Unsuspected Isolated Peritoneal Metastasis of Prostate Cancer Detected with Digital F-18 PSMA PET/CT Scan.

We report the case of a prostate cancer (PC) patient referred to our center to perform F-18 prostate-specific membrane antigen (PSMA) digital positron emission tomography / computed tomography (PET/CT) scan for biochemical recurrence. PET/CT was unremarkable except for a tiny PSMA-expressing nodule on the right paracolic gutter, which increased in size and PSMA-expression on repeat imaging. Excision of the lesion was consistent with PC peritoneal metastasis. The isolated location of the lesion was atypical for PC metastasis. In the era of highly sensitive digital PET/CT detectors, it is always important to investigate abnormal uptake of F-18 PSMA regardless of the location.

Targeting non-coding RNAs as a promising biomarker in peritoneal metastasis: Background, mechanism, and therapeutic approach.

Peritoneal metastasis (PM) pathophysiology is complex and not fully understood. PM, originating from gastrointestinal (GI) cancer, is a condition that significantly worsens patient prognosis due to its complex nature and limited treatment options. The non-coding RNAs (ncRNAs) have been shown to play pivotal roles in cancer biology, influencing tumorigenesis, progression, metastasis, and therapeutic resistance. Increasing evidence has demonstrated the regulatory functions of different classes of ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in PM. Identifying biomarkers for early detection of PM is a crucial step towards improving patient outcomes, and how ncRNA profiles correlate with survival rates, response to therapy, and recurrence risks have raised much attention in recent years. Additionally, exploring innovative therapeutic approaches utilizing ncRNAs, such as targeted therapy and gene silencing, may offer new horizons in treating this dire condition. Recent advances in systemic treatments and the development of novel loco-regional therapies have opened doors to multimodal treatment approaches. Radical surgeries combined with hyperthermic intraperitoneal chemotherapy (HIPEC) have shown promising results, leading to extended patient survival. Current research is focused on the molecular characterization of PM, which is crucial for early detection and developing future therapeutic strategies. By summarizing the latest findings, this study underscores the transformative potential of ncRNAs in enhancing the diagnosis, prognosis, and treatment of PM in GI cancer, paving the way for more personalized and effective clinical strategies.

Research progress of epithelial-mesenchymal transformation-related transcription factors in peritoneal metastases.

Metastasis is the leading cause of mortality in patients with malignant tumors, particularly characterized by peritoneal metastases originating from gastric, ovarian, and colorectal cancers. Regarded as the terminal phase of tumor progression, peritoneal metastasis presents limited therapeutic avenues and is associated with a dismal prognosis for patients. The epithelial-mesenchymal transition (EMT) is a crucial phenomenon in which epithelial cells undergo significant changes in both morphology and functionality, transitioning to a mesenchymal-like phenotype. This transition plays a pivotal role in facilitating tumor metastasis, with transcription factors being key mediators of EMT's effects. Consequently, we provide a retrospective summary of the efforts to identify specific targets among EMT-related transcription factors, aimed at modulating the onset and progression of peritoneal metastatic cancer. This summary offers vital theoretical underpinnings for developing treatment strategies against peritoneal metastasis.

Evaluation of 68Ga-FAPI PET/CT and 18F-FDG PET/CT for the diagnosis of recurrent colorectal cancers.

Objective: The present study aimed to compare the diagnostic value of gallium-68-labeled fibroblast activation protein inhibitor positron emission tomography/computed tomography (68Ga-FAPI PET/CT) and fluorine-18-labeled fluorodeoxyglucose PET/CT (18F-FDG PET/CT) for detecting recurrent colorectal cancers (CRCs). Materials and Methods: Fifty-six patients (age: 18-80 years, 31 men and 25 women) with suspected recurrent CRC were enrolled and underwent 18F-FDG PET/CT and 68Ga-FAPI PET/CT sequentially within 1 week. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), and diagnostic accuracy were estimated and compared between the two modalities by using Student's t-test. The Wilcoxon signed-rank test was used to compare peritoneal carcinoma index (PCI) scores between the two imaging modalities. Results: 68Ga-FAPI PET/CT showed higher sensitivity for detecting recurrence (93 % vs. 79 %); lymph node metastasis (89 % vs. 78 %), particularly peritoneal lymph node metastasis (92 % vs. 63 %); and metastatic implantation on the intestinal wall (100 % vs. 25 %) compared to 18F-FDG PET/CT. However, 68Ga-FAPI PET/CT showed lower sensitivity for detecting bone metastasis (67 % vs. 100 %). The mean SUVmax values of peritoneal metastases and metastatic implantation on the intestinal wall were 4.28 ± 2.70 and 7.58 ± 1.66 for 18F-FDG PET/CT and 5.66 ± 1.97 and 6.70 ± 0.25 for 68Ga-FAPI PET/CT, respectively. Furthermore, 68Ga-FAPI PET/CT showed significantly higher TBR for peritoneal metastatic lesions (4.22 ± 1.47 vs. 1.41 ± 0.89, p < 0.0001) and metastatic implantation on the intestinal wall (5.63 ± 1.24 vs. 2.20 ± 0.5, p = 0.02) compared to 18F-FDG PET/CT. For the same patient, 68Ga-FAPI PET/CT yielded a more accurate PCI score and a greater area under the curve value for the receiver operating characteristic curve (p < 0.01) than 18F-FDG PET/CT. Conclusion: 68Ga-FAPI PET/CT was superior to 18F-FDG PET/CT for detecting recurrence and peritoneal metastases. Hence, we propose the combination of these two modalities for better clinical diagnosis and management of patients with CRC.

Robotic and Laparoscopic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy, Multicenter Study From Saudi Arabia.

BACKGROUND: Peritoneal metastasis (PM) is a common evolution of abdominal tumors. Without aggressive multimodal treatment, it is associated with a poor prognosis. The aim of this study is to present a multicenter results from Saudi Arabia on minimally invasive CRS and HIIPEC. METHODS: A retrospective analysis of a prospective maintained multicenter database was queried for all patients treated with laparoscopic or robotic CRS and HIPEC between 2019 and 2024 in Saudi Arabia. Surgical and oncological outcome was analyzed. RESULTS: Eleven consecutive patients underwent minimally invasive CRS and HIPEC between 2019 and 2024. Eight patients (72.7%) were operated by laparoscopy, one of them by single port access and three patients (27.3%) were operated robotically. Six patients (54.5%) were female. Median age was 42 (29-64). Primary tumor was PMP from the appendix, colon, and MCM in 6 (54.5%), 4 (36.4%), and 1 (9.1%) respectively. The median duration to complete the surgical procedure for all patients was 330 (230-580) min and for robotic CRS the median docking time was 570 (330-580) min. Median PCI was 2 (1-7) and completeness Cytoreduction (CC score 0) was achieved in the all patients (100%). Median hospital stay was 8 days (3-20). Four patients had one night postoperative ICU stay. Major morbidity (CTCAE) 3 and 4 occurred in three patients (27.3%) (Port site hernia, bleeding, and wound infection). No readmission to the hospital and no 90 days mortalities. CONCLUSION: The minimally invasive approach by laparoscopy or robot is a feasible and promising option for CRS and HIPEC. It reduces the hospital stay, early return to intended oncological treatment (RIOT). Further prospective clinical studies are needed to evaluate this approach.

Survival Outcomes of Cytoreductive Surgery with HIPEC in Gastric Adenocarcinoma: A National Cancer Database Study.

BACKGROUND: This study aimed to assess the impact of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) on the survival outcomes for patients with gastric cancer and peritoneal carcinomatosis (PC). METHODS: A retrospective analysis of the National Cancer Database from 2004 to 2020 identified patients with topography and histology codes consistent with gastric adenocarcinoma who underwent CRS/HIPEC. The exclusion criteria ruled out known other distant metastasis and missing key data. The study compared the CRS/HIPEC group with patients who had stage IV disease (with the same exclusions for distant metastases) and received systemic chemotherapy but no surgery to the primary site. RESULTS: The study included 148 patients who underwent CRS/HIPEC. Their median age was 57 years (interquartile range [IQR], 47-66 years), with 57.4% of the patients identifying as male and 73.6% identifying as white. Most of the CRS/HIPEC patients had locally advanced disease, with 33.8% having pT4 disease and 23% patients having pN3 status. The Charlson-Deyo scores were 0 for 77% and 1 for 16.9% of the patients. The overall survival (OS) among the stage IV patients managed with CRS/HIPEC was significantly longer than for the patients receiving only systemic chemotherapy (median survival, 18.1 vs 9.3 months; p < 0.001), and the 1-year OS was 72.6% versus 38.8% (p < 0.05)). Among the stage IV patients, CRS/HIPEC showed better survival than systemic chemotherapy (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.44-0.73; p < .001) when control was used for the Charlson Deyo score, histology, age, and sex. CONCLUSIONS: These results suggest the association of CRS/HIPEC with improved survival for selected patients with gastric adenocarcinoma and peritoneal disease. Some of this difference may have been due to selection bias, but the differences in the survival curves are robust.

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for Gastric Cancer Peritoneal Metastases: Results from the Lithuanian PIPAC Program.

BACKGROUND: Peritoneal metastases (PM) of gastric cancer (GC) are considered a terminal condition, with reported median survival ranging from 2 to 9 months. Standard treatment typically involves systemic chemotherapy alone or combined with targeted therapy or immunotherapy, though efficacy is limited. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a novel technique for treating GC PM, although it remains an experimental treatment under investigation. This study aimed to summarize the outcomes of GC PM treatment with PIPAC from the Lithuanian PIPAC program. METHODS: All patients who underwent PIPAC for GC PM at Vilnius University Hospital Santaros Klinikos between 2015 and 2022 were included in this retrospective study. The safety of PIPAC was assessed by postoperative complications according to the Clavien-Dindo classification. Efficacy was evaluated based on the peritoneal carcinomatosis index (PCI), ascites dynamics throughout the treatment, and long-term outcomes. RESULTS: In total, 32 patients underwent 71 PIPAC procedures. Intraoperative and postoperative morbidity related to PIPAC occurred after three (4.2%) procedures. Following PIPAC, there was a tendency towards a decrease in median PCI from 10 (Q1 3; Q3 13) to 7 (Q1 2; Q3 12), p = 0.75, and a decrease in median ascites volume from 1300 mL (Q1 500; Q3 3600) at the first PIPAC to 700 mL (Q1 250; Q3 4750) at the last PIPAC, p = 0.56; however, these differences were not statistically significant. The median overall survival after PM diagnosis was 12.5 months (95% CI 10-17), and the median survival after the first PIPAC procedure was 5 months (95% CI 4-10). CONCLUSIONS: PIPAC is a safe and feasible treatment option for GC PM; however, well-designed prospective studies are needed to fully assess its efficacy.

Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Peritoneal Sarcomatosis.

(1) Background: Cytoreductive surgery (CRS) with HIPEC is considered the standard of care for selected patients with peritoneal carcinomatosis, but evidence-based treatment recommendations for the therapy of peritoneal sarcomatosis are scarce. (2) Methods: We retrospectively analyzed all adult patients treated with CRS and HIPEC for peritoneal sarcomatosis between 2017 and 2024. (3) Results: Ten patients with a median age of 46.1 years (range: 23-77 years) with metachronous (40%) or synchronous (60%) peritoneal sarcomatosis from six different tumor entities were treated according to tumor board recommendation using CRS and HIPEC with cisplatin and doxorubicin over 60 min at 42.0 °C. The length of stay in the intensive care unit and hospital was 1.24 (0.6-1.9 days) and 11.1 days (6-17 days), respectively. Complete cytoreduction was achieved in 90% of the patients, with a median PSI of 11.5. Postoperative complications occurred in five cases, but no surgical revisions were necessary, and no acute kidney damage was recorded. (4) Conclusions: CRS with HIPEC in the presence of peritoneal sarcomatosis could be safely performed in our collective. Whether this resulted in an oncological treatment benefit cannot be concluded in view of the heterogeneous and small collective. Therefore, larger and prospective studies are warranted.

Minimally Invasive Surgery: Is It a Risk Factor for Postoperative Peritoneal Metastasis in pT4 Colon Cancer?

BACKGROUND: Performing laparoscopic surgery for T4 colon cancer remains controversial because of concerns about whether its oncologic outcomes are comparable to those of open surgery, and postoperative peritoneal metastasis (PM) has been reported to occur more frequently in laparoscopic colectomy for T4 colon cancer. We investigated whether minimally invasive surgery (MIS) demonstrated a higher PM rate than open surgery and analyzed the risk factors for PM in pT4 colon cancer. METHODS: This study included 392 patients with pT4 colon cancer who underwent curative surgery at a referral hospital between January 2000 and December 2018. Patients with previous neoadjuvant therapy, synchronous malignancy, metastasis, or those who underwent hyperthermic intraperitoneal chemotherapy were excluded. RESULTS: The MIS group had fewer high-risk clinical features, such as tumors too large for endoscope admission or complications like perforation and fistula. The group also exhibited shorter operative time, intraoperative blood loss, multivisceral resection, hospital stay, fewer postoperative complications, smaller tumor size, lower pT4b ratio, and higher pN+ rates. Multivariate analysis revealed that high-risk clinical features, MIS, pT4b, pN+, tumor size < 5 cm, high histological grade, lymphovascular invasion, and postoperative complications were significant risk factors for PM. During the median 59-month follow-up, the 5-year cumulative incidence of PM was elevated in the MIS group (17.5% vs. 8.2%; P = 0.057). No significant differences were observed in the 5-year overall and disease-free survival rates. CONCLUSIONS: Minimally invasive surgery increases the risk of postoperative PM in patients with pT4 colon cancer. Surgeons may require thorough tumor staging and radical resection to prevent PM.

PIPAC Pharmacologic and Clinical Data.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) emerged as an innovative intraperitoneal chemotherapy delivery system to overcome the issue of limited efficacy of systemic therapies to induce response in peritoneal malignancies. Promising results for patients with mesothelioma peritonei and peritoneal metastasis from gastric, ovarian, colorectal, pancreatic, and hepatobiliary tumors origin are changing the landscape for patients otherwise just facing palliative treatment. Ongoing trials will shed more light on the actual benefits of PIPAC.

Efficacy and safety of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with pancreatic cancer peritoneal metastasis.

OBJECTIVES: Pancreatic cancer with peritoneal metastasis presents a challenging prognosis, with limited effective treatment options available. This study aims to evaluate the efficacy and safety of combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment strategy for this patient group. METHODS: A retrospective analysis was conducted on patients with peritoneal metastasis of pancreatic cancer who underwent CRS + HIPEC treatment at Beijing Shijitan Hospital from March 2017 to December 2023. The study focused on assessing clinical features, the incidence of sever adverse events (SAEs), and overall survival (OS). RESULTS: A total of 10 patients were enrolled in this study. The median OS was 24.2 months, suggesting an improvement over traditional therapies. While SAEs were noted, including two cases of severe complications necessitating additional surgical interventions, no perioperative fatalities were recorded. The overall survival time for patients with CC0/1 was not significantly different from that of patients with CC2/3, and no prognostic predictors were identified. CONCLUSIONS: The combination of CRS and HIPEC appears to be a viable and promising treatment modality for patients with peritoneal metastasis of pancreatic cancer, offering an improved survival rate with manageable safety concerns. Further research is needed to refine patient selection criteria and to explore the long-term benefits of this approach.

[Corrigendum] DJ­1 is involved in the peritoneal metastasis of gastric cancer through activation of the Akt signaling pathway.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that the western blot data shown for the MMP­9 experiment in Fig. 4 on p. 1493 were strikingly similar to the western blots shown for the total­Akt experiments in Fig. 6 on p. 1494. After having re­examined their original data files, the authors realized that Fig. 6 had been inadvertently assembled incorrectly. The revised version of Fig. 6, containing the correct data for the total­Akt experiments, is shown below. Note that the corrections made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 31: 1489­1497, 2014; DOI: 10.3892/or.2013.2961].

Implication of Capillary Morphogenesis Gene 2 (CMG2) in the Disease Progression and Peritoneal Metastasis of Pancreatic Cancer.

Capillary morphogenesis gene 2 (CMG2) mediates cell-matrix interactions to facilitate cell adhesion and migration. CMG2 has been implicated in the disease progression of breast cancer, prostate cancer and gastric cancer. The present study aims to determine the role of CMG2 in the disease progression and peritoneal metastasis of pancreatic cancer. Pancreatic tumour samples were collected from Peking University Cancer Hospital. CMG2 expression was determined using quantitative PCR. After the creation of knockdown and overexpression of CMG2 in pancreatic cancer cells, the effect of CMG2 on several cell functions and adhesion to the peritoneum was examined. Potential pathways regulated by CMG2 were found via proteomics analysis and drug tests. CMG2 was upregulated in pancreatic cancer tissues and associated with a poor prognosis. CMG2 was increased in metastatic lesions and those primary tumours with distant metastases. CMG2 promotes cell-cell, cell-matrix and cell-hyaluronic acid adhesion, which may be mediated by epidermal growth factor receptor (EGFR) and focal adhesion kinase (FAK) pathway activation.

Gut Roseburia is a protective marker for peritoneal metastasis of gastric cancer.

BACKGROUND: Gastric cancer (GC), particularly for advanced stage of GC, commonly undergoes peritoneal metastasis (PM), which is the leading cause of GC-related death. However, there currently has no reliable biomarker to predict the onset of GCPM. It is well known that the imbalance of gut microbiota contributes to the development and metastasis of gastrointestinal tumors. Unfortunately, little is known about how the alternation in gut microbiota is associated with the onset of GCPM. METHODS: Our current study analyzed structural characteristics and functional prediction of gut microbiota in GC patients with PM (PM group) and without PM (non-PM group). Fresh fecal samples were collected from a discovery cohort (PM = 38, non-PM = 54) and a validation cohort (PM = 15, non-PM = 21) of GC patients and their 16S ribosomal RNA (16s rRNA) gene amplicons were sequenced, followed by bioinformatics. RESULTS: The results indicated an increase in the biodiversity of gut microbiota in the non-PM group of the discovery cohort, compared with the PM group. Moreover, LEfSe analysis found 31 significantly different microorganisms, of which the Roseburia ranked the fifth in the random forest (RF) model. The characteristics of intestinal microbiota in GCPM patients were changed, and the abundance of Roseburia in gut microbiota from the GCPM patients was reduced and receiver operating characteristic (ROC) analysis revealed that the reduced abundance of gut Roseburia effectively predicted the onset of GCPM. CONCLUSION: This signature was also observed in the validation cohort. Therefore, Roseburia is a protective microbial marker and the reduced abundance of Roseburia in gut microbiota may help early diagnosis of GCPM.

Is Hyperthermic Intraperitoneal Chemotherapy Appropriate for Colon Cancer?

Colorectal cancer (CRC) with peritoneal metastases is a complex disease and its management presents significant clinical challenges. In well-selected patients at experienced centers, CRS/hyperthermic intraperitoneal chemotherapy (HIPEC) can be performed with acceptable morbidity and is associated with prolonged survival. Based on the results of recent randomized controlled trials, HIPEC using oxaliplatin after CRS with shortened perfusion periods (30 minutes) is no longer recommended. There is a movement toward utilizing mitomycin C as a first-line intraperitoneal agent with extended perfusion times (90-120 minutes); however, there is currently little prospective evidence to support its widespread use.

Identification and validation of Rab GTPases RAB13 as biomarkers for peritoneal metastasis and immune cell infiltration in colorectal cancer patients.

Background: As one of the most common cancer, colorectal cancer (CRC) is with high morbidity and mortality. Peritoneal metastasis (PM) is a fatal state of CRC, and few patients may benefit from traditional therapies. There is a complex interaction between PM and immune cell infiltration. Therefore, we aimed to determine biomarkers associated with colorectal cancer peritoneal metastasis (CRCPM) and their relationship with immune cell infiltration. Methods: By informatic analysis, differently expressed genes (DEGs) were selected and hub genes were screened out. RAB13, one of the hub genes, was identificated from public databases and validated in CRC tissues. The ESTIMATE, CEBERSORT and TIMER algorithms were applied to analyze the correlation between RAB13 and immune infiltration in CRC. RAB13's expression in different cells were analyzed at the single-cell level in scRNA-Seq. The Gene Set Enrichment Analysis (GSEA) was performed for RAB13 enrichment and further confirmed. Using oncoPredict algorithm, RAB13's impact on drug sensitivity was evaluated. Results: High RAB13 expression was identified in public databases and led to a poor prognosis. RAB13 was found to be positively correlated with the macrophages and other immune cells infiltration and from scRNA-Seq, RAB13 was found to be located in CRC cells and macrophages. GSEA revealed that high RAB13 expression enriched in a various of biological signaling, and oncoPredict algorithm showed that RAB13 expression was correlated with paclitaxel sensitivity. Conclusion: Our study indicated clinical role of RAB13 in CRC-PM, suggesting its potential as a therapeutic target in the future.

Targeting SNCA in the treatment of malignant ascites in gastrointestinal cancer.

Peritoneal tumor dissemination and subsequent malignant tumor ascites (MTA) occur unexpectedly and repeatedly in patients with gastrointestinal (GI) cancers, and worsen quality of life and prognosis of the patients. Various treatments have been clinically developed for these patients, while most of the MTA cases are refractory to the treatments. Thus, effective treatments are urgently needed to improve the clinical outcomes. In this study, we identified α-synuclein (SNCA) as an immunological determinant of MTA progression in GI cancer through translational research using mouse tumor models and clinical specimens collected from gastric cancer patients. We found that the SNCA+ subsets were significantly increased in CD3+ T cells, CD56+ NK cells, and CD11b+ myeloid cells within MTA and peripheral blood cells (PBCs) of MTA cases, albeit almost absent in PBCs of healthy donors, and spleen of naive mice. Of note, the SNCA+ T-cell subset was rarely seen in patients that intraperitoneal lavage fluid without tumor cells was collected before surgery as a tumor-free control, suggesting a possible cancer-induced product, especially within the peritoneal cavity. In vivo treatment with anti-SNCA blocking mAb significantly induced anti-tumor effects in mouse MTA models, and synergistically improved anti-PD1 therapeutic efficacy, providing a significantly better prognosis. These suggest that SNCA is involved in severe immunosuppression in the MTA cases, and that blocking SNCA is effective in dramatically improving the immune status in the hosts. Targeting SNCA will be a promising strategy to improve clinical outcomes in the treatment of GI cancer patients, especially with MTA.

Preclinical toxicological assessment of amido-bridged nucleic acid-modified antisense oligonucleotides targeting synaptotagmin XIII for intra-abdominal treatment of peritoneal metastasis of gastric cancer.

BACKGROUND: Peritoneal metastasis of gastric cancer is closely associated with dismal prognosis. In previous preclinical proof-of-concept studies, an amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotide (ASO), designated ASO-4733 that targets the gene encoding synaptotagmin XIII (SYT13), inhibited cellular functions required for the formation of peritoneal metastasis of gastric cancer cells. ASO-4733 achieved therapeutic effects when intra-abdominally administered to mouse xenograft models. Here, we conducted an analysis of Syt13-deficient mice to determine the pharmacokinetics and toxicity of intra-abdominal administration of ASO-4733. METHODS: The effects of Syt13-deficiency in mice were determined. Good Laboratory Practice toxicity tests and the toxicokinetics of intra-abdominal administration of ASO-4733 were conducted in cynomolgus monkeys and rats. The pharmacokinetics of ASO-4733 administered intravenously or intra-abdominally to rats were investigated. RESULTS: Syt13-deficient mice exhibited normal reproduction, organ functions, and motor functions. Weekly intra-abdominal administration of ASO-4733 (125 mg/kg), corresponding to a 50-fold increase of the estimated clinical dose for 4 weeks, was well tolerated by cynomolgus monkeys. In rats, off-target toxicity (not attributable to hybridization) was observed after weekly intra-abdominal administration of ASO-4733. Blood concentrations of ASO-4733 were lower and rose more slowly after intra-abdominal administration compared with intravenous administration. CONCLUSIONS: The preclinical profile of intra-abdominal administration of ASO-4733 demonstrated its suitability for entry into clinical trials of patients with peritoneal metastasis of gastric cancer.

The role of diagnostic laparoscopy in locally advanced cervical cancer staging.

OBJECTIVE: Peritoneal involvement may be overlooked in patients with locally advanced cervical cancer (LACC). This may lead to underestimation of prognosis and to undertreatment limited to locoregional disease locations. However, staging laparoscopy in LACC is not routinely performed. The primary aim of this study was to determine the proportion of peritoneal metastasis by laparoscopy and the factors associated with peritoneal metastasis in patients with LACC. Secondary aims were to evaluate the performance of staging imaging in detecting peritoneal disease and the prognosis of patients with peritoneal metastasis. METHODS: Retrospective single-institution study including consecutive patients with newly diagnosed LACC (FIGO 2018 stage IB3 and IIA2-IVA) between 06/2015 and 06/2020. All women underwent PET/CT scan, MRI scan and diagnostic laparoscopy at the time of examination under anesthesia (EUA), as part of cervical cancer staging. Peritoneal metastasis was histologically confirmed in all cases. RESULTS: 251 patients were included. 33 (13.2 %) had peritoneal metastasis. The treatment plan was changed for 28/33 (84.8 %) patients with peritoneal metastasis (11.1 % of the entire LACC cohort). Multivariate analysis demonstrated that grade 3 (OR:1.572, 95%CI:1.021-2.419; p = 0.040) and AJCC stage T3-4 (OR:3.435, 95%CI:1.482-7.960; p = 0.004) were variables associated with increased risk of peritoneal metastasis. Sensitivity of PET/CT-scan and MRI-scan in detecting peritoneal metastasis was 4.5 % (95%CI:0.1-22.8) and 13.8 % (95%CI:3.9-31.7), respectively. Peritoneal metastasis was independently associated with worse PFS and OS (HR:3.008, 95%CI:1.779-5.087, p < 0.001 and HR:4.078, 95%CI:2.232-7.451; p < 0.001, respectively). CONCLUSION: LACC patients with grade 3 histology and/or AJCC stage T3-4 had high-risk of peritoneal metastasis and diagnostic laparoscopy might be considered as part of cervical cancer staging in these patients. Peritoneal metastasis was an independent factor associated with worse PFS and OS.

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.