Gastrointestinal Malignancies Research Articles

Hepatic arterial infusion chemotherapy with implantable arterial access port for advanced-stage hepatocellular carcinoma: a case report

BackgroundHepatocellular carcinoma (HCC) is a common gastrointestinal malignancy characterized by high incidence rates and a poor prognosis. Common treatment modalities include surgery, ablation, and transarterial chemoembolization (TACE). Hepatic arterial infusion chemotherapy (HAIC) has long been used in the treatment of unresectable liver cancer. In recent years, the combination of anti-angiogenesis therapy and immune checkpoint inhibitors has shown significant advances in the treatment of middle- and advanced-stage liver cancer. This report presents a case of HCC in which sustained benefits are achieved through a combination of HAIC of infusional oxaliplatin, leucovorin, and fluorouracil (FOLFOX), targeted therapy, and immunotherapy.Main bodyA 64-year-old male patient was diagnosed with a parenchymal mass in the liver by a three-dimensional color ultrasound one month before admission, prompting consideration of liver cancer. Subsequently, computed tomography (CT) imaging performed at our hospital identified mass shadows in the right lobe of the liver and diffuse nodules throughout the liver, suggesting malignant lesions. Upon admission, the patient presented poor general health and baseline indicators. Following symptomatic treatment, the patient underwent a therapeutic regimen that combined transarterial infusion port FOLFOX-HAIC with Lenvatinib and Sintilimab. This combined treatment resulted in significant liver tumor necrosis and effectively managed the patient’s condition.ConclusionThe combined approach of using FOLFO-HAIC transarterial infusion alongside anti-angiogenesis therapy and immune checkpoint inhibitors has shown promising results that provide substantial benefits. This combined regimen has demonstrated the potential to improve treatment compliance among certain patients. Given these encouraging outcomes, further investigation into this combination therapy regimen is warranted to understand better its efficacy and potential broader applications in clinical settings.

Diagnostic Accuracy of Crush Smear Cytology in Gastrointestinal Malignancy

Diagnostic Accuracy of Crush Smear Cytology in Gastrointestinal Malignancy

Frequency of Common and Uncommon BRAF Alterations among Colorectal and Non-Colorectal Gastrointestinal Malignancies

Background: The predictive and prognostic role of BRAF alterations has been evaluated in colorectal cancer (CRC); however, BRAF alterations have not been fully characterized in non-CRC gastrointestinal (GI) malignancies. In the present study, we report the frequency and spectrum of BRAF alterations among patients with non-CRC GI malignancies. Methods: Patients with CRC and non-CRC GI malignancies who underwent somatic tumor profiling via a tissue-based or liquid-based assay were included in this study. Gain-of-function BRAF alterations were defined as pathogenic/likely pathogenic somatic short variants (SVs), copy number amplifications ≥8, or fusions (RNA or DNA). Results: Among 51,560 patients with somatic profiling, 40% had CRC and 60% had non-CRC GI malignancies. BRAF GOF alterations were seen more frequently in CRC (8.9%) compared to non-CRC GI malignancies (2.2%) (p < 0.001). Non-CRC GI malignancies with the highest prevalence of BRAF GOF alterations were bile duct cancers (4.1%) and small intestine cancers (4.0%). Among BRAF GOF alterations, class II (28% vs. 6.8%, p < 0.001) and class III (23% vs. 14%, p < 0.001) were more common in non-CRC GI malignancies. Among class II alterations, rates of BRAF amplifications (3.1% vs. 0.3%, p < 0.001) and BRAF fusions (12% vs. 2.2%, p < 0.001) were higher in non-CRC GI malignancies compared to CRC. Conclusions: Non-CRC GI malignancies demonstrate a distinct BRAF alteration profile compared to CRC, with a higher frequency of class II and III mutations, and more specifically, a higher incidence of BRAF fusions. Future studies should evaluate clinical implications for the management of non-CRC GI patients with BRAF alterations, especially BRAF fusions.

State-of-the-art and trends in fibroblast growth factor receptor-directed therapies in gastro-intestinal malignancies.

This review is timely and relevant due to the increasing recognition of the significance of the fibroblast growth factor receptor (FGFR) family in cancer biology. Understanding the role of FGFRs and their dysregulation in various cancers is crucial for developing targeted therapies and improving patient outcomes. The review highlights the importance of the FGFR family in cellular processes such as growth, proliferation, and survival. It discusses how abnormalities in FGFR2, including overexpression, gene amplification, and other genetic alterations, contribute to cancer progression, particularly in gastro-intestinal cancers. The paper also emphasizes the promising results of FGFR-targeted therapies, especially tyrosine kinase inhibitors, in certain cancers such as cholangiocarcinoma and oesophagogastric cancers. The findings underscore the potential of FGFR-targeted therapies in treating cancers with FGFR dysregulation. However, the review also addresses the challenges associated with these therapies, including toxicities and mechanisms of resistance. Understanding these complexities is essential for optimizing the efficacy of FGFR-targeted treatments and improving patient outcomes in clinical practice and research efforts.

The effect of intraoperative low-dose ketamine versus dexmedetomidine infusion on postoperative bowel recovery in patients undergoing gastrointestinal malignancy surgeries: Placebo-controlled, randomized trial

Abstract Background and Aims: No studies have compared the effects of ketamine and dexmedetomidine on bowel recovery. We evaluated the effects of intraoperative low-dose ketamine or dexmedetomidine infusion on postoperative bowel recovery in patients undergoing gastrointestinal (GI) malignancy surgeries. Material and Methods: This placebo-controlled, randomized study was carried out in 84 American Society of Anesthesiologists II patients, aged 18–70 years, of either gender, undergoing elective open GI malignancy surgeries. Patients received intraoperative infusion of ketamine @ 0.1 mg kg-1 h-1 (KET), dexmedetomidine @ 0.25 μg kg-1 h-1 (DEX), or normal saline (placebo). Primary outcome was the time to first flatus and/or stool. Secondary outcomes included time to extubation, total analgesic requirement, postoperative pain scores, time to feeds, duration of intensive care unit (ICU) and hospital stay, and the incidence of adverse events. Continuous data were analyzed by the one-way analysis of variance (ANOVA) or the Kruskal–Wallis test. Categorical data were analyzed by the Chi-square test or the Fisher’s exact test. Results: Median time to passage of flatus and/or stool was 3 [interquartile range (IQR) 2–3] days in the KET group, 2 [IQR 2–3] days in the DEX group, and 2 [IQR 2–3] days in the placebo group (P = 0.53 for placebo vs. KET, 0.81 for placebo vs. DEX, and 0.99 for KET vs. DEX). Pain scores and analgesic consumption were significantly less in the intervention groups versus placebo (P < 0.001). No difference was seen in other secondary outcomes. Conclusion: Low-dose ketamine or dexmedetomidine did not result in early bowel recovery despite lower pain scores and opioid consumption in patients undergoing open GI malignancy surgeries. Key Message: What is known: Ketamine and dexmedetomidine may promote bowel recovery by improving analgesia and decreasing opioid usage.Main findings: This randomized controlled trial found no evidence of earlier bowel recovery with ketamine or dexmedetomidine versus placebo despite lower pain scores and analgesic consumption in the ketamine and dexmedetomidine groups.

Risk Factors of Chemotherapy-Induced Thrombocytopenia After Oxaliplatin-Containing Chemotherapy for Gastrointestinal Malignancies.

Thrombocytopenia is among the most common chemotherapy-related hematologic toxicities. We aim to determine the predictors of oxaliplatin chemotherapy-induced thrombocytopenia in patients with gastrointestinal tumors to guide the clinic. Clinical data of 750 patients with a malignant gastrointestinal tumor were included as the primary cohort. Basic clinical data, serological indices, and anthropometric indices of these patients were collected. According to the presence or absence of CIT, univariate analysis was performed to identify significant factors for multivariate analysis. In R language software, nomogram was constructed based on the results of multi-factor analysis, and the calibration curve and ROC curve were drawn. Univariate analysis identified 17 factors as closely related to CIT occurrence, namely age, lymph node metastasis (N) stage, metastasis (M) stage, lung metastasis, other site metastasis, chemotherapy regimen, course of treatment, total dose of oxaliplatin, AST, albumin, neutrophils, monocytes, baseline platelets, transferrin, natural killer (NK) cell, phase angle, and SMI (P < 0.10). The binary logistic multivariate regression analysis revealed five independent risk factors for developing CIT (P < 0.05), including the M stage, total dose of oxaliplatin, albumin, baseline thrombocyte count, and NK cell. Based on the results of multivariate logistic regression analysis, R software was used to establish a nomogram model. The calibration curve shows that the combined predictor has good consistency. The area under the ROC curve was 0.877 and the best cut-off value was 0.3579613 (sensitivity, 78.9%; specificity, 81.8%), which showed the better prediction efficiency. The total dose of oxaliplatin, M stage, albumin, baseline platelet count, and NK cell was independent risk factors for CIT. The sequentially constructed histogram model had a good predictive effect on the risk of thrombocytopenia caused by oxaliplatin chemotherapy in patients with gastrointestinal malignancies.

ChatGPT's Gastrointestinal Tumor Board Tango: A limping dance partner?

ObjectivesThis study aimed to assess the consistency and replicability of treatment recommendations provided by ChatGPT 3.5 compared to gastrointestinal tumor cases presented at multidisciplinary tumor boards (MTBs). It also aimed to distinguish between general and case-specific responses and investigated the precision of ChatGPT's recommendations in replicating exact treatment plans, particularly regarding chemotherapy regimens and follow-up protocols. Material and methodsA retrospective study was carried out on 115 cases of gastrointestinal malignancies, selected from 448 patients reviewed in MTB meetings. A senior resident fed patient data into ChatGPT 3.5 to produce treatment recommendations, which were then evaluated against the tumor board's decisions by senior oncology fellows. ResultsAmong the examined cases, ChatGPT 3.5 provided general information about the malignancy without considering individual patient characteristics in 19% of cases. However, only in 81% of cases, ChatGPT generated responses that were specific to the individual clinical scenarios. In the subset of case-specific responses, 83% of recommendations exhibited overall treatment strategy concordance between ChatGPT and MTB. However, the exact treatment concordance dropped to 65%, notably lower in recommending specific chemotherapy regimens. Cases recommended for surgery showed the highest concordance rates, while those involving chemotherapy recommendations faced challenges in precision. ConclusionsChatGPT 3.5 demonstrates potential in aligning conceptual approaches to treatment strategies with MTB guidelines. However, it falls short in accurately duplicating specific treatment plans, especially concerning chemotherapy regimens and follow-up procedures. Ethical concerns and challenges in achieving exact replication necessitate prudence when considering ChatGPT 3.5 for direct clinical decision-making in MTBs.

Molecular study of KRAS mutations in Iraqi patients with gastrointestinal tract cancer

Molecular study of KRAS mutations in Iraqi patients with gastrointestinal tract cancer

The Effect of Different Anesthesia Depths on Postoperative Cognitive Function of Tumor Patients Monitored by Narcotrend

Abstract Objectives The study aimed to examine the influence of different anesthesia depths monitored by Narcotrend on postoperative cognitive dysfunction (POCD) in elderly patients undergoing radical resection of gastrointestinal malignancies. Methods Individuals in the control group (n = 40) maintained the Narcotrend index (NTI) at 50 to 59 monitored by Narcotrend, whereas the experimental group at 30 to 39. The mini-mental state examination (MMSE) scale and serum S100β concentration were used to evaluate the cognitive function. Cerebral oxygen metabolism and inflammation were evaluated, presenting as regional oxygen saturations of brain (rSO2) and cerebral oxygen uptake rate (CERO2), serum tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Results Experimental group presented prominently high levels of rSO2 and low levels of CERO2 relative to controls, meanwhile with reduced serum TNF-α and IL-6. Individuals receiving deep anesthesia owned low levels of S100β and enhanced MMSE score, which showed negative correlation. Low incidence rate of POCD was detected in the experimental group. Both age (hazard ratio = 5.219, 95% confidence interval = 1.813–15.025) and NTI score (hazard ratio = 3.707, 95% confidence interval = 1.292–10.633) were independent influence factors for the onset of POCD. Conclusion NTI maintained at 30 to 39 can reduce the incidence of POCD in the early postoperative period for elderly patients receiving gastrointestinal tumors surgery, the contribution might be attributed to the improvement of perioperative cerebral oxygen metabolism and inflammatory stress response.

State of the art and upcoming trends in HER2-directed therapies in gastrointestinal malignancies.

This review critically evaluates the evolution and current status of human epidermal growth factor receptor 2 (HER2)-directed therapies in upper gastrointestinal (GI) malignancies, a timely and relevant inquiry given the dynamic shifts in therapeutic strategies over the past decade. Initial enthusiasm following the Trastuzumab for Gastric Cancer (ToGA) study's demonstration of trastuzumab's efficacy, however, encountered hurdles due to subsequent trials showing limited progress, underscoring the necessity for a reevaluation of therapeutic approaches and the exploration of novel agents. The review highlights significant breakthroughs in the form of immune checkpoint inhibitors and innovative therapeutic technologies, which have redefined treatment paradigms and shown promising efficacy in HER2-positive cases. Emerging treatments such as trastuzumab deruxtecan (T-DXd), zanidatamab and evorpacept further illustrate the ongoing efforts to leverage unique mechanisms of action for improved HER2-positive antitumor activity. The advancements in HER2-directed therapies underscore a pivotal era in the management of upper GI malignancies. These developments not only reflect the profound impact of integrating novel therapeutic combinations but also highlight the critical role of ongoing research in overcoming resistance mechanisms and tailoring treatment to individual disease profiles.

Response Evaluation Criteria in Gastrointestinal and Abdominal Cancers: Which to Use and How to Measure.

As the management of gastrointestinal malignancy has evolved, tumor response assessment has expanded from size-based assessments to those that include tumor enhancement, in addition to functional data such as those derived from PET and diffusion-weighted imaging. Accurate interpretation of tumor response therefore requires knowledge of imaging modalities used in gastrointestinal malignancy, anticancer therapies, and tumor biology. Targeted therapies such as immunotherapy pose additional considerations due to unique imaging response patterns and drug toxicity; as a consequence, immunotherapy response criteria have been developed. Some gastrointestinal malignancies require assessment with tumor-specific criteria when assessing response, often to guide clinical management (such as watchful waiting in rectal cancer or suitability for surgery in pancreatic cancer). Moreover, anatomic measurements can underestimate therapeutic response when applied to molecular-targeted therapies or locoregional therapies in hypervascular malignancies such as hepatocellular carcinoma. In these cases, responding tumors may exhibit morphologic changes including cystic degeneration, necrosis, and hemorrhage, often without significant reduction in size. Awareness of pitfalls when interpreting gastrointestinal tumor response is required to correctly interpret response assessment imaging and guide appropriate oncologic management. Data-driven image analyses such as radiomics have been investigated in a variety of gastrointestinal tumors, such as identifying those more likely to respond to therapy or recur, with the aim of delivering precision medicine. Multimedia-enhanced radiology reports can facilitate communication of gastrointestinal tumor response by automatically embedding response categories, key data, and representative images. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Ferroptosis and its role in gastric and colorectal cancers.

Ferroptosis is a novel mechanism of programmed cell death, characterized by intracellular iron overload, intensified lipid peroxidation, and abnormal accumulation of reactive oxygen species, which ultimately resulting in cell membrane impairment and demise. Research has revealed that cancer cells exhibit a greater demand for iron compared to normal cells, indicating a potential susceptibility of cancer cells to ferroptosis. Stomach and colorectal cancers are common gastrointestinal malignancies, and their elevated occurrence and mortality rates render them a global health concern. Despite significant advancements in medical treatments, certain unfavorable consequences and drug resistance persist. Consequently, directing attention towards the phenomenon of ferroptosis in gastric and colorectal cancers holds promise for enhancing therapeutic efficacy. This review aims to elucidate the intricate cellular metabolism associated with ferroptosis, encompassing lipid and amino acid metabolism, as well as iron metabolic processes. Furthermore, the significance of ferroptosis in the context of gastric and colorectal cancer is thoroughly examined and discussed.

Unveiling Discrepant and Rare Dihydropyrimidine Dehydrogenase (DPYD) Results Using an In-House Genotyping Test: A Case Series.

Fluoropyrimidine chemotherapy is a primary component of many solid tumor treatment regimens, particularly those for gastrointestinal malignancies. Approximately one-third of patients receiving fluoropyrimidine-based chemotherapies experience serious adverse effects. This risk is substantially higher in patients carrying DPYD genetic variants, which cause reduced fluoropyrimidine metabolism and inactivation (ie, dihydropyridine dehydrogenase [DPD] deficiency). Despite the known relationship between DPD deficiency and severe toxicity risk, including drug-related fatalities, pretreatment DPYD testing is not standard of care in the United States. We developed an in-house DPYD genotyping test that detects 5 clinically actionable variants associated with DPD deficiency, and genotyped 827 patients receiving fluoropyrimidines, of which 49 (6%) were identified as heterozygous carriers. We highlight 3 unique cases: (1) a patient with a false-negative result from a commercial laboratory that only tested for the c.1905 + 1G>A (*2A) variant, (2) a White patient in whom the c.557A>G variant (typically observed in people of African ancestry) was detected, and (3) a patient with the rare c.1679T>G (*13) variant. Lastly, we evaluated which DPYD variants are detected by commercial laboratories offering DPYD genotyping in the United States and found 6 of 13 (46%) did not test for all 5 variants included on our panel. We estimated that 20.4% to 81.6% of DPYD heterozygous carriers identified on our panel would have had a false-negative result if tested by 1 of these 6 laboratories. The sensitivity and negative predictive value of the diagnostic tests from these laboratories ranged from 18.4% to 79.6% and 95.1% to 98.7%, respectively. These cases underscore the importance of comprehensive DPYD genotyping to accurately identify patients with DPD deficiency who may require lower fluoropyrimidine doses to mitigate severe toxicities and hospitalizations. Clinicians should be aware of test limitations and variability in variant detection by commercial laboratories, and seek assistance by pharmacogenetic experts or available resources for test selection and result interpretation.

LncRNA CASC15 activated by TCF12 promote colorectal cancer progression via EMT.

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. LncRNA CASC15 has also been found to play a vital role in malignant tumors. Our objective is to explore the role of CASC15 in colorectal cancer and its regulation of EMT and to clarify the reasons for its up-regulated expression in CRC. Quantitative real-time PCR was performed to evaluate the expression of CASC15 in CRC. The biology function of CASC15 on CRC was assessed by in vitro experiments, including CCK8, colony formation, transwell assays and flow cytometry. Luciferase reporter assays were used to confirm the regulation between TCF12 and CASC15. Quantitative real-time PCR and western blot analysis were used to evaluate the biomarkers associated with epithelial-mesenchymal transition (EMT). We found that CASC15 was remarkably upregulated in CRC and positively correlated with poorer relapse-free survival. CASC15 knockdown significantly suppressed the proliferation and migration of CRC. Furthermore, CASC15 downregulation mediated apoptosis of CRC. Mechanistically, TCF12 activates CASC15 transcription to mediate its up-regulation, which activates EMT and promotes CRC progression. Our study identified TCF12/CASC15/EMT as a new regulatory signal axis of CRC. CASC15 may be a new molecular marker and target for CRC.

A Five-gene Signature Based on MicroRNA for Predicting Prognosis and Immunotherapy in Stomach Adenocarcinoma.

We aimed to classify molecular subtypes and establish a prognostic gene signature based on miRNAs for the prognostic prediction and therapeutic response in Stomach adenocarcinoma (STAD). STAD is a common diagnosed gastrointestinal malignancy and its heterogeneity is a big challenge that influences prognosis and precision therapies. Present study was designed to classify molecular subtypes and construct a prognostic gene signature based on miRNAs for the prognostic prediction and therapeutic response in STAD. The objective of this study is to investigate the molecular subtypes and prognostic model for STAD. A STAD specific miRNA-messenger RNA (mRNA) competing endogenous RNA (ceRNA) network was generated using the RNA-Seq and miRNA expression profiles from The Cancer Genome Atlas (TCGA) database, in which miRNA-related mRNAs were screened. Molecular subtypes were then determined using miRNA-related genes. Through univariate Cox analysis and multivariate regression analysis, a prognostic model was established in GSE84437 Train dataset and validated in GSE84437 Test, TCGA, GSE84437 and GSE66229 datasets. Immunotherapy datasets were employed for assessing the performance of the risk model. Finally, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was applied to validate the expression of hub genes used for the risk score signature. We constructed a ceRNA network containing 84 miRNAs and 907 mRNAs and determined two molecular subtypes based on 26 genes from the intersection of TCGASTAD and GSE84437 datasets. Subtype S2 had poor prognosis, lower tumor mutational burden, higher immune score and lower response to immunotherapy. Subtype S1 was more sensitive to Sorafenib, Pyrimethamine, Salubrinal, Gemcitabine, Vinorelbine and AKT inhibitor VIII. Next, a five-gene signature was generated and its robustness was validated in Test and external datasets. This risk model also had a good prediction performance in immunotherapy datasets. This study promotes the underlying mechanisms of miRNA-based genes in STAD and offers directions for classification. A five-gene signature accurately predicts the prognosis and helps therapeutic options.

Stereotactic radiosurgery for brain metastasis from cholangiocarcinoma.

Accounting for approximately 15% of primary liver cancers and 3% of gastrointestinal malignancies, cholangiocarcinoma (CCA) poses a serious health concern given its high mortality rate. Managing brain metastases (BMs) from CCA is challenging because of their rarity and poor prognosis, with little guidance on treatment from the literature. In this study, the authors aimed to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in managing BMs from CCA. This multicenter retrospective study included 13 CCA patients with 41 BMs treated with SRS from October 2006 to April 2022 at eight institutions affiliated with the International Radiosurgery Research Foundation. Inclusion criteria were a CCA diagnosis, an age over 18 years, no other malignancies, single-fraction SRS treatment for BMs, and at least one follow-up image. Data on demographics, tumor characteristics, treatment details, and outcomes were collected. The primary endpoints were local control (LC), intracranial progression-free survival (PFS), and overall survival (OS). The secondary endpoint was the development of adverse radiation effects (AREs). The median radiological follow-up was 5 months (range 1-18 months). At the last follow-up, LC was achieved in 39 (95.1%) of 41 BMs. New distant metastases were observed in 3 patients (23.1%), and the mean intracranial PFS was 9.4 months (95% CI 6.5-12.3 months). Six-month and 1-year OS rates were 38.5% and 11.5%, respectively, and the median OS was 6 months (95% CI 4.9-7.2 months). Concurrent immunotherapy was associated with a high risk of local failure (HR 29.665, 95% CI 1.799-489.206, p = 0.018), and the absence of systemic chemotherapy before SRS was linked to reduced OS (HR 6.658, 95% CI 1.173-37.776, p = 0.032). Regarding AREs, only 1 patient (7.7%) experienced right hemiparesis and was treated with corticosteroid therapy. SRS is an effective option for managing BMs in CCA patients, showing promise in LC and a high safety profile.

Polyp segmentation network based on lightweight model and reverse attention mechanisms

AbstractColorectal cancer is a common gastrointestinal malignancy. Early screening and segmentation of colorectal polyps are of great clinical significance. Colonoscopy is the most effective method to detect polyps, but some polyps may be missed in the detection process. On this basis, the use of computer‐aided diagnosis technology is particularly important for colorectal polyp segmentation. To improve the detection rate of intestinal polyps under colonoscopy, a polyp segmentation network (MobileRaNet) based on a lightweight model and reverse attention (RA) mechanism was proposed to accurately segment polyps in colonoscopy images. The coordinated attention module is used to improve MobileNetV3 and make it the backbone network (CaNet). Second, a part of the output of the high‐level feature from the backbone network is passed into the parallel axial receptive field module (PA_RFB) to extract the global dependency representation without losing the details. Third, a global map is generated based on this combined feature as the initial boot area of the subsequent components. Finally, the RA module is used to mine the target region and boundary clues to improve the segmentation accuracy. To verify the effectiveness and lightweight performance of the algorithm, five challenging datasets, including CVC‐ColonDB, CVC‐300, and Kvasir, are used in this paper. In six indexes, including MeanDice, MeanIoU, and MAE, compared with seven typical models such as PraNet and TransUnet, accuracy, FLOPs, parameters, and FPS were compared. The experimental results show that the MobileRaNet proposed in this paper has improved the performance of the five datasets to varying degrees, especially the MeanDice and MeanIOU indexes of the Kvasir dataset reach 91.2% and 85.6%, which are, respectively, increased by 1.4% and 1.6% compared with PraNet. Compared with PraNet, FLOPs and parameters decreased by 83.3% and 76.7%, respectively.

Probiotics for Inflammatory Bowel Disease; A Deep Dive into Their Impact on Disease Course and Associated Health Risks.

To date, the underlying pathology of inflammatory bowel disease (IBD) is undetermined. Disturbance of intestinal gut microbiota was implicated in many health diseases, including IBD. Increasing evidence suggests that probiotics play a beneficial role in restoring the balance of the gut ecosystem. This review searched multiple databases for relevant works that examined probiotics' possible benefits in adults with IBD. Probiotic mode of action in ulcerative colitis patients and Crohn's disease were examined with respect to probiotic strain, their benefits, and their advantages in adult cases. Eligible studies for inclusion were assessed and analyzed. They were effective in reducing IBD disease course, inducing and maintaining remission, particularly for ulcerative colitis patients, with good efficacy and safety profile. However, the evidence for Crohn's disease was lacking. Probiotics positively affect IBD-related risks, reducing the risk of gastrointestinal malignancy and optimizing treating them. Additionally, they improved reduced fertility odds for both genders. The osteoporosis risk among IBD patients was also reduced, although the duration of use and dose were still not established. There was an encouraging role for them in reducing IBD -cardiovascular risks among cases with acute myocardial infarction and those with chronic heart failure. Finally, they had novel use in reducing IBD-related depression and improved overall mental health. In conclusion, we recommend probiotics as an adjuvant therapeutic option for IBD therapy for ulcerative colitis; however, their role in Crohn's disease needs further research.

Baicalein triggers ferroptosis in colorectal cancer cells via blocking the JAK2/STAT3/GPX4 axis.

Colorectal cancer (CRC) is a prevalent form of gastrointestinal malignancy with challenges in chemotherapy resistance and side effects. Effective and low toxic drugs for CRC treatment are urgently needed. Ferroptosis is a novel mode of cell death, which has garnered attention for its therapeutic potential against cancer. Baicalein (5, 6, 7-trihydroxyflavone) is the primary flavone extracted from the dried roots of Scutellaria baicalensis that exhibits anticancer effects against several malignancies including CRC. In this study, we investigated whether baicalein induced ferroptosis in CRC cells. We showed that baicalein (1-64 μM) dose-dependently inhibited the viability of human CRC lines HCT116 and DLD1. Co-treatment with the ferroptosis inhibitor liproxstatin-1 (1 μM) significantly mitigated baicalein-induced CRC cell death, whereas autophagy inhibitor chloroquine (25 μM), necroptosis inhibitor necrostatin-1 (10 μM), or pan-caspase inhibitor Z-VAD-FMK (10 μM) did not rescue baicalein-induced CRC cell death. RNA-seq analysis confirmed that the inhibitory effect ofbaicalein on CRC cells isassociated with ferroptosis induction. We revealed that baicalein (7.5-30 μM) dose-dependently decreased the expression levels of GPX4, key regulator of ferroptosis, in HCT116 and DLD1 cells by blocking janus kinase 2 (JAK2)/STAT3 signaling pathway via direct interaction with JAK2, ultimately leading to ferroptosis in CRC cells. In a CRC xenograft mouse model, administration of baicalein (10, 20 mg/kg, i.g., every two days for two weeks) dose-dependently inhibited the tumor growth with significant ferroptosis induced by inhibiting the JAK2/STAT3/GPX4 axis in tumor tissue. This study demonstrates that ferroptosis contributes to baicalein-induced anti-CRC activity through blockade of the JAK2/STAT3/GPX4 signaling pathway, which provides evidence for the therapeutic application of baicalein against CRC.

Evaluation of Unsolicited Feedback from Patients with Cancer and Their Families as a Strategy to Improve Cancer Care Delivery

Background: Unsolicited patient feedback (compliments and complaints) should allow the healthcare system to address and improve individual and overall patient, family, and staff experiences. We evaluated feedback at a tertiary cancer centre to identify potential areas for optimizing care delivery. Methods: unsolicited feedback submitted to the Patient Relations Department, relating to the Divisions of Medical and Radiation Oncology, at the Ottawa Hospital, was analyzed. Results: Of 580 individual reports submitted from 2016 to 2022, patient demographics were available for 97% (563/580). Median patient age was 65 years (range 17–101), and 53% (301/563) were female. The most common cancer types were breast (127/545, 23%) and gastrointestinal (119/545, 22%) malignancies, and most (64%, 311/486) patients had metastatic disease. Feedback was submitted mainly by patients (291/579, 50%), and predominantly negative (489/569, 86%). The main reasons for complaints included: communication (29%, 162/566) and attitude/conduct of care (28%, 159/566). While feedback rates were initially stable, an increase occurred from 2019 to 2021. Conclusions: Unsolicited feedback remains mostly negative, and relates to physician communication. If we are to drive meaningful changes in care delivery, more standardized means of assessing feedback and implementation strategies are needed. In addition, in an era of increased healthcare provider burnout, strategies to enhance formal positive feedback are also warranted.