Hepatic Artery Ligation Research Articles

Abstract C004: A window-of-opportunity trial using neoadjuvant hepatic artery chemotherapy for patients with localized pancreas cancer: Interim analysis of safety and feasibility

Abstract Less than 20% of patients diagnosed with pancreatic cancer will present with localized disease and receive both resection and systemic therapy. Within this group of patients, actual 10-year survival is approximately 5%. The liver is the most common site of recurrent disease and is associated with the worst survival outcomes. Randomized trials in patients with localized colorectal cancer have shown the addition of single-dose, neoadjuvant hepatic artery (HA) chemotherapy, which administers a high-dose of chemotherapy directly to the liver, improves liver metastasis-free and overall survival. Because PDAC and colorectal cancer have similar recurrence patterns and are treated with similar systemic therapy, we hypothesized this strategy could improve recurrence rates and potentially overall survival in patients with localized PDAC. This is a prospective, non-randomized window-of-opportunity trial testing single-dose neoadjuvant HA chemotherapy in patients with resectable or borderline resectable PDAC. Target enrollment is 20 patients treated in two arms: three months of mFOLFIRINOX before surgery and three months after, or upfront surgery followed by six months of mFOLFIRINOX. In both arms, patients undergo diagnostic laparoscopy and percutaneous delivery of the experimental HA therapy (floxuridine and oxaliplatin) one week before surgery. Patients then undergo resection of their primary tumor, followed by short-term follow-up, where safety evaluations are performed for 30 days. Patients then enter long-term follow-up, where efficacy will be assessed every three months for up to three years. The primary endpoint is safety and feasibility. Secondary endpoints include three-year disease-free, liver metastasis-free, and overall survival. To date, eight patients have been screened and seven enrolled: four in the neoadjuvant therapy arm and three in the upfront resection arm. All patients have completed the treatment period and 86% have completed short-term follow-up. Mean age was 63+/-11 years and 57% were female. Mean CA 19-9 prior to resection was 60.3+/-50 U/mL. Conventional hepatic artery anatomy was present in 57% of patients. HA chemotherapy was delivered through the proper hepatic artery in 86% of patients, and via the left and right hepatic arteries in 14%. Concomitant ligation or embolization of accessory hepatic arteries was required in 43%. The mean tumor size was 2.5+/-0.8 cm and lymph node metastases were present in 86%; three patients had a microscopically positive resection margin. Four of the seven patients experienced adverse events, including one grade 2 event, three grade 3 events, and one grade 4 event. However, none were attributed to the experimental therapy. At this interim analysis, single-dose neoadjuvant HA chemotherapy appears to be feasible and safe in patients undergoing resection of localized PDAC. We anticipate enrollment to be completed within the calendar year. Long- term follow-up will be required to resolve survival outcomes and correlative endpoints. Citation Format: Ethan S Agritelley, Elishama N Kanu, Jiayin Bao, Ashley A Fletcher, Holly Skinner, Adi Molvin, Stacy Murray, Charles Y Kim, Brendan Cline, Eric Mastria, David Y Johnson, Nicholas C DeVito, Gerard C Blobe, James L Abbruzzese, Erika J Crosby, Allison Martin, Niharika B Mettu, Peter J Allen, Daniel P Nussbaum. A window-of-opportunity trial using neoadjuvant hepatic artery chemotherapy for patients with localized pancreas cancer: Interim analysis of safety and feasibility [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C004.

Laparoscopic anatomical right hepatectomy using a four-incision anterior approach: Technical details and surgical outcomes (with Video)

With the continuous advancements of laparoscopic techniques, many surgeons have enhanced the feasibility and safety of this approach for carefully selected patients. This study aims to offer a comprehensive account of the technical aspects and surgical outcomes associated with laparoscopic anatomical right hepatectomy, explicitly utilizing a four-incision anterior approach. The surgical procedure involved several maneuvers, including blocking the Glissonean pedicle, ligation of the right hepatic artery, right branch of the portal vein, and the right hepatic duct, removal of the liver parenchyma along the ischemic line, and determination of the liver section based on four anatomical landmarks: the right anterior Glissonian pedicle, middle hepatic vein, root of the right hepatic vein, and retrohepatic inferior vena cava. The article provides clear visualization of these anatomical landmarks following right hepatectomy. Proper patient positioning and precise incision placement are crucial factors for ensuring the success of the laparoscopic right anterior hepatectomy procedure. The separation of the extrahepatic Glissonean pedicle at the liver hilum to determine the hepatic resection ischemia line, as well as the identification of liver sections using four anatomical landmarks are essential steps in the liver resection process. The laparoscopic anatomical right hepatectomy using a four-incision anterior approach was performed smoothly, with standard intraoperative techniques completed. Measures are in place to address any complications that may arise during the surgery.

Life-Threatening Ruptured Hepatic Artery Pseudoaneurysm Post-Liver Transplant: A Case Report

IntroductionHepatic artery pseudoaneurysm after liver transplantation is a rare condition, which can lead to spontaneous bleeding depending on its extent and location. Treatment involves endovascular and surgical approaches, and in cases of graft failure, liver retransplantation. Case ReportA 42-year-old female underwent deceased donor liver transplantation due to cryptogenic cirrhosis and schistosomiasis with an uneventful postoperative course. However, 18 days after the operation, she presented to the emergency department with abdominal pain, hypotension, and lipothymia. Computed tomography scan revealed a hepatic artery anastomotic pseudoaneurysm, and, due to hemodynamic instability, emergency laparotomy was indicated. During operation, the pseudoaneurysm was found to be ruptured and the recipient hepatic artery was ligated due to life-threatening bleeding. She later developed ischemic cholangiopathy and biliary complications, eventually undergoing retransplantation seven months after the emergency operation. The patient remains well 11 months after the retransplantation. ConclusionWe report a rare case of life-threatening rupture of hepatic artery anastomotic pseudoaneurysm, which required emergency ligation of the recipient hepatic artery and subsequent liver retransplantation due to biliary complications.

Prognostic PET [11C]-acetate uptake is associated with hypoxia gene expression in patients with late-stage hepatocellular carcinoma – a bench to bed study

BackgroundPositron Emission Tomography (PET) with combined [18F]-FDG and [11C]-acetate (dual-tracer) is used for the management of hepatocellular carcinoma (HCC) patients, although its prognostic value and underlying molecular mechanism remain poorly understood. We hypothesized that radiotracer uptake might be associated with tumor hypoxia and validated our findings in public and local human HCC cohorts.MethodsTwelve orthotopic HCC xenografts were established using MHCC97L cells in female nude mice, with 5 having undergone hepatic artery ligation (HAL) to create tumor hypoxia in vivo. Tumors in both Control and HAL-treated xenografts were imaged with [11C]-acetate and [18F]-FDG PET-MR and RNA sequencing was performed on the resected tumors. Semiquantitative analysis of PET findings was then performed, and the findings were then validated on the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort and patients from our institution.ResultsHAL-treated mice showed lower [11C]-acetate (HAL-treated vs. Control, tumor-to-liver SUV ratio (SUVTLR): 2.14[2.05–2.21] vs 3.11[2.75–5.43], p = 0.02) but not [18F]-FDG (HAL-treated vs. Control, SUVTLR: 3.73[3.12–4.35] vs 3.86[3.7–5.29], p = 0.83) tumor uptakes. Gene expression analysis showed the PET phenotype is associated with upregulation of hallmark hypoxia signature. The prognostic value of the hypoxia gene signature was tested on the TCGA-LIHC cohort with upregulation of hypoxia gene signature associated with poorer overall survival (OS) in late-stage (stage III and IV) HCC patients (n = 66, OS 2.05 vs 1.67 years, p = 0.046). Using a local cohort of late-stage HCC patients who underwent dual-tracer PET-CT, tumors without [11C]-acetate uptake are associated with poorer prognosis (n = 51, OS 0.25 versus 1.21 years, p < 0.0001) and multivariable analyses showed [11C]-acetate tumor uptake as an independent predictor of OS (HR 0.17 95%C 0.06–0.42, p < 0.0001).Conclusions[11C]-acetate uptake is associated with alteration of tumor hypoxia gene expression and poorer prognosis in patients with advanced HCC.

Multidisciplinary management of high-grade pediatric liver injuries.

To present our experience of multidisciplinary management of high-grade pediatric liver injuries. Pediatric high-grade liver injuries pose significant challenge to management due to associated morbidity and mortality. Emergency surgical intervention to control hemorrhage and biliary leak in these patients is usually suboptimal. Conservative management in selected high-grade liver injuries is now becoming standard of care. Management of hemobilia due to pseudoaneurysm formation and traumatic bile leaks requires multidisciplinary management. A retrospective review was undertaken for patients presenting with blunt liver injuries at two tertiary care centers inKarachi, Pakistan, from March 2021 to December 2022. Twenty-eight patients were identified, and four patients fulfilled the criteria for grade 4 and above blunt liver injury during this period. One case with grade 4 liver injury developed hemobilia on 7th day of injury. He required two settings of angioembolization but had recurrent leak from pseudoaneurysm. He ultimately needed right hepatic artery ligation. Second patient presented with massive biliary peritonitis 2days following injury. He was managed initially with tube laparostomy followed by ERCP and stent placement. The third patient developed large hemoperitoneum managed conservatively. One case with grade 5 injury expired during emergency surgery. Conservative management of advanced liver injuries can result in significant morbidity and mortality due to high risk of complications. Trauma surgeons need to have multidisciplinary team for management of these patients to gain optimal outcome.

Portosystemic shunting prevents hepatocellular carcinoma in non-alcoholic fatty liver disease mouse models.

Non-alcoholic fatty liver disease (NAFLD) is one of the leading cause of hepatocellular carcinoma (HCC). This association is supported by the translocation of bacteria products into the portal system, which acts on the liver through the gut-liver axis. We hypothesize that portosystemic shunting can disrupt this relationship, and prevent NAFLD-associated HCC. HCC carcinogenesis was tested in C57BL/6 mice fed a high-fat high-sucrose diet (HFD) and injected with diethylnitrosamine (DEN) at two weeks of age, and in double transgenic LAP-tTA and TRE-MYC (LAP-Myc) mice fed a methionine-choline-deficient diet. Portosystemic shunts were established by transposing the spleen to the sub-cutaneous tissue at eight weeks of age. Spleen transposition led to a consistent deviation of part of the portal flow and a significant decrease in portal pressure. It was associated with a decrease in the number of HCC in both models. This effect was supported by the presence of less severe liver steatosis after 40 weeks, and lower expression levels of liver fatty acid synthase. Also, shunted mice exhibited lower liver oxygen levels, a key factor in preventing HCC as confirmed by the development of less HCCs in mice with hepatic artery ligation. The present data show that portosystemic shunting prevents NAFLD-associated HCC, utilizing two independent mouse models. This effect is supported by the development of less steatosis, and a restored liver oxygen level. Portal pressure modulation and shunting deserve further exploration as potential prevention/treatment options for NAFLD and HCC.

Surgical Techniques for Severe Liver Injury: A Comprehensive Review of Current Approaches and Advancements

In abdominal trauma, the liver is the most injured organ and treatment is usually determined by hemodynamics. Severe liver injury with extensive parenchymal injury and uncontrollable bleeding may rapidly evolve into the lethal triad of death (acidosis, hypothermia, and coagulopathy), requiring damage control surgery (DCS). Damage control resuscitation for trauma treatment reduces the need for DCS by enabling rapid control of massive bleeding. Thus, definitive surgery can be completed in one operation. Despite the systematic application of damage control resuscitation, definitive surgery cannot be achieved in severe, and extensive liver injuries. Therefore, understanding, and acquiring damage control surgical techniques is necessary to achieve DCS for severe liver injury. The Western Trauma Association and the World Society of Emergency Surgery have proposed algorithms for the nonoperative and operative management of blunt hepatic trauma. The algorithms list several surgical skills, including electrocautery or argon beam, manual compression, perihepatic packing, the Pringle maneuver, liver suture, omental packing, selective hepatic artery ligation, balloon tamponade, hepatic vascular isolation, and the shunt operation. These techniques require a multidisciplinary approach and individual honing of skills by the surgeon. Trauma surgeons, even hepatobiliary surgeons, must practice damage control techniques in severe liver injury models (animals or cadavers).

Abstract No. 138 Safety and Efficacy of Portal Vein Embolization after Hepatic Arterial Infusion Pump Placement

Hepatic arterial infusion (HAI) combined with systemic chemotherapy is used to treat patients with advanced liver cancers in a staged operative approach. At the time of HAI pump placement, upwards of 60% of patients require ligation of aberrant hepatic arteries. We sought to characterize the safety and efficacy of portal vein embolization (PVE) for inducing liver hypertrophy in patients who underwent HAI with and without hepatic arterial ligation. An IRB-approved retrospective review was conducted on all patients who underwent PVE between the years of 2015 and 2022, with and without preceding or subsequent HAI. Segmental liver volumes, the standardized future liver remnants (sFLR), percent volumetric changes, and the kinetic growth rates (KGR) were calculated using semi-automatic liver segmentation (IntelliSpace, Version 11.1, Philips Medical Systems, Netherlands) performed on multiphasic liver computed tomography scans prior to and 4-12 weeks after PVE. The impact of hepatic artery ligation was assessed by analyzing hepatic resection outcomes following PVE. Between January 2015 and August 2022, 48 patients underwent technically successful PVE with 12 (25%) having a HAI pump as part of their operative clearance strategy. There were 9 HAI pumps (19%) placed before PVE and 3 (6%) after PVE. Among the 9 patients who underwent PVE after HAI, sFLR increased from 21.1 ± 6.8% (mean ± std) to 34.8 ± 6.0%, with KGR of 2.2 ± 1.8% (3 patients had KGRs below 2% but sFLR >30% prior to hepatectomy). Seven (78%) of these patients had hepatic artery ligation during HAI pump placement including 5 replaced right hepatic arteries and 5 accessory left hepatic arteries (4 patients required ligation of both). All patients with ligated right hepatic arteries developed robust intrahepatic left-to-right collateralization prior to PVE. Of these 9 patients, 5 (56%) proceeded to an extended right hepatectomy, 1 (11%) to a right hepatectomy. Three patients did not undergo hepatic resection due to interval development of extrahepatic disease. The median time from PVE to hepatic resection was 59 days. There were no biliary complications in the patients treated with PVE after HAI. PVE to induce liver hypertrophy in sequence with HAI for patients with advanced liver cancer was not associated with increased biliary complication or compromised hepatic function. HAI with or without prior hepatic arterial ligation should not be used to exclude patients from PVE.

Preoperative liver arterial conditioning in patients scheduled for a Mayo Clinic class Ia distal pancreatectomy: embolization or ligation?

BackgroundLiver ischemia may occur during intraoperative common hepatic artery ligation in Mayo Clinic class I distal pancreatectomy with en bloc celiac axis resection (DP-CAR). Preoperative liver arterial conditioning could be used to avoid this outcome. This retrospective study compared arterial embolization (AE) or laparoscopic ligation (LL) of the common hepatic artery before class Ia DP-CAR. MethodsFrom 2014 to 2022, 18 patients were scheduled for class Ia DP-CAR after neoadjuvant FOLFIRINOX treatment. Two were excluded due to hepatic artery variation, six underwent AE, ten underwent LL. ResultsTwo procedural complications occurred in the AE group: an incomplete dissection of the proper hepatic artery and a distal migration of coils in the right branch of the hepatic artery. Neither complication prevented surgery. The median delay between conditioning and DP-CAR was 19 days; decreased to five days in the last six patients. None required arterial reconstruction. Morbidity and 90-day mortality rates were 26.7% and 12.5%, respectively. No patient developed postoperative liver insufficiency after LL. ConclusionPreoperative AE and LL seem comparable in averting arterial reconstruction and postoperative liver insufficiency in patients scheduled for class Ia DP-CAR. However, serious complications that may arise during AE led us to prefer the LL technique.

Effect and mechanism of pirfenidone combined with 2-methoxy-estradiol perfusion through portal vein on hepatic artery hypoxia-induced hepatic fibrosis

PurposeThe aim of this study was to explore the effect and mechanism of pirfenidone (PFD) combined with 2-methoxyestradiol (2-ME2) perfusion through portal vein on hepatic artery hypoxia-induced hepatic fibrosis. Materials and methodsSprague-Dawley rats were divided into 5 groups (n ​= ​3/group): control group, hepatic artery ligation (HAL) group, HAL ​+ ​PFD (portal vein perfusion of PFD) group, HAL+2-ME2 (portal vein perfusion of 2-ME2) group and HAL ​+ ​PFD+2-ME2 group depending on whether they received HAL and/or portal vein perfusion (PFD and/or 2-ME2). Livers were harvested for pathology, western blotting (WB), and quantitative real-time PCR (qRT-PCR). ResultsSirius red staining showed that portal vein perfusion of drugs resulted in degradation of liver fibrosis. Immunohistochemistry showed decreased hypoxia-inducible factor-1 α (HIF-1α) and α-smooth muscle actin (α-SMA) after portal intravenous drugs infusion compared with HAL group (P ​< ​0.05). WB analysis showed increased Smad7 in HAL ​+ ​PFD group compared with HAL group (P ​< ​0.05). qRT-PCR analysis showed decreased matrix metallo-proteinase 2 (MMP2), transforming growth factor β1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1), and Collagen I mRNA in HAL ​+ ​PFD group except for tissue inhibitor of metalloproteinase-1 (TIMP-1) compared with HAL group (P ​< ​0.05). Compared with HAL ​+ ​PFD group, the addition of 2-ME2 did not lead to better results in qRT-PCR analysis. ConclusionsThe portal vein perfusion of PFD significantly reduced the hepatic artery hypoxia-induced fibrosis degree in treated rats by down-regulating the expression of HIF-1α, α-SMA, MMP2, TGF-β1, MCP-1, and Collagen I, as well as up-regulating the TIMP-1 expression and Smad7 protein level. Combined 2-ME2 infusion was not better than PFD alone.

The Antitumor Impact of Combining Hepatic Artery Ligation With Copper Chelators for Liver Cancer.

Hepatocellular carcinoma (HCC) is one of the main cancer-related mortality worldwide. Thus, there is a constant search for improvement in treatment strategies to enhance the prognosis of this malignancy. The study aims to investigate the combined antitumor activity of ammonium tetrathiomolybdate (TM, copper chelator) combined with hepatic artery ligation (HAL) for liver cancer. A total of 40 Sprague-Dawley (SD) rats bearing hepatic tumors were randomly divided into four groups: the control group without any treatment (control), HAL only (HAL), given TM by gavage (TM), and given TM combined with HAL (HAL + TM). The concentrations of serum copper were measured at the predetermined time points. Tumor growth rate, overall survival (OS), expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and microvessel density (MVD), as determined by immunohistochemical examination, were compared. HAL treatment transiently could elevate alanine transaminase (ALT) and aspartate transaminase (AST) but resumed to baseline within 1 week. Serum copper was significantly increased in tumor-bearing animals over time. The values of serum copper in the three treatment groups were significantly lower than those in the control group at different time points, with the lowest values observed in the TM group (P < .05). The average tumor size was 30.33 ± 2.58, 20.83 ± 2.93, 16.80 ± 3.84, and 10.88 ± 1.08 mm in the control, HAL, TM, and HAL + TM groups, respectively (HAL + TM vs other groups, all P < .05). In addition, the expression levels of HIF-1α, VEGF, and MVD were significantly lower in the HAL + TM group than those in the other groups (P < .05). The OS of rats in the combined groups was significantly prolonged combined to the other groups (P < .05), with survival time of 19.1 ± 0.64, 25.4 ± 1.24, 25.3 ± 1.78, and 29.9 ± 2.22 days in the control, HAL, TM, and HAL + TM groups, respectively. These findings suggest that combined treatment with TM and HAL holds great potential for liver cancer treatment by reducing tumor hypoxia and angiogenesis. The observed results indicate that these combinations may offer a novel target and strategy for interventional therapy of liver cancer.

Robotic Celiac Artery Resection with Distal Pancreatic Splenectomy Following Common Hepatic Artery Ligation. A Novel Approach to Pancreatic Cancer Encasing Celiac Axis

Robotic Celiac Artery Resection with Distal Pancreatic Splenectomy Following Common Hepatic Artery Ligation. A Novel Approach to Pancreatic Cancer Encasing Celiac Axis

Liver Dysfunction After Use of Nathanson Retractor During Laparoscopic Gastrectomy for Gastric Cancer.

Background: Cardiopulmonary complications and liver dysfunction are also specific complications and problems associated with laparoscopic surgery. The main causes of postoperative liver dysfunction, which may often occur after laparoscopic surgery, include carbon dioxide pneumoperitoneum and ligation of the aberrant left hepatic artery. Hepatic steatosis may develop as a natural consequence of neoadjuvant therapy, although rarely, owing to chemotherapy. Nathanson retractor may cause a prolonged elevation in liver enzymes of these patients compared with those who do not receive neoadjuvant therapy. Materials and Methods: The data of 151 patients who underwent laparoscopic radical gastrectomy between January 2017 and January 2022 for histologically proven primary gastric cancer in our clinic were retrospectively reviewed. Results: The mean length of hospital stay was 6.21 days. The mean time normalization of the aspartate aminotransferase (AST) value was 2.45 ± 1.83 (range, 0-12) days postoperatively. The analysis of the correlation between the preoperative and postoperative 1-day values of alanine aminotransferase (ALT) and AST revealed a significant difference between the preoperative and postoperative 1-day median values of both parameters (P < .001). Each one unit increase in ALT led to an increase of 0.338 days in the length of intensive care stay and an increase of 0.345 days in the overall length of hospital stay. As the time to normalization of the AST value increased, the length of both intensive care stay and hospital stay increased. Each one unit increase in AST resulted in an increase of 0.316 days in the length of intensive care stay and an increase of 0.376 days in the overall length of hospital stay. Conclusion: Alternative retraction methods can be used safely in laparoscopic surgery for gastric cancer patients receiving neoadjuvant therapy. We are of the opinion that the Nathanson retractor should be used only during dissection of the relevant regions to shorten the intraoperative intermittent release or the time of use.

Preoperative liver arterial conditioning in patients scheduled for a mayo clinic class IA distal pancreatectomy: Embolization or ligation?

Patients who undergo intraoperative ligation of the common hepatic artery in Mayo Clinic class I distal pancreatectomy with en bloc celiac axis resection (DP-CAR) might be exposed to liver ischemia. To avoid serious adverse postoperative outcomes related to arterial reconstruction, preoperative liver arterial conditioning by embolization or ligation is used. Here, we report our experience of preoperative liver conditioning by arterial embolization (AE) or laparoscopic ligation (LL) of the common hepatic artery before Class Ia DP-CAR. From 2014 to 2021, 15 patients were scheduled for a Class Ia DP-CAR after neoadjuvant FOLFIRINOX treatment. Six patients underwent AE, while nine underwent LL. Two procedural complications occurred in the AE group: one patient had an incomplete dissection of the proper hepatic artery, and one patient had distal migration of coils in the right branch of the hepatic artery. None of these complications prevented surgery. The median delay between liver conditioning and DP-CAR was 19 days; this delay decreased to 5 days in the last five patients. Arterial reconstruction was not performed. The severe morbidity and 90-days mortality rates were 26.7% and 13.3%, respectively. No patient developed postoperative liver insufficiency. No differences were noted between the groups in terms of the postoperative course. Preoperative AE and LL were comparable in terms of avoiding arterial reconstruction and postoperative liver insufficiency in patients scheduled for class Ia DP-CAR. However, the possible serious complications that may arise during AE led us to prefer the LL technique.

Non-invasive PET/MR Imaging in an Orthotopic Mouse Model of Hepatocellular Carcinoma.

Preclinical experimental models of hepatocellular carcinoma (HCC) that recapitulate human disease represent an important tool to study tumorigenesis and evaluate novel therapeutic approaches. Non-invasive whole-body imaging using positron emission tomography (PET) provides critical insights into the in vivo characteristics of tissues at the molecular level in real-time. We present here a protocol for orthotopic HCC xenograft creation with and without hepatic artery ligation (HAL) to induce tumor hypoxia and the assessment of their tumor metabolism in vivo using [18F]Fluoromisonidazole ([18F]FMISO) and [18F]Fluorodeoxyglucose ([18F]FDG) PET/magnetic resonance (MR) imaging. Tumor hypoxia could be readily visualized using the hypoxia marker [18F]FMISO, and it was found that the [18F]FMISO uptake was higher in HCC mice that underwent HAL than in the non-HAL group, whereas [18F]FDG could not distinguish tumor hypoxia between the two groups. HAL tumors also displayed a higher level of hypoxia-inducible factor (HIF)-1α expression in response to hypoxia. Quantification of HAL tumors showed a 2.3-fold increase in [18F]FMISO uptake based on the standardized value uptake (SUV) approach.

Hyperspectral evaluation of liver oxygenation in a murine model of metabolic associated liver disease and hepatocellular carcinoma

Abstract Objective Untreated MAFLD is a continuum of disease ranging from hepatic steatosis to cirrhosis and hepatocellular carcinoma (HCC). Throughout the disease progression, a change in hepatic hemodynamics occurs as portal hypertension. Hepatic arterial buffer response is a compensatory mechanism to maintain liver perfusion facing reduction of portal flow. These changes could also impair hepatic oxygenation homeostasis. The aim of this study is to test this hypothesis in mouse models and to shed light on the oxygenation of fatty, portal hypertensive liver and its impact on HCC carcinogenesis. Methods C57BL/6 mice were fed a HFD starting from 4 weeks of age, porto-systemic shunts (or sham) were created at 8 weeks, and monitored up to 40 weeks. ND-fed non-shunted mice were used as control group. Hyperspectral imaging (HSI) was utilized to quantify tissue oxygenation (StO2) of ND, HFD and HFD-shunted mice. In a second set of experiment, we explored the role of a common hepatic artery ligation in the studied DEN-induced HFD mouse model. Results HFD induced hepatic steatosis and portal pressure compared to ND. Porto-systemic shunt could deviate about 67% of the portal flow through the spleen to the systemic circulation, thus reducing portal pressure close-to-normal levels. Compared to control mice, HFD feeding increased liver oxygenation (p=0.0004), while shunting restored a close to normal level (p&amp;lt;0.001). The oxygenation of small bowel is decreased in a similar manner in both HFD and HFD-shunted mice. In HFD-fed mice, artery ligation led to less carcinogenesis compared to mice without artery ligation (p=0.026). In addition, artery ligation was also associated with smaller HCCs (p=0.027). Conclusion Early stages of MAFLD alter hepatic oxygen homeostasis. Fatty liver, when associated to portal hypertension, express higher liver oxygenation levels, compared to control group. This could due to hepatocyte ballooning with a narrowing of portal system, thus bring portal hypertension state with a simultaneous arterial buffer response. Additionally, small bowel of portal hypertensive mice showed lower oxygen levels mirroring an intestinal venous congestion typical of portal hypertension. Oxygen deprivation, through artery ligation, decreases HCC carcinogenesis and reduces HCC nodules volume. Yet further research is needed but oxygen homeostasis seems play a role in MAFLD progression as well in HCC pathophysiology.

Giant hepatic angiomyolipoma presenting with severe anemia: A surgical case report and review of literature.

BackgroundAngiomyolipoma (AML) is a solid benign neoplasm with mesenchymal features. The clinical signs and symptoms of hepatic angiomyolipoma are nonspecific, and treatment strategy is variable.PresentationA 35-years-old male patient has admitted to the hospital with symptoms of severe anemia. Abdominal multi-slice computed tomography (MSCT) and Gadoxetic acid (GA)-enhanced magnetic resonance imaging (MRI) revealed a heterogeneous 23 × 17 cm-in-sized tumor with heterogeneous enhancement and increased angiogenesis. Percutaneous hepatic biopsy was proceeded and in immunohistochemistry, tumor cells responded positively to the HMB-45, SMA, and Glutamine stains, the CD-34 stain was positive for blood vessels as well as Ki-67 sporadically positive, but the Heppar1, S-100, CK stains reacted negative. The final pathologic result was consistent with the primary hepatic angiomyolipoma. The final surgical management was extended right hepatectomy with ligation of the right hepatic artery (RHA) and vein (RHV), as well as the middle hepatic vein (MHV), one month after portal embolization as well as to enlarge the remnant liver volume.DiscussionA hepatic angiomyolipoma (HAML) primary origin is relatively rare, the clinical manifestations are variable and non-specific. Histological examination and immunohistochemistry staining are considered as the gold standard for HAML diagnosis. HAML are commonly expressed benign behaviors, but HAML cases with malignant behaviors were reported in a cumulative incidence. Radical surgery must be still the most effective and major treatment approach.ConclusionThe present case being the first case with initial syndrome of severe anemia accounted in the English literature. Giant angiomyolipoma is composed of blood vessels and could lead to extensive internal tumoral hemorrhage. We here present a report of this case with had primary hepatic angiomyolipoma with clinical picture of severe anemia.

Pseudoaneurysm of the right hepatic artery after laparoscopic cholecystectomy: A case report

Pseudo aneurysms after laparoscopic cholecystectomy are rare and manifest as late hemobilia which is difficult to diagnose and manage. This condition mainly affects the right branch of the hepatic artery and the prognosis is poor. We report the case of an patient diagnosed with a pseudo aneurysm 10 days after laparoscopic cholecystectomy. Following radiological exploration, hemobilia was identified on the 10th postoperative day. In this case, selective embolization was not possible and therefore a ligation of the right hepatic artery was performed. The postoperative period was marked by the reappearance of hemobilia evoking the diagnosis of vascular shunts in the hepatic hilum, and double ligation of the right hepatic artery was required.

Right hepatic trisectionectomy combined total caudate lobectomy with non-touch technique for advanced hilar cholangiocarcinoma: A surgical case report (with video).

BackgroundExtended resection such as right trisegmentectomy combined with total caudate lobectomy with non-touch technique for advanced hilar cholangiocarcinoma (CCA) is still challenging for all Hepato-pancreato-biliary surgeons.PresentationA 45-year-old female with advanced hilar CCA involved the right intrahepatic bile ducts in continuity with the left medial sectional bile duct without PV invasion had undergone right trisegmentectomy combined with total caudate lobectomy with non-touch technique. Dissection of the hepatic peduncle by Lorta-Jacob Procedure, ligation, and resection of the right hepatic artery (RHA) and the right portal vein (PV), before that determine whether portal bifurcation's tumor infiltration or not. Mobilization of the right liver lobe, ligate all the short hepatic veins from the caudal to cranial direction, as well as the right hepatic vein (RHV) and the middle hepatic vein (MHV). Complete caudate lobectomy with right–left approach. Determine hepatic parenchyma cut, left cholangiostomy to the division of the subsegments 2,3, stitch formation of the subsegments 2,3 bile duct. Determine negative upper section of the biliary tract. The operative time was 432 min, and the blood loss was 750 ml. Postoperative recovery was uneventful without any major complications but developed intra-abdominal abscess that required percutaneous drainage.DiscussionExtended resection procedures such as extend right/left trisectionectomy, hepato-pancreaticoduodenectomy (HPD) and/or combined vascular resection are only curative treatment for advanced hilar CCA. There hadn't been any reported cases describing step-by-step right trisegmentectomy combined with total caudate lobectomy with non-touch technique with clear illustrations and videos yet.ConclusionCareful preparation with preoperative biliary drainage as well as precise evaluation of the functional capacity of the future liver remnant, as well as meticulous experience of surgeons in hepatic anatomy and non-touch resection technique are key points for success in extended resection for advanced hilar CCA.

Histone chaperone FACT complex coordinates with HIF to mediate an expeditious transcription program to adapt to poorly oxygenated cancers.

Cancer cells adapt to hypoxia through HIFs (hypoxia-inducible factors), which initiate the transcription of numerous genes for cancer cell survival in the hypoxia microenvironment. In this study, we find that the FACT (facilitates chromatin transcription) complex works cooperatively with HIFs to facilitate the expeditious expression of HIF targets for hypoxia adaptation. Knockout (KO) of the FACT complex abolishes HIF-mediated transcription by impeding transcription elongation in hypoxic cancer cells. Interestingly, the FACT complex is post-translationally regulated by PHD/VHL-mediated hydroxylation and proteasomal degradation, in similar fashion to HIF-1/2α. Metabolic tracing confirms that FACT KO suppresses glycolytic flux and impairs lactate extrusion, leading to intracellular acidification and apoptosis in cancer cells. Therapeutically, hepatic artery ligation and anti-angiogenic inhibitors adversely induce intratumoral hypoxia, while co-treatment with FACT inhibitor curaxin remarkably hinders the growth of hypoxic tumors. In summary, our findings suggest that the FACT complex is a critical component of hypoxia adaptation and a therapeutic target for hypoxic tumors.