Regional Nodes Research Articles

Self-Tumor Antigens in Solid Tumors Turned into Vaccines by α-gal Micelle Immunotherapy.

A major reason for the failure of the immune system to detect tumor antigens (TAs) is the insufficient uptake, processing, and presentation of TAs by antigen-presenting cells (APCs). The immunogenicity of TAs in the individual patient can be markedly increased by the in situ targeting of tumor cells for robust uptake by APCs, without the need to identify and characterize the TAs. This is feasible by the intra-tumoral injection of α-gal micelles comprised of glycolipids presenting the carbohydrate-antigen "α-gal epitope" (Galα1-3Galβ1-4GlcNAc-R). Humans produce a natural antibody called "anti-Gal" (constituting ~1% of immunoglobulins), which binds to α-gal epitopes. Tumor-injected α-gal micelles spontaneously insert into tumor cell membranes, so that multiple α-gal epitopes are presented on tumor cells. Anti-Gal binding to these epitopes activates the complement system, resulting in the killing of tumor cells, and the recruitment of multiple APCs (dendritic cells and macrophages) into treated tumors by the chemotactic complement cleavage peptides C5a and C3a. In this process of converting the treated tumor into a personalized TA vaccine, the recruited APC phagocytose anti-Gal opsonized tumor cells and cell membranes, process the internalized TAs and transport them to regional lymph-nodes. TA peptides presented on APCs activate TA-specific T cells to proliferate and destroy the metastatic tumor cells presenting the TAs. Studies in anti-Gal-producing mice demonstrated the induction of effective protection against distant metastases of the highly tumorigenic B16 melanoma following injection of natural and synthetic α-gal micelles into primary tumors. This treatment was further found to synergize with checkpoint inhibitor therapy by the anti-PD1 antibody. Phase-1 clinical trials indicated that α-gal micelle immunotherapy is safe and can induce the infiltration of CD4+ and CD8+ T cells into untreated distant metastases. It is suggested that, in addition to converting treated metastases into an autologous TA vaccine, this treatment should be considered as a neoadjuvant therapy, administering α-gal micelles into primary tumors immediately following their detection. Such an immunotherapy will convert tumors into a personalized anti-TA vaccine for the period prior to their resection.

Diagnostic performance of simultaneous PET-magnetic resonance versus PET-computed tomography in oncology with an overview on clinical utility and referral pattern of PET-magnetic resonance: a single institutional study.

PET-magnetic resonance (PETMR) imaging is an upcoming investigative modality with a few installations in Asia and only three in India. PET-Computed tomography (PETCT) is an established diagnostic cornerstone for oncological indications but with limited resolution for small lesions due to low soft-tissue contrast and additional radiation exposure. Our primary objective was to evaluate the diagnostic performance of simultaneous PETMR and PETCT in lesion detection in oncological practice. Secondly to assess the referral pattern and study the clinical utility of PETMR in a university hospital practice. A total of 100 consecutive biopsy-proven cancer patients (breast or lung malignancy with suspected metastases) underwent 18F fluorodeoxyglucose (FDG) PETMR and PETCT for staging as a single injection, double examination protocol. Morphological lesion detection on correlative imaging/histopathology was used as the gold standard. Analysing the referral pattern, a total of 9366 patients underwent simultaneous PETMR imaging for indications in the past 5 years since installation. 18F FDG PETMR detected 100% of primary tumours in breast/lung carcinoma (Ca) patients while PETCT was positive in 96%. Overall accuracy of nodal metastases detection for PETMR and PETCT was 96 and 88%, while for distant metastases the accuracy was 100 and 93%, respectively. FDG PETMR proved more sensitive and specific than PETCT for regional nodal (P = 0.011 and P < 0.001) and distant metastases detection (P = 0.017 and P < 0.001, respectively). Analysing the general referral pattern for PETMR, the majority were oncology referrals (66.5, 33.5%) when compared to nononcological indications. About 66.24% were FDG based, followed by Ga prostate-specific membrane antigen and dodecane tetraacetic acid. The general utility of PETMR was found incremental in better delineation of small lesions especially in head, neck, liver, brain and gynaecological malignancies. In our past 5 years of PETMR practice, we found that simultaneous PETMR is a highly recommended ideal imaging technique for oncological and nononcological indications. It has excellent diagnostic performance with high sensitivity, specificity and accuracy when compared to PETCT in tumour, nodal metastases staging in specific subgroup of breast and lung malignancy patients.

Development and validation of a prognostic nomogram for predicting liver metastasis in thyroid cancer: a study based on the surveillance, epidemiology, and end results database

This study aimed to create a prognostic nomogram to predict the risk of liver metastasis (LM) in thyroid cancer (TC) patients and assess survival outcomes for those with LM. Data were collected from the SEER database, covering TC patients from 2010 to 2020, totaling 110,039 individuals, including 142 with LM. Logistic regression and stepwise regression based on the Akaike information criterion (AIC) identified significant factors influencing LM occurrence: age, histological type, tumor size, bone metastasis, lung metastasis, and T stage (p < 0.05). A nomogram was constructed using these factors, achieving a Cindex of 0.977, with ROC curve analysis showing an area under the curve (AUC) of 0.977. For patients with TCLM, follicular TC, medullary TC, papillary TC, and examined regional nodes were associated with better prognosis (p < 0.001, HR < 1), while concurrent brain metastasis indicated poorer outcomes (HR = 2.747, p = 0.037). In conclusion, this nomogram effectively predicts LM risk and evaluates prognosis for TCLM patients, aiding clinicians in personalized treatment decisions

Regional lymph node changes on breast MRI in patients with early-stage breast cancer receiving neoadjuvant chemo-immunotherapy

Abstract Purpose Establishing breast MRI imaging patterns associated with neoadjuvant immunotherapy is needed to monitor response. We analyzed serial breast MRIs in patients receiving neoadjuvant chemo-immunotherapy on the I-SPY2 clinical trial. Methods Patients with stage 2–3 HER2-negative breast cancer were randomized to weekly paclitaxel (control), weekly paclitaxel and pembrolizumab, or weekly paclitaxel, pembrolizumab and intra-tumoral injection of SD-101, a TLR9 agonist. All patients received AC. Regional lymph nodes were retrospectively evaluated on breast MRI at baseline, 3, 12 and 20 weeks by a single blinded radiologist. MRIs were assessed for development of new regional lymphadenopathy, or increase in the longest diameter or cortical thickness of the largest abnormal regional lymph node. Results Between 12/2015 and 4/2021, a total of 43 patients enrolled in the control (n = 16) and paclitaxel + pembrolizumab ± SD-101 (n = 27) arms. 12 of 27 patients (44.4%) receiving chemo-immunotherapy experienced increased lymphadenopathy within the first 12 weeks compared to 1 of 16 patients (6.3%) in the control group (p = 0.014). Most patients with increased lymphadenopathy were in the SD101/pembro arm (n = 10, p = 0.002). Increased lymphadenopathy was observed despite concomitant decrease in breast tumor size at all time points. 11 of 12 patients with increased lymphadenopathy had pathologically negative nodes at surgery. There was no association between lymphadenopathy and lower residual cancer burden or immune-related toxicity. Conclusions The combination of neoadjuvant paclitaxel and pembrolizumab ± SD101 intratumoral injection was associated with early increases in regional lymphadenopathy on MRI despite decreased breast tumor size. Increased lymphadenopathy was not associated with node positive disease at surgery.

Abstract PR004: Differential gene expression analysis comparing Black and White patients with HPV-positive oropharyngeal squamous cell carcinoma reveals suppressed immune response and higher rates P16/HPV DNA discordance in Black patients

Abstract Background-Human papilloma virus (HPV-positive (+)) oropharynx cancer (OPC) are a distinct neoplastic entity associated with a significant survival advantage compared to HPV- OPCs. The survival advantage is so great that the presence of regional cervical lymph node metastasis is no longer considered an advanced stage III/IV cancer. The survival advantage associated with HPV+ OPC is not the same for Black patients compared to all other races and emerging data now suggests Black patients with HPV+ OPC have survival outcomes similar to White patients with HPV- OPC. We conducted a differential gene expression analysis and high-risk HPV serotyping comparing genomic difference between treatment naïve Black and White patients with HPV+ OPC. Methods: Surgical samples were obtained from Duke, the University of Texas Medical Branch, and the University of Mississippi, through an IRB approved protocol. HPV status determined by p16 immunohistochemistry (IHC). We performed digital spatial profiling and conducted a differential gene expression analysis in 14 Black and 13 White patients using the Nanostring™ Whole Transcriptome Atlas. Morphology markers included CD45, PANCK, and alpha SMA to label lymphocytes, epithelium, and stroma, respectively. A component of the bioinformatics pipeline included conducing a KEGG pathway analysis using pre-ranked test statistics from self-reported Black and White patients HPV+ OPC. The presence of high-risk oncogenic HPV was determined in parallel by RT-PCR (Creative Biogene). P16, CD68 and CD3 expression was measured by IHC using standard techniques. Results: There was a significant decrease in antigen processing and presentation and T-cell receptor signaling pathways in CD45+ lymphocytes (p&amp;lt;0.0002) and B-Cell receptor and chemokine signaling pathways in PANCK+ tumor epithelial cells (p&amp;lt;0.03) in Black patients compared to White patients with HPV+ OPC. There was a significant difference in p16 expression and the absence of HPV DNA in Black patients compared to White patients (p&amp;lt;0.017). 32% of Black patients with p16+ OPC were HPV DNA negative. There was no p16/HPV16 DNA discordance observed in the White patient cohort. Three patients were co-infected with other carcinogenic HPV serotypes (45, 51, and 59) in addition to HPV16 (two Black and one White). CD68 expression, associated with M1-like anti-tumor macrophages, was significantly decreased in Black patients with p16+/HPV16+ OPC, compared to White patients (p&amp;lt;0.017), suggesting alterations in tumor immune response may be important in cancer disparities. Conclusion: The favorable prognosis associated with HPV+ OPC, including recruitment in currently ongoing radiation de-escalation clinical trials cannot be widely applied to all patients with HPV+ OPC and studies addressing racial disparities, HPV/p16 discordance, and predictors of poor response represent a significant health equity gap in the field of OPC disparities. Citation Format: Tammara L. Watts, Katerine Gonzalez, Xiangfeng Shen, Layne Rogers, Nosa Osazuwa-Peters, Gina D. Jefferson, Cecilia G. Clement, Danielle Range, Russel R Kahmke, Walter T Lee, Daniel J. Rocke, Trinitia Y Cannon, Yvonne Mowery, Kouros Owzar. Differential gene expression analysis comparing Black and White patients with HPV-positive oropharyngeal squamous cell carcinoma reveals suppressed immune response and higher rates P16/HPV DNA discordance in Black patients [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr PR004.

Pancreatoduodenectomy after Ivor-Lewis Santi oesophagectomy with gastric tube reconstruction. An European multicentre experience

BackgroundPancreaticoduodenectomy (PD) is the standard surgery to treat tumors and other conditions affecting the head of the pancreas. PD involves the division of the gastroduodenal artery (GDA) and its branches, to allow for complete dissection of lymph nodes. However, PD in patients with prior esophageal resection presents challenges due to altered anatomy and risks compromising gastric tube vascularization. GDA preservation becomes crucial to avoid ischemia, although this may pose oncological risks by potentially leaving behind regional lymph nodes. This article reviews European surgical center experiences and techniques for PD in patients with prior esophageal surgery, focusing on short-term outcomes. MethodsWe have collected all the experiences carried out in European surgical centers and evaluated the techniques applied for PD in patients who had prior esophageal surgery while analyzing short-term outcomes. ResultsEight patients from 5 European centers were identified. Six patients were diagnosed with pancreatic adenocarcinoma, including one borderline case. Intraoperatively, the gastroduodenal artery (GDA) was preserved in all cases, with portal vein reconstruction required in only one instance due to tumor invasion. No ischemia or venous congestion of the gastric tube was observed during the surgical procedure. Post-operative complications that occurred included POPF type C in 1 (12.5 %), PPH type C in 1 (12.5 %). The median number of harvested lymph nodes was 21 [14–24]. with a median of 1.5 positive lymph nodes. R1 resection was present in 62.5 % of cases. ConclusionPerforming pancreaticoduodenectomy subsequent to Ivor Lewis esophagectomy is a technical challenge, but seems feasiable and safe in selected patients. GDA-preserving pancreaticoduodenectomy emerges as a valuable and time-efficient variation of the conventional procedure, it can be considered oncologically appropriate, but studies confirming its long-term impact on radicality are still needed.

Oncological outcomes in patients with residual triple-negative breast cancer after preoperative chemotherapy.

This study aimed to evaluate the clinical outcomes and prognostic implications of regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NAC) in patients with residual triple-negative breast cancer (TNBC). We analyzed 152 patients with residual TNBC who underwent breast-conserving surgery after NAC between December 2008 and December 2017. Most patients (n = 133; 87.5%) received taxane-based chemotherapy. Adjuvant radiotherapy (RT) was administered at a total dose of 45-65 Gy in 15-30 fractions to the whole breast, with some patients also receiving RT to regional nodes. Survival was calculated using the Kaplan-Meier method, and prognostic factors influencing survival were analyzed using the Cox proportional-hazards model. During a median follow-up of 66 months (range, 9 to 179 months), the 5-year disease-free survival (DFS) rate was 68.0%. The 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 83.6%, 72.6%, and 78.7%, respectively. In the univariate analysis, the cN stage, ypT stage, ypN stage, axillary operation type, and RT field were associated with DFS. Multivariate analysis revealed that higher ypT stage (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.00-3.82; p = 0.049) and ypN stage (HR = 4.7; 95% CI 1.57-14.24; p = 0.006) were associated with inferior DFS. Among clinically node-positive patients, those who received RT to the breast only had a 5-year DFS of 73.7%, whereas those who received RNI achieved a DFS of 59.6% (p = 0.164). There were no differences between the DFS and RNI. In patients with residual TNBC, higher ypT and ypN stages were associated with poorer outcomes after NAC. RNI did not appear to improve DFS. More intensive treatments incorporating systemic therapy and RT should be considered for these patients.

Stage IV gastric cancer with microsatellite instability–high achieving long-term survival by gastrectomy after nivolumab as third-line therapy: a case report and literature review

BackgroundThe prognosis for stage IV gastric cancer remains poor; however, the advent of immune checkpoint inhibitors (ICIs) such as nivolumab has increased the number of patients with long-term survival. Patients with microsatellite instability (MSI)–high gastric cancer have been recognized as a highly effective population for ICIs. Herein, we report a patient with MSI–high advanced gastric cancer treated with gastrectomy after the administration of nivolumab as third-line therapy.Case presentationA 73-year-old woman presented with a type 3 tumor in the lower part of the gastric body, which was diagnosed as gastric cancer through biopsy. Staging laparoscopy revealed that the tumor had invaded the pancreas and the posterior lobe of the transverse mesocolon, and disseminated nodules were found near the ligament of Treitz. After 4 courses of S-1 plus cisplatin therapy, laparoscopic gastrojejunal bypass was performed because of difficulty in oral intake. She received S-1 plus oxaliplatin therapy after a gastrojejunal bypass; however, her regional lymph nodes were enlarged. After six courses of paclitaxel plus ramucirumab as second-line chemotherapy, computed tomography (CT) showed exacerbation of peritoneal dissemination; thus, nivolumab was selected as the third-line therapy. The tumor was characterized by MSI–high. At 24 courses, CT and gastroscopy revealed a complete clinical response of the tumor; however, re-growth of the primary tumor was observed at 36 courses. The patient underwent distal gastrectomy with D1 + lymph node dissection, and received S-1 monotherapy as adjuvant therapy for 1 year. No recurrence was noted at 39 months after the surgery.ConclusionsWe report a patient with highly advanced gastric cancer with peritoneal dissemination, which worsened during second-line therapy and was successfully treated with gastrectomy after nivolumab administration as a third-line therapy. MSI–high gastric cancer is a target that should be actively considered for the administration of ICIs, such as nivolumab, and multidisciplinary treatment combined with chemotherapy and gastrectomy, including conversion surgery, can lead to patients’ long-term survival.

Machine learning to predict distant metastasis and prognostic analysis of moderately differentiated gastric adenocarcinoma patients: a novel focus on lymph node indicators.

Moderately differentiated gastric adenocarcinoma (MDGA) has a high risk of metastasis and individual variation, which strongly affects patient prognosis. Using large-scale datasets and machine learning algorithms for prediction can improve individualized treatment. The specific efficacy of several lymph node indicators in predicting distant metastasis (DM) and patient prognosis in MDGA remains obscure. We collected data from MDGA patients from the SEER database from 2010 to 2019. Additionally, we collected data from MDGA patients in China. We used nine machine learning algorithms to predict DM. Subsequently, we used Cox regression analysis to determine the risk factors affecting overall survival (OS) and cancer-specific survival (CSS) in DM patients and constructed nomograms. Furthermore, we used logistic regression and Cox regression analyses to assess the specific impact of six lymph node indicators on DM incidence and patient prognosis. We collected data from 5,377 MDGA patients from the SEER database and 109 MDGC patients from hospitals. T stage, N stage, tumor size, primary site, number of positive lymph nodes, and chemotherapy were identified as independent risk factors for DM. The random forest prediction model had the best overall predictive performance (AUC = 0.919). T stage, primary site, chemotherapy, and the number of regional lymph nodes were identified as prognostic factors for OS. Moreover, T stage, number of regional lymph nodes, primary site, and chemotherapy were also influential factors for CSS. The nomograms showed good predictive value and stability in predicting the 1-, 3-, and 5-year OS and CSS in DM patients. Additionally, the log odds of a metastatic lymph node and the number of negative lymph nodes may be risk factors for DM, while the regional lymph node ratio and the number of regional lymph nodes are prognostic factors for OS. The random forest prediction model accurately identified high-risk populations, and we established OS and CSS survival prediction models for MDGA patients with DM. Our hospital samples demonstrated different characteristics of lymph node indicators in terms of distant metastasis and prognosis.

13-year survival oligometastatic Merkel cell carcinoma: a case report

BackgroundMerkel cell carcinomas are rare, aggressive skin tumors with high metastatic potential and poor prognosis. Their treatment is classically based on surgery with adjuvant external radiotherapy for localized tumors or on immunotherapy or chemotherapy, sometimes associated with radiotherapy, for metastatic stages. Those tumors are highly radiosensitive due to their neuroendocrine and undifferentiated nature, but they usually fail to rapidly respond to treatment.Case presentationWe report the case of a 65-year-old retired female patient of Caucasian (German) origin with locally advanced Merkel cell carcinoma of the buttock, with pancreatic metastases synchronous at diagnosis, treated with local radiotherapy of the right buttock without regional lymph node irradiation followed by a sequential chemotherapy; 1 year later, the patient developed an isolated pancreatic recurrence treated with exclusive radiotherapy. The patient was still alive at 13 years with complete remission.ConclusionExternal radiotherapy can be an effective alternative to surgery for locally advanced or even oligometastatic Merkel cell carcinomas.

Sentinel lymph node biopsy for early stage vulvar squamous cell carcinoma

Background Patients with regional lymph node involvement from squamous cell carcinoma (SCC) of the vulva have a 48% 5-year relative survival. Recently, sentinel lymph node (SLN) biopsy has become a viable alternative to inguinofemoral lymphadenectomy. We sought to identify risk factors for predicting a positive SLN in patients with vulvar SCC. Methods A retrospective review of 29 patients with vulvar SCC was performed from 2016 to 2021 at a tertiary care center. Clinicopathologic data were collected in addition to SLN status, including number of lymph nodes removed. Results The average depth of invasion was 7.9 mm, average tumor size was 1.8 cm, 3 of 23 patients had perineural invasion, and 4 of 23 patients had lymphovascular invasion. One patient who did not map on lymphoscintigraphy and five patients with recurrent vulvar SCC were excluded from final analysis. The average number of SLNs removed was two. One patient had a positive SLN: the depth of invasion was 17 mm, tumor size was 5.1 cm, and lymphovascular invasion was present. Conclusions Most patients with early stage vulvar SCC had a negative SLN biopsy. Further study is needed to determine the patient subset that could avoid SLN biopsy altogether.

Disconnection of alpha oscillations within default mode network associated with memory dysfunction in amnestic MCI

ObjectiveEpisodic memory dysfunction and alterations of functional connectivity (FC) in default mode network (DMN) were found in patients with amnestic mild cognitive impairment (aMCI). However, previous studies were limited in probing certain oscillations within the DMN. This study employed measures of resting-state FC across various oscillations within the DMN to comprehensively examine the FC and its association with episodic memory performance in aMCI. MethodsTwenty-six healthy controls (HC) and 30 patients with aMCI were recruited to perform resting-state magnetoencephalographic recordings. We compared the spectral powers and peak frequency values in each frequency band and FC within the DMN between these two groups. The associations of FC values with memory performance were also examined. ResultsNo significant between-group differences in spectral powers and peak frequency values were observed in the regional nodes. Patients with aMCI exhibited diminished alpha-band FC as compared to HC. Furthermore, lower alpha-band FC between the medial temporal cortex - and the posterior cingulate cortex/precuneus was correlated with poorer memory performance. ConclusionsAberrant DMN connectivity, particularly in the alpha frequency range, might be a neural correlate of episodic memory impairment. SignificanceOur results inform the potential development of brain stimulation in managing memory impairments in aMCI.

Model for detecting metastatic deposits in lymph nodes of colorectal carcinoma on digital/ non-WSI images

IntroductionColorectal cancer (CRC) constitutes around 10% of global cancer diagnoses and death due to cancer. Treatment involves the surgical resection of the tumor and regional lymph nodes. Assessment of multiple lymph node demands meticulous examination by skilled pathologists, which can be arduous, prompting consideration for an artificial intelligence (AI)-supported workflow due to the growing number of slides to be examined, demanding heightened precision and the global shortage of pathologists.MethodThis was a retrospective cross-sectional study including digital images of glass slides containing sections of positive and negative lymph nodes obtained from radical resection of primary CRC. Lymph nodes from 165 previously diagnosed cases were selected from Agha Khan University Hospital, from Jan 2021 to Jan 2022. The images were prepared at 10X and uploaded into an open source software, Q path and deep learning model Ensemble was applied for the identification of tumor deposits in lymph node.ResultsOut of the 87 positive lymph nodes detected by AI, 73(84%) were true positive and 14(16%) were false positive. The total number of negative lymph nodes detected by AI was 78. Out of these, 69(88.5%) were true negative and 9 (11.5%) were false negative. The sensitivity was 89% and specificity 83.1%. The odds ratio was 40 with a confidence interval of 16.26–98.3. P-value was < 0.05 (< 0.0001).ConclusionThough it was a small study but its results were really appreciating and we encourage more such studies with big sample data in future.

Prognostic significance of ratio of positive lymph nodes in patients with operable major salivary ductal carcinoma

AbstractPurposeMajor salivary duct carcinomas (MSDCs) often involve the regional lymph nodes (LNs). However, the clinical value of LN parameters in patients with MSDCs is unclear. We aimed to investigate the optimal cut‐off points for number of positive LNs (PLNN) and ratio of positive LNs (PLNRs) and their prognostic value in patients with MSDC.Study DesignRetrospective cohort.MethodsWe retrospectively reviewed relevant data extracted from the Surveillance, Epidemiology, and End Results database on patients with MSDC who had undergone surgery between 2004 and 2016. The optimal PLNN and positive lymph node ratio (PLNR) cut‐off points were identified using the X‐tile program. Kaplan–Meier and Cox regression analyses were performed to determine prognostic factors.ResultsOverall, 290 patients were enrolled, 57.6% of whom had LN metastases. Advanced T stage in the submandibular gland and unpaired lesions were associated with LN involvement. Positive LNs, late T stage, and submandibular gland location were associated with poor overall survival (OS). The 5‐year OS rates of patients with negative and positive LNs were 74.3% and 36.5%, respectively. PLNN &gt; 16 and PLNR &gt; 0.48 were the best cut‐off points. The 5‐year OS of patients with PLNN ≤ 16 and PLNN &gt; 16 was 42.8% and 15.4%, respectively. The 5‐year OS rates were 46.8% for patients with PLNR ≤ 0.48 and 26.3% for patients with PLNR &gt; 0.48. PLNR was a strong prognostic factor for patients with MSDC with LN metastases.ConclusionsPLNR reflects both the effects of LN dissection and PLNN. Furthermore, its prognostic value in patients with MSDC exceeds that of PLNN. Patients with high PLNRs should be followed closely after surgery.

Features of the course of COVID-19 in children with the spread of the Omicron variant

The aim of the study was to assess the symptoms and identify risk factors for prolonged and complicated COVID-19 during the spread of the Omicron variant in children aged 1 month to 18 years. Materials and methods. The study included 110 children with confirmed COVID-19 of mild or moderate severity at the time of the first examination. The average age of the patients was 6.86±5.09 years. The clinical symptoms, duration of each of the identified symptoms, and complications were evaluated. Acomparative analysis of possible risk factors for prolonged course and development of pneumonia was carried out. Results. The most common cases in children with COVID-19 were an increase in body temperature (in93%), runny nose (in65%), cough (in59%), hyperemia of the posterior pharyngeal wall (in95%) and tonsils (in93%), an increase in regional lymph nodes - in 43%. Among children with the duration of COVID-19 for 10 days or more, astatistically significant late request for medical help (onaverage, by 8.26±5.46 days, compared with 3.00 ± 1.32 days with the duration of the disease up to 10 days). Pneumonia is most often registered among preschool children. The average age in the group of children diagnosed with pneumonia is significantly less than in children who did not have signs of pneumonia of this complication (4.66 ±4.78 and 7.17±4.81, respectively). Conclusions: With the spread of the Omicron variant COVID-19 in children, infection with the SARS-CoV-2 coronavirus is accompanied by symptoms of acute respiratory infection with an increase in body temperature, sore throat, hyperemia of the posterior wall of the pharynx and tonsils. Often there is an increase in regional lymph nodes, runny nose, cough, vomiting, less often - diarrhea. The prolonged course is facilitated by the late onset of adequate therapy. During the study, pneumonia was detected in 25% of children.

Pathological complete response of locally advanced triple-negative breast cancer: case report

Background. Triple-negative breast cancer is the most aggressive molecular subtype among breast malignancies. Due to the high proliferative activity of tumor cells and the lack of targets for targeted therapy, neoadjuvant chemotherapy plays the main role in complex treatment of this subtype. The optimal time to start neoadjuvant chemotherapy is defined as less than 8 weeks. Delays in time to treatment initiation may adversely affect treatment outcomes, as well as cause local or systemic disease progression. Achieving complete pathological response after neoadjuvant chemotherapy reduces the relative risk of relapse by more than 70 %, which, in turn, leads to a significant improvement in long-term survival of these patients. Description of the clinical case. A 32-year-old woman came to the clinic 15 months after being diagnosed with triple-negative breast cancer. The patient was treated with alternative medicine methods for 15 months, and upon admission to the hospital, the patient had pronounced local tumor growth with massive decay, tumor lysis syndrome and nutritional disorders. We decided to perform neoadjuvant chemotherapy: 12 cycles of weekly paclitaxel + carboplatin, followed by 4 cycles of dose-dense doxorubicin + cyclophosphamide. Chemotherapy resulted in a significant reduction in tumor size and improvement of health status of the patient. There were no clinically significant side effects requiring hospitalization or dose reduction. Upon completion of neoadjuvant treatment, the patient underwent mastectomy. The histological examination revealed a complete pathological response of the primary tumor and regional lymph nodes. The patient underwent adjuvant external beam radiation therapy. The patient is alive 3 years after diagnosis and 1.5 years after treatment completion. She plans delayed breast reconstruction with contralateral breast augmentation. Conclusion. This is a rare case of locally advanced triple-negative breast cancer with pathological complete response to neoadjuvant chemotherapy 15 months after diagnosis.

Challenge Dose Titration in a Mycobacterium bovis Infection Model in Goats.

Goats are natural hosts of Mycobacterium (M.) bovis, and affected herds can be the cause of significant economic losses. Similarites in disease course and lesions of M. bovis infections in goats and M. tuberculosis in humans make goats good models for human tuberculosis. The aim of this investigation was to characterize M. bovis challenge models in goats. For this, goats were endobronchially inoculated with three doses of M. bovis or culture medium. Clinical signs, shedding, and immune responses were monitored until 146 days post inoculation (dpi). At necropsy, lesions were examined by computed tomography, histology, and bacteriological culture. Infected goats did not develop clinical signs. M. bovis was cultured from feces, but never from nasal swabs. IGRAs were positive from 28 dpi onwards, antibodies at 140 dpi, and SICCT at 146 dpi. The increase in CD25+, IFN-γ+, and IFN-γ-releasing T-cell subpopulations was time-related, but not dose-dependent. All infected goats developed paucibacillary granulomas in the lungs and regional lymph nodes. M. bovis was regularly cultured. Dose-dependent effects included the size of pulmonary lesions, caverns, intestinal lesions, and early generalization in the high-dose group. In summary, reproducible challenge models with dose-dependent differences in lesions were established, which may serve for testing vaccines for veterinary or medical use.

Prognostic significance of anatomic site-specific depth of invasion in oral squamous cell carcinoma - An eastern Indian multi-center study

A crucial parameter in determining the prognosis of oral cavity cancer is depth of invasion (DOI). This research aimed to correlate pathological DOI at different intra-oral anatomical sites for oral squamous cell carcinoma (OSCC) with the risk of regional lymph node metastasis (LNM). This study also investigated the correlation of 3-year overall survival (OS) and disease-specific survival (DSS) with tumor depth. DOI measurement of the primary tumor at different intra-oral anatomic sites of clinically node negative patients who underwent curative surgery with elective neck dissection (END) was carried out as per AJCC 8th Edition staging guidelines in 3 DOI groups of ≤5 mm(A), >5 to ≤10 mm(B) and >10 mm(C). Association of groupwise DOI values with histopathological parameters including LNM and 3 years survival was evaluated. Univariate and multivariate logistic regression analysis (Odds ratio (OR) = 1.1 95 % CI: 1.0–1.2, p < 0.05) showed DOI to be a significant predictor for sub-clinical nodal metastasis observed in 136/382 OSCC patients. Receiver operating curve suggested that at 5 mm DOI (4 mm for early-stage OSCC), the risk of occult LNM was >20 % for all intra-oral sites combined. DOI <5 mm group demonstrated a superior 3-year OS (OR = 19.8 % CI: 7.8–49.9) and DSS (OR = 14.7 % CI: 5.9–37.0). Thus, DOI is an independent predictor of nodal metastasis and has significant association with LNM, OS and DSS. Our findings suggest that a DOI of ≥4 mm is an accurate cut-off value for performing END in early-stage OSCC and > 5 mm for advanced cases across all evaluated oral anatomic sites.

Increasing the efficiency of coagulation in resonant gaps due to acoustic flow formation

Relevance. The urgent need to eliminate environmental pollution from industrial emissions of various solid particles. At the same time, maximum attention is paid to cleaning exhaust gases from particles of 2.5 microns in size or less. One of the most promising ways to increase the efficiency of existing gas purification equipment in capturing such particles is their coagulation by exposing the gas flow to high-intensity acoustic vibrations of ultrasonic frequency. However, at low concentrations, even at the maximum permissible sound pressure level, the coagulation efficiency of particles smaller than 2.5 microns is insufficient to increase the recovery rate of gas cleaning equipment. Therefore, there is an urgent need to find new ways to further improve the efficiency of ultrasonic coagulation of particles smaller than 2.5 μm. Aim. To determine the conditions for the formation of vortex flows in ultrasonic fields with the maximum ultrasonic influence in terms of sound pressure level. Conducting comparative studies of the coagulation of particles with a size of 2.5 microns with and without vortex flows. This will make it possible to determine the real values of increasing the efficiency of ultrasonic coagulation during turbulization of a gas-dispersed flow by acoustic flows in comparison with coagulation in a uniform ultrasonic field and without it. Objects. Coagulation of particles under the influence of homogeneous and inhomogeneous ultrasonic fields. Methods. Computer modeling of the formed ultrasonic field by the finite element method using harmonic acoustic analysis. The paper considers the experimental method for studying the process of combining particles under the influence of ultrasonic vibrations. To determine the characteristics of an aerosol during experimental studies, a TIPAS-1 meter based on the small-angle scattering method and the spectral transparency method was used. Results. The paper introduces the results of studies of coagulation of particles with a size of 2.5 microns or less in an ultrasonic field formed in resonant gaps by oscillating disk emitters. The authors proposed to increase the efficiency of coagulation in resonant gaps through the use of ultrasonic disk emitters capable of forming alternating zones of maximum and minimum amplitude oscillations in the resonant gaps. The creation of such zones ensured the formation of vortex-type acoustic flows capable of moving particles within the nodal regions of a standing wave and between them. The involvement of small particles in the formed flows made it possible to increase the probability of their collision. It was established that more effective ultrasonic coagulation provides an increase in the degree of inertial capture for particles of 2.5 microns in size by 6% – from 89 to 95%, for particles of 1.5 microns in size by 7% – from 85 to 92%, and for particles of 0.5 microns by 9% – from 76 to 85%.

EP362 - Small Cell Ca of the Gall Bladder: A rare tumour of the gall bladder

Abstract Small cell carcinoma (SCC) of the gallbladder is an extremely rare tumour. Despite aggressive and varied treatments, its prognosis is poor. A 53/F presented with complaints of pain in abdomen and fever since 3 days. Patient was vitally stable and tenderness present over the epigastric, Right hypochondrium and Right lumbar region. Except leucocytosis, all labs were WNL. CECT Abdomen pelvis was suggestive of suspicious Gall bladder perforation with necrotic lymph nodes in the peri-pancreatic region. The patient was taken for exploratory laparotomy and a perforated gall bladder was seen intra op and cholecystectomy was performed. Histopathology findings were suggestive of small cell carcinoma - gall bladder and IHC markers (Synaptophysin, CD56, Ki67, EMA, CK19) sent for confirmatory findings were raised. Post op PET CT shows periportal, paracaval and aortocaval metastatic lymph nodes. Chemotherapy regimen (cisplatin + itoposide) was started post op and patient is under follow up. The incidence of SCC of the GB is approximately 0.5% of all GB cancers. Among NETs of the gastrointestinal tract, SCC of the GB compromises 0.2%. Less than 100 cases of this tumour have been documented in the English literature. Surgery is the mainstay of GB cancer treatment. Due to poor prognosis of SCC of the GB, even when curative surgery is possible, additional treatment methods such as chemoradiation should be considered.