MRI-Diagnosed Tumour Deposits and EMVI Status Have Superior Prognostic Accuracy to Current Clinical TNM Staging in Rectal Cancer.

BACKGROUND DATA: MRI assessment of rectal cancer not only assesses tumour depth and surgical resectability but also extramural disease which affects prognosis. We have observed that non-nodal tumour nodules (tumour deposits; mrTDs) have a distinct MRI appearance compared to lymph node metastases (mrLNMs). OBJECTIVE: We aimed to assess whether mrTDs and mrLNMs have different prognostic implications and compare these to other known prognostic markers. METHODS: This was a retrospective cohort study of 233 patients undergoing resection for rectal cancer from January 2007-October 2015. Data were obtained from electronic records and MRIs blindly re-reported. Survival was determined using Kaplan-Meier method. Prognostic markers were evaluated using Cox regression and competing risks analysis. Inter-observer agreement for mrTD was measured using Cohen's Kappa. RESULTS: On multivariable analysis, baseline mrTD/mrEMVI (extramural venous invasion) status was the only significant MRI factor for adverse survival (HR 2.36 (1.54-3.61) for OS, 2.37 (1.47-3.80) for DFS (both p < 0.001), superseding T and N categories. mrLNMs were associated with good prognosis (HR 0.50 (0.31-0.80)p= 0.004 for OS, 0.60 (0.40-0.90)p = 0.014 for DFS). On multivariable analysis, mrTDs/mrEMVI were strongly associated with distant recurrence (HR 6.53 (2.52-16.91) p = < 0.001) whereas T and N category were not. In a subgroup analysis of post-treatment MRIs in post-chemoradiotherapy (CRT) patients, mrTD/mrEMVI status was again the only significant prognostic factor; furthermore those who showed a good treatment response had a prognosis similar to patients who were negative at baseline. Inter-observer agreement for detection of mrTDs was κ0.77 and κ0.83. CONCLUSION: Current MRI staging predicting T and N status does not adequately predict prognosis. Positive mrTD/mrEMVI status has greater prognostic accuracy and would be superior in determining treatment and follow-up protocols. CRT may be a highly effective treatment strategy in mrTD/mrEMVI positive patients

Serum microRNAs in HIV-infected individuals as pre-diagnosis biomarkers for AIDS-NHL.

ObjectiveTo determine if changes in levels of serum microRNAs (miRNAs) were seen preceding the diagnosis of AIDS-related non-Hodgkin lymphoma (AIDS-NHL).DesignSerum miRNA levels were compared in 3 subject groups from the Multicenter AIDS Cohort Study: HIV-negative men (n = 43), HIV-positive men who did not develop NHL (n = 45), and HIV-positive men before AIDS-NHL diagnosis (n = 62, median time before diagnosis, 8.8 months).MethodsA total of 175 serum-enriched miRNAs were initially screened to identify differentially expressed miRNAs among these groups and the results validated by quantitative polymerase chain reaction. Receiver-operating characteristic analysis was then performed to assess biomarker utility.ResultsHigher levels of miR-21 and miR-122, and a lower level of miR-223, were able to discriminate HIV-infected from the HIV-uninfected groups, suggesting that these miRNAs are biomarkers for HIV infection but are not AIDS-NHL specific. Among the HIV-infected groups, a higher level of miR-222 was able to discriminate diffuse large B-cell lymphoma (DLBCL) and primary central nervous system lymphoma (PCNSL) subjects from HIV-infected subjects who did not develop NHL, with area under the receiver-operating characteristic curve of 0.777 and 0.792, respectively. At miR-222 cutoff values of 0.105 for DLBCL and 0.109 for PCNSL, the sensitivity and specificity were 75% and 77%, and 80% and 82%, respectively.ConclusionsAltered serum levels of miR-21, miR-122, and miR-223 are seen in HIV-infected individuals. Higher serum level of miR-222 has clear potential as a serum biomarker for earlier detection of DLBCL and PCNSL among HIV-infected individuals

Serum microRNAs in HIV-infected individuals as pre-diagnosis biomarkers for AIDS-NHL.

ObjectiveTo determine if changes in levels of serum microRNAs (miRNAs) were seen preceding the diagnosis of AIDS-related non-Hodgkin lymphoma (AIDS-NHL).DesignSerum miRNA levels were compared in 3 subject groups from the Multicenter AIDS Cohort Study: HIV-negative men (n = 43), HIV-positive men who did not develop NHL (n = 45), and HIV-positive men before AIDS-NHL diagnosis (n = 62, median time before diagnosis, 8.8 months).MethodsA total of 175 serum-enriched miRNAs were initially screened to identify differentially expressed miRNAs among these groups and the results validated by quantitative polymerase chain reaction. Receiver-operating characteristic analysis was then performed to assess biomarker utility.ResultsHigher levels of miR-21 and miR-122, and a lower level of miR-223, were able to discriminate HIV-infected from the HIV-uninfected groups, suggesting that these miRNAs are biomarkers for HIV infection but are not AIDS-NHL specific. Among the HIV-infected groups, a higher level of miR-222 was able to discriminate diffuse large B-cell lymphoma (DLBCL) and primary central nervous system lymphoma (PCNSL) subjects from HIV-infected subjects who did not develop NHL, with area under the receiver-operating characteristic curve of 0.777 and 0.792, respectively. At miR-222 cutoff values of 0.105 for DLBCL and 0.109 for PCNSL, the sensitivity and specificity were 75% and 77%, and 80% and 82%, respectively.ConclusionsAltered serum levels of miR-21, miR-122, and miR-223 are seen in HIV-infected individuals. Higher serum level of miR-222 has clear potential as a serum biomarker for earlier detection of DLBCL and PCNSL among HIV-infected individuals

Anal Cancer Screening in Men Who Have Sex With Men in the Multicenter AIDS Cohort Study.

ObjectiveTo evaluate the prevalence of anal cytology (ACyt) abnormalities among HIV-infected and HIV-uninfected men who have sex with men (MSM).DesignMulticenter cohort study of 723 HIV-infected and 788 HIV-uninfected MSM with ACyt, with a second ACyt collected 2 years later. A referral for high-resolution anoscopy was suggested for abnormal ACyt.MethodsACyt samples were collected using a polyester swab and liquid cytology media and read in a central laboratory.ResultsPrevalence of any abnormal ACyt was 25% in HIV-uninfected MSM and increased to 38%, 41%, and 47% among HIV-infected MSM with current CD4 T-cell counts ≥500, 350-499, and &lt;350 cells/mm (P &lt; 0.001), respectively. Anal HPV16 DNA was also more common in HIV-infected than HIV-uninfected MSM (25% versus 16%, P &lt; 0.001). Abnormal baseline ACyt together with prevalent HPV16 DNA detection was present in only 7% of HIV-uninfected MSM compared to 18% of HIV-infected MSM with current CD4 &lt; 350, P &lt; 0.001. Among HIV-infected men, 56% of the men with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions ASCs-US/LSILs and 81% of men with atypical squamous cells cannot exclude high-grade (ASC-H/)/high-grade squamous intraepithelial lesions (HSIL) had lower grade ACyt findings 18-30 months later ("regressed"). However, 19% of untreated HIV-infected men with ASC-H/HSIL cytology maintained that same grade of cytology in their second test approximately 2 years later, and 15% with ASC-US/LSIL "progressed" to ASC-H/HSIL. Abnormal ACyt had high sensitivity (96%) but low specificity (17%) for biopsy-proven HSIL.ConclusionsPrevalence of abnormal ACyt remains elevated in HIV-infected men during the current antiretroviral therapy era

Anal Cancer Screening in Men Who Have Sex With Men in the Multicenter AIDS Cohort Study.

ObjectiveTo evaluate the prevalence of anal cytology (ACyt) abnormalities among HIV-infected and HIV-uninfected men who have sex with men (MSM).DesignMulticenter cohort study of 723 HIV-infected and 788 HIV-uninfected MSM with ACyt, with a second ACyt collected 2 years later. A referral for high-resolution anoscopy was suggested for abnormal ACyt.MethodsACyt samples were collected using a polyester swab and liquid cytology media and read in a central laboratory.ResultsPrevalence of any abnormal ACyt was 25% in HIV-uninfected MSM and increased to 38%, 41%, and 47% among HIV-infected MSM with current CD4 T-cell counts ≥500, 350-499, and &lt;350 cells/mm (P &lt; 0.001), respectively. Anal HPV16 DNA was also more common in HIV-infected than HIV-uninfected MSM (25% versus 16%, P &lt; 0.001). Abnormal baseline ACyt together with prevalent HPV16 DNA detection was present in only 7% of HIV-uninfected MSM compared to 18% of HIV-infected MSM with current CD4 &lt; 350, P &lt; 0.001. Among HIV-infected men, 56% of the men with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions ASCs-US/LSILs and 81% of men with atypical squamous cells cannot exclude high-grade (ASC-H/)/high-grade squamous intraepithelial lesions (HSIL) had lower grade ACyt findings 18-30 months later ("regressed"). However, 19% of untreated HIV-infected men with ASC-H/HSIL cytology maintained that same grade of cytology in their second test approximately 2 years later, and 15% with ASC-US/LSIL "progressed" to ASC-H/HSIL. Abnormal ACyt had high sensitivity (96%) but low specificity (17%) for biopsy-proven HSIL.ConclusionsPrevalence of abnormal ACyt remains elevated in HIV-infected men during the current antiretroviral therapy era