LRG1 promotes metastatic colorectal cancer growth through HER3 signaling.

BACKGROUND AND AIMS: Therapy failure in patients with metastatic colorectal cancer (mCRC, ∼80% occur in the liver) remains an overarching challenge. Preclinical studies demonstrated that HER3 promotes CRC cell survival, but therapies blocking the neuregulin-induced canonical HER3 signaling have made little impact in the clinic. Recent studies suggest that the liver microenvironment promotes CRC growth by activating HER3 in a neuregulin-independent fashion, thus elucidation of these mechanisms may reveal new strategies for treating patients with mCRC. METHODS: Patient-derived primary liver endothelial cells (ECs) were used to interrogate EC-CRC crosstalk. We conducted proteomic analysis to identify EC-secreted factor(s) that triggers non-canonical HER3 activation in CRC, and determined the subsequent effects on mCRC using diverse murine mCRC models. In vitro studies with genetic and pharmacological interventions were used to map the non-canonical HER3 pathway. RESULTS: We demonstrated that EC-secreted leucine-rich alpha-2-glycoprotein 1 (LRG1) directly binds and activates HER3 and promotes CRC growth distinct from neuregulin, the canonical HER3 ligand. Blocking host-derived LRG1 by gene knockout or a neutralizing antibody impaired mCRC outgrowth in the liver and prolonged mouse survival. We identified protein synthesis activated by the PI3K-PDK1-RSK-eIF4B axis as the biologically relevant signaling cascade downstream of the LRG1-HER3 interaction, which was not blocked by conventional HER3-specific antibodies that failed in prior clinical trials. CONCLUSIONS: LRG1 is a novel HER3 ligand and mediates liver-mCRC crosstalk. The LRG1-HER3 signaling axis is distinct from canonical HER3 signaling and represents a new therapeutic opportunity to treat patients with mCRC, and potentially other types of liver metastases.

Sarcomatoid Carcinoma of the Small Intestine: A Case Report.

Sarcomatoid carcinoma of the gastrointestinal tract is an extremely rare and aggressive tumor with both epithelial and mesenchymal characteristics, and it typically has a poor prognosis. We report the case of a 74-year-old male diagnosed with sarcomatoid carcinoma of the duodenum. The patient presented with gastrointestinal bleeding and was found to have a vascular tumor in the third part of the duodenum. Initial duodenal biopsies, repeat biopsies, and extensive immunohistochemical analysis confirmed a diagnosis of sarcomatoid carcinoma. Despite radical surgery and multiple lines of chemotherapy, including carboplatin and paclitaxel, the disease demonstrated aggressive progression, ultimately leading to the patient's death two years post-diagnosis. This report highlights the challenges in diagnosing and treating sarcomatoid carcinoma of the small intestine, the limited efficacy of current therapeutic options, and the need for further research to establish effective treatment protocols.

Squamous Cell Carcinoma of the Esophagus in an Adolescent: A Case Report.

Esophageal cancer is more common with increasing age and rarely seen below the age of 45. The current case report is a case of squamous cell carcinoma of the esophagus in a 17-year-old male patient who presented with progressive dysphagia and significant weight loss. Contrast-enhanced computed tomography (CECT) neck, chest, and abdomen showed a lesion involving the middle and lower third of the esophagus with contiguous involvement of the gastroesophageal junction (GEJ), extending from D7 to D11 vertebral segments and completely occluding the lumen. He was managed with chemoradiation, in which three cycles of chemotherapy (Carboplatin 220 mg and Paclitaxel 80 mg) were given, followed by 18 fractions of 40Gy radiotherapy. After this period of chemoradiation, he developed weakness and breathlessness; he was not able to ambulate and became completely bedridden. He underwent a feeding jejunostomy for nutrition, then neoadjuvant chemoradiotherapy (NACRT) and oncological resection with thoracoscopy-assisted transhiatal esophagectomy. The patient had bubbles in the intercostal tube drain while doing incentive spirometry and basal crepitations, so on the next day, a gastric Conray was done, which showed a suspected contrast leak into bilateral lung fields. CECT neck, chest, and abdomen confirmed the minor leak and was managed conservatively. The abdominal wound developed erythema on the seventh day and was opened showing a small amount of sanguinopurulent discharge, for which daily dressing was done along with antibiotic cefuroxime. On the seventh and eighth days, the patient experienced hoarseness in their voice, a condition managed with supportive care. The patient was successfully discharged after completing all management protocols. The report clearly highlights the need to suspect malignancy in young adults presenting with dysphagia.

Parkinson's disease and the risk of gastrointestinal cancers: a two-sample Mendelian randomization study.

Background: The association between Parkinson's disease (PD) and gastrointestinal (GI) cancers remains unknown. This study aims to assess the causal effect of PD on colon cancer (CC), gastric cancer (GC), esophageal cancer (EC), and rectal cancer (RC) using the two-sample Mendelian randomization (MR) method. Methods: Five pairs of summary datasets of genome-wide association studies (GWAS) from publicly available studies [Integrative Epidemiology Unit (IEU) OpenGWAS project, FinnGen, and GWAS Catalog database] were enrolled. The inverse variance weighted (IVW) method was used as the primary outcome for MR analysis. Cochran Q-derived, MR-Egger intercept test, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) methods, and leave-one-out analysis were used to test heterogeneity and directional pleiotropy. Results: For the European population, no significant causal effect of PD on the risk of CC was found [odds ratio (OR) =0.9; 95%, confidence interval (CI): 1.00-1.11; P=0.42]. The same applied to the East Asian population (OR =1.05; 95% CI: 0.66-1.66; P=0.63). As for GC, no causal effect was found (OR =0.94, 95% CI: 0.89-0.99; P=0.22). Moreover, the genetic liability for PD was not associated with EC (OR =1.00; 95% CI: 0.99-1.00; P=0.32). Finally, no evidence was found for any causal effect of genetic liability for PD on an increased risk of RC (OR =1.00; 95% CI: 0.99-1.00; P=0.71). Conclusions: There is no causal effect of genetic liability for PD on an increased risk of GI cancer.

Particle therapy in gastrointestinal cancer-a narrative review.

Background and Objective: Radiation therapy is one of the main pillars in the treatment of gastrointestinal (GI) cancers, especially esophageal and anorectal malignancies. The worldwide standard of care is yet an irradiation with photons. Though not commonly used, charged particles offer some physical advantages with a highly conformal dose distribution, which allows an even better sparing of organs at risk. In addition to dosimetric advantages, heavy-ion beams like carbon ions may offer an additional set of biological advantages. Because particle therapy is not standard of care, data are scarce-especially concerning the use in GI malignancies. The aim of this review is to provide a compact overview of the currently available literature. Methods: PubMed and Web of Science databases were searched for publications on particle radiotherapy in GI cancer (e.g., proton therapy in esophageal cancer, carbon ion radiotherapy in pancreatic cancer). Key Content and Findings: Here we present a review of the current data on particle therapy with regard to esophageal, pancreatic, hepatic and anorectal malignancies. Conclusions: Data on particle therapy in GI cancer are scarce. Nevertheless, the current literature shows some promising results. Further clinical evidence, especially randomized trials, is crucial to augment the role of particle radiotherapy in GI cancer.

Integrating Deep Learning-Based Dose Distribution Prediction with Bayesian Networks for Decision Support in Radiotherapy for Upper Gastrointestinal cancer.

Purpose: Selecting the better techniques to harbor optimal motion management, either a stereotactic linear accelerator delivery using TrueBeam (TBX) or Magnetic Resonance (MR)-guided gated delivery using MRIdian (MRG), is time-consuming and costly. To address this challenge, we aimed to develop a decision-supporting algorithm based on a combination of deep learning-generated dose distributions and clinical data. Materials and Methods: We retrospectively analyzed 65 patients with liver or pancreatic cancer who underwent both TBX and MRG simulations and planning process. We trained three-dimensional U-Net deep learning models to predict dose distributions and generated dose volume histograms (DVHs) for each system. We integrated predicted DVH metrics into a Bayesian network (BN) model incorporating clinical data. Results: The MRG prediction model outperformed the TBX model, demonstrating statistically significant superiorities in predicting normalized dose to the PTV and liver. We developed a final BN prediction model integrating the predictive DVH metrics with patient factors like age, PTV size, and tumor location. This BN model an area under the receiver operating characteristic curve index of 83.56%. The decision tree derived from the BN model showed that the tumor location (abutting vs. apart of PTV to hollow viscus organs) was the most important factor to determine TBX or MRG. Conclusion: We demonstrated a decision-supporting algorithm for selecting optimal RT plans in upper gastrointestinal cancers, incorporating both deep learning-based dose prediction and BN-based treatment selection. This approach might streamline the decision-making process, saving resources and improving treatment outcomes for patients undergoing RT.

Deciphering the Role of Exosomal Non-Coding RNA (ncRNA) in Drug Resistance of Gastrointestinal Tumors; an Updated Review.

One of the most prevalent types of cancer worldwide today is gastric intestinal (GI) tumors. To guarantee their lives, people with a developed GI require palliative care. This covers the application of targeted medicines in addition to chemotherapy treatments including cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, and pemetrexed. Because of the evidence of drug resistance emerging in poor patient outcomes and prognoses, determining the exact process of medication resistance is motivated. Besides, it is noteworthy that exosomes and noncoding RNAs, like microRNAs and long non-coding RNAs (lncRNAs), produced from tumor cells are implicated in both GI medication resistance and the carcinogenesis and development of GI disease. Biochemical events related to the cell cycle, differentiation of cells, growth, and pluripotency, in addition to gene transcription, splicing, and epigenetics, are all regulated by noncoding RNAs (ncRNAs). Therefore, it should come as a wonder that several ncRNAs have been connected in recent years to drug susceptibility and resistance as well as tumorigenesis. Additionally, through communicating directly with medications, altering the transcriptome of tumor cells, and affecting the immune system, exosomes may govern treatment resistance. Because of this, exosomal lncRNAs often act as a competitive endogenous RNA (ceRNA) of miRNAs to carry out its role in modifying drug resistance. In light of this, we provide an overview of the roles and processes of ncRNA-enriched exosomes in GI medication resistance.

Upper gastrointestinal bleeding as a warning sign of gastrointestinal cancer.

Background: Upper gastrointestinal bleeding (UGIB) is a prevalent etiology for hospital admissions on a global scale. However, the significance of UGIB as a warning sign of gastrointestinal (GI) cancer is frequently disregarded due to its uncommon and atypical symptoms. Methods: In the Kailuan study, participants diagnosed with UGIB were assigned as the case group and were randomly matched in a 1:4 ratio with a control group of comparable age and sex from 2006 to 2018 in Tangshan. The statistical analysis included a total of 1250 UGIB patients and 5000 individuals without UGIB. The impact of UGIB on cancer incidence was evaluated using a Cox proportional hazards model, enabling the investigation of both site-specific and time-dependent effects of UGIB on cancer incidence. Results: The mean age of the patients was 60.91 ± 13.08 years. Over an average follow-up period of 8.92 years, there were 102 cases of cancer in the UGIB group and 210 cases in the non-UGIB group. The results of the Cox model analysis indicated that the strength of association between UGIB and cancer depends on specific cancer site. Excluding patients with follow-up periods of less than 1, 3, and 5 years weakened the associations between UGIB and GI cancer in sensitivity analysis. Conclusion: UGIB may serve as a sign of occult cancer, necessitating thorough evaluation of middle-aged and elderly patients presenting with this warning symptom to detect the possibility of missing a cancer diagnosis.

Critical role of the long non-coding RNAs (lncRNAs) in radiotherapy (RT)-resistance of gastrointestinal (GI) cancer: Is there a way to defeat this resistance?

Radiotherapy (RT) is a frequently used treatment for cervical cancer, effectively decreasing the likelihood of the disease returning in the same area and extending the lifespan of individuals with cervical cancer. Nevertheless, the primary reason for treatment failure in cancer patients is the cancer cells' resistance to radiation therapy (RT). Long non-coding RNAs (LncRNAs) are a subset of RNA molecules that do not code for proteins and are longer than 200 nucleotides. They have a significant impact on the regulation of gastrointestinal (GI) cancers biological processes. Recent research has shown that lncRNAs have a significant impact in controlling the responsiveness of GI cancer to radiation. This review provides a concise overview of the composition and operation of lncRNAs as well as the intricate molecular process behind radiosensitivity in GI cancer. Additionally, it compiles a comprehensive list of lncRNAs that are linked to radiosensitivity in such cancers. Furthermore, it delves into the potential practical implementation of these lncRNAs in modulating radiosensitivity in GI cancer.

Current trends in the management of Gastro-oEsophageal cancers: Updates to the ESSO core curriculum (ESSO-ETC-UGI-WG initiative).

Gastro-oEsophageal Cancers (GECs) are severe diseases whose management is rapidly evolving. The European Society of Surgical Oncology (ESSO) is committed to the generation and spread of knowledge, and promotes the multidisciplinary management of cancer patients through its core curriculum. The present work discusses the approach to GECs, including the management of oligometastatic oesophagogastric cancers (OMEC), the diagnosis and management of peritoneal metastases from gastric cancer (GC), the management of Siewert Type II tumors, the importance of mesogastric excision, the role of robotic surgery, textbook outcomes, organ preserving options, the use of molecular markers and immune check-point inhibitors in the management of patients with GECs, as well as the improvement of current clinical practice guidelines for the management of patients with GECs. The aim of the present review is to provide a concise overview of the state-of-the-art on the management of patients with GECs and, at the same time, to share the latest advancements in the field and to foster the debate between surgical oncologists treating GECs worldwide. We are sure that our work will, at the same time, give an update to the advanced surgical oncologists and help the training surgical oncologists to settle down the foundations for their future practice.

A prognostic model established using bile acid genes to predict the immunity and survival of patients with gastrointestinal cancer.

BACKGROUND: The metabolism of abnormal bile acids (BAs) is implicated in the initiation and development of gastrointestinal (GI) cancer. However, there was a lack of research on the molecular mechanisms of BAs metabolism in GI. METHODS: Genes involved in BAs metabolism were excavated from public databases of The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database, and Molecular Signatures Database (MSigDB). ConsensusClusterPlus was used to classify molecular subtypes for GI. To develop a RiskScore model for predicting GI prognosis, univariate Cox analysis was performed on the genes in protein-protein interaction (PPI) network, followed by using Lasso regression and stepwise regression to refine the model and to determine the key prognostic genes. Tumor immune microenvironment in GI patients from different risk groups was assessed using the ESTIMATE algorithm and enrichment analysis. Reverse transcription-quantitative real-time PCR (RT-qPCR), Transwell assay, and wound healing assay were carried out to validate the expression and functions of the model genes. RESULTS: This study defined three molecular subtypes (C1, C2, and C3). Specifically, C1 had the best prognosis, while C3 had the worst prognosis with high immune checkpoint gene expression levels and TIDE scores. We selected nine key genes (AXIN2, ATOH1, CHST13, PNMA2, GYG2, MAGEA3, SNCG, HEYL, and RASSF10) that significantly affected the prognosis of GI and used them to develop a RiskScore model accordingly. Combining the verification results from a nomogram, the prediction of the model was proven to be accurate. The high RiskScore group was significantly enriched in tumor and immune-related pathways. Compared with normal gastric mucosal epithelial cells, the mRNA levels of the nine genes were differential in the gastric cancer cells. Inhibition of PNMA2 suppressed migration and invasion of the cancer cells. CONCLUSION: We distinguished three GI molecular subtypes with different prognosis based on the genes related to BAs metabolism and developed a RiskScore model, contributing to the diagnosis and treatment of patients with GI.

Quality of life following perioperative optimization with nutritional supplements in patients undergoing gastrointestinal surgery for cancer: A randomized, placebo-controlled feasibility clinical trial.

BACKGROUND: Up to two thirds of patients presenting for abdominal cancer surgery are malnourished pre-operatively. Perioperative nutritional supplementation has been proposed to improve surgical outcomes, though its effect on quality of life (QoL) is not yet understood. METHODS: A randomized controlled feasibility trial for perioperative nutrition among patients undergoing major abdominal cancer surgery was conducted. Participants in the intervention group received supplements for 30 days before surgery. Participants completed two QoL questionnaires (EORTC-QLQ-C-30 and FACT-G) at baseline, then 4 and 12 weeks postoperatively. Participants were compared between and within groups at baseline, Weeks 4, and 12 using t tests. Minimal clinically important differences (MCIDs) were considered as a 10-point worsening from baseline. RESULTS: Sixty-six participants were available for analysis in this study, including 33 in the intervention and 30 in the control arms. Baseline demographics were balanced between groups except for different rates of pancreas cancer (36% intervention vs. 9% control) and colorectal cancer (19% intervention vs. 34% control). At baseline, participants in the intervention group had lower overall QoL (59% vs. 77%, p = 0.01), role functioning (72% vs 88%, p = 0.045), and cognitive functioning (79% vs 90%, p = 0.047). Following surgery, role and physical functioning worsened in the control group, without significant differences between groups. Role functioning was persistently worsened at 12 weeks in the control group. The rates of MCIDs were similar between both intervention and control groups. DISCUSSION: Perioperative nutrition was associated with preservation of QoL in the postoperative period following major abdominal cancer surgery compared to placebo. SUMMARY: Among patients undergoing surgery for cancer, the majority present at high risk for malnutrition. In this placebo-controlled randomized trial among patients undergoing major abdominal surgery for cancer, preoperative nutrition supplementation was associated with the preservation of QoL in the postoperative period.

PD-1 inhibition combined with intensity-modulated radiotherapy, to better serve patients with retroperitoneal lymph node metastases from gastrointestinal cancer.

Background: Gastrointestinal (GI) cancer is the most frequent kind of cancer to involve the retroperitoneal lymph nodes (RPLNs). Radiotherapy (RT) is common treatment of RPLN metastases in patients with GI cancer, while RT is local. Meanwhile, most patients have extra-retroperitoneal metastases. Immunotherapy plus RT have showed effective in advanced non-small cell lung cancer. However, whether the combination therapy is effective on GI cancer with RPLN metastases. In our study, we would estimate the effect of programmed death-1 (PD-1) inhibition in association with intensity modulated radiation therapy (IMRT). Methods: Metastatic GI cancer patients with RPLN who were treated at a single institution were retrospectively evaluated from October 2016 to April 2023, who all had measurable lesion and received any therapy of PD-1 inhibitors alone, IMRT alone or PD-1 inhibitors plus IMRT. The follow-ups were assessed by abdominal computed tomography (CT) every 2 or 3 months to progression, dose-limiting toxicity or death. Results: Among the 98 patients, 46 were treated by PD-1 inhibitors combined with IMRT, 26 were by PD-1 inhibitors only and 26 were by IMRT only. Of those, the median age 62 years (range, 25-84 years). Median progression-free survival (PFS) was 7.5 months and median overall survival (OS) was 10.8 months across the 3 therapy groups. Univariate analysis (UVA) indicated that therapy method (P=0.032) and tumor response (P=0.035) were significantly related to PFS. In the PD-1 inhibitors plus IMRT group, 1 patient (2.2%) achieved complete response (CR), 30 (65.2%) had partial remission, and 14 (30.4%) had stable disease. There was no case with CR by IMRT or PD-1 inhibitors alone. Objective response rate (67.4%) and disease control rate (97.8%) were higher in the PD-1 inhibitors combined with IMRT group. In the PD-1 inhibitors plus IMRT and PD-1 inhibitors alone groups, hepatitis B virus (HBV)-positive patients had better OS (P=0.041) on UVA. Meanwhile, in the PD-1 inhibitors plus IMRT group, we observed superior PFS (P=0.041) and OS (P=0.049) in HBV-positive patients on UVA. Conclusions: PD-1 inhibitors plus IMRT may be a better method for advanced GI cancer patients with RPLN metastases. HBV-positive patients can benefit from either PD-1 inhibitors alone or in combination with IMRT.

Is every psychiatrist an oncology psychiatrist?-Special needs for special populations: a scoping review.

BACKGROUND: The evolution of psychiatric care for patients with cancer has played out over the last century. The first collaboration of psychiatry, oncology surgery, and radiation-oncology occurred in the mid-1950s and represented the early seeds of psycho-oncology. The role of a psychiatrist specializing in treating patients with cancer, a psychosocial oncologist or psycho-oncologist, spans the care continuum from prevention to end of life. The specific needs of patients with gastrointestinal (GI) malignancies range from management of anxiety and depression to focused management for adjustment to an ostomy to sexual dysfunction to treatment in the face of a neuroendocrine tumor (NET). METHODS: This is a scoping review; we compiled and summarized psychiatric illnesses commonly encountered in care of patients with cancer in addition to unique GI oncology-related issues. We conducted an electronic PubMed search between 1990-2022. We are presenting the data and providing our insight into psychosocial oncology care for this special population. RESULTS: The field of psycho-oncology is relatively new. We failed to identify any randomized prospective studies, the majority of the studies were retrospective or longitudinal. The majority of the publications were in the form of review. We reviewed the GI literature to identify the psychological impact of ostomies, sexual impairment and metabolically active NETs. We provide suggested treatment interventions targeting the biological, psychological, and social aspects of patient and family lives. CONCLUSIONS: The role of a psychosocial oncologist as part of the collaborative multidisciplinary treatment team provides nuanced care with attention to unique cancer-related issues that arise during the disease course. The psycho-oncologist brings expertise in combining targeted therapeutic strategies with pharmacologic interventions to address the multi-dimensional symptomatology patients experience. Using a layered approach, patients with mild symptoms can be supported by the general team, while those with moderate to severe symptoms require specialty psychiatric consultation.

Pregnancy, delivery and neonatal outcomes in women with gastrointestinal system cancer in pregnancy. An evaluation of a population database.

OBJECTIVES: Gastrointestinal system (GIS) cancer in pregnancy is a rare disease. Our aim was to evaluate the association between this type of cancer and pregnancy, delivery and neonatal outcomes. METHODS: We conducted a retrospective population-based cohort study using the Healthcare Cost and Utilization Project, Nation-wide Inpatient Sample (HCUP-NIS). We included all women who delivered or had a maternal death in the US between 2004 and 2014. We compared women with an ICD-9 diagnosis of GIS cancer to those without. Pregnancy, delivery, and neonatal outcomes were compared between the two groups. RESULTS: A total of 9,096,788 women met inclusion criteria. Amongst them, 194 women (2/100,000) had a diagnosis of GIS cancer during pregnancy. Women with GIS cancer, compared to those without, were more likely to be Caucasian, older than 35 years of age, and to suffer from obesity, chronic hypertension, pregestational diabetes and thyroid disease. The cancer group had a lower rate of spontaneous vaginal delivery (aOR 0.2, 95 % CI 0.13-0.27, p<0.001), and a higher rate of preterm delivery (aOR 1.85, 95 % CI 1.21-2.82, p=0.04), and of maternal complications such as blood transfusion (aOR 24.7, 95 % CI 17.11-35.66, p<0.001), disseminated intravascular coagulation (aOR 14.56, 95 % CI 3.56-59.55, p<0.001), venous thromboembolism (aOR 9.4, 95 % CI 2.3-38.42, p=0.002) and maternal death (aOR 8.02, 95 % CI 2.55-25.34, p<0.001). Neonatal outcomes were comparable between the two groups. CONCLUSIONS: Women with a diagnosis of GIS cancer in pregnancy have a higher incidence of maternal complications including maternal death, without any differences in neonatal outcomes.

Long-term exposure to ambient fine particulate matter constituents and mortality from total and site-specific gastrointestinal cancer.

BACKGROUND: Ambient fine particulate matter (PM2.5) exposure has been associated with an increased risk of gastrointestinal cancer mortality, but the attributable constituents remain unclear. OBJECTIVES: To investigate the association of long-term exposure to PM2.5 constituents with total and site-specific gastrointestinal cancer mortality using a difference-in-differences approach in Jiangsu province, China during 2015-2020. METHODS: We split Jiangsu into 53 spatial units and computed their yearly death number of total gastrointestinal, esophagus, stomach, colorectum, liver, and pancreas cancer. Utilizing a high-quality grid dataset on PM2.5 constituents, we estimated 10-year population-weighted exposure to black carbon (BC), organic carbon (OC), sulfate, nitrate, ammonium, and chloride in each spatial unit. The effect of constituents on gastrointestinal cancer mortality was assessed by controlling time trends, spatial differences, gross domestic product (GDP), and seasonal temperatures. RESULTS: Overall, 524,019 gastrointestinal cancer deaths were ascertained in 84.77 million population. Each interquartile range increment of BC (0.46 µg/m3), OC (4.56 µg/m3), and nitrate (1.41 µg/m3) was significantly associated with a 27%, 26%, and 34% increased risk of total gastrointestinal cancer mortality, respectively, and these associations remained significant in PM2.5-adjusted models and constituent-residual models. We also identified robust associations of BC, OC, and nitrate exposures with site-specific gastrointestinal cancer mortality. The mortality risk generally displayed increased trends across the total exposure range and rose steeper at higher levels. We did not identify robust associations for sulfate, ammonium, or chlorine exposure. Higher mortality risk ascribed to constituent exposures was identified in total gastrointestinal and liver cancer among women, stomach cancer among men, and total gastrointestinal and stomach cancer among low-GDP regions. CONCLUSIONS: This study offers consistent evidence that long-term exposure to PM2.5-bound BC, OC, and nitrate is associated with total and site-specific gastrointestinal cancer mortality, indicating that these constituents need to be controlled to mitigate the adverse effect of PM2.5 on gastrointestinal cancer mortality.

The renin-angiotensin-aldosterone system (RAAS) signaling pathways and cancer: foes versus allies.

The renin-angiotensin-aldosterone system (RAAS), is an old system with new fundamental roles in cancer biology which influences cell growth, migration, death, and metastasis. RAAS signaling enhances cell proliferation in malignancy directly and indirectly by affecting tumor cells and modulating angiogenesis. Cancer development may be influenced by the balance between the ACE/Ang II/AT1R and the ACE2/Ang 1-7/Mas receptor pathways. The interactions between Ang II/AT1R and Ang I/AT2R as well as Ang1-7/Mas and alamandine/MrgD receptors in the RAAS pathway can significantly impact the development of cancer. Ang I/AT2R, Ang1-7/Mas, and alamandine/MrgD interactions can have anticancer effects while Ang II/AT1R interactions can be involved in the development of cancer. Evidence suggests that inhibitors of the RAAS, which are conventionally used to treat cardiovascular diseases, may be beneficial in cancer therapies.Herein, we aim to provide a thorough description of the elements of RAAS and their molecular play in cancer. Alongside this, the role of RAAS components in sex-dependent cancers as well as GI cancers will be discussed with the hope of enlightening new venues for adjuvant cancer treatment.

Colon Cancer Survivorship in Patients Who Have Received Adjuvant Chemotherapy.

The number of colon cancer survivors in the United States is increasing due to improved early detection, better treatments that extend survival, and the growing aging population who are at high risk for cancer. Following initial active treatment, colon cancer survivors experience a wide range of long-term physical, psychological, and socio-economic effects that impact their overall well-being. Healthcare providers caring for survivors need to prioritize not only monitoring for cancer recurrence but also optimizing their overall health through addressing these long-term effects; managing their comorbidities; promoting healthy behaviors (like exercise, nutrition, and weight loss); and screening for a second primary cancer depending on their risk. Personalized survivorship care plans should be formulated clearly outlining the roles of various healthcare providers involved in their care. Our review article focuses on these various aspects of colon cancer survivorship, including surveillance for cancer recurrence specific to those who received adjuvant chemotherapy with curative intent.

A review of anti-tumour effects of Ganoderma lucidum in gastrointestinal cancer.

Gastrointestinal (GI) cancer is the most common cancer in the world and one of the main causes of cancer-related death. Clinically, surgical excision and chemotherapy are the main treatment methods for GI cancer, which is unfortunately accompanied with serious adverse reactions and drug toxicity, bringing irreversible damage to patients and seriously affecting the quality of life. Ganoderma lucidum (G. lucidum) has a long history of medicinal and edible use in China. Its bioactive compounds mainly include polysaccharides, triterpenes, and proteins, which have potential anti-tumor activities by inhibiting proliferation, inducing apoptosis, inhibiting metastasis, and regulating autophagy. Currently, there is no in-depth review on the anti-tumor effect of G. lucidum in GI cancer. Therefore, this review is an attempt to compile the basic characteristics, anti-GI caner mechanisms, and clinical application of G. lucidum, aiming to provide a reference for further research on the role of G. lucidum in the prevention and treatment of GI cancer from the perspective of traditional Chinese and western medicine.

Spontaneous Biloma With a Hepatic Mass.

We report a case of an 86-year-old Hispanic male who presented with generalized itching and jaundice. Computed tomography (CT) imaging revealed a hepatic mass and an extensive spontaneous biloma, a condition rarely associated with malignancy. Subsequent biopsy of the mass confirmed moderately differentiated adenocarcinoma of the pancreaticobiliary tract. The patient underwent successful percutaneous drainage of the biloma and was discharged with a plan for further outpatient management. This case study highlights a rare manifestation of spontaneous biloma related to malignancy, broadening the clinical understanding of its association with malignancy, diagnosis, and management.