Spatially Resolved Niche and Tumor Microenvironmental Alterations in Gastric Cancer Peritoneal Metastases.

BACKGROUND AND AIMS: Peritoneal metastasis (PM) in gastric cancer (GC) is associated with poor prognosis and significant morbidity. We sought to understand the genomic, transcriptomic, and tumor microenvironment (TME) features that contribute to peritoneal organotropism in GC. METHODS: We conducted a comprehensive multi-omic analysis of 548 samples from 326 patients, including primary tumors, matched normal tissues; peritoneal metastases, and adjacent-normal peritoneal tissues. We used whole exome sequencing, whole transcriptome sequencing, and digital spatial profiling to investigate molecular alterations, gene expression patterns, and TME characteristics associated with PM. RESULTS: Our analysis identified specific genomic alterations in primary tumors, including mutations in ELF3, CDH1, and PIGR, and TME signatures, such as stromal infiltration and M2 macrophage enrichment, associated with increased risk of PM. We observed distinct transcriptional programs and immune compositions in GCPM compared with liver metastases, highlighting the importance of the TME in transcoelomic metastasis. We found differential expression of therapeutic targets between primary tumors and PM, with lower CLDN18.2 and FGFR2b expression in PM. We unravel the roles of the TME in niche reprogramming within the peritoneum, and provide evidence of pre-metastatic niche conditioning even in early GC without clinical PM. These findings were further validated using a humanized mouse model, which demonstrated niche remodeling in the peritoneum during transcoelomic metastasis. CONCLUSION: Our study provides a comprehensive molecular characterization of GCPM and unveils key biological principles underlying transcoelomic metastasis. The identified predictive markers, therapeutic targets, and TME alterations offer potential avenues for targeted interventions and improved patient outcomes.

Effect of the learning curve of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on the treatment of colorectal peritoneal metastasis.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) are increasingly utilised in the management of colorectal peritoneal metastases (CPM). This combined modality is associated with a significant learning curve (LC) and is often criticised for its associated morbidity. This study aims to inspect the LC of this procedure in our institute. METHODS: A retrospective review of the institution's prospectively maintained database of CRS-HIPEC cases was performed. Patients treated for CPM were stratified into two groups: Group 1 consists of patients in our initial 100 cases of CRS-HIPEC and Group 2 comprises patients treated subsequently. Perioperative prognostic factors and oncological outcomes were analysed. RESULTS: Between 2001 and 2016, 77 patients with CPM underwent CRS-HIPEC, of which 31 patients (40.3%) were in Group 1 and 46 patients (59.7%) in Group 2. Median follow-up duration was 96 months in Group 1 and 25 months in Group 2. There were no differences in OS (35 months vs 46 months, p = 0.054) and DFS (13 months vs 14 months, p = 0.676) between the groups. There were more patients with higher PCI (≥12) (57.1% vs 22.2%, p = 0.006) and high-grade complications (25.8% vs 8.7%, p = 0.045) in Group 1. Group 2 patients had a shorter hospitalisation (14 days vs 11 days, p = 0.015) and SICU stay (1 day vs 0 days, p < 0.001). CONCLUSION: An improvement in the perioperative outcomes after CRS-HIPEC for CPM may be partly attributed to overcoming the LC and incorporation of better patient selection methods.

Utility of positron emission tomography/computed tomography (PET/CT) imaging in the evaluation of sarcomas: A systematic review.

BACKGROUND: Sarcomas are a heterogeneous group of malignant tumours with variable clinical outcomes. Their presence in multiple body locations represents significant diagnostic and therapeutic challenges. Positron emission tomography/computed tomography (PET/CT) is an imaging tool that provides semiquantitative measurements of radiotracer concentration in tissue, such as SUVmax (standardised uptake value) and is increasingly used in clinical practice. This systematic review aims to evaluate the utility of PET/CT in sarcoma grading and prognostication, evaluation of treatment response, staging and restaging. METHODS: Relevant studies published from January 2003 to August 2017 evaluating the utility of PET/CT in sarcoma grading and prognostication, staging, evaluation of treatment response and restaging were systematically searched for in scientific databases (e.g. PubMed, Medline and Embase) using key terms, including "soft tissue sarcoma," "osteosarcoma," "utility" and "PET/CT". Additionally, references of identified studies were reviewed. Study quality was assessed by "Quality Assessment of Diagnostic Accuracy Studies". RESULTS: A total of 12 prospective studies (level II to III evidence) were included in the review for tumour grading and prognostication. There was a strong correlation between SUV and tumour grade where majority of intermediate/ high-grade STS have a significantly higher SUVmax. PET/CT has also shown potential in prognostication where decrease in SUVmax correlated with recurrence-free survival in both osteosarcoma and STS. Furthermore, 8 prospective trials of level II to IV evidence according to Oxford Centre of Evidence-based Medicine (CEBM) demonstrated the use of PET/CT in early identification of patients who will respond to treatment where ≥60% decrease in FDG uptake resulted in sensitivity and specificity of 100% and 71% respectively for assessment of histopathologic response. 11 retrospective trials (level III to IV evidence) reported on the use of PET/CT in staging and restaging with heterogeneous results. CONCLUSION: Overall, higher quality evidence demonstrated PET/CT to be an important contributor towards sarcoma grading, prognostication and evaluation of treatment response. Larger prospective trials will be helpful to further establish the clinical value of PET/CT in sarcoma staging and restaging.