Gastrointestinal stromal tumors in elderly patients

Background: Gastrointestinal stromal tumors (GISTs) account for 1 to 3% of all primary malignant tumors of the gastrointestinal tract. The global incidence of GISTs varies in the range of 7-15 cases per 1 million people per year. In about 95% of cases, the incidence is sporadic. Despite the fact that some success has been achieved in the treatment of this pathology, the problem of GISTs treatment is urgent, especially in elderly and senile patients in particular. The aim of the study: To study the age-related characteristics of GISTs development in patients of older age groups. Material(s) and Method(s): A retrospective analysis of 56 clinical cases of GISTs in patients of different age groups according to the WHO classification was carried out in the study. Result(s): The most common variant of the immunohistochemical structure was the spindle cell one 62.5%. In most cases, tumors were localized in the stomach 82.2%. Elderly patients had larger tumor sizes compared with young and middle-Aged patients. In patients of older age groups, the disease was most often detected at stage II. In most cases, a comorbid pathology was detected, most often a combination of several diseases of the cardiovascular system. Conclusion(s): In patients of older age groups, the spindle cell structure of the GISTs is most common, the tumor was most often localized in the stomach (77.4%), most often the tumor was localized along the lesser curvature. In most cases, the tumor was up to 10.0 cm in diameter. On average, the disease was detected at stage II. Comorbid pathology occurred in 87.3% of cases. In 2020-2021, the disease was detected more often, the of tumors sizes were smaller, due to an increase in the number of CT scans of the chest for the diagnosis of the new coronavirus infection.Copyright © 2022 AME Publishing Company. All rights reserved.

Multidisciplinary management of a quickly growing pediatric atypical Spitz nevus, mimicking melanoma, during the COVID-19 pandemic

Spitzoid melanoma is very rare tumour in the pediatric population, with clinical and non-uniform behaviour, different from adult melanoma [1]. It can be difficult to differentiate an atypical Spitz nevus from a Spitzoid melanoma, resulting in diagnostic problems. In addition, in our clinical case, the COVID-19pandemiccaused significant delays both in the diagnosis and in the surgical treatment of our patient. We present the clinical case of a 4-year-old child suffering from a localized polypoid cutaneous neoformation on the dorsum of the left hand, which started immediately before the lockdown and steadily increased during the COVID-19 pandemic. After a general clinical framing, the child underwent an excisional biopsy at our Department of Plastic and Reconstructive Surgery, at the Policlinico of Foggia. Subsequently, two independent anatomic pathology groups examined the specimen. Definitive diagnosis was made only after careful genetic analysis in combination with supporting histological and immunohistochemical examinations. This clinical case shows how during the pandemic we have been facing advanced forms of tumours, compared to the previous period and highlight show an interdisciplinary and multicenter collaboration allowed a quick diagnosis of certainty, demonstrating the utility of molecular pathology as a fundamental aid in clinical/surgical practice. © 2022 The Authors

Identification of shared genes and possible therapeutic target between systemic lupus erythematosus and COVID-19

Background/purpose: Coronavirus disease 2019 (COVID-19) has led to a rapid increase in mortality worldwide. Systemic lupus erythematosus (SLE) was a high-risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) infection, Whereas the molecular mechanisms underlying SLE and CVOID-19 are not well understood. This study aims to discover the common molecular mechanisms and genetic biomarkers of SLE and COVID-19, providing new ideas for the treatment of COVID-19. Method(s): RNA sequencing data of peripheral blood mononuclear cells (PBMC) from 6 SLE datasets and 8 COVID-19 datasets were obtained from the GEO database. Highly related modular genes associated with COVID-19 and SLE were identified by weighted gene co-expression network analysis (WGCNA). The differentially expressed genes (DEGs) between patients and healthy controls (HCs) were identified by the limma package. Common shared DEGs from COVID-19 and SLE were identified. Cytoscape and MCODE plugin were utilized for exploring the protein-protein interaction network (PPI) and identifying shared hub genes. Potential biological functions and pathways were also explored from the common DEGs. For better analysis of detailed biological mechanisms, both xCell algorithm and the cMap in CLUE (https://clue.io/) were utilized for discovering immune cell infiltration and predicting potential drugs that negatively regulate the highly expressed genes. Result(s): With identified 498 up-regulated common DEGs in SLE and COVID-19 related genes, total 11 and 13 gene modules of SLE and COVID-19 were identified espectively After overlapping differential genes, the final intersection gene set contains 218 genes. The PPI, especially the functional subnet module consists of upregulated genes by MCODE showed a great deal IFN related genes involved in the regulation of immunity. GO biological processes also showed possible functions were defense response to virus and mitotic cell cycle. Moreover, changes of most immune cells were strongly consistent between SLE and COVID-19. CDK inhibitors identified may be more likely to inhibit two diseases. Conclusion(s): Our study examined in detail the common molecular mechanisms of SLE and COVID-19, in which cellular response to cytokine stimulus, like regulating IFN, which might be the key target of both diseases. CDK is associated with the progression of SLE and COVID-19, which may be the potential therapeutic drug for SLE patients with COVID-19 infection.

Sentinel Lymph Node Biopsy in Melanoma Patients a Year after Introduction of COVID-19 Epidemic Restrictions: A Comparison with Pre-COVID Period in the National Referral Melanoma Centre

Aim/Introduction: Since its introduction in March 2020, the COVID-19 epidemic restrictions altered cancer care including melanoma. Shortly thereafter, we adjusted the clinical management of melanoma patients according to epidemicspecific recommendations provided by the multidisciplinary team for melanoma from the National Referral Melanoma Centre (NRMC), designed according to the National Comprehensive Cancer Network (NCCN). Our study aims to determine whether histopathologic features and sentinel lymph node biopsy (SLNB) in melanoma patients have been changed a year after the introduction of COVID-19 epidemic guidelines. Material(s) and Method(s): We retrospectively reviewed data of melanoma patients of stages IA to IIC (AJCC Staging System 8thedition) who underwent SLNB at our NRMC. We compared melanoma patients who had undergone SLNB during the 6-month (March-Aug) pre-COVID-19 period in 2019 with patients operated on during the corresponding period in the COVID-19 era in 2021. Selected patients underwent FDG PETCT before SLNB. After peritumoral injection of 99mTc-nanocolloid, dynamic and static planar imaging and in certain cases followed by SPECT/CT was performed. Result(s): Seventy-eight melanoma patients had undergone SLNB during the specified period in 2021 (Covid-19 group), and 61 patients during the same period in 2019 (pre-COVID-19 group). Among COVID-19 group, the most frequent melanoma location was trunk (57.7% vs. 44.3%), followed by arms (15.4% vs. 14.8%), legs (15.4% vs. 18.0%) and head and neck (11.5% vs. 23%), although the groups did not differ significantly (p=0.256). The pre-COVID-19 and COVID-19 group did not differ with regard to mean age (59.00 vs. 60.68 years, p = 0.525), gender (47.5% vs. 51.3% men, p=0.733), mean tumor thickness (2.63 vs.2.69 mm, p = 0.903), mean mitotic count (5.53 vs. 4.63/mm2 = 0.368) or presence of ulceration (31% vs. 32%, p=1.00). The mean time from primary melanoma excision to SLNB performance was slightly longer in COVID-19 group (54.67 vs.49.98 days, p=0.303). Patients in COVID-19 group more frequently underwent PET-CT before SLNB (17.9 % vs. 14.8%, p=0.653) and less frequently performed SPECT-CT (21.8% vs.29.5%, p=0.329), however without significant difference. The number of patients having tumor-positive SLNs (17.1% vs. 25.4%, p=0.287) and those with residual melanoma (5.1% vs. 4.9%, p=1.000) did not differ between the COVID-19 and pre-COVID-19 group, respectively. Conclusion(s): Besides slight differences in location of primary melanoma, interval to SLNB performance, and SPECT-CT use, we demonstrated that SLNB management and histopathologic features in our melanoma patients followed the pre-pandemic period a year after starting COVID-19 epidemic restrictions.

Enterogenous Cyst and Glioblastoma: A Brief Histopathological Review of Two Uncommon Cystic Lesions of the Central Nervous System

Intracranial cystic lesions are common findings in cerebral imaging and might represent a broad spectrum of conditions. These entities can be divided into nonneoplastic lesions, comprising Rathke cleft cyst, arachnoid cyst, and colloid cyst, as well as neoplastic lesions, including benign and malignant components of neoplasms such as pilocytic astrocytoma, hemangioblastoma, and ganglioglioma. Surgical resection and histological evaluation are currently the most effective methods to classify cysts of the central nervous system. The authors report two uncommon cases presenting as cystic lesions of the encephalic parenchyma-a enterogenous cyst and a glioblastoma-and discuss typical histological findings and differential diagnosis.

Seeing is believing

Frontier optical-imaging modalities exemplified by the lattice light-sheet microscope sets new visualization standards to see, analyze and understand three dimensional processes at diffraction limited resolution and high-temporal precision with unprecedented duration of minutes or hours in the complex and dynamic environment of living cells in isolation and within tissues of an organism. We are also witnessing an artificial intelligence (AI) inspired transforming revolution that is helping set up robust training and inference robust tools aimed to reveal biological insights from these massive data sets. We believe this ability for large-scale imaging with minimal perturbations combined with use of AI methods is ideally suited to support hypothesis-generating research geared towards new discoveries. This talk will illustrate how we uncovered a templating process mediating the formation of nuclear pores during mitosis and unexpected entry pathways leading to infection by SARS-CoV-2 by combined use of these approaches.

How Does Time from Biopsy to Surgery Affect Nodal Status for Patients with Malignant Melanoma?

INTRODUCTION: It is believed that greater time from diagnosis to surgery increases the likelihood of sentinel lymph node positivity for patients with melanoma who present with clinical N0M0 disease. There is a paucity of data, however, on a safe window for surgery, which has become particularly relevant during the COVID-19 pandemic. We sought to determine how the risk of N+ disease changed with increasing time to surgery, and to evaluate what may be a safe window for surgery. METHODS: We performed an IRB approved retrospective review of patients diagnosed with clinical N0M0 malignant melanoma who underwent wide local excision and sentinel lymph node biopsy at two institutions from 1/2018-6/2021. Student's t-test, Wilcoxon-Mann-Whitney, bivariate and multivariable logistic regression analyses were performed where appropriate. RESULTS: There were 437 patients identified, 140 (32%) surgically treated within 30 days, 238 (55%) 31-60 days, and 59 (13%) 60+ days post-diagnosis, 128 (29%) with positive sentinel lymph node(s) (Table with demographics). Time to surgery was not a significant predictor of N+ disease for 0-30 vs 31-60 days (OR 0.72;95% CI 0.46-1.13) or 0-30 vs 60+ days (OR 0.65;95% CI 0.33-1.29). This remained true adjusting for T-stage, mitosis, ulceration, and institution (OR 0.75 95% CI 0.45-1.20, and OR 0.62;95% CI 0.29-1.30, respectively), and when only examining T3-T4 lesions (OR 0.91;95% CI 0.46-1.83 and OR 0.88;95% CI 0.32-2.45, respectively). T-stage expectedly was the greatest predictor of N+ disease (T1 vs T2 OR 3.08;95% CI 1.44-6.59, vs T3 OR 5.89;95% CI 2.64-13.10, vs T4 OR 10.63;95% CI 4.08-27.68). CONCLUSIONS: Increased time from melanoma diagnosis to wide local excision and sentinel lymph node biopsy did not appear to significantly influence final nodal positivity rate in patients who presented with clinical N0M0 disease. These findings warrant further evaluation to determine if it is safe to wait up to 60 days or longer prior to undergoing surgical treatment for malignant melanoma.

Healing Field: Using Alternating Electric Fields to Prevent Cytokine Storm by Suppressing Clonal Expansion of the Activated Lymphocytes in the Blood Sample of the COVID-19 Patients.

In the case of the COVID-19 early diagnosis, numerous tech innovations have been introduced, and many are currently employed worldwide. But, all of the medical procedures for the treatment of this disease, up to now, are just limited to chemical drugs. All of the scientists believe that the major challenge toward the mortality of the COVID-19 patients is the out-of-control immune system activation and the subsequent cytokine production. During this process, the adaptive immune system is highly activated, and many of the lymphocytes start to clonally expand; hence many cytokines are also released. So, any attempt to harness this cytokine storm and calm down the immune outrage is appreciated. While the battleground for the immune hyperactivation is the lung ambient of the infected patients, the only medical treatment for suppressing the hypercytokinemia is based on the immunosuppressor drugs that systemically dampen the immunity with many unavoidable side effects. Here, we applied the alternating electric field to suppress the expansion of the highly activated lymphocytes, and by reducing the number of the renewed cells, the produced cytokines were also decreased. Applying this method to the blood of the COVID-19 patients in vitro showed ∼33% reduction in the average concentration of the three main cytokines after 4 days of stimulation. This method could carefully be utilized to locally suppress the hyperactivated immune cells in the lung of the COVID-19 patients without any need for systemic suppression of the immune system by the chemical drugs.

OBSTRUCTIVE LARGE CELL NEUROENDOCRINE COLON CANCER: CASE REPORT OF A RARE DISEASE

Purpose/Background: Colonic large cell type neuroendocrine carcinoma (LCNEC) is a rare type of neuroendocrine tumor with only 13 reported cases in the literature. Due to their rarity, there is currently no standardized management. Hypothesis/Aim: We present a case of colonic LCNEC presenting with obstruction requiring urgent surgical intervention. Methods/Interventions: A 43-year-old male presented to the emergency department with several days of abdominal pain and constipation for 48 hours. Physical exam revealed diffuse abdominal pain. A computed tomography scan of the abdomen and pelvis was concerning for a distal transverse colon mass causing obstruction and multiple hepatic lesions. (Figure 1, A-C). The patient was taken to the operating room for urgent exploration and was found to have a transverse colonic mass was identified just proximal to the splenic flexure. Resection was performed and a side-to-side anastomosis of the right and descending colon was created with a protective loop ileostomy. Liver lesions were biopsied. Pathologic analysis revealed invasion into the peri-colorectal tissue consistent with a T3 lesion. Lymphovascular (LV) and perineural invasion were also present. Seven out 27 total lymph nodes (LN) were positive for cancer and the hepatic nodule was positive for cancer. Histological analysis revealed large cells with prominent nucleoli, abundant cytoplasm, marked pleomorphism, frequent mitosis, and apoptotic bodies consistent with LCNEC (Figure 1, D). Immunohistochemistry showed that the tumor was positive for AE1/1, CK 20, synaptophysin, and chromogranin A. The Ki-67 index was over 95%. Results/Outcome(s): Postoperatively the patient was started on a regimen of cisplatin and etoposide. He was readmitted during his second cycle of chemotherapy with high ileostomy output, E. coli bacteremia and COVID-19. Repeat imaging showed progression of his disease (Figure 1, E). The patient had a precipitous decline in helath and decided to pursue comfort measures. He had a survival time of 3 months after diagnosis. Limitations: The limitation of this study is that it is a single case. Conclusions/Discussion: NECs account for 0.6% of all colorectal cancers with LCNECs responsible for ~0.2% of NECs. At the time of diagnosis, LV invasion, LN spread, and distant metastases are usually present, which coincides with a median survival of 4-16 months. First line treatment for localized colorectal NECs is primary resection. The National Comprehensive Cancer Network (NCCN) guidelines recommend combined cisplatin and etoposide may be appropriate for locally advanced tumors;however, multiple studies have shown to show no improvement in median survival. Our patient presented with obstruction requiring surgical intervention, which extended the patients life by 3 additional months. Further research to define the best course of treatment for advanced colonic LCNECs will be difficult due to the infrequency of the disease. (Figure Presented).

Oral Epithelium Response of Electronic Cigarette Smoking

Rationale: Smoking electronic cigarettes (e-cigarettes) is increasing in popularity, but little information is available as to the biologic consequences to the cell populations impacted by the e-cigarette smoke. Based on the knowledge that the oral epithelium is the initial site exposed to e-cigarette smoke, the authors assessed the hypothesis that e-cigarette smoking modifies the biology of oral epithelium of healthy e-cigarette smokers. Methods: Oral biopsies of n = 23 healthy nonsmoker controls and n= 24 healthy e-cigarette smokers (e-cigarette smokers for an average of 2.0±1.0 years) matched for age, gender, and ethnicity were compared based on pathology and RNA transcriptome (mRNA and miRNA) using Illumina Hi-Seq 2000 sequencing. The mRNA data were assessed in e-cigarette smokers compared to nonsmokers genome-wide (n = 19,724): genes previously identified as significantly dysregulated in the oral epithelium of e-cigarette smokers vs. nonsmokers (n = 758);genes previously identified as significantly dysregulated in the small airway epithelium of nonsmokers following an acute exposure to e-cigarettes (n = 71);and genes related to the initial steps of COVID-19 infection, including ACE2, the COVID-19 receptor (n = 9). The miRNA of e-cigarette smokers and nonsmokers was compared on a genome-wide basis (n = 1,100 mature and human miRNAs). All comparisons were performed using ANOVA, Benajmini-Hochberg corrected. P value <.05 was considered significant. Results: The morphology of the epithelium and lamina propria in e-cigarette smokers was normal, with no thickening of the epithelium, dysplasia, basilar hyperplasia, dyskeratosis, and no abnormal vascularity or inflammatory infiltration. The basilar layer in e-cigarette smokers appeared normal, with normal mitotic activity and no nuclear pleomorphism. Assessment of the transcriptome, both on mRNA and miRNA levels, based on all gene lists did not identify any genes significantly modified in the oral epithelium of e-cigarette smokers compared to nonsmokers. Conclusion: The oral epithelium pathology and transcriptome of e-cigarette smokers are not modified in response to e-cigarette smoking.