Unilateral drainage and chemotherapy prolong the patency of a plastic stent placed above the sphincter of Oddi in patients with malignant hilar biliary obstruction.

Objectives: To evaluate the results of inside stent therapy for unresectable malignant hilar biliary obstruction and identify factors related to stent patency duration. Methods: Of 44 patients who underwent initial inside-stent placement above the sphincter of Oddi from April 2017 to December 2022, 42 with the resolution of jaundice (clinical success rate, 95.5%) were retrospectively analyzed. Univariate and multivariate logistic regression analysis identified factors associated with stent patency duration. Results: Univariate analysis revealed significant differences in the drainage method (406 days for unilateral drainage vs. 305 days for bilateral drainage of the right and left liver lobes, p = 0.022) with or without chemotherapy (406 days with vs. 154 days without, p = 0.038). Multivariate analysis (Cox proportional hazards analysis) revealed similar results, with unilateral drainage (p = 0.031) and chemotherapy (p = 0.048) identified as independent factors associated with prolonged stent patency. Early adverse events were observed in two patients (4.8%; one cholangitis, one pancreatitis). Conclusions: Inside-stent therapy was safely performed in patients with malignant hilar biliary obstruction. Simple unilateral drainage and chemotherapy may prolong stent patency.

A versatile nanoplatform carrying cascade Pt nanozymes remodeling tumor microenvironment for amplified sonodynamic/chemo therapy of thyroid cancer.

Thyroid cancer is increasing globally, with anaplastic thyroid carcinoma (ATC) being the most aggressive type and having a poor prognosis. Current clinical treatments for thyroid cancer present numerous challenges, including invasiveness and the necessity of lifelong medication. Furthermore, a significant portion of patients with ATC experience cancer recurrence and metastasis. To overcome this dilemma, we developed a pH-responsive biomimetic nanocarrier (CLP@HP-A) through the incorporation of Chlorin e6 (Ce6) and Lenvatinib (Len) within hollow polydopamine nanoparticles (HP) that were further modified with platinum nanoparticles (Pt), enabling synergistic chemotherapy and sonodynamic therapy. The CLP@HP-A nanocarriers exhibited specific binding with galectin-3 receptors, facilitating their internalization through receptor-mediated endocytosis for targeted drug delivery. Upon exposure to ultrasound (US) irradiation, Ce6 rapidly generated reactive oxygen species (ROS) to induce significant oxidative stress and trigger apoptosis in tumor cells. Additionally, Pt not only alleviated tumor hypoxia by catalyzing the conversion of H2O2 to oxygen (O2) but also augmented intracellular ROS levels through the production of hydroxyl radicals (•OH), thereby enhancing the efficacy of sonodynamic therapy. Moreover, Len demonstrated a potent cytotoxic effect on thyroid cancer cells through the induction of apoptosis. Transcriptomics analysis findings additionally corroborated that CLP@HP-A effectively triggered cancer cell apoptosis, thereby serving as a crucial mechanism for its cytotoxic effects. In conclusion, the integration of sonodynamic/chemo combination therapy with targeted drug delivery systems offers a novel approach to the management of malignant tumors.

Rational construction of CQDs-based targeted multifunctional nanoplatform for synergistic chemo-photothermal tumor therapy.

Photothermal therapy combined with chemotherapy has shown great promise in the treatment of cancer. In this synergistic system, a safe, stable, and efficient photothermal agent is desired. Herein, an effective photothermal agent, carbon quantum dots (CQDs), was initially synthesized and then rationally constructed a folic acid (FA)-targeted photothermal multifunctional nanoplatform by encapsulating CQDs and the anticancer drug doxorubicin (DOX) in the liposomes. Indocyanine green (ICG), a near infrared (NIR) photothermal agent, approved by the U.S. Food and Drug Administration, was embedded in the bilayer membrane to further enhance the photothermal effects and facilitate the rapid cleavage of liposomes for drug release. Triggered by the NIR laser, this engineered photothermal multifunctional nanoplatform, not only exhibited an excellent performance with the photothermal conversion efficiency of up to 47.14%, but also achieved controlled release of the payloads. In vitro, and in vivo experiments demonstrated that the photothermal multifunctional nanoplatform had excellent biocompatibility, enhanced tumor-specific targeting, stimuli-responsive drug release, effective cancer cell killing and tumor suppression through multi-modal synergistic therapy. The successful construction of this NIR light-triggered targeted photothermal multifunctional nanoplatform will provide a promising strategy for the design and development of synergistic chemo-photothermal combination therapy and improve the therapeutic efficacy of cancer treatment.

Emerging roles of non-coding RNAs in modulating the PI3K/Akt pathway in cancer.

Cancer progression results from the dysregulation of molecular pathways, each with unique features that can either promote or inhibit tumor growth. The complexity of carcinogenesis makes it challenging for researchers to target all pathways in cancer therapy, emphasizing the importance of focusing on specific pathways for targeted treatment. One such pathway is the PI3K/Akt pathway, which is often overexpressed in cancer. As tumor cells progress, the expression of PI3K/Akt increases, further driving cancer advancement. This study aims to explore how ncRNAs regulate the expression of PI3K/Akt. NcRNAs are found in both the cytoplasm and nucleus, and their functions vary depending on their location. They can bind to the promoters of PI3K or Akt, either reducing or increasing their expression, thus influencing tumorigenesis. The ncRNA/PI3K/Akt axis plays a crucial role in determining cell proliferation, metastasis, epithelial-mesenchymal transition (EMT), and even chemoresistance and radioresistance in human cancers. Anti-tumor compounds can target ncRNAs to modulate the PI3K/Akt axis. Moreover, ncRNAs can regulate the PI3K/Akt pathway both directly and indirectly.

Efficacy and prognosis of neoadjuvant chemotherapy in HER2 low-expressing breast cancer: a retrospective single-center study.

Purpose: Human epidermal growth factor receptor 2 (HER2) is vital for breast cancer prognosis. The aim of this study was to analyze the clinicopathological data of HER2-negative breast cancer patients receiving neoadjuvant chemotherapy and the associated factors affecting the pathological complete response rate (pCR) and prognosis. Methods: Clinical data of 173 patients with primary HER2-negative breast cancer, who initially received neoadjuvant chemotherapy followed by surgical treatment at the Breast Surgery Department of Bethune Hospital in Shanxi Province from January 2012 to December 2022, were collected. Results: Compared to HER2-0 patients, HER2-low patients had higher T staging (p = 0.008), higher Ki67 proliferation index (p < 0.001), lower N staging (p = 0.001), and lower pCR rate (p < 0.001). Univariate analysis revealed that T stage, TNM stage, HR status, HER2 status, and Ki67 are risk factors that affect the pCR rate in HER-2 negative. Multivariate analysis identified HR status as an independent predictor of pCR rate. Kaplan-Meier survival curves showed that menstrual status, N staging, T staging, TNM staging, and pCR status affected the prognosis of HER2-low breast cancer patients (p < 0.05). Conclusion: HER2-low breast cancer exhibits distinct biological behaviors, suggesting personalized treatment approaches.

Predictive models and treatment efficacy for liver cancer patients with bone metastases: A comprehensive analysis of prognostic factors and nomogram development.

Background: Bone metastasis considerably undermines the prognosis of advanced primary liver cancer patients. Though its impact is well-recognized, the clinical field still lacks robust predictive models that can accurately forecast patient outcomes and aid in treatment effectiveness evaluation. Addressing this gap is paramount for improving patient management and survival. Materials and methods: We conducted an extensive analysis using data from the SEER database (2010-2020). COX regression analysis was applied to identify prognostic factors for primary liver cancer with bone metastasis (PLCBM). Nomograms were developed and validated to predict survival outcomes in PLCBM patients. Additionally, propensity score matching and Kaplan-Meier survival analyses lent additional insight by dissecting the survival advantage conferred by various treatment strategies. Results: A total of 470 patients with PLCBM were included in our study. The median overall survival (OS) and cancer-specific survival (CSS) for these patients were both 5 months. We unveiled several independent prognosticators for OS and CSS, spanning demographic to therapeutic parameters like marital status, cancer grade, histological type, and treatments received. This discovery enabled the formulation of two novel nomograms-now verified to eclipse the predictive prowess of the traditional TNM staging system regarding discrimination and clinical utility. Additionally, propensity score matching analysis showed the effectiveness of surgeries, radiotherapy, and chemotherapy in improving OS and CSS outcomes for PLCBM patients. Conclusions: Our investigation stands out by introducing pioneering nomograms for prognostic evaluation in PLCBM, a leap forward compared to existing tools. Far exceeding mere academic exercise, these nomograms hold immense clinical value, serving as a foundation for nuanced risk stratification systems and delivering dynamic, interactive guides, allowing healthcare professionals and patients to assess individual bone metastasis survival probabilities and personalize treatment selection.

Serious Gaming for Chemotherapy-Induced Nausea and Vomiting in Older Adults With Cancer: Protocol for a Randomized Clinical Trial.

BACKGROUND: Older adults are at high risk for toxicity due to cancer treatment and increased risk for adverse events related to chemotherapy-induced nausea and vomiting (CINV). Unfortunately, older adults report multiple treatment-related symptoms but use few strategies to self-manage these symptoms due to erroneous beliefs related to the effectiveness of commonly taught self-management strategies. We developed a novel serious game, Managing at Home (MAH), to help older adults learn how to effectively self-manage CINV at home. OBJECTIVE: This study has 2 aims. Aim 1 is to examine changes in CINV severity, self-management behaviors, functioning, quality of life, cognitive representation, and health care use within the intervention group from baseline (T1) to completion of the study (T6). Aim 2 is to determine the efficacy of the MAH intervention by comparing differences in primary outcomes (CINV severity and health care use) and secondary outcomes (self-management behaviors, functioning, and quality of life) between the intervention and control groups at each follow-up visit (T2-T6) and completion of the study (T6). METHODS: This is a longitudinal randomized clinical trial. We will collect data from 500 older adults receiving cancer-related chemotherapy at baseline (T1) and at each treatment cycle until cycle 6 (T6). Participants will be enrolled if they are 60 years or older of age, are newly diagnosed with cancer, being treated with any chemotherapy agent with moderate or high emetic potential, are on a 2-, 3-, or 4-week treatment cycle, are proficient in English, and have a telephone. Previous diagnosis or treatment for cancer, end-stage disease with less than 6 months to live, and uncorrected visual or hearing impairment are exclusion criteria. RESULTS: This study was funded in September 2022 and received institutional review board approval in October 2022. As of July 2023, the enrollment of participants is ongoing and currently has 130 enrolled participants. Data collection and analysis will be complete in 2027. CONCLUSIONS: This study addresses self-management of CINV in older adults using an innovative serious game. The MAH intervention uses simulation and gaming technology to engage older adults in active learning in order to reframe erroneous perceptions about symptom self-management. If shown to be effective, it can easily be adapted to include other cancer-related symptoms or other chronic illnesses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05838638; https://clinicaltrials.gov/study/NCT05838638. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/64673.

Nivolumab plus ipilimumab with chemotherapy for non-small cell lung cancer with untreated brain metastases: A multicenter single-arm phase 2 trial (NIke, LOGiK 2004).

BACKGROUND: The effect of dual immunotherapy combined with platinum-based chemotherapy on untreated brain metastases derived from non-small cell lung cancer (NSCLC) has remained unclear. METHODS: This multicenter single-arm phase 2 study enrolled patients with chemotherapy-naïve advanced NSCLC and at least one brain metastasis ≥ 5 mm in size that had not been previously treated. Patients received nivolumab plus ipilimumab combined with platinum-doublet chemotherapy (two cycles), followed by nivolumab-ipilimumab alone. The primary endpoint of the study was intracranial response rate as determined by modified Response Evaluation Criteria in Solid Tumors (RECIST) for brain metastases of ≥ 5 mm as target lesions. RESULTS: A total of 30 patients from 18 institutions was enrolled in this study. The median age was 66.5 years (range, 47-83 years), and 26 patients (87 %) had a non-squamous cell carcinoma histology. The median size of all target brain lesions was 8.4 mm, with a range of 5-39 mm. The intracranial response rate assessed by modified RECIST was 50.0 % (95 % CI, 33.2-66.8 %), with the rate of complete response being 20.0 %, and the study met its primary endpoint. The systemic response rate was 53.3 % (95 % CI, 36.1-69.8 %), and responses for intracranial and extracranial lesions were generally consistent. The median intracranial progression-free survival was 8.1 months, and both the median intracranial duration of response and time to brain radiotherapy were not reached. CONCLUSION: Nivolumab plus ipilimumab combined with platinum-based chemotherapy showed promising intracranial activity in NSCLC patients with untreated brain metastases. TRIAL REGISTRATION: jRCT071210019.

Standard chemotherapy impacts on in vitro cellular heterogeneity in spheroids enriched with cancer stem cells (CSCs) derived from triple-negative breast cancer cell line.

Triple-negative breast cancer is a heterogeneous disease with high recurrence and mortality, linked to cancer stem cells (CSCs). Our study characterized distinct cell subpopulations and signaling pathways to explore chemoresistance. We observed cellular heterogeneity among and within the cells regarding phenotyping and drug response. In untreated BT-549 cells, we noted plasticity properties in both CD44+/CD24+/CD146+ hybrid cells and CD44-/CD24+/CD146+ epithelial cells, enabling phenotypic conversion into CD44+/CD24-/CD146- epithelial-mesenchymal transition (EMT)-like like breast CSCs (BCSCs). Additionally, non-BCSCs may give rise to ALDH+ epithelial-like BCSCs. Enriched BCSCs demonstrated the potential to differentiation into CD44-/CD24-/CD146- cells and exhibited self-renewal capabilities. Similar phenotypic plasticity was not observed in untreated Hs 578T and HMT-3522 S1 cells. BT-549 cells were more resistant to paclitaxel/PTX than to doxorubicin/DOX, a phenomenon potentially linked to the presence of CD24+ cells prior to treatment. Under the CSCs-enriched spheroids model, BT-549 demonstrated extreme resistance to DOX, likely due to the enrichment of BCSCs CD44+/CD24-/CD146- and the tumor cells CD44-/CD24-/CD146-. Additionally, DOX treatment induced the enrichment of plastic and chemoresistant cells, further exacerbating resistance mechanisms. BT-549 exhibited high heterogeneity, leading to significant alterations in cell subpopulations under BCSCs enrichment, demonstrating increased phenotypic plasticity during EMT. This phenomenon appears to play a major role in DOX resistance, as indicated by the presence of the refractory cells CD44+/CD24-/CD146- BCSCs EMT-like, CD44-/CD24-/CD146- tumor cells, and elevated STAT3 expression. Gene expression data from BT-549 CSCs-enriched spheroids suggests that ferroptosis may be occurring via autophagic regulation triggered by RAB7A, highlighting this gene as a potential therapeutic target.

[Toward optimizing AML treatment in the elderly].

Traditionally, the goal of AML therapy has been to induce remission with intensive chemotherapy, reduce tumor volume as much as possible with consolidation therapy, and achieve cure by allogeneic transplantation in patients with a poor prognosis. However, in elderly patients and patients with co-morbidities, toxicity often outweighs the therapeutic benefit of intensive chemotherapy. Now that low-intensity chemotherapy, such as methylation inhibitors and venetoclax, has emerged as a promising treatment option for elderly patients, it is more important than ever to consider age and comorbidities in treatment selection. The recently proposed comorbidity-based risk stratification system for AML enables prognostic stratification in not only patients who received intensive chemotherapy, but also those who received low-intensity chemotherapy. Optimization of treatment intensity based on such risk stratification should improve both treatment efficacy and safety, and ultimately improve the prognosis of AML.

Implementation of a Multidisciplinary Enhanced Recovery After Surgery (ERAS) Program for Cytoreductive Surgery (CRS) With Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

BACKGROUND AND OBJECTIVES: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) can be associated with prolonged hospital stays. A novel Enhanced Recovery After Surgery (ERAS) based on ERAS Society guidelines was designed and implemented. The primary outcome was ERAS compliance. Secondary outcomes included length of stay (LOS) and postoperative complications. METHODS: A retrospective study on patients who underwent CRS/HIPEC between 2018 and 2022, with ERAS implementation in 2022. Health records were reviewed. Statistical analysis included descriptive statistics, Wilcoxon tests, Student t-test, and χ2 and binomial negative regression. Health Ethics Research Board approval was obtained. RESULTS: Eighty patients underwent CRS/HIPEC: 59 in the pre-ERAS group and 21 in the post-ERAS group. Groups were similar in age, comorbidities, and Peritoneal Carcinomatosis Index. ERAS compliance increased from 32.8% to 70.8% (p < 0.001). Median LOS decreased from 14 to 9 days (p < 0.001). Comparing pre-ERAS to post-ERAS showed no significant difference in the major morbidity rate (13.6% vs. 9.5%) or 30-day readmission (9.4% vs. 4.8%) and no mortalities. Controlling for patient characteristics, the mean LOS decreased by 6.94 days (p < 0.001). CONCLUSION: Implementation of an ERAS CRS/HIPEC program is safe and allows for improved compliance to ERAS protocols and a significant reduction in LOS.

Investigation of 5-fluorouracil cardiotoxicity in combinational therapy: Influence of risk factors and demographics in a Pakistani population.

INTRODUCTION: 5-Fluorouracil (5-FU) is a chemotherapeutic agent used to treat various types of cancers. Although widely used, it has consistently been attributed to cardiotoxicities after administration. The purpose of this study was to assess the parameters and predictors of cardiotoxicities associated with various 5-FU-based chemotherapeutic protocols in patients with GI/colorectal cancer, as well as the correlation of these cardiotoxic events with age, sex, cumulative dose, and risk factors such as obesity, hypertension, and family history of cardiac diseases. METHODS: A prospective study consisting of 396 patients of both sexes was conducted in the oncology ward of Nishtar Hospital in Multan, Pakistan. Patients were grouped according to the therapeutic protocol they received (5-FU monotherapy or in combination, with different dosing regimens). Electrocardiography and serum troponin levels were used to assess 5-FU-induced cardiotoxicity. In cases where cardiotoxicity was detected, 5-FU treatment was interrupted; nitroglycerin, nitrates, and calcium channel blockers were administered; and cardiac monitoring was initiated. 5-FU was discontinued in all cases of acute myocardial infarction. RESULTS: Of the 396 patients, 28.5% reported different cardiotoxic symptoms after receiving various 5-FU-containing protocols. 35% had anginal pain, 13% suffered a myocardial infarction, 11% developed hypertension, and 10% presented heart failure. Patients receiving 5-FU combination therapy showed cardiotoxic events that were significantly different from those on 5-FU monotherapy. Based on the ECG results, only the QTc-d interval increased significantly (p < 0.001) after therapy. 68% of the patients had troponin levels > 2 ng/mL at the end of treatment. CONCLUSIONS: Pre-existing cardiac diseases, treatment duration, smoking, and obesity were found to be influential components in the development of cardiotoxicity, and patients with cancer should be closely monitored during 5-FU chemotherapy.

Hydrogel-based platforms for site-specific doxorubicin release in cancer therapy.

Hydrogels are promising candidates for the delivery of therapeutics in the treatment of human cancers. Regarding to the biocomaptiiblity, high drug and encapsulation efficacy and adjustable physico-chemical features, the hydrogels have been widely utilized for the delivery of chemotherapy drugs. Doxorubicin (DOX) is one of the most common chemotherapy drugs used in cancer therapy through impairing topoisomerase II function and increasing oxidative damage. However, the tumor cells have developed resistance into DOX-mediated cytotoxic impacts, requiring the delivery systems to increase internalization and anti-cancer activity of this drug. The hydrogels can deliver DOX in a sustained manner to maximize its anti-cancer activity, improving cancer elimination and reduction in side effects and drug resistance. The natural-based hydrogels such as chitosan, alginate and gelatin hydrogels have shown favourable biocompatibility and degradability in DOX delivery for tumor suppression. The hydrogels are able to co-deliver DOX with other drugs or genes to enhance drug sensitivity and mediate polychemotherapy, synergistically suppressing cancer progression. The incorporation of nanoparticles in the structure of hydrogels can improve the sustained release of DOX and enhancing intracellular internalization, accelerating DOX's cytotoxicity. Furthermore, the stimuli-responsive hydrogels including pH-, redox- and thermo-sensitive platforms are able to improve the specific release of DOX at the tumor site. The DOX-loaded hydrogels can be further employed in the clinic for the treatment of cancer patients and improving efficacy of chemotherapy.

Dr. Sidney Farber (1903-1973): Founder of Pediatric Pathology and the Father of Modern Chemotherapy.

Dr. Sidney Farber (Farber) was a distinguished pediatric pathologist and widely recognized pioneer of modern chemotherapy. In 1948, his influential study showed that various anti-folates, particularly 4-aminopteroylglutamic acid, also known as aminopterin, induced transient disease control in kids who had acute undifferentiated leukemia. The findings laid the basis for developing and using additional chemotherapies, individually or in combination, for treating pediatric and adult cancers. Farber also introduced actinomycin D to treat Wilms tumor in various stages. Underneath his oversight, the 'Jimmy Fund,' one of the earliest dedicated pediatric oncology centers, and the Children's Cancer Research Foundation, which subsequently evolved into the Dana-Farber Cancer Institute, was established. Farber is known as the "Founder of Pediatric Pathology" and the "Father of Modern Chemotherapy," citing his immense contributions. This article is a tribute to the great scientist Farber for his significant contributions to the scientific field and the countless individuals he has impacted.

Current research status of transarterial therapies for hepatocellular carcinoma.

With continuous advancements in interventional radiology, considerable progress has been made in transarterial therapies for hepatocellular carcinoma (HCC) in recent years, and an increasing number of research papers on transarterial therapies for HCC have been published. In this editorial, we comment on the article by Ma et al published in the recent issue of the World Journal of Gastro intestinal Oncology: "Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable HCC". We focus specifically on the current research status and future directions of transarterial therapies. In the future, more studies are needed to determine the optimal transarterial local treatment for HCC. With the emergence of checkpoint immunotherapy modalities, it is expected that the results of trials of transarterial local therapy combined with systemic therapy will bring new hope to HCC patients.

Efficacy and safety of chemoradiotherapy plus immune checkpoint inhibitors for the treatment of locally advanced cervical cancer: a systematic review and meta-analysis.

Background: Radiotherapy plus concurrent chemotherapy is a standard method for treating locally advanced cervical cancer (LACC). Immune checkpoint inhibitors (ICIs) are widely applied in the treatment of recurrent cervical cancer, metastatic cervical cancer or LACC. The efficacy and safety of radiotherapy plus immunotherapy for LACC require further investigation. The objective of this review and meta-analysis was to analyze the efficacy and safety of concurrent chemoradiotherapy (CCRT) combined with ICIs for treating LACC on the basis of the results of randomized controlled trials (RCTs). Methods: We comprehensively searched electronic databases to identify RCTs that focused on CCRT plus ICIs for LACC treatment. The outcomes included the objective response rate (ORR) and progression-free survival (PFS), overall survival (OS) and adverse events (AEs). A standard method for systematic review and meta-analysis was used. Review Manager 5.4 was used for data combination and analyses. Results: Three RCTs involving 1882 participants with LACC were identified and included in the systematic review and meta-analysis. CCRT plus ICIs improved the rates of PFS (hazard ratio [HR]: 0.76, 95% confidence interval [CI]: CI: 0.64, 0.91, P = 0.002) and OS (HR: 0.7695% CI (95% CI 0.58-0.99, P = 0.04) in patients with LACC. Compared with the control group, the CCRT plus immunotherapy group had an increased ORR (OR: 1.37, 95% CI: 1.02,1.85, P=0.04). The two methods had similar rates (HR=1.99, 95% CI: 0.99, 1.43; P=0.07) of treatment-related grade 3 or higher AEs. The CCRT plus immunotherapy group had a higher rate than did the control group (HR: 2.68, 95% CI: 1.38, 5.21; P=0.004) in terms of any grade immunotherapy-related AEs. Conclusions: CCRT plus ICIs is efficacious and safe for the management of LACC. The addition of ICIs to CCRT improved the rates of PFS and OS in patients with LACC. The adverse effects of immunotherapy-related AEs should be strictly examined and managed in a timely manner.

Metabolic mediators: microbial-derived metabolites as key regulators of anti-tumor immunity, immunotherapy, and chemotherapy.

The human microbiome has recently emerged as a focal point in cancer research, specifically in anti-tumor immunity, immunotherapy, and chemotherapy. This review explores microbial-derived metabolites, emphasizing their crucial roles in shaping fundamental aspects of cancer treatment. Metabolites such as short-chain fatty acids (SCFAs), Trimethylamine N-Oxide (TMAO), and Tryptophan Metabolites take the spotlight, underscoring their diverse origins and functions and their profound impact on the host immune system. The focus is on SCFAs' remarkable ability to modulate immune responses, reduce inflammation, and enhance anti-tumor immunity within the intricate tumor microenvironment (TME). The review critically evaluates TMAO, intricately tied to dietary choices and gut microbiota composition, assessing its implications for cancer susceptibility, progression, and immunosuppression. Additionally, the involvement of tryptophan and other amino acid metabolites in shaping immune responses is discussed, highlighting their influence on immune checkpoints, immunosuppression, and immunotherapy effectiveness. The examination extends to their dynamic interaction with chemotherapy, emphasizing the potential of microbial-derived metabolites to alter treatment protocols and optimize outcomes for cancer patients. A comprehensive understanding of their role in cancer therapy is attained by exploring their impacts on drug metabolism, therapeutic responses, and resistance development. In conclusion, this review underscores the pivotal contributions of microbial-derived metabolites in regulating anti-tumor immunity, immunotherapy responses, and chemotherapy outcomes. By illuminating the intricate interactions between these metabolites and cancer therapy, the article enhances our understanding of cancer biology, paving the way for the development of more effective treatment options in the ongoing battle against cancer.

Liver transplantation following two conversions in a patient with huge hepatocellular carcinoma and portal vein invasion: A case report.

BACKGROUND: Surgical resection and liver transplantation (LT) are the most effective curative options for hepatocellular carcinoma (HCC). However, few patients with huge HCC (> 10 cm in diameter), especially those with portal vein tumor thrombus (PVTT), can receive these treatments. Selective internal radiation therapy (SIRT) can be used as a conversion therapy for them because it has the dual benefit of shrinking tumors and increasing residual hepatic volume. However, in patients with huge HCC, high lung absorbed dose often prevents them from receiving SIRT. CASE SUMMARY: A 35-year-old man was admitted because of emaciation and pain in the hepatic region for about 1 month. The computed tomography scan showed a 20.2 cm × 19.8 cm tumor located in the right lobe-left medial lobes with right portal vein and right hepatic vein invasion. After the pathological type of HCC was confirmed by biopsy, two conversions were presented. The first one was drug-eluting bead transarterial chemoembolization plus hepatic arterial infusion chemotherapy and lenvatinib and sintilimab, converted to SIRT, and the second one was sequential SIRT with continued systemic treatment. The tumor size significantly decreased from 20.2 cm × 19.8 cm to 16.2 cm × 13.8 cm, then sequentially to 7.8 cm × 6.8 cm. In the meantime, the ratio of spared volume to total liver volume increased gradually from 34.4% to 55.7%, then to 62.9%. Furthermore, there was visualization of the portal vein, indicating regression of the tumor thrombus. Finally, owing to the new tumor in the left lateral lobe, the patient underwent LT instead of resection without major complications. CONCLUSION: Patients with inoperable huge HCC with PVTT could be converted to SIRT first and accept surgery sequentially.