Presence Of Vessel Invasion Research Articles

Vessel invasion as a predictive factor for recurrence after surgery in stage I lung adenocarcinoma.

Patients with early-stage lung cancer who underwent R0 resection often encounter disease recurrence, especially during the early phase; thus, it is deemed vital to determine the predictive factors for recurrence after surgery. In this study, we aimed to identify the independent variables associated with recurrence after complete surgical resection of pathological stage I lung adenocarcinoma. We retrospectively reviewed the medical records of 169 patients who underwent pulmonary resection for primary lung adenocarcinoma pathological stage I with curative intent lung cancer surgery from 2015 to December 2018at our institution for information on the recurrence of the disease. Per the multivariate analysis, the presence of micropapillary pattern and vessel invasion were found to be independent predictors of disease recurrence after surgery (odds ratio [OR]: 9.36, 95% confidence interval [CI]: 2.42-36.2, P=0.0012; and OR: 4.50, 95% CI: 1.52-13.4, P=0.0068, respectively). Vessel invasion was also found to be an independent predictor of disease recurrence after surgery within a year (OR 11.4, 95% CI 3.08-42.5, P=0.0003). The presence of vessel invasion may help in distinguishing patients with the highest risk of early-phase disease recurrence after surgery. Patients with stage I adenocarcinoma with vessel invasion should undergo intensive surveillance after surgery.

Chemoradiotherapy Is Inferior to Chemotherapy Alone in Adjuvant Setting for Signet Ring Cell Containing Gastric Cancer.

BackgroundSignet ring cell containing gastric cancer (SRCGC) is a rare subtype of gastric cancer, and its adjuvant therapy is based on general gastric cancer. However, the effectiveness of radiotherapy for those SRCGC patients remains unknown.PurposeThe purpose of the study was to analyze whether the addition of radiotherapy to adjuvant chemotherapy (CT) can benefit survival in resected SRCGC patients.MethodsPatients with SRCGC, who underwent D2 gastrectomy followed by adjuvant chemotherapy or chemoradiotherapy (CRT), were retrospectively collected. According to the proportion of signet ring cells, patients were histologically classified as pure SRCGC (pSRCGC) containing 100% of signet ring cells, mixed SRCGC (mSRCGC) containing >50% of signet ring cells, and contaminated SRCGC (cSRCGC) containing <50% of signet ring cells. Among the 272 patients, 156 were treated by CT alone and 116 by CRT. The primary endpoint was 3-year overall survival rate (3-year OS rate).ResultsWith a median follow-up of 80.5 months, the 3-year OS rate was significantly higher in the CT group (70.5% vs. 58.6%, HR = 0.633, P = 0.017) compared with CRT group. Three independent characteristics were predictive of a poor overall survival: CRT treatment (P = 0.019), tumor size ≥5 cm (P < 0.001), and the presence of vessel invasion (P = 0.009). Subgroup analyses showed CRT significantly impaired prognosis in SRCGC patients in the cSRCGC subset, as well as lesions located in lower-middle sites, subtotal gastrectomy, male, <60 year, and no vessel invasion. Peritoneal was the most common recurrence site in SRCGC patients. The adverse events leukopenia and neutropenia were more common in the CRT group (P = 0.007).ConclusionsAdjuvant chemoradiotherapy was associated with poor survival compared with adjuvant chemotherapy in SRCGC patients with D2 gastrectomy.

A Positive Correlation Between the EZH2 and PD-L1 Expression in Resected Lung Adenocarcinomas

Enhancer of zeste homolog 2 (EZH2) is reported to be involved in lung cancer pathogenesis via the epigenetic regulation of various genes. Recently, EZH2 was shown to control mechanisms of adaptive resistance to immunotherapy in melanoma; however, the association between EZH2 and programmed death-ligand 1 (PD-L1), which reflects the tumor microenvironment, remains poorly understood. A total of 428 patients with resected lung adenocarcinoma were analyzed for their EZH2 and PD-L1 expression by immunohistochemistry and evaluated to determine the association between the EZH2 and PD-L1 expression. Among 428 patients, the EZH2 expression was identified in 219 (51.2%) patients, while the PD-L1 expression was observed in 88 (20.6%) patients. The recurrence-free and overall survival were significantly shorter in patients with the EZH2 expression than in those without it. A multivariate analysis showed that EZH2 remained an independent prognosticator for recurrence-free and overall survival. Patients with theEZH2-positive lung adenocarcinoma exhibited a significantly higher expression of PD-L1 than did those without it. A logistic regression analysis with backward elimination revealed that the presence of lymphatic andvessel invasion and PD-L1 positivity were independently associated with the EZH2 expression, while age over 70 years, the presence of vessel invasion, wild-type epidermal growth factor receptor, and EZH2 positivity were significantly associated with the PD-L1 expression. EZH2-expressing lung adenocarcinomas were shown to express the PD-L1 protein more frequently than were nonexpressing lesions. This study provides the first evidence of a possible association between the EZH2 and PD-L1 expression in patients with resected lung adenocarcinoma.

Soluble human leukocyte antigen‐G expression in hepatitis B virus infection and hepatocellular carcinoma

We investigated soluble human leukocyte antigen-G (sHLA-G) expression according to the phases of hepatitis B virus (HBV) infections and hepatocellular carcinoma (HCC). A total of 267 sera from anti-HBs positive healthy individuals (n = 50), chronic HBV carriers (n = 45), as well as patients with active hepatitis B (n = 46), liver cirrhosis (LC, n = 46) and early stage HCC (n = 80) were collected and assayed for sHLA-G. Relationships between sHLA-G levels and clinicopathologic parameters including HCC stages, differentiation grades, and levels of aminotransferases, HBV DNA and alpha-fetoprotein (AFP) were assessed. Concentrations of sHLA-G were higher in the active hepatitis B and HCC groups (median sHLA-G 53.7 and 178.8 U/ml, respectively) in comparison to other groups (P < 0.05), and there were no significant differences among sHLA-G levels of the anti-HBs positive, chronic HBV carrier and LC groups. Serum sHLA-G concentrations were not shown to be associated with clinicopathologic indices including the levels of aminotransferases, AFP, anti-HBs titer, HBV DNA, as well as HCC stages, numbers of tumor nodules, pathologic grades and presence of vessel invasion. The receiver-operating characteristic area under the curve (AUC) value of sHLA-G for differentiating HCC from LC was 0.98, which was greater than that of AFP (0.78) (P < 0.0001), and sensitivity and specificity of sHLA-G were, respectively, 90.0% and 95.7% for HCC when applying a cutoff level of 97.3 U/ml. Serum sHLA-G levels could be used as a diagnostic marker for HCC. Although sHLA-G levels did not reflect the severity of HBV infections and HCC, they were related with phases of the disease.

Expression of matrix metalloproteinase-2 and insulin-like growth factor-1 in gastric carcinoma and their clinicopathological significance

To investigate the expression of matrix metalloproteinase-2 (MMP-2) and insulin-like growth factor-1 (IGF-1) in gastric carcinoma and their clinicopathological significance. Expressions of MMP-2 and IGF-1 were examined by using immunohistochemical SP staining and cross-compared with clinicopathological features of gastric carcinoma. High expression of MMP-2 and IGF-1 were observed in 70.4% (307/436) and 49.5% (216/436) of gastric carcinoma tissues respectively, significantly higher than those in non-tumor gastric mucosa (3.3% and 5.4%, respectively; all P < 0.05). The high expression rate of MMP-2 and IGF-1 were significantly associated with the patient age, tumor size, tumor location, Lauren classification, TNM staging, depth of tumor infiltration, presence of vessel invasion, lymph node and distant metastasis (all P < 0.05). In addition, the expression of MMP-2 was positively linked with the expression level of IGF-1 (P < 0.05). Univariate analysis showed that high expression of MMP-2, was significantly associated with poor prognosis of tumor of TNM stage I and II (all P < 0.05), high expression of IGF-1 was significantly correlated with poor prognosis of patients with TNM stage I, II and III tumor (all P < 0.05). Cox multivariate analysis indicated that the high expressions of MMP-2 and IGF-1 could be independent prognostic indices for gastric carcinoma. High expression of MMP-2 and IGF-1 proteins are significantly correlated with the invasion and metastasis of gastric carcinoma, it is helpful to simultaneously detect the expressions of MMP-2 and IGF-1 proteins in predicting prognosis of patients with gastric carcinoma.

Accuracy and prognostic impact of a vessel invasion grading system for stage IA non-small cell lung cancer

Background Despite the recognition that lymphatic and blood vessel invasion is an important prognostic factor in lung cancer, there is no common definition for pathological evaluation of vessel invasion. The aim of the present study was to determine whether D2-40 immunostaining can increase the accuracy of detection of lymphatic vessel invasion and whether our new grading system of vessel invasion by “degree” could be used instead of conventional evaluation by “presence” for pathological stage IA non-small cell lung cancer (NSCLC). Methods The vessel invasion classification was re-evaluated in 221 recent paraffin-embedded sections of p-stage IA NSCLC stained by Hematoxylin-Eosin (HE), Elastica-Van-Gieson (EVG), and D2-40. Results After re-assessment using D2-40 immunostaining, 41.2% (31 of 75) of ly1 cases by HE/EVG changed to ly0, and 14.9% (17 of 114) of ly0 cases by HE/EVG changed to ly1. Overall, 4 of 28 ly2 cases on conventional staining were changed to ly1, and 2 were changed to ly0 using D2-40 immunostaining. When the patients were divided into two groups by the presence of vessel invasion (v/ly0 vs. 1, 2, 3), there was no significant difference in cancer-specific survival ( p = 0.1107, 0.0875, respectively), while when they were divided according to degree of vessel invasion (v/ly0, 1 vs. 2, 3), there was a statistically significant difference ( p = 0.0038, p = 0.0002, respectively). On multivariate analysis, lymphatic vessel invasion had a significant impact on cancer-specific survival ( p = 0.0061). Conclusion Our results suggest that D2-40 immunostaining provides a precise diagnosis of lymphatic vessel invasion, and our new grading system of vessel invasion by “degree” is accurate and has prognostic value in early lung cancer.

Upstaging by Vessel Invasion Improves the Pathology Staging System of Non-Small Cell Lung Cancer

There is a need for a more complete classification system of lung cancer. To address this issue, we assessed whether the new staging could differentiate patients with early-stage cancers who have poorer prognosis and improve the unbalanced patient numbers with overlapping prognoses arising from the current TNM staging system. The study included 995 patients with pathology stages I and II non-small cell lung cancer (NSCLC) who underwent surgical resection at two institutions. We subclassified patients with stage IA and IB NSCLC based on the presence of vessel invasion (Vi). Stage IA Vi and stage IB non-Vi were combined into new stage IB, as were stages IB Vi and IIA into new stage IIA. The numbers of patients of stages IA, IB, IIA, and IIB were 477, 314, 55, and 149, and their 5-year survival rates were 86.0%, 66.2%, 60.7%, and 50.4%, respectively. Vi groups showed significantly poorer prognosis than non-Vi groups at stage IA (p = 0.011) and at stage IB (p = 0.036). The numbers of patients of new stages IA, IB, and IIA were 333, 260, and 253, and their 5-year survival rates were 88.7%, 76.4%, and 61.2%, respectively. Regression analysis indicated that the new staging improved predictability of overall survival according to disease stage, and Akaike information criterion (3023.7) was significantly lower than that for current staging system (3032.5). Upstaging of Vi groups allows differentiation of patients with early-stage cancers with poor prognosis and improves the unbalanced numbers of patients and prediction of prognosis in cases of lung cancer.

Endoscopic mucosal resection for early adenocarcinoma arising in Barrett's esophagus

A 58‐year‐old man was diagnosed to have an esophageal adenocarcinoma arising in Barrett's esophagus by screening examination at the previous hospital. Endoscopically, a slightly reddish elevated lesion with a central depressed component was detected in the Barrett's epithelium. Endoscopic ultrasonography showed the thickness of the second layer of the esophagus and no enlarged lymph node. Histological examination of a biopsy specimen revealed well or moderately differentiated adenocarcinoma. From these findings, the lesion was diagnosed as a mucosal esophageal cancer, type IIa + IIc, arising in Barrett's esophagus. As he refused operation, the lesion was resected endoscopically with his informed consent. Histologically, the resected specimens showed moderately differentiated adenocarcinoma arising in Barrett's esophagus. The adenocarcinoma had invaded the superficial muscularis mucosa, but was limited to the deep one with no vessel invasion. Barrett's esophagus often has a double muscularis mucosa. Connective tissues containing vascular and lymphatic vessels exist between them. However, one consideration is whether the existence of vessels between the double muscularis mucosa and the presence of vessel invasion are risk factors for metastasis. In order for a definitive indication for endoscopic mucosal resection, the frequency of lymph node and distant metastasis in cases of early Barrett's cancer needs to be investigated.

Clinical relevance of the concentrations of both pyrimidine nucleoside phosphorylase (PyNPase) and dihydropyrimidine dehydrogenase (DPD) in colorectal cancer.

Pyrimidine nucleoside phosphorylase (PyNPase) converts 5'-deoxy-5-fluorouridine (5'-DFUR) to 5'-fluorouracil (5-FU), which exerts an anti-cancer effect before being catabolized by dihydropyrimidine dehydrogenase (DPD). We examined the possible correlation of the tissue concentrations of both PyNPase and DPD with the clinicopathological features of colorectal cancer. In 36 cases of colorectal cancer, the concentrations of both PyNPase and DPD in fresh-frozen samples from either tumor or normal tissue were quantified using ELISA. The concentration of PyNPase was found to be significantly higher in the tumor than in the normal tissue (p = 0.001), whereas DPD showed no difference. The tumor/normal tissue ratio of PyNPase was higher in advanced stage cases, and also in the presence of liver metastasis, lymph node metastasis and vessel invasion (each p < 0.05). On the other hand, the tumor/normal tissue ratio of DPD was also higher in advanced stage cases and also in the presence of vessel invasion (each p < 0.05), thus indicating a poor response to 5-FU. The PyNPase/DPD ratio, which is known to be correlated with the tissue concentration of 5'-DFUR, was higher in the tumor than in the normal tissue (p = 0.001). The tumor/normal tissue ratios of both PyNPase and DPD might be useful candidates for predicting the prognosis of colorectal cancer. The PyNPase/DPD ratio was higher in the tumor tissue than in the normal tissue; however, further investigations are needed to clarify the effectiveness of fluoropyrimidine therapy.

Risk factors which predict pattern of recurrence after curative surgery for patients with advanced gastric cancer

The objective of the study was to define risk factors for peritoneal dissemination and haematogenous metastasis after curative resection of patients with an advanced gastric cancer. In retrospective analyses of 405 patients, 168 died of a tumour recurrence. Patients who died of gastric cancer were more likely to have large, invasive tumours which had spread throughout the stomach, metastasized to lymph nodes, and vessel invasion by gastric cancerous cells ( P < 0.01 or P < 0.05). Of the 168 deaths, 60 (35.7%) were secondary to haematogenous recurrence, 53 (31.5%) were related to peritoneal dissemination, and 19 (11.3%) were related to a local recurrence. To determine the independent risk factors related to peritoneal dissemination and haematogenous metastasis, multivariate analyses using a stepwise logistic model suggested that serosal invasion ( P < 0.01, relative risk = 2.57) and Borrmann type 4 ( P < 0.01, relative risk = 1.95) were the greatest risk factors for peritoneal dissemination. The presence of lymph node metastasis ( P < 0.01, relative risk = 2.62) and presence of vessel invasion by cancerous cells ( P < 0.05, relative risk = 1.59) were the greatest risk factors for a haematogenous metastasis.

Prognostic significance of peritumoral vessel invasion in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis

To assess the prognostic significance of peritumoral vessel invasion, data were examined for 1,510 women entered into the Ludwig Breast Cancer Group Trials I to IV evaluating adjuvant therapy for operable breast cancer with axillary nodal metastasis. Vessel invasion by tumor cells was identified by routine light microscopy in 59 per cent (889 of 1,510) of the patients and was equally distributed between premenopausal/perimenopausal (60 per cent, 468 of 778) and postmenopausal (58 per cent, 421 of 732) women. In logrank analyses stratified by nodal status (one to three or four or more positive nodes), the four-year disease-free survival (DFS) rate was significantly lower in patients with vessel invasion than in women without vessel invasion (50 per cent versus 65 per cent, P less than 0.0001). This DFS difference was seen for both premenopausal/perimenopausal (P = 0.0004) and postmenopausal (P = 0.0002) patients. The four-year overall survival rate was also lower in patients with vessel invasion (71 per cent versus 82 per cent, P = 0.0006), both for premenopausal/perimenopausal (P = 0.002) and postmenopausal (P = 0.04) women. The presence of vessel invasion was significantly associated with increasing numbers of positive axillary lymph nodes, rising tumor grade, nonstellate tumor border growth pattern, and higher steroid hormone receptor content of the primary tumor. The assessment of peritumoral vessel invasion continued to have prognostic significance for DFS (P less than 0.0001) and overall survival (P = 0.003) when evaluated in multivariate models controlling for treatment assigned, nodal status, tumor size, estrogen receptor status, menopausal status, and age. Depending on the subpopulation, patients with vessel invasion had a 41 per cent to 54 per cent greater risk of treatment failure than those without vessel invasion and a 29 per cent to 64 per cent greater risk of death. The percentage of treatment failures at distant sites was higher for women with than for those without vessel invasion (27 per cent versus 18 per cent, P = 0.003). In patients with axillary lymph node metastases, peritumoral vessel invasion may be a sign of increased systemic disease burden.