Node Metastatic Lesions Research Articles

Transesophageal endoscopic ultrasound-guided aspiration of mediastinal lymph node. Clinical case

In oncologic practice, metastatic lesions in the mediastinal lymph nodes are primarily associated with lung cancer because of its high morbidity. However, lesions in mediastinal lymph nodes are quite common in the context of various other benign and malignant processes. Therefore, due to the anatomy of this zone, difficulties of visualization of specific lymph node groups, complicated differential diagnosis of benign and malignant processes, the problem of sampling biological materials from the affected area remains important and unsolved. Transesophageal endoscopic ultrasound-guided aspiration is a highly effective and safe method of diagnosis and staging of oncologic diseases associated with metastatic lesions in the mediastinal lymph nodes.

Receptor expression testing of the synchronous axillary nodal metastasis in early-stage breast cancer: Comparison of primary tumor and its draining nodes.

e12542 Background: Early stage (Stage I-III) human epidermal receptor -2 (HER2) positive and triple negative breast cancers (TNBC) tend to behave more aggressively than hormone positive breast cancers with higher and earlier incidences of recurrences. Oftentimes, testing for receptor subtypes is done only on the primary tumor and not on the synchronous axillary metastasis, with the assumption that the axillary metastasis is congruous to the primary lesion. Current guidelines also do not specify a requisite to do this testing. Information about the receptor expression types is fundamental for the treatment of breast cancer. We aimed to determine if there is significant discordance between the primary and ipsilateral axillary metastasis in early-stage breast cancer. Methods: We conducted a retrospective analysis via electronic medical record review of a large institutional database from 2008 to 2020. Sample for this study included all patients with a diagnosis of early-stage breast cancer (Stage I - III) with triple negative or HER2 positive tumors. Data on demographics, comorbidities, receptor status, staging, and mortality were collected. Results: Electronic charts from 448 patients were reviewed. 140 patients had axillary node positive disease. 40 (29%) of the 140 patients underwent testing for receptors subtypes on both primary and axillary nodal metastasis. 8 (20%) of the 40 patients had discordance in their receptor subtype expressed in their respective axillary nodal metastasis. 32 (80%) of the 40 patients had axillary receptor expression congruous to the primary tumor. At the time of our review, there was no statistically significant mortality between discordant compared to concordant group (13% vs 20%; p=0.54). 2 patients were lost to follow up. Conclusions: Our data suggests that one in every five axillary metastatic breast cancers can have receptor subtypes discordant compared to the receptors expressed on the primary tumor. Knowledge about any such discordance between the primary and respective axillary metastasis has a consequential impact on the treatment approach for early-stage breast cancer. This is especially true if the patient’s nodal metastatic lesions indeed prove HER2 receptor positivity or do not express any receptors (TNBC). Consequently, patients may be being deprived of benefits from advances in treatment of these cancers, such as targeted therapies towards HER2 receptor, hormonal treatments when indicated, or the utilization of neoadjuvant chemotherapy. A strong case can be thus made to revise current standards to include receptor testing on all primary and synchronous axillary metastasis. Further testing is needed to validate our findings.

Serum high-density lipoprotein cholesterol levels predict early recurrence and prognosis of intrahepatic cholangiocarcinoma after surgical resection

IntroductionDysregulation in lipid metabolism contributes to the occurrence and development of various cancers. The connection between changes in lipid metabolism and the development of intrahepatic cholangiocarcinoma remains uncertain. Our objective was to investigate the significance of blood lipid levels in patients with intrahepatic cholangiocarcinoma who have undergone surgery. MethodsNinety-seven ICC patients who underwent surgery were retrospectively enrolled. After 92.2 months of follow-up, the Kaplan-Meier analysis and Cox proportional hazard model were used to calculate overall survival and recurrence-free survival. ResultsThe median age of this cohort was 56 years, and 79 (81.4 %) of them were male. Eighty-eight (90.7 %) patients presented with tumor recurrence and 73 (75.3 %) died. In multivariate analyses, high-density lipoprotein cholesterol level (<0.91 vs. ≥ 0.91 mmol/L, hazard ratio [HR] = 2.55; 95 % CI: 1.38–4.71), lymph node metastasis (Yes vs. No, HR = 2.58; 95 % CI: 1.28–5.19), etiology factor (chronic HBV infection vs. others, HR = 0.5; 95 % CI: 0.28–0.88) and multiple tumor lesions (Yes vs. No, HR = 1.85; 95 % CI: 1.01–3.39) were independent predictors of overall survival. However, only high-density lipoprotein cholesterol level (HR = 1.86; 95 % CI: 1.19–2.92) emerged as the independent factor for recurrence-free survival. High-density lipoprotein cholesterol level (HR = 2.07; 95 % CI: 1.26–3.41), etiology factor (HR = 0.49; 95 % CI: 0.29–0.84), and multiple tumor lesions (HR = 2.00; 95 % CI: 1.14–3.51) were independent predictors of early recurrence. For patients who did not experience the spread of cancer to the lymph nodes, there was a significant correlation between the level of high-density lipoprotein cholesterol and their overall survival, recurrence-free survival, and early recurrence. For patients with low pre-operation high-density lipoprotein cholesterol levels, high post-operation high-density lipoprotein cholesterol levels were associated with better prognosis. ConclusionsLow serum high-density lipoprotein cholesterol level might serve as a sign of poor clinical outcomes (overall survival and recurrence-free survival) and early recurrence among intrahepatic cholangiocarcinoma patients. Strengthening the monitoring and intervention of intrahepatic cholangiocarcinoma patients with poor prognosis might be critical for improving the prognosis.

Options to apply national developments in the assessment of sentinel lymph node involvement in breast cancer

Background. Breast cancer is the leading oncopathology of women. The routine radical surgery performed in this pathology includes lymph node dissection, which provokes development of postmastectomy syndrome. However, the removal of non-metastatic lymph nodes is not rational according to the subsequent disability of the patients. This can be avoided by using a sentinel lymph node (SLN) biopsy procedure. At this stage of oncology development, there are several ways to visualize SLN. The fluorescent method is among the most promising. This technique has been used for many years. However, it is not sufficiently implemented in clinical practice. There are still several questions about the procedure for its performance. In addition, it requires the introduction and improvement of domestic developments, including reducing financial costs.Aim. To study the use of indocyanine green of domestic production (LLC Firm “FERMENT”, Russia) and the IC-GOR detection system (LLC “MedKomplekt”, Russia) for SLN biopsy in patients with early breast cancer.Materials and methods. From February to September 2023, biopsy of SLN using indocyanine green (LLC Firm “FERMENT”, Russia) was performed in 53 patients with early breast cancer without clinically detectable lesion of regional lymph nodes. In all cases, according to the clinical examination, the patients had an operable stage of breast cancer (cT1–3N0M0). 5 mg of indocyanine green, dissolved in 4 ml of water for injection, was administered after sanitizing of the surgical field intradermally and subcutaneously at 2 points in the upper-outer quadrant of the breast along the edge of the areola in 40 patients (75.5 %) or paratumorally in 13 patients (24.5 %). An incision in the axilla about 4 cm long was made no earlier than 10–15 minutes after injection of indocyanine green (when visualizing the track 1 cm beyond its distal end to avoid crossing the lymph duct, after which the drug can flow into the wound). After imaging, all detected lymph nodes were removed for planned morphological examination. Standard lymph node dissection of 1 and 2 level was performed in all patients. Middle age of patients was 64.5 years (from 37 to 85 year). In 40 patients (75.5 %) modified radical mastectomy was performed, breast conserving surgery was done in 13 cases (24.5 %).Results. SLN were visualized in 51 patients out of 53 (96.2 %). After the final morphological examination, the majority of patients in the group were ranged in the IA and IIA stages of the disease – 15 (28.3 %) and 28 (52.8 %), respectively. Metastasis in the SLN were found in 9 patients (17.0 %). Besides, in 3 cases (5.7 %) metastasis in the lymph nodes were found after lymph node dissection. In 4 cases (7.6 %) metastasis were found during lymph node dissection but were not detected in the removed SLN. Thus, in the study group 13 (24.5 %) patients had metastatic lymph node lesion despite negative clinical status. The total number of removed SLN in the study group was 169 (from 1 to 6), the average number of removed lymph nodes was 3.3. Any negative events, allergic and general reactions to indocyanine were not reported.Conclusion. Our technique of contrasting SLN with indocyanine green is adequate and reproducible. The frequency of detection of SLN with this method is 96.2 %, with an acceptable level of false negative results is 7.6 %. Indocyanine green (LLC Firm “FERMENT”, Russia) and the LED fluoroscopic cancer detector IC-GOR (LLC “MedKomplekt”, Russia) can be recommended for performing a SLN biopsy.

A rare clinical case of diagnosis and treatment of metastases of Merkel carcinoma in the right inguinal lymph nodes without an identified primary focus

Introduction. Merkel’s carcinoma is a neuroendocrine malignant epithelial skin tumor, rapidly progressive, prone to local recurrence and metastasis to regional lymph nodes and internal organs. The etiology and pathogenesis of Merkel’s carcinoma are still an insufficiently studied issue. Because of its rare occurrence, only single observations of Merkel’s carcinoma metastasis without an identified primary focus, most often with regional lymph node involvement, have been described in the world literature.Clinical case. This article presents a clinical case of metastatic lesion of inguinal lymph nodes with microinvasion into femoral artery in Merkel’s carcinoma without identified primary focus. After a comprehensive examination and onco-consilium the patient underwent surgical treatment in the scope of cytoreductive excision of the inguinal lymph node conglomerate on the right side and artery prosthesis with an autovenous graft. According to the routine postoperative pathomorphologic and immunohistochemical studies, the diagnosis of Merkel’s carcinoma metastasis was finally confirmed.Conclusion. Identification and description of such clinical cases are practically significant and can serve for formation of certain algorithms for treatment of Merkel’s carcinoma both with local manifestations and in progressive forms. Patients with Merkel’s carcinoma should be discussed in oncological consiliums, as treatment may include surgical stage, including biopsy of sentinel lymph nodes, adjuvant radiotherapy, chemotherapy and immunotherapy in case of tumor dissemination.

Sentinel lymph node biopsy experience in squamous cell carcinoma of the oral mucosa сT1–2N0M0

Introduction. Head and neck cancer is the 7th most common malignancy worldwide; squamous cell carcinoma of the oral mucosa are almost a third of tumors of that localization. Metastatic lesions of the neck lymph nodes are an unfavorable prognostic factor for malignant tumors of that location since it is associated with a 50 % decrease in overall survival. In this regard, the detection of metastases to the neck lymph nodes is an important component of high-quality oncological care for patients with that pathology.Aim. To evaluate the efficiency of sentinel lymph node biopsy in squamous cell carcinoma of cavity of mouth mucosa cT1–2N0М0.Materials and methods. 72 patients were included in trial at the age from 21 to 74 (mean 57.3) with confirmed squamous cell carcinoma of cavity of mouth mucosa cT1–2N0М0. No evidence of regional metastasis, by preoperative examination, including ultrasound, computed tomography with intravenous contrast was observed. All patients received radioisotope research to determine localization of sentinel lymph nodes, and then biopsy of that nodes was performed. Before obtaining information about the status of the sentinel lymph node, radical neck dissection was not performed. Pathology report with immunohistochemical investigation was performed by pathologist of A. F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center, Ministry of Health of Russia.Results. When assessing efficiency of sentinel lymph node method, true positives results (detection of metastasis in sentinel lymph node) were achieved in 3 (4.17 %) out of 72 cases. Follow up time was from 1 to 69 months. Among those cases, where metastasis in sentinel lymph nodes were not detected, relapse in regional lymph nodes was developed in 3 (4.35 %) out of 69 cases. Radical neck dissection was performed in cases with metastasis in sentinel lymph nodes. The specificity of method was 95 %, the predictive value of a negative result was 0.04.Conclusion. Sentinel lymph neck node biopsy is an effective method of subclinical locoregional metastases detection in cancer of oral mucosa cT1–2N0M0. In our study of sentinel lymph neck node biopsy, oncological outcomes were comparable to radical neck dissection, with fewer postoperative complications.

Agreement between PSMA-RADS and E-PSMA systems in classifying [18F]PSMA-1007 PET/CT lesions among prostate cancer patients: exploring the correlation between lesion size and uptake.

To determine the agreement between the PSMA-RADS and E-PSMA standardized reporting systems in the classification of [18F]PSMA-1007-uptaking lesions identified on PET/CT scan in patients with prostate cancer (PCa) and post-prostatectomy with suspected recurrent disease (local recurrence, regional nodal involvement and distant metastases), based on biochemical recurrence, while also exploring the correlation between lesion size and tracer uptake. A retrospective cross-sectional study of 32 post-prostatectomy PCa patients who had suspected recurrent disease based on biochemical recurrence post-prostatectomy (prostate-specific antigen values that are 0.2 ng/mL or higher) underwent [18F]PSMA-1007 PET/CT scan. The recurrent disease PCa lesions were characterized and subsequently classified using two standardized reporting systems (PSMA-RADS and E-PSMA). The lesions were grouped based on anatomical site, their size and SUVmax were compared using Kruskal-Wallis test with Dunn-Bonferroni post hoc tests. Spearman correlation coefficients were calculated between the size of the lesions and their SUVmax of the radiotracer [18F]PSMA-1007 for all the lesions and when grouped by anatomical site. Additionally, the agreement between lesion classifications was assessed using Cohen's kappa index. Only 32 (69.98 ± 8.27, men) patients met the inclusion criteria, a total of 149 lesions with avid uptake of [18F]PSMA-1007 were identified. Positive correlation (r = 0.516, p < 0.001) was observed between the size of the metastatic prostate cancer lymph node lesions and their [18F]PSMA-1007 uptake. Substantial agreement was noted between the PSMA-RADS and E-PSMA classification system scores among all lesions (κ = 0.70, p < 0.001), with notable discrepancies primarily among lymph node lesions. Our findings revealed a positive correlation between the size of the metastatic prostate cancer lymph node lesions and [18F]PSMA-1007 uptake, and although there was substantial agreement between the PSMA-RADS and E-PSMA classification systems, there were discrepancies mainly among the lymph node lesions.

Leukemoid Reaction in an Elderly Patient with Aortic Valve Infective Endocarditis and Pancreatic Adenocarcinoma

Leukemoid reaction (LR) associated with solid tumors has been documented for many decades. LR is often associated with an unfavorable prognosis and aggressive course of the disease. However, the differential diagnosis of LR is of significant difficulty when a patient has several potential etiological factors, each of them individually may cause LR or, on the contrary, lead to a systemic reaction of the body within a single pathogenetic chain.We present a clinical observation of an elderly patient admitted to the intensive care unit due to the first-time encountered weakness in the right extremities. Clinical and instrumental examination revealed an acute cerebral ischemia with leukocytosis increase up to 60.000 cells/μL with leukocyte formula left shift and subsequent patient decompensation with lethal outcome, despite the intensive treatment.Autopsy revealed a low-differentiated adenocarcinoma of the pancreatic tail with multiple metastatic lesions in regional lymph nodes and liver, as well as a competing disease — acute infective endocarditis of the aortic valve, which was the cause of sepsis development with septicemia type and thromboembolism both in the great circulation circle with the presence of ischemic cerebral infarction, spleen infarcts, and in the small circle with the development of thromboembolism in the right segmental branches of the pulmonary artery. Given the advanced stage of pancreatic cancer and lack of direct evidence of sepsis at primary diagnosis, paraneoplastic nature of LR is more likely, but infective endocarditis and concomitant pathology also may have contributed to the development of LR.

Association of circulating tumor HPV16DNA levels and quantitative PET parameters in patients with HPV-positive head and neck squamous cell carcinoma

Circulating tumor DNA (ctDNA), which circulates in the blood after being shed from cancer cells in the body, has recently gained attention as an excellent tumor marker. The purpose of this study was to evaluate whether ct human papillomavirus (HPV) 16 DNA (ctHPV16DNA) levels were associated with quantitative PET parameters in patients with HPV-positive head and neck (HN) squamous cell carcinoma (SCC). Fifty patients with oropharyngeal SCC (OPSCC) and 5 with SCC of unknown primary (SCCUP) before treatment were included. They all underwent blood sampling to test ctHPV16DNA levels and FDG PET-CT examinations. Quantitative PET parameters included SUVmax, metabolic tumor volume (MTV), MTV of whole-body lesions (wbMTV), and 56 texture features. ctHPV16DNA levels were compared to texture features of primary tumors in OPSCC patients (Group A) or the largest primary or metastatic lymph node lesions in OPSCC and SCCUP patients (Group B) and to other PET parameters. Spearman rank correlation test and multiple regression analysis were used to confirm the associations between ctHPV16DNA levels and PET parameters. ctHPV16DNA levels moderately correlated with wbMTV, but not with SUVmax or MTV in Groups A and B. ctHPV16DNA levels exhibited a weak negative correlation with low gray-level zone emphasis in Groups A and B. Multiple regression analysis revealed that wbMTV and high gray-level zone emphasis were the significant factors for ctHPV16DNA levels in Group B. These results were not observed in Group A. This study demonstrated that ctHPV16DNA levels correlated with the whole-body tumor burden and tumor heterogeneity visualized on FDG PET-CT in patients with HPV-positive HNSCC.

Tactics of combined/complex treatment of patients with breast cancer with isolated metastatic lesions of supraclavicular or parasternal lymph nodes

Purpose. To evaluate the treatment tactics for patients with breast cancer (BC) with isolated metastatic lesions of the supraclavicular or parasternal lymph nodes (LNs). Material and methods. We analyzed the data of 134 patients with breast cancer, who were divided into 2 groups: 1st (n=83) – patients with lesions of the supraclavicular and parasternal lymph nodes, both isolated and in combination with lesions of any other groups of lymph nodes; 2nd (n=51) – patients with isolated or combined lesions of only subclavian or axillary lymph nodes. In group 1, lymphadenectomy was performed in 27 patients (subgroup 1A), radiation therapy of the affected lymph nodes was performed in 56 (subgroup 1B). In group 2, patients received chemotherapy for the affected lymph nodes. Results. Survival after 1 year of observation was almost the same in subgroups 1A (surgical treatment of lymph nodes) and 1B (radiation therapy of lymph nodes) – 96.3 and 96.4%, respectively; after 3 years of observation – 77.8 and 80.4%, respectively; 5-year survival rate – 33.3 and 44.6%, respectively. However, the data obtained were statistically unreliable. Conclusion. When comparing 5-year overall survival, surgical removal of metastatic supraclavicular and parasternal lymph nodes is inferior to radiation therapy. Thus, it can be assumed that excluding the surgical stage of LN treatment does not worsen the results of therapy in the group of patients with breast cancer and metastatic lesions of supraclavicular or parasternal LNs.

СОБСТВЕННЫЙ ОПЫТ ПРИМЕНЕНИЯ РАДИОФАРМАЦЕВТИЧЕСКОГО ПРЕПАРАТА 99mТс-СЕНТИСКАН ПРИ ВИЗУАЛИЗАЦИИ СТОРОЖЕВЫХ ЛИМФАТИЧЕСКИХ УЗЛОВ У БОЛЬНЫХ РАКОМ МОЛОЧНОЙ ЖЕЛЕЗЫ

Purpose: To study the capabilities of the new radiopharmaceutical 99mTc-sentiscan in the visualization of sentinel lymph nodes in patients with breast cancer. Material and methods: A survey of 178 people diagnosed with breast cancer. Patients were divided into two groups depending on the route of administration of the radiopharmaceutical. The day before surgical treatment, all subjects were injected with a radiopharmaceutical using a syringe with an activity of no more than 120 MBq, in a volume of 0.3‒0.4 ml. The visualized sentinel lymph nodes were marked on the skin using a patented device – «Device for external marking of sentinel lymph nodes during radionuclide visualization». Intraoperative search for sentinel lymph nodes was carried out using gamma detectors Gamma-Finder II or Radical, followed by urgent histological examination. Results: Radioisotope visualization of sentinel lymph nodes using the domestic radiopharmaceutical 99mTc-sentiscan: in the first group (the drug was administered peritumorally) was 100 %, the average number of visualized lymph nodes in this group was 2.2; in the second group (the drug was administered subareolarly) ‒ 99.1 %, the average number of visualized lymph nodes ‒ 2.6. In the first group of patients, metastatic lesions of sentinel lymph nodes were detected in 8 cases (13.1 %), and in the second group ‒ in 14 (11.9 %). All lymph nodes were mapped in the axillary region on the side of the tumor process. Conclusion: The possibility of the radiopharmaceutical 99mTc-sentiscan for the identification and biopsy of sentinel lymph nodes in patients with breast cancer was assessed. The use of the domestic 99mTc-sentiscan makes it possible to visualize sentinel lymph nodes in patients with breast cancer and detect their location in 99.1‒100 % of cases. Taking into account the results obtained, the expanded indications for the use of the radiopharmaceutical and the cost of the kits, 99mTc-sentiscan is more preferable for use in clinical practice.

3D-modeling Capabilities in Assessing Resectability of Pancreatic Head Tumors

Background. Pancreatic head cancer ranks 6–7th among oncologic diseases and 4–5th among causes of mortality, with only 5% of patients achieving 5-year survival rate to date. Despite the successes of modern diagnostics and surgical treatment, the problem of early detection, staging of oncologic process and, as a consequence, combined treatment of pancreatic head cancer remains actual.Objective: increasing the accuracy of diagnostics and estimation of resectability of the pancreatic head cancer on the basis of the complex use of the radiation methods of investigation with pancreaticoduodenal zone 3D-reconstructions.Material and methods. The study included 93 patients (44 (47.31%) males and 49 (52.69%) females) with complicated pancreatoduodenal masses treated from 2019 to 2022 at the Surgical Department of the City Mariinsky Hospital. The patients’ age varied from 44 to 90 years, the mean age was 67±0.74 years. All patients underwent magnetic resonance imaging (MRI) on an Ingenia MR tomograph (Philips Medical Systems, Netherlands) with a magnetic field induction of 3 Tesla. The native examination of the abdomen and retroperitoneum, supplemented with MR-cholangiopancreatography protocol, and dynamic contrast enhancement with data collection in arterial, portal, and delayed phases were carried out. T2-weighted images were then performed using turbospin-echo technology, including fat-suppressed images, to evaluate structural changes and the presence of fluid in fascial spaces. Patients also underwent endoscopic ultrasound of the pancreaticoduodenal zone using the push and pull method, and abdominal multislice computed tomography (MSCT). To build 3D models, we used free 3D-slicer and Mimics programs, which allowed to build semi-automatic model for further evaluation of anatomo-topographic relations.Results. MSCT 3D modeling revealed tumor invasion into the superior mesenteric vein in 6 (23.06%) patients, whereas MRI models showed tumor invasion in 4 (15.38%) patients, intraoperatively the results were confirmed in 5 patients (19.23%). According to both MSCT and MRI modeling data, the invasion of the ventral trunk occurred in 1 (5.2%) case, which was confirmed intraoperatively. Inferior vena cava invasion on MSCT and MRI models was detected in 3 (11.54%) patients, whereas intraoperatively – in 4 (15.38%) patients. The MSCT and MRI 3D models coincided with the data on invasion of the ventral trunk in 1 (3.85%) patient and the superior mesenteric artery in 2 (7.69%) patients, which was fully confirmed intraoperatively.Conclusion. 3D modeling on the basis of MRI and MSCT studies is an informative method in preoperative staging of pancreatic head cancer and its resectability. This method allows to objectively determine the localization and prevalence of the tumor process on adjacent anatomical structures, as well as visually demonstrate the metastatic lesion of regional lymph nodes. By the parameters of diagnostic efficiency, 3D models are maximally close to the intraoperative picture, which allows planning both the volume and the course of surgical intervention.

Expression of AHR-regulated and PD-L1-regulated microRNAs in squamous cell lung cancer

Introduction. Despite modern advances in research into the risk of development, immunological control and treatment options for lung cancer (LC), it is the leading cause of death from cancer. Tobacco smoking remains the predominant risk factor for the development of lung cancer, especially one of its aggressive subtypes, squamous cell lung cancer (SCLC). Benzo[a]pyrene, a component of cigarette smoke, promotes the activation of the aryl-hydrocarbon receptor (AhR). AhR regulates the expression of many oncogenes, including PD-L1, the positive status of which is an indication for immunotherapy, one of the main treatment strategies for SCLC. However, to improve the effectiveness of treatment of SCLC, further search for new diagnostic, prognostic and therapeutic markers is necessary. MicroRNAs (miRs), which are highly stable and present in biological fluids, can act as such markers.Objective. Search for microRNAs that could potentially serve as diagnostic markers or therapeutic targets for SCLC. For this purpose, microRNAs were selected whose promoter regions contain AhR binding sites or whose target is PD-L1.Materials and methods. A biocollection of tumor and conditionally normal lung tissue samples (n = 40) was collected at the thoracic department of the Novosibirsk Clinical Oncology Dispensary. The relative levels of selected miRNAs were examined using real-time reverse transcription-PCR (RT-PCR) technique.Results. The levels of miR-342 and miR-181a in SCLC tissues were reduced by 3 times relative to conditionally normal tissue. The expression of miR-181a and miR-155 is associated with tumor size (lower levels in tumors larger than 3 cm) and the presence of metastases in the lymph nodes (3- and 2-fold lower levels in cases with metastases). The level of miR-146a decreased by 3 times in patients with metastatic lesions of lymph nodes. A significant relationship between the levels of miR-93, miR-181a and miR-155 and the expression status of PD-L1 was also found.Conclusions. The expression profile of miR-146a, miR-93, miR-181a and miR-155 differs in SCLC patients depending on PD-L1 status and the presence or absence of lymph node metastases.

Tactics of combined/complex treatment of breast cancer patients with isolated metastatic lesion of supraclavicular or parasternal lymph nodes

The article presents data on 134 breast cancer patients who were diagnosed with lesions of the parasternal, supraclavicular, subclavian and axillary lymph nodes. The effectiveness of surgical or radiation exposure to the supraclavicular/parasternal lymph nodes in their metastatic lesion was analyzed. The survival assessment showed that after 1 year of follow-up, the values of the indicator were almost the same, amounting to 96.3 and 96.4 %, respectively, in groups 1A (surgical treatment) and 1B (radiation therapy). After 3 years, the indicator value was slightly higher in subgroup 1B – 80.4 %, while in group 1A it was 77.8 %, 5-year survival in group 1A was at the level of 33.3 %, in group 1B the indicator value was higher and amounted to 44.6 %, in group 2–78.4 %. At the same time, there were no statistically significant differences in all the terms of the study. We believe that the results of our study are fully consistent with the current trend in the treatment of breast cancer, which can be defined by the phrase ‘the less surgery, the better’. According to our data, surgical removal of metastatically altered supraclavicular and parasternal lymph nodes is inferior to radiation therapy when comparing 5-year overall survival.

Synthesis and Preliminary Study of 99mTc-Labeled HYNIC-FAPi for Imaging of Fibroblast Activation Proteins in Tumors.

Fibroblast activation protein (FAP) is an emerging target for cancer diagnosis. Different types of FAP inhibitor (FAPI)-based radiotracers have been developed and applied for tumor imaging. However, few FAPI tracers for single photon emission computed tomography (SPECT) imaging have been reported. SPECT imaging is less expensive and more widely distributed than positron emission tomography (PET), and thus, 99mTc-labeled FAPIs would be more available to patients in developing regions. Herein, we developed a FAPI-04-derived radiotracer, HYNIC-FAPi-04 (HFAPi), for SPECT imaging. 99mTc-HFAPi, with a radiochemical purity of >98%, was prepared using a kit formula within 30 min. The specificity of 99mTc-HFAPi for FAP was validated by a cell binding assay in vitro and SPECT/CT imaging in vivo. The binding affinity (Kd value) of 99mTc-HFAPi for human FAP and murine FAP was 4.49 and 2.07 nmol/L, respectively. SPECT/CT imaging in HT1080-hFAP tumor-bearing mice showed the specific FAP targeting ability of 99mTc-HFAPi in vivo. In U87MG tumor-bearing mice, 99mTc-HFAPi had a higher tumor uptake compared with that of HT1080-hFAP and 4T1-mFAP tumor models. Interestingly, 99mTc-HFAPi showed a relatively high uptake in some murine joints. 99mTc-HFAPi accumulated in tumor lesions with a high tumor-to-background ratio. A preliminary clinical study was also performed in breast cancer patients. Additionally, 99mTc-HFAPi exhibited an advantage over 18F-FDG in the detection of lymph node metastatic lesions in breast cancer patients, which is helpful in improving treatment strategies. In short, 99mTc-HFAPi showed excellent affinity and specificity for FAP and is a promising SPECT radiotracer for (re)staging and treatment planning of breast cancers.

Fluorescence lymphography for sentinal lymph node biopsy in breast cancer

To study diagnostic value of fluorescence lymphography for sentinel lymph node biopsy in breast cancer. The study enrolled 25 patients with breast cancer T1-2N0-1M0 between March 2023 and July 2023. Eight ones underwent neoadjuvant chemotherapy. In 3 patients, morphologically verified metastases cN1 in axillary lymph nodes regressed after treatment. After sentinel lymph node biopsy, all patients underwent standard axillary lymphadenectomy. Subareolar injection of indocyanine green 1 ml (5 mg/ml) was performed immediately before surgery. Fluorescence imaging was performed using the MARS system. Detection rate was 100%. Mean number of sentinel lymph nodes was 2. Metastatic lesions of sentinel lymph nodes were observed in 6 patients (24%) with micro-metastases in 2 cases. In 50% of cases, metastatic lesion did not extend beyond sentinel lymph nodes. False negative result was obtained in 1 (4%) patient. Mean number of metastases was 1.8 (max 3 in one patient). Sentinel lymph node biopsy with fluorescence lymphography is a sensitive method. The advantages of this technique are visualization of subcutaneous lymphatic vessels and skin incision for access to sentinel lymph nodes, as well as visualization of sentinel lymph nodes after skin incision.

Preventive axillary lymphovenous anastomoses simultaneously with lymph node dissection in the treatment of breast cancer for prevention of lymphedema of the upper limb (LYMPHA technique)

To analyze the effect the LYMPHA technique on the incidence of upper limb lymphedema in patients with breast cancer after complete axillary lymph node dissection. There were 89 patients with breast cancer and signs of metastatic lesion of axillary lymph nodes who underwent complete axillary lymph dissection. In group 1 (41 patients), the LYMPHA technique was used simultaneously with lymph node dissection; in group 2 (48 patients) - lymph node dissection alone. The follow-up period was 1 year. The LYMPHA technique prolonged surgery and decreased duration of postoperative lymphorrhea. The incidence of upper limb lymphedema was 9.8% and 22.9%, respectively. The LYMPHA technique was effective for prevention of upper limb lymphedema after complete axillary lymph node dissection in the treatment of breast cancer.

Diagnostic value of fluorescence lymphography for sentinel lymph node biopsy in breast cancer. Summary experience of several specialized centers

To study the diagnostic value of fluorescent lymphography for sentinel lymph node biopsy in breast cancer. The cohort study, conducted at 4 specilized centers between June 2019 and March 2024, included 333 patients with cT1-4 N0-1M0 breast cancer. 50 patients received neoadjuvant systemic therapy, 14 of them had single metastases, confirmed by cytological or histological methods, which clinically completely regressed after systemic treatment. Immediately before the operation, 1 ml (5mg) of indocyanine green was injected subareolarly or subcutaneously into the tumor projection. Fluorescence imaging was performed using various devices for ICG navigation in the open surgical field - MARS, IC-Flow, Stryker SPY-PHI, IC-GOR. In 78 patients after sentinel lymph node biopsy standard axillary lymphadenectomy was performed. Detection level was 99.1%. The average number of sentinel lymph nodes was 3.4. Metastatic lesions of sentinel lymph nodes were detected in 54 of 330 patients (16.4%). The average number of metastatic lymph nodes was 1.6; in 90.7% of cases metastases to 1-2 lymph nodes were registered. Intraoperative morphological examination revealed metastases only in 59% of cases. No systemic adverse events were recorded. The false-negative error rate in the group of patients who underwent axillary lymphadenectomy was 6.6%. The overall accuracy of fluorescent lymphography for sentinel lymph node biopsy in breast cancer was 94%. The SLNB technique using fluorescence lymphography is safe and highly accurate as a stand-alone method.

D2 and D3 lymph node dissection for colon cancer

To evaluate surgical and oncological results of standard and extended lymph node dissection (D2 and D3) in patients with colon cancer. We analyzed treatment outcomes in 74 patients with colon cancer stage T1-4aN0-2M0 who underwent right- and left-sided hemicolectomy, resection of sigmoid colon with standard and extended lymph node dissection (D2 and D3). Surgical approach and level of D3 lymph node dissection did not increase intra- and postoperative morbidity. Laparoscopic interventions were followed by significantly lower intraoperative blood loss and earlier gas discharge. Metastatic lesion of apical lymph nodes was observed in 5 out of 36 patients who underwent D3 lymph node dissection (13.8%), and metastases in regional lymph nodes rN1-2 were found in all these patients. Overall 5-year survival was 86%. Disease-free and overall 5-year survival were similar after D2 and D3 lymph node dissection. D3 lymph node dissection is safe for colon cancer. Metastatic lesions of apical lymph nodes during D3 lymph node dissection were detected only in patients with lesions of regional lymph nodes (rN1-2). Disease-free and overall 5-year survival were similar after D2 and D3 lymph node dissection.

CCL21 and CLDN11 Are Key Driving Factors of Lymph Node Metastasis in Gastric Cancer.

Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide. Understanding the molecular mechanisms of GC metastasis is crucial for improving patient survival outcomes. RNA sequencing and analysis were performed on tissue samples from primary and lymph node metastatic lesions of gastric cancer. Differential gene analysis and functional pathway analysis were conducted. Immune infiltrating environment and protein expression levels were evaluated using immunohistochemistry. Cell experiments were conducted to investigate the role of CCL21 in GC metastasis. ACTG2, CNN1, DES, MUC6, and PGC were significantly upregulated in primary tumor cells, while CCL21, MS4A1, CR2, CLDN11, and FDCSP were significantly upregulated in metastatic tumor cells. Functional pathway analysis revealed enrichment in pathways related to immune response. CLDN11 and CCL21 were found to play important roles in promoting gastric cancer metastasis. Cell experiments confirmed the role of CCL21 in promoting GC cell growth and metastasis. CCL21 is highly expressed in GC tissues and binds to CCR7, leading to upregulation of CLDN11. This results in GC-lymph node metastasis and abnormal activation of immune cells (B cells and CD4+ T cells). Inhibition of CCL21 and CLDN11 proteins may be a promising strategy for treating GC and preventing lymph node metastasis. These findings provide specific molecular markers for early lymph node metastases of GC, which can aid in developing treatment strategies and predicting patient prognosis.