Case Report of Succesful Multidisiplinary Treatment for Patient with Metastatic Lung Cancer and Relapsed/Refractory Chronic Lymphatic Leukemia/Small Lymphocytic Lymphoma

Introduction: Croatian National Cancer Registry of Croatian Institute for Public Health reported that in year 2020 lung cancer was the second most common cancer site diagnosed in men with 16% and the third most common in women with 10% incidence among all cancer sites. Unfortunatelly lung cancer has the highest mortality in both men and women. Haematological malignancies had 7% share in all malignancies in both male and female cances cases. In 2020 190 newly diagnosed cases of lymphatic leukemia in men and 128 cases in women were reporeted, meaning 1.5 and 1.2% of all malignancies, respectively. Chronic lymphatic leukemia (CLL) is an advanced age disease and incidence increases with age. Impaired immunity, T and B cell dysfunction in CLL, chromosomal aberations, long-term immunosuppressive therapy and genetic factors can all cause secondary malignancies. Co- occurence of solid tumors and CLL is very rare. Although patiens with CLL have an increased risk of developing second primary malignancies including lung carcinoma, the data about their clinical outcomes are lacking. Parekh et al. retrospectively analyzed patients with simultaneous CLL and lung carcinoma over a 20-year period, and they found that ~2% of patients with CLL actually developed lung carcinoma. The authors claimed that up to 38% of patients will also develop a third neoplasm more likely of the skin (melanoma and basal cell carcinoma), larynx (laryngeal carcinoma) or colon. Currently there are no specific guidelines for concurrent CLL and non-small cell lung carcinoma (NSCLC) treatment. Usually, when the tumors are diagnosed simultaneously, treatment is based to target the most aggressive malignancy, as the clinical outcomes depend on the response of the tumor with the poorest prognosis. For this reason, a multidisciplinary approach is mandatory. Case report: A patient with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation was diagnosed in 2019 (at the age of 71) with B chronic lymphocytic leukemia with bulky tumor (inguinal lymph nodes 8x5 cm), stage B according to Binet, intermediate risk. He was treated with 6 cycles of chemoimmunotherapy (rituximab/cyclofosfamid/fludarabine). In 10/2019 remission was confirmed, but MSCT described tumor in the posterior segment of upper right lung lobe measuring 20x17 mm and bilateral metastases up to 11 mm. Bronchoscopy and biopsy were performed, and EGFR neg, ALK neg, ROS 1 neg, PD-L1>50% adenocarcinoma was confirmed. He was referred to Clinical Hospital Center Osijek where monotherapy with pembrolizumab in a standard dose of 200 mg intravenously was started in 01/2020. Partial remission was confirmed in October 2020. Immunotherapy was discontinued due to development of pneumonitis, dysphagia and severe weight loss (20kg), but without radiologically confirmed disease progression. At that time he was referred to our hospital for further treatment. Gastroscopy has shown erosive gastritis with active duodenal ulcus, Forrest III. Supportive therapy and proton pump inhibitor were introduced. After complete regression of pneumonitis, improvement of general condition and resolution of dysphagia, no signs of lung cancer progression were found and pembrolizumab was reintroduced in 12/2021. Hypothyroidism was diagnosed in 01/2021 and levothyroxine replacement ther apy was started. In 03/2021 he underwent surgical removal of basal cell carcinoma of skin on the right temporal region with lobe reconstruction. From 02/2021, when pembrolizumab was reintroduced, regression in tumor size was continously confirmed with complete recovery of general condition. He was hospitalized for COVID 19 infection in 09/2021, and due to complications pembrolizumab was discontinued till 11/2021. Lung cancer immunotherapy proceeded till 11/2022, when Multidisciplinary team decided to finish pembrolizumab because of CLL relapse. CLL was in remission till August 2022 when due to B symptoms, lymphcytosis, anemia and generalized lymphadenopathy, hematological workup including biopsy of cervical lymph node was performed and CLL/SLL relapse was confirmed. Initially chlorambucil was introduced, but disease was refractory. Based on cytogenetic test results (IGHV unmutated, negative TP53) and due to cardiovascular comorbidity (contraindication for BTK inhibitors) venetoclax and rituximab were started in 01/2023. After just 1 cycle of treatment normal blood count as well as regression of B symptoms and peripheral lymphadenopathy occured, indicating the probability of complete disease remission. In our patient with metastatic lung adenocarcinoma excellent disease control is achieved during 41 month of treatment in first line setting. Furthermore, relapsed/refractory CLL/SLL is currently in confirmed remission. Conclusion(s): Successful treatment of patients with multiple primary malignancies is based on multidisciplinarity, early recognition and management of side effects, treatment of comorbidities with the aim of prolonging life, controlling symptoms of disease and preserving quality of life.

THE IMPACT OF THE SARS-COV-2 PANDEMIC ON THE EPIDEMIOLOGICAL PICTURE AND CHARACTERISTICS OF COLORECTAL CANCER - A RETROSPECTIVE ANALYSIS OF THE DEPARTMENT OF ONCOLOGY AND RADIOTHERAPY, UH of SPLIT, FOR THE YEAR 2020 IN COMPARISON TO PRE PANDEMIC 2017

Introduction: Colorectal cancer is the third most common cause of cancer in the world, after lung and breast cancer, while in Croatia is the most common malignant disease. Among the EU members, Croatia ranks ninth in terms of the incidence of colon cancer and a high second place by mortality. Since 2007, Croatia has had a National Colon Cancer Early Detection Program, but the response rate is still very low - 36% (25-52% depending on county and year).2 Despite the prevention program, approximately 13% of patients in Croatia is initially diagnosed with metastatic disease.1 According to the results of the CONCORD 3 study3, Croatia is at the bottom of the five-year survival (48%) compared to some other western countries (up to 71%) in the world. Method(s): A retrospective analysis was conducted at the Clinic of Oncology and Radiotherapy, CHC Split. Patients with newly diagnosed colorectal adenocarcinoma enrolled in the clinic from January 1, 2020 to December 31, 2020 were processed. The data were analyzed using descriptive statistics methods, with the use of Microsoft Excel tools. Result(s): A retrospective analysis of the medical history identified 269 patients (compared to 387 in 2017) presented at the multidisciplinary team (MDT) of CHC Split who were diagnosed with colorectal adenocarcinoma in 2020. All patients were presented to the MDT before starting the treatment. The median age of patients was 66 years, and the youngest patient was 22 years old. Patients from other counties who did not undergo the entire treatment/monitoring in our institution were excluded from the analysis. 52 patients (19.3%) were diagnosed in the metastatic stage of the disease, in stage 0 4 patients (1.5%), in stage I 32 (12%), in stage II 91 (34%), and in stage III 88 (33%). In 2 patients, the stage couldn't be precisely determined. There is a significant decrease in the number (81 in 2017 and 52 in 2020) but no percentage wise (20.9% in 2017 and 19.3% in 2020) of patients diagnosed with de novo metastatic colorectal cancer compared to the previous analysis from 2017, when 81 of them were detected. Patients diagnosed with metastatic disease were mostly in good general condition: ECOG 0 status 21 patients (40.3%), ECOG 1 24 patients (46.2%), ECOG 2 7 patients (13.5%), while no patient was ECOG status 3 or 4. 32 (57.7%) patients had a left-sided tumor, while 20 (42.3%) patients had a right-sided tumor. Conclusion(s): The results of our retrospective analysis showed a significant decrease in the number of patients compared to previous years. The effect of the smaller number of newly diagnosed patients will be analyzed and the real consequences will be seen, however, the appearance of patients in the later stages of the disease is to be expected.

Primary signet ring cell carcinoma of the male urethra.

Malignant tumours of the male urethra are rare and commonly present at an advanced stage. The most common type of urethral cancer is urothelial carcinoma, followed by squamous cell carcinoma. Less than 5% of urethral cancers are adenocarcinoma. We report a young male with signet ring cell carcinoma of the membranous urethra who presented with recurrent lower urinary tract symptoms. Although he was initially treated for a urinary tract infection, the correct diagnosis was made with an appropriate imaging workup. He underwent radical urethrectomy with total pelvic exenteration with bilateral extended pelvic lymph node dissection. Ileal conduit and colostomy were performed as urinary and bowel diversions, respectively. The patient received adjuvant chemotherapy, however, succumbed to COVID-19 8 months after the procedure. This case has been presented to highlight the high index of suspicion required to diagnose this rare malignancy.

Commencing colorectal cancer screening at age 45 years in U.S. racial groups.

Screening for colorectal cancer (CRC) is cost-effective for reducing its mortality among the average-risk population. In the US, CRC incidence and mortality differ among racial/ethnic groups, with non-Hispanic Blacks (NHB) and American Indian/Alaska Natives showing highest incidence and mortality and earlier presentation. Since 2005, some professional societies have recommended CRC screening for NHB to commence at 45 years or earlier; this was not implemented due to lack of recommendation from key groups that influence insurance payment coverage. In 2017 the highly influential U.S. Multi-Society Task Force for Colorectal Cancer recommended screening to commence at 45 years for NHB; this recommendation was supplanted by data showing an increase in early-onset CRCs in non-Hispanic Whites approaching the under-50-year rates observed for NHB. Subsequently the American Cancer Society and the USPSTF recommended that the entire average-risk population move to commence CRC screening at 45 years. Implementing screening in 45-49-year-olds has its challenges as younger groups compared with older groups participate less in preventive care. The US had made extensive progress pre-COVID-19 in closing the disparity gap for CRC screening in NHB above age 50 years; implementing screening at younger ages will take ingenuity, foresight, and creative strategy to reach a broader-aged population while preventing widening the screening disparity gap. Approaches such as navigation for non-invasive and minimally invasive CRC screening tests, removal of financial barriers such as co-pays, and complete follow up to abnormal non-invasive screening tests will need to become the norm for broad implementation and success across all racial/ethnic groups.

A Challenging Case of Metastatic Non-Small Cell Carcinoma of the Lung.

Primary lung carcinoma with distant metastasis is a life-threatening diagnosis that presents many unique challenges due to the severity of the disease at the time of presentation. We investigated a life-threatening primary lung carcinoma with distant metastasis in a 73-year-old transgender woman, which posed unique challenges due to the advanced stage of the disease at presentation. The patient exhibited nonspecific musculoskeletal and neurological symptoms resulting from the primary lung carcinoma metastasizing to her liver, bones, and brain. We evaluated various imaging modalities that aided in determining the disease's severity and identifying complications related to metastasis. Although these efforts can offer symptomatic relief, the overall prognosis remains poor when metastasis spreads to multiple organs, particularly the brain, as remission may no longer be attainable.

Pseudomyxoma peritonei - Jelly Belly: To Tap or Not

Introduction: Mucinous adenocarcinomas of the appendix are defined as epithelial neoplasms often causing cystic dilation of the appendix due to accumulation of gelatinous material. Pseudomyxoma peritonei is an extremely rare complication of appendiceal mucinous adenocarcinomas with an estimated incidence rate of one to 2 people per million per year. Here-in we present a unique case of enterocutaneous fistula formation secondary to percutaneous biopsy of an enlarging omental mass in the setting of pseudomyxoma peritonei. Case Description/Methods: A 50-year-old male with a past medical history of metastatic appendiceal mucinous adenocarcinoma presented to the ED with abdominal pain, nausea, and vomiting. The patient had previously undergone 2 debulking surgeries over the past 2 years prior to admission and has since been on FOLFOX therapy. Due to the COVID pandemic, the patient did not follow-up in the 2 years period from previous admission. A CT scan was now notable for a new enlarging omental mass despite the recent debulking surgery. Given the enlarging mass, a decision was made to pursue a percutaneous biopsy of the mass due to concern for potential new malignancy. Two weeks after the biopsy, the patient presented to our facility due to worsening erythema and drainage from the biopsy site. The patient met SIRS criteria, thus broad-spectrum antibiotics were initiated. A CT of the abdomen and pelvis with oral and IV contrast was obtained, which demonstrated a 9 cm abscess or continuation of intra-abdominal multilocular cystic lesion/ pseudomyxoma peritonei. The surgical team was consulted. Patient had 100 cc of purulent and mucinous drainage expressed from biopsy site. The patient was then placed for transfer to a hospital capable of advanced surgical management for evaluation and potential resection of fistula formation. The patient had a successful reductive surgery and intraoperative chemotherapy (Figure). Discussion(s): Given the rarity of pseudomyxoma peritonei, appropriate management is not always straightforward. A literature review yielded no previous reports of enterocutaneous fistula as a complication of percutaneous drainage in the setting of pseudomyxoma peritonei. We recommend that percutaneous drainage not be sought in individuals with this diagnosis due to potential for fistula formation.

A Case Series of Kodamaea Ohmeri Infection: The Hidden Threat Unleashed

Intro: Kodamaea ohmeri, previously known as Pichia ohmeri, is an ascomycetous yeast that has emerged as an important cause of fungemia in immunocompromised patients. During the anamorphic stage this organism is also known as Candida guillermondii var. membranaefaciens. Method(s): We report five cases of Kodamaea ohmeri encountered from multicenter in Malaysia. Antifungal agent of choice will be discussed based on literature review. Finding(s): The cases were: (1) a contaminated peritoneal fluid in an adult patient on peritoneal dialysis;(2) a 60-year-old man with infected diabetic foot isolated K. ohmeri from a bone sample. Both cases discharged well without active antifungal fungal therapy. We observed fatality cases involving (3) an old man with underlying gastric adenocarcinoma who complicated with catheter- related bloodstream infection caused by K. ohmeri;(4) a patient with ventilator- associated pneumonia and septicaemic shock secondary to perforated terminal ileum;(5) and a severely ill COVID-19 stage 5b patient who passed away due to systemic fungaemia caused by K. ohmeri. Discussion(s): All three fatal cases received either amphotericin B or caspofungin as active antifungal agent. Literature evidence has shown that 40% of patient met demise despite on active antifungal agent, suggesting that currently no definitive antifungal agent proven to be a superior treatment option for K. ohmeri infection. Removal of indwelling medical device combined with antifungal therapy has favorable clinical outcome. Conclusion(s): Therefore, K. ohmeri infection in severely ill patients should be considered as a critical condition. Potential of alternative antifungal combinations need to be explored for an effective treatment option.Copyright © 2023

Barking up the Wrong Hepatobiliary Tree: A Case of Elevated CA19-9

Introduction: Incidental elevations in Carbohydrate Antigen 19-9 (CA19-9) can trigger extensive medical evaluations for malignancy. Though classically associated with pancreatic cancer, CA19-9 is a nonspecific manifestation of multiple benign and malignant disease processes. Case Description/Methods: An asymptomatic, healthy 50-year-old female presented to primary care for an elevated CA19-9 level obtained for pancreatic cancer screening in Asia in 2019. Her evaluation in 2019 included abdominopelvic CT and magnetic retrograde cholangiopancreatography, which were normal. She was offered endoscopic ultrasonography to further evaluate pancreaticobiliary etiologies but was lost to follow-up amid the COVID-19 pandemic. She returned to the US in 2021, and basic laboratory testing and routine cervical cancer screening were performed. She was referred to Gastroenterology (GI) for further evaluation. Cervical cytology revealed atypical endometrial cells, and endometrial biopsy by gynecology was concerning for gastric-type endocervical adenocarcinoma. Transvaginal ultrasound revealed a thickened endometrial stripe, and pan CT revealed duodenal thickening, for which GI performed bidirectional endoscopy without significant abnormalities and no pancreatic or metastatic disease. Repeat CA19- 9 increased. She was referred to gynecologic oncology, where cervical biopsy and pelvic MRI confirmed an endocervical mass. She was diagnosed with Stage IIB gastric-type endocervical adenocarcinoma and underwent hysterectomy and left salpingectomy with adjuvant chemoradiation. Discussion(s): CA19-9 is synthesized in multiple organ systems. Elevations in asymptomatic patients are rarely predictive of pancreatic cancer but may expose patients to unnecessary testing and inadvertent harms without identifying malignancy. Thus, CA19-9 is not recommended for pancreatic cancer screening. Incidental elevations do warrant repeat testing. Benign processes will yield stable or decreasing levels, while rising levels suggest progressive or malignant processes. If concern for pancreatic malignancy is low, a reasonable investigation includes chest X-ray or CT, metabolic studies, hemoglobin A1c, liver and thyroid function panels, abdominopelvic CT or gynecologic cancer evaluation, and any other age-indicated cancer screening. In this case, prior imaging studies suggested low concern for pancreatic cancer. Her subsequent evaluation aligned with this suggested work-up and revealed gynecologic cancer as the ultimate etiology for her elevated CA19-9.

cGAS-STING PATHWAY LIMITS SARS-CoV-2 REPLICATION IN ACE2+ AIRWAY CELL LINES

Background: We previously screened 10 human lung and upper airway cell lines expressing variable levels of endogenous ACE2/TMPRSS2. We found that H522 human lung adenocarcinoma cells supported SARS-CoV-2 replication independent of ACE2, whereas the ACE2 positive cell lines were not permissive to infection. Type I/III interferons (IFNs) potently restrict SARS-CoV-2 replication through the actions of hundreds of interferon-stimulated genes (ISGs) that are upregulated upon IFN signaling. Here we report that a number of ACE2 positive airway cell lines are unable to support SARS-CoV-2 replication due to basal activation of the cGAS-STING DNA sensing pathway and subsequent upregulation of IFNs and ISGs which restrict SARS-CoV-2 replication. Method(s): SARS-CoV-2 WT strain 2019-nCoV/USA-WA1/2020 viral replication was detected through analysis of cell associated RNA. RNA sequencing was used to study the basal level of genes in the type-I IFN pathway in the 10 cell lines, which was further validated by western blotting and qRT-PCR. A panel of 5 cell lines, with varying expression levels of ACE2 and TMPRSS2, were pre-treated with Ruxolitinib, a JAK1/2 inhibitor. A siRNA-mediated screen was used to determine the molecular basis of basally high expression of ISGs in cell lines. CRISPR knockout of IFN-alpha receptor and cGAS-STING pathway components was conducted in parallel Results: Here we show that higher basal levels of IFN pathway activity underlie the inability of ACE2+ cell lines to support virus replication. Importantly, this IFN-induced block can be overcome by chemical inhibition and genetic disruption of the IFN signaling pathway or by ACE2 overexpression, suggesting that one or more saturable ISGs underlie the lack of permissivity of these cells. Ruxolitinib treatment increased SARS-CoV-2 RNA levels by nearly 3 logs in OE21 and SCC25. Furthermore, the baseline activation of the STING-cGAS pathway accounts for the high ISG levels and genetic disruption of the cGAS-STING pathway enhances levels by nearly 2 and 3 logs of virus replication in the two separate ACE2+ cell line models respectively. Conclusion(s): Our findings demonstrate that cGAS-STING-dependent activation of IFN-mediated innate immunity underlies the inability of ACE2+ airway cell lines to support SARS-CoV-2 replication. Our study highlights that in addition to ACE2, basal activation of cGAS-STING pathway, IFNs and ISGs may play a key role in defining SARS-CoV-2 cellular tropism and may explain the complex SARS-CoV- 2 pathogenesis in vivo.

EBUS audit: assessing the diagnostic performance of the service at UHL

Introduction: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an important diagnostic procedure in the lung cancer pathway. False-negative or inadequate sampling can lead to inaccurate staging or delay in diagnosis. This study was conducted to assess the performance of the Cancer EBUS service at a tertiary hospital. Method(s): We conducted a retrospective analysis of patients who underwent EBUS-TBNA for suspected cancer between 1st June 2021 to 31st May 2022. Request forms, CT reports, EBUS reports and pathology reports were reviewed for analysis. Result(s): 205 EBUS-TBNA procedures were performed. All patients had an appropriate staging CT prior to procedure. The mean time to test was 10.5 days (7.4). 77 (38%) had tests within 7 days of request. 293 lymph nodes and 10 mass lesions were sampled. The mean time to pathological results being received was 2.9 days (1.8). Final histology showed 39 (19%) cases of lung adenocarcinomas, 3 (1%) lung non-small cell carcinomas, 25 (12%) lung squamous cell carcinomas, 25 (12%) small cell cancers, 4 (2%) lung NOS, 3 (1%) pulmonary carcinoid, 2 (1%) lymphoma, 12 (6%) other cancers, 12 granulomata and 1 thyroid tissue (6%). 43 (21%) cases showed lymphoid tissue and 28 (14%) were reported as inadequate. No samples were taken in 8 cases (4%). Adequate tissue for predictive marker testing was available in 93% (66) of cases of non-small cell lung cancer (NSCLC). Complications were encountered in 9 cases (4%). Only 3 cases (1.5%) required any form of intervention. [Figure presented] Conclusion(s): Our data provides assurance of safety while also highlighting specific areas for attention regarding performance and time to test that can be addressed and our sensitivity was comparable to national standards. The increased waiting times may be partly related to COVID-19 precautions and will require reauditing at a later date. Disclosure: No significant relationships.Copyright © 2023 Elsevier B.V.

Histomorphological Spectrum of Lung Lesions at Autopsy-A Tertiary Care Centre Experience

Background and aims: A wide variety of pathological conditions involve the lungs. In autopsy, the lungs are examined for disease, injury and other findings suggesting cause of death or related changes.Aims & Objectives: The present study aimed to study the histomorphological spectrum of lung lesions at autopsy and to assess the frequency of different types of lesions;and to associate histomorphological changes with cause of death.Material and Methods: It was a one-year observational study conducted in the Department of Pathology, Govt. Medical College, Jammu. Lung tissue pieces from all medicolegal autopsies received were fixed, examined grossly, processed;paraffin embedded sections obtained were stained with Hematoxylin and Eosin stain and examined under microscope. Findings were recorded and tabulated. Result(s): Out of 264 cases, males were predominantly affected (84%);median age was 38 years. The various changes observed were congestion (68%), edema (45.4%), pneumonia (5%), granulomatous inflammation (3%), diffuse alveolar damage (1.5%), haemorrhage (14.4%), interstitial changes (60%), malaria (0.4%) and malignancy (0.4%). Natural deaths were the commonest cause (75, 28%) followed by asphyxial deaths (65, 24.6%). Conclusion(s): Histopathological examination of lung autopsies highlights many incidental findings, establishes underlying cause of death, serves as a learning tool and also holds scope for detection of newer diseases.Copyright © 2023 JK Science.

7th Turkey in vitro Diagnostics (IVD) Symposium

The proceedings contain 75 papers. The topics discussed include: development of different product groups in the cleaning industry with synthesized nanosilver;investigation of the antimetastatic potential of thymbra spicata in human breast adenocarcinoma cells combined with standard chemotherapy;the effect of toll-interancing protein on inflammatory status of hepatocellular carcinoma cell line;surgery and inflammation: surgical inflammation;biochemistry of inflammation;its mediators and activities;pathophysiology of inflammation;classic and new biomarkers of inflammation;thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress;metabolic shift of the kynurenine pathway in inflammatory conditions;and evaluation of HBA1C level in patients with COVID-19.

Pulmonary artery resection and reconstruction in locally advanced lung cancer with moderate hemoptysis

Lobectomy with pulmonary artery (PA) angioplasty in locally advanced lung cancer is an alternative to pneumonectomy. It is feasible, oncologically effective and the procedure of choice in patients with recurrent hemoptysis and limited pulmonary reserves. We present a case of a successful left upper lobectomy with PA resection and reconstruction by an autologous pericardial patch.Copyright © 2022 EDIZIONI MINERVA MEDICA.

A Case Report Of The Effects Of Chemotherapy On Post-heart-transplant Gene Expression Profiling

Introduction: Malignancies are a major complication of heart transplant (HT). Noninvasive surveillance after HT using gene expression (GEP) profiling and donor derived cell free DNA (dd-cfDNA) are noninferior to biopsy and are widely utilized. The interpretation of % dd-cfDNA, is not well understood in malignancies with a conceptual increase in the recipient fraction. The effect of chemotherapy on GEP in the setting of post-HT surveillance has not been described to the best of our knowledge. Hypothesis: Induction of chemotherapy will cause global transcriptional reduction in GEP. Method(s): GEP was performed with AlloMap (AM, CareDx), which evaluates expression levels of 11 mononuclear cell genes, involved in lymphocyte activation, T-cell priming, cell migration, hematopoietic proliferation, steroid sensitivity, and platelet activation. Scores range from 0-40, higher scores have a stronger correlation with rejection. At our center a total of 995 draws were analyzed from 2019-2022. In parallel dd-cfDNA, which informs about graft injury was analyzed using AlloSure (AS, CareDx). Case Events: A 71-year-old male HT recipient for nonischemic cardiomyopathy and no rejection history was diagnosed with metastatic gastric adenocarcinoma at 16 months post-HT. Following diagnosis, mycophenolic acid was stopped, prednisone 5 mg was started, and tacrolimus trough goal was gradually lowered to 4-6 given infectious complications. Palliative chemotherapy with folinic acid, fluorouracil (5-FU), oxaliplatin (FOLFOX) was initiated at 18 months post-HT with planned dose reduction of oxaliplatin and holding of 5-FU bolus to reduce risk of myelosuppression given comorbidities. Oxaliplatin was stopped at 18 months post HT. Due to COVID he last received 5-FU at 33 months post-HT. Graft function remained stable and DSA negative. At 36 months post-HT, he developed a bowel obstruction without surgical options for interventions and expired shortly thereafter. Result(s): With initiation of prednisone and following chemotherapy there was a drastic decrease in AM scores (Fig. A). Steroid therapy led to an 18% decline in AM scores, the greatest decrease occurred with chemotherapy, with 67% decline from the mean when compared to all center patients (Fig B). Dd-cfDNA levels remained stable during the course aside from one early elevation. Conclusion(s): To the best of our knowledge this is the first published case on the effect of chemotherapy on GEP profiling in the setting of post-HT surveillance. This case advises caution when interpreting GEP in the setting of chemotherapy showing great reduction in GEP scores. While dd-cfDNA levels remained relatively stable after malignancy diagnosis and treatment initiation further studies will need to inform on the use of both GEP and dd-cfDNA in these patients.Copyright © 2022

Changes in demographic and smoking history trends in patients referred to a London thoracic malignancy specialist centre between 2010-2021: The Guy's Cancer Centre experience

Background In the UK it is estimated that 10-15% of lung cancer cases occur in never-smokers. This study demonstrates the changes of the demographic characteristics, including the smoking status, of all the patients referred to the thoracic malignancy unit at Guy's Cancer Centre, South East London, between 2010 and 2021. Methods We included patients with a documented ICD10 diagnosis of bronchus and lung malignancy who were referred to Guy's thoracic malignancy unit from 2010 until 2021. A total of 6861 patients with a diagnosis of lung cancer were identified. We collected baseline demographic and clinical characteristics, including smoking status and socio-economic status for all the patients. Descriptive statistics were utilised to highlight the dynamic changes over the years of the referred patients. Results The number of referrals per year remained overall stable from 2010 until 2019, with a decrease in the number of referrals in 2020 and 2021, most likely due to the COVID-19 pandemic. We observed a gradual increase in the percentage of never smokers among the lung cancer patients: 5%, 8%, 10% and 13% of the referred patients were never smokers in the years 2010, 2015, 2018 and 2021 respectively. Median age remained stable across the years (range 68-71 years). Male percentage was 56%, 55%, 53% and 53% in 2010, 2015, 2018 and 2021 respectively. From the patients that we had a documented ethnic background the proportion of White/Black/Asian/Other or Mixed ethnicity remained stable across the years with a median 87%, 7%, 3%, and 3% respectively. The most common histological diagnosis was adenocarcinoma, followed by squamous cell carcinoma and small cell lung carcinoma. Conclusions The proportion of never-smoking to smoking related lung cancer has gradually increased between 2010 and 2021. There was little variability in age, sex and ethnic background. Never-smoking lung cancer is a distinct biological entity, therefore, further research should focus on the understanding of the aetiology and the risk factors leading to the development of lung cancer, in the absence of a history of tobacco exposure. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

Cribriform adenocarcinoma of the minor salivary glands: a case report.

BACKGROUND: Polymorphous adenocarcinoma is the third most common malignant salivary gland tumor. Within polymorphous adenocarcinoma, cribriform adenocarcinoma of salivary glands is a rare subtype and resembles papillary thyroid carcinoma histopathologically. Diagnostically, cribriform adenocarcinoma of salivary glands is challenging for pathologists and surgeons alike as initial presentation and cytologic nuclear features can be easily confused with papillary thyroid carcinoma arising from a thyroglossal duct remnant or lingual thyroid. CASE PRESENTATION: A healthy 64-year-old Caucasian woman presented to a community otolaryngologist with a 4-year history of progressive postnasal drip, globus sensation, and eventual dysphonia. Flexible fiberoptic laryngoscopy showed a large, smooth, vallecular lesion filling the oropharynx. Computed tomography imaging of the neck showed a rounded heterogeneous mass centered within the right aspect of the oropharynx measuring 4.2 × 4.4 × 4.5 cm. Fine needle aspiration biopsy was suspicious for papillary carcinoma due to microscopic findings of malignant cells, nuclear grooves, and a powdery chromatin pattern. In the operating room, the tumor was resected en bloc using a lateral pharyngotomy approach with partial resection of the right lateral hyoid. A limited cervical lymphadenectomy was performed to facilitate the lateral pharyngotomy approach and two out of three lymph nodes demonstrated regional metastatic disease. Nuclear grooves, nuclear membrane notching, and occasional intranuclear pseudoinclusions were identified, which are overlapping histopathological characteristics of papillary thyroid carcinoma and cribriform adenocarcinoma of salivary glands. It was negative for thyroglobulin and thyroid transcription factor-1, which was in keeping with cribriform adenocarcinoma of salivary glands rather than papillary thyroid carcinoma. CONCLUSION: It is difficult to distinguish cribriform adenocarcinoma of salivary glands from papillary thyroid carcinoma solely by cytology, and the distinct characteristics of regional lymph node metastasis coupled with nuanced histologic differences should be emphasized in the evaluation of patients presenting with neck lymphadenopathy and an unknown primary or tongue mass. If sufficient fine needle aspiration biopsy material is available, thyroid transcription factor-1, thyroglobulin, or molecular testing may prove useful in differentiating cribriform adenocarcinoma of salivary glands from papillary thyroid carcinoma. A misdiagnosis of papillary thyroid carcinoma may lead to inappropriate treatment including unnecessary thyroidectomy. Therefore, it is critical for both pathologists and surgeons to be aware of this uncommon entity to avoid misdiagnosis and subsequent mismanagement.

The impact of the COVID-19 pandemic on delay in diagnosis and management of lung cancer in developing countries

Introduction: The COVID-19 pandemic has caused an overload within health care structures in Tunisia, impacting negatively on the management of other pathologies. In this study, we estimated the impact of the COVID-19 pandemic on delay in diagnosis and management of lung cancer in a Department of Pulmonology in Tunisia. Method(s): A retrospective study including patients with lung cancer managed between January 2019 and December 2021 in the Pulmonology IV Department of Abderrahmane Mami Hospital. The patients were divided into two groups: Group 1(G1):(n= 59) included patients diagnosed before Covid-19 pandemic (January/December 2019). Group 2 (G2): (n =71) diagnosed during the Covid-19 pandemic (march 2020/December 2021). Result(s): One hundred and thirty male patients were included with an average age of 60.8 years. The mean delay between the onset of symptoms and the first consultation was 43.27 days in G1 versus 39.92 in G2 . The mean delay between first consultation and the histological diagnosis was significantly longer in G2 (34.3 days vs 31.85 days in G1;p = 0.037). The most common histological type in both groups was adenocarcinoma. Sixty point six percent of patients of G2 were diagnosed at metastatic stage (vs 47.5 % in G1 ). The mean delay between histological diagnosis and initiation of specific treatment was significantly longer in G2 (60.34 days vs 41.67 days in G1 ;p = 0.014). Conclusion(s): The study demonstrates the significant impact of COVID-19 on diagnostic and therapeutic delays for lung cancer patients in our department. A specific care pathway needs to be created in order to ensure treatment within the optimal deadlines.

Acute ischemic stroke due to floating thrombus of ascending aorta: An acute and subacute complication of SARS-CoV-2 infection

Objective: To describe ischemic stroke due to floating thrombus of ascending aorta occurring as acute and subacute complication of SARS-CoV-2 infection. Material(s) and Method(s): consecutive identification in clinical practice of ischemic strokes secondary to aortic arch thrombosis and history of acute or recent Covid-19 infection. Result(s): two patients had ischemic stroke with evidence of aortic arch thrombosis. The first case had concomitant acute Covid-19 infection, the second had recent Covid-19 infection. Both patients underwent intravenous thrombolysis, and subsequent anticoagulation. One patient died due to cerebral hemorrhage. Discussion and Conclusion(s): aortic arch thrombosis can be an incidental finding in acute ischemic stroke in patients with concomitant and recent COVID-19 disease. However, the infection may lead to thrombosis in non-atherosclerotic vessels and to cerebral embolism. Our findings support active radiological search for aortic thrombosis during acute stroke in patients with acute or recent COVID-19 disease.Copyright © 2022

Immunohistochemical profile of cell cycle control, proliferation and differentiation proteins of the pulmonary atypical alveolar epithelium with COVID-19-induced diffuse alveolar damage as compared to pulmonary [lepidic-growth] adenocarcinoma.

We aim aim to compare immunophenotypic charac-teritics of atypical epithelium (AE) with COVID-19-induced diffuse alveolar damage (DAD) and pulmonary lepidic-growth adenocarcinoma, accounting for cell cycle control, proliferation and differentiation]. Methods. We examined pulmonary tissue specimens from twenty-four fatal cases of CO VID-19-induced acute respiratory damage syndrome confirmed by autopsy (Group 1) and four cases of pulmonary lepidic-growth adenocarcinoma (Group 2). Perpendicular dimensions of 10 nuclei were measured on the H&E slides, means of their sums of products (SPNM) were calculated. We have used p53, Ki67, pi6, p63 antibodies for immunohistochemical staining in each case. We evaluate colour intensity, rate of stained cells of AE and the product of these parameters. We evaluated separately Nuclear and cyto-plasmic staining (couple) and only cytoplasmic staining (cyt) for pi6 expression. We measured proliferative index only at KI-67 stained slides. U-test and Spearman rank correlation test were used for statistical analysis. Results. Expression of p63 was higher in group 1 (p=0.001), while pi6 was more frequently expressed in group 2 (p=0.002). We have found no statistically significant differences (p>0.1) in the p53 and Ki67 expression. Group 1 showed There was negative correlation between the number of days from onset of symptoms and the following variables: Ki67 (r=M).587, p=0.003);SPNM (r 0.406, p=0.049). Conclusion. The present study has shown heterogeneity in levels of cell cycle control expression, proliferation and differentiation of atypical epithelium in the pulmonary lep-idic-growth adenocarcinoma and CO VID-19-induced diffuse alveolar damage.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.