The body is dependent on the exogenous supply of omega-3 polyunsaturated fatty acids (n3-PUFA). These essential fatty acids are key players in regulating metabolic signaling but also exert anti-inflammatory and anti-carcinogenic properties. The liver is a major metabolic organ involved in fatty acid metabolism. Under experimental conditions, n3-PUFA exert beneficial effect on hepatic steatosis, regeneration and inflammatory insults such as ischemic injury after surgery. Some of these effects have also been observed in human subjects. However, it is unclear whether perioperative administration of n3-PUFA is sufficient to protect the liver from ischemic injury. Therefore, we designed a randomized controlled trial (RCT) assessing n3-PUFA (pre-) conditioning strategies in patients scheduled for liver surgery. The Omegaven™ trial is a multi-centric, double-blind, randomized, placebo- controlled trial applying two single doses of Omegaven™ or placebo on 258 patients undergoing major liver resection. Primary endpoints are morbidity and mortality one month after hospital discharge, defined by the Clavien- Dindo classification of surgical complications (Ann Surg 240(2):205–13, 2004) as well as the Comprehensive Complication Index (CCI) (Ann Surg 258(1):1–7, 2013). Secondary outcome variables include length of Intensive Care Unit (ICU) and hospital stay, postoperative liver function tests, fatty acid and eicosanoid concentration, inflammatory markers in serum and in liver tissue. An interim analysis is scheduled after the first 30 patients per randomization group. Long-term administration of n3-PUFA have a beneficial effect on metabolism and hepatic injury. Patients often require surgery without much delay, thus long-term n3-PUFA uptake is not possible. Also, lack of compliance may lead to incomplete n3-PUFA substitution. Hence, perioperative Omegaven™ may provide an easy and controllable way to ensure hepaative application of tic protection. ClinicalTrial.gov: ID: NCT01884948 , registered June 14, 2013; Institution Ethical Board Approval: KEK-ZH-Nr. 2010–0038; Swissmedic Notification: 2012DR3215.

DPCAR’s short- and long-term outcomes are highly diverse, while the causes and prevention of ischemic complications are unclear. To assess oncological, surgical, and hemodynamic outcomes of 40 consecutive DPCARs for pancreatic (n37) and gastric tumors (n3) (2009–2021), retrospective analyses of mortality, morbidity, survival, and hemodynamic consequences after DPCAR were undertaken using case history data, IOUS, and pre- and postoperative CT measurements. In postoperative complications (42.5%), the pancreatic fistula was the most frequent event (27%), 90-day mortality was 7.5. With 27 months median follow-up, median overall (OS) and progression-free survival (PFS) for PDAC were 29 and 18 months, respectively; with 1-, 3-, and 5-years, the OS were 90, 60, and 28%, with an R0-resection rate of 92.5%. Liver and gastric ischemia developed in 0 and 5 (12.5%) cases. Comparison of clinical and vascular geometry data revealed fast adaptation of collateral circulation, insignificant changes in proper hepatic artery diameter, and high risk of ischemic gastropathy if the preoperative diameter of pancreaticoduodenal artery was <2 mm. DP CAR can be performed with acceptable morbidity and survival. OS and RFS in this super-selective cohort were compared to those for resectable cancer. The changes in the postoperative arterial geometry could explain the causes of ischemic complications and determine directions for their prevention.

The “vein definition” for locally advanced pancreatic ductal adenocarcinoma (LA PDAC) assumes portal-to-superior mesenteric vein (PV/SMV) unreconstructability due to tumor involvement or occlusion. Radical pancreatectomies with SMV resection without PV/SMV reconstruction are scarcely discussed in the literature. Retrospective analysis of 19 radical pancreatectomies for “low” LA PDAC with SMV and all its tributaries resection without PV/SMV reconstruction has shown zero mortality; overall morbidity—56%; Dindo–Clavien—3–10.5%; R0—rate—82%; mean operative procedure time—355 ± 154 min; mean blood loss—330 ± 170 mL; delayed gastric emptying—25%; and clinically relevant postoperative pancreatic fistula—8%. In three cases, surgery was associated with superior mesenteric (n2) and common hepatic artery (n1) resection. Surgery was completed without vein reconstruction (n13) and with inferior mesenteric-to-splenic anastomosis (n6). There were no cases of liver, gastric, or intestinal ischemia. A specific complication of the SMV resection without reconstruction was 2–3 days-long intestinal edema (48%). Median overall survival was 25 months, and median progression-free survival was 18 months. All the relapses, except two, were distant. The possibility of successful SMV resection without PV/SMV reconstruction can be predicted before surgery by CT-based reconstructions. The mandatory anatomical conditions for the procedure were as follows: (1) preserved SMV-SV confluence; (2) occluded SMV for any reason (tumor or thrombus); (3) well-developed inferior mesenteric vein collaterals with dilated intestinal veins; (4) no right-sided vein collaterals; and (5) no varices in the upper abdomen. Conclusion: “Low” LA PDACs involving SMV with all its tributaries can be radically and safely resected in highly and specifically selected cases without PV/SMV reconstruction with an acceptable survival rate.

The key challenge of cell-free tumor DNA (cftDNA) analysis in pancreatic ductal adenocarcinoma (PDAC) is overcoming its low detection rate, which is mainly explained by the overall scarcity of this biomarker in plasma. Obstructive jaundice is a frequent event in PDAC, which enables bile collection as a part of routine treatment. The aim of this study was to evaluate the performance of KRAS-mutated cftDNA detection-based liquid biopsy of plasma and bile in patients with pancreatic neoplasms using digital droplet PCR. The study included healthy volunteers (n = 38), patients with PDAC (n = 95, of which 20 had obstructive jaundice) and other pancreatic neoplasms (OPN) (n = 18). The sensitivity and specificity compared to the control group were 61% and 100% (AUC-ROC—0.805), and compared to the OPN group, they were 61% and 94% (AUC-ROC—0.794), respectively. Bile exhibited higher cftDNA levels than plasma (248.6 [6.743; 1068] vs. 3.26 [0; 19.225] copies/mL) and a two-fold higher detection rate (p < 0.01). Plasma cftDNA levels were associated with distant metastases, tumor size, and CA 19-9 (p < 0.05). The probability of survival was worse in patients with higher levels of cftDNA in plasma (hazard ratio—2.4; 95% CI: 1.3–4.6; p = 0.005) but not in bile (p > 0.05). Bile is a promising alternative to plasma in patients with obstructive jaundice, at least for the diagnostic purposes of liquid biopsy.

INTRODUCTION: Plasma liquid biopsy with tumor cell-free DNA detection is one of the most promising technologies in pancreatic ductal adenocarcinoma diagnosis. Due to low levels of this biomarker in plasma its detectability turns out to be lower than expected. However, some patients with this disease present with biliary obstruction, which enables collection of bile for tumor cell-free DNA analysis. THE AIM: To comparison of diagnostic potential of cell-free tumor DNA detection-based liquid biopsy of plasma and bile in pancreatic ductal adenocarcinoma patients. MATERIAL AND METHODS: The pilot study included 15 primary untreated pancreatic ductal adenocarcinoma patients with biliary obstruction. Cell-free DNA was isolated from 5 mL of plasma and 5 mL of bile. Tumor cell-free DNA detection was performed using digital droplet PCR with KRAS gene mutations analysis: G12A, G12C, G12D, G12R, G12S, G12V, G13D и Q61H (183AC), Q61H (183AT), Q61K, Q61L, Q61R. False-positive droplets threshold was established during the analysis of plasma cell-free DNA samples from 15 healthy volunteers. RESULTS: Tumor cell-free DNA was detected in 13 out of 15 bile samples, whereas among paired plasma samples only 9 were positive. All plasma positive samples had a paired positive bile sample. Tumor cell-free DNA levels were statistically significantly higher in bile than in plasma: 538.0 (4.11960.0) vs. 4.4 (027.6) copies/mL (p=0.005). CONCLUSION: Bile liquid biopsy in pancreatic ductal adenocarcinoma patients with biliary obstruction is a promising alternative to plasma analysis, due to higher concentrations of tumor cell-free DNA.

Background: Spleen-preserving (SP) distal pancreatectomy (DP) with splenic vessels resection (SVR) (Warsaw procedure, WP) is an option for the treatment of tumors with low malignant potential. The reverse blood flow through the short gastric arteries (SGA) explains the preservation of the spleen after SVR, but leaves the source of the blood supply to the SGAs hidden. The types of blood supply to the spleen after WP and their incidence have not been previously described, nor has the significance of these types for locally advanced pancreatic head cancer (LAPHC) surgery been determined. Aim: To determine the main types of spleen blood supply after WP, and to assess the feasibility and safety of splenic artery (SA) rotation for the organ-preserving surgery of LAPHC. Methods: Retrospective analyses of demographic and perioperative data, including CT scans, overall (OS) and progression-free (PFS) survival after 71 SP DP SVR and 41 SP SVR pancreaticoduodenectomies (PD) and total pancreatectomies (TP) for LAPHC (2007–2025). Results: In 134 SP procedures, SA was resected in 115 cases (71DP, 9 TP, 3 central, and 32 PD). Indications for surgery were MCN (41), IPMN (14), CSA (3), NEN (25), SPPN (8), PHDAC (40), sarcoma (1), autoimmune (1), and calculous chronic pancreatitis (1). There were no deaths or ischemia-related splenectomies. Morbidity—31% (n23); Dindo–Clavien (D-C) > 3b-2.8%; POPF-grade B-n7 (10.6%); splenic infarctions on CT after SVR-n18 (23%), one symptomatic. CT revealed three types of arterial blood supply to the spleen after SPDP SVR: left gastric artery (LGA) type (n50, 70, 5%), gastro-epyploic arcade (GEA) type (n9, 12, 5%), and an intermediate type (n12, 17%). Spleen- and pancreas tail-preserving SVR pancreatectomies for LAPHC (n41) were accompanied by rotation of the SA to substitute resected SMA (n19) and CHA (n15) for 26 Whipples and 8TPs. There were no ischemic complications. D-C > 3–19.5%. Median OS and PFS for PDAC were 35 and 21 months for 29.5 months median follow-up. Conclusions: Despite the preservation of blood flow through all potential sources of splenic blood supply following resection of the splenic artery, the main collaterals supplying the spleen after WP are LGA branches (~90%). This knowledge, with strict adherence to the developed criteria, allows for the safe preservation of the spleen, pancreatic tail, and stomach during pancreatectomies with SA resection, including its rotation for the substitution of the SMA and CHA in LAPHC.