Lesion-to-anal-verge distance in rectosigmoid endometriosis on transvaginal sonography vs magnetic resonance imaging: prospective study.

OBJECTIVES: To compare transvaginal sonography (TVS) and magnetic resonance imaging (MRI) with intraoperative measurement (IOM) using a rectal probe in the estimation of the location of rectosigmoid endometriotic lesions, i.e. lesion-to-anal-verge distance (LAVD), and to compare two different MRI techniques for measuring LAVD. METHODS: This was a prospective single-center observational study that included women undergoing surgery for symptomatic rectosigmoid endometriosis by discoid (DR) or segmental (SR) resection from December 2018 to December 2019. TVS and MRI were performed presurgically for each participant to evaluate LAVD, and the measurements on imaging were compared with IOM using a rectal probe. Clinically acceptable difference and limits of agreement (LoA) between TVS and MRI compared with IOM were set at ± 20 mm. Two different measuring methods for MRI, MRICenter and MRIDirect , were proposed and evaluated, as there is currently no guideline to describe deep endometriosis on MRI. Bland-Altman plots and LoA were used to assess agreement of TVS and both MRI methods with IOM. Systematic and proportional biases were assessed using paired t-test and Bland-Altman plots. RESULTS: Seventy-five women were eligible for inclusion. Twenty-eight women were excluded, leaving 47 women for the analysis. Twenty-three DR and 26 SR procedures were performed, with both procedures performed in two women. The Bland-Altman plots showed that there were no systematic differences between TVS or MRICenter when compared with IOM for all included participants. MRIDirect systematically underestimated LAVD for lesions located further from the anal verge. TVS, MRICenter and MRIDirect had LoA outside the preset clinically acceptable difference when compared with IOM. LAVD was within the clinically acceptable difference from IOM of ± 20 mm in 70% (33/47) of women on TVS, 72% (34/47) of women on MRICenter and 47% (22/47) of women on MRIDirect . CONCLUSIONS: TVS should be the preferred method to estimate the location of a rectosigmoid endometriotic lesion, i.e. LAVD, as it is more available, less expensive and has a similar accuracy to that of MRI. Estimating LAVD can be relevant for planning colorectal surgery for rectosigmoid endometriosis. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Strengths and limitations of diagnostic tools for endometriosis and relevance in diagnostic test accuracy research.

Endometriosis is a chronic systemic disease that can cause pain, infertility and reduced quality of life. Diagnosing endometriosis remains challenging, which yields diagnostic delays for patients. Research on diagnostic test accuracy in endometriosis can be difficult due to verification bias, as not all patients with endometriosis undergo definitive diagnostic testing. The purpose of this State-of-the-Art Review is to provide a comprehensive update on the strengths and limitations of the diagnostic modalities used in endometriosis and discuss the relevance of diagnostic test accuracy research pertaining to each. We performed a comprehensive literature review of the following methods: clinical assessment including history and physical examination, biomarkers, diagnostic imaging, surgical diagnosis and histopathology. Our review suggests that, although non-invasive diagnostic methods, such as clinical assessment, ultrasound and magnetic resonance imaging, do not yet qualify formally as replacement tests for surgery in diagnosing all subtypes of endometriosis, they are likely to be appropriate for advanced stages of endometriosis. We also demonstrate in our review that all methods have strengths and limitations, leading to our conclusion that there should not be a single gold-standard diagnostic method for endometriosis, but rather, multiple accepted diagnostic methods appropriate for different circumstances. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Pediatric COVID-19 Cases in Counties With and Without School Mask Requirements - United States, July 1-September 4, 2021.

Consistent and correct mask use is a critical strategy for preventing the transmission of SARS-CoV-2, the virus that causes COVID-19 (1). CDC recommends that schools require universal indoor mask use for students, staff members, and others in kindergarten through grade 12 (K-12) school settings (2). As U.S. schools opened for the 2021-22 school year in the midst of increasing community spread of COVID-19, some states, counties, and school districts implemented mask requirements in schools. To assess the impact of masking in schools on COVID-19 incidence among K-12 students across the United States, CDC assessed differences between county-level pediatric COVID-19 case rates in schools with and without school mask requirements.

Transvaginal sonography determines accurately extent of infiltration of rectosigmoid deep endometriosis.

OBJECTIVE: To investigate the agreement of measurements of the three diameters of rectosigmoid deep endometriosis (DE) lesions between presurgical evaluation using transvaginal sonography (TVS) and postsurgical specimen measurement (PSM). METHODS: This was a prospective observational multicenter study including symptomatic women undergoing surgical treatment for DE involving the rectosigmoid, by either discoid or segmental resection, from April 2017 to December 2019. TVS was performed presurgically to evaluate lesion size (craniocaudal-midsagittal length, anteroposterior thickness and transverse diameter), in accordance with the International Deep Endometriosis Analysis (IDEA) group consensus statement, and was compared with PSM. The agreement of lesion dimensions between the two methods was assessed by Bland-Altman plots and limits of agreement and additionally by the intraclass correlation coefficient (ICC) and Pearson's correlation coefficient. Systematic and proportional bias was assessed using the paired t-test. RESULTS: A total of 207 consecutive women were eligible for inclusion. Forty-one women were excluded, leaving 166 women for final analysis. A total of 123 segmental resections and 46 discoid resections were performed (both procedures were performed in three women). The mean difference between TVS and PSM was 0.90 (95% CI, 0.85-0.95) mm for lesion length measurements, 1.03 (95% CI, 0.98-1.09) mm for lesion thickness measurements and 0.84 (95% CI, 0.79-0.89) mm for transverse diameter measurements. Bland-Altman analysis demonstrated good agreement between the two methods for measurements of lesion length. Furthermore, there was good reliability and correlation between TVS and PSM for lesion length measurements, as demonstrated by an ICC of 0.82 (95% CI, 0.75-0.87) and Pearson's correlation coefficient of 0.72 (95% CI, 0.62-0.80), moderate-to-good reliability and correlation for lesion thickness measurements, with an ICC of 0.76 (95% CI, 0.67-0.82) and Pearson's correlation coefficient of 0.61 (95% CI, 0.51-0.70), and poor-to-moderate reliability and correlation for transverse diameter measurements, with an ICC of 0.58 (95% CI, 0.39-0.71) and Pearson's correlation coefficient of 0.46 (95% CI, 0.33-0.58). CONCLUSION: Preoperative TVS determines accurately rectosigmoid DE lesion length. TVS can thereby contribute to optimal planning of surgical treatment options in women with rectosigmoid DE. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Transvaginal sonography accurately measures lesion-to-anal-verge distance in women with deep endometriosis of the rectosigmoid.

OBJECTIVES: First, to investigate the accuracy of transvaginal sonography (TVS) for presurgical evaluation of the distance between the most caudal part of the endometriotic lesion and the anal verge (lesion-to-anal-verge distance (LAVD)) in women with rectosigmoid deep endometriosis (DE), compared with intraoperative measurement (IOM). Second, to assess the agreement between anastomosis height and LAVD measured using TVS. METHODS: This was a prospective observational multicenter study of symptomatic women who were scheduled for surgical treatment of rectosigmoid DE, by either discoid or segmental resection, between April 2017 and September 2019. Presurgical TVS was performed to evaluate the LAVD in two ways, depending on the level of the lesion. Method 1: for lesions at the level of the rectovaginal septum (RVS), the caudal part of the lesion was identified on TVS and an index finger was placed on the TVS probe at the level of the anal verge. The probe was withdrawn and the distance from the tip of the TVS probe down to the index finger was measured using a ruler, representing the LAVD. Method 2: for lesions above the RVS, the distance between the caudal part of the lesion and the lower lip of the posterior cervix was measured in a frozen image (LAVD-1), and the distance between the lower lip of the posterior cervix and the anal verge (LAVD-2) was measured using Method 1. These two measurements (LAVD-1 and LAVD-2) were added together and the result represented the total LAVD. During surgery, a rectal probe was used to perform IOM of LAVD, which was considered as the gold standard test. Agreement between LAVD measured using TVS and the IOM was assessed using Bland-Altman analysis. The intraclass correlation coefficient (ICC) for absolute agreement and Spearman's correlation coefficient were also calculated. Systematic and proportional bias were tested for significance using the paired t-test. Similar analysis was performed to assess agreement between LAVD measured using TVS and anastomosis height. RESULTS: A total of 147 consecutive women were considered eligible for inclusion. Fourteen women were excluded initially. Thirty-four discoid resections and 102 segmental resections were performed; both procedures were performed in three women. Two more women were excluded from the final analysis because the measurements represented extreme outliers. The mean LAVD measured using TVS was 114.8 ± 36.5 mm and the mean IOM was 116.9 ± 42.3 mm. There was no statistically significant difference between LAVD measured using TVS and IOM (mean difference, -2.12 mm (95% CI, -6.33 to 2.05 mm); P = 0.32). Bland-Altman analysis showed that there was good agreement between the two methods. The ICC was 0.81 (95% CI, 0.74-0.86) and Spearman's correlation coefficient was 0.68 (95% CI, 0.56-0.77). The mean difference between LAVD measured using TVS and anastomosis height was statistically, but not clinically, significant (mean difference, 10.25 mm (95% CI, 5.94-14.32 mm); P = 0.0005), and the ICC was 0.78 (95% CI, 0.66-0.85). CONCLUSIONS: There is good agreement between the LAVD measured using TVS and the IOM in women with rectosigmoid DE. As a consequence, TVS could be useful for estimation of the height of the final surgical anastomosis in women undergoing full-thickness resection for rectosigmoid DE. This is of pivotal importance in reducing the risk of complications and need for a temporary stoma, and could improve patient counseling. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Learning curve for detection of pelvic parts of ureters by transvaginal sonography: feasibility study.

OBJECTIVE: To investigate how many examinations it takes to be able to identify the pelvic parts of the ureters on transvaginal sonography (TVS). METHODS: This was a prospective study including consecutive women attending a gynecological outpatient clinic in a tertiary referral setting. Prior to commencement of the study, three trainees, with a focus on gynecological surgery and TVS but with no experience in identifying ureters, each observed an expert examiner performing 10 routine TVS examinations, including identification of both ureters. All were standardized gynecological TVS examinations, with visualization of the pelvic part of both ureters. Consecutive women were then examined, first by the expert, unobserved by the trainees, and then by one of the three trainees, in the presence of the expert. To ensure that identification of the pelvic parts of the ureters could be incorporated feasibly into routine gynecological TVS in a tertiary referral setting, a time limit of 150 s was set for successful identification of each ureter. A successful examination was defined by identifying both ureters within the time limit. The number of women examined by each trainee was determined by how quickly they achieved proficiency, which was evaluated using the learning curve cumulative summation (LC-CUSUM) score. RESULTS: Between January 2017 and June 2017, a total of 140 women were recruited for the study, with 135 patients being included in the final analysis. The three trainees were able to identify the right ureter after a maximum of 48 (range, 34-48) TVS examinations, and the left ureter after a maximum of 47 (range, 27-47) TVS examinations. CONCLUSIONS: Sonographers and/or gynecologists who are familiar with gynecological TVS should be able to become proficient in identifying both ureters after 40-50 TVS examinations. Detection of the ureters is a feasible part of the TVS workup of patients attending a clinic in a tertiary referral center. © 2019 the Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Curva de aprendizaje para la detección de las partes pélvicas de los uréteres mediante ecografía transvaginal: estudio de viabilidad OBJETIVO: Investigar cuántos exámenes se necesitan para poder identificar las partes pélvicas de los uréteres en la ecografía transvaginal (ETV). MÉTODOS: Se trata de un estudio prospectivo que incluyó a mujeres que acudieron consecutivamente a una clínica ginecológica ambulatoria en un entorno de especialistas terciarios. Antes de comenzar el estudio, tres pasantes con interés en la cirugía ginecológica y la ETV pero sin experiencia en la identificación de uréteres, observaron respectivamente a un examinador con experiencia mientras realizaba 10 exámenes rutinarios de ETV, incluida la identificación de ambos uréteres. Todos eran exámenes ginecológicos estandarizados por ETV, con visualización de la parte pélvica de ambos uréteres. A continuación, las mujeres fueron examinadas en orden consecutivo, primero por el experto, sin ser observadas por los aprendices, y luego por uno de los tres aprendices, en presencia del experto. Para asegurar que la identificación de las partes pélvicas de los uréteres se pudiera incorporar de manera factible a la ETV ginecológica rutinaria en un entorno de especialistas terciarios, se fijó un plazo de 150 segundos para la identificación satisfactoria de cada uréter. El éxito del examen se definió mediante la identificación de ambos uréteres dentro del plazo establecido. El número de mujeres examinadas por cada aprendiz se determinó por la rapidez con que alcanzaron la competencia, que se evaluó utilizando la puntuación de la suma acumulativa de la curva de aprendizaje (LC-CUSUM, por sus siglas en inglés). RESULTADOS: Entre enero y junio de 2017, se reclutó un total de 140 mujeres para el estudio, y 135 de ellas se incluyeron en el análisis final. Los tres aprendices pudieron identificar el uréter derecho después de un máximo de 48 (rango, 34-48) exámenes de ETV, y el uréter izquierdo después de un máximo de 47 (rango, 27-47) exámenes de ETV. CONCLUSIONES: Los ecografistas y/o ginecólogos que están familiarizados con la ETV ginecológica deberían ser capaces de llegar a ser competentes en la identificación de ambos uréteres después de 40-50 exámenes de ETV. La detección de los uréteres es una parte factible de la ETV de los pacientes que acuden a una clínica en un centro de especialistas terciario. © 2019 Los autores. Ultrasonido en Obstetricia y Ginecología publicado por John Wiley & Sons Ltd. en nombre de la Sociedad Internacional de Ultrasonido en Obstetricia y Ginecología.

Enhanced targeting of triple-negative breast carcinoma and malignant melanoma by photochemical internalization of CSPG4-targeting immunotoxins.

Triple-negative breast cancer (TNBC) and malignant melanoma are highly aggressive cancers that widely express the cell surface chondroitin sulfate proteoglycan 4 (CSPG4/NG2). CSPG4 plays an important role in tumor cell growth and survival and promotes chemo- and radiotherapy resistance, suggesting that CSPG4 is an attractive target in cancer therapy. In the present work, we applied the drug delivery technology photochemical internalization (PCI) in combination with the novel CSPG4-targeting immunotoxin 225.28-saporin as an efficient and specific strategy to kill aggressive TNBC and amelanotic melanoma cells. Light-activation of the clinically relevant photosensitizer TPCS2a (fimaporfin) and 225.28-saporin was found to act in a synergistic manner, and was superior to both PCI of saporin and PCI-no-drug (TPCS2a + light only) in three TNBC cell lines (MDA-MB-231, MDA-MB-435 and SUM149) and two BRAFV600E mutated malignant melanoma cell lines (Melmet 1 and Melmet 5). The cytotoxic effect was highly dependent on the light dose and expression of CSPG4 since no enhanced cytotoxicity of PCI of 225.28-saporin compared to PCI of saporin was observed in the CSPG4-negative MCF-7 cells. The PCI of a smaller, and clinically relevant CSPG4-targeting toxin (scFvMEL-rGel) validated the CSPG4-targeting concept in vitro and induced a strong inhibition of tumor growth in the amelanotic melanoma xenograft A-375 model. In conclusion, the combination of the drug delivery technology PCI and CSPG4-targeting immunotoxins is an efficient, specific and light-controlled strategy for the elimination of aggressive cells of TNBC and malignant melanoma origin. This study lays the foundation for further preclinical evaluation of PCI in combination with CSPG4-targeting.

Early detection of hepatocellular carcinoma using autoantibody profiles from a panel of tumor-associated antigens.

BACKGROUND: Multiple antigen miniarrays used for detecting autoantibodies to tumor-associated antigens (TAAs) can be a useful approach for cancer detection and diagnosis. We here address a very specific question: might there be autoimmune responses to TAAs which precede clinical detection of hepatocellular carcinoma (HCC) in HBV and HCV chronic liver disease patients under continuous medical surveillance, and if so, could these anti-TAAs be added to the armamentarium of diagnostic tests? METHODS: We here examine the utility of a panel of 12 TAAs for the diagnosis of hepatocellular carcinoma (HCC). We derived a predictive rule for the presence of HCC based on the panel, from a cohort comprising 160 HCC patients and 90 normals. We then applied this rule to sequential anti-TAA data from a cohort of 17 HCC patients, from whom this information was available prior to diagnosis. RESULTS: The predictors (autoantibodies to HCC1, P16, P53, P90, and survivin) indicated the presence of HCC prior to diagnosis in 16 of the 17 patients, at a median lead time of 0.75 year. CONCLUSIONS: We believe these findings warrant further study of anti-TAA profiles as biomarkers for primary or early diagnosis of HCC.

Identification of autoantibodies to ECH1 and HNRNPA2B1 as potential biomarkers in the early detection of lung cancer.

Identification of biomarkers for early detection of lung cancer (LC) is important, in turn leading to more effective treatment and reduction of mortality. Serological proteome analysis (SERPA) was used to identify proteins around 34 kD as ECH1 and HNRNPA2B1, which had been recognized by serum autoantibody from 25 LC patients. In the validation study, including 90 sera from LC patients and 89 sera from normal individuals, autoantibody to ECH1 achieved an area under the curve (AUC) of 0.799 with sensitivity of 62.2% and specificity of 95.5% in discriminating LC from normal individuals, and showed negative correlation with tumor size (rs = -0.256, p = 0.023). Autoantibody to HNRNPA2B1 performed an AUC of 0.874 with sensitivity of 72.2% and specificity of 95.5%, and showed negative correlation with lymph node metastasis (rs = -0.279, p = 0.012). By using longitudinal preclinical samples, autoantibody to ECH1 showed an AUC of 0.763 with sensitivity of 60.0% and specificity of 89.3% in distinguishing early stage LC from matched normal controls, and elevated autoantibody levels could be detected greater than 2 y before LC diagnosis. ECH1 and HNRNPA2B1 are autoantigens that elicit autoimmune responses in LC and their autoantibody can be the potential biomarkers for the early detection of LC.

Historical observations contributing insights on etiopathogenesis of rheumatoid arthritis and role of rheumatoid factor.

When studies on rheumatoid arthritis (RA) that were made many decades ago and could be considered "historical" in nature are analyzed in the context of recent observations, important insights on RA and on the function of rheumatoid factor (RF) become apparent. RF in the role of antibody to immune complexes (ICs) appears to be involved in activation of the complement system and in the production of chemotactic and inflammatory mediators, creating a condition that can be sustained and reinitiated. In the synovial cavity, a state of nonresolving inflammation is produced with the formation of citrullinated protein antigen-antibody complexes or other forms of ICs. This is followed by a second wave of IC production in the form of RF acting as antibody reactive with the initial ICs. Both of these processes are associated with complement consumption and production of inflammatory mediators. We present a model of an initiation phase of RA that might represent an example of repetitive formation of ICs and complement-mediated inflammation. Targeting therapy at this phase of RA to break the cycles of recurrent inflammation might be a novel approach to aid in further control of the disease.

Autoantibodies against tumor-associated antigens in the early detection of lung cancer.

OBJECTIVES: Autoantibodies against tumor-associated antigens (TAAs) identified in patients with advanced lung cancer may be detected in subjects with early lung cancer or even predate the diagnosis. The purpose of this study is to address the temporal relationship between lung cancer development and serum autoantibody response. MATERIALS AND METHODS: Two cohorts of patients with newly diagnosed lung cancer were included. The first cohort included 90 sera from patients with lung cancer (Stages I-III) and 89 normal control sera. In the second cohort, 93 serial serum samples from 25 patients with CT-scan screen-detected stage I lung cancer were collected before the diagnosis of lung cancer (average 32 months) and 56 controls were matched on age, gender, and smoking. Autoantibody levels were measured by immunoassay. RESULTS: Measurement of autoantibodies against seven TAAs (14-3-3ζ, c-Myc, MDM2, NPM1, p16, p53 and cyclin B1) individually could discriminate lung cancer patients from normal individuals in the first cohort and the area under curve (AUC) was 0.863 based on a panel of seven autoantibodies, with sensitivity of 68.9% and specificity of 79.5%. Autoantibodies in serial pre-diagnostic serum samples against the same panel of seven TAAs were detected prior to lung cancer diagnosis with sensitivity of 76.0% and specificity of 73.2% (AUC) (95%CI): 0.885 (0.797-0.973)). Elevated autoantibody levels could be detected greater than four years prior to lung cancer diagnosis. CONCLUSION: A panel of seven TAAs may enhance the early detection of lung cancer, consistent with a humoral immune response to TAAs that can be detected months to years prior to the diagnosis.

Tumor-associated antigen CAPERα and microvessel density in hepatocellular carcinoma.

PURPOSE: CAPERα, a tumor-associated antigen, was identified from a cDNA clone with autoantibody from a patient with hepatocellular carcinoma (HCC). It has been implicated, by way of alternative splicing of VEGF pre-mRNA, in the regulation of microvessel formation in Ewing's sarcoma. In this study, we looked for possible association of alterations in CAPERα with microvessel density in HCC. METHODS: Enzyme-linked immunosorbent assay using recombinant CAPERα as antigen were used to detect antibody against CAPERα. Immunohistochemistry (IHC) on liver sections was performed to analyze expression profiles of CAPERα, VEGF and CD34 in HCC and control tissues and was further used to assess the correlation of expression among CAPERα, VEGF and CD34 in HCC development. RESULTS: Autoantibody to CAPERα was highest in HCC (22/76, 28.9%), not detected in prostate cancer (0/79) and at 3.4% (3/88) in breast cancer. In immunohistochemical analysis of grades II and III HCC tissues, significantly decreased immunostaining for CAPERα was observed and this correlated directly with decreased immunostaining for VEGF (R=0.534, P=0.0003). Using CD34 immunostaining for detecting newly formed microvessels, strong staining was observed in grades II and III HCC. Normal liver sections, all of which have high expression of CAPERα were totally negative for CD34 immunostaining. A significant inverse correlation was seen between CAPERα and CD34 immunostaining (R=-0.481, P=0.0012). CONCLUSIONS: Decreased expression of CAPERα appears to be correlated with appearance of microvessels. It would be of interest to elucidate the cause of altered CAPERα since new formation of microvessels is important in progression of HCC.

Single centre experience of hypothermic machine perfusion of kidneys from extended criteria deceased heart-beating donors: a comparative study.

INTRODUCTION: Kidneys from extended criteria donors are associated with higher rates of delayed graft function (DGF). Hypothermic machine perfusion (MP) for storage is associated with more favourable outcomes. METHODS: A retrospective analysis was performed in 93 patients where the kidney was stored using hypothermic MP (LifePort(®)) and compared to an age-matched control group where the kidney was stored in cold static storage (CSS) using University of Wisconsin solution. RESULTS: Median age was similar in both groups (59.2 years in MP vs 59.9 years in CSS, p = 0.5598). Mean cold storage time was 15.6 h in MP vs 17.9 h in CSS. Post transplant mean serum creatinine was as follows; MP group-144.7 µmol/L at 1 month; 138.3 µmol/L at 3 months and 129.5 µmol/L at 12 months. In the CSS group-163 µmol/L at 1 month; 154.9 µmol/L at 3 months and 140.2 µmol/L at 12 months. There was a statistically significant difference at 1 month (p = 0.0096) and 3 months (p = 0.0236). DGF was defined as the need for haemodialysis within 7 days post transplant. In the MP group, DGF occurred in 17.2 % patients with mean of 6 days (range 1-18). In the CSS group, 25.8 % patients with mean of 8.1 days (range 3-25). One-year graft survival rate was better in the MP group (97.85 vs 96.77 %). CONCLUSION: Our experience to date recommends the use of hypothermic MP for storage of kidneys from extended criteria deceased heart-beating donors.

Using immunomic approach to enhance tumor-associated autoantibody detection in diagnosis of hepatocellular carcinoma.

To explore the possibility of using a mini-array of multiple tumor-associated antigens (TAAs) as an approach to the diagnosis of hepatocellular carcinoma (HCC), 14 TAAs were selected to examine autoantibodies in sera from patients with chronic hepatitis, liver cirrhosis and HCC by immunoassays. Antibody frequency to any individual TAA in HCC varied from 6.6% to 21.1%. With the successive addition of TAAs to the panel of TAAs, there was a stepwise increase of positive antibody reactions. The sensitivity and specificity of 14 TAAs for immunodiagnosis of HCC was 69.7% and 83.0%, respectively. This TAA mini-array also identified 43.8% of HCC patients who had normal alpha-fetoprotein (AFP) levels in serum. In summary, this study further supports the hypothesis that a customized TAA array used for detecting anti-TAA autoantibodies can constitute a promising and powerful tool for immunodiagnosis of HCC and may be especially useful in patients with normal AFP levels.

Antinuclear antibodies defining autoimmunity pathways.

Immunofluorescent imaging has been a powerful technique in helping to identify intracellular nuclear and cytoplasmic molecules which are target antigens of autoantibodies in systemic autoimmune disorders. Patterns of staining can be correlated with molecules engaged in specific cellular functions and distributed in distinct cellular domains. Different autoimmune disorders have different profiles of autoantibodies, and immunodiagnostics has become an important adjunct in differential diagnosis. An important finding that has eluded explanation is the presence of autoantibodies to many different antigens, manifested strikingly in systemic lupus erythematosus. In cancer, the occurrence of autoantibodies to tumor-associated antigens is not uncommon and a characteristic feature is also the presence of multiple autoantibodies. The targeted tumor-associated antigens are either oncogene or tumor suppressor gene products or their coactivators, which are altered or mutated and driving the autoimmune response. Most cancer cells have between two and eight mutated genes before oncogenic transformation occurs, initiating a process called synthetic lethality in tumorigenesis pathways. These observations beg the question of whether there are similar mechanisms in systemic lupus erythematosus and other disorders driving autoimmunity pathways. Targeting molecules that are synthetic lethal to each other is in the forefront of the search for anticancer therapy, and this could also be an objective in systemic autoimmune disorders.

Incidence and long-term outcomes of squamous cell bladder cancer after deceased donor renal transplantation.

OBJECTIVE: To review the incidence and long-term outcomes of squamous cell carcinoma (SCC) of the bladder in patients after kidney transplantation. METHODS: Between January 1976 and March 2013, five patients from one center (0.0013%) developed SCC of the bladder after undergoing a deceased donor kidney transplant. Their relevant risk factors included long-term self-intermittent catheterization/indwelling catheter (n = 2), smoking history (n = 2), and a prior history of cyclophosphamide treatment for vasculitis (n = 1). Primary outcome variables were overall patient survival and latency period between transplantation and SCC diagnosis. RESULTS: The duration of long-term follow-up was 94 ± 89 (range: 4-239) months. The latency period between transplantation and bladder SCC was 87 ± 87 (range: 2-228) months, and all five patients were immunosuppressed with tacrolimus, mycophenolate mofetil, and prednisone. Four patients had suspected metastases upon presentation, and one patient presented with organ-confined disease. This patient underwent a radical cystectomy and remains disease free eight months post-operatively. Despite radical treatment, the remaining four patients died from metastatic disease 7 ± 4.4 (range: 2-11) months after their initial diagnosis. CONCLUSION: SCC of the bladder has a poor prognosis particularly in renal transplant patients. Early detection with flexible cystourethroscopy in patients with risk factors for SCC may improve long-term outcomes in this patient cohort.

A review of inpatient urology consultations in an Irish tertiary referral centre.

INTRODUCTION: Our institution is a 680-bed tertiary referral centre with broad medical and surgical subspecialty services. We retrospectively audited the pattern of inpatient consultations from all specialities within our institution to the urology department over a 1-year period. METHODS: All consultations to the urology service were identified from our computerised inpatient consultation system from July 2010 to June 2011. Follow up data on investigations, interventions and subsequent outpatient appointments were also identified by review of individual patient discharge letters. RESULTS: Seven hundred and twenty five inpatient consultations were received over the period. The male to female ratio was 7:3. Mean age of patients was 66 (15-96) years. Seventy three percent of referrals were from medical sub-specialities, most commonly nephrology (17%), gastroenterology (11%) and respiratory medicine (9%). The remainder were from general surgery (16%) and other surgical sub specialities (11%). Interns (66%) and senior house officers (SHO) (28%) communicated the majority of consults. Male lower urinary tract/benign prostate related issues resulted in 25% of all consultations. Less than half of consults (47%) resulted in interventions initiated by urology, most commonly of which were catheter insertions (48%) and endoscopic procedures (35%). Only 43% of consultations were followed up in the outpatients setting. CONCLUSIONS: Inpatient consultations constitute a significant workload for urology services. The majority of these referrals did not require any urological intervention and could have been seen routinely in the outpatient setting. Providing structured referral guidelines and achieving better communication with referring teams may help to optimise this service.