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.

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.

Gastroesophageal reflux is an emerging concern after peroral endoscopic myotomy (POEM) with a reported incidence of up to 50 % [1]. Recently, a novel natural orifice transluminal endoscopic surgery (NOTES) procedure that creates an endoscopic anterior partial fundoplication (POEM + F) was reported [2]. We report on four patients with achalasia cardia treated using POEM + F. Four patients (three women, one man; mean age 38.8 years) with type II achalasia confirmed on esophagogastroduodenoscopy (EGD) and high-resolution manometry (HRM) consented to undergo POEM + F. The mean Eckhardt score was 10 and symptom duration 9.5 months. All procedures were performed under general anesthesia. A standard anterior POEM was performed using a gastroscope (GIF-190H; Olympus Corporation, Tokyo, Japan) with a distal transparent attachment. After completion of a full-thickness myotomy across the gastroesophageal junction, a 5.7 mm ultraslim gastroscope (GIF-190P) was introduced alongside the gastroscope into the gastric fundus. Using double-endoscope transillumination with the gastroscope in the tunnel ([Fig. 1]), the serosa overlying the myotomy was divided for entry into the peritoneal cavity. The scope was angled upward and to the left to reach the gastric fundus ([Fig. 2]), which was grasped and retracted into the tunnel to create the wrap. The procedure was continuously monitored by ultraslim gastroscope ([Fig. 3]). Once the wrap was satisfactory, the spot on the fundic serosa was marked. The gastroscope was withdrawn from the tunnel, a 3 cm endoloop clasped in a reconstrainable clip was passed through the scope ([Fig. 4]), and the scope was reintroduced into the peritoneal cavity. The endoloop was fixed to the fundus using four clips. The gastroscope was withdrawn into the tunnel and the loop was proximally fixed to the end of the myotomy and peritoneal opening. The endoloop was tightened, the loop tail trimmed using a loop cutter, and the mucosal incision was closed ([Video 1]). Video 1 Video illustrating the technical steps to perform a peroral endoscopic myotomy and endoscopic fundoplication (POEM + F). Each step is accompanied by detailed narration describing the technical nuances of the procedure. After 24 hours of fasting, the patients resumed oral diet and were discharged. On follow-up at four weeks, EGD revealed an intact wrap in all patients ([Fig. 5]). Eckhardt scores had normalized and no patient reported symptoms of gastroesophageal reflux disease. On follow-up, pH studies in two of four patients confirmed the absence of abnormal acid reflux. Endoscopy_UCTN_Code_TTT_1AO_2AJ

Skin cancers are rather uncommon malignancies comprising less than 1% of all the cancers in India. Drawstring dermatitis is a type of frictional dermatitis that can result from traditional tightly worn garments like “sari” and “salwaar-kameez”. The resulting chronic friction at the waist can lead to lichenified grooves, post inflammatory depigmentation/leukoderma and aggravating pre-existing dermatoses like vitiligo and lichen planus. Chronic friction combined with sweating and humid environment of the tropics predisposes to candida, dermatophytes and bacterial infections. Rarely, squamous cell carcinoma has been reported. Prevention of the condition lies in weight reduction and tying the drawstrings loosely, especially in those inclined to develop koebnerizing conditions. Saree cancer is a rare type of squamous cell carcinoma (SCC). Saree and dhoti are traditional male and female costumes, respectively, which is unique to the Indian subcontinent. Constant wear of this clothing tightly around the waist results in changes in pigmentation and scaling of the skin, acanthosis, scar and ulceration and subsequent, gradual malignant changes. The process of repeated trauma over a long time and consequent interference with the healing process may be the reason for malignant transformation. We are presenting a rare case of saree cancer in a 68-year-old woman, with distant ulceroproliferative growth in left loin, along the waistline, which showed well-differentiated SCC on biopsy. Wide excision with primary closure was done.

Advancement in science and technology has brought a remarkable change in the field of drug discovery. Earlier it was very difficult to predict the target for receptor but nowadays, it is easy and robust task to dock the target protein with ligand and binding affinity is calculated. Docking helps in the virtual screening of drug along with its hit identification. There are two approaches through which docking can be carried out, shape complementary and stimulation approach. There are many procedures involved in carrying out docking and all require different software's and algorithms. Molecular docking serves as a good platform to screen a large number of ligands and is useful in Drug-DNA studies. This review mainly focuses on the general idea of molecular docking and discusses its major applications, different types of interaction involved and types of docking.