Increased EpCAM expression in malignant insulinoma: potential clinical implications

ObjectiveEpCAM (CD326) is overexpressed in progenitor cells of endocrine pancreatic islands of Langerhans during fetal development and was suggested to act as a morphoregulatory molecule in pancreatic island ontogeny. We tested whether EpCAM overexpression is reactivated in insulinomas, endocrine tumors arising in the pancreas.Design/methodWe used monoclonal anti-EpCAM antibody Ber-Ep4 for immunohistochemistry on formalin-fixed and paraffin-embedded tumor material. We analyzed 53 insulinomas: 40 benign (disease stage<IIa) and 13 malignant tumors (disease stage IIIb/IV). Disease stage disposition followed new TNM classification of the European Neuroendocrine Tumor Society (ENETS) for foregut neuroendocrine tumors (2006). Additionally, ten insulinoma metastases were analyzed. Clinical follow-up was available for overall survival analysis from 49 patients. The EpCAM expression of the islands of Langerhans was classified as 2+ in healthy pancreatic tissue.ResultsIn 38% of the benign insulinomas (disease stage<IIa), we found strong (3+) EpCAM expression. In contrast, malignant insulinomas (disease stage IIIb/IV) and their metastases exhibited a strong (3+) EpCAM expression with 78 and 80% respectively, significantly more frequent (P<0.01). The malignant tissue was characterized by a significantly lower number of unstained cells and significantly higher number of 3+ stained cells. Quantitative PCR for EpCAM mRNA validated strong EpCAM expression in malignant insulinoma. Kaplan–Meier curves indicated survival disadvantage for EpCAM 3+ insulinomas, but this was not statistically significant (log-rank test).ConclusionThis first EpCAM expression study in benign/malignant insulinomas indicates that strong EpCAM expression could help to identify patients at risk for malignant disease and might be used as a therapeutic target for antibody-based therapies in patients with metastatic insulinoma.

Download Full-text

Risk of Metastatic Ovarian Involvement in Nongynecologic Malignancies

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e3182332cd1 ◽

2012 ◽

Vol 22 (1) ◽

pp. 3-8 ◽

Cited By ~ 4

Author(s):

Kidong Kim ◽

Soo Youn Cho ◽

Sang-Il Park ◽

Hye Jin Kang ◽

Beob-Jong Kim ◽

...

Keyword(s):

Overall Survival ◽

Malignant Tumors ◽

Rank Test ◽

Benign Tumors ◽

Binary Logistic Regression Analysis ◽

Fisher Exact Test ◽

Tumor Type ◽

Metastatic Tumors ◽

Number Of Patients ◽

Adnexal Tumors

ObjectiveThe objectives were to evaluate the risk of malignant adnexal tumors in women with nongynecologic malignancies and to identify variables associated with the risk of malignant adnexal tumors.MethodsThe eligibility criteria included the diagnosis of a nongynecologic malignancy and adnexal tumors, which were resected or subjected to biopsy at our institute between 1999 and 2010. The risk of malignant adnexal tumors was assessed by dividing the number of patients with metastatic tumors to the adnexa or primary adnexal cancers by the total number of patients. The association of clinicopathologic variables with the risk of malignant adnexal tumors was evaluated using the Fisher exact test and binary logistic regression analysis. In patients with metastatic tumors to the adnexa, the association of clinicopathologic variables with overall survival after adnexal surgery was examined using the log-rank test.ResultsIn 166 patients with adnexal tumors, 41 benign tumors, 113 metastatic tumors to the adnexa, and 12 primary adnexal cancers were diagnosed. Age older than 46 years, a tumor type associated with a high risk for malignant adnexal tumors, and bilateral tumors significantly increased the risk of malignant adnexal tumors. The overall survival of the patients with stomach cancer was significantly worse than the patients with colorectal or breast cancers.ConclusionOne hundred twenty-five of the 166 patients with nongynecologic malignancies who had adnexal tumors managed surgically were shown to have malignant tumors, and most of the tumors were metastatic from primary sites. The risk of malignant adnexal tumors was associated with age, nongynecologic malignancy, and bilaterality.

Download Full-text

Bevacizumab biosimilar (MB02) and reference bevacizumab in patients with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC) (STELLA study): Multiple Imputation analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e15003 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e15003-e15003

Author(s):

Dmytro Trukhin ◽

Elena Poddubskaya ◽

Andric Zoran ◽

Igor Bondarenko ◽

Serhii Shevnia ◽

...

Keyword(s):

Multiple Imputation ◽

Primary Endpoint ◽

Tumour Response ◽

Stage Iiib ◽

Added Value ◽

Phase Iii ◽

Disease Stage ◽

Efficacy Data ◽

Sensitive Analysis ◽

Response Data

e15003 Background: Stella Trial is a phase III, multinational, double-blind and randomized study to confirm clinical similarity between MB02 and EU-bevacizumab in patients with stage IIIB/IV no squamous NSCLC. 627 subjects with newly diagnosed or recurrent stage IIIb/IV NSCLC were randomized 1:1 to receive either MB02 or EU-bevacizumab plus chemotherapy (paclitaxel and carboplatin) every 3-week cycle for six cycles (week 18) followed by MB02/bevacizumab in blinded monotherapy until disease progression, treatment intolerance, death, patient withdrawal or end of study (w52). An approach targeting the MI of the continuous sum of target diameters (mm), and subsequent categorization of Overall Response (OR) was performed as sensitivity analysis for the assessment of the primary endpoint. Multiple Imputation (MI) has emerged as a credible method to assess the effects of missing data (MD), an inescapable problem with a potential ability to undermine research results' strength and validity in a clinical study, providing the user with a valuable toolset to sufficiently account for the varying types of MD and appropriately adjust the assumptions. Methods: The primary endpoint of the study was Objective Response Rate (ORR) at week 18 per an Independent Radiological Committee (IRC) in the Intention to treat set (ITT). The ORR was analysed with a Cochran-Mantel-Haenszel model, including the stratification factors of sex, smoking status, disease diagnosis and disease stage, comparing the stratified estimates risk difference (RD). In addition, these results were analysed implementing a pattern-mixture MI process accounting for missing at random (MAR) and missing not at random (MNAR) data based on the sum of target diameters in subjects without tumour response data or falling into the categories NonCR/NonPD or non-evaluable (NE). Results: The clinical equivalence of MB02 with EU-bevacizumab is demonstrated by the efficacy data provided through the primary endpoint and the MI sensitive analysis applied. The MI (MAR and MNAR) represents an added value that supports the biosimilarity of MB02 and EU-bevacizumab. The results for the primary analysis of the RD in ORR at w18 in the ITT set were entirely contained within the boundaries of predefined margins (±12): -4.02 [95% CI: -11.76 to 3.71]). Under MI, the ORR RD showed similarity at 95% CIs (-1.92; 95% CI: -10.02 to 6.19) and using the multiple imputations for subjects without tumour response data (missing, NonCR/NonPD or NE), the ORR RD was -2.22 with 95% CI of (-10.54 to 6.10) at w18 in the ITT. Conclusions: The clinical equivalence of MB02 with EU-bevacizumab is demonstrated by the efficacy data provided through the primary endpoint and the MI sensitive analysis applied. The MI (MAR and MNAR) represent an added value that supports the biosimilarity of MB02 and EU-bevacizumab. Clinical trial information: NCT03296163.

Download Full-text

Malignant Cutaneous Tumors

10.2310/tywc.1080 ◽

2018 ◽

Author(s):

Allan C Halpern ◽

Patricia L. Myskowski

Keyword(s):

Cell Carcinoma ◽

Malignant Tumors ◽

Tnm Classification ◽

Kaposi Sarcoma ◽

Dermatofibrosarcoma Protuberans ◽

Staging System ◽

Primary Cutaneous Melanoma ◽

Primary Tumors ◽

Paget Disease ◽

Cutaneous Lymphomas

This chapter reviews the most common malignant cutaneous tumors. The section on malignant tumors of the epidermis discusses nonmelanoma skin cancer (i.e., basal cell carcinoma and squamous cell carcinoma) and malignant melanoma. The section on malignant tumors of the dermis covers metastatic tumors, primary tumors (Merkel cell carcinoma, Paget disease, extramammary Paget disease, angiosarcoma, and dermatofibrosarcoma protuberans), and Kaposi sarcoma (i.e., classic Kaposi sarcoma, African Kaposi sarcoma, organ-transplant Kaposi sarcoma, and HIV-associated Kaposi sarcoma). The final section covers cutaneous lymphomas. The coverage of each disease includes a discussion of epidemiology, etiology, diagnosis, differential diagnosis, treatment, and prognosis. Tables provide the adjusted estimated relative risks of melanoma by nevus type and number, the American Joint Committee on Cancer (AJCC) TNM classification and staging system, the estimated probability of 10-year survival in patients with primary cutaneous melanoma, and an overview of overview of therapy for cutaneous T cell lymphoma. Figures illustrate the presentation of many malignant cutaneous tumors. This review contains 10 highly rendered figures, 5 tables, and 105 references.

Download Full-text

Malignant Cutaneous Tumors

10.2310/fm.1080 ◽

2018 ◽

Author(s):

Allan C Halpern ◽

Patricia L. Myskowski

Keyword(s):

Cell Carcinoma ◽

Malignant Tumors ◽

Tnm Classification ◽

Kaposi Sarcoma ◽

Dermatofibrosarcoma Protuberans ◽

Staging System ◽

Primary Cutaneous Melanoma ◽

Primary Tumors ◽

Paget Disease ◽

Cutaneous Lymphomas

Download Full-text

Modified Graner's Technique with\without Vascularized Capitate Lengthening for Kienböck Disease Stage IIIb—A Pilot Study

Journal of Wrist Surgery ◽

10.1055/s-0041-1731328 ◽

2021 ◽

Author(s):

Ahmed Naeem Atiyya ◽

Abdelrahman Eldiasty ◽

Islam Koriem ◽

Amr Nabil

Keyword(s):

Outcome Measures ◽

Stage Iiib ◽

Disease Stage ◽

Functional Evaluation ◽

Mayo Wrist Score ◽

Number Of Patients ◽

Case Series Study ◽

Kienböck Disease ◽

Mid Term Results

Abstract Background Intercarpal fusions are used to treat stage IIIb Kienböck disease. They increase force transfer across the radioscaphoid articulation with predisposition to arthritis. Description of Technique This technique is excision of lunate followed by proximal transfer of capitate, with scaphocapitate and triquetrocapitate fusion to increase area of load transfer mimicking wrist hemiarthroplasty. Our purpose is to evaluate mid-term results of this technique. Patients and Methods A prospective case series study was conducted on 11 patients with stage IIIb and IIIc. In seven cases, transfer of the capitate was performed by osteotomizing the capitate just distal to its waist, proximal migration to replace the excised lunate then bone grafting. In four cases, proximal transfer of vascularized pedicled capitate was done. Clinical outcome measures included pain (visual analog scale), grip strength, range of motion, and functional evaluation by modified Mayo wrist score and scoring system of Evans. Radiological outcome measures included healing of fusion mass, progression of the disease, and occurrence of avascular necrosis to the capitate. Results Follow-up period averaged 54 months. Scaphocapitate fusion healing averaged 11 weeks. Union of the lengthened capitate occurred in 10 patients only. There was postoperative improvement in pain scores, grip, Evans, and modified Mayo wrist score. There was postoperative decrease in wrist flexion and extension. One patient showed resorption of the capitate head with progressive radioscaphoid arthritis-necessitated wrist fusion. Conclusion The mid-term results of this technique may be satisfactory due to low incidence of degenerative arthritis in the radioscaphoid joint. However, longer follow-up with recruiting larger number of patients is needed.

Download Full-text

Differences in Cell of Origin (COO) Affect Outcomes in Caucasian(C) but Not in African American(AA) Patients with Diffuse Large B-Cell Lymphoma(DLBCL)

Blood ◽

10.1182/blood.v126.23.1460.1460 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1460-1460 ◽

Cited By ~ 2

Author(s):

Uma Borate ◽

Deniz Peker ◽

James M. Foran ◽

Luciano J Costa

Keyword(s):

B Cell ◽

B Cell Lymphoma ◽

Disease Stage ◽

Rank Test ◽

Advanced Stage ◽

Cell Of Origin ◽

First Line ◽

First Line Therapy ◽

Log Rank Test ◽

Line Therapy

Abstract Introduction: DLBCL is an aggressive mature B-cell neoplasm with a low incidence in African Americans and other minority groups. The differences in outcomes based on DLBCL Cell of Origin(COO) immunophenotypic subtypes as defined by the Hans algorithm using CD10, Bcl-6, and MUM1 namely germinal center B-cell (GCB) and non-GCB have been based on predominantly Caucasian patients (pts) and their impact on outcomes in AA patients have not been well studied. Material and Methods: A retrospective review of clinicopathologic data from patients diagnosed and treated for DLBCL at UAB between 2002-2011 was conducted following IRB approval .The data collected included patient demographics (age, sex, self identified race), DLBCL subtype (GCB vs. non-GCB based on the Hans algorithm), disease stage, first line therapy regimens and patient outcomes. We analyzed group differences in both C and AA pts with GCB and non-GCB subtypes of DLBCL in all the parameters mentioned above using the chi square test for categorical variables,. In addition, OS was examined using Kaplan Meier curves and the log rank test. We performed univariate and multivariate analyses to examine the effects of variables of interest on OS. All results were considered statistically significant at α=0.05 level. Results: We included a total of 259 pts in our analysis after excluding patients with missing demographics, disease related data, primary mediastianal DLBCL, missing first line therapy data and outcomes data as well as race identified as other than C or AA. 45 patients (17.4%) of patients self identified as AA and 214 (82.6%) self identified as Caucasian. The mean age of presentation for AA pts was 52 yrs compared to 58 years for C patients (p=0.045) and 28 (62.2%) AA patients presented with advanced Stage III and IV disease compared to 89 (44.6%) of C patients (P=0.04) both being statistically significant. Based on COO characterization using immunophenotype by Hans algorithm, 27 AA pts (60%) and 145(67%) of C pts were GCB by immunophenotype(p=0.317). 95% of all patients received R-CHOP as first line therapy , 3.5% received R-CVP and the remaining received a combination of Rituximab alone, FCR or radiation therapy .On analyzing OS based on COO, AA patients did not demonstrate a significant difference in OS based on COO with both GCB and non-GCB groups having a median OS of 84 months ( p=0.74)( 95% CI 72-121 months). However, the median OS for C pts with GCB phenotype was 104 months compared to 25 months for the non-GCB phenotype and the median OS was 55 months +/-12.6 months for the C pt group as a whole( p<0.001 by log rank test )which was highly statistically significant.Multivariate analyses of different factors affecting OS showed only COO (p<0.001), age(p=0.07) and stage of DLBCL at presentation(p=0.027) to affect OS significantly.Race,Gender and IPI score did not appear to impact OS significantly. Conclusion: Our study aimed to study the impact of COO and Race on OS in DLBCL especially in AA pts where this has not been well characterized. Our results show that as expected the incidence of DLBCL is lower in AA patients compared to C pts. However, DLBCL presents at younger age and with more advanced stage in AA than in C patients. Although distribution of COO is similar in AA and C patients, our findings suggest that COO may not have the same effect on prognosis among AA pts as it does among the C pt population where we see non-GCB patients do significantly worse than their GCB counterparts. This may reflect a different disease biology in AA patients that has yet to be understood. Our study limitations include not taking into account disease relapse, second line therapy and effect of autologous bone marrow transplantation on overall survival. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Predictors for response to cetuximab in a prospective clinical trial (E2303) of patients with head and neck squamous cell carcinoma (HNSCC).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.5576 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 5576-5576 ◽

Cited By ~ 1

Author(s):

Amanda Psyrri ◽

Ju-Whei Lee ◽

Eirini Pectasides ◽

Maria Vassilakopoulou ◽

Barbara Burtness ◽

...

Keyword(s):

Clinical Trial ◽

Phase Ii ◽

Cox Regression ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Disease Stage ◽

Rank Test ◽

Free Survival ◽

Cox Regression Analysis ◽

Event Time

5576 Background: Theidentification of resistance mechanisms to Epidermal Growth Factor Receptor (EGFR) inhibitors remains critical lack in the management of HNSCC. We sought to determine predictors for response to cetuximab in a phase II clinical trial. Methods: 63 patients (pts) with operable stage III/IV HNSCC participated in E2303, an Eastern Cooperative Oncology Group (ECOG) phase II trial of induction chemotherapy with weekly cetuximab, paclitaxel and carboplatin x 6 followed by chemoradiotherapy with the same regimen. A tissue microarray was constructed and EGFR, ERK1/2, Met, pAkt and STAT protein expression levels were assessed using AQUA. The objectives of analysis were to determine association of biomarkers with E2303 efficacy outcomes (best objective response (OR), overall survival (OS), progression-free survival (PFS), and event-free survival (EFS)). The logistic regression model was used to examine relationship between marker measurements (on a continuous scale) and OR. The univariate and multivariate Cox proportional hazards models were used to evaluate the relationship between markers and event-time distributions. Fisher’s exact test was used to evaluate differences in response rate between groups (high vs. low AQUA scores). Event-time distributions were estimated by the Kaplan-Meier method and compared by the log-rank test. Results: Cytoplasmic ERK1/2 levels weresignificantly associated with PFS and OS (p=0.03 and 0.01, respectively). Nuclear ERK1/2 levels were significantly associated with OS (p=0.02) and tended towards significance for PFS (p=0.09). The multivariate Cox regression analysis shows that cytoplasmic and nuclear ERK1/2 are significantly associated with OS and PFS after controlling for primary site and disease stage, respectively There was no significant association between cytoplasmic or nuclear ERK1/2 status and OR (p-values 0.98 and 0.41, respectively).No association was found between expression of any of other biomarkers and outcome measures. Our data analysis was based on 35 pts with marker data available. Conclusions: Ras/MAPK/ERKpathway may be associated with resistance to cetuximab in HNSCC.

Download Full-text

Outcomes of appendiceal adenocarcinomas compared to right and left-sided colorectal adenocarcinomas: An analysis from the National Cancer Database (NCDB).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.42 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 42-42

Author(s):

Kanika Gupta Nair ◽

Wei Wei ◽

Michael Cruise ◽

Katherine Tullio ◽

Bassam N. Estfan

Keyword(s):

Stage Iv ◽

Stage I ◽

Disease Stage ◽

Rank Test ◽

National Cancer Database ◽

Kaplan Meier ◽

Stage Iv Disease ◽

The Difference ◽

The Right ◽

Colorectal Adenocarcinomas

42 Background: Appendiceal carcinomas (AC) account for 1-2% of colorectal cancers (CRC) and are generally treated like other CRC. However, there is limited data to guide treatment. While AC originate on the right side of the colon, it is unclear if they behave like as right-sided CRC (R-CRC). We seek to learn how AC differ from right versus left-sided CRC (L-CRC). Methods: We identified histologically confirmed cases of appendiceal and colorectal adenocarcinomas with information about stage and overall survival (OS) diagnosed between 2004 and 2016 from the National Cancer Database. Kaplan-Meier method and log-rank test were used to estimate and compare OS. Results: 833,939 patients met our inclusion criteria: 15,138 (1.8%) AC, 447,551 (53.7%) L-CRC, 308,794 (37.0%) R-CRC, and 62,456 (7.5%) transverse CRC (T-CRC). Median age at diagnosis of all patients was 68 years (range:18-90); AC was lowest at 61 years for stage I-III disease and 58 years for stage IV disease. Stage IV AC was more common in females 3628/5739 (63.22%). AC had the best OS among site groups in stage I-III. Median OS for stage I-III AC was 128.8 months (95% CI: 117.9-139.0), with 5-year OS rate of 0.69 (95% CI: 0.67-0.70); L-CRC median OS was 111.6 months (95% CI: 110.9-112.4), with 5-year OS rate of 0.681 (95% CI: 0.680-0.683); R-CRC median OS was 88.5 months (95% CI: 87.8-89.1), with 5-year OS rate of 0.613 (95% CI: 0.611-0.615); and T-CRC median OS was 86.2 months (95% CI: 84.7-87.6), with 5-year OS rate of 0.608 (95% CI: 0.604-0.613) (p <0.0001) (Table). Similar difference was observed in stage IV patients (Table). Conclusions: Patients with AC had significantly better OS for stages I-III and stage IV compared to patients with L-CRC, R-CRC, and T-CRC, though outcomes were more similar to L-CRC. The difference is more evidence for patients with stage IV disease. T-CRC had similar OS to R-CRC, as anticipated. [Table: see text]

Download Full-text

Value of Both WHO and TNM Classification Systems for Patients with Pancreatic Endocrine Tumors: Results of a Single-Center Series

World Journal of Surgery ◽

10.1007/s00268-009-0182-4 ◽

2009 ◽

Vol 33 (11) ◽

pp. 2458-2463 ◽

Cited By ~ 18

Author(s):

Riccardo Casadei ◽

Claudio Ricci ◽

Raffaele Pezzilli ◽

Davide Campana ◽

Paola Tomassetti ◽

...

Keyword(s):

Tnm Classification ◽

Classification Systems ◽

Endocrine Tumors ◽

Single Center ◽

Pancreatic Endocrine Tumors

Download Full-text

Chitinase 3-like proteins as diagnostic and prognostic biomarkers of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458514561906 ◽

2015 ◽

Vol 21 (10) ◽

pp. 1251-1261 ◽

Cited By ~ 67

Author(s):

G Hinsinger ◽

N Galéotti ◽

N Nabholz ◽

S Urbach ◽

V Rigau ◽

...

Keyword(s):

Multiple Sclerosis ◽

Prognostic Biomarkers ◽

Disease Stage ◽

Rank Test ◽

Differential Analysis ◽

Diagnostic Biomarkers ◽

Relapsing Remitting ◽

Optimized Treatment ◽

Disease Stages ◽

In Cis

Background: Despite sensitivity of MRI to diagnose multiple sclerosis (MS), prognostic biomarkers are still needed for optimized treatment. Objective: The objective of this paper is to identify cerebrospinal fluid (CSF) diagnostic biomarkers of MS using quantitative proteomics and to analyze their expression at different disease stages. Methods: We conducted differential analysis of the CSF proteome from control and relapsing–remitting MS (RRMS) patients followed by verification by ELISA of candidate biomarkers in CSF and serum in control, clinically isolated syndrome (CIS), RRMS and progressive MS (PMS) patients. Results: Twenty-two of the 527 quantified proteins exhibited different abundances in control and RRMS CSF. These include chitinase 3-like protein 1 (CHI3L1) and 2 (CHI3L2), which showed a strong expression in brain of MS patients, especially in astrocytes and microglial cells from white matter plaques. CSF and serum CHI3L1 levels increased with the disease stage and CIS patients with high CSF (>189 ng/ml) and serum (>33 ng/ml) CHI3L1 converted more rapidly to RRMS (log rank test, p < 0.05 and p < 0.001, respectively). In contrast, CSF CHI3L2 levels were lower in PMS than in RRMS patients. Accordingly, CSF CHI3L1/CHI3L2 ratio accurately discriminated PMS from RRMS. Conclusions: CSF CHI3L1 and CHI3L2 and serum CHI3L1 might help to define MS disease stage and have a prognostic value in CIS.

Download Full-text