Clinical implications and mechanism of histopathological growth pattern in colorectal cancer liver metastases.

Liver is the most common site of metastases of colorectal cancer, and liver metastases present with distinct histopathological growth patterns (HGPs), including desmoplastic, pushing and replacement HGPs and two rare HGPs. HGP is a miniature of tumor-host reaction and reflects tumor biology and pathological features as well as host immune dynamics. Many studies have revealed the association of HGPs with carcinogenesis, angiogenesis, and clinical outcomes and indicates HGP functions as bond between microscopic characteristics and clinical implications. These findings make HGP a candidate marker in risk stratification and guiding treatment decision-making, and a target of imaging observation for patient screening. Of note, it is crucial to determine the underlying mechanism shaping HGP, for instance, immune infiltration and extracellular matrix remodeling in desmoplastic HGP, and aggressive characteristics and special vascularization in replacement HGP (rHGP). We highlight the importance of aggressive features, vascularization, host immune and organ structure in formation of HGP, hence propose a novel "advance under camouflage" hypothesis to explain the formation of rHGP.

Nomogram Based on Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio to Predict Recurrence in Patients with Hepatocellular Carcinoma after Radiofrequency Ablation.

OBJECTIVES: To investigate the prognostic value of pre-procedure neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and construct a nomogram to predict disease-free survival (DFS) in patients receiving radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) within Milan criteria. METHODS: The data of 515 patients of HCC within Milan criteria receiving RFA were retrospectively collected. The patients were divided into two groups: the training group (n = 382) and the validation group (n = 133). Several preprocedural variables were analyzed in the two groups to determine the prognostic factors. RESULTS: The median DFS time of the training and validation group was 28.4 months and 24.5 months, respectively. Multivariate analyses showed that number of lesions, alpha-feto protein levels, NLR and PLR were independent risk factors of DFS. According to the time-dependent receiver operating characteristic curve (t-ROC), the optimal cutoff value of the NLR and PLR was 1.55 and 75.30, respectively, with sensitivity of 0.737 and 0.648 and specificity of 0.541 and 0.508, respectively. The area under curve (AUC) of the t-ROC curves for the NLR was 0.662 and PLR was 0.597. The DFS was significantly higher in the NLR ≤ 1.55 group compared to NLR > 1.55 group and the PLR ≤ 75.30 group compared to PLR > 75.30 group in both training and validation datasets. Nomogram was developed based on the prognostic factors indicated by the Cox regression to predict 1-, 2-, 3- and 5-year DFS probabilities. CONCLUSIONS: The cutoff value of the NLR and PLR was 1.55 and 75.30. This new nomogram based on NLR and PLR may provide good and individualized prediction of recurrence for HCC patients within Milan criteria after RFA.

Hepatic arterial administration of sorafenib and iodized oil effectively attenuates tumor growth and intrahepatic metastasis in rabbit VX2 hepatocellular carcinoma model.

AIM: To investigate the therapeutic effect of the hepatic arterial administration of sorafenib in rabbit VX-2 hepatocellular carcinoma (HCC) model. METHODS: Rabbit VX-2 HCC models were established via implanting VX-2 tumors into the livers, and randomly divided into four groups, respectively treated with (1) The hepatic arterial administration of iodized oil alone (TACE-i), (2) The hepatic arterial administration of iodized oil and pharmorubicin (TACE-ip), (3) The hepatic arterial administration of iodized and cis-DDP (TACE-ic), (4) The hepatic arterial administration of iodized and sorafenib (TACE-is). The growth rate and intrahepatic metastasis of implanted VX-2 tumor in each rabbit were measured. Microvessel density (MVD) in the adjacent tissues of implanted VX-2 tumor were estimated by detecting the expression of CD34 and VEGF level in tumor adjacent tissues were also examined by Immunohistochemistry. RESULTS: Compared with other groups, TACE-is treatment group presented a better effect on inhibiting tumor growth rate and intrahepatic metastasis in rabbit VX-2 HCC model. The angiogenesis (assessed by MVD) in the adjacent tissues were suppressed more dramatically in TACE-is treated group. Moreover, TACE-is treatment did not significantly increase the levels of alanine transaminase and creatinine compared to the group with TACE-i treatment. CONCLUSION: The hepatic arterial administration of sorafenib and iodized oil (TACE-is) effectively attenuates tumor growth and intrahepatic metastasis in rabbit VX-2 HCC model without obvious hepatic and renal toxicity. One of the related mechanisms may be due to the inhibition of angiogenesis in the adjacent tissues. Our data indicated that TACE-is may be a secure and effective treatment for HCC.

Hepatocellular carcinoma associated with Budd-Chiari syndrome: imaging features and transcatheter arterial chemoembolization.

BACKGROUND: Budd-Chiari syndrome (BCS) often leads to hepatocellular carcinoma (HCC). Transcatheter arterial chemoembolization (TACE) has been increasingly used to treat BCS patients with HCC. The purposes of this study were to illustrate imaging features in BCS patients with HCC, and to analyze the effects of TACE on BCS patients with HCC. METHODS: 246 consecutive patients with primary BCS were retrospectively studied. 14 BCS patients with HCC were included in this study. BCS were treated with angioplasty and/or stenting, and HCC were managed with TACE. Imaging features on ultrasonography, CT, MRI, and angiography and the serum AFP level were analyzed. RESULTS: Inferior vena cava block and stricture of hepatic venous outflow tract more frequently occurred. Portal vein invasion was found in only 2 patients (14.2%). Imaging studies showed that most nodules of HCC were near the edge of liver, irregular, more than 3 cm in diameter, heterogeneous mass and solitary (≤3 nodules). HCC in patients associated with BCS was isointense or hypointense in nonenhanced CT images, and exhibited heterogeneous enhancement during the arterial phase and washout during the portal venous phase on enhanced CT and MRI. The serum AFP level significantly declined after TACE treatment. CONCLUSIONS: BCS patients with inferior vena cava block and stricture of hepatic venous outflow tract seems to be associated with HCC. A single, large, irregular nodule with a peripheral location appears to be HCC. TACE can effectively treat HCC in BCS patients.

Interventional embolization of giant thoracic tumors before surgical resection.

BACKGROUND: Preoperative embolization of tumors is a well-established procedure that has been successfully applied in various clinical situations. Preoperative embolization can reduce the vascularity of tumors resulting in a clearer operative field, less difficult dissection, decreased blood loss, and, in some cases, a decrease in tumor size. However, few studies have been conducted regarding the preoperative embolization of giant thoracic tumors. PURPOSE: To examine the effectiveness and safety of interventional embolization of giant thoracic tumors before surgical resection. MATERIAL AND METHODS: A total of 14 consecutive patients with giant thoracic tumors received angiography and the feeding arteries of the tumors were embolized using polyvinyl alcohol (PVA) particles and gelatin sponges 1 day before surgical resection. The patient records were retrospectively reviewed and data regarding diagnoses, embolization, and surgical resection were recorded. RESULTS: Angiography revealed the feeding arteries of the tumors to be characterized by multiple branches and thickened vessel trunks with abnormal distal branches superimposed of the tumor shadow. Embolization was successfully without complications in all patients, and all feeding vessels of each tumor were occluded. Embolization reduced the severity of bleeding during surgery and decreased the difficulty of resection of the tumor. No intraoperative or postoperative complications occurred. CONCLUSION: Interventional embolization is a safe and efficient method to facilitate the surgical resection of giant thoracic tumors.

Efficacy and safety of transcatheter chemoembolization of the internal thoracic artery in patients with hepatocellular carcinoma.

BACKGROUND: Embolization of collateral arteries is important for transcatheter hepatic arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). We evaluated the efficacy and safety of TACE, and the prevention and management of complications among patients in whom the internal thoracic artery (ITA) was involved. METHODS: A total of 3614 cases of HCC were treated with 12 645 TACEs and 211 of these cases were given ITA angiography, including 156 cases of which the ITA was involved. We performed 562 TACEs in the 156 cases. We analyzed imaging examinations, types of embolization, and the incidence, prevention, and treatment of complications. RESULTS: The ITA was successfully embolized in 156 cases. Angiography of the ITA showed that the major trunks were thickened with an increased number of branching vessels, contributing to intrahepatic and extrahepatic tumor blood supply. Different embolization methods were selected according to the blood supply, to effectively embolize the tumor and mitigate or avoid serious complications. TACE with ITA embolization extended the mean interval time between two treatments from 2.54 months (1 - 17 months) to 4.23 months (1 - 30 months) compared with that without ITA embolization. The ITA supplied the HCC in the following instances: HCC was located in the ventral hepatic area and abutted the diaphragm (P = 0.0064) and repeated TACE (P = 0.0003). The survival rate of TACE with ITA embolization for HCC was better than TACE without ITA embolization (P < 0.00001). CONCLUSIONS: In cases with massive HCC or nodular HCC, the ITA may be involved in supplying blood to the tumor. This occurs when the tumor is positioned in the ventral hepatic area and abuts the diaphragm (S2, S4, and S8), and especially if cases have a previous history of TACE. In this case series, embolization was effective, extended the mean interval time of interventional therapy, and prolonged survival time.

Acute symptomatic mesenteric venous thrombosis: treatment by catheter-directed thrombolysis with transjugular intrahepatic route.

OBJECTIVE: To assess the feasibility and effectiveness of transjugular intrahepatic route aspiration thrombectomy and catheter-directed thrombolytic therapy in patients with acute superior mesenteric venous thrombosis. MATERIALS AND METHODS: During a period of 8 years, 12 patients with acute thrombosis of the superior mesenteric vein (SMV) were treated by transjugular intrahepatic approach. The mean age was 41.2 years. After access to the portal system via the transjugular approach, the pigtail catheter fragmentation of the thrombus, local urokinase injection, and manual aspiration thrombectomy were used for treatment of the SMV thrombosis initially, followed by continuous thrombolytic therapy via an indwelling infusion catheter in the SMV, which was performed for 2 to 6 days (4.2 ± 1.8 days). The adequacy of anticoagulation was performed during treatment, throughout hospitalization, and after discharge. RESULTS: Technical success was achieved in all 12 patients. Substantial clinical improvement was seen in these patients after the procedure. Minor complications at the jugular puncture site were observed in 4 patients, but the thrombolytic therapy was not interrupted. Contrast-enhanced computed tomography (CT) scan before discharge demonstrated nearly complete disappearance of SMV thrombosis in all patients. The 12 patients were discharged 5-10 days (7.6 ± 2.0) after admission. Mean duration of follow-up after hospital discharge was 37.7 months, and no recurrent episodes of SMV thrombosis developed during that time period. CONCLUSION: Catheter-directed thrombus aspiration, mechanical fragmentation, and local thrombolytic infusion via the transjugular intrahepatic route is a safe and effective therapy for the management of patients with acute symptomatic SMV thrombosis.

Role of interventional endovascular therapy for delayed hemorrhage after pancreaticoduodenectomy.

BACKGROUND: Delayed massive hemorrhage (DMH) after pancreaticoduodenectomy (PD) is a serious complication and one of the most common causes of mortality after PD. Its ideal management remains unclear. This paper is to present our experience in the endovascular treatment of patients with DMH after PD using different techniques and materials. METHODS: During a seven years period, 19 patients (fifteen men, four women) with DMH arter PD were treated with endovascular procedures, including transcatheter arterial embolization (TAE) with coils embolization in eight cases, with coils plus N-butyl-2-cyanoacrylate (NBCA)-Lipiodol mixture in six cases, and stent-graft placement in five cases. The mean age of the patients was 58.2 years. Follow-up, including clinical condition, liver function tests, and Doppler ultrasound examinations, was documented. RESULTS: The immediate technical success rate was 84.2% (16/19). There were no significant procedure-related complications. Hemostasis was not achieved with interventional procedures in three patients: one died of uncontrolled bleeding four days after the second TAE, and two patients required emergency laparotomy without re-angiography because of worsening clinical status. Among the 16 patients with successfully stopped bleeding who became hemodynamically stable after the procedure without evidence of further bleeding, two patients died during the peri-interventional procedure period because of multiple organ failure, and fourteen patients survived to hospital discharge. The mean length of follow-up was 14.6 months. Recurrent bleeding after discharge did not occur in any of these cases. Clinical and laboratory follow-up findings were unremarkable. Doppler ultrasound examination verified patency of the hepatic artery in the four patients with stent-graft placement during the follow-up period (5 months-29 months; mean, 15.3 months). CONCLUSIONS: Interventional endovascular procedure is a safe and technically feasible solution to control DMH. The first-line treatment for the bleeding is TAE. Stent-graft placement with preservation of the organ arterial flow, if technically possible, is a valuable alternative to TAE and surgical intervention for management of DMH.

Stent-grafts placement for treatment of massive hemorrhage from ruptured hepatic artery after pancreaticoduodenectomy.

AIM: To present a series of cases with life-threatening hemorrhage from ruptured hepatic artery pseudoaneurysm after pancreaticoduodenectomy (PD) treated with placement of stent-grafts. METHODS: Massive hemorrhage from ruptured hepatic artery pseudoaneurysm after PD in 9 patients (6 men, 3 women) at the age of 23-75 years (mean 48 years), were treated with placement of percutaneous endovascular balloon-expandable coronary stent-grafts. All patients were not suitable for embolization because of a non-patent portal vein. One or more stent-grafts, ranging 3-6 mm in diameter and 16-55 mm in length, were placed to exclude ruptured pseudoaneurysm. Follow-up data, including clinical condition, liver function tests, and Doppler ultrasound examination, were recorded at the outpatient clinic. RESULTS: Immediate technical success was achieved in all the 9 patients. All stent-grafts were deployed in the intended position for immediate cessation of bleeding and preservation of satisfactory hepatic arterial blood flow. No significant procedure-related complications occurred. Recurrent bleeding occurred in 2 patients at 16 and 24 h, respectively, after placement of stent-grafts and treated with surgical revision. One patient died of sepsis 12 d after the interventional procedure. The remaining 6 patients were survived when they were discharged. The mean follow-up time was 10.5 mo (range 4-16 mo). No patient had recurrent bleeding after discharge. Doppler ultrasound examination verified the patency of hepatic artery and stent-grafts during the follow-up. CONCLUSION: Placement of stent-grafts is an effective and safe procedure for acute life-threatening hemorrhage from ruptured hepatic artery pseudoaneurysm.

Endovascular embolization of pulmonary arteriovenous malformations.

BACKGROUND: The major consequence of pulmonary arteriovenous malformations (PAVMs) is the direct inflow of blood from the pulmonary artery to the pulmonary vein which induces hypoxemia. Severe complications include transient ischemic attacks, paradoxical embolization in the central nervous system, massive hemoptysis or hemothorax, etc. The conventional treatment is surgical intervention. However, this can be very traumatic and dangerous. Endovascular embolization has advantages over surgery such as a faithful therapeutic effect, a low complication rate, repeatability, etc. METHODS: Patients (n = 23) with symptomatic PAVMs underwent endovascular embolization; 11 were males and 12 were females, with ages ranging from 6 months to 58 years. During the embolization, microcoils were applied in 6 cases and standard steel coils were used in 17 cases. RESULTS: Multiple PAVMs lesions were found in 16 cases and single PAVMs lesion was found in 7 cases. Embolotherapy was carried out 28 times for 23 patients. The success rate was 100%. The results of pulmonary arteriography after treatment showed that single lesion disappeared completely while the main abnormal vessels in multiple lesions also disappeared. The mean blood oxygen saturation increased from (78.04 + or - 8.22)% to (95.13 + or - 3.67)% after the procedure. A correlated groups t test showed changes in blood oxygen saturation before and after embolization (t = 9.101, P < 0.001). Symptoms of cardiac insufficiency disappeared in 5 cases and vascular murmur in the chest disappeared in 13 cases. After embolization, mild chest pain occurred in 11 cases, small amounts of pleural effusion occurred in 5 cases, and 1 patient died 2 months later because of a pyogenic infection secondary to the pulmonary infarction. Among the 22 remaining cases, with overall follow-up ranging from 18 months to 12 years, general conditions were fine, daily lives were normal and there were no neurologic symptoms or signs, except for 3 patients with diffused PAVMs who had persistent blood oxygen saturation between 85% and 90%. Symptoms of hypoxia never recurred in the other cases. CONCLUSIONS: Endovascular embolization of pulmonary arteriovenous malformations can significantly improve blood oxygen saturation and reduce serious complications such as cerebral infaction. Therefore, this kind of interventional procedure is a safe and effective treatment method with a low complication rate.

Interventional treatment for symptomatic acute-subacute portal and superior mesenteric vein thrombosis.

AIM: To summarize our methods and experience with interventional treatment for symptomatic acute-subacute portal vein and superior mesenteric vein thrombosis (PV-SMV) thrombosis. METHODS: Forty-six patients (30 males, 16 females, aged 17-68 years) with symptomatic acute-subacute portal and superior mesenteric vein thrombosis were accurately diagnosed with Doppler ultrasound scans, computed tomography and magnetic resonance imaging. They were treated with interventional therapy, including direct thrombolysis (26 cases through a transjugular intrahepatic portosystemic shunt; 6 through percutaneous transhepatic portal vein cannulation) and indirect thrombolysis (10 through the femoral artery to superior mesenteric artery catheterization; 4 through the radial artery to superior mesenteric artery catheterization). RESULTS: The blood reperfusion of PV-SMV was achieved completely or partially in 34 patients 3-13 d after thrombolysis. In 11 patients there was no PV-SMV blood reperfusion but the number of collateral vessels increased significantly. Symptoms in these 45 patients were improved dramatically without severe operational complications. In 1 patient, the thrombi did not respond to the interventional treatment and resulted in intestinal necrosis, which required surgical treatment. In 3 patients with interventional treatment, thrombi re-formed 1, 3 and 4 mo after treatment. In these 3 patients, indirect PV-SMV thrombolysis was performed again and was successful. CONCLUSION: Interventional treatment, including direct or indirect PV-SMV thrombolysis, is a safe and effective method for patients with symptomatic acute-subacute PV-SMV thrombosis.

Emergency intervention therapy for renal vascular injury.

OBJECTIVE: To evaluate the efficacy and safety of the interventional techniques in the treatment of renal vascular injury. METHODS: A total of 16 patients with renal vascular injuries were treated by superselective arterial embolization. The renal injuries resulted from renal biopsy in 7 patients, endovascular intervention in 2, percutaneous puncture and pyelostomy in 2, local resection of renal tumor in 1 and trauma in 4. With regards to clinical manifestations, there was hemorrhagic shock in 8 patients, severe flank pain in 14, and hematuria in 14. CT and ultrasonography confirmed that 15 patients had perirenal hematoma. The embolization was performed with microcoils in 13 and standard stainless steel coils in 3 patients, associated with polyvinyl alcohol particles (PVA) in 9, and gelfoam particles in 6 cases. RESULTS: Renal angiogram revealed arteriovenous fistula in renal parenchyma in 9 cases, pseudoaneurysm in 3 and extravasation of contrast media in 4. The arterial embolization was successful in all 16 cases in a single session. The angiography at the end of therapy showed that abnormal vessels had disappeared without other major intrarenal arterial branch occlusion. In 13 patients with hemodynamical compromise, blood loss-related symptoms were immediately relieved after blood transfusion. In 14 patients with severe flank pain, the pain was progressively relieved. Hematuria ceased in 14 patients 2-14 days after the embolization procedures. The renal function was impaired after the procedure in 6 cases, in which preoperative renal insufficiency was exacerbated in 3 and developed new renal dysfunction in 3, 2 of whom received hemodialysis. The ultrasonography showed that perirenal hematoma was gradually absorbed within 2-6 months after the procedure. All patients were followed up in 6-78 months (mean, 48 months). Six patients died of primary diseases (5 cases of renal failure and multiple organ failure and 1 case of malignant tumor). Ten patients survived without bleeding and further intervention. The deterioration of renal function did not occur and the serum creatinine and blood urea were in normal range. CONCLUSION: Transcatheter selective renal arterial embolization is a safe and effective method in the treatment of renal vascular injuries.

Supplementary inferior phrenic artery embolization in the interventional treatment of hemoptysis.

BACKGROUND: Transcatheter bronchial artery embolization (BAE) is widely used for the treatment of hemoptysis and the immediate success rate is high, but there are still some hemorrhage recurrences. One of the common reasons for failure of BAE is collateral branches as blood supply. The inferior phrenic artery (IPA) is one of the most common collateral branches that is scarcely reported. Our purpose was to observe manifestations of IPA supplying to hemoptysis and evaluate the efficacy and safety of IPA embolization. METHODS: Angiography during interventional treatment of 178 hemoptysis patients in the past 7 years confirmed that IPA hemorrhage resulted in hemoptysis in 25 patients (26 - 67 years old) who had: lung cancer (11 patients), bronchiectasis (11 patients), chronic lung inflammation (2 patients), and pulmonary tuberculosis (1 patient). Among the 25 patients, 7 patients had twice interventional operations within one week and 6 patients still experienced intraoperative hemoptysis after conventional embolization of the bronchial artery, the internal thoracic artery, and the intercostal artery, then had the second interventional operation immediately. The total number of cases were 191. Selective embolization of the IPA was performed using polyvinyl alcohol microspheres, gelatin sponge particles, and microcoil. The safety and clinical significance of IPA embolization were evaluated. The Pearson chi(2) test and Fisher's exact probability test were used in this study. RESULTS: Selective IPA angiography showed increased diameter of the IPA, disorganization of the branches, and varying degrees of angiogenesis. In 11 cases, contrast material was seen in vessels supplying the tumor and in the tumor. In 9 cases, contrast material had leaked into the area supplied by the IPA; in 8 cases, non-specific flake-like deposits of contrast material were seen; and in 14 cases, abnormal communication or shunt was visualized. Lesions were closely related to the pleura in 25 patients. Fifteen lesions were close to the diaphragmatic pleura, seven close to the mediastinal pleura, and three close to the lateral pleura of the lower lung. Eleven cases had inferior thoracic pleural thickening and adhesions. The IPA was embolized in 25 cases, and the success rate of hemostasis was 100%. The IPA was not embolized in the other 166 cases, and the success rate of hemostasis was 92.17 %. In the 25 cases with IPA embolization, the involvement of the IPA in the blood supply of the hemoptysis was correlated with the duration of the disease (P = 0.0344). The involvement of IPA in the blood supply of the hemoptysis was not correlated with the characteristic of the lung lesions (benign or malignant) (P = 1.0000). Duration of follow-up was 8 months to 5 years. Hemoptysis recurred in four patients 1, 2, 3, and 6 months after interventional operation, respectively, and was controlled by conservative treatment. Twenty-one patients had no recurrence of hemoptysis. CONCLUSIONS: Bleeding from the IPA can result in hemoptysis and failure of BAE in the treatment of hemoptysis. If IPA hemorrhage contributes to hemoptysis, supplementary IPA embolization may be a safe and effective treatment.

[Clinical application of the three-dimensional CT of the flat-panel digital subtraction angiography system].

OBJECTIVE: To evaluate the clinical value of the three-dimensional (3D) CT module of the flat-panel digital subtraction angiography (DSA) system. METHODS: A retrospective analysis was conducted among 278 patients receiving examination with rotational 3D-CT of INNOVA 3100 flat-panel DSA system. AW4.3-04 workstation was used to perform the 3D reconstruction and INNOVA CT reconstruction, and the imaging data were analyzed in comparison with the clinical results. RESULTS: The 3D-CT of the flat panel DSA system displayed the conditions of cerebral aneurysms in 54 cases, cerebral arteriovenous malformation in 25 cases, and the intracranial conditions in 24 cases. The blood supply and tumor vessels were clearly displayed in 57 cases, and the effects of embolization and endovascular stenting were evaluated in 27 and 21 cases, respectively. The rotational 3D-CT was used to evaluate complete embolization in 24 cases, and failed to display the feeding arteries of small tumors in 11 cases. The vascular lesions, biliary tract lesions, and the occurrence of hemorrhage during interventional therapy were observed in 58, 5 and 25 cases, respectively. CONCLUSION: The 3D-CT module of the flat-panel DSA system can easily display abnormal vascular lesions and provide comprehensive anatomical information to facilitate interventional therapies and complication monitoring.