Ganatra, Nency

741 Background: IP strategies directly target the peritoneal compartment in PDAC, where systemic chemotherapy alone demonstrates poor efficacy. Approaches include HIPEC, normothermic intraperitoneal paclitaxel (NIPEC/IP-PTX) given with systemic therapy, and PIPAC. This systematic review synthesizes evidence on feasibility, perioperative safety, and clinical outcomes of IP therapy in PDAC. Methods: We conducted a systematic search in PubMed, Embase, Scopus, and Cochrane databases for studies published through August 2025. Eligible studies included prospective or retrospective studies evaluating HIPEC, NIPEC/IP-PTX, or PIPAC with extractable safety or oncologic outcomes. Outcomes included feasibility, 30-day mortality, perioperative complications, locoregional recurrence (LRR) in the adjuvant setting, overall survival (OS) from peritoneal metastasis (PM) diagnosis or first IP therapy, conversion-to-resection, and histologic/radiologic response. Results: Sixteen studies met criteria, including 7 on HIPEC, 5 on NIPEC/IP-PTX, and 4 on PIPAC. In the adjuvant setting, 2 HIPEC studies demonstrated high feasibility (>85%), 0–5% 30-day mortality, and complication rates comparable to pancreatectomy. A randomized trial reported significantly lower LRR with adjuvant gemcitabine HIPEC. Median OS in treated arms was ~17–18 months, with 1-year OS ~63%. In the cytoreductive surgery (CRS) plus HIPEC setting for isolated peritoneal metastases, patients achieved CC-0/1 cytoreduction in most cases, with median OS ~24–41 months and 1-, 2-, and 3-year OS ranging 60–91%, 33–66%, and 39–59%, respectively. Thirty-day mortality was 0–4.3%, and major morbidity 20–43%. For NIPEC/IP-PTX, multicenter and single-institution cohorts consistently reported median OS ~14–16 months, 1-year OS ~60%, and conversion-to-resection rates of 17–24%. Ascites control and feasibility were reproducible, and device-related adverse events were generally manageable. PIPAC programs established oxaliplatin at 120 mg/m² as the recommended dose, with ~50–60% histologic regression by PRGS and disease stabilization in 50–60% after 1–2 cycles. Median OS in PDAC subsets was ~9–13 months, with low major toxicity, though early discontinuation was frequent in progressive disease. Conclusions: Intraperitoneal therapies for PDAC are feasible and show promising biologic and clinical signals. Adjuvant HIPEC reduces locoregional recurrence without excess mortality; CRS plus HIPEC can achieve multi-year survival in selected patients with isolated PM metastases; NIPEC/IP-PTX offers reproducible survival and conversion-to-resection; and PIPAC provides histologic regression with acceptable safety.

117 Background: Oxaliplatin remains a cornerstone of colorectal cancer (CRC) chemotherapy but is frequently complicated by chemotherapy-associated liver injury (CALI). This manifests as sinusoidal obstruction syndrome (SOS), nodular regenerative hyperplasia (NRH), or porto-sinusoidal vascular disorder (PSVD). These microvascular changes lead to portal hypertension (PH), splenomegaly, and thrombocytopenia, interrupting chemotherapy delivery and compromising survivorship. Despite increasing recognition, the incidence, spectrum, and management of oxaliplatin-induced portal hypertension (OIPH) remain undefined. Methods: We systematically reviewed PubMed, Embase, and Cochrane through August 2025 for prospective and retrospective cohorts of oxaliplatin-treated CRC patients reporting OIPH incidence, pathology, radiology, or interventional management. Case reports were excluded. Outcomes included incidence, latency, complications, misdiagnosis, and interventions such as bevacizumab and partial splenic embolization (PSE). Results: Eight studies including 730 patients were analyzed. OIPH developed in ~20–30% of patients, with 2–5% progressing to clinically overt disease requiring variceal banding, Transjugular Intrahepatic Portosystemic Shunt (TIPS), PSE, or management of liver failure. Latency to presentation was typically 4–10 years after oxaliplatin exposure. Common features included splenomegaly, thrombocytopenia, varices, and ascites. Histopathology consistently showed sinusoidal dilatation, congestion, perisinusoidal fibrosis, NRH, and microthrombi, confirming endothelial-mediated injury. Up to half of chronic cases were misclassified as metabolic dysfunction–associated steatotic liver disease (MASLD/NAFLD) or cryptogenic cirrhosis. Bevacizumab demonstrated consistent hepatoprotection, delaying splenic enlargement and reducing thrombocytopenia, likely via preservation of sinusoidal endothelial integrity and reduction of von Willebrand factor–mediated platelet microthrombi. Interventional radiology provided therapeutic options: in a prospective phase II study, PSE restored platelet counts >130×10⁹/L in 94% and enabled chemotherapy resumption within a median of 14 days, with no grade ≥3 adverse events. Conclusions: OIPH is an under-recognized complication of CRC chemotherapy, with latency spanning years after treatment. Splenomegaly and thrombocytopenia serve as early clinical signals, while misdiagnosis as MASLD or cirrhosis is common. Bevacizumab provides hepatoprotection, and PSE offers a safe and effective option for chemotherapy-limiting thrombocytopenia. Routine monitoring of spleen volume and platelet trends should be integrated into follow-up, and prospective validation of prophylactic and interventional strategies is urgently needed.

Background: Peritoneal metastasis represents an aggressive disease pattern in pancreatic ductal adenocarcinoma (PDAC), traditionally associated with poor survival and limited therapeutic options. Emerging intraperitoneal chemotherapy strategies—including hyperthermic intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal paclitaxel (NIPEC/IP-PTX), and pressurized intraperitoneal aerosol chemotherapy (PIPAC)—have been investigated to improve local tumor control and survival outcomes. Methods: We systematically reviewed published studies evaluating HIPEC, NIPEC/IP-PTX, and PIPAC in PDAC, including adjuvant, cytoreductive, and palliative settings. Study characteristics, feasibility, perioperative outcomes, oncologic outcomes, and risk of bias were analyzed. Results: Across modalities, intraperitoneal treatment strategies demonstrated acceptable feasibility and safety profiles in appropriately selected patients. Adjuvant HIPEC following pancreatectomy showed reduced local–regional recurrence signals in limited cohorts. CRS + HIPEC among patients with isolated peritoneal metastases yielded encouraging multi-year survival in highly selected candidates achieving complete cytoreduction. NIPEC/IP-PTX demonstrated favorable ascites control, symptom relief, and potential conversion to resection in select patients. PIPAC was primarily used in unresectable, heavily pretreated, palliative peritoneal metastasis settings, with goals centered on disease stabilization, histologic regression, and symptom control rather than curative intent. Conclusions: Intraperitoneal chemotherapy strategies in PDAC appear feasible with signals of meaningful clinical benefit in select settings. While CRS + HIPEC may benefit carefully selected metastatic patients, NIPEC/IP-PTX and PIPAC hold value primarily in symptom control and disease stabilization. Larger prospective trials are needed to define patient selection, optimize treatment protocols, and clarify survival benefit.