Positive Histology Research Articles

Which Minor Criteria is the Most Accurate Predictor for the Diagnosis of Hip and Knee Periprosthetic Joint Infection in the Asian Population?

BackgroundThe aim of this study was to evaluate the diagnostic performance of minor criteria from the 2018 International Consensus Meeting (ICM) for the diagnosis of chronic periprosthetic joint infection (PJI) in an Asian population. MethodsWe retrospectively reviewed 76 patients who underwent a revision knee or hip arthroplasty at an academic institution between September 2018 and December 2019. All major and minor 2018 ICM criteria were available for all patients included. Cases with at least 1 major criterion or score ≥6 in minor criteria were considered as infected. The diagnostic performance was evaluated by a receiver operative characteristic curve analysis and area under the curve (AUC) for each minor criterion. An AUC value of more than 0.9 was considered outstanding and 0.8-0.9 as excellent. ResultsWhen using 2018 ICM threshold, the diagnostic performance ranked based on AUC was the following: alpha defensin (0.92), positive histology (0.83), leukocyte esterase (0.82), synovial white blood cell (0.81), serum erythrocyte sedimentation rate (0.78), synovial polymorphonuclear neutrophils (0.77), serum C-reactive protein (0.74), D-dimer (0.59), single positive culture (0.53), and positive intraoperative purulence (0.51). Alpha defensin was considered as an outstanding test among the 2018 ICM minor criteria. Positive histology, leukocyte esterase, and synovial white blood cell were considered as excellent tests. ConclusionBased on our findings, alpha-defensin has the best diagnostic performance in Asian population among the minor criteria of 2018 ICM.

MP51-13 FLUORINE-18 (18F) PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA) POSITRON EMISSION TOMOGRAPHY (PET) AND THE DIAGNOSIS AND STAGING OF PRIMARY PROSTATE CANCER (PCA)

MP51-13 FLUORINE-18 (18F) PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA) POSITRON EMISSION TOMOGRAPHY (PET) AND THE DIAGNOSIS AND STAGING OF PRIMARY PROSTATE CANCER (PCA)

Evaluation of pleural fluid cytology for the diagnosis of malignant pleural effusion: a retrospective cohort study.

BackgroundCytological examination of pleural fluid has good specificity, but imperfect sensitivity for the diagnosis of malignant pleural effusion (MPE). Published estimates of sensitivity vary and predictors of false negative cytology are not well established.AimsTo estimate pleural fluid cytology sensitivity and identify risk factors for false negative cytology.MethodsWe conducted a retrospective cohort study of patients who had cytology testing of pleural fluid at Christchurch Hospital, New Zealand, from July 2017 to October 2019. Data on clinical and pleural fluid characteristics were collected. MPE was defined by positive pleural fluid cytology, tissue histology or multidisciplinary meeting consensus. We estimated sensitivity of the first pleural cytology assessment. We performed multivariate logistic regression to ascertain patient groups at greatest risk of false negative results.ResultsInitial pleural fluid cytology was diagnostic in 117 of 156 patients, providing a sensitivity (95% confidence interval (CI)) of 75.0% (67.4–81.6%). The sensitivity was 79.0% (66.8–88.3%) for lung cancer, 91.3% (72.0–98.9%) for breast cancer and 33.3% (95% CI 11.8–61.6%) for mesothelioma. Cloudy appearance of pleural fluid (odds ratio (OR) 0.12; 95% CI 0.03–0.54) and yellow/gold pleural fluid (OR 0.24; 95% CI 0.06–0.96) reduced the odds of false negative pleural cytology. Pleural thickening on computed tomography scan (OR 3.3; 95% CI 1.2–9.4) was a risk factor for false negative cytology.ConclusionSensitivity of pleural fluid cytology was greatest in primary lung and breast cancer, and lowest in mesothelioma. Clinicians should be alert to false negative results when suspecting mesothelioma or if pleural thickening is present.

Oncologic Outcomes of Squamous Cell Carcinoma Versus Urothelial Carcinoma With Squamous Differentiation After Radical Cystectomy for Bladder Carcinoma.

In this study we aim to compare clinicopathological characteristics and cancer specific survival between patients treated with radical cystectomy for pure squamous cell carcinoma (SCC) and urothelial carcinoma with squamous differentiation (SqD). We reviewed data of 1737 consecutive patients treated with radical cystectomy and urinary diversion between January 2004 and February 2014. Only patients with pure SCC or SqD were included in the analysis. Squamous differentiation was defined as intercellular bridges or keratinization in the tumor. Clinicopathological data and recurrence free survival (RFS) were compared between patients diagnosed with SCC and SqD. SCC and SqD were found in 318 and 223 patients, respectively. Mean age was 57 ± 8.3 years in SCC and 58.8 ± 7.8 in SqD (P=.008). A higher proportion of female patients was observed in SCC group compared to SqD (31.8% vs. 22% P < .0001). Patients with SqD were more likely to have extravesical (58.3% vs. 46.2%: P=.006) and nodal positive disease (34.5% vs. 14.5%: P < .0001) than pure SCC patients. Bilharzial eggs were found in 61% of SCC vs. 46% of SqD (P=.001).; The median (IQR) follow up period for SCC and SqD was 63 (12-112) months and 23 months (9-74.7), respectively. The 5-year RFS for SCC and SqD were 77% and 59.8 %, respectively (P < .0001).; Multivariate cox regression analysis identified advanced pT stage (OR: 1.9, 95% CI: 1.3-2.86, P=.0001), nodal positive disease (OR: 1.6, 95% CI: 1.1-2.48, P=.01) and SqD histology (OR: 1.6, 95% CI: 1.14-2.31, P=.007 as independent predictors of 5-year RFS. Patient with SCC had significantly higher 5-year RFS in comparison to SqD. The higher rate of extravesical disease and lymph node metastasis in SqD patients is indicative of aggressive behavior of this histologic type.

Development and Validation of Novel Nomograms to Predict the Overall Survival and Cancer-Specific Survival of Cervical Cancer Patients With Lymph Node Metastasis.

ObjectiveThe objective of this study was to establish and validate novel individualized nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in cervical cancer patients with lymph node metastasis.MethodsA total of 2,956 cervical cancer patients diagnosed with lymph node metastasis (American Joint Committee on Cancer, AJCC N stage=N1) between 2000 and 2018 were included in this study. Univariate and multivariate Cox regression models were applied to identify independent prognostic predictors, and the nomograms were established to predict the OS and CSS. The concordance index (C-index), calibration curves, and receiver operating characteristic (ROC) curves were applied to estimate the precision and discriminability of the nomograms. Decision-curve analysis (DCA) was used to assess the clinical utility of the nomograms.ResultsTumor size, log odds of positive lymph nodes (LODDS), radiotherapy, surgery, T stage, histology, and grade resulted as significant independent predictors both for OS and CSS. The C-index value of the prognostic nomogram for predicting OS was 0.788 (95% CI, 0.762–0.814) and 0.777 (95% CI, 0.758–0.796) in the training and validation cohorts, respectively. Meanwhile, the C-index value of the prognostic nomogram for predicting CSS was 0.792 (95% CI, 0.767–0.817) and 0.781 (95% CI, 0.764–0.798) in the training and validation cohorts, respectively. The calibration curves for the nomograms revealed gratifying consistency between predictions and actual observations for both 3- and 5-year OS and CSS. The 3- and 5-year area under the curves (AUCs) for the nomogram of OS and CSS ranged from 0.781 to 0.828. Finally, the DCA curves emerged as robust positive net benefits across a wide scale of threshold probabilities.ConclusionWe have successfully constructed nomograms that could predict 3- and 5-year OS and CSS of cervical cancer patients with lymph node metastasis and may assist clinicians in decision-making and personalized treatment planning.

Demographic factors associated with length of stay in hospital and histological diagnosis in adults undergoing appendicectomy

Appendicectomy remains of the most common emergency operations in the United Kingdom. The exact etiologies of appendicitis remain unclear with only potential causes suggested in the literature. Social deprivation and ethnicity have both been demonstrated to influence outcomes following many operations. There are currently no studies evaluating their roles with regards to severity and outcomes following appendicectomy. Demographic data were retrieved from health records for adult patients who underwent appendicectomy between 2010-2016 within a single NHS trust. To measure social deprivation, Indices of Multiple Deprivation (IMD) rankings were used. Histology reports were reviewed and diagnosis classified into predefined categories: non-inflamed appendix, uncomplicated appendicitis, complicated appendicitis and gangrenous appendicitis. Three thousand four hundred and forty-four patients were identified. Mean age was 37.8 years (range 73 years). Using a generalized linear model, South Asian ethnicity specifically was found to be independently predictive of increased length of stay following appendicectomy (p <0.001). Amongst South Asian patients, social deprivation was found to be further predictive of longer hospital stay (p= 0.005). Deprivation was found to be a predictor of complicated appendicitis but not of gangrenous appendicitis (p= 0.01). Male gender and age were also independent predictors of positive histology for appendicitis (p <0.001 and p= 0.021 respectively). This study is the first to report an independent association between South Asian ethnicity and increased length of stay for patients undergoing appendicectomy in a single NHS trust. The associations reported in this study may be a result of differences in the pathophysiology of acute appendicitis or represent inequalities in healthcare provision across ethnic and socioeconomic groups.

Hyperbilirubinemia as a Possible Predictor of Appendiceal Perforation in Acute Appendicitis: A Prospective Study.

Introduction: Acute appendicitis, a common abdominal surgical emergency, can mostly be diagnosed clinically by assessing the symptoms and physical findings but confirmation of the diagnosis solely depends upon the histopathological study of the resected appendix specimen, being supplemented by a few laboratory tests and ultrasonography (USG). In spite of all these available investigations, the diagnosis of acute appendicitis, because of its nebulous presentation and the variability of signs, remains a Herculean task for the surgeon.Methods: This is a prospective study conducted on 125 patients diagnosed with acute appendicitis and posted for appendicectomy. Total serum bilirubin (TSB), and total leucocyte count (TLC) were done in all cases. USG of the abdomen was done in all the cases to confirm the diagnosis and to rule out other causes of acute abdomen. TLC more than 11 x 103 cells/µL and TSB more than 1.1 mg/dL were considered positive. They were operated on and their diagnoses were confirmed post-operatively by histopathological examination. Patients were subdivided according to histopathological findings into: normal appendix (n = 11), uncomplicated acute appendicitis (n = 86), gangrenous appendicitis (n = 10) and perforated appendix (n = 18). Laboratory results, operative findings, and histopathological findings were compiled, analyzed, and compared with reference values.Results: Out of 125 patients, 114 (91.2%) were histologically positive for acute appendicitis, while 11 (8.8%) had normal histology. TLC was elevated in 95 (76 %) patients and it was normal in 30 (24%) cases. Among the patients with leucocytosis, only 90 (94.74%) had positive histology for acute appendicitis, while the remaining five (5.26%) had normal histology. Among the 30 patients who had normal TLC, 24 had positive histology for acute appendicitis, while the remaining six had normal histology. The specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) were 78.95%, 54.55%, 94.74%, and 20%respectively. Similarly, 67 patients (53.6%) had elevated TSB, while it was within normal limits in 58 (46.4%) patients. From the patients with hyperbilirubinemia, 65 (97.01%) had positive histology for acute appendicitis, while the remaining two (2.99%) had normal histology. Among 58 patients who had normal TSB, 49 had positive histology for acute appendicitis, while the rest nine had normal histology. The specificity, sensitivity, PPV, and NPV are 57.02%, 81.82%, 97.01%, and 15.52% respectively. However, when both TLC and TSB were compared as markers of appendicular perforation, the sensitivity, specificity, PPV, and NPV of total serum bilirubin were found to be 89.29% against 21.43%; 53.49% vs. 2.33%; 38.46% vs. 6.67% and 93.88% vs. 8.33% of total leukocyte counts respectively.Conclusion: Elevated total serum bilirubin could be used as a better predictor of appendiceal perforation in acute appendicitis.

Survival outcomes following radical cystectomy in patients with prior pelvic radiation for prostate cancer: A matched cohort analysis.

To determine the impact of prior pelvic radiation therapy (XRT) on outcomes following radical cystectomy (RC) for bladder cancer. We performed a retrospective review comparing patients with bladder cancer requiring RC and prior history of XRT for prostate cancer to those undergoing RC without XRT history at our institution from 2011-2018. Propensity score matching was performed with the following variables: age, chronic kidney disease, nutritional deficiency, neoadjuvant chemotherapy use, Charlson comorbidity index, surgical approach, urinary diversion type, and pathologic T-stage. Perioperative, pathologic and oncologic outcomes were analyzed. Categorical variables were assessed utilizing the Pearson Chi Square Test, and continuous variables with the Wilcoxon rank-sum test. The Kaplan-Meier method with stratified-log rank was used to compare survival outcomes. Multivariable Cox proportional hazards models were utilized to identify predictors of overall and recurrence free survival. 227 patients were included, of which 47 had radiotherapy for prostate cancer. 47% of patients in the radiation cohort received external beam radiation therapy, 47% received brachytherapy and 7% received both. There were no differences in recurrence-free survival (P = 0.82) or overall survival (P = 0.25). Statistically significant differences in perioperative or postoperative outcomes such as 90-day complication, readmission, mortality rates, or ureteroenteric anastomotic stricture rates were not found. Rates of node-positive disease, median lymph node yield, positive surgical margin rates, lymphovascular invasion, or variant histology were not significantly different between cohorts. After matching for T-stage and other clinical variables, history of pelvic XRT for prostate cancer in patients who later required RC for bladder cancer, was not associated with an increased rate of perioperative complications or an independent predictor of RFS or OS.

Study of diagnostic utility of Xpert MTB/Rif test on pleural fluid in the evaluation of patients presenting with Pleural Tuberculosis in Nepal.

Existing tests for the diagnosis of pleural tuberculosis (TB) have major limitations in terms of accuracy, time to diagnosis and drug resistance testing. A test which can diagnose pleural TB and detect resistance, like Xpert MTB/Rif, would be optimal for rapid diagnosis and treatment. A prospective observational study was done in a tertiary care hospital in Eastern Nepal. Fifty-one patients with clinic-radiologic suspicion of pleural TB were included. The results of pleural fluid Xpert MTB/Rif were compared with two Composite Reference Standards. Composite Reference Standard-1 consisted of positive pleural fluid smear, positive culture, positive histology of pleural biopsy, and positive sputum results. Composite Reference Standard-2 included those with Composite Reference Standard-1 and those with high ADA values (>40 U/l) with response to anti-tubercular treatment at 8 weeks of follow-up. Thirty-six patients were diagnosed as Pleural TB. Nine fulfilled Composite Reference Standard-1. Pleural fluid Xpert MTB/Rif was positive in five cases with Composite Reference Standard-1 and nine cases with Composite Reference Standard-2. The sensitivity, specificity, positive predictive value and negative predictive value with reference to Composite Reference Standard-1 were 55.56%, 88.10%, 50%, and 90.24%, respectively. Using Composite Reference Standard-2 as reference, sensitivity, specificity, positive predictive value and negative predictive value were 25%, 93.33%, 90%, and 34.15%, respectively. Two cases were diagnosed Xpert Rif resistant on pleural fluid. Due to low sensitivity, the Xpert MTB/Rif test cannot be recommended as initial test of diagnosis in a high prevalence setting. At the same time its clinical utility lies in testing of patients suspected to have drug-resistant pleural tuberculosis.

Lessons From a Quality Improvement Project to Standardize the Process of Gastric Biopsy Culture for Helicobacter pylori.

We conducted a quality improvement (QI) project with the aims of increasing the rate of successful primary culture. The QI project involved educational efforts among our gastroenterologists, endoscopy suite personnel, and laboratory personnel. We compared the frequency of gastric biopsy culture sent in patients with international classification of diseases 9th revision code 041.86, and 10th revision codes B96.81 evaluated by pediatric gastroenterologists at Boston Children's Hospital during the 9 months before the QI intervention (February 1, 2019 to October 31, 2019) and 9 months after the QI intervention (November 1 2019 to July 31 2020). We also compared the rate of culture growth in patients with positive histology (culture positivity), and antimicrobial susceptibilities before and after November 1, 2019. We observed an increased frequency of gastric biopsy acquisition by any gastroenterologist, obtained in 39% (28 of 71) preintervention patients compared with 67% (36 of 54) intervention patients (P = 0.004). There was an increase in the percentage of culture positivity across study periods from 21% (3 of 14) preintervention to 45% (5 of 11) postintervention (P = 0.39; 95% confidence interval, 0.64-7.00). Educational initiatives and collaborative work with staff physicians, endoscopy personnel, and hospital laboratory appear to be effective tools to increase usage of gastric biopsy culture as a diagnostic tool for H pylori infection and to increase culture positivity. Improving the surveillance of local resistance rates will improve the selection of the most effective primary treatment in specific geographic areas.

6 The Value of Ultrasound in Diagnosing Acute Appendicitis

Abstract Aim The diagnosis of acute appendicitis relies on a thorough history and examination and can often be challenging. Ultrasound is widely considered to be the most appropriate first line investigation; however non-diagnostic ultrasounds are not uncommon and do lead to delays in diagnosis and/or definitive treatment by creating a need for further clinical assessment. The purpose of this study was to determine the sensitivity and specificity of ultrasound diagnosis of appendicitis in patient treated at Doncaster Royal Infirmary, and to determine the local negative appendicectomy rate. Method This was a retrospective analysis of 99 patients undergoing appendicectomy, with a prior ultrasound abdomen within one week of the procedure being undertaken. Data was collected from review of patient's hospital medical records (discharge summaries, clinic letters, PACs). Results 99 patient aged 8-76 years were studied. Male to female ratios was 3:1. The sensitivity and specificity of ultrasound was 16% (95% CI - 7% to 29%) and 96% (95% CI - 86% to 99%) respectively with PPV of 80% and NPV of 52%. The accuracy of ultrasound diagnosis was found to be 55% (95% CI 44% to 65%). The negative appendicectomy rate was 48%. Conclusions From our study, ultrasound cannot reliably identify nor exclude appendicitis. Less than 16% of patients who had proven appendicitis (positive histology) had scans that indicated. Almost 50% of the normal/indeterminate scans were false negatives. Furthermore, 20% of positive ultrasound reports were false positives. A collaborative quality improvement project with the imaging department is planned to address these findings.

Prognostic relevance of pleural invasion for resected NSCLC patients undergoing adjuvant treatments: A propensity score-matched analysis of SEER database

BackgroundAdjuvant chemotherapy demonstrated a clear benefit in resected non-small cell lung cancer (NSCLC) with nodal disease (stages II-III), and a minimal benefit in tumors >4 cm (stage II, TNM 8th edition). Pleural invasion (PL), classified as visceral pleural invasion (VPI, which includes PL1 and PL2, and parietal pleural invasion (PL3), is an established negative prognostic factor. However, whether PL should influence the decisional algorithm of postoperative chemotherapy is controversial. MethodsA survival analysis of NSCLC patients who underwent radical surgery between 2010 and 2015 included in the SEER database was performed. Tumor stage and size, number of examined and positive nodes, histology, PL, and treatment data were extracted. Propensity score matching was performed. The benefit of chemotherapy was analyzed in two subgroups: standard of care (SOC), including patients with positive nodes or tumors ≥ 4 cm; non-SOC, including patients with tumors < 4 cm and negative nodes. ResultsRecords of 30,858 patients were extracted. 11,708 patients were included in the propensity score-matched analysis. In the SOC subgroup, including 8089 patients, all pleural invasion degrees were associated with progressively increased risk for death and shorter overall survival (OS), independently from chemotherapy administration. However, chemotherapy significantly improved the median OS regardless of the extent of PL. In the non-SOC subgroup, including 3619 patients, only PL3 was associated with increased mortality. The administration of chemotherapy did not improve survival outcomes. ConclusionChemotherapy should be strongly recommended in patients in the SOC-subgroup with pleural invasion. VPI is not associated with unfavorable prognosis in the non-SOC subgroup.

PD53-03 LONG TERM OUTCOMES OF DYNAMIC SENTINEL LYMPH NODE BIOPSY (DSNB) FOR CLINICALLY IMPALPABLE (CN0) PENILE CANCER PATIENTS-AN EUROGEN STUDY

You have accessJournal of UrologyPenile & Testicular Cancer: Penile & Testicular Cancer II (PD53)1 Sep 2021PD53-03 LONG TERM OUTCOMES OF DYNAMIC SENTINEL LYMPH NODE BIOPSY (DSNB) FOR CLINICALLY IMPALPABLE (CN0) PENILE CANCER PATIENTS-AN EUROGEN STUDY Edoardo Pozzi, Omer Onur Cakir, Fabio Castiglione, Nicolo' Schifano, Paul Hadway, Raj Nigam, Rowland Rees, Maarten Albersen, Arie Parnham, Maurice Lau, Hussain M. Alnajjar, Vijay Sangar, and Asif Muneer Edoardo PozziEdoardo Pozzi More articles by this author , Omer Onur CakirOmer Onur Cakir More articles by this author , Fabio CastiglioneFabio Castiglione More articles by this author , Nicolo' SchifanoNicolo' Schifano More articles by this author , Paul HadwayPaul Hadway More articles by this author , Raj NigamRaj Nigam More articles by this author , Rowland ReesRowland Rees More articles by this author , Maarten AlbersenMaarten Albersen More articles by this author , Arie ParnhamArie Parnham More articles by this author , Maurice LauMaurice Lau More articles by this author , Hussain M. AlnajjarHussain M. Alnajjar More articles by this author , Vijay SangarVijay Sangar More articles by this author , and Asif MuneerAsif Muneer More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002080.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Dynamic sentinel lymph node biopsy (DSNB) is routinely offered to patients presenting with penile cancer ³T1G2 and clinically impalpable inguinal lymph nodes (cN0). We aimed to assess the diagnostic accuracy of DSNB, cancer specific survival (CSS) in patients with positive DSNB and positive LN at further radical lymph node groin dissection (RLND). METHODS: An eUROGEN retrospective study of 509 penile cancer patients undergoing DSNB. Age, type of primary surgery, complications after DSNB, tumour stage, tumour grade were all reported. Number of true positives, true negatives, false negatives and false positives were recorded. False negative was defined as inguinal lymph node recurrence within 12 months from a previous negative DSNB. Sensitivity and specificity of DSNB were calculated. Kaplan-Meier analysis was used to estimate the 5-years CSS and recurrence free-survival rates among patients with positive DNSB and RLND. RESULTS: Overall, 509 patients with cN0 penile cancer were identified. The median follow-up for local recurrence and CSS were 62.5 months (IQR 28.5-91) and 63.5 months (IQR 26.5-90) respectively. All patients underwent DSNB at the time of primary surgery or as a delayed procedure. A total of 993 groins were studied. 37 patients had positive histology at DSNB. 37 patients underwent further RLND with 34 of them having positive histology at RLND. At DSNB true positives were 37 (7.27%), false negatives 3 (0.59). Sensitivity and specificity were 92.5% and 100% respectively. Multivariable Cox regression analysis identified positive LN histology both at DSNB and at RLND as predictors for reduced CSS (HR 4.59, CI: 2.35-8.95, p<0.0001) and (HR 5.64, p = 0.0004). Likewise, positive LN histology at DSNB and RLND was a predictor for reduced recurrence free survival HR 4.04 and HR 6.98 all p<0.0001. At Kaplan-Meier analysis, the 5-years CSS for positive LN histology at DSNB/RLND were 69.7% and 69.6% respectively. CONCLUSIONS: DSNB is now an established procedure with a sensitivity of 92.5%. Positive histology after DSNB and subsequent RLND is a strong predictor of reduced CSS and recurrence free survival. Source of Funding: n/a © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e917-e917 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Edoardo Pozzi More articles by this author Omer Onur Cakir More articles by this author Fabio Castiglione More articles by this author Nicolo' Schifano More articles by this author Paul Hadway More articles by this author Raj Nigam More articles by this author Rowland Rees More articles by this author Maarten Albersen More articles by this author Arie Parnham More articles by this author Maurice Lau More articles by this author Hussain M. Alnajjar More articles by this author Vijay Sangar More articles by this author Asif Muneer More articles by this author Expand All Advertisement Loading ...

Abstract 1375: Activity of pemetrexed in patients with driver oncogene positive non-small cell lung cancer and squamous histology

Abstract Pemetrexed, a multi-targeted antifolate chemotherapy agent, has been used both as a single agent chemotherapy as well as in combination given its favorable side effect profile, and has been the only effective continuation maintenance chemotherapy regimen after initial doublet use associated with increased overall survival (OS) among non-squamous non-small cell lung cancers. The current labelled indications for pemetrexed in NSCLC are restricted to those with non-squamous histology due to previous studies that showed worse outcomes in patients with squamous histology when compared to non-squamous histology. More recently, however, in the era of increased molecular profiling of NSCLC, it has been observed that patients with ALK, ROS1, and RET gene fusions have demonstrated marked sensitivity to pemetrexed. This retrospective case series, therefore, evaluated the response to pemetrexed among a cohort of 9 oncogene-driven patients with squamous (or adenosquamous) histologies who did receive pemetrexed based chemotherapy. Response rates, progression free survival (PFS), and OS for these patients were compared to a historical group of patients published in previous studies that examined pemetrexed response. The results indicated a positive response to pemetrexed in patients with an actionable driver oncogene occurring in the context of squamous or adenosquamous histology. Patients in the oncogene-driven adenosquamous/squamous group had significantly higher response rates as compared to the historical squamous cell group and no significant difference in response rates as compared to the historical adenocarcinoma comparison group. In summary, contrary to prior studies, this case series does suggest that pemetrexed may be a viable treatment option in patients with squamous cell histology who also have a targetable mutation. Citation Format: Yunan Nie, Tejas Patil, David Ross Camidge. Activity of pemetrexed in patients with driver oncogene positive non-small cell lung cancer and squamous histology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1375.

Bone turnover markers can predict healing time in medication-related osteonecrosis of the jaw

ObjectivesMedication-related osteonecrosis of the jaw (MRONJ) is a severe and difficult-to-treat adverse event of bone-modifying agents. Therefore predictive strategies determining patients at risk for a prolonged healing duration are needed to optimize treatment. Thus, the present study evaluates whether or not bone turnover markers can be used to predict the healing duration in MRONJ patients.Materials and methodsThe present study is a retrospective data analysis of patients suffering from MRONJ and positive histology for Actinomyces spp., who were identified at the General Hospital Vienna from 2014 to 2018. During the first visit, the patients’ demographics and levels of bone formation parameters were compiled. Healing times were analysed by Cox regression in dependence on these factors.ResultsA total of 52 patients were identified who fulfilled the inclusion criteria. The indication for bone-modifying agents was breast cancer (n = 21), prostate cancer (n = 14), multiple myeloma (n = 6) and other malignant diseases (n = 11). In 43 (82.7%) of our patients, we were able to document complete mucosal healing. Furthermore, patients who responded faster to therapy showed higher levels of C-telopeptide (P < 0.05), osteocalcin (P < 0.05) and bone-specific alkaline phosphatase (P < 0.05), but lower levels of 1.25-dihydroxyvitamin D (P < 0.05) than slower responding patients. No correlation was found regarding parathyroid hormone or calcitonin levels. Interestingly, patients who had a slower response were less likely to report dental procedures, but more likely to report a history of chemotherapy.ConclusionCTX and osteocalcin levels may be used for predicting healing duration for MRONJ.

The Role of Lipid Profile as an Independent Predictor of Non-alcoholic Steatosis and Steatohepatitis in Morbidly Obese Patients.

Background and Aims: Obesity is one of the major health problems worldwide. Morbid obesity (body mass index >40 kg/m2 or over 35 with a comorbidity) is associated, apart from other diseases, with an increased risk of non-alcoholic fatty liver disease (NAFLD). Moreover, dyslipidemia is an important comorbidity that is frequently found in NAFLD patients. The aim of this study was to analyze whether serum lipids in morbidly obese patients are associated with the spectrum of NAFLD.Methods: Total serum cholesterol, LDL cholesterol, HDL cholesterol, non-HDL cholesterol, VLDL, and triglycerides were analyzed in 90 morbidly obese patients. The association of lipid profile parameters with histopathological, elastographic, and sonographic indices of NAFLD, non-alcoholic steatohepatitis (NASH), and liver fibrosis were explored.Results: The mean levels of serum total cholesterol, LDL-C, and non-HDL cholesterol in patients with positive histology for liver steatosis and NASH were significantly higher than those in patients with negative histology. None of the indices showed a strong association with NAFLD, NASH, or liver fibrosis after adjustment for potential confounders.Conclusion: A slight predictive value of lipid profile is not sufficiently enough to use solely as a non-invasive test in predicting NASH or liver fibrosis.

The predictive role of parathyroid hormone for non-alcoholic fatty liver disease based on invasive and non-invasive findings in candidates of bariatric surgery

Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and hepatic fibrosis are the most detrimental hepatic abnormalities associated with increased body weight with devastating clinical outcomes. Therefore, there is a substantial necessity for efficient management strategies, including significant weight reduction. Bariatric surgery has been used as a therapeutic approach in a selected obese patient with NAFLD/NASH and other cardiometabolic comorbidities. The study is focused on the predictive role of PTH with the indices of hepatic steatosis/NAFLD and NASH based on liver biopsy, elastography, and sonography in morbidly obese patients. Ninety patients with BMI between 35 and 40 kg/m2 with more than two comorbidities who referred to Imam Reza outpatient clinic from December 2016 to September 2017 were recruited and underwent initial assessments, including demographic profiles, psychological assessment, anthropometric measurements, hepatic biopsy, and basic laboratory tests. Liver stiffness was evaluated using two-dimensional shear wave elastography (2D-SWE) at least two weeks before liver biopsy. The histological analysis of the liver was performed using biopsy samples which obtained from left hepatic lobe during bariatric surgery under direct surgeon observation using a 16-gauge Tru-cut needle. The study was approved by the ethical committee (IR.MUMS.fm.REC.1396.312). The level of PTH was significantly high in patients with positive histology for hepatic fibrosis, steatosis, and NASH/NAFLD compared to patients with negative histology (p = 0.005, p = 0.009, and p = 0.013, respectively). Also, patients with liver fibrosis confirmed by elastography had significantly higher serum PTH concentration than patients without fibrosis (p = 0.011). PTH was also positively correlated with hepatic fibrosis, NASH, and steatosis (p = 0.007, p = 0.012, p = 0.023, respectively). High levels of PTH was significantly associated with histological indices of (hepatic fibrosis, steatosis, NAFLD and NASH) and elasticity indices. Therefore, it is imperative to assess for high levels of PTH in the morbidly obese population pre-and post-bariatric surgery. However, for a more robust and comprehensive assessment, a randomized controlled trial is needed. The study was conducted in accordance with the practice guidance in the diagnosis and management of NAFLD from the American association for the study of liver disease (AASLD) 2018. Evidence obtained from well-designed cohort or case-control analytic studies.

Outcome of Petrosal Venous Sampling in Consecutive 68 Patients From a Major Neurosurgical Center in the United Kingdom

Background: Cushing’s disease is a challenging endocrine disorder caused by non-physiological cortisol excess from adrenocorticotropic hormone (ACTH) secreting pituitary adenoma. Inferior petrosal venous sampling (IPSS) is considered the gold standard investigation to differentiate Cushing’s disease from ectopic ACTH syndrome. Methods: This retrospective study included all patients who underwent IPSS between January 2011 and October 2020 at The National Hospital for Neurology and Neurosurgery in London. Patients demographics, radiological, surgical, endocrinological and, histological data were retrieved. We assessed the accuracy of IPSS in localizing ACTH secreting pituitary adenoma and its concordance with neuroimaging and surgical findings at the time of tumor resection. Results: In total 68 patients underwent IPSS, 22 males and 46 females. The median age was 42 years. IPSS was performed prior to primary surgery in 61 patients (90%) and before secondary surgery in 4 patients (6%). Three patients (4%) are awaiting surgery at the time of our study. Fifty-two patients (80%) had positive histology of ACTH expressing adenoma. Four patients (8%) had ectopic ACTH syndrome. The sensitivity of IPSS in predicting Cushing’s disease prior to corticotropin-releasing hormone (CRH) stimulation was 91% (95% CI [83% to 97%]) and accuracy of 88% (95% CI [77% to 95%]). The sensitivity of IPSS post CRH administration was 96% (95% CI [87% to 100%]) with accuracy of 86% (95% CI [75% to 93%]). Data on lateralization of pituitary adenoma were available for 63 patients. Prior to CRH stimulation, lateralization was right sided in 35 patients (56%), left sided in 15 (24%), and 13 patients (20%) did not have adequate interpetrosal sinus ACTH ratio. Lateralization post CRH stimulation was right sided in 40 patients (64%), left sided in 20 (32%), and 3 patients (4%) did not achieve adequate ACTH gradient ratio between two sides. Eighteen patients (30%) switched adenoma lateralization between pre and post CRH stimulation. Post CRH IPSS was consistent with neuroradiology in localizing pituitary adenomas in 59% (29 out of 49 patients) and concordant with surgical findings in 41% (25 out of 61 patients). Patients with ectopic ACTH syndrome had negative IPSS at all stages. IPSS procedure failed in 2 patients (3%). No post procedure complications were reported. Conclusion: IPSS has high sensitivity in diagnosing pituitary driven Cushing’s disease with good safety profile. However, the reliability in lateralizing pituitary adenoma is debated. One third of patients in this cohort switched lateralization before and after CRH administration. Studies on monkeys and rats showed that CRH induces coronary vasodilation and reduction in systemic vascular resistance.This suggest that CRH might have vasoactive effect on pituitary blood vessels with subsequent influence on IPS:P ACTH gradient ratio between the two sides.

Utility of vertebral biopsy before vertebroplasty in patients with diagnosis of vertebral compression fracture.

To demonstrate the utility of a biopsy performed just beforevertebroplastyin patients with diagnosis of vertebral compression fracture (VCF) and no history of neoplastic or hematologic diseases. Osteoporosis is the most frequent cause of vertebral compression fracture, with trauma and pathologic vertebral weakening being other common causes. Since secondary fractures at imaging investigation can present as simple compression fractures, it is important to identify an underlying pathology. The aim of this paper is to evaluate the frequency of unexpected positive histology in vertebral samples withdrawn from patients undergoing avertebroplasty to evaluate if a vertebral biopsy canroutinelybe used in case of VCF and when a secondary cause is not suspected. We retrospectively evaluated the results of324 biopsies performed from February 2003 to March 2019 just beforevertebroplastyin 1183 patients diagnosed with one or more vertebral compression fractures and with no history of neoplastic or hematological diseases and with no suspicious findings for secondary fractures at imaging. Biopsy was not diagnostic in 9/324 cases (2.8%); osteoporosis was the diagnosis in 295 cases (91%); in the remaining 20 cases (6.2%), histology was positive for an underlying pathology: 12/20 (60% of positive cases) multiple myeloma; 5/20 (25%) lymphoma/leukemia; 1/20 (5%) spondylitis; 1/20 (5%) metastasis; 1/20(5%) hemangioma. A significantly higher incidence of positive biopsies was found in patients younger than 73 (p = 0.01) with17 of 20 (85%) positive biopsies. No complications related to thebiopticmaneuver were found, according toCIRSEguidelines on percutaneous needle biopsy. Vertebral biopsy is a safe procedure with no related complications. In our series, an unexpected diagnosis was found in 6% of cases with impact on patient's clinical management. Positive unexpected histology was significantly higher in younger patients. Inconclusion, webelieve that a biopsy is useful and should be performed on all patients with vertebral compression fractures before avertebroplasty.

Diagnostic Accuracy of Bone Culture Versus Biopsy in Diabetic Foot Osteomyelitis.

To compare the diagnostic accuracy of bone culture (microbiology) and biopsy (histology) in patients with acute or chronic diabetic foot osteomyelitis (DFO). This cross-sectional study involved patients for whom providers had a clinical suspicion of DFO. Two bone samples were taken: one for microbiologic testing and another for histologic testing. The sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio were calculated for bone culture results in relation to the probability of DFO diagnosis. Fifty-two patients were included; 69% had positive bone culture results, and 90.4% had positive histology results (P = .013), and of those 90.4%, 25.5% had acute and 74.5% had chronic DFO. The sensitivity of the microbiologic bone culture result was 0.70, the specificity was 0.40, the positive predictive value was 0.92, and the negative predictive value was 0.13. Histology provides more accurate diagnosis of DFO than microbiology, especially for patients with chronic DFO. These patients could be underdiagnosed because of false-negative results provided by bone culture. Providers should perform both tests to confirm the presence of DFO.