Ovarian cancer (OC) remains one of the leading causes of gynecologic cancer mortality, largely due to late diagnosis, frequent relapse, and the emergence of chemoresistance. An important but often-overlooked contributor to treatment failure is the heterogeneous penetration of anticancer drugs within tumors. Structural and biochemical barriers-including abnormal vasculature, elevated interstitial pressure, dense extracellular matrix, drug efflux transporters, and malignant ascites-generate steep intratumoral concentration gradients that conventional preclinical models fail to capture. As a result, systemic pharmacokinetic measurements frequently provide limited insight into tumor-level drug exposure. Patient-derived organoids (PDOs) have emerged as physiologically relevant 3D models that preserve the genetic, architectural, and functional characteristics of the original tumor. These systems enable controlled investigation of pharmacokinetic and pharmacodynamic processes, including drug penetration, metabolism, retention, and exposure-response relationships. Adding cell-free malignant ascites supernatant enhances PDOs' ability to mimic the metastatic peritoneal microenvironment of OC. This review discusses recent advances in PDO technologies and examines how PDO-derived data can inform intratumoral pharmacokinetics and dosing strategies using physiologically based pharmacokinetic modeling and in vitro-in vivo extrapolation. Emerging hybrid platforms, including organoid-on-chip systems, vascularized co-cultures, and multi-omics integration, are crucial to improve translational prediction and support precision oncology.

A 47-year-old woman with metastatic pancreatic adenocarcinoma, diagnosed five months earlier and treated with palliative chemotherapy, was admitted with fever, jaundice, and right upper quadrant pain consistent with ascending cholangitis. Treatment with antibiotics was initiated and an endoscopic retrograde cholangiography was performed, whereby a biliary stent was placed to relieve malignant biliary obstruction. Physical examination revealed moderate ascites. Careful inspection of the umbilicus revealed a small nodular lesion located within the umbilical fold that became visible only after eversion of the umbilicus. The lesion had developed gradually over several weeks. Computed tomography confirmed the known pancreatic malignancy with metastatic disease and ascites. On re-review of the images, a small soft tissue nodule replacing the umbilicus was also visible. The lesion was clinically consistent with a Sister Mary Joseph nodule, an umbilical metastasis most commonly associated with advanced gastrointestinal or gynecologic malignancies. These lesions may arise through lymphatic or hematogenous spread or through direct extension into the umbilicus. This case highlights that umbilical metastases may be subtle and located within the umbilical fold, requiring careful physical examination to be detected.

Malignant ascites treatment remains challenging. Hyperthermia is a promising adjunct to intraperitoneal therapies, but its mechanisms are unclear. We aimed to investigate whether combining hyperthermia with endostatin and cisplatin alleviates malignant ascites by reprogramming immune microenvironment. A total of 28 patients with malignant ascites were enrolled and divided into three groups: untreated, recombinant human endostatin plus cisplatin, and hyperthermia combined with recombinant human endostatin and cisplatin. Ascites volume was monitored by B-ultrasound. VEGF, IL-10, and IFN-γ levels in ascitic fluid were measured via ELISA. Immune cell proportions and macrophage polarization were analyzed by flow cytometry. A murine malignant ascites model was established. Mice were treated according to same therapeutic groupings. Tumor burden was assessed via in vivo fluorescence imaging, ascites volume measurement, body weight changes, and survival analysis. Cytokine levels and macrophage polarization in murine ascites were also evaluated. Hyperthermia combined with endostatin and cisplatin reduced ascites volume and modulated ascitic microenvironment in patients with malignant ascites. Triple therapy of hyperthermia, endostatin, and cisplatin functioned dually to eliminate pro-tumoral leukocytes in ascites and reprogram macrophages into M1 phenotypes. Hyperthermia synergized with endostatin and cisplatin to suppress malignant ascites progression, mitigate systemic toxicity, and extend survival in mice. Triple therapy modulated ascitic microenvironment and promoted macrophage M1 polarization in a murine malignant ascites model. Macrophage ablation abolished therapeutic efficacy of triple therapy in malignant ascites mice. The combined strategy of hyperthermia, endostatin, and cisplatin suppresses malignant ascites in gastrointestinal cancer through inducing M1 macrophage polarization.

Berberine, a bio-alkaloid from medicinal plants, shows therapeutic potential against various ailments, including cancer. This study evaluated berberine's effects on the PI3K/Akt pathway and efferocytosis in an adenocarcinoma model to reduce cisplatin chemotherapy side effects and Ehrlich ascites carcinoma (EAC) proliferation. Eighty Swiss albino mice were divided into eight groups: control, berberine, cisplatin, cisplatin & berberine, EAC, EAC & berberine, EAC & cisplatin, and EAC & cisplatin & berberine. Tumor response, weight change, cell count, survival analysis, biochemical analysis, molecular studies, and histopathological assessment were performed. Results showed berberine enhanced cisplatin's antitumor efficacy in EAC-bearing mice by reducing tumor volume and cell counts. Berberine ameliorated cisplatin's hepato-renal toxicity and downregulated Akt1, Axl, Mertk, and Gas6 gene expression. Histopathological analysis showed berberine's ability to recover cisplatin's lethal effects on liver tissue. In conclusion, berberine showed promising effects on the PI3K/Akt pathway and efferocytosis, reducing cisplatin's side effects and EAC proliferation.

Objective: To analyze the clinical characteristics and key points of diagnosis and treatment in patients with pseudomyxoma peritonei (PMP) presenting with external abdominal hernia as the initial manifestation. Methods: A descriptive case-series study was conducted. From May 2015 to September 2024, a total of 569 patients diagnosed with PMP and treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) were admitted to Beijing Shijitan Hospital. Among them, 13 patients (2.3%) presented with external abdominal hernia as the initial clinical manifestation. Clinical data of these 13 patients were retrospectively analyzed, including the type of inguinal hernia, pathological diagnosis, peritoneal cancer index (PCI), interval from pathological diagnosis to first CRS+HIPEC, completeness of cytoreduction (CC) score, operation duration, and serious adverse events within 30 postoperative days and prognosis. Results: The median age of the 13 patients was 51 years (range 33-71 years), including 10 males. Twelve patients presented with inguinal hernia as the initial symptom: 6 with right inguinal hernia, 5 with left inguinal hernia, and 1 with bilateral inguinal hernia. The remaining 1 patient had an umbilical hernia. The hernia contents were tumor tissue and mucus in 11 patients, while 2 patients had complete spontaneous reduction of hernia contents. Pathological diagnosis showed low-grade in 10 cases, acellular mucus, high-grade, and high-grade with signet-ring cells in 1 case each. The median interval from pathological diagnosis to first standard CRS+HIPEC was 2.5 (range 0.6-11.6) months . Perioperative assessment showed that 7 patients had PCI < 20, 9 patients had CC score 0-1, median ascites volume was 800 (range 0-20 000) ml, median Karnofsky performance status score was 90 (range 80-100), and median operation duration was 655 (range 403-1018) minutes . Seven patients developed postoperative serious adverse events: 4 involving the respiratory system, 1 the circulatory system, 1 the digestive system, and 1 with infection. No deaths occurred within 30 postoperative days. The median follow-up was 61.2 months (95%CI: 36.3-86.1), the mean overall survival was 124.3 months (95%CI: 92.1-156.6), and 2 patients died. Conclusions: In PMP patients presenting with external abdominal hernia as the initial symptom, inguinal hernia is the most common type, and most hernia contents cannot be reduced spontaneously. If PMP is suspected during surgery for external abdominal hernia, prompt referral to a specialized peritoneal metastasis center for CRS+HIPEC is recommended.