T1 N0 M0 Research Articles

Comparative analysis of survival rates of pre- and postmenopausal patients with early breast cancer

Introduction. Breast cancer, which occurs in young women, is more often classified as a biologically aggressive subtype (HER2+ and triple negative) compared with postmenopausal patients. At the same time, it is important to know whether age, in itself, determines a less favorable outcome of the disease in young patients.Aim. To evaluate overall and recurrence-free survival rates in premenopausal and postmenopausal patients who underwent various levels of surgery and received neoadjuvant and adjuvant systemic therapy.Materials and methods. Of the 3,450 analyzed patients, the final analysis included 265 patients with breast cancer (clinical stage T1–3N0–1M0) who received treatment between 2011 and 2019, who were divided into 2 groups depending on age category, biological tumor subtype, types of neoadjuvant and adjuvant treatment.Results. Of 265 included patients, 162 (61.1 %) were premenopausal women, 103 (38.9 %) were postmenopausal women. The median follow-up was 5 years. The 5-year overall survival was 96.8 % (95 % confidence interval (CI) 92.6–98.7) in premenopausal patients and 95.1 % (95 % CI 88.5–97.9) in postmenopausal patients. The differences in overall survival estimated using the likelihood ratio test were not statistically significant (p = 0.927). The 5-year recurrencefree survival rate was 77.6 % (95 % CI 70.3–83.3) in premenopausal patients and 84.2 % (95 % CI 75.6–90.0) in postmenopausal patients. The differences in disease-free survival estimated using the likelihood ratio test were not statistically significant (p = 0.253).Conclusion. When comparing patients with early breast cancer, overall and relapse-free survival did not depend on menopausal status. It is necessary to conduct randomized trials to determine the effectiveness of drug therapy.

CNA landscape of HER2-negative breast cancer during administration of taxane-containing schemes of neoadjuvant chemotherapy

Introduction. Evaluation of when and how to include taxanes in preoperative chemotherapy is becoming more important in the era when molecular and genetic approaches allow to develop biologically targeted therapeutic medications and select patients who can benefit from certain cytotoxic agents.Aim. To analyze the use of CNA genetic landscape (CNA – copy number aberration) luminal B HER2-negative (HER2 – human epidermal growth factor receptor type 2) breast cancer during taxane-containing neoadjuvant chemotherapy (NCT) for identification of the groups of potential CNA markers of objective response to treatment and CNA markers of prognosis of hematogenous metastases.Materials and methods. The study included 28 patients with luminal B HER2-negative breast cancer T1–4N0–3M0 stage IIA–IIIB aged 24–67 years (mean age 44.6 ± 0.3 years). In neoadjuvant regimen, the patients received 4–8 courses of chemotherapy per the ACT, AT schemes and taxotere as monotherapy. As study samples, paired tumor biopsies taken prior to treatment under ultrasound control and operative material after neoadjuvant therapy were used. Micromatrix analysis was performed using high density DNA CytoScanTM HD Array (Affymetrix, uSA). The results were processed using Chromosome Analysis Suite 4.0 (Affymetrix, uSA) software. Statistical data processing was performed in Statistica 8.0 (StatSoft Inc., uSA) software.Results. Objective response was observed in the absence of amplification in the 20q11.22 (р = 0.003) region and presence of amplifications in the 16p13.2 (р = 0.027) locus in the tumor prior to treatment. After NCT, hematogenous metastases developed in the tumor in the presence of a small number of amplifications in the 20q13.33 (р = 0.002) locus.Conclusion. Potential predictive CNA markers of objective response to treatment and prognostic CNA markers of hematogenous metastases during administration of taxane-containing schemes of neoadjuvant chemotherapy were identified.

Temporal Trends in the Utilization and Survival Outcomes of Lobar, Segmental, and Wedge Resection for Early-Stage NSCLC, 2004 to 2020.

Temporal Trends in the Utilization and Survival Outcomes of Lobar, Segmental, and Wedge Resection for Early-Stage NSCLC, 2004 to 2020.

Outcomes of radical cystectomy in a resource-limited setting: a pilot study

BackgroundRadical cystectomy is a cornerstone treatment for muscle-invasive bladder cancer, but its implementation in resource-limited settings is challenged by limited access to trained professionals and inadequate healthcare infrastructure. This pilot study aims to analyze perioperative complications and mortality associated with radical cystectomy and urinary diversion at Gezira Hospital for Renal Diseases and Surgery (GHRDS) in Sudan. These findings reflect the outcomes of an in-country training program established by the Society of International Urology (SIU) to address surgical capacity gaps in resource-limited settings.MethodsWe conducted a retrospective analysis of patient who underwent radical cystectomy with ileal conduit urinary diversion between January 2015 and December 2019. Data were collected from medical records, including demographic details, perioperative complications classified by the modified Clavien-Dindo system, and histopathological findings.ResultsA total of 30 patients were included in the study. The median age was 65 years, and 77% were male. The majority of patients (76%) had transitional cell carcinoma, followed by squamous cell carcinoma (17%) and adenocarcinoma (7%). The clinical stage at presentation were T1 N0 M0 (23%) and T2 N0 M0 (77%). A total of 32 complications were observed, with 91% classified as low-grade. Infectious complications were the most common (50%), followed by gastrointestinal and respiratory issues. Severe complications occurred in 13% of cases, and in-hospital mortality was 3%.ConclusionThis study demonstrates the feasibility of performing radical cystectomy in a resource-constrained environment, supported by a collaborative training program involving international expertise and local participants. While outcomes were encouraging, key areas for improvement include infection control, critical care capacity, and early detection of bladder cancer. These findings underscore the importance of sustainable in-service training programs in building surgical capacity in resource-limited settings. Future research should focus on long-term outcomes and strategies to reduce complications.

Comparative evaluation of the quality of life of patients after mastectomy and non-flapped breast reconstructions for cancer

Purpose of the study: to compare the quality of life of patients who underwent mastectomy and non-flapped breast reconstructions for cancer.The study included 90 patients, diagnosed with breast cancer 0–IIA st. T1–2N0M0. The minimum age of the patients was 30 years old, the maximum was 65 years, the average age was (49.76 ± 8.54) years old. Patients were divided into three groups of 30 women depending on the type of surgical treatment of the tumor and breast reconstruction: 1st group – Madden surgery with a subsectoral expander installation and replacement with a silicone endoprosthesis, 2nd group – Madden surgery with prepectoral expander installation, staged lipofilling and replacement with silicone endoprosthesis, 3rd group – radical subcutaneous mastectomy with one-stage prepectoral breast reconstruction. The quality of life was assessed using a set of Breast-Q scales.The data obtained make it possible to draw conclusions about the effectiveness of subcutaneous mastectomy with one-stage prepectoral breast reconstruction according to the method proposed by the authors due to the tendency to a more intensive increase of the quality of life of patients at the stages of rehabilitation in such aspects as psychosocial, physical and sexual well-being.

Unmet needs in the management of patients with bilateral synchronous renal masses: the rationale for clinical decision-making.

Bilateral synchronous renal masses (BSRMs) are a rare finding, and the optimal treatment strategy remains undetermined. This study depicts the management of BSRM at eight European high-volume centers. This is a retrospective analysis of prospective institutional databases collecting all patients presenting with clinical T1-2 N0 M0 BSRMs between 1993 and 2020 at 8 tertiary referral high-volume centers for renal cancer treatment in Europe. The treatment options included active surveillance (AS), tumor ablation (TA) and surgery (partial and radical nephrectomy). Overall, 134 patients were analyzed. Renal mass biopsy prior treatment was performed in 8% of cases. 15%, 4%, and 81% of patients underwent AS, a combination of surgery and TA, and bilateral (one-stage or two-stage) surgery. Among patients undergoing bilateral surgery (N.=109), a staged approach was chosen in 78% (N.=85) of cases treating the lower complexity tumor first in 51/85 (60%) cases and in 34/85 (40%) treating the higher complexity tumor first. Concordance of the histological analysis was found in 77% of patients with 10% of bilateral benign masses. Even if considering only referral centers, a high heterogeneity for decision-making in the treatment of BSRM should be expected. Advances in genetic diagnosis, the implementation of novel imaging technologies, and the strengthening role of alternative treatment, may lead to a standardized decision-making process in the setting of BSRMs.

A Comparison of Stereotactic Radiation Therapy in Elderly Patients with Central or Peripheral Stage I-II (T1-3 N0 M0) Non-Small Cell Lung Cancer.

The objective of this study was to compare the clinical outcomes of stereotactic body radiation therapy (SBRT) in elderly patients aged 65 or older with clinical stage I-II non-small-cell lung cancer (NSCLC), specifically examining the differences between centrally located lung tumors and peripherally located lung tumors. From April 2009 to January 2020, a total of 136 patients with 136 tumors (65 central, 71 peripheral; NSCLC) at an early stage (T1-3N0M0) were treated with SBRT at a single institution. Central/peripheral location was assessed retrospectively on planning CT scans. A propensity score matching analysis was utilized to compare the two groups. In addition, the prognosis and related toxicity were compared between the two study arms. A total of 33 central tumors and 33 peripheral tumors were matched and analyzed. The results showed no significant differences in overall survival (OS) and progression-free survival (PFS) between the two groups. The 2-year OS was 71.88% (95% CI, 57.87%-89.27%) in the central lung cancer group, while it was 93.94% (95% CI, 86.14%-100.00%) in the peripheral lung cancer group (P=0.462). The 2-year PFS was 43.75% in the central lung cancer group, while it was 78.79% in the peripheral lung cancer group (P=0.279). Further subgroup analysis indicated that the location of peripheral tumor have a positive impact on OS in patients with adenocarcinoma. The occurrence of local failure, regional failure, or distant failure was comparable between central and peripheral tumors. There was no statistically significant difference in toxicity between the central and the peripheral tumor groups. The outcomes of SBRT for central tumors versus peripheral lung tumors in elderly patients with early-stage NSCLC were similar. SBRT demonstrated a similar level of safety in terms of toxicity for both central and peripheral lung tumors.

Integrin profle of circulating tumour cells in breast cancer patients

Background. Integrins, as adhesion molecules, play a key role in the interaction of cells with the basal membrane and intercellular matrix. Numerous studies demonstrate evidence of increased expression of integrins on tumor cells in different types of cancer. Thus, β3 and αV integrins are associated with stem-like features of tumor cells, and β4 integrin as α6β4 heterodimer provides anchorage-independent survival of malignant mammary epithelial cells. However, all the described functions of integrins have been investigated exclusively on primary tumor cells. The functional significance and expression pattern of integrins on circulating tumor cells (CTCs) remains unclear. The aim of the study was to evaluate the β3, β4 and αvβ5 integrin expression on CTCs and its association with molecular subtype, stage and lymph node metastasis in breast cancer patients Material and Methods. The study included 22 patients with T1–4N0–3M0 invasive ductal breast carcinoma. Venous blood was taken from patients without neoadjuvant chemotherapy (group 1) and after neoadjuvant chemotherapy (group 2) in the volume of 12 ml into vacuum tubes with EDTA. The expression of CTC integrins including stemness features CD44/CD24, CD133 and ALDH1, and epithelial-mesenchymal transition (EMT) (N-cadherin) was evaluated by flow cytometry. Results. CTCs with β3+β4-αvβ5- and β3-β4+αvβ5+ phenotypes and stemness properties were associated with larger tumor size (T4) in breast cancer patients. The β3 integrin expression was associated with more aggressive molecular subtypes of breast cancer. Administration of neoadjuvant chemotherapy did not affect the expression pattern of β3, β4 and αvβ5 integrins in CTCs. Conclusion. In breast cancer, most CTCs expressed β3, β4 and αvβ5 integrins despite the lack of attachment to the basal membrane and intercellular matrix. The expression of the above integrins on CTCs was associated with breast cancer molecular subtype, stage and lymph node metastasis, and therefore its evaluation can be considered as one of the objectives of liquid biopsy study.

Subpopulation composition of PD-L1-positive lymphocytes in the primary tumour in luminal breast cancer patients

The relationship between the tumour and the microenvironment is of great interest because it may determine the efficacy of new agents aimed at targeting the anti-tumour immune response, such as immune checkpoint inhibitors (ICI s), which have been used to treat breast cancer. PD -L1 status in immune cells should be examined when prescribing ICI s for breast cancer. This highlights the importance of studying the characteristics of the tumour microenvironment, the main approach being to uncover its heterogeneity. The aim of this study was to investigate the subpopulation composition of PD -L1-positive lymphocytes in the tumour microenvironment, separately in each luminal subtype of BC, and to compare it according to the PD -L1 status of the tumour. Material and Methods. Fifty-two primary tumour samples were obtained from patients with invasive luminal A, luminal B HER2- and luminal B HER2+ subtypes of breast cancer (T1–2N0–1M0). No drug therapy was administered prior to surgery to any patient in this study. Cytotoxic lymphocytes (CTL s), B lymphocytes, T helper lymphocytes, T regulatory lymphocytes and their PD -L1 expression in tumour tissue samples were assessed by flow cytometry, and tumour PD -L1 status was determined by Ventana SP 142 immunohistochemistry. Results. All of the key lymphocyte populations we identified were present in almost all patients. The number of PD -L1-positive Th2 lymphocytes was significantly higher in the luminal A and luminal B HER2- BC samples compared to the luminal B HER2+ cases (р=0.0240 and p=0.0092, respectively). When the proportion of PD -L1-positive cells was calculated, the proportion of PD -L1-positive Th2 lymphocytes and T regulatory lymphocytes was significantly lower in luminal B HER2-compared to luminal A BC. Cytotoxic lymphocytes, Th2 lymphocytes and T-regulatory lymphocytes represented the predominant PD -L1-positive immune cells in the breast cancer microenvironment and were present in higher numbers in PD -L1-positive luminal B HER2-. Conclusions. Different lymphocyte populations, including those expressing PD -L1, can be found in the breast cancer microenvironment and there are differences in their numbers between different luminal breast cancers. This may explain the discordant prognostic and predictive value of the microenvironment in luminal breast cancer when considered as a single molecular subtype.

A study of microRNAs as new prognostic biomarkers in anal cancer patients.

MicroRNA (MiR) influences the growth of cancer by regulation of mRNA for 50-60% of all genes. We present as per our knowledge the first global analysis of microRNA expression in anal cancer patients and their prognostic impact. Twenty-nine patients with T1-4 N0-3 M0 anal cancer treated with curative intent from September 2003 to April 2011 were included in the study. RNA was extracted from fresh frozen tissue and sequenced using NGS. Differentially expressed microRNAs were identified using the R-package DEseq2 and the endpoints were time to progression (TTP) and cancer specific survival (CSS). Five microRNAs were significantly associated with 5-year progression free survival (PFS): Low expression of two microRNAs was associated with higher PFS, miR-1246 (100% vs. 55.6%, p = 0.008), and miR-135b-5p (92.9% vs. 59.3%, p = 0.041). On the other hand, high expressions of three microRNAs were associated with higher PFS, miR-148a-3p (93.3% vs. 53.6%, p = 0.025), miR-99a-5p (92.9% vs. 57.1%, p = 0.016), and let-7c-3p (92.9% vs. 57.1%, p = 0.016). Corresponding findings were documented for CSS. Our study identified five microRNAs as prognostic markers in anal cancer. MiR-1246 and microRNA-135b-5p were oncoMiRs (miRs with oncogene effects), while miR-148a-3p, miR- 99a-5p, and let-7c-3p acted as tumour suppressors in anal cancer patients.

Impacts of Positive Margins and Surgical Extent on Outcomes After Early-Stage Lung Cancer Resection

Impacts of Positive Margins and Surgical Extent on Outcomes After Early-Stage Lung Cancer Resection

Advanced Squamous Cell Carcinoma of the Skin Induced by Long-Term Hydroxyurea Treatment in a Patient with Essential Thrombocythemia

Abstract Background and Objective SCCs represents 20-30% of the non-melanocytic skin cancers. It is the second most common skin cancer in the U.S. The main risk factors for SCCs development are: skin phototype l-ll, excessive UV-exposure, chronic inflammatory skin diseases, radiation exposure and drug usage. Hydroxyurea is a drug used for the treatment of chronic myeloid leukemia, polycythemia vera and essential thrombocythemia. The therapy is associated with development of actinic keratoses, Bowen's disease, squamous cell carcinoma and basal cell carcinoma. Patients and methods We present a 70-year-old female patient suffering from essential thrombocythemia, undergoing treatment with hydroxyurea since 2005, who developed advanced squamous cell carcinoma of the skin of the face and wrists. Results The patient was diagnosed with advanced moderately differentiated SCCs (Grade 2), stage III (T4 N0 M0). Immunotherapy with cemiplimab 350 mg i.v. every 21 days was initiated. After 6 therapeutic cycles decrease of erythema and desquamation was registered. In 2022 the patient had an ischemie stroke, decompensated heart failure and acute kidney insufficiency. Unfortunately the patient died. Conclusions Patients undergoing long-term hydroxyurea treatment are prone to develop multiple squamous cell carcinomas of the skin and are subject to regular dermatological examinations.

A randomised phase II study of extended pleurectomy/decortication preceded or followed by chemotherapy in patients with early-stage pleural mesothelioma: EORTC 1205.

The role of surgery in pleural mesothelioma remains controversial. It may be appropriate in highly selected patients as part of a multimodality treatment including chemotherapy. Recent years have seen a shift from extrapleural pleuropneumonectomy toward extended pleurectomy/decortication. The most optimal sequence of surgery and chemotherapy remains unknown. EORTC-1205-LCG was a multicentric, noncomparative phase 2 trial, 1:1 randomising between immediate (arm A) and deferred surgery (arm B), followed or preceded by chemotherapy. Eligible patients (Eastern Cooperative Oncology Group 0-1) had treatment-naïve, borderline resectable T1-3 N0-1 M0 mesothelioma of any histology. Primary outcome was rate of success at 20 weeks, a composite end-point including 1) successfully completing both treatments within 20 weeks; 2) being alive with no signs of progressive disease; and 3) no residual grade 3-4 toxicity. Secondary end-points were toxicity, overall survival, progression-free survival and process indicators of surgical quality. 69 patients were included in this trial. 56 (81%) patients completed three cycles of chemotherapy and 58 (84%) patients underwent surgery. Of the 64 patients in the primary analysis, 21 out of 30 patients in arm A (70.0%; 80% CI 56.8-81.0%) and 17 out of 34 patients (50.0%; 80% CI 37.8-62.2%) in arm B reached the statistical end-point for rate of success. Median progression-free survival and overall survival were 10.8 (95% CI 8.5-17.2) months and 27.1 (95% CI 22.6-64.3) months in arm A, and 8.0 (95% CI 7.2-21.9) months and 33.8 (95% CI 23.8-44.6) months in arm B. Macroscopic complete resection was obtained in 82.8% of patients. 30- and 90-day mortality were both 1.7%. No new safety signals were found, but treatment-related morbidity was high. EORTC 1205 did not succeed in selecting a preferred sequence of pre- or post-operative chemotherapy. Either procedure is feasible with a low mortality, albeit consistent morbidity. A shared informed decision between surgeon and patient remains essential.

Is a completion axillary dissection in patients with early breast cancer with a positive sentinel node necessary? An NCDB-based trial emulation of ACOSOG Z0011.

e12592 Background: The ACOSOG Z0011 Study is a practice-changing phase III clinical trial that promotes the de-escalation of axillary surgery in early breast cancer patients, which supports no completion axillary lymph node dissection (ALND) in clinically node negative patients with 1 or 2 positive sentinel lymph nodes (pSLN). Strong evidence for patients with 3 positive SLN was still lacking. We emulated the Z0011 trial using the National Cancer Database (NCDB) to validate the post-trial evidence in the real-world setting followed by a deeper investigation in the subgroups by the number of pSLN. Methods: NCDB PUF 2020 was queried for clinical T1-2 N0 M0 breast cancer patients diagnosed 2010-2017. The inclusion and exclusion criteria were the same as in the Z0011 trial except for the inclusion of 3 positive sentinel lymph nodes. Sentinel lymph node biopsy (SLNB) alone and ALND were defined using Site-Specific Factor 19. The primary endpoint, overall survival (OS), was modeled by the Cox proportional hazard model. The propensity score-based average treatment effect on the treated (ATT) weighting schema was implemented to generate pseudo samples based on this eligible study population and its subgroups as pSLN = 1, 2, and 3, where covariate balance between the two cohorts was achieved for all observed demographic and disease characteristics. Results: 25,774 patients were included in the analysis. 20311 (78.8%) patients were in the SLNB alone group, and 5463 (21.2%) patients were in the ALND group respectively. The utility rate of SLNB increased steadily over the years from 53.7% in 2010 to 91.0% in 2017. The median age was 60, which was older than that in the Z0011 trial (55). The median follow-up time was 6.78 [95% CI: 4.98-8.81] years. By multivariable analysis using the original sample, SLNB alone and the ALND group had similar survival (HR = 0.99 [95% CI: 0.90-1.09]; P = 0.83). By ATT weighting, the SLNB group had significantly improved survival (HR= 0.88 [95% CI: 0.82-0.95]; P = 0.001). The magnitude of HR is close to that in the Z0011 trial (HR= 0.87 [95% CI: 0.62-1.23]), but the statistical significance was mainly driven by a much larger sample size in this study. In the subgroup ATT weighting analysis for pSLN = 1, the SLNB group had significantly better survival compared to the ALND group (HR = 0.85 [95% CI: 0.79-0.93]; P < 0.001). Survival was equivalent for subgroup patients with pSLN = 2 (HR = 1.04 [95% CI: 0.91-1.19]; P = 0.54), while in the subgroup of pSLN = 3 patients, the SLNB group had a significantly worse survival when compared to the ALND group (HR, 1.22 [95% CI, 1.04-1.45]; P = 0.02). Conclusions: This NCDB-based Trial-Emulation study validates the result of the ACOSOG Z0011 clinical trial through a post-trial and real-world setting, where we confirmed that patients with 1 or 2 pSLN are suitable for SLNB alone, but for patients with 3 pSLN, ALND may still maintain a viable option.

Stereotactic Body Radiotherapy for Centrally Located Inoperable Early-Stage NSCLC: EORTC 22113–08113 LungTech Phase II Trial Results

Stereotactic Body Radiotherapy for Centrally Located Inoperable Early-Stage NSCLC: EORTC 22113–08113 LungTech Phase II Trial Results

Comparative analysis of morphological changes in the mucosa of the small and large bronchi in non-small cell lung cancer

Background. Despite advances in surgical and therapy techniques, non-small cell lung cancer (NSCLC) is one of the most common cancers and the leading cause of cancer-related death. Therefore, it is increasingly important to search for markers that predict the risk of tumor progression. The study of the morphology of the epithelium of the bronchi of different calibers has great potential for solving this problem. The aim of the study was to comparatively evaluate the characteristics and frequency of occurrence of various combinations of morphological changes in the epithelium of the bronchi of large and small calibers in patients with lung squamous cell carcinoma and lung adenocarcinoma. Material and methods. lung samples were collected from 151 NSCLC patients (stage T1–4N0–3M0), who underwent surgery at the cancer Research institute, TNRMC. Various morphological changes in the bronchial epithelium were analyzed. Results. The study of the frequency of occurrence of various morphological changes in small-caliber bronchi showed that basal cell hyperplasia occurred in 90.8 % of cases. Diffuse isolated basal cell hyperplasia was observed in 33.8 % of cases. Focal basal cell hyperplasia was diagnosed in 38.4 % of cases. A combination of basal cell hyperplasia with squamous metaplasia was observed in 18.5 % of cases. The study of the frequency of occurrence in large-caliber bronchi demonstrated that basal cell hyperplasia was the most common morphological variant (93.4 %, including diffuse isolated basal cell hyperplasia in 33.8 % and focal basal cell hyperplasia in 38.4 %). The combination of basal cell hyperplasia and squamous metaplasia was found in 19.8 %. The combination of basal cell hyperplasia with squamous metaplasia and dysplasia was found in 1.3 % compared to the epithelium of small-caliber bronchi. Conclusion. The obtained results on the frequency of occurrence of morphological changes in large-caliber bronchi are of theoretical interest for further research to identify groups at high risk of progression of non-small cell lung cancer.

Peri-operative outcomes following radical prostatectomy in the setting of advanced prostate cancer.

To compare the peri-operative outcomes of radical prostatectomy (RP) for locally advanced, node-positive, and metastatic prostate cancer (PCa), as determined through pathological staging, using the American College of Surgeons National Surgical Quality Improvement Project. We identified RP procedures performed between 2019 and 2021. Patients were stratified by pathological staging to compare the effect of locally advanced disease (T3-4), node positivity (N+) and metastasis (M+) vs localised PCa (T1-2 N0 M0). Baseline demographics and 30-day outcomes, including operating time, length of hospital stay (LOS), 30-day mortality, readmissions, reoperations, major complications, minor complications and surgery-specific complications, were compared between groups. Pathological staging data were available for 9276 RPs. Baseline demographics were comparable. There was a slightly higher rate of minor complications in the locally advanced cohort, but no significant difference in major complications, 30-day mortality, readmissions, or rectal injuries. Node positivity was associated with longer operating time, LOS, and some slightly increased rates of 30-day complications. RP in patients with metastatic disease appeared to be similarly safe to RP in patients with M0 disease, although it was associated with a longer LOS and slightly increased rates of certain complications. For patients with pathologically determined locally advanced, node-positive, and metastatic PCa, RP appears to be safe, and is not associated with significantly higher rates of 30-day mortality or major complications compared to RP for localised PCa. This study adds to the growing body of literature investigating the role of RP for advanced PCa; further studies are needed to better characterise the risks and benefits of surgery in such patients.

Transcriptional, growth factors, components of the AKT/mTOR signaling pathway, receptors and ligands of programmed cell death expression in melanoma

Introduction. Melanoma is the most dangerous neoplasm of the skin, characterized by a malignant and aggressive course. Transcriptional and growth factors, components of the AKT/mTOR signaling pathway, receptors and ligands of programmed cell death are involved in significant processes of oncogenesis.Aim. To study the expression of components of the AKT/mTOR (mTOR – mammalian target of rapamycin) signaling pathway, transcription and growth factors, expression of AMPK, LC3B, programmed cell death 1 (PD-1), programmed death-ligand 1 PD-L1 and programmed death-ligand 2 (PD-L2) in skin and mucosal tumor tissues.Materials and methods. The study included 21 patients with a verified diagnosis of melanoma of the skin of various localizations and mucous membranes of the nasal cavity T1a–4bN0M0 (I–IV stages) and 18 patients with basal cell carcinoma of the skin of various localizations T1–4N0M0 (I–VIA stages), aged 45 to 72 years old, who were treated in the department of head and neck tumors of the Cancer Research Institute, Tomsk National Research Medical Center. The presence of tumor ulceration was determined by microscopy and registration of the true absence of the epidermis over the tumor or due to traumatization of the epidermis. Expression of components of the AKT/mTOR signaling pathway, transcription and growth factors, expression of AMPK, LC3B, PD-1, PD-L1 and PD-L2 in the tumor tissue was determined by real-time polymerase chain reaction.Results. An increase in the expression of 70 S6 kinase and VHL was found in melanoma tissues compared to basal cell carcinoma. At the same time, the presence of signs of ulceration was associated with a low level of c-RAF, nuclear factor kappa B (NF-kB) p50 and hypoxia-inducible factor 1 (HIF-1) matrix RNA (mRNA) against the background of an increase in the expression of the hypoxia-inducible factor 2 (HIF-2) transcription factor. The study of the molecular features of neoplasms in relation to the tumor thickness according to Breslow revealed the contribution of transcription and growth factors, the intensity of intracellular signaling processes, modification of the microenvironment, autophagy and neoangiogenesis.Conclusion. The molecular and biological features of melanomas associated with invasive tumor growth have been identified. An increase in the expression of 70 S6 kinase and VHL are characteristic of a malignant skin tumor. The presence of signs of ulceration and tumor invasion were associated with a change in the transcriptional characteristics of factors with the induction of key markers, oncogenesis, which contributes to the formation of the invasive potential of the tumor.

Analysis of molecular phenotypes in normal mucosa and colorectal cancer in embryonic anatomical parts of the colon

Background: Differences in the embryonic development of the colonic mucosa determine the physiological embryonic-anatomical asymmetry of its structure and can manifest themselves via different molecular phenotypes (expression profiles) of the colon segments. These molecular characteristics are hypothesized to determine differences in the carcinogenesis mechanisms and influence the prognosis of right- or left-sided colorectal cancer (CRC). Studies of the tumors molecular phenotypes depending on their localization may be of interest for assessment of the prognosis and choice of treatment for CRC.
 Aim: To perform comparative analysis of molecular phenotypes of the normal colonic mucosa and adenocarcinoma CRC tissues depending on the natural embryonic anatomic asymmetry of the colon.
 Materials and methods: We performed a retrospective study of molecular phenotypes (mRNA expression of 61 genes) from different embryonic-anatomical parts of healthy colon and CRC. The normal group included 254 samples of mucosa from three different parts of the colon from 74 healthy donors who had no cancer and no organic abnormalities of the colon, including 90 samples from the right colon, 116 from the left colon, and 48 from the rectum. The CRC group consisted of 154 samples of localized stage T1–4N0–2M0 adenocarcinoma from 154 patients who had not received neoadjuvant radio- and chemotherapy, including 40 samples from the right colon, 54 from the left colon, and 60 from the rectum. The relative mRNA abundance of 61 genes was assessed by reverse-transcriptase polymerase chain reaction. In both groups, the resulting expression phenotypes were compared between the anatomical parts of the colon. Statistical management of the data included the discriminant analysis with stepwise inclusion of variables.
 Results: Based on the assessment of the mRNA level of the studied genes, a discriminant model was built that allows for classification of the normal group samples according to their anatomic origin in the colon with an accuracy of 95.8%. The most significant (p 0.05) for classification are the following 19 genes: CCND1, SCUBE2, TERT, BAG1, NDRG, IL1b, IL2Ra, IL7, ESR1, TGFb, IGF1, MMP9, MMP11, PAPPA, CD45, CD69, TLR2, TLR4, LIFR. The discriminant model built for the CRC group included 27 genes and made it possible to differentiate samples from three parts of colon with an accuracy of 75.2%. A statistically significant (p 0.05) contribution to the samples differentiation by the discriminant model was made by the COX-2, BIRC5, LIFR, TPA, IL1b, MMP11, MMP7, and P16INK4A genes. When combining samples from the two groups into one model in accordance with their embryonic-anatomical origin, there was a clear separation of tumor tissue samples and healthy colonic mucosa in the discriminant function space.
 Conclusion: The analysis of CRC gene expression profiles using the discriminant model showed that genetic changes in the colonic mucosa in CRC flatten the molecular phenotypic boundaries of the embryonic-anatomical parts. These changes are specific to CRC, forming a particular “pathological” molecular phenotype.

Clinical T2 N0 M0 Esophageal Cancer: Identifying Predictive Factors of Upstaging

Clinical T2 N0 M0 Esophageal Cancer: Identifying Predictive Factors of Upstaging