T1 N0 M0 Research Articles

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

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

Laparoscopic Central Pancreatectomy with Modified Blumgart Pancreatojejunostomy for Pancreatic Neuroendocrine Tumor.

This report with a video describes a laparoscopic central pancreatectomy with modified Blumgart pancreatojejunostomy for pancreatic neuroendocrine tumor. A 71-year-old woman presented with a single 17 mm lesion in the pancreatic neck, responsible for dilatation of the main pancreatic duct. Cancer staging showed no additional location. Somatostatin receptor imaging was positive. After a multidisciplinary discussion in the French national reference network for the management of neuroendocrine tumor (RENATEN) surgery with central pancreatectomy was decided. The operation time was 320 min and the estimated blood loss was less than 100 ml. Final pathology confirmed a pancreatic NET of 13 mm staged as T1 N0 M0 R0 G1 with a Ki-67 of 2%. After lymph node dissection, five nodes were analyzed and were found to be noninvaded. The postoperative course was uneventful. Laparoscopic central pancreatectomy is an excellent alternative for sparing pancreatic parenchyma.

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.

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.

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

BackgroundSublobar resection of early-stage non-small cell lung cancer (NSCLC) is increasingly considered appropriate but may compromise margins compared with lobectomy. This study evaluated resection extent, margin status, and survival in patients with clinical stage I NSCLC. MethodsPatients with clinical T1-2 N0 M0 NSCLC in the National Cancer Database (2006-2020) who were treated with primary surgery were compared stratified by margin status. The potential benefit of radiation was explored in subgroup analysis of patients who underwent sublobar resection with positive margins. ResultsPositive margins occurred in 5089 (2.8%) of 181,824 patients and were more common in sublobar resections compared with lobectomy (4.3% vs 2.4%; P < .001). Sublobar resection had the strongest association with positive margins in multivariable analysis (odds ratio, 2.06; 95% CI, 1.91-2.23; P < .001). Patients with positive margins were more likely to undergo both adjuvant chemotherapy (16% vs 13%; P < .001) and radiation (17% vs 1%; P < .001) but had worse survival in univariate analysis (44.0% 5-year overall survival vs 69.2%; P < .001) and multivariable Cox analysis (hazard ratio, 1.71; 95% CI, 1.63-1.78; P < .001) in the entire cohort, as well as in a univariate subset analysis of lobectomy (46.9% vs 70.4%; P < .001) and sublobar resection (37.5% vs 64.1%; P < .001). Postoperative radiation for patients who underwent sublobar resection with positive margins did not improve 5-year overall survival (36.3% for irradiated patients vs 38.3% for nonirradiated patients; P = .57), and patients who underwent sublobar resection with positive margins who were treated with radiation had survival inferior to that of patients who underwent lobectomy with negative margins. ConclusionsPositive margins occur more frequently after sublobar resection of clinical stage I NSCLC compared with lobectomy. Patients with positive margins have worse survival than patients who undergo complete resection and are not rescued by postoperative radiation.

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 &lt; 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

IntroductionThe international phase II single-arm LungTech trial 22113-08113 of the European Organization for Research and Treatment of Cancer assessed the safety and efficacy of stereotactic body radiotherapy (SBRT) in patients with centrally located early-stage NSCLC. MethodsPatients with inoperable non-metastatic central NSCLC (T1-T3 N0 M0, ≤7cm) were included. After prospective central imaging review and radiation therapy quality assurance for any eligible patient, SBRT (8 × 7.5 Gy) was delivered. The primary endpoint was freedom from local progression probability three years after the start of SBRT. ResultsThe trial was closed early due to poor accrual related to repeated safety-related pauses in recruitment. Between August 2015 and December 2017, 39 patients from six European countries were included and 31 were treated per protocol and analyzed. Patients were mainly male (58%) with a median age of 75 years. Baseline comorbidities were mainly respiratory (68%) and cardiac (48%). Median tumor size was 2.6 cm (range 1.2–5.5) and most cancers were T1 (51.6%) or T2a (38.7%) N0 M0 and of squamous cell origin (48.4%). Six patients (19.4%) had an ultracentral tumor location. The median follow-up was 3.6 years. The rates of 3-year freedom from local progression and overall survival were 81.5% (90% confidence interval [CI]: 62.7%–91.4%) and 61.1% (90% CI: 44.1%–74.4%), respectively. Cumulative incidence rates of local, regional, and distant progression at three years were 6.7% (90% CI: 1.6%–17.1%), 3.3% (90% CI: 0.4%–12.4%), and 29.8% (90% CI: 16.8%–44.1%), respectively. SBRT-related acute adverse events and late adverse events ≥ G3 were reported in 6.5% (n = 2, including one G5 pneumonitis in a patient with prior interstitial lung disease) and 19.4% (n = 6, including one lethal hemoptysis after a lung biopsy in a patient receiving anticoagulants), respectively. ConclusionsThe LungTech trial suggests that SBRT with 8 × 7.5Gy for central lung tumors in inoperable patients is associated with acceptable local control rates. However, late severe adverse events may occur after completion of treatment. This SBRT regimen is a viable treatment option after a thorough risk–benefit discussion with patients. To minimize potentially fatal toxicity, careful management of dose constraints, and post-SBRT interventions is crucial.

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.&#x0D; 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.&#x0D; 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.&#x0D; 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.&#x0D; 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

BackgroundInaccuracy of clinical staging renders management of clinical T2 N0 M0 (cT2 N0 M0) esophageal cancer difficult. When an underlying advanced-stage disease is understaged to cT2 N0 M0, patients miss the opportunity to gain the potential benefits of neoadjuvant therapy. This study aimed to identify preoperative factors that predict underlying advanced-stage esophageal cancer. MethodsFrom 2000 to 2020, 1579 patients with esophageal cancer underwent esophagectomy. Sixty patients who underwent upfront surgery for cT2 N0 M0 esophageal cancer were included in this study. The median age was 62.5 years, and 78% (n = 47) of these patients were male. Radiologic, clinical, and endoscopic factors were evaluated as preoperative markers. The Fisher exact and the Wilcoxon rank sum tests were used for categoric and continuous variables, respectively. Random forest classification was used to identify preoperative factors for predicting upstaging and downstaging. ResultsOf the 60 patients, 8 (13%) were found to have pathologic T2 N0 M0 esophageal cancer. Sixteen (27%) patients had cancer that was pathologically downstaged, and 36 (60%) had upstaged disease. Seven (19%) patients had upstaged cancer on the basis of the pathologic T stage, 14 (39%) had upstaging on the basis of the pathologic N stage, and 15 (42%) had upstaging on the basis of both T and N stages. Dysphagia (P = .003) and tumor maximum standardized uptake value (P = .048) were predictors of upstaging, with a combined predictive value of up to 75%. ConclusionsThe presence of dysphagia and of high maximum standardized uptake value (≥5) of the tumor is predictive of more advanced underlying disease for patients with cT2 N0 M0 esophageal cancer, and these patients should be considered for neoadjuvant therapy.

Association of integrin expression in tumor tissue with hematogenic metastasis of breast cancer

Background. Distant hematogenous metastasis is the leading cause of tumor-related death from breast cancer. To prevent metastasis, prognostic markers for predicting the risk and location of hematogenous metastases are required. In this regard, it is of great importance to study the expression of integrins involved in the most important processes that determine the progression of cancer.The objective of the study was to investigate the association of integrin expression in tumor tissue with hematogenous metastasis of patients with breast cancer.Material and Methods. The study included 72 patients (average age – 51 ± 12 years) with stage T1–4N0–3M0–1 unspecifed invasive ductal breast carcinoma, with all molecular biological subtypes (luminal A, luminal B, HER2-positive and triple negative). The biopsy material was examined before the start of antitumor treatment. Expression of integrins in tumor cells was assessed by immunohistochemical methods. Antibodies CD61 (integrin β3, Invitrogen, USA), CD104 (integrin β4, Invitrogen, USA), CD51 (integrin αV, Invitrogen, USA) were used.Results. In patients with hematogenous metastases, cytoplasmic rather than cytoplasmic/membrane colocalization, CD61 expression was more often detected (p=0.036). Cytoplasmic and membrane colocalization of CD104 was more frequently detected in brain metastases compared to lung (p=0.026) and bone (p=0.036) metastases. Expression of CD51 integrin was more often associated with lung metastases than with bone metastases (p=0.045).Conclusion. The frequency and localization of hematogenous metastases in breast cancer patients are associated with the presence and localization of CD61, CD104 and CD51 expression in the tumor cell.

Primary gastric rhabdomyosarcoma. A rare cause of an upper gastrointestinal bleeding.

Adenocarcinoma accounts for 90% of malignant gastric tumours. Lymphomas, gastrointestinal stromal tumours (GIST) and other less frequent tumours account for 10%. However, rhabdomyosarcoma (RMS) remains a rare cause within the broad differential diagnosis of gastric lesions. Most cases of gastrointestinal RMS in adults are metastatic disease so primary RMS is extremely rare. A few cases reports of esophageal and gastric RMS have been published. This is a 76-year-old patient with a history of oncological oncology of poorly differentiated lung adenocarcinoma T2N1M0 in 2008 treated with surgery with no signs of recurrence. She presented to emergency with occasional episodes of melena and iron deficiency anemia for the last 3 months. The laboratory findings showed moderated anemia. Gastroscopy was performed and a prominent submucosal and ulcerated bulge was observed at the posterior wall of the gastric body and fundus. A histologic examination reveled tissue fragments composed of small round spindle-shaped cells. Tumor cells had atypical nuclei showing dense chromatin ad pale to eosinophilic cytoplasm. Immunohistochemically, the tumor was positive for AE1/3, desmin, myogenin and CD56. Patient was diagnosed with primary gastric RMS. Thoraco-abdominopelvic CT showed a locally advanced stage (T2 N1M0).

Prognostic factors for local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision

Prognostic factors for local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision. BackgroundThe standard curative treatment for locally advanced rectal cancer of the middle and lower thirds is long-course chemoradiotherapy followed by total mesorectal excision. PurposeTo evaluate the prognostic factors associated with local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision. MethodsRetrospective study including patients with rectal cancer T3–4N0M0 or T (any)N + M0 located within 10 cm from the anal border, or patients with T2N0M0 located within 5 cm, treated by long course chemoradiotherapy followed by total mesorectal excision with curative intent. Clinical, demographic, radiologic, surgical, and anatomopathological data were collected. Local recurrence was estimated using the Kaplan-Meier function, and risk was estimated according to each characteristic using univariate and multivariate analyses. Results270 patients were included, 57.8% male and mean age 61.7 (30‒88) years. At initial staging, 6.7% of patients were stage I, 21.5% stage II, and 71.8% stage III. Open surgery was performed in 65.2%, with sphincter preservation in 78.1%. Mortality within 30 postoperative days was 0.7%. After 49.4 (0.5‒86.1) months of median follow-up, overall and local recurrences were 26.3% and 5.9%. On multivariate analyses, local recurrence was associated with involvement of the mesorectal fascia on restaging MRI (HR = 9.11, p = 0.001) and with pathologic involvement of radial surgical margin (HR = 8.19, p < 0.001). ConclusionLocal recurrence of rectal cancer treated with long-course chemoradiation and total mesorectal excision is low and is associated with pathologic involvement of the radial surgical margin and can be predicted on restaging MRI.

The role of radiation therapy in the treatment of early-stage skin cancer

Introduction. Radiation therapy remains one of the main methods of radical treatment of early-stage skin cancer. Its position in combination and comprehensive treatment has changed significantly as improvements of radiotherapy techniques and introduction of modern technologies led to increased effectiveness and comfort of the method and allowed to achieve better prognostic outcomes.Aim. To evaluate the role of radiotherapy in treatment of patients with early-stage skin cancer (T1–2N0M0).Materials and methods. A retrospective and prospective analyses of data from 1049 patients with early-stage skin cancer were performed. In 527 (50.23 %) cases, the tumor was localized mainly on the head and neck: 48 % of patients had nonkeratinizing squamous cell carcinoma of the skin, 7.59 % of patients had keratinizing squamous cell carcinoma, 44.41 % of patients had basal cell carcinoma.Results. Data from 527 patients (51.04 % man and 48.96 % women) with early-stage skin cancer (T1–2N0M0) who received treatment and are registered at the Republican Oncological Scientific Center of the Ministry of Health and Social Protection of the Tajikistan Republic were analyzed. The disease was more common in patients aged between 60 and 90 years. The main factor in stage determination was tumor size in accordance with the Tumor, Nodus and Metastasis (TNM) classification. In 240 (46.54 %) patients, the size of primary tumor was less than 2 cm in the largest diameter (T1N0M0), in 287 (54.46 %) patients its maximal size was between 2 and 4 cm (T2N0M0). Selection of treatment method was mainly based on morphological characteristics and location of the tumor. In 121 (50.42 %) patients with skin cancer T1N0M0, radiation therapy was performed as monotherapy in a radical program; in 88 (36.37 %) patients in combination with cobalt therapy and surgery; in 23 (9.59%) patients in combination with cobalt therapy, polychemotherapy and surgery; in 8 (3.41%) patients in combination with cobalt therapy and polychemotherapy.The capabilities of radiation therapy both as monotherapy and in combination with other treatment methods before and after surgical treatment present ample opportunities for clinicians to achieve good outcomes. The use of radiation therapy as monotherapy in a radical program in patients with T1N0M0 stage skin cancer is effective in 96.4 % of cases, in patients with stage T2N0M0 the effectiveness can reach 91.2 %.Conclusion. Radiation therapy can be successfully used in treatment of early-stage skin cancer along with other methods. Its use both independently and as part of combination and comprehensive therapy allows to achieve reliable treatment outcomes. Adequate selection of radiation therapy option in treatment of early-stage skin cancer is the key to longterm clinical remission and improvement of patients’ quality life.

Возможности использования профилирования экспрессии мРНК для прогноза прогрессирования локальных стадий колоректального рака

Progression assessment enables implementation of the colorectal cancer (CRC) tertiary prevention measures aimed at early detection and timely treatment of metastatic cancer. The study was aimed to develop a model of CRC progression using pathomorphological and molecular genetic characteristics of tumors. Relative expression of mRNAs of 63 genes from various functional groups was determined in the tumor specimens of 223 patients with stage T1–4N0–2M0 CRC. The median follow-up period was 42 months. Binary logistic regression models were constructed, in which likelihood of progression within 36 months after the CRC diagnosis was a target variable. Explanatory variables were as follows: tumor grade, angiolymphatic invasion, ratio of the number of metastatic lymph nodes to the total number of lymph nodes in the surgical specimen, patient’s age and tumor localization, as well as expression levels of genes CCNB1, Ki67, GRB7, IGF1, Il2, Il6, Il8, GATA3. Prediction accuracy of the model using clinical and morphological characteristics was 56.6%. Inclusion of CCNB1, Ki67, GRB7, IGF1, Il2, Il6, Il8, GATA3 expression profiles in the model increased accuracy to 80.6%. Thus, prediction of CRC progression for treatment personalization requires additional parameters beyond information acquired within the framework of conventional morphological TNM classification. The use of molecular markers as predictors significantly increases the CRC progression prediction accuracy. Further research is needed for validation and quality improvement of prognostic models.