Prelude to malignancy: A gene expression signature in normal mammary gland from breast cancer patients suggests pre-tumorous alterations and is associated with adverse outcomes.

Despite advances in early detection and treatment strategies, breast cancer recurrence and mortality remain a significant health issue. Recent insights suggest the prognostic potential of microscopically healthy mammary gland, in the vicinity of the breast lesion. Nonetheless, a comprehensive understanding of the gene expression profiles in these tissues and their relationship to patient outcomes remain missing. Furthermore, the increasing trend towards breast-conserving surgery may inadvertently lead to the retention of existing cancer-predisposing mutations within the normal mammary gland. This study assessed the transcriptomic profiles of 242 samples from 83 breast cancer patients with unfavorable outcomes, including paired uninvolved mammary gland samples collected at varying distances from primary lesions. As a reference, control samples from 53 mammoplasty individuals without cancer history were studied. A custom panel of 634 genes linked to breast cancer progression and metastasis was employed for expression profiling, followed by whole-transcriptome verification experiments and statistical analyses to discern molecular signatures and their clinical relevance. A distinct gene expression signature was identified in uninvolved mammary gland samples, featuring key cellular components encoding keratins, CDH1, CDH3, EPCAM cell adhesion proteins, matrix metallopeptidases, oncogenes, tumor suppressors, along with crucial genes (FOXA1, RAB25, NRG1, SPDEF, TRIM29, and GABRP) having dual roles in cancer. Enrichment analyses revealed disruptions in epithelial integrity, cell adhesion, and estrogen signaling. This signature, named KAOS for Keratin-Adhesion-Oncogenes-Suppressors, was significantly associated with reduced tumor size but increased mortality rates. Integrating molecular assessment of non-malignant mammary tissue into disease management could enhance survival prediction and facilitate personalized patient care.

Two-Axial Measurement of the Angular Microdeflection of a Laser Beam Using One Single-Axis Sensor.

The majority of current methods for measuring the angular deflection of a laser beam enable measurement only in one selected plane. However, there are tasks in which measurements of laser beam deflections in 3D are required. In this paper, we present a way of enabling two-axial measurements of the deflection of a beam based on a single-axis sensor. The key idea is to direct a laser beam, alternately, into one of two arms of a measurement system. In the first arm, the beam is transmitted directly to the angular sensor, while in the second, the beam is directed to the sensor via a special optical element that rotates the plane of the beam deflection; in other words, this element changes the deflection in the horizontal plane into a deflection in the vertical plane, and vice versa. To alternate the path of the beam, a variable phase retarder and a polarising beamsplitter are used. The proposed technique was experimentally verified, and the results confirm its effectiveness.

Efficacy of endoscopic surveillance in the detection of local recurrence after radical rectal cancer surgery is limited? A retrospective study.

BACKGROUND: Rectal cancer, one of most common neoplasms, is characterized by an overall survival rate exceeding 60%. Nonetheless, local recurrence (LR) following surgery for rectal cancer remains a formidable clinical problem. The aim of this study was to assess the value of postoperative endoscopic surveillance (PES) for the early detection of LR in rectal cancer after radical anterior resection with sigmoid-rectal anastomosis. METHODS: We performed an anterior resection in 228 patients with stages I­III rectal cancer who had undergone surgery from 2001 to 2008 in the Oncology Center in Bydgoszcz, Poland. Of these patients, 169 had perioperative radiotherapy or radiochemotherapy. All patients underwent PES with abdominal and pelvic imaging (abdominal ultrasound, computed tomography, magnetic resonance) and clinical examination. Sensitivities, specificities, positive likelihood ratios, negative likelihood ratios, and receiver operating characteristic curves were calculated to compare the value of colonoscopy versus imaging techniques for the diagnosis of LR. RESULTS: During the 5-year follow-up, recurrences occurred in 49 (21%) patients; of these, 15 (6%) had LR, which was most often located outside the intestinal lumen (n = 10, 4%). Anastomotic LR occurred in 5 (2%) patients. The mean time to anastomotic LR was 30 months after initial surgery, similar to that of other locations (29 months). Both imaging and endoscopy were shown to be efficient techniques for the diagnosis of LR in anastomotic sites. In the study group, endoscopy did not provide any additional benefit in patients who were receiving radiation therapy. CONCLUSIONS: The benefit of PES for the detection of LR after curative treatment of rectal cancer is limited and not superior to imaging techniques. It remains a useful method, however, for the histopathological confirmation of suspected or confirmed recurrence.

Clinical Reality and Treatment for Local Recurrence of Rectal Cancer: A Single-Center Retrospective Study.

Background and Objectives: Despite advances in treatment, local recurrence remains a great concern in patients with rectal cancer. The aim of this study was to investigate the incidence and risk factors of local recurrence of rectal cancer in our single center over a 7-year-period. Materials and Methods: Patients with stage I-III rectal cancer were treated with curative intent. The necessity for radiotherapy and chemotherapy was determined before surgery and/or postoperative histopathological results. Results: Of 365 rectal cancer patients, 76 (20.8%) developed recurrent disease. In total, 27 (7.4%) patients presented with a local tumor recurrence (isolated in 40.7% of cases). Radiotherapy was performed in 296 (81.1%) patients. The most often used schema was 5 × 5 Gy followed by immediate surgery (n = 214, 58.6%). Local recurrence occurred less frequently in patients treated with 5 × 5 Gy radiotherapy followed by surgery (n = 9, 4%). Surgical procedures of relapses were performed in 12 patients, six of whom were operated with radical intent. Only two (7.4%) patients lived more than 5 years after local recurrence treatment. The incidence of local recurrence was associated with primary tumor distal location and worse prognosis. The median overall survival of patients after local recurrence treatment was 19 months. Conclusions: Individualized rectal cancer patient selection and systematic treatment algorithms should be used clinical practice to minimize likelihood of relapse. 5 × 5 Gy radiotherapy followed by immediate surgery allows good local control in resectable cT2N+/cT3N0 patients. Radical resection of isolated local recurrence offers the best chances of cure.

Prospective evaluation of the quality of life of patients undergoing surgery for colorectal cancer depending on the surgical technique.

PURPOSE: Monitoring of the quality of life of patients in addition to satisfactory survival indexes in order to choose an optimal treatment method is a trend in contemporary oncological surgery. The goal of the study was to prospectively evaluate the quality of life of patients treated for colorectal cancer depending on the type of surgical technique (open surgery (OS) vs. laparoscopic surgery (LS)). METHODS: The quality of life was evaluated thrice in the study groups (on the day of admission to the ward (I), 6 months (II), and 18 months after the procedure (III)). The following questionnaires were used in this evaluation: QLQ-C30 European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, QLQ-CR29 Quality of Life Questionnaire (module-colorectal cancer), and Acceptance of Illness Scale (AIS). RESULTS: Sixty-seven patients completed this prospective clinical cohort study (LS-32; OS-35). The QLQ-C30 questionnaire demonstrated improvement in functional scales among patients treated with LS technique (p < 0.05) as well as with regard to overall quality of life 6 months after surgery (p < 0,001), while at 18 months postsurgery, statistically significant differences were noted for physical function (p = 0.001) and overall quality of life (p < 0.0001). AIS scale analysis demonstrated that patients treated with laparoscopy were characterized by better acceptance of illness (p < 0.05). Statistically significant differences between OS and LS groups were noted based on the QLQ-CR29 questionnaire with regard to the following scales: body image (p = 0.041) and body mass problem (p = 0.024)-patients treated with LS technique had better scores. CONCLUSIONS: Laparoscopic surgery gives patients a chance for better quality of life.

Signatures of post-zygotic structural genetic aberrations in the cells of histologically normal breast tissue that can predispose to sporadic breast cancer.

Sporadic breast cancer (SBC) is a common disease without robust means of early risk prediction in the population. We studied 282 females with SBC, focusing on copy number aberrations in cancer-free breast tissue (uninvolved margin, UM) outside the primary tumor (PT). In total, 1162 UMs (1-14 per breast) were studied. Comparative analysis between UM(s), PT(s), and blood/skin from the same patient as a control is the core of the study design. We identified 108 patients with at least one aberrant UM, representing 38.3% of cases. Gains in gene copy number were the principal type of mutations in microscopically normal breast cells, suggesting that oncogenic activation of genes via increased gene copy number is a predominant mechanism for initiation of SBC pathogenesis. The gain of ERBB2, with overexpression of HER2 protein, was the most common aberration in normal cells. Five additional growth factor receptor genes (EGFR, FGFR1, IGF1R, LIFR, and NGFR) also showed recurrent gains, and these were occasionally present in combination with the gain of ERBB2. All the aberrations found in the normal breast cells were previously described in cancer literature, suggesting their causative, driving role in pathogenesis of SBC. We demonstrate that analysis of normal cells from cancer patients leads to identification of signatures that may increase risk of SBC and our results could influence the choice of surgical intervention to remove all predisposing cells. Early detection of copy number gains suggesting a predisposition toward cancer development, long before detectable tumors are formed, is a key to the anticipated shift into a preventive paradigm of personalized medicine for breast cancer.

Contemporary enteral and parenteral nutrition before surgery for gastrointestinal cancers: a literature review.

BACKGROUND: Gastrointestinal cancers are among the most recognised oncological diseases in well-developed countries. Tumours located in the digestive tract may cause the fast occurrence of malnutrition. MAIN TEXT: The perioperative period is a special time for systemic metabolism. Thanks to published guidelines, early universal control nutritional status before treatment, patients may have a chance to get suitable nutritional intervention. Although the first line of the intervention-nutritional consultation as well as the fortification of a diet and oral nutritional support (ONS)-is not debatable, in a case of inability of undergoing an oral feeding, the choice of the way of administration in patients before a surgery may represent a serious clinical obstacle. CONCLUSIONS: Although there is broad agreement in the staging, classification, and role of surgery and nutritional status for outcomes of treatment of gastrointestinal cancers, there the way of nutritional intervention in patients with gastrointestinal cancer are still discussed.

Gastric cancer increases transmigratory potential of peripheral blood monocytes by upregulation of ß1- and ß2-integrins.

INTRODUCTION: Immune responses within the tumor depend on the ability of leukocytes to migrate from peripheral circulation into the local microenvironment. This process is controlled by mechanisms that guide leukocytes to the side of inflammation, allowing them to cross vascular endothelial barrier. Monocytes/macrophages are the predominant population of leukocyte infiltrate of many tumors, including, gastric cancer. However, to date mechanisms that control monocyte trafficking to the side of tumor growth are not fully elucidated. AIM OF THE STUDY: It this study we aimed to evaluate transmigratory potential of peripheral blood monocytes from gastric cancer patients. MATERIAL AND METHODS: By using multicolor flow cytometry we assessed expression of ß1- and ß2-integrins on peripheral blood monocytes from gastric cancer patients. RESULTS: We found increased frequencies of VLA-4 and VLA-6 expressing monocytes and increased expression of analyzed ß2-integrins in gastric cancer patients when compared to age matched controls. CONCLUSIONS: In summary, this study revealed that gastric cancer increases transmigratory potential of peripheral blood monocytes.

Keratin 7 expression in lymph node metastases but not in the primary tumour correlates with distant metastases and poor prognosis in colon carcinoma.

Colorectal carcinoma (CRC) is one of the leading causes of cancer-related deaths worldwide. Alterations in keratin expression, including keratin 7 (K7), are frequent findings in multiple cancers, and they constitute a prognostic factor. The aim of our study was to evaluate the prognostic significance of K7 in the primary tumour and lymph node metastases in two separate cohorts of patients: the first one with lymph node involvement (LN+, 129 cases) and the second one free of LN metastases (LN-, 85 cases). Keratin 7 expression in CRC was analysed on tissue microarrays with immunohistochemistry and evaluated using the h-score. In the LN+ group K7 positivity was identified in 7/129 (5.4%) of primary tumours (PT) and lymph node metastases (LNM); concordance between them was 94% ( 0.396). Keratin 7 was expressed in 8/85 cases (9.4%) in the LN- group. K7 expression in LNM of the LN+ cohort correlated with shorter overall survival (OS) (p = 0.047) and presence of distant metastases at diagnosis (p = 0.005). Expression of K7 in the primary tumour in both cohorts did not correlate with survival. We conclude that the status of K7 expression in metastatic lymph nodes from CRC is a poor prognostic factor.

Preliminary results of Polish national multicenter LILEO study on ileostomy reversal.

<b><br>Introduction:</b> Ileostomy reversal is a common surgical procedure and currently standardized perioperative and surgical protocols are lacking.</br> <b><br>Aim:</b> LILEO study was designed to perform a multicenter analysis on numerous perioperative parameters and estimation of the incidence of postoperative complications.</br> <b><br>Materials and methods:</b> The study is an open multicenter prospective cohort study. Preliminary results of the LILEO study after 3 months were available from 18 Polish surgical centers comprising full data of 59 patients who underwent ileostomy reversal.</br> <b><br>Results:</b> Parameters such as preoperative care, surgical technique, postoperative course and complications were analyzed. Preoperative fasting was used in 49.1% of patients. Fifty nine percent of anastomosis were handsewn and in 72.9% of patients had primary single suture wound closure. Mean length of hospital stay was 7.9 days (min 2 days, max 26 days). Complications occurred overall in 20 patients (33.9%). In 11.9% of patient's complications had grade III A/B in Clavien-Dindo classification.</br> <b><br>Discussion:</b> The perioperative care in the group of patients undergoing ileostomy reversal still lacks standardized and optimized treatment.</br> <b><br>Conclusions:</b> Ileostomy removal is a procedure with high risk of postoperative complications. Standardization of perioperative care based on further multicenter national study could result in a decrease of complications rate.</br>.

Preliminary results of Polish national multicenter study on colostomy reversal - LICO (Liquidation of Colostomy) study.

Introduction: Creation of colostomy is still a commonly performed procedure in emergency settings, when intestinal anastomosis cannot be performed safely. Reversing a stoma has been linked with high rates of morbidity and also mortality. Aim: The primary goal of the study was to identify the risk of postoperative complications in patients undergoing colostomy liquidation. The secondary goal was to assess perioperative care parameters. Material and methods: The LIquidation of COlostomy (LICO) study is an open multicenter prospective cohort study that began in October 2022 and will continue until December 2023. Data from 20 Polish surgical departments were collected. Overall 45 patients were reported over the initial 3 months; based on that group we performed a preliminary analysis. Results: Mean operative time was 163 min. Patients were operated on by specialists in 93.3% of cases. Complications occurred in 15 (33.3%) patients. Wound infection was the most common complication (17.8%). In 3 (6.7%) cases anastomotic leakage was diagnosed, and in 2 of those cases reoperation was required. The overall mortality rate was 2.2%. The mean length of hospital stay was 10.1 days. Preoperative fasting was used in 53.3% of patients, and the mechanical bowel preparation rate was 75.6%. Only in 8.9% of cases was laparoscopic access used for stoma reversal, and only in 1 out of 45 cases was mesh used for incisional peristomal hernia prophylactics. The stoma site was closed by single sutures in 73.3%, and negative pressure assisted closure was performed in 6.7% of patients. Conclusions: Colostomy liquidation is associated with significant morbidity and minor mortality in the Polish population. Standardized perioperative care should be established for stoma reversal surgery.

Mass Spectrometry Proteomics Characterization of Plasma Biomarkers for Colorectal Cancer Associated With Inflammation.

Background: Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using colonoscopy, limited by its invasiveness and high cost. Therefore, non-invasive, cost-effective, and accurate alternatives are urgently needed. Objective and design: This retrospective multi-center plasma proteomics study was performed to identify potential blood-based biomarkers in 36 CRC patients and 26 healthy volunteers by high-resolution mass spectrometry proteomics followed by the validation in an independent CRC cohort (60 CRC patients and 44 healthy subjects) of identified selected biomarkers. Results: Among the 322 identified plasma proteins, 37 were changed between CRC patients and healthy volunteers and were associated with the complement cascade, cholesterol metabolism, and SERPIN family members. Increased levels in CRC patients of the complement proteins C1QB, C4B, and C5 as well as pro-inflammatory proteins, lipopolysaccharide-binding protein (LBP) and serum amyloid A4, constitutive (SAA4) were revealed for first time. Importantly, increased level of C5 was verified in an independent validation CRC cohort. Increased C4B and C8A levels were correlated with cancer-associated inflammation and CRC progression, while cancer-associated inflammation was linked to the acute-phase reactant leucine-rich alpha-2-glycoprotein 1 (LRG1) and ceruloplasmin. Moreover, a 4-protein signature including C4B, C8A, apolipoprotein C2 (APO) C2, and immunoglobulin heavy constant gamma 2 was changed between early and late CRC stages. Conclusion: Our results suggest that C5 could be a potential biomarker for CRC diagnosis. Further validation studies will aid the application of these new potential biomarkers to improve CRC diagnosis and patient care.

Loss of Y in regulatory T lymphocytes in the tumor micro-environment of primary colorectal cancers and liver metastases.

Male sex is a risk factor for colorectal cancer (CRC) with higher illness burden and earlier onset. Thus, we hypothesized that loss of chromosome Y (LOY) in the tumor micro-environment (TME) might be involved in oncogenesis. Previous studies show that LOY in circulating leukocytes of aging men was associated with shorter survival and non-hematological cancer, as well as higher LOY in CD4 + T-lymphocytes in men with prostate cancer vs. controls. However, nothing is known about LOY in leukocytes infiltrating TME and we address this aspect here. We studied frequency and functional effects of LOY in blood, TME and non-tumorous tissue. Regulatory T-lymphocytes (Tregs) in TME had the highest frequency of LOY (22%) in comparison to CD4 + T-lymphocytes and cytotoxic CD8 + T-lymphocytes. LOY score using scRNA-seq was also linked to higher expression of PDCD1, TIGIT and IKZF2 in Tregs. PDCD1 and TIGIT encode immune checkpoint receptors involved in the regulation of Tregs function. Our study sets the direction for further functional research regarding a probable role of LOY in intensifying features related to the suppressive phenotype of Tregs in TME and consequently a possible influence on immunotherapy response in CRC patients.

Collaborating with the enemy: function of macrophages in the development of neoplastic disease.

Due to the profile of released mediators (such as cytokines, chemokines, growth factors, etc.), neoplastic cells modulate the activity of immune system, directly affecting its components both locally and peripherally. This is reflected by the limited antineoplastic activity of the immune system (immunosuppressive effect), induction of tolerance to neoplastic antigens, and the promotion of processes associated with the proliferation of neoplastic tissue. Most of these responses are macrophages dependent, since these cells show proangiogenic properties, attenuate the adaptive response (anergization of naïve T lymphocytes, induction of Treg cell formation, polarization of immune response towards Th2, etc.), and support invasion and metastases formation. Tumor-associated macrophages (TAMs), a predominant component of leukocytic infiltrate, "cooperate" with the neoplastic tissue, leading to the intensified proliferation and the immune escape of the latter. This paper characterizes the function of macrophages in the development of neoplastic disease.

Evaluation of FLT-PET/CT usefulness in diagnosis and qualification for surgical treatment of gastric cancer.

AIM OF THE STUDY: Evaluation of FLT/PET/ CT usefulness in diagnosis and qualification for surgical treatment of gastric cancer. MATERIAL AND METHODS: The FLT/PET/CT test was carried out in a group of 50 gastric cancer patients. Based on the test result, a decision followed about the therapeutic procedure to be applied. A comparison was made with regards to the consistency of the cancer growth advancement degree evaluation in the initial preoperative FLT/PET/CT test against the evaluation of postoperative degree of cancer advancement in histopathology. RESULTS: In the group of 50 diagnosed patients a surgical treatment was used for 37 patients. 21 resections were performed out of which 19 operations were radical In the group of 16 non-resective operations 2 post-laparotomic patients were selected for inductive treatment. In the group of 13 patients who did not undergo any surgery, 10 were directed to palliative care and 3 for inductive treatment. In the group of 50 patients, the applied FLT-PET/CT test confirmed presence of primary tumor in 49 patients. The presence of increased uptake of FLT in the local lymph nodes during the preoperative FLT-PET/CT test was confirmed in 22 cases. In 14 patients with FLT-PET/Ct N(+) with the M(-) feature resection surgery was performed. The increased uptake of FLT in localizing metastases (nodal and non-nodal) FLT-PET/CT (M+) was detected in 22 patients. The presence of nodal metastases in the postoperative histopathology examination (hpN+) was detected in 14 cases. In these cases preoperative FLT-PET/CT test proved the N(+) feature in 11 patients. The result FLT-PET/CT N(-) was truly negative in 2 patients, and false negative in 1 patient. In the group of 7 operated hpN(-) patients, in 3 patients a preoperative result FLT-PET/ CT N(+) (false positive result) was obtained. The consistency (positive) of nodal metastases identification in FLT-PET/CT as compared to post-surgical histopathology examination scored 11/15, which equals 73.3%. In the group of patients in whom resection surgery was performed, 4 false negative results were obtained [hp(N+), FLT-PET/CT (N-)] and 3 false positive results [hp(N-), FLT-PET/CT N(+)]. CONCLUSIONS: The initial test results indicate that FLT-PET/CT is an effective method in evaluating the primary tumor and the regional lymph nodes and is useful and beneficial in the diagnosis and further treatment evaluation of gastric cancer. FLT-PET/CT examination facilitates making proper therapeutic decisions - it allows the number of unnecessary laparotomies to be lowered.

The Role of Health Behaviors in Quality of Life: A Longitudinal Study of Patients with Colorectal Cancer.

Colorectal cancer (CRC) is the third most common malignancy and the second most common cancer-related cause of death worldwide. CRC incidence depends, in part, on the health behaviors that make up an individual's lifestyle. We aimed to assess the influence of health behaviors and quality of life (QoL) among patients with CRC receiving surgical treatment. In this single-center questionnaire study, 151 patients were surveyed 1 week before and 6 months after colorectal procedures (laparoscopic hemicolectomy, low rectal anterior resection, abdominoperineal resection, and others). This study demonstrated a significant decrease in alcohol consumption and physical activity following the execution of colorectal procedures. No statistically significant changes were observed in smoking or the consumption of healthy food. Global QoL did not change significantly; however, a decrease in physical and role-related functioning was observed. Significant improvements in emotional functioning were also observed. A detailed analysis showed that physical and social functioning were related to smoking, the consumption of healthy food, physical activity, and additional therapies. Emotional functioning was related to smoking, the consumption of healthy food, and complementary treatments. Six months following an operation, it was also dependent on alcohol intake. Physical functioning was the area that decreased the most in the six months after colorectal tumor surgery compared to the period before surgery. Health behaviors such as cessation of smoking, engagement in physical activity, and the consumption of healthy food contributed to a higher quality of life among patients prior to resecting colorectal cancer and six months after the procedure. Patients who received adjuvant/neoadjuvant therapy had a lower quality of life than patients who did not receive this type of therapy. The kind of surgery (laparoscopic hemicolectomy, lower anterior rectum resection, or abdominoperineal rectum resection) was not related to QoL six months after surgery.

The Prevalence of Back Pain in Patients Operated on Due to Colorectal Cancer Depending on the Type of Surgical Procedure Performed.

PURPOSE: Low back pain presents a serious challenge for numerous medical specialties. The purpose of this study was to assess disability due to low back pain in patients operated on due to colorectal cancer depending on the type of surgery performed. METHODS: This prospective observational study was carried out in the period of July 2019 through March 2020. Included in the study were patients with colorectal cancer for scheduled surgeries including anterior resection of rectum (AR), laparoscopic anterior resection of rectum (LAR), Hartmann's procedure (HART), or abdominoperineal resection of rectum (APR). The Oswestry Low Back Pain Disability Questionnaire was used as the research tool. The study patients were surveyed at three time points: before surgery, six months after surgery, and one year after surgery. RESULTS: The analysis of study results revealed that an increase in the degree of disability and functioning impairment occurred in all groups between time points I and II, with the differences being statistically significant (p < 0.05). The inter-group comparative analysis of the total Oswestry questionnaire scores revealed statistically significant differences, with the impairment of function being most severe within the APR group and least severe within the LAR group. CONCLUSION: The study results showed that low back pain contributes to impaired functioning of patients operated on due to colorectal cancer regardless of the type of procedure performed. A reduction in the degree of disability due to low back pain was observed one year after the procedure in patients having undergone LAR.

The Current Treatment Trends and Survival Patterns in Melanoma Patients with Positive Sentinel Lymph Node Biopsy (SLNB): A Multicenter Nationwide Study.

BACKGROUND: In melanoma treatment, an approach following positive sentinel lymph node biopsy (SLNB) has been recently deescalated from completion lymph node dissection (CLND) to active surveillance based on phase III trials data. In this study, we aim to evaluate treatment strategies in SLNB-positive melanoma patients in real-world practice. METHODS: Five-hundred-fifty-seven melanoma SLNB-positive patients from seven comprehensive cancer centers treated between 2017 and 2021 were included. Kaplan-Meier methods and the Cox Proportional-Hazards Model were used for analysis. RESULTS: The median follow-up was 25 months. Between 2017 and 2021, the percentage of patients undergoing CLND decreased (88-41%), while the use of adjuvant treatment increased (11-51%). The 3-year OS and RFS rates were 77.9% and 59.6%, respectively. Adjuvant therapy prolonged RFS (HR:0.69, p = 0.036)), but CLND did not (HR:1.22, p = 0.272). There were no statistically significant differences in OS for either adjuvant systemic treatment or CLND. Lower progression risk was also found, and time-dependent hazard ratios estimation in patients treated with systemic adjuvant therapy was confirmed (HR:0.20, p = 0.002 for BRAF inhibitors and HR:0.50, p = 0.015 for anti-PD-1 inhibitors). CONCLUSIONS: Treatment of SLNB-positive melanoma patients is constantly evolving, and the role of surgery is currently rather limited. Whether CLND has been performed or not, in a group of SLNB-positive patients, adjuvant systemic treatment should be offered to all eligible patients.

Plasma protein changes reflect colorectal cancer development and associated inflammation.

Introduction: Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of death worldwide. Efficient non-invasive blood-based biomarkers for CRC early detection and prognosis are urgently needed. Methods: To identify novel potential plasma biomarkers, we applied a proximity extension assay (PEA), an antibody-based proteomics strategy to quantify the abundance of plasma proteins in CRC development and cancer-associated inflammation from few µL of plasma sample. Results: Among the 690 quantified proteins, levels of 202 plasma proteins were significantly changed in CRC patients compared to age-and-sex-matched healthy subjects. We identified novel protein changes involved in Th17 activity, oncogenic pathways, and cancer-related inflammation with potential implications in the CRC diagnosis. Moreover, the interferon γ (IFNG), interleukin (IL) 32, and IL17C were identified as associated with the early stages of CRC, whereas lysophosphatidic acid phosphatase type 6 (ACP6), Fms-related tyrosine kinase 4 (FLT4), and MANSC domain-containing protein 1 (MANSC1) were correlated with the late-stages of CRC. Discussion: Further study to characterize the newly identified plasma protein changes from larger cohorts will facilitate the identification of potential novel diagnostic, prognostic biomarkers for CRC.