International consensus on the management of metastatic gastric cancer: step by step in the foggy landscape : Bertinoro Workshop, November 2022.

BACKGROUND: Many gastric cancer patients in Western countries are diagnosed as metastatic with a median overall survival of less than twelve months using standard chemotherapy. Innovative treatments, like targeted therapy or immunotherapy, have recently proved to ameliorate prognosis, but a general agreement on managing oligometastatic disease has yet to be achieved. An international multi-disciplinary workshop was held in Bertinoro, Italy, in November 2022 to verify whether achieving a consensus on at least some topics was possible. METHODS: A two-round Delphi process was carried out, where participants were asked to answer 32 multiple-choice questions about CT, laparoscopic staging and biomarkers, systemic treatment for different localization, role and indication of palliative care. Consensus was established with at least a 67% agreement. RESULTS: The assembly agreed to define oligometastases as a "dynamic" disease which either regresses or remains stable in response to systemic treatment. In addition, the definition of oligometastases was restricted to the following sites: para-aortic nodal stations, liver, lung, and peritoneum, excluding bones. In detail, the following conditions should be considered as oligometastases: involvement of para-aortic stations, in particular 16a2 or 16b1; up to three technically resectable liver metastases; three unilateral or two bilateral lung metastases; peritoneal carcinomatosis with PCI ≤ 6. No consensus was achieved on how to classify positive cytology, which was considered as oligometastatic by 55% of participants only if converted to negative after chemotherapy. CONCLUSION: As assessed at the time of diagnosis, surgical treatment of oligometastases should aim at R0 curativity on the entire disease volume, including both the primary tumor and its metastases. Conversion surgery was defined as surgery on the residual volume of disease, which was initially not resectable for technical and/or oncological reasons but nevertheless responded to first-line treatment.

Textbook Oncological Outcome in European GASTRODATA.

OBJECTIVE: To assess the rate of textbook outcome (TO) and textbook oncological outcome (TOO) in the European population based on the GASTRODATA registry. BACKGROUND: TO is a composite parameter assessing surgical quality and strongly correlates with improved overall survival. Following the standard of treatment for locally advanced gastric cancer, TOO was proposed as a quality and optimal multimodal treatment parameter. METHODS: TO was achieved when all the following criteria were met: no intraoperative complications, radical resection according to the surgeon, pR0 resection, retrieval of at least 15 lymph nodes, no severe postoperative complications, no reintervention, no admission to the intensive care unit, no prolonged length of stay, no postoperative mortality and no hospital readmission. TOO was defined as TO with the addition of perioperative chemotherapy compliance. RESULTS: Of the 2558 patients, 1700 were included in the analysis. TO was achieved in 1164 (68.5%) patients. The use of neoadjuvant chemotherapy [odds ratio (OR) = 1.33, 95% CI: 1.04-1.70] and D2 or D2+ lymphadenectomy (OR = 1.55, 95% CI: 1.15-2.10) had a positive impact on TO achievement. Older age (OR = 0.73, 95% CI: 0.54-0.94), pT3/4 (OR = 0.79, 95% CI: 0.63-0.99), ASA 3/4 (OR = 0.68, 95% CI: 0.54-0.86) and total gastrectomy (OR = 0.56, 95% CI: 0.45-0.70), had a negative impact on TO achievement. TOO was achieved in 388 (22.8%) patients. Older age (OR = 0.37, 95% CI: 0.27-0.53), pT3 or pT4 (OR = 0.52, 95% CI: 0.39-0.69), and ASA 3 or 4 (OR = 0.58, 95% CI: 0.43-0.79) had a negative impact on TOO achievement. CONCLUSIONS: Despite successively improved surgical outcomes, stage-appropriate chemotherapy in adherence to the current guidelines for multimodal treatment of gastric cancer remains poor. Further implementation of oncologic quality metrics should include greater emphasis on perioperative chemotherapy and adequate lymphadenectomy.

Systemic inflammatory response markers for prediction of response to neoadjuvant chemotherapy in patients with advanced gastric cancer.

BACKGROUND: Tumour development is greatly influenced by the systemic inflammatory response. Inflammatory factors, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphcyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), mirror the balance between systemic inflammation and anti-tumour response. The current investigation examined the predictive and prognostic value of NLR, PLR, and LMR in advanced gastric cancer (GC) patients. METHODS: This study is a retrospective, observational analysis involving 105 GC patients treated with neoadjuvant chemotherapy (NAC). Thestudy population included patients who met the eligibility criteria.The relationship between NLR, PLR, LMR and demographic and clinical variables was assessed using theΧ2test. Survival data were analysed by Kaplan-Meier curves. RESULTS: High NLR levels were associated with more advanced tumour stage.Higher risk of no tumour regression after NAC was observed if a high pretreatment level of NLR or PLR was found. All patients with an increase in NLR after NAC had a significantly higher risk of no tumor response.In groups high (no change), increase, decrease, and low (no change), NLR and PLR OS medians were: 33, 67, 78, and not reached-NR and 34, 29, 36, and NR, respectively. All patients had a significantly higher risk of death if NLR increased after NAC. An increase in post-NAC PLR level was associated with an increased risk of death only if the PLR baseline value was low. CONCLUSION: NLR and PLR are promising predictive and prognostic factors in advanced GC patients treated with NAC.

Vista of the Future: Novel Immunotherapy Based on the Human V-Set Immunoregulatory Receptor for Digestive System Tumors.

While gastrointestinal tumors remain a multifactorial and prevalent group of malignancies commonly treated surgically in combination with chemotherapy and radiotherapy, advancements regarding immunotherapeutic approaches continue to occur. Entering a new era of immunotherapy focused on overcoming resistance to preceding therapies caused the emergence of new therapeutic strategies. A promising solution surfaces with a V-domain Ig suppressor of T-cell activation (VISTA), a negative regulator of a T-cell function expressed in hematopoietic cells. Due to VISTA's ability to act as both a ligand and a receptor, several therapeutic approaches can be potentially developed. A broad expression of VISTA was discovered on various tumor-growth-controlling cells, which proved to increase in specific tumor microenvironment (TME) conditions, thus serving as a rationale behind the development of new VISTA-targeting. Nevertheless, VISTA's ligands and signaling pathways are still not fully understood. The uncertain results of clinical trials suggest the need for future examining inhibitor agents for VISTA and implicating a double immunotherapeutic blockade. However, more research is needed before the breakthrough can be achieved. This review discusses perspectives and novel approaches presented in the current literature. Based on the results of the ongoing studies, VISTA might be considered a potential target in combined therapy, especially for treating gastrointestinal malignancies.

New clinical and biological insights from the international TARGIT-A randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer.

BACKGROUND: The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses. METHODS: In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0-N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT. RESULTS: Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt . Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17-0.88) P = 0.0091. CONCLUSION: TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect. TRIAL REGISTRATION: ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009).

Current Challenges in Breast Implantation.

Breast implantation (BI) is the most common plastic surgery worldwide performed among women. Generally, BI is performed both in aesthetic and oncoplastic procedures. Recently, the prevalence of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) or breast implant illness (BII) has aroused concerns. As a result, several countries, like Australia, Korea or the United Kingdom, introduced national registries dedicated to the safety and quality of BI surgeries. This narrative review aimed to focus on the clinical challenges, management and the current state of knowledge of BI. Both short and long-term outcomes of BI are determined by various alternatives and differences, which surgeons must consider during the planning and performing breast augmentation along with further complications or risk of reoperation. Proper preoperative decisions and aspects of surgical technique emerged to be equally important. The number of performed breast reconstructions is increasing, providing the finest aesthetic results and improving patient's quality of life. Choice of prosthesis varies according to individual preferences and anatomical variables. A newly diagnosed cases of BIA-ALCL with lacking data on prevention, diagnosis, and treatment are placing it as a compelling medical challenge. Similarly, BII remains one of the most controversial subjects in reconstructive breast surgery due to unspecified diagnostic procedures, and recommendations.

Incidence and Grading of Complications After Gastrectomy for Cancer Using the GASTRODATA Registry: A European Retrospective Observational Study.

OBJECTIVE: Utilizing a standardized dataset based on a newly developed list of 27 univocally defined complications, this study analyzed data to assess the incidence and grading of complications and evaluate outcomes associated with gastrectomy for cancer in Europe. SUMMARY BACKGROUND DATA: The absence of a standardized system for recording gastrectomy-associated complications makes it difficult to compare results from different hospitals and countries. METHODS: Using a secure online platform (www.gastrodata.org), referral centers for gastric cancer in 11 European countries belonging to the Gastrectomy Complications Consensus Group recorded clinical, oncological, and surgical data, and outcome measures at hospital discharge and at 30 and 90 days postoperatively. This retrospective observational study included all consecutive resections over a 2-year period. RESULTS: A total of 1349 gastrectomies performed between January 2017 and December 2018 were entered into the database. Neoadjuvant chemotherapy was administered to 577 patients (42.8%). Total (46.1%) and subtotal (46.4%) gastrectomy were the predominant resections. D2 or D2+ lymphadenectomy was performed in almost 80% of operations. The overall complications' incidence was 29.8%; 402 patients developed 625 complications, with the most frequent being nonsurgical infections (23%), anastomotic leak (9.8%), other postoperative abnormal fluid from drainage and/or abdominal collections (9.3%), pleural effusion (8.3%), postoperative bleeding (5.6%), and other major complications requiring invasive treatment (5.6%). The median Clavien-Dindo score and Comprehensive Complications Index were IIIa and 26.2, respectively. In-hospital, 30-day, and 90-day mortality were 3.2%, 3.6%, and 4.5%, respectively. CONCLUSIONS: The use of a standardized platform to collect European data on perioperative complications revealed that gastrectomy for gastric cancer is still associated with heavy morbidity and mortality. Actions are needed to limit the incidence of, and to effectively treat, the most frequent and most lethal complications.

Proximal Gastric Resection with Posterior Esophago-Gastrostomy and Partial Neo-Fundoplication in the Treatment of Advanced Upper Gastric Carcinoma.

BACKGROUND: Proximal gastric resection (PGR) is rarely used in western countries because of frequent postoperative reflux and uncommon diagnosis of early gastric cancer (GC). OBJECTIVES: We hypothesized that the PGR with an anti-reflux procedure may be an attractive option even in advanced proximal GC after downstaging with the neo-adjuvant chemotherapy. METHOD: A novel technique of end-to-side esophago-gastrostomy with the posterior wall of the gastric stump and partial neo-fundoplication to prevent reflux symptoms has been introduced. An observational retrospective study was undertaken to evaluate early and late outcomes of the innovative technique in patients with advanced proximal GC after neoadjuvant chemotherapy. RESULTS: Twenty consecutive patients with the diagnosis of loco-regionally advanced GC, localized in the subcardiac region or proximal upper third of the stomach, were selected for the study. Eleven (55%) patients completed preoperative neo-adjuvant chemotherapy. The mean postoperative hospitalization time was 13.3 (± 8.3) days. There was one postoperative in-hospital death due to acute circulatory insufficiency. The mean comprehensive complication index was 11.94 (±24.82). Two patients were diagnosed with a complete pathological response (ypT0N0). Median survival was 41.8 (95% CI 27.9-41.8) months. The 5-year survival rate was 42%. At a median follow-up of 26 months, reflux symptoms were present in 7 (35%) patients who had to use antireflux medication. Anastomotic stenosis was observed in 1 patient during the follow-up. Mean scores of reflux symptoms on medication were not significantly different to those in patients without medication. The Overall Satisfaction Score for patients on medication was 7.57 ± 1.92, whereas it was 8.83 ± 1.34 (p = 0.2; Student t test) for those with no medication. CONCLUSIONS: Proximal gastrectomy is feasible and may be safely used in patients with advanced GC after neo-adjuvant chemotherapy with acceptable survival. Posterior esophago-gastrostomy with partial neo-fundoplication reduces the postoperative reflux, while patients with persistent reflux symptoms can be effectively treated with an antireflux therapy.

Neoadjuvant chemotherapy with or without oxaliplatin after short-course radiotherapy in high-risk rectal cancer: A subgroup analysis from a prospective study.

AIM: To evaluate the role of oxaliplatin in neoadjuvant chemotherapy delivered after short-course irradiation. BACKGROUND: Using oxaliplatin in the above setting is uncertain. PATIENTS AND METHODS: A subgroup of 136 patients managed by short-course radiotherapy and 3 cycles of consolidation chemotherapy within the framework of a randomised study was included in this post-hoc analysis. Sixty-seven patients received FOLFOX4 (oxaliplatin group) while oxaliplatin was omitted in the second period of accrual in 69 patients because of protocol amendment (fluorouracil-only group). RESULTS: Grade 3+ acute toxicity from neoadjuvant treatment was observed in 30% of patients in the oxaliplatin group vs. 16% in the fluorouracil-only group (p = 0.053). The corresponding proportions of patients having radical surgery or achieving complete pathological response were 72% vs. 77% (odds ratio [OR] = 0.88; 95% confidence interval [CI]: 0.39-1.98; p = 0.75) and 15% vs. 7% (OR = 2.25; 95% CI: 0.83-6.94; p = 0.16), respectively. The long-term outcomes were similar in the two groups. Overall and disease-free survival rates at 5 years were 63% vs. 56% (p = 0.78) and 49% vs. 44% (p = 0.59), respectively. The corresponding numbers for cumulative incidence of local failure or distant metastases were 33% vs. 38% (hazard ratio [HR] = 0.89; 95% CI: 0.52-1.52; p = 0.68) and 33% vs. 33% (HR = 0.78; 95% CI: 0.43-1.40; p = 0.41), respectively. CONCLUSION: Our findings do not support adding oxaliplatin to three cycles of chemotherapy delivered after short-course irradiation.

Yield of staging laparoscopy in gastric cancer is influenced by Laurén histologic subtype.

BACKGROUND: Staging laparoscopy (SL) with cytologic lavage is a useful staging procedure that allows tailoring the treatment of advanced gastric cancer (GC). The current study aimed to evaluate the total yield of SL in patients with various Laurén histo-types of GC, before planned neoadjuvant chemotherapy and gastrectomy. METHODS: After exclusion of distant metastatic disease on imaging modalities, 173 patients with primary advanced gastric adenocarcinoma who underwent SL between August 2016 and September 2018, were eligible for the analysis. Patients sex, age, Lauren histo-type, tumor location, grade, cT, and cN were assessed in bivariate analysis. Multivariable logistic regression analysis was used to identify independent factors associated with peritoneal metastases. RESULTS: Peritoneal metastases, ascites, and positive cytology were found in 39 (22.5%), 17 (9.8%) and 38 (22%) patients, respectively. The total yield of the SL in the current study was 36.4%. Multivariable logistic regression analysis revealed that serosal involvement (cT4) and diffuse histo-type were independent predictors of peritoneal metastases (OR, 15; 95% CI, 1.9-119, P = .02 and OR, 2.4; 95% CI, 1.2-4.6, P = .01, respectively). CONCLUSIONS: Although cT4 and diffuse tumors show the highest association with peritoneal metastases, SL is a valuable diagnostic procedure in all advanced GC patients.

International consensus on a complications list after gastrectomy for cancer.

BACKGROUND: Perioperative complications can affect outcomes after gastrectomy for cancer, with high mortality and morbidity rates ranging between 10 and 40%. The absence of a standardized system for recording complications generates wide variation in evaluating their impacts on outcomes and hinders proposals of quality-improvement projects. The aim of this study was to provide a list of defined gastrectomy complications approved through international consensus. METHODS: The Gastrectomy Complications Consensus Group consists of 34 European gastric cancer experts who are members of the International Gastric Cancer Association. A group meeting established the work plan for study implementation through Delphi surveys. A consensus was reached regarding a set of standardized methods to define gastrectomy complications. RESULTS: A standardized list of 27 defined complications (grouped into 3 intraoperative, 14 postoperative general, and 10 postoperative surgical complications) was created to provide a simple but accurate template for recording individual gastrectomy complications. A consensus was reached for both the list of complications that should be considered major adverse events after gastrectomy for cancer and their specific definitions. The study group also agreed that an assessment of each surgical case should be completed at patient discharge and 90 days postoperatively using a Complication Recording Sheet. CONCLUSION: The list of defined complications (soon to be validated in an international multicenter study) and the ongoing development of an electronic datasheet app to record them provide the basic infrastructure to reach the ultimate goals of standardized international data collection, establishment of benchmark results, and fostering of quality-improvement projects.

Intraoperative radiotherapy with low energy photons in recurrent colorectal cancer: a single centre retrospective study.

AIM OF THE STUDY: Intraoperative radiotherapy (IORT) may improve outcome of surgical treatment of recurrent colorectal cancer (CRC). The aim of this study is to determine the feasibility, safety and long-term results of surgical treatment of recurrent CRC with orthovolt IORT. MATERIAL AND METHODS: Fifty-nine consecutive CRC patients with local recurrence (LR), undergoing surgery, were included in the retrospective analysis of prospectively collected data. The modified Wanebo classification was used to stage LR (Tr). Twenty-five (43%) patients received IORT using INTRABEAM(®) PRS 500. The complications were classified according to the Clavien-Dindo classification. RESULTS: There were 32 males and 27 females, with a median age of 63 years. Multi-visceral resections were performed in 37 (63%) patients. Median hospitalization time after surgery with IORT was 7 days. One (1.7%) in-hospital postoperative death was reported. Grade 3/4 postoperative complications were found in 11 (19%) patients. Intraoperative radiotherapy had no effect on the postoperative hospitalization time, morbidity and mortality. Median survival after R0 resection was 32 months. Complete resection (R0), no synchronous liver metastases (M0), and no lateral and posterior pelvic wall involvement, were significant predictors of improved survival. Stage of LR was found to be an independent prognostic factor in the multivariate analysis (p = 0.03); Cox regression model). In patients with LR stage < Tr5, a 3-year overall survival (OS) rate was 52%. CONCLUSIONS: Combination of surgical resection and orthovolt IORT is a safe and feasible procedure that does not increase the risk of postoperative complications or prolongs the hospital stay. Despite aggressive surgery supported by IORT, the advanced stage of LR is a limiting factor of long-term survival.

Imaging methods for the local lymphatic system of the axilla in early breast cancer in patients qualified for sentinel lymph node biopsy.

Breast cancer is the most common malignancy in women in well-developed countries. Despite a constant increase in its incidence, the percentage of patients diagnosed with the disease in the non-invasive stage is also rising. This allows more frequently for the use of breast-preserving surgical techniques, involving the breast and the regional lymphatic system. According to current guidelines of expert panels and research societies, the recommended method of identifying the sentinel lymph node is the use of an isotope marker with a dye (a combined isotope and dye method). Cooperation with a nuclear medicine unit is essential (performing a preoperative lymphoscintigraphic scan to identify the lymphatic drainage basin and sentinel lymph node). In the case of smaller centers treating breast cancer, it can be associated with a number of difficulties, including organizational ones, and also increasing general treatment costs. A possible solution to these problems is to use alternative techniques of visualizing the sentinel lymph node, which do not require a radiotracer. In this paper we discuss the currently available methods of mapping the lymphatic system of the axillary region in patients with early breast cancer. The review is limited to reporting on methods of proven (based on clinical research) high diagnostic value.

Imagine a world without cancer.

BACKGROUND: Since the "War on Cancer" was declared in 1971, the United States alone has expended some $300 billion on research, with a heavy focus on the role of genomics in anticancer therapy. Voluminous data have been collected and analyzed. However, in hindsight, any achievements made have not been realized in clinical practice in terms of overall survival or quality of life extended. This might be justified because cancer is not one disease but a conglomeration of multiple diseases, with widespread heterogeneity even within a single tumor type. DISCUSSION: Only a few types of cancer have been described that are associated with one major signaling pathway. This enabled the initial successful deployment of targeted therapy for such cancers. However, soon after this targeted approach was initiated, it was subverted as cancer cells learned and reacted to the initial treatments, oftentimes rendering the treatment less effective or even completely ineffective. During the past 30 plus years, the cancer classification used had, as its primary aim, the facilitation of communication and the exchange of information amongst those caring for cancer patients with the end goal of establishing a standardized approach for the diagnosis and treatment of cancers. This approach should be modified based on the recent research to affect a change from a service-based to an outcome-based approach. The vision of achieving long-term control and/or eradicating or curing cancer is far from being realized, but not impossible. In order to meet the challenges in getting there, any newly proposed anticancer strategy must integrate a personalized treatment outcome approach. This concept is predicated on tumor- and patient-associated variables, combined with an individualized response assessment strategy for therapy modification as suggested by the patient's own results. As combined strategies may be outcome-orientated and integrate tumor-, patient- as well as cancer-preventive variables, this approach is likely to result in an optimized anticancer strategy. SUMMARY: Herein, we introduce such an anticancer strategy for all cancer patients, experts, and organizations: Imagine a World without Cancer.

Exploring the Survival Determinants in Recurrent Ovarian Cancer: The Role of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Recurrent ovarian cancer (ROC) significantly challenges gynecological oncology due to its poor outcomes. This study assesses the impact of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) on ROC survival rates. MATERIALS AND METHODS: Conducted at the Medical University of Lublin from April 2011 to November 2022, this retrospective observational study involved 71 patients with histologically confirmed ROC who underwent CRS and subsequent HIPEC. RESULTS: The median overall survival (OS) was 41.1 months, with 3-year and 5-year survival rates post-treatment of 0.50 and 0.33, respectively. Patients undergoing radical surgery for primary ovarian cancer had a median OS of 61.9 months. The key survival-related factors included the Peritoneal Carcinomatosis Index (PCI) score, AGO score, platinum sensitivity, and ECOG status. CONCLUSIONS: The key factors enhancing ROC patients' survival include radical surgery, optimal performance status, platinum sensitivity, a positive AGO score, and a lower PCI. This study highlights the predictive value of the platinum resistance and AGO score in patient outcomes, underlining their role in treatment planning. Further prospective research is needed to confirm these results and improve patient selection for this treatment approach.

Gut Microbiota-Adversary or Ally? Its Role and Significance in Colorectal Cancer Pathogenesis, Progression, and Treatment.

In 2022, colorectal cancer (CRC) was the third most prevalent malignancy worldwide. The therapeutic approach for CRC typically involves a multimodal regimen. The human gut microbiota comprises over 35,000 bacterial species. The composition of the gut microbiota is influenced by dietary intake, which plays a crucial role in food absorption, nutrient extraction, and the development of low-grade inflammation. Dysbiosis in the gut microbiota is a key driver of inflammation and is strongly associated with CRC development. While the gut microbiome influences CRC initiation and progression, emerging evidence suggests a role for the gut microbiome in modulating the efficacy and toxicity of cancer treatments. Therapeutic strategies targeting the gut microbiome, such as probiotics, hold promise as effective interventions in the modern therapeutical approach to CRC. For example, Microbiota Implementation to Reduce Anastomotic Colorectal Leaks (MIRACLe) implementation has resulted in improvements in clinical outcomes, including reduced incidence of anastomotic leakage (AL), surgical site infections (SSIs), reoperation, as well as shorter recovery times and hospital stays compared with the control group. Therefore, this review aims to describe the current state of knowledge regarding the involvement of the gut microbiota in CRC pathogenesis and its potential therapeutic implications to treat CRC.

Current Status of Treatment among Patients with Appendiceal Tumors-Old Challenges and New Solutions?

The 5th edition of the World Health Organization (WHO) classification of tumors of the digestive system distinguishes four categories of appendiceal tumors (ATs): serrated lesions and polyps, mucinous neoplasms, adenocarcinomas, and neuroendocrine neoplasms (NENs). The differential diagnosis of ATs can be challenging in medical practice, due to their rarity and lack of data from randomized controlled trials on a large, diverse group of patients. ATs are usually noted in specimens obtained during appendectomies due to clinical acute appendicitis. In the European population, most ATs (65%) occur over the age of 50 and among women (56.8%). According to histological type, 54.6% are neuroendocrine tumors (NETs); 26.8% cystic, mucinous, and serous neoplasms; and 18.6% adenocarcinoma not otherwise specified (NOS). On pathologic analysis, most AT findings are benign lesions or small NENs that do not require further therapeutic measures. The presence of appendiceal mucinous neoplasm (AMN) can lead to pseudomyxoma peritonei (PMP). While the multimodal treatment for abdominal malignancies has evolved over the past several decades, the clinical workup and treatment of ATs remain a challenge. Therefore, this review aims to describe the diagnostic possibilities, molecular-based diagnosis, staging, differences in the treatment process, and prognostic factors associated with ATs.

Prognostic Value of Inflammatory Burden Index in Advanced Gastric Cancer Patients Undergoing Multimodal Treatment.

Since increasing evidence underlines the prominent role of systemic inflammation in carcinogenesis, the inflammation burden index (IBI) has emerged as a promising biomarker to estimate survival outcomes among cancer patients. The IBI has only been validated in Eastern gastric cancer (GC) patients; therefore, the aim of this study was to evaluate the IBI as a prognostic biomarker in Central European GC patients undergoing multimodal treatment. Ninety-three patients with histologically confirmed GC who underwent multimodal treatment between 2013 and 2021 were included. Patient recruitment started with the standardization of neoadjuvant chemotherapy (NAC). Blood samples were obtained one day prior to surgical treatment. The textbook outcome (TO) served as the measure of surgical quality, and tumor responses to NAC were evaluated according to Becker's system tumor regression grade (TRG). A high IBI was associated with an increased risk of postoperative complications (OR 2.95, 95% CI 1.13-7.72). In multivariate analysis, a high IBI (HR = 2.56, 95% CI 1.28-5.13) and a high neutrophil-to-lymphocyte ratio (NLR, HR = 2.55, 95% CI 1.32-4.94) were associated with an increased risk of death, while NAC administration (HR = 0.40, 95% CI 0.18-0.90) and TO achievement (HR = 0.42, 95% CI 0.22-0.81) were associated with a lower risk of death. The IBI was associated with postoperative complications and mortality among GC patients undergoing multimodal treatment.

The unique monoclonal antibodies and immunochemical assay for comprehensive determination of the cell-bound and soluble HER2 in different biological samples.

The expression of the HER2 (human epidermal growth factor receptor 2) protein in cancer cells is a well-established cancer marker used for diagnostic and therapeutic purposes in modern treatment protocols, especially in breast cancer. The gold-standard immunohistochemical diagnostic methods with the specific anti-HER2 antibodies are utilized in the clinic to measure expression level of the membrane-bound receptor. However, a soluble extracellular domain (ECD) of HER2 is released to the extracellular matrix, thus the blood assays for HER2 measurements present an attractive way for HER2 level determination. There is a need for accurate and validated assays that can be used to correlate the concentration of the circulating HER2 protein with disease clinical manifestations. Here we describe two monoclonal antibodies binding HER2 with a unique sequence of the complementarity-determining regions that recognize HER2 ECD. Development and validation of the sandwich enzyme-linked immunosorbent assay (ELISA) for quantification of the soluble HER2 in a variety of biological samples is also presented. The assay provides HER2 quantitation within a concentrations range from 1.56 to 100 ng/ml with sensitivity at the level of 0.5 ng/ml that meets the expectations for measurements of HER2 in the blood and tumor tissue samples. The method presents satisfactory intra- and inter-assay precision and accuracy for immunochemical quantification of biomarkers in biological samples. The utility of the generated monoclonal anti-HER2 antibodies has been confirmed for use in the precise measurement of HER2 (both cell-bound and soluble) in several types of biological material, including serum, solid tumor tissue, and cell culture medium. Additionally, the developed immunochemical tools have a potential for HER2 detection, not only in a wide range of sample types but also independently of the sample storage/pre-processing, allowing for comprehensive HER2 analysis in tissue (IHC), cultured cells (immunofluorescence) and blood (ELISA).