International External Validation of Risk Prediction Model of 90-Day Mortality after Gastrectomy for Cancer Using Machine Learning.

BACKGROUND: Radical gastrectomy remains the main treatment for gastric cancer, despite its high mortality. A clinical predictive model of 90-day mortality (90DM) risk after gastric cancer surgery based on the Spanish EURECCA registry database was developed using a matching learning algorithm. We performed an external validation of this model based on data from an international multicenter cohort of patients. METHODS: A cohort of patients from the European GASTRODATA database was selected. Demographic, clinical, and treatment variables in the original and validation cohorts were compared. The performance of the model was evaluated using the area under the curve (AUC) for a random forest model. RESULTS: The validation cohort included 2546 patients from 24 European hospitals. The advanced clinical T- and N-category, neoadjuvant therapy, open procedures, total gastrectomy rates, and mean volume of the centers were significantly higher in the validation cohort. The 90DM rate was also higher in the validation cohort (5.6%) vs. the original cohort (3.7%). The AUC in the validation model was 0.716. CONCLUSION: The externally validated model for predicting the 90DM risk in gastric cancer patients undergoing gastrectomy with curative intent continues to be as useful as the original model in clinical practice.

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.

Textbook Neoadjuvant Outcome-Novel Composite Measure of Oncological Outcomes among Gastric Cancer Patients Undergoing Multimodal Treatment.

The incidence of gastric cancer (GC) is expected to increase to 1.77 million cases by 2040. To improve treatment outcomes, GC patients are increasingly treated with neoadjuvant chemotherapy (NAC) prior to curative-intent resection. Although NAC enhances locoregional control and comprehensive patient care, survival rates remain poor, and further investigations should establish outcomes assessment of current clinical pathways. Individually assessed parameters have served as benchmarks for treatment quality in the past decades. The Outcome4Medicine Consensus Conference underscores the inadequacy of isolated metrics, leading to increased recognition and adoption of composite measures. One of the most simple and comprehensive is the "All or None" method, which refers to an approach where a specific set of criteria must be fulfilled for an individual to achieve the overall measure. This narrative review aims to present the rationale for the implementation of a novel composite measure, Textbook Neoadjuvant Outcome (TNO). TNO integrates five objective and well-established components: Treatment Toxicity, Laboratory Tests, Imaging, Time to Surgery, and Nutrition. It represents a desired, multidisciplinary care and hospitalization of GC patients undergoing NAC to identify the treatment- and patient-related data required to establish high-quality oncological care further. A key strength of this narrative review is the clinical feasibility and research background supporting the implementation of the first and novel composite measure representing the "ideal" and holistic care among patients with locally advanced esophago-gastric junction (EGJ) and GC in the preoperative period after NAC. Further analysis will correlate clinical outcomes with the prognostic factors evaluated within the TNO framework.

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.

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.

MalnutritiOn assessment with biOelectrical impedaNce analysis in gastRic cancer patIentS undergoing multimodaltrEatment (MOONRISE)-Study protocol for a single-arm multicenter cross-sectional longitudinal study.

European data suggests that over 30% of gastric cancer (GC) patients are diagnosed with sarcopenia before surgery, while unintentional weight loss occurs in approximately 30% of patients following gastrectomy. Preoperative sarcopenia significantly increases the risk of major postoperative complications, and preoperative body weight loss remains a superior predictor of outcome and an independent prognostic factor for overall survival (OS) in patients with GC. A standardized approach of nutritional risk screening of GC patients is yet to be established. Therefore, the MOONRISE study aims to prospectively analyze the changes in nutritional status and body composition at each stage of multimodal treatment among GC patients from five Western expert centers. Specifically, we seek to assess the association between nutritional status and body composition on tumor response following neoadjuvant chemotherapy (NAC). Secondary outcomes of the study are treatment toxicity, postoperative complications, quality of life (QoL), and OS. Patients with locally advanced gastric adenocarcinoma scheduled for multimodal treatment will be included in the study. Four consecutive nutritional status assessments will be performed throughout the treatment. The following study was registered in ClinicalTrials.gov (Identifier: NCT05723718) and will be conducted in accordance with the STROBE statement. The anticipated duration of the study is 12-24 months, depending on the recruitment status. Results of this study will reveal whether nutritional status and body composition assessment based on BIA will become a validated and objective tool to support clinical decisions in 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).

A Clinical Viewpoint on the Use of Targeted Therapy in Advanced Gastric Cancer.

The development of therapies for advanced gastric cancer (GC) has made significant progress over the past few years. The identification of new molecules and molecular targets is expanding our understanding of the disease's intricate nature. The end of the classical oncology era, which relied on well-studied chemotherapeutic agents, is giving rise to novel and unexplored challenges, which will cause a significant transformation of the current oncological knowledge in the next few years. The integration of established clinically effective regimens in additional studies will be crucial in managing these innovative aspects of GC. This study aims to present an in-depth and comprehensive review of the clinical advancements in targeted therapy and immunotherapy for advanced GC.

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.

Techniques of staging laparoscopy and peritoneal fluid assessment in gastric cancer: a systematic review.

BACKGROUND: Staging laparoscopy for gastric cancer is recommended to assess the tumor's locoregional extension and exclude peritoneal disease. As there is no consensus on optimizing the procedure's diagnostic accuracy, we aimed to systematically review the literature on operative techniques, followed by peritoneal lavage fluid assessment in gastric cancer patients. Specifically, we sought to indicate the most common characteristics of the procedure and cytological evaluation. METHODS: This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The protocol for this systematic review was registered on PROSPERO database (CRD: 42022306746). On September 2022, a search was carried out using Embase, Medline ALL, Cochrane Central Register of Controlled Trials, and Web of Science Core Collection. RESULTS: The search identified 1632 studies on staging laparoscopy and 2190 studies on peritoneal fluid assessment. Some 212 studies were included. Open Hasson was the method of choice in accessing the peritoneal cavity in 65% of the studies, followed by establishing a pneumoperitoneum at 10-12 mmHg in 52% of reports. Most frequently, the patient was positioned supine (70%), while a 30° scope and three ports were used to assess the peritoneal cavity clockwise (72%, 77%, and 85%, respectively). Right and left upper abdomen quadrants were the predominant area of laparoscopic exploration (both 65%), followed by the primary tumor region (54%), liver and pelvis (both 30%), and small bowel and spleen (19% and 17%, respectively). Regions of peritoneal lavage and aspiration were limited to the pelvis (50%), followed by right and left upper abdomen quadrants (37.5% and 50%, respectively). No studies compared different methods of operative techniques or analysis of ascites/fluid. CONCLUSIONS: This study indicates a high heterogeneity in the technique of staging laparoscopy and peritoneal fluid assessment in gastric cancer patients. Further research and initiatives to reach a consensus on the standardization of the procedure are warranted.

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.

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.

Staging LaParoscopy to Assess Lymph NOde InvoLvement in Advanced GAstric Cancer (POLA)-Study protocol for a single-arm prospective observational multicenter study.

INTRODUCTION: In the era of neoadjuvant chemotherapy in advanced gastric cancer (GC), the role of staging laparoscopy (SL) will become more established. However, despite guidelines recommendations, SL for optimal preoperative staging remains underutilized. Diagnostic value of near-infrared (NIR) / indocyanine green (ICG) guided sentinel node (SN) mapping in GC confirmed its technical feasibility, however no data exist regarding its potential role in pathological nodal staging. To the best of our knowledge, current study is the first to evaluate the role of ICG in nodal staging of advanced GC patients undergoing SL. MATERIALS AND METHODS: This single-arm prospective observational multicenter study was approved by the Bioethical Committee of Medical University of Lublin (Ethic Code: KE-0254/331/2018). The protocol is registered at clinicaltrial.gov (NCT05720598), and the study results will be reported according to the Strengthening of Reporting of Observational Studies in Epidemiology (STROBE) statement. The primary endpoint of this study is the identification rate of ICG-guided SN in advanced GC patients. The secondary endpoints include pathological and molecular assessment of retrieved SNs and other pretreatment clinical variables potentially associated with SL: pattern of perigastric ICG distribution according to patients' pathological and clinical characteristics, neoadjuvant chemotherapy compliance, 30-day morbidity, and mortality. CONCLUSION: POLA study is the first to investigate the clinical value of ICG-enhanced sentinel node biopsy during staging laparoscopy in advanced GC patients in a Western cohort. Identifying pN status before multimodal treatment will improve GC staging process.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC), Oncological Outcomes and Long-Term Survival among Patients with Gastric Cancer and Limited Peritoneal Disease Progression after Neoadjuvant Chemotherapy.

INTRODUCTION: The role of surgery in stage IV gastric cancer with peritoneal metastasis (PM) remains unclear. The objective of the current single-center study was to define the impact of gastrectomy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on outcomes among Central European GC patients with limited peritoneal disease progression after neoadjuvant chemotherapy (NAC). METHODS: Patients with histologically confirmed GC who underwent curative-intent multimodal treatment between 2013 and 2023 were included. Patients without adenocarcinoma, who did not undergo gastrectomy, had early (cT1) or metastatic GC at the time of initial diagnosis, who underwent multivisceral resection, incomplete cytoreduction or palliative care, died before planned curative-intent treatment, or had incomplete clinical or pathological missing information were excluded. RESULTS: A total of 74 patients who underwent curative-intent treatment for GC with PM were included in the final analytic cohort. Patients who underwent gastrectomy with CRS+HIPEC were less likely to achieve TOO (CRS+HIPEC: 28% vs. CRS: 57.1%, p = 0.033) compared with individuals after CRS alone. Specifically, patients who underwent gastrectomy with CRS+HIPEC had a higher likelihood of postoperative complications (CRS+HIPEC: 48% vs. CRS: 20.4%, p = 0.018) and longer hospital LOS (median, CRS+HIPEC: 12 vs. CRS: 10, p = 0.019). While administration of HIPEC did not impact long-term survival (median OS, CRS+HIPEC: 16 months vs. CRS: 12 months, p = 0.55), postoperative complications (median OS, CCI < 30:16 months vs. CCI > 30:5 months, p = 0.024) and ICU stay (median OS, no ICU stay: 16 months vs. ICU stay: 5 months, p = 0.008) were associated with worsened long-term survival among GC patients with PM. CONCLUSIONS: Data from the current study demonstrated a lack of survival benefit among advanced GC patients with PM undergoing gastrectomy with CRS+HIPEC when compared with individuals after gastrectomy with CRS alone. Administration of perioperative chemotherapy and achievement of TO failed to withstand the peritoneal disease progression during NAC.

FGFR Inhibitors in Cholangiocarcinoma-A Novel Yet Primary Approach: Where Do We Stand Now and Where to Head Next in Targeting This Axis?

Cholangiocarcinomas (CCAs) are rare but aggressive tumours with poor diagnosis and limited treatment options. Molecular targeted therapies became a promising proposal for patients after progression under first-line chemical treatment. In light of an escalating prevalence of CCA, it is crucial to fully comprehend its pathophysiology, aetiology, and possible targets in therapy. Such knowledge would play a pivotal role in searching for new therapeutic approaches concerning diseases' symptoms and their underlying causes. Growing evidence showed that fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) pathway dysregulation is involved in a variety of processes during embryonic development and homeostasis as well as tumorigenesis. CCA is known for its close correlation with the FGF/FGFR pathway and targeting this axis has been proposed in treatment guidelines. Bearing in mind the significance of molecular targeted therapies in different neoplasms, it seems most reasonable to move towards intensive research and testing on these in the case of CCA. However, there is still a need for more data covering this topic. Although positive results of many pre-clinical and clinical studies are discussed in this review, many difficulties lie ahead. Furthermore, this review presents up-to-date literature regarding the outcomes of the latest clinical data and discussion over future directions of FGFR-directed therapies in patients with CCA.

Interfacial and Transport Phenomena between Liquid Metal and Solid Structural Materials.

Research activities in materials science typically range from basic and curiosity-motivated research to that which is applications-oriented, and the well-known Materials Science paradigm is usually followed: Processing → Microstructure → Properties → Performance [...].