Objectives The prognosis of patients with peritoneal metastases (PM) is poor, and these patients have a brief overall survival. Most patients with advanced PM receive palliative therapy to maintain their quality of life. In our current study, we investigated whether patient-specific 3D-tissue slices from patients with PM subjected to pressurized intraperitoneal aerosol chemotherapy could be cultured in vitro . Methods Biopsies from gastric cancer patients with PM were characterized for cytokeratin-positive tumor cells and the proliferation marker Ki-67. Biopsies from seven patients were cut to 350 µM thick slices in a standardized manner, cultured with 10 µM 5-fluorouracil, doxorubicin, cisplatin, oxaliplatin, or irinotecan for 96 h, and then examined histopathologically and via immunohistochemistry for persistent cytokeratin and Ki-67 expression. Results In vitro cultured slices revealed a similar morphology to un-cultured specimens, and Ki-67-positive tumor cell areas were present after 96 h. The total amount of tumor cells per slice was determined by pan-cytokeratin staining. In the doxorubicin-treated slices, the cytokeratin-positive tumor cell fraction and proliferative (Ki-67pos) cells were decreased. Patient-specific 3D-tissue-slice cultures from peritoneal biopsies were cultured in vitro for up to 4 days. Conclusions Potentially, these cultures are a reliable model to evaluate the chemosensitivity of patients with PM. Further investigation is needed to match the chemosensitivity with the clinical course of these patients.
Objectives Despite the introduction of multimodal treatment regimens, the prognosis of gastric cancer peritoneal metastasis (GCPM) remains poor. To establish efficient therapies, a deeper understanding of pathophysiological mechanisms in the development of GCPM is necessary and this requires adequate functional models. Therefore, we established a three-dimensional model to study tumor adhesion, invasion and growth. Methods A co-culture of peritoneal mesothelial cells with fibroblasts and collagen I was cultivated to further seed human gastric cancer cell lines on the surface. Different imaging techniques (optical microscopy, immunohistochemistry, scanning (SEM) and transmission (TEM) electron microscopy) served as tools to proof the sustainability of the model. Results We demonstrated the feasibility of creating a robust GCPM model. We showed that the model is reproducible under various conditions (6-, 12-, and 24-wells) and pre-analytical processing is possible. The imaging was feasible and allowed the comparison of morphological changes on the GCPM model to normal human peritoneum. Conclusions We established a reproducible and robust organotypic model of GCPM which can be used to generate deeper knowledge on the pathophysiology of GCPM and might serve as a platform for testing different chemotherapy schemes in order to establish a personalized treatment for patients with GCPM.
Objectives The main prognostic factor for peritoneal metastasis (PM) is the complete resection of the disease during cytoreductive surgery. Accurate patient selection is therefore essential for determining eligibility for this type of surgery. The peritoneal carcinomatosis index (PCI) is a widely used tool for assessing the extent of carcinomatosis. This study aimed to evaluate the inter-observer reproducibility of PCI assessments via laparoscopy and identify factors influencing this reproducibility. Methods Between November 2020 and November 2022, 25 laparoscopic PCI assessment videos were reviewed by six surgeons from two centers. The total PCI score, regional PCI scores, and the number of visualized PCI areas were recorded. Inter-observer concordance was analyzed. Results The median PCI score was 12 out of 39 (range 0–39), and the median number of visualized PCI regions was 10 out of 13 (range 1–13). The intraclass correlation coefficient (ICC) for the total PCI score was 0.846 (95 % CI 0.738, 0.927). A history of abdominal surgery significantly impacted PCI assessment reproducibility (p=0.029). Conclusions This study found a high inter-observer concordance in laparoscopic PCI assessments. Previous abdominal surgery negatively affected reproducibility, highlighting a challenge in evaluating the PCI in these patients.
Objectives Pressurised intraperitoneal aerosol chemotherapy (PIPAC) is a novel surgical technique for patients with peritoneal metastases not amenable to curative treatment. PIPAC delivers pressurised aerosolised chemotherapy using a hyperbaric capnoperitonem established laparoscopically. This study sought to investigate the feasibility and safety of PIPAC in an Australian population. Methods We undertook a cohort analysis of prospectively-collected data on patients undergoing PIPAC across two Australian hospitals. Participants were planned to have three PIPAC procedures, each 6 weeks apart. Study outcomes included post-operative complications including 30-day mortality, length of stay (LOS) and patient quality of life (EORTC QLQ-C30 scores). Results 18 patients underwent 50 completed procedures. 13 patients had two or more PIPACs. The most common primary malignancy was colorectal cancer (n=8), followed by gastric cancer (n=4), appendiceal cancer (n=4) and mesothelioma (n=2). One grade four but no grade five complications occurred, with zero 30-day mortality. Median LOS was 1 day. Mean EORTC QLQ-C30 score increased from 47.8 at baseline to 53 post second PIPAC. Due to the heterogeneity of our cohort, survival analysis and statistical comparisons were unable to be made. Conclusion PIPAC is feasible, safe and well tolerated in an Australian population with a lack of severe complications and zero 30 day mortality. Due to the small number of patients and the heterogeneity of our study’s sample, it was not possible to perform survival analysis. The study is nonetheless valuable as the first investigation of implementation of PIPAC in Australia.