Vascular invasion in pancreatic cancer:Imaging modalities,preoperative diagnosis and surgical management

Pancreatic cancer is associated with a poor prognosis,and surgical resection remains the only chance for curative therapy.In the absence of metastatic disease,which would preclude resection,assessment of vascular invasion is an important parameter for determining resectability of pancreatic cancer.A frequent error is to misdiagnose an involved major vessel.Obviously,surgical exploration with pathological examination remains the"gold standard"in terms of evaluation of resectability,especially from the point of view of vascular involvement.However,current imaging modalities have improved and allow detection of vascular invasion with more accuracy.A venous resection in pancreatic cancer is a feasible technique and relatively reliable.Nevertheless,a survival benefit is not achieved by curative resection in patients with pancreatic cancer and vascular invasion.Although the discovery of an arterial invasion during the operation might require an aggressive management,discovery before the operation should be considered as a contraindication.Detection of vascular invasion remains one of the most important challenges in pancreatic surgery.The aim of this article is to provide a complete review of the different imaging modalities in the detection of vascular invasion in pancreatic cancer.

Relationship between vascular invasion and microvessel density and micrometastasis

AIM： To evaluate the relationship between vascular invasion and microvessel density （MVD） of tissue and micrometastasis in blood. METHODS： Vascular invasion was detected by both hematoxylin and eosin staining and immunohistochemiscal staining. Blood samples were collected from 17 patients with vascular invasion and 29 patients without vascular invasion and examined for cytokeratin20 （CK20） expression by reverse transcriptase-polymerase chain reaction （RT-PCR） analysis. Microvessel density of tissue samples was also determined by immunohistochemistry using antibodies to CD105. RESULTS： CK20 was detected in 12 of the 17 patients with vascular invasion and in 9 of the 29 patients without vascular invasion. Positive RT-PCR was significantly correlated with vascular invasion （70.6% vs 30.0%, P 〈 0.05）. The average MVD was significantly higher in patients with positive vascular invasion than in patients with negative vascular invasion （29.2 ± 3.3 vs 25.4 ± 4.7, P 〈 0.05）. The vascular invasion detected with hematoxylin-eosin staining was less than that with immunohistochemical staining. There was a significant difference between the two staining methods （19.6% vs 36.9%, P 〈 0.05）. CONCLUSION： Positive CK20 RT-PCR, depth of tumor invasion, lymph node status, metastasis and MVD are significantly correlated with vascular invasion. Immunohistochemical staining is more sensitive than hematoxylin-eosin staining for detecting vascular invasion.

Vascular Invasion as An Independent Prognostic Indicator in Radically Resected Non-small Cell Lung Cancer

Objective： A retrospective study was performed to analyze the impact of vascular invasion on prognosis in a series of radically resected non-small cell lung cancer （NSCLC） and the subgroup of T1-4 nodal negative NSCLC patients. Methods： A total of 259 NSCLC patients who had undergone radical resection were entered into this study. Detailed clinical data including five-year survival were obtained for all the patients. The tumors were reviewed for the presence or absence of vascular invasion. Fisher＇s exact tests were used to assess the relationship between vascular invasion and other clinicopathological variables. Survival time was defined as the interval from the date of operation to either death from lung cancer or the last follow-up. Univariate analysis of survival curve was performed by the Kaplan-Meier method using the Log rank test. Multivariate survival analysis was carried out by Cox regression. P〈0.05 was considered statistically significant. Results： In 259 patients, 33 cases were diagnosed as having vascular invasion. The overall 5-year survival was 37.5%. Patients with vascular invasion had a median survival of 20 months compared with 43 months for those without vascular invasion （P〈0.01）. Multivariate analysis indicated that vascular invasion was a significant independent prognostic predictor for shortened cancer-related survival in the patients. The relative risk for cancer-related survival was 2.2-fold greater in patients with vascular invasion （95% CI： 1.45-3.32）. Subgroup analysis revealed that patients with vascular invasion had a 5-year survival of 11.1% compared with 57.1% for those without vascular invasion in the resected lung cancer patients at T1-4N0M0 （P=0.002）. Conclusion： Vascular invasion can serve as an independent prognostic factor in radically resected NSCLC.

Predictive value of tumor markers in patients with recurrent hepatocellular carcinoma in different vascular invasion pattern

BACKGROUND： Four tumor markers for hepatocellular carcinoma（HCC）, alpha-fetoprotein（AFP）, glypican-3（GPC3）, vascular endothelial growth factor（VEGF） and des-gammacarboxy prothrombin（DCP）, are closely associated with tumor invasion and patient＇s survival. This study estimated the predictability of preoperative tumor marker levels along with pathological parameters on HCC recurrence after hepatectomy.METHODS： A total of 140 patients with HCC who underwent hepatectomy between January 2012 and August 2012 were enrolled. The demographics, clinical and follow-up data were collected and analyzed. The patients were divided into two groups： patients with macroscopic vascular invasion（Ma VI ＋） and those without Ma VI（Ma VI-）. The predictive value of tumor markers and clinical parameters were evaluated by univariate and multivariate analysis.RESULTS： In all patients, tumor size（〉8 cm） and Ma VI were closely related to HCC recurrence after hepatectomy. For Ma VI＋ patients, VEGF（〉900 pg/m L） was a significant predictor for recurrence（RR=2.421; 95% CI： 1.272-4.606; P=0.007）. The 1- and 2-year tumor-free survival rates for Ma VI＋ patients with VEGF ≤900 pg/m L versus for those with VEGF 〉900 pg/m L were 51.5% and 17.6% versus 19.0% and 4.8%（P〈0.001）. For Ma VI- patients, DCP 〉445 m Au/m L and tumor size 〉8 cm were two independent risk factors for tumor recurrence（RR=2.307, 95% CI： 1.132-4.703, P=0.021; RR=3.150, 95% CI： 1.392-7.127, P=0.006; respectively）. The 1- and 2-year tumor-free survival rates for the patients with DCP ≤445 m Au/m L and those with DCP 〉445 m Au/m L were 90.4% and 70.7% versus 73.2% and 50.5% respectively（P=0.048）. The 1-and 2-year tumor-free survival rates for the patients with tumor size ≤8 cm and 〉8 cm were 83.2% and 62.1% versus 50.0% and 30.0%, respectively（P=0.003）.CONCLUSIONS： The Ma VI＋ patients with VEGF ≤900 pg/m L had a relatively high tumor-free survival than those with VEGF 〉900 pg/m L. In the Ma VI- patients, DCP 〉445 m Au/m L and tumor size 〉8 cm were predictive factors for postoperative recurrence.

Grading severity of microscopic vascular invasion was independently associated with recurrence and survival following hepatectomy for solitary hepatocellular carcinoma

Background:Hepatectomy is the preferred treatment for solitary hepatocellular carcinoma(HCC)without macrovascular invasion and distant metastasis,but long-term survival remains unsatisfactory in certain patients.We sought to identify whether the grading severity of microscopic vascular invasion(MVI)was associated with recurrence and survival among patients with solitary HCC.Methods:Consecutive patients who underwent hepatectomy for solitary HCC were identified from a multicenter prospectively-collected database.Patients were categorized into three groups according to the MVI grading system proposed by the Liver Cancer Pathology Group of China:M0(no MVI),M1(1-5 sites of MVI occurring≤1.0 cm away from the tumor),and M2(>5 sites occurring≤1.0 cm or any site occurring>1 cm away from the tumor).Recurrence-free survival(RFS)and overall survival(OS)were compared among the groups.Results:Among 227 patients,97(42.7%),83(36.6%),and 47(20.7%)patients had M0,M1,and M2,respectively.Median RFS rates among patients with M0,M1,and M2 were 38.3,35.1,11.6 months,respectively,while OS rates were 66.8,62.3,30.6 months,respectively(both P<0.001).Multivariate Cox-regression analyses demonstrated that both M1 and M2 were independent risk factors for RFS(hazard ratio 1.20,95%CI:1.03-1.89,P=0.040;and hazard ratio 1.67,95%CI:1.06-2.64,P=0.027)and OS(hazard ratio 1.28,95%CI:1.05-2.07,P=0.035;and hazard ratio 1.97,95%CI:1.15-3.38,P=0.013).Conclusions:Grading severity of MVI was independently associated with RFS and OS after hepatectomy for solitary HCC.Enhanced surveillance for recurrence and potentially adjuvant therapy may be considered for patients with MVI,especially individuals with more severe MVI grading(M2).

Energy spectrum computed tomography multi-parameter imaging in preoperative assessment of vascular and neuroinvasive status in gastric cancer

BACKGROUND Vascular and nerve infiltration are important indicators for the progression and prognosis of gastric cancer(GC),but traditional imaging methods have some limitations in preoperative evaluation.In recent years,energy spectrum computed tomography(CT)multiparameter imaging technology has been gradually applied in clinical practice because of its advantages in tissue contrast and lesion detail display.AIM To explore and analyze the value of multiparameter energy spectrum CT imaging in the preoperative assessment of vascular invasion(LVI)and nerve invasion(PNI)in GC patients.METHODS Data from 62 patients with GC confirmed by pathology and accompanied by energy spectrum CT scanning at our hospital between September 2022 and September 2023,including 46 males and 16 females aged 36-71(57.5±9.1)years,were retrospectively collected.The patients were divided into a positive group(42 patients)and a negative group(20 patients)according to the presence of LVI/PNI.The CT values(CT40 keV,CT70 keV),iodine concentration(IC),and normalized IC(NIC)of lesions in the upper energy spectrum CT images of the arterial phase,venous phase,and delayed phase 40 and 70 keV were measured,and the slopes of the energy spectrum curves[K(40-70)]from 40 to 70 keV were calculated.Arterial Core Tip:To investigate the application value of multiparameter energy spectrum computed tomography(CT)imaging in the preoperative assessment of vascular and nerve infiltration in patients with gastric cancer(GC).The imaging data of GC patients were retrospectively analyzed to evaluate the accuracy and sensitivity of CT for identifying and quantifying vascular and nerve infiltration and for comparison with postoperative pathological results.The purpose of this study was to verify the clinical feasibility and potential advantages of multiparameter energy spectrum CT imaging in guiding preoperative diagnosis and treatment decision-making and to provide a new imaging basis for improving the diagnostic accuracy and prognosis of GC patients.

Prognostic significance of Borrmann type combined with vessel invasion status in advanced gastric cancer

BACKGROUND Borrmann classification(types I-IV)for the detection of advanced gastric cancer has been accepted worldwide,and lymphatic and/or blood vessel invasion(LBVI)status is related to the poor prognosis after gastric cancer.AIM To evaluate the significance of Borrmann type combined with LBVI status in predicting the prognosis of advanced gastric cancer.METHODS We retrospectively studied the clinicopathological characteristics and long-term survival data of 2604 patients who were diagnosed with advanced gastric adenocarcinoma at Harbin Medical University Cancer Hospital from January 2009 to December 2013.Categorical variables were evaluated by the Pearson’sχ^2 test,the Kaplan-Meier method was used to identify differences in cumulative survival rates,and the Cox proportional hazards model was used for multivariate prognostic analysis.RESULTS A total of 2604 patients were included in this study.The presence of LVBI[LBVI(+)]and Borrmann type(P=0.001),tumor location(P<0.001),tumor size(P<0.001),histological type(P<0.001),tumor invasion depth(P<0.001),number of metastatic lymph nodes(P<0.001),and surgical method(P<0.001)were significantly correlated with survival.When analyzing the combination of the Borrmann classification and LBVI status,we found that patients with Borrmann type Ⅲ disease and LBVI(+)had a similar 5-year survival rate to those with Borrmann IV+LBVI(-)(16.4%vs 13.1%,P=0.065)and those with Borrmann IV+LBVI(+)(16.4%vs 11.2%,P=0.112).Subgroup analysis showed that the above results were true for any pT stage and any tumor location.Multivariate Cox regression analysis showed that Borrmann classification(P=0.023),vascular infiltration(P<0.001),tumor size(P=0.012),pT stage(P<0.001),pN stage(P<0.001),and extent of radical surgery(P<0.001)were independent prognostic factors for survival.CONCLUSION Since patients with Borrmann Ⅲ disease and LBVI(+)have the same poor prognosis as those with Borrmann IV disease,more attention should be paid to patients with Borrmann Ⅲ disease and LBVI(+)during diagnosis and treatment,regardless of the pT stage and tumor location,to obtain better survival results.

Scientific Hepatectomy for Hepatocellular Carcinoma

With advances in imaging technology and surgical instruments,hepatectomy can be perfectly performed with technical precision for hepatocellular carcinoma(HCC).However,the 5-year tumor recurrence rates remain greater than 70%.Thus,the strategy for hepatectomy needs to be reappraised based on insights of scientific advances.Scientific evidence has suggested that the main causes of recurrence after hepatectomy for HCC are mainly related to underlying cirrhosis and the vascular spread of tumor cells that basically cannot be eradicated by hepatectomy.Liver transplantation and systemic therapy could be the solution to prevent postoperative recurrence in this regard.Therefore,determining the severity of liver cirrhosis for choosing the appropriate surgical modality,such as liver transplantation or hepatectomy,for HCC and integrating newly emerging immune-related adjuvant and/or neoadjuvant therapy into the strategy of hepatectomy for HCC have become new aspects of exploration to optimize the strategy of hepatectomy.In this new area,hepatectomy for HCC has evolved from a pure technical concept emphasizing anatomic resection into a scientific concept embracing technical considerations and scientific advances in underlying liver cirrhosis,vascular invasion,and systemic therapy.By introducing the concept of scientific hepatectomy,the indications,timing,and surgical techniques of hepatectomy will be further scientifically optimized for individual patients,and recurrence rates will be decreased and long-term survival will be further prolonged.

A comparison of survival and pathologic features of non-alcoholic steatohepatitis and hepatitis C virus patients with hepatocellular carcinoma

AIM： To compare the clinical outcome and pathologic features of non-alcoholic steatohepatitis （NASH） patients with hepatocellular carcinoma （HCC） and hepatitic C virus （HCV） patients with HCC （another group in which HCC is commonly seen） undergoing liver transplantation. METHODS： Patients transplanted for HCV and NASH at our institution from January 2000 to April 2011 were analyzed. All explanted liver histology and pre-trans- plant liver biopsies were examined by two specialist liver histopathologists. Patient demographics, disease free survival, explant liver characteristics and HCC features （tumour number, cumulative tumour size, vascular invasion and differentiation） were compared between HCV and NASH liver transplant recipients. RESULTS： A total of 102 patients with NA^SH and 283 patients with HCV were transplanted. The incidence of HCC in NASH transplant recipients was 16.7% （17/102）. The incidence of HCC in HCV transplant recipients was 22.6% （64/283）. Patients with NASH-HCC were statisti- cally older than HCV-HCC patients （P 〈 0.001）. A signif- icantly higher proportion of HCV-HCC patients had vas- cular invasion （23.4% vs 6.4%, P = 0.002） and poorly differentiated HCC （4.7% vs 0%, P 〈 0.001） compared to the NASH-HCC group. A trend of poorer recurrence free survival at 5 years was seen in HCV-HCC patients compared to NASH-HCC who underwent a Liver trans- plantation （P = 0.11）. CONCLUSION： Patients transplanted for NASH-HCC appear to have less aggressive turnout features com- pared to those with HCV-HCC, which likely in part ac- counts for their improved recurrence free survival.

Des-gamma-carboxy prothrombin as an important prognostic indicator in patients with small hepatocellular carcinoma

AIM:To clarify the effect of a high des-gamma-carboxy prothrombin (DCP) level on the invasiveness and prognosis of small hepatocellular carcinoma. METHODS: Among 142 consecutive patients with known DCP levels, who underwent hepatectomy because of hepatocellular carcinoma, 85 patients met the criteria for small hepatocellular carcinoma, i.e. one ≤ 5 cm sized single tumor or no more than three ≤ 3 cm sized tumors. RESULTS: The overall survival rate of the 142 patients was 92.1% for 1 year, 69.6% for 3 years, and 56.9% for 5 years. Multivariate analysis showed that microscopic vascular invasion (P = 0.03) and serum DCP ≥ 400 mAU/mL (P = 0.02) were independent prognostic factors. In the group of patients who met the criteria for small hepatocellular carcinoma, DCP ≥ 400 mAU/mL was found to be an independent prognostic factor for recurrence-free (P = 0.02) and overall survival (P = 0.0005). In patients who did not meet the criteria, the presence of vascular invasion was an independent factor for recurrence-free (P = 0.02) and overall survivals (P = 0.01). In 75% of patients with small hepatocellular carcinoma and high DCP levels, recurrence occurred extrahepatically. CONCLUSION: For small hepatocellular carcinoma, a high preoperative DCP level appears indicative fortumor recurrence. Because many patients with a high preoperative DCP level develop extrahepatic recurrence, it is necessary to screen the whole body.

A preliminary study on correlations of triple-phase multi-slice CT scan with histological differentiation and intratumoral microvascular/lymphatic invasion in gastric cancer

Background Many studies have shown that cancer cell differentiation and microvascular invasion play a principle role in cancer progression and metastasis, and non-invasive imaging techniques such as CT, MRI and US assessing the differentiation and the surgical resectibility and the prognosis of cancers are now of great importance. This study aimed to explore the correlation of triple-phase multi-slice CT scan with the histological differentiation and intratumor microvascular/lymphatic invasion of progressive gastric cancer.Methods The present study included 64 patients with gastric cancer, all of whom underwent routinal and dual-phase contrast enhancement multi-slice CT examinations of the upper abdomen before surgery. The post-operative specimens were used for determination of histological differentiation, cancer cell invasion of intratumoral microvascular/lyrnphatic vessel identified by CD34 and D2-40 expression. Correlations between contrast enhancement ratio （CER） of triple-phase multi-slice CT scan in gastric cancer and histological differentiation as well as intraturnoral microvascular/lymphatic invasion were compared and analyzed.Results There was a significant correlation between CER of triple-phase CT scan in gastric cancer and tumor histological differentiation （P〈0.05）. CER of the arterial phase in gastric cancer with intratumoral microvascular invasion was significantly higher than that without invasion （0.61±0.28 vs. 0.46±0.14, P 〈0.05）; CER of the arterial-parenchymal phase was significantly lower in gastric cancer with intratumoral microvascular invasion than that without invasion （1.81±0.39 vs. 2.28±0.80, P〈0.05）. However, CER of the parenchymal phase in gastric cancer with intratumoral lymphatic invasion was significantly higher than that without invasion （1.25±0.57 vs. 1.00±0.35, P〈0.05）.Conclusions CER of triple-phase multi-slice CT scan in gastric cancer is closely correlated with intratumoral microvascular and lymphatic invasion, and also could be used as a marker for histological differentiation.

Treatment for hepatocellular carcinoma with tumor thrombosis in the hepatic vein or inferior vena cava:A comprehensive review

Hepatocellular carcinoma(HCC)is the most common type of liver cancer with a high mortality rate worldwide.The percentage of HCC patients with vascular invasion is high.However,tumor thrombus in the hepatic vein(HVTT)has a lower incidence than tumor thrombus in the portal vein(PVTT).Conventionally,HCC patients with HVTT are treated the same as HCC patients with PVTT and offered sorafenib or other systemic agents.However,according to recent studies,it is evident that HCC with HVTT shows different outcomes when classified into different subgroups.In this review,we discuss the recent progress and changes in treatment of HCC with HVTT.