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One of the early symptoms of chronic venous disease (CVD) is varicose veins (VV) of the lower limbs. There are many etiological environmental factors influencing the development of chronic venous insufficiency (CVI), although genetic factors and family history of the disease play a key role. All these factors induce changes in the hemodynamic in the venous system of the lower limbs leading to blood stasis, hypoxia, inflammation, oxidative stress, proteolytic activity of matrix metalloproteinases (MMPs), changes in microcirculation and, consequently, the remodeling of the venous wall. The aim of this review is to present current knowledge on CVD, including the pathophysiology and mechanisms related to vein wall remodeling. Particular emphasis has been placed on describing the role of inflammation and oxidative stress and the involvement of extracellular hemoglobin as pathogenetic factors of VV. Additionally, active substances used in the treatment of VV were discussed.

Varicose veins of lower extremities (VVs) are a common multifactorial vascular disease. Genetic factors underlying VVs development remain largely unknown. Here we report the first large-scale study of VVs performed on a freely available genetic data of 408,455 European-ancestry individuals. We identified the 12 reliably associated loci that explain 13% of the SNP-based heritability, and prioritized the most likely causal genes CASZ1, PIEZO1, PPP3R1, EBF1, STIM2, HFE, GATA2, NFATC2, and SOX9. VVs-associated variants within these loci exhibited pleiotropic effects on several phenotypes including blood pressure/hypertension and blood cell traits. Gene set enrichment analysis revealed gene categories related to abnormal vasculogenesis. Genetic correlation analysis confirmed known epidemiological associations between VVs and deep venous thrombosis, weight, rough labor, and standing job, and found a genetic overlap with multiple traits that have not been previously suspected to share common genetic background with VVs. These traits included educational attainment, fluid intelligence and prospective memory scores, walking pace (negative correlation with VVs), smoking, height, number of operations, pain, and gonarthrosis (positive correlation with VVs). Finally, Mendelian randomization analysis provided evidence for causal effects of plasma levels of MICB and CD209 proteins, and anthropometric traits such as waist and hip circumference, height, weight, and both fat and fat-free mass. Our results provide novel insight into both VVs genetics and etiology. The revealed genes and proteins can be considered as good candidates for follow-up functional studies and might be of interest as potential drug targets.

Background Pancreatectomies with superior mesenteric artery (SMA) resection are technically challenging. 1 With the advent of FOLFIRNOX chemotherapy, resection of the SMA is performed in selected patients with locally advanced pancreatic cancer (LAPC), 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 – 10 in centers of excellence by highly skilled pancreatic-vascular surgeons treating a large volume of LAPCs. 4 , 5 , 6 , 7 , 8 , 9 – 10 Methods The patient was a 64-year-old female with an LAPC treated with 11 cycles of FOLFIRINOX induction chemotherapy. The SMA, the superior mesenteric vein (SMV), and a replaced right hepatic artery (r-RHA) were encased. A temporary mesenterico-portal shunt (TMPS), using a 25 cm Goretex tube between the origin of the SMV and the right side of the portal vein, 11 was used. This TMPS (1) lessens portal hypertension in case of SMV obstruction; (2) maintains adequate liver venous perfusion during dissection; (3) gives the mesentery enough mobility to avoid graft for SMA resection; and (4) avoids simultaneous venous and arterial clamping. A mesenteric approach was performed to isolate the SMA. 12 Upon heparin bolus, the r-RHA was re-implanted on the gastroduodenal artery stump, the SMA on the aorta, the SMV on the portal vein, and the splenic vein on the left renal vein. Results Postoperative course was uneventful. Pathology showed pT4N0R1 pancreatic adenocarcinomas. Three years later, the patient recurred on the left adrenal gland and was treated by external radiotherapy. Five years later, the patients is alive under chemotherapy. Conclusions Pancreaticoduodenectomy with SMA and SMV using a transitory mesentericoportal shunt ( The Strasbourg technique ) is a standardized technique used to manage patients with LAPC at our unit.

Background Robotic pancreatoduodenectomy is an increasingly accepted alternative for the treatment of pancreatic ductal adenocarcinoma (PDAC). 1 However, the ability to perform a meticulous robotic-assisted superior mesenteric artery (SMA) dissection to obtain a margin-negative resection remains unknown. 2 PDAC within the head of the pancreas (HOP) that involves the superior mesenteric vein (SMV) and portal vein (PV) requires total venous control (TVC) and a ‘vein-to-the-right’ (or anterior artery-first) approach to SMA dissection to minimize venous congestion and operative blood loss. 3 – 5 Here, we demonstrate a robotic pancreatoduodenectomy with TVC and a ‘vein-to-the-right’ approach. Methods A 70-year-old woman with cT2N0M0 HOP PDAC with lateral SMV involvement and right gastroepiploic vein occlusion underwent robotic pancreatoduodenectomy after neoadjuvant chemotherapy. After transecting the pancreas, we achieved TVC by dividing the small venous tributaries and encircling the SMV, splenic vein, and PV. We then proceeded with a ‘vein-to-the-right’ approach. The inferior pancreatoduodenal arteries were divided to minimize HOP inflow and decrease specimen bleeding. Once the specimen was dissected off the periadventitial plane of the distal SMA, the SMV dissection was carefully performed using a partial side-wall vein resection using a vascular stapler. Results Total operative time was 7.5 h and estimated blood loss was 25 mL. The patient recovered well postoperatively and was discharged on postoperative day 3. Final pathology exhibited a 2.4 cm, moderately to poorly differentiated adenocarcinoma with negative margins (ypT2N1, 2/38 lymph nodes positive). Conclusion For tumors with lateral vein involvement, robotic pancreatoduodenectomy can be safely performed via TVC and a ‘vein-to-the-right’ approach.

Abstract Importance and Objective Pancreatic cancer can lead to severe stenosis of the portomesenteric venous (PV/SMV) confluence due to extrinsic compression or direct invasion. This can result in venous hypertension associated with post-prandial abdominal pain, gastrointestinal bleeding, and ascites. In patients with unresectable tumors, transhepatic PV/SMV stenting has been reported; however, its safety and efficacy are poorly understood. Design, Setting and Participants All unresectable pancreatic cancer patients referred to Interventional Radiology to undergo palliative transhepatic PV/SMV stenting (2011–2024) were collected. Patient demographics, CT scans, transhepatic venograms, and clinical outcomes were reviewed. Intervention, Main Outcomes and Results In total, 129 patients were included; 92% had pancreatic ductal adenocarcinoma. Tumors were unresectable due to unreconstructable vascular involvement, metastatic disease, or poor performance status. Nearly 81% were symptomatic, while the remaining 24 asymptomatic patients presented with significant venous hypertensive varices and collaterals on imaging. Complete venous occlusion was seen in 39% of patients at the PV, the SMV, or the PV/SMV confluence; 97% of procedures were successful, with 4 technical failures at obtaining distal venous wire access. Adverse events occurred in 4 patients. Radiological follow-up was available in 94% of patients. Post-procedural primary stent patency was 80% at a median follow-up time of 20 months. Follow-up was available in 102 of the 105 symptomatic patients, with 85% reporting an improvement in symptoms. Conclusions and Relevance Palliative transhepatic PV/SMV stenting is a technically feasible and safe procedure in well-selected patients. Symptoms improvement can be seen in most patients. High-volume centers should consider this technique for patients with unresectable tumors who present with symptomatic stenosis or short segment occlusion.

Background Venous resection may be required to achieve complete resection of pancreatic cancers. We assessed the ability of radiographic criteria to predict the need for superior mesenteric–portal vein (SMV-PV) resection and the presence of histologic vein invasion. Methods All patients who underwent pancreaticoduodenectomy from 2004 to 2011 at the authors’ institution were identified. Preoperative pancreatic protocol CT images were re-reviewed to characterize the extent of tumor–vein circumferential interface (TVI) as demonstrating no interface, ≤180° of vessel circumference, >180° of vessel circumference, or occlusion. Findings were correlated with the need for venous resection, histologic venous invasion, and survival. Results A total of 254 patients underwent pancreaticoduodenectomy and met inclusion criteria; 98 (39.6 %) required SMV-PV resection. In our cohort, 76.4 % of patients received neoadjuvant chemoradiation. The TVI classification system predicted with fair accuracy both the need for SMV-PV resection at the time of surgery and histologic invasion of the vein. In particular, 89.5 % of patients with TVI >180° or occlusion required SMV-PV resection. Of those, 82.4 % had documented histologic SMV-PV invasion. TVI ≤180° was associated with favorable overall survival compared to a greater circumferential interface. Conclusions A tomographic classification of the tumor–SMV-PV interface can predict the need for venous resection, pathologic venous involvement, and survival. To assist in treatment planning, a standardized assessment of this anatomic relationship should be routinely performed.

Background and aimsPortosinusoidal vascular disease (PSVD) is a broad term encompassing varied histological patterns with changes in portal tracts and sinusoids without cirrhosis. We aimed to assess whether there is any clinical and pathological difference among the various histological categories of PSVD.Patients and methodsThis study included liver biopsy cases classified as PSVD (2020–2022). Clinical and laboratory parameters were obtained from the electronic records. PSVD cases were histologically categorised as obliterative portal venopathy (OPV), OPV with fibrosis (OPV-F), incomplete septal cirrhosis (ISC), nodular regenerative hyperplasia (NRH), mega sinusoids with fibrosis (MSF) and unclassified. Follow-up complications were recorded.ResultsPSVD categories were OPV (45 (26%)), OPV-F (37 (21.4%)), ISC (20 (11.6%)), NRH (19 (11%)), MSF (19 (11%)) and unclassified (33 (19%)). Elevated hepatic venous pressure gradient (HVPG) was noted in OPV-F (10 (IQR: 12–14.7)) and ISC (12 (IQR: 9–14)) mm Hg with higher fibrosis quantity in liver tissue and elevated procollagen III aminoterminal propeptide, which correlated with HVPG. On immunohistochemistry, OPV-F and ISC showed lesser expression of ADAMT13 in liver biopsies (p<0.001). On follow-up, ascites development was more in OPV-F and ISC than in other categories (p=0.001). Higher liver stiffness measurement (LSM) values were recorded in MSF and NRH, compared with other categories, but it did not correlate with fibrosis in liver biopsy.ConclusionsOPV-F and ISC had higher HVPG, fibrosis, and more ascites development on follow-up than the other categories of PSVD, and all are not the same. In contrast, MSF and NRH have spuriously high LSM.

Purpose The role of pancreatectomy with en bloc venous resection and the prognostic impact of pathological venous invasion are still debated. The authors analyzed perioperative, survival results, and prognostic factors of pancreatectomy with en bloc portal (PV) or superior mesenteric vein (SMV) resection for borderline resectable pancreatic carcinoma, focusing on predictive factors of histological venous invasion and its prognostic role. Methods A multicenter database of 406 patients submitted to pancreatectomy with en bloc SMV and/or PV resection for pancreatic adenocarcinoma was analyzed retrospectively. Univariate and multivariate analysis of factors related to histological venous invasion were performed using logistic regression model. Prognostic factors were analyzed with log-rank test and multivariate proportional hazard regression analysis. Results Complications occurred in 51.9 % of patients and postoperative death in 7.1 %. Histological invasion of the resected vein was confirmed in 56.7 % of specimens. Five-year survival was 24.4 % with median survival of 24 months. Vein invasion at preoperative computed tomography (CT), N status, number of metastatic lymph nodes, preoperative serum albumin were related to pathological venous invasion at univariate analysis, and vein invasion at CT was independently related to venous invasion at multivariate analysis. Use of preoperative biliary drain was significantly associated with postoperative complications. Multivariate proportional hazard regression analysis demonstrated a significant correlation between overall survival and histological venous invasion and administration of adjuvant therapy. Conclusions This study identifies predictive factors of pathological venous invasion and prognostic factors for overall survival, including pathological venous invasion, which may help with patients’ selection for different treatment protocols.

Background Liver venous deprivation (LVD) is known to induce better future liver remnant (FLR) hypertrophy than portal vein embolization (PVE). The role of LVD, compared with PVE, in inducing FLR hypertrophy and allowing safe hepatectomy for patients with extensive colorectal liver metastases (CLM) and high-risk factors for inadequate hypertrophy remains unclear. Methods Patients undergoing LVD ( n  = 22) were matched to patients undergoing PVE ( n  = 279) in a 1:3 ratio based on propensity scores, prior to planned hepatectomy for CLM at a single center (1998–2023). The propensity scores accounted for high-risk factors for inadequate hypertrophy, namely pre-procedure standardized FLR (sFLR), body mass index, number of systemic therapy cycles, an extension of PVE to segment IV portal vein branches, prior resection, and chemotherapy-associated liver injury. Results The matched cohort included 78 patients (LVD, n  = 22; PVE, n  = 56). Baseline characteristics were comparable. The number of tumors in the whole liver was similar but more LVD patients had five or more tumors in the left liver (32% vs. 11%; p =  0.024). Post-procedure sFLR was similar but LVD patients had a significantly higher degree of hypertrophy (16% vs. 11%; p =  0.017) and kinetic growth rate (3.9 vs. 2.4% per week; p =  0.006). More LVD patients underwent extended right hepatectomy (93% vs. 55%; p =  0.008). Only one patient had postoperative hepatic insufficiency after PVE, and no patients died within 90 days of hepatectomy. Conclusion In patients with extensive CLM and high-risk factors, LVD is associated with better FLR hypertrophy compared with PVE and allows for safely performing curative-intent extended major hepatectomy.

Purpose Portal vein and superior mesenteric vein thrombosis (PVT/SMVT) are potentially morbid complications of radiation dose–escalated local therapy for pancreatic cancer. We retrospectively reviewed records for patients treated with and without intraoperative radiation (IORT) to identify risk factors for PVT/SMVT. Methods Ninety-six patients with locally advanced or borderline resectable pancreatic adenocarcinoma received neoadjuvant therapy followed by surgical exploration from 2009 to 2014. Patients at risk for close or positive surgical margins received IORT boost to a biologically effective dose (BED10) > 100. Prognostic factors for PVT/SMVT were evaluated using competing risks regression. Results Median follow-up was 79 months for surviving patients. Fifty-six patients (58%) received IORT. Twenty-nine patients (30%) developed PVT/SMVT at a median time of 18 months. On univariate competing risks regression, operative blood loss and venous repair with a vascular interposition graft, but not IORT dose escalation or diabetes history, were significantly associated with PVT/SMVT. The development of thrombosis in the absence of recurrence was significantly associated with a longstanding diabetes history, post-neoadjuvant treatment CA19-9, and operative blood loss. All 4 patients who underwent both IORT and vascular repair with a graft developed PVT/SMVT. PVT/SMVT in the absence of recurrence is not associated with significantly worsened overall survival but led to frequent medical interventions. Conclusions Approximately 30% of patients who underwent neoadjuvant chemoradiation for PDAC developed PVT/SMVT a median of 18 months following surgery. This was significantly associated with venous reconstruction with vascular grafts, but not with escalating radiation dose. PVT/SMVT in the absence of recurrence was associated with significant morbidity.