Evaluation of Cytotoxic T Lymphocytes and Natural Killer Cell Distribution in Oral Squamous Cell Carcinoma and Oral Epithelial Dysplasia: An Immunohistochemical Study.

Background The tumor microenvironment comprises stromal cells, a few immune cells, vascular channels, and an extracellular matrix. The immune cells play a pivotal role in arresting the development of various tumors by identifying and killing the abnormal tumor cells. These immune cells with cytotoxic function include the natural killer (NK) cells and CD8+ T lymphocytes. Human NK cells express the cell surface marker CD57 and can be identified by using monoclonal antibodies. CD8+ cytotoxic T cells are a critical subpopulation of T cells and are important mediators of adaptive immunity. The anti-tumor immunity is important to assess the prognosis of tumors and develop new therapies. This study aimed to evaluate the immunohistochemical expression of CD8 and CD57 immune cells in oral squamous cell carcinoma (OSCC), oral epithelial dysplasia (OED), and normal oral mucosa. Methodology Clinically diagnosed and histopathologically confirmed cases of OSCC (n = 22), oral leukoplakia with OED (n = 22), and normal oral mucosa (n = 22) comprised the study groups. The tissue sections were subjected to immunohistochemical analysis for CD8 and CD57 expression by calculation of the mean labeling index. The results were statistically analyzed using a one-way analysis of variance, Bonferroni multiple comparison test, and Student's t-test. SPSS software version 20.0 (IBM Corp., Armonk, NY, USA) was used for the statistical analysis, and the significance level was set at 0.05. Results An overall statistically significant difference was obtained in the number of CD8+ T lymphocyte cells and CD57+ NK cells when compared between OSCC, OED, and normal oral mucosa (p = 0.01). Variations in the number of CD8+ T lymphocyte cells and CD57+ NK cells were observed when a comparison was made between OED and OSCC and between OSCC and normal mucosal samples (p = 0.01). The study results showed that the mean labeling index of CD8 and CD57 increased in OSCC when compared to OED and normal mucosa (p = 0.01). Conclusions Samples of OED with moderate or severe dysplasia and samples of OSCC were accompanied by a higher level of infiltrating immune cells such as T cells, B cells, NK cells, and macrophages when compared to normal mucosa. The results suggested that the expression of CD8 and CD57 cells increased from normal mucosa to OED and the highest expression was found in OSCC. CD8 and CD57 could be used as surrogate markers to assess the malignant potential of the lesion and to determine the prognosis of patients with oral cancer.

Comparison of LED and LASER Colonoscopy About Linked Color Imaging and Blue Laser/Light Imaging of Colorectal Tumors in a Multinational Study.

INTRODUCTION: In light-emitting diode (LED) and LASER colonoscopy, linked color imaging (LCI) and blue light/laser imaging (BLI) are used for lesion detection and characterization worldwide. We analyzed the difference of LCI and BLI images of colorectal lesions between LED and LASER in a multinational study. METHODS: We prospectively observed lesions with white light imaging (WLI), LCI, and BLI using both LED and LASER colonoscopies from January 2020 to August 2021. Images were graded by 27 endoscopists from nine countries using the polyp visibility score: 4 (excellent), 3 (good), 2 (fair), and 1 (poor) and the comparison score (LED better/similar/LASER better) for WLI/LCI/BLI images of each lesion. RESULTS: Finally, 32 lesions (polyp size: 20.0 ± 15.2 mm) including 9 serrated lesions, 13 adenomas, and 10 T1 cancers were evaluated. The polyp visibility scores of LCI/WLI for international and Japan-expert endoscopists were 3.17 ± 0.73/3.17 ± 0.79 (p = 0.92) and 3.34 ± 0.78/2.84 ± 1.22 (p < 0.01) for LED and 3.30 ± 0.71/3.12 ± 0.77 (p < 0.01) and 3.31 ± 0.82/2.78 ± 1.23 (p < 0.01) for LASER. Regarding the comparison of lesion visibility about between LED and LASER colonoscopy in international endoscopists, a significant difference was achieved not for WLI, but for LCI. The rates of LED better/similar/LASER better for brightness under WLI were 54.5%/31.6%/13.9% (International) and 75.0%/21.9%/3.1% (Japan expert). Those under LCI were 39.2%/35.4%/25.3% (International) and 31.3%/53.1%/15.6% (Japan expert). There were no significant differences in the diagnostic accuracy and the comparison score of BLI images between LED and LASER. CONCLUSIONS: The differences of lesion visibility for WLI/LCI/BLI between LED and LASER in international endoscopists could be compared to those in Japanese endoscopists.

Bowel cleansing efficacy of 1 L NER1006versus macrogol and 3 L polyethylene glycol using split-dose administration.

Background and Aim: Colonoscopies are an important diagnostic technique in the detection of colorectal cancer and colonic disease. Adequate examination is dependent on the degree of mucosal visibility, with poor cleansing impeding the detection of neoplasms. These patients require shorter colonoscopy surveillance intervals, longer hospital stays, and increased healthcare costs-rendering a screening colonoscopy cost-ineffective. In Australia and the Gold Coast Hospital and Health Service (GCHHS), macrogol and 3 L of polyethylene glycol are the preferred regimen given its safety profile and efficacy. Yet, little is known locally about the use of the new low-volume bowel preparation NER1006 (Plenvu) given its recent registration with the Therapeutic Goods of Australia (TGA). The primary outcome assessed the bowel cleansing efficacy of NER1006 compared with 7 days of macrogol and 3 L of polyethylene glycol using the Boston Bowel Preparation Scale (BBPS), while also assessing the influence of notable patient characteristics such as age, gender, body mass index (BMI), and the patients Charlson comorbidity index (CCI). Secondary outcomes assessed the polyp detection rate and procedural factors including cecal intubation, scope withdrawal time, and rebooking rates. Methods: Data from all patients who underwent an outpatient colonoscopy procedure at GCHHS between 1 July 2020 and 30 September 2020 were analyzed. Patients were aged 50-74 years of age and were referred for a screening colonoscopy due to a positive fecal occult blood test (FOBT) result from the National Bowel Cancer Screening Program. Results: Of the 238 patients who met the inclusion criteria, 108 patients received NER1006 and 130 patients received macrogol and 3 L polyethylene glycol. NER1006 achieved superior overall (P < 0.001) and right-sided colon cleansing (P = 0.016). There was an even distribution of males and females (P = 0.118), the mean age of both cohorts was <65 years of age. The macrogol and 3 L polyethylene glycol group had a statistically higher BMI (P < 0.001) and CCI (P < 0.001). Cecal intubation success was achieved in both cohorts (≥95%) and scope withdrawal time was ≥6 min, polyp detection was non-superior (P = 0.824), but superior in NER1006 when BBPS ≥6 (P = 0.002). Rebooking rates were significantly lower in the NER1006 group (P = 0.013). Conclusion: This study demonstrated that NER1006 was superior in terms of overall and right-sided bowel cleansing as a primary endpoint. Patient factors demonstrated to be independent predictors of inadequate bowel preparation. Future studies should aim to explore the safety and tolerability of NER1006 while also assessing the bowel cleansing effectiveness in patients with a high BMI and comorbidity index.

A multicentric, 2 × 2 factorial, randomised, open-label trial to evaluate the clinical effectiveness of structured physical activity training and cognitive behavioural therapy versus usual care in heart failure patients: a protocol for the PACT-HF trial.

Background: Heart failure (HF) is a multi-morbid chronic condition, which adversely affects the quality of life of the affected individual. Engaging the patient and their caregivers in self-care is known to reduce mortality, rehospitalisation and improve quality of life among HF patients. The PACT-HF trial will answer whether clinical benefits in terms of mortality and hospitalisation outcomes can be demonstrated by using a pragmatic design to explore the specific effects of physical activity, and cognitive behavioural therapy in HF patients in India. Methods: We will conduct a 2 × 2 factorial, randomized, open-label trial, which aims to see if rehabilitation strategies of structured physical activity training and cognitive behavioural therapy for depression and self-management reduce the risk of repeat hospitalisation and deaths in HF patients in India. Patients will be randomised to (1) physical activity + usual care (2) cognitive behaviour therapy + usual care, (3) physical activity + cognitive behaviour therapy + usual care, and (4) usual care at 1:1:1:1 ratio. Time to mortality will be the primary outcome. A composite of mortality and hospitalisation for HF will be the main secondary outcome. Additional secondary outcomes will include 'days alive and out of hospital', cumulative hospitalisation, quality of life, Minnesota Living with Heart Failure questionnaire score, depression score, six minutes walking distance, handgrip strength, and adherence to medicines and lifestyle.  The effects of intervention on the primary outcome will be estimated from Cox proportional hazard models. For the continuous secondary outcome variables, differences between randomised groups will be estimated from linear mixed models or generalised estimating equations (GEE) as appropriate. Discussion: PACT-HF is designed to provide reliable evidence about the balance of benefits and risks conferred by physical activity and cognitive behavioural therapy-based cardiac rehabilitation for those with HF, irrespective of their initial disease severity.

Third Asia-Pacific consensus recommendations on colorectal cancer screening and postpolypectomy surveillance.

The Asia-Pacific region has the largest number of cases of colorectal cancer (CRC) and one of the highest levels of mortality due to this condition in the world. Since the publishing of two consensus recommendations in 2008 and 2015, significant advancements have been made in our knowledge of epidemiology, pathology and the natural history of the adenoma-carcinoma progression. Based on the most updated epidemiological and clinical studies in this region, considering literature from international studies, and adopting the modified Delphi process, the Asia-Pacific Working Group on Colorectal Cancer Screening has updated and revised their recommendations on (1) screening methods and preferred strategies; (2) age for starting and terminating screening for CRC; (3) screening for individuals with a family history of CRC or advanced adenoma; (4) surveillance for those with adenomas; (5) screening and surveillance for sessile serrated lesions and (6) quality assurance of screening programmes. Thirteen countries/regions in the Asia-Pacific region were represented in this exercise. International advisors from North America and Europe were invited to participate.

Factors influencing endoscopic estimation of colon polyp size in a colon model.

BACKGROUND/AIMS: Colorectal polyps are removed to prevent progression to colorectal cancer. Polyp size is an important factor for risk stratification of malignant transformation. Endoscopic size estimation correlates poorly with pathological reports and several factors have been suggested to influence size estimation. We aimed to gain insight into the factors influencing endoscopic polyp size estimation. METHODS: Images of polyps in an artificial model were obtained at 1, 3, and 5 cm from the colonoscope's tip. Participants were asked to estimate the diameter and volume of each polyp. RESULTS: Fifteen endoscopists from three large-volume centers participated in this study. With an intraclass correlation coefficient of 0.66 (95% confidence interval [CI], 0.62-0.71) for diameter and 0.56 (95% CI, 0.50-0.62) for volume. Polyp size estimated at 3 cm from the colonoscope's tip yielded the best results. A lower distance between the tip and the polyp was associated with a larger estimated polyp size. CONCLUSION: Correct endoscopic estimation of polyp size remains challenging. This finding can affect size estimation skills and future training programs for endoscopists.

Endoscopic Diagnosis of Nonpedunculated Dysplasia during Surveillance of Ulcerative Colitis: A Survey-Based Multinational Study.

Background/Aims: Endoscopic diagnosis of dysplasia or colitic cancer in patients with ulcerative colitis (UC) is more challenging than that of colorectal neoplasia in non-colitic patients. We aimed to evaluate the accuracy of the endoscopic diagnosis of "nonpedunculated" dysplasia or colitic cancer in UC patients. Methods: Ten endoscopists from four countries were surveyed using photographs of 61 histologically confirmed dysplastic or non-dysplastic lesions retrieved from the UC registry database of Asan Medical Center. The participants provided their assessment based on the given photographs and their intention to perform biopsy. Results: The overall diagnostic performance of the 10 participants is summarized as follows: sensitivity of 88.2% (95% confidence interval [CI], 84.3% to 91.5%), specificity of 34.8% (95% CI, 29.1% to 40.8%), positive predictive value of 63.0% (95% CI, 60.8% to 65.2%), negative predictive value of 70.2% (95% CI, 62.7% to 76.6%), and accuracy of 64.6% (95% CI, 60.7% to 68.4%). The interobserver agreement on the intention to perform a biopsy was poor (Fleiss kappa=0.169). Of the three endoscopic characteristics of the lesions, including ulceration, distinctness of the borders, and pit patterns, only neoplastic pit patterns were significantly predictive of dysplasia (odds ratio, 3.710; 95% CI, 2.001 to 6.881). The diagnostic sensitivity and specificity of neoplastic pit patterns were 68.2% (95% CI, 63.0% to 73.2%) and 63.3% (95% CI, 57.3% to 69.1%), respectively. Conclusions: Diagnostic performance based on the endoscopist's intention to perform a biopsy for nonpedunculated potentially dysplastic lesions in UC patients was suboptimal according to this survey-based study.

Dietary n-3 polyunsaturated fatty acids and the aetiology of ulcerative colitis: a UK prospective cohort study.

OBJECTIVES: The aetiology of ulcerative colitis (UC) is largely unknown, although it is plausible that dietary n-3 polyunsaturated fatty acids (PUFAs) may be protective. Metabolites derived from n-3 PUFAs are less proinflammatory than those from n-6 PUFAs. Earlier, no prospective cohort studies have investigated this hypothesis, using dietary information collected from food diaries. The aim of this study was to investigate the total dietary intake of n-3 PUFAs and the specific n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the risk of developing incident UC. METHODOLOGY: Twenty-five thousand six hundred and thirty-nine participants, living in Norfolk UK, aged 45-74 years (median age at recruitment of 59.2 years), completed 7-day food diaries. These were interpreted using a computer programme, which converted food items into nutrients, including n-3 PUFAs. The cohort was monitored for participants who developed UC. Each case was matched with four controls and an analysis performed using conditional logistic regression. RESULTS: In the cohort, 22 incident cases of UC were identified after a median follow-up time of 4.2 years (range 1.8-8.3 years). A statistically significant protective odds ratio (OR) for the trend across tertiles was found for DHA [OR = 0.43, 95% confidence interval (CI)=0.22-0.86, P = 0.02] and borderline statistically significant differences for trends for total total n-3 PUFAs (OR = 0.56, 95% CI=0.28-1.13, P = 0.10) and EPA (OR = 0.53, 95% CI=0.27-1.03, P = 0.06) after adjusting for age, sex, total energy intake, smoking, and other fatty acids. CONCLUSION: Total dietary n-3 PUFAs, EPA, and DHA, particularly DHA were associated with protection from UC in a cohort aged over 45 years. If the association is causal, then increasing the population's intake of n-3 PUFAs from oily fish may help prevent UC.