Global incidences of oropharyngeal squamous cell carcinoma (OPSCC) are rising due to an association with high-risk human papillomavirus (HPV). Although there is an improved overall survival of HPV-related OPSCC; up to 25% of the patients develop recurrent or distant metastatic disease with a fatal outcomes. Biomarkers to monitor this disease are not established. This meta-analysis reviews the role of cell-free HPV DNA in liquid biopsy (LB) as a biomarker for HPV-related OPSCC. Pubmed, Livivo, and Cochrane Library databases were searched from inception to August, 2020. All studies were analyzed by Meta-DiSc 1.4 and Stata 16.0 statistical software. In total, 16 studies were considered for systematic review, whereas 11 studies met inclusion criteria for meta-analysis, respectively. Pooled sensitivity of cfHPV-DNA at first diagnosis and during follow-up was 0.81 (95% CI; 0.78–0.84) and 0.73 (95% CI; 0.57–0.86), while pooled specificity was 0.98 (95% CI; 0.96–0.99) and 1 (95% CI; 0.99–1). The diagnostic odds ratio (DOR) at first diagnosis was 200.60 (95% CI; 93.31–431.22) and 300.31 (95% CI; 60.94–1479.88) during follow-up. The area under the curve (AUC) of summary receiver operating characteristic (SROC) was 0.99 at first diagnosis and 1.00 during follow-up, respectively. In conclusion, cfHPV-DNA presents a potential biomarker with high specificity in patients with HPV-related OPSCC.
Tumor growth and survival requires a particularly effective immunosuppressant tumor microenvironment (TME) to escape destruction by the immune system. While immunosuppressive checkpoint markers like programmed cell death 1 ligand (PD-L1) are already being targeted in clinical practice, lymphocyte-activation-protein 3 (LAG-3), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) and V-domain Ig suppressor of T cell activation (VISTA) inhibitors are currently under investigation in clinical trials. Reliable findings on the expression status of those immune checkpoint inhibitors on tumor-infiltrating lymphocytes (TILs) in the TME of oropharyngeal squamous cell carcinoma (OPSCC) are lacking. This work aims to describe the expression of LAG-3, TIM-3, and VISTA expression in the TME of OPSCC. We created a tissue microarray of paraffin-embedded tumor tissue of 241 OPSCC. Expression of the immune checkpoint protein LAG-3, TIM-3, and VISTA in OPSCC was evaluated using immunohistochemistry and results were correlated with CD8+ T-cell inflammation and human papillomavirus (HPV)-status. 73 OPSCC stained positive for LAG-3 (31%; HPV+:44%; HPV-:26%, p = 0.006), 122 OPSCC stained positive for TIM-3 (51%; HPV+:70%; HPV-:44%, p < 0.001) and 168 OPSCC (70%; HPV+:75%; HPV-:68%, p = 0.313) for VISTA. CD8+ T-cells were significantly associated with LAG-3, TIM-3 and VISTA expression (p < 0.001, p < 0.001, p = 0.007). Immune checkpoint therapy targeting LAG-3, TIM-3, and/or VISTA could be a promising treatment strategy especially in HPV-related OPSCC. Future clinical trials investigating the efficacy of a checkpoint blockade in consideration of LAG-3, TIM-3, and VISTA expression are required.
Background and Aims: Although Peroral Endoscopic Myotomy (POEM) is highly effective for the management of achalasia, clinical failures may occur. The optimal management of patients who fail POEM is not well known. This study aims to compare the outcomes of different management strategies in patients who had failed POEM.
Patients and Methods: This is an international, multicenter, retrospective study at 16 tertiary centers between 1/2012 and 11/2019. All patients who underwent POEM and experienced persistent or recurrent symptoms (Eckardt score (ES) > 3) were included. The primary outcome was to compare the rate of clinical success (ES ≤ 3) between different management strategies.
Results: A total of 99 patients (50 (50.5%) males, mean age 51.4 (16.2) yrs.) experienced clinical failure during the study period with a mean ES of 5.5 (0.2). A total of 29 (32.2%) patients were managed conservatively and 70 (71%) underwent re-treatment [repeat POEM 33 (33%), pneumatic dilation (PD) 30 (30%), and laparoscopic Heller myotomy (LHM) 7 (7.1%)]. During a median follow-up of 10 (IQR: 3-20) months, clinical success was highest in patients who underwent repeat POEM (25/33 (76%), mean ES 2.1 (2.1)), followed by PD (18/30 (60%), mean ES 2.8 (2.3)), and LHM (2/7 (29%), 4 (1.8)) (p=0.12). A total of 11 (37.9%, mean ES 4 (1.8)) patients in the conservative achieved clinical success.
Conclusion: This study comprehensively assessed an international cohort of patients who underwent management of failed POEM. Repeat POEM and PD achieved acceptable clinical success with excellent safety profile.
Objective The purpose of this study was to report short-term outcomes of cryoablation of early-stage renal tumors (T1a and T1b) at a tertiary hospital in India.
Methods This was a retrospective study of consecutive patients who underwent cryoablation for renal cell carcinoma (RCC) from November 2018 to June 2020. Cryoablation was performed under combined ultrasound and computed tomography guidance using a helium-argon cryoablation system. Tumor number, size, location, nephrometry score, relationship of the tumor with pelvicalyceal system, and adjacent organs were tabulated, and technical and clinical success evaluated. Early and late recurrence and complications were also assessed.
Results Eleven patients (median age: 62 years) with 11 tumors underwent cryoablation. The mean tumor size was 2.58 cm (range: 1.62–5.62 cm) with 10 lesions being T1a and one lesion T1b. Tissue sampling was done in 9/11 patients, 3 were papillary RCC and the rest, clear cell RCC. In two patients, the tumor was completely endophytic, three patients had partially endophytic tumors while 6 patients had exophytic lesions. The median nephrometry score was 6 (range: 4–11, Mode 4). Technical success was achieved in all patients. Complete response was achieved in 81% (9/11) of the patients at 1-month follow-up. Median follow-up period was 6 months. Two patients showed residual disease on follow-up imaging at 1 and 3 months, respectively.
Conclusion Cryoablation is a promising, relatively new minimally invasive therapy for treating small renal tumors in India. It is safe, technically feasible, and shows excellent short-term efficacy.
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