sections or both. The diagnosis was confirmed by clinical outcome. RESULTS: Male/female ratio was 61/41. Mean age was 65±12 years (range, 22-94). Mean lesion size was 3.1±1.8 cm (range, 0.6-10 cm); 68% were >2 cm and 75% were located in the pancreatic head. The average number of needle passes was two (range, 1-4 passes). Final tissue diagnosis was malignant in 66 (65%) patients. Sensitivity, specificity and accuracy were 73%, 94% and 81%, respectively, for cytology alone, and 63%, 100% and 78%, for cell blocks alone. Eighty-two patients (80%) had cytology and cell blocks, which matched in 64 (78%) patients. EUS-FNA results that relied on both techniques had 84% sensitivity, 94% specificity and 88% accuracy. Cytology revealed 13 malignancies not diagnosed on cell blocks, while cell blocks revealed five malignancies not diagnosed by cytology. Malignant lesions were more common in men; they were larger in size and located in the pancreatic head. CONCLUSION: EUS-FNA cytology was more sensitive than cell blocks but less specific for the diagnosis of solid pancreatic lesions. The two methods are complementary and implementing both improves the diagnostic value of EUS-FNA.

Joint infection after knee arthroscopy: medicolegal aspects.

INTRODUCTION: Septic knee arthritis following arthroscopy is a rare but dreaded complication: it might compromise patients' functional prognosis and engage surgeon's liability. This study analyzes the context of such infection occurrences, their management as well as their medicolegal consequences. PATIENTS AND METHODS: Twenty-two cases of knee septic arthritis following arthroscopy were examined during the medicolegal litigation process and collected for assessment from a medical liability specialised insurer. Half of the patients were manual workers who worked on their knees, and seven knees had a previous surgical history. The procedures performed at arthroscopy included seven ligamentoplasties, nine meniscotomies, three arthroscopic lavages, one arthrolysis, one chondroma removal and one plica resection. Seven patients, to some point, received corticosteroids: three preoperative joint injections, three intraoperative injections, and one oral corticotherapy. RESULTS: Clinical signs of septic arthritis appeared after a median interval of 8 days (0-37), twice after a hemarthrosis and once after an articular burn. The median delay before treatment initiation was 4.2 days, and in 10 cases this therapeutic delay exceeded 3 days. On average, 3.5 additional procedures (1-9) were required to treat the infection and its residual sequels. Two total knee prostheses were implanted. Only two patients were free of disabling sequellae, and in five patients these sequels affected their livelihood. The medicolegal consequences were a partially permanent disability averaging 5% (0-20), a total temporary work incapacity of 120 days (40-790), a suffering burden averaging 3 out of 7 (0-4.5) points on the scale conventionally used in France. Twelve of these legal claims led to court ordered patient compensation. DISCUSSION: Some risk factors of articular infection are known and well-identified. They can be linked to the patient's condition (addiction to smoking, surgical history, professional activity) or to medical management (intra-articular corticoid injections, interventions under oral anticoagulants, inadvertently overheated irrigation fluid). When infection is suspected, it is often the needle-aspirated fluid's inappropriate handling (such as absence of bacteriological testing or defective waiting time for the results), which delays the diagnostic or therapeutic management of this complication. All failures of infection diagnosis or treatment heavily contribute to malpractice claims against the surgeon. Early and appropriate management of postoperative infections helps limiting the risk of functional sequellae for the patient and reduces the risk of malpractice litigation for the practitioner. LEVEL OF EVIDENCE: Level IV; economic and decision analysis, retrospective study.

Nuclear and cytoplasmic expression of ErbB-4 in prostate cancer.

PURPOSE: To evaluate cytoplasmic and nuclear ErbB-4 expression in prostate cancer specimens and its association with outcome. BASIC PROCEDURES: Specimens of 50 prostate cancer patients were investigated for ErbB-4 overexpression using Immunohistochemistry staining. Cytoplasmic and nuclear staining was graded as 0-3 according to its intensity. The prognostic parameters were tumor stage, PSA level, Gleason score, probability of positive lymph nodes (Partin's tables and Roach equation), and 5-year disease free survival (Kattan nomogram). MAIN FINDINGS: Overexpression of ErbB-4 (> or = 1) was detected in 30 (60%) patients and overexpression using cytoplasmic and nuclear staining was > or = 2 in 19 (38%) and 17 (34%) patients, respectively. In only one third of the specimens was there any similarity between the 2 types of staining. Advanced tumor stage, high pretreatment PSA levels and high Gleason scores were evenly distributed among the patients with low (< or = 1) and intermediate/high (> or = 2) ErbB-4 expression. The probability of lymph node involvement and 5-year disease free survival were similar in both types of staining. PRINCIPAL CONCLUSIONS: ErbB-4 was overexpressed (cytoplasmic and nuclear staining) in approximately one third of prostate cancer patients. The rate of similarity between the 2 staining types was only 33%: overexpression was evenly distributed among intermediate/high and low risk prostate cancer patients with both staining methods.

Diagnosis of intrathoracic lesions: are sequential fine-needle aspiration (FNA) and core needle biopsy (CNB) combined better than either investigation alone?

AIM: To assess the diagnostic accuracy of sequential computed tomography (CT)-guided percutaneous fine-needle aspiration (FNA) and core-needle biopsy (CNB) in comparison with FNA and CNB performed separately for diagnosing intrathoracic lesions. SUBJECTS AND METHODS: Five hundred and eighty-two consecutive patients with thoracic lesions who underwent same-session sequential CT-guided FNA and CNB procedures were studied. The final diagnosis, which was achieved by either agreement of percutaneous procedures with clinical follow-up, bronchoscopy or thoracotomy was available for all cases. The diagnostic yield of the combined FNA+CNB procedures was compared with that of each alone. RESULTS: Adequate samples were obtained in 541 (93%) of FNAs and 513 (88%) of CNBs. Of 582 lesions, 419 (72%) were malignant and 163 (28%) were benign. For malignant lesions, the sensitivity, specificity and accuracy of the procedures were: 376/419 (89.7%), 136/163 (83.4%), and 88% for FNA; 317/419 (75.6%), 138/163 (84.7%), and 78% for CNB; 400/419 (95.5%), 154/163 (94.5%), and 95% for FNA+CNB. The sequential procedures showed significantly better sensitivity, specificity and accuracy compared with either FNA or CNB separately (p<0.003). For the 163 benign lesions, 76 (47%) had a specific benign pathological diagnosis. The diagnosis was obtained in 16/76 (21%) by FNA, in 54/76 (71%) by CNB, and in 60/76 (79%) by FNA+CNB. There was no significant difference between the results of the sequential procedures and CNB alone (p>0.05). CONCLUSIONS: Sequential FNA and CNB improve the diagnostic accuracy of percutaneous CT-guided procedures in malignant lesions. There was only mild improvement, which was not statistically significant, for the diagnosis of benign specific lesions by the sequential procedures compared with the yield of CNB alone.

Establishment and characterization of a pancreatic carcinoma cell line derived from malignant pleural effusion.

BACKGROUND/AIMS: A novel cell line, designated p34, was developed from the malignant pleural effusion of a patient with carcinoma of pancreas. The objective of this work was to characterize this cell line. METHOD: The in vitro studies included karyotype analysis, immunohistochemistry, XTT cell proliferation assay, analysis of the cell cycle by FACS and cell sensitivity to chemotherapeutic drugs and irradiation. Subcutaneous and intra-spleen inoculations into nude mice were carried out to study the tumorigenicity and the metastatic tendency of this cell line. RESULTS: The p34 cell line showed typical morphological characteristics of epithelial pancreatic tumor cells. The cells were hyperdiploid with a modal number of 48, and had two markers, deletion in the short arm of chromosome 2 and duplication of the short arm of chromosome 8. The doubling time was 16 h. Subcutaneous inoculation of the cells into nude mice yielded 100% tumorigenicity, and intra-spleen inoculation resulted in extensive intra-abdominal spread. The antiproliferative effect of chemotherapy (gemcitabine, cisplatin, taxol and vinorelbine), chemopreventive agents (celecoxib and curcumin) and radiotherapy showed dose-dependent cytotoxicity. CONCLUSIONS: This p34 cell line can be used as a new model for studying various aspects of the biology of human pancreatic cancer and potential treatment approaches for the disease.

Lung cancer in patients with HIV infection: is it AIDS-related?

HIV-infected individuals have an increased risk of malignancy, especially non-Hodgkin's lymphoma and Kaposi's sarcoma. Recently, several workers have noted a raised prevalence of lung cancer in HIV-positive subjects. We describe the diagnosis and clinical course for four HIV-seropositive patients who presented with lung cancer. All of the patients were young and were heavy smokers. They were all on highly active antiretroviral therapy (HAART), although the adherence varied from poor to excellent. The CD4 cell counts of these patients ranged from 200 to 686 cells/microL and their viral loads ranged from undetectable to 29,000 HIV-1 RNA copies/mL. After initial diagnosis of HIV infection between 5 and 13 years previously, they all presented with advanced lung cancer, with a very short clinical course, and all four died within 2-9 months of diagnosis. A comparison of the incidence of lung cancer in patients with HIV infection at our centre with that in the general population suggests that there is an increased prevalence in the HIV-infected patients. We review the literature and discuss whether lung cancer in HIV infection is coincidental or related to the primary disease.

Biochemical characterization of a phosphinate inhibitor of Escherichia coli MurC.

The bacterial UDP-N-acetylmuramyl-L-alanine ligase (MurC) from Escherichia coli, an essential, cytoplasmic peptidoglycan biosynthetic enzyme, catalyzes the ATP-dependent ligation of L-alanine (Ala) and UDP-N-acetylmuramic acid (UNAM) to form UDP-N-acetylmuramyl-L-alanine (UNAM-Ala). The phosphinate inhibitor 1 was designed and prepared as a multisubstrate/transition state analogue. The compound exhibits mixed-type inhibition with respect to all three enzyme substrates (ATP, UNAM, Ala), suggesting that this compound forms dead-end complexes with multiple enzyme states. Results from isothermal titration calorimetry (ITC) studies supported these findings as exothermic binding was observed under conditions with free enzyme (K(d) = 1.80-2.79 microM, 95% CI), enzyme saturated with ATP (K(d) = 0.097-0.108 microM, 95% CI), and enzyme saturated with the reaction product ADP (K(d) = 0.371-0.751 microM, 95% CI). Titrations run under conditions of saturating UNAM or the product UNAM-Ala did not show heat effects consistent with competitive compound binding to the active site. The potent binding affinity observed in the presence of ATP is consistent with the inhibitor design and the proposed Ordered Ter-Ter mechanism for this enzyme; however, the additional binding pathways suggest that the inhibitor can also serve as a product analogue.

Correlation between c-erbB-4 receptor expression and response to gemcitabine-cisplatin chemotherapy in non-small-cell lung cancer.

BACKGROUND: While the overexpression of c-erbB gene family in several malignancies is associated with poorer prognosis, the association between the expression of the cellular markers and the response to chemotherapy is not yet clear. In this study we investigated the expression of c-erbB-4 receptor in NSCLC and correlated it with the response to gemcitabine-cisplatin combination chemotherapy. PATIENTS AND METHODS: Forty-three NSCLC patients with histologically or cytologically proven disease were treated with gemcitabine-cisplatin combination chemotherapy. Immunohistochemical stains for c-erbB-4 receptor were performed in 20 cases on paraffin sections using the avidin-biotin-peroxidase method. RESULTS: Two patients achieved complete response (5%), and 16 achieved partial response (37%) yielding an overall objective response rate of 42%. Minimal response was observed in seven patients (16%) and disease stabilization in 7%. Immunohistochemical stain was positive for the presence of c-erbB-4 receptor in 25% of patients, and negative in 75%. No response was documented in c-erbB-4 positive patients (0 of 5) while an objective response (complete, partial or minimal) was seen in 11 of 15 (73%) c-erbB-4 negative patients. Negative stain for c-erbB-4 significantly favored response to gemcitabine-cisplatin combination (P < 0.01). CONCLUSION: C-erbB-4 expression status showed no correlation with survival and cannot be accepted at this time as a guiding factor for therapeutic management. These interesting results deserve further evaluation in a large-scale prospective trial before treatment recommendations on the basis of c-erbB-4 presence can be finally made.

TB or not TB: cavitary bronchiolitis obliterans organizing pneumonia mimicking pulmonary tuberculosis.

Two patients with subacute symptoms and signs compatible with pulmonary tuberculosis (TB) had right upper lobe cavitary infiltrates shown on chest radiography. In both patients, purified protein derivative and microbiologic testing excluded TB, and tissue examination yielded typical histologic changes of bronchiolitis obliterans organizing pneumonia (BOOP). Glucocorticoid therapy led to clinical and radiologic resolution. Though probably rare in this situation, BOOP should be considered in the differential diagnosis of patients presenting with clinical and radiologic features of pulmonary TB.

DNA amplification for the diagnosis of cat-scratch disease in small-quantity clinical specimens.

Diagnosis of cat-scratch disease (CSD) by polymerase chain reaction (PCR) of lymph node fineneedle aspiration (FNA) and primary lesion specimens can be difficult owing to the minute amount of available material. A PCR assay specifically suited to test these specimens was developed. First, small-quantity (10 microL) samples were prepared from 17 CSD-positive and 16 CSD-negative specimens, and DNA extraction and amplification from these samples were compared using 3 methods. Sensitivity and specificity of PCR were 100% using material collected on glass microscope slides and by using Qiagen (Hilden, Germany) columns for DNA extraction. Then, this method was used to test 11 archival glass microscope slides of FNA (7 malignant neoplasms, 4 undiagnosed lymphadenitis) and 2 primary lesion specimens. Two of the 4 lymphadenitis samples and the 2 primary lesion specimens were PCR positive. The technique presented could facilitate CSD diagnosis from a wider range of clinical samples.

Inhibitors of the bacterial cell wall biosynthesis enzyme MurC.

A series of phosphinate transition-state analogues of the L-alanine adding enzyme (MurC) of bacterial peptidoglycan biosynthesis was prepared and tested as inhibitors of the Escherichia coli enzyme. Compound 4 was identified as a potent inhibitor of MurC from Escherichia coli with an IC(50) of 49nM.

Percutaneous core needle biopsy vs. fine needle aspiration in diagnosing benign lung lesions.

OBJECTIVE: To determine the diagnostic value of percutaneous core needle biopsy (PCNB) in comparison with fine needle aspiration (FNA) in patients with benign pulmonary lesions. STUDY DESIGN: A retrospective review was undertaken of computed tomography-guided PCNBs and FNAs performed between 1988 and 1997. Both FNA and PCNB biopsies were carried out sequentially at the same visit in every patient. RESULTS: A specific benign diagnosis was made in 10/60 cases (16.7%) by FNA and in 49/60 (81.7%) by PCNB. PCNB findings resulted in significant modification of the diagnosis established by FNA. The only significant complication encountered was pneumothorax, at a rate of 11.7%, which is compatible with that reported in the literature for complications induced by FNA alone. CONCLUSION: Radiologically guided PCNB is a safe procedure, can provide sufficient histologic material for a specific diagnosis of peripheral lung disease and can avoid more-invasive surgical procedures in many cases. Our experience demonstrated that the histologic analysis provided by PCNB can greatly increase the diagnostic accuracy in benign pulmonary diseases as compared with the yield of FNA.

Pleuropulmonary metastasis from an intracranial glioblastoma.

We present an unusual case of glioblastoma with intrathoracic and liver metastasis. The clinical diagnosis was confirmed by a percutaneous core needle biopsy from a metastatic lung lesion. The pathogenetic and diagnostic aspects of the case are discussed.

Primary liposarcoma of the mediastinum.

Patient. A 62-year-old man presented with effort dyspnea, non-productive cough and weakness of 4 month duration. He had no findings on physical examination.Discussion. Chest X-ray revealed a large mass in the left anterior mediastinum. Computerized tomography of the chest showed a well-delineated homogeneous mediastinal mass with fat-equivalent density and a small pleural effusion. Fiberoptic bronchoscopy revealed narrowing of the left main bronchus, secondary to external compression. The bronchial mucosa was normal and brush cytology was negative. A CT-guided fine needle aspiration (FNA) of the mass yielded fragments of cells embedded in myxoid background material and closely packed atypical lipoblasts, compatible with liposarcoma. The patient underwent a left lateral thoracotomy and margibnal resection of the mass. The histopathological examination confirmed the diagnosis of mixed-type liposarcoma, consisted of myxoid and pleomorphic liposarcoma. Postoperative two-field radiation therapy was delivered to the mediastinum for a total midplane dose of 40 Gy. After a disease-free interval of 8 months the disease recurred in the mediastinum and pleura. Palliative chemotherapy achieved a short duration partial response but the patient succumbed to local recurrence 2 years after the diagnosis.