Presence Of Lymphatic Vessel Invasion Research Articles

Detecting the location of lung cancer on thoracoscopic images using deep convolutional neural networks.

The prevalence of minimally invasive surgeries has increased the need for tumor detection using thoracoscopic images during lung cancer surgery. We conducted this study to analyze the efficacy of a deep convolutional neural network (DCNN) for tumor detection using recorded thoracoscopic images of pulmonary surfaces. We collected 644 intraoperative thoracoscopic images of changes in pulmonary appearance from 427 patients with lung cancer between 2012 and 2021. The lesion areas on the thoracoscopic images were detected by bounding boxes using an advanced version of YOLO, a well-known DCNN for object detection. The DCNN model was trained and evaluated by a 15-fold cross-validation scheme. Each predicted bounding box was considered successful detection when it overlapped more than 50% of the lesion areas annotated by board-certified surgeons. Precision, recall, and F1-measured values of 91.9%, 90.5%, and 91.1%, respectively, were obtained. The presence of lymphatic vessel invasion was associated with successful detection (p = 0.045). The presence of pathological pleural invasion also showed a tendency toward successful detection (p = 0.081). The proposed DCNN-based algorithm yielded an accuracy of more than 90% tumor detection. These algorithms will help surgeons detect lung cancer displayed on a screen automatically.

A Nomogram to Predict Disease-Free Survival Following Neoadjuvant Chemotherapy for Triple Negative Breast Cancer.

BackgroundNeoadjuvant chemotherapy (NACT) is considered a standard treatment strategy for locally advanced triple negative breast cancer (TNBC). TNBC patients who achieve a pathologic complete response (pCR) are predicted to have a better prognosis while unfavorable chemo-sensitivity is still associated with a higher risk of disease relapse. The objective of this study was to construct a nomogram to predict disease-free survival (DFS) for TNBC patients following NACT.MethodsA total of 165 TNBC patients who underwent standard NACT and surgery were retrospectively reviewed, and data on their clinicopathological factors before and after NACT were collected. Independent prognostic factors for DFS were identified by Cox regression based on lower Akaike information criteria (AIC) and Bayesian information criterion (BIC). A nomogram to predict the 2-year and 5-year DFS following NACT for TNBC was constructed based on training cohort (n = 132) and validated by a validation cohort (n = 33).ResultsEither limited or full pCR (breast-only pCR, node-only pCR, or both-pCR) indicated significantly improved DFS and overall survival (OS) (p < 0.001). Lager residual tumor size (hazard ratio [HR] 1.175, p = 0.011) and the presence of lymphatic vessel invasion (LVI) (HR 3.168, p = 0.001) were identified as independent predictors of disease relapse in the training cohort. Five variables, including age, primary tumor size, histological grade, residual tumor size, and LVI were used to establish the nomogram. The C-index of the nomogram was 0.815, and calibration curves showed an acceptable consistency between the actual and nomogram-predicted 2-year and 5-year DFS. The proposed nomogram demonstrated superior predictive performance compared with Residual Cancer Burden (RCB) classification and the 8th American Joint Committee on Cancer Post Neoadjuvant Therapy Classification (AJCC ypTNM) staging system (area under the curve [AUC] for 2-year DFS: 0.870 vs. 0.758 vs. 0.711, respectively; AUC for 5-year DFS: 0.794 vs. 0.731 vs. 0.702, respectively) in the validation cohort.ConclusionsThe nomogram proposed in our study enabled to quantify the risk of disease relapse and demonstrated superior predictive performance than a survival predict instrument. It was an easy-to-use tool for clinicians to guide individualized surveillance of TNBC patients following standard NACT.

Clinicopathologic Characteristics of Epstein-Barr Virus-Associated Gastric Cancer Over the Past Decade in Japan.

Epstein–Barr virus (EBV) is a ubiquitous human herpes virus, but related with several types of malignancies. Among EBV-related malignancies, EBV-associated gastric carcinoma (EBVaGC) has the largest patient’s number. We screened for EBV infection in 1067 GC lesions of 1132 patients who underwent surgical resection from 2007 to 2017 in Japan and examined clinicopathological features of EBVaGC. EBV infection was detected by in situ hybridization with EBV-encoded small RNA 1(EBER-1 ISH). EBV was infected in 80 GC lesions (7.1%). Mean age was significantly lower in patients with EBVaGC than with EBV-negative GC. EBVaGC was more frequent in men than in women. EBVaGC was found twice as frequent in the upper or middle stomach as in the lower stomach. Early EBVaGC was more frequent, and submucosally invaded cases were dominant. The presence of lymphatic vessel invasion was less in EBVaGC, but frequency of lymph node metastasis was similar. Carcinoma with lymphoid stroma (CLS) was found in 3.8% (43/1132) of all lesions with 60.5% of EBV positivity. The synchronous or metachronous multiple GC was frequent in EBVaGC. We clarified clinicopathologic characteristics of EBVaGC over the past decade in Japan. EBV infection should be examined in gastric cancer cases showing these characteristics.

Clinical Impact of Muscle Quantity and Quality in Colorectal Cancer Patients: A Propensity Score Matching Analysis.

Sarcopenia is defined as the loss of skeletal muscle mass, accompanied by decreased muscle strength, and consists of myopenia and myosteatosis. Recent evidence has suggested the predictive value of sarcopenia for the risk of perioperative and oncological outcomes in various malignancies. The aim of this study was to clarify the clinical impact of myopenia and myosteatosis in colorectal cancer (CRC) patients. We analyzed the preoperative psoas muscle mass index and intramuscular adipose tissue content using preoperative computed tomography images from 308 CRC patients using statistical methods. Despite no significant correlation between myosteatosis and prognosis, preoperative myopenia significantly correlated with clinicopathological factors for disease development, including advanced tumor depth (P=0.009), presence of lymphatic vessel invasion (P=0.006), distant metastasis (P=0.0007), and advanced stage classification (P=0.013). Presence of preoperative myopenia was an independent prognostic factor for both cancer-specific survival (hazard ratio [HR]: 2.75, 95% confidence interval [CI]: 1.5-5.05, P=0.001) and disease-free survival (HR: 3.15, 95% CI: 1.8-5.51, P=0.0001), and was an independent risk factor for postoperative infectious complications in CRC patients (odds ratio: 2.03, 95% CI:1.17-3.55, P=0.013). Furthermore, these findings were successfully validated using propensity score matching analysis. Preoperative myopenia could be useful for perioperative management, and quantification of preoperative skeletal muscle mass could identify patients as a high risk for perioperative and oncological outcomes in CRC patients.

Lymphatic Vessel Invasion and Lymph Node Metastasis in Patients with Clinical Stage I Non-Small Cell Lung Cancer

The aim of this study was to investigate the association between the presence of lymphatic vessel invasion (LVI) in primary tumors and lymph node (LN) metastasis in clinical stage I non-small cell lung cancer (NSCLC) patients. A total of 76 patients who underwent complete resection for clinical stage I adenocarcinoma and squamous cell carcinoma were retrospectively examined. Tumors consisted of 51 cases of adenocarcinoma and 25 cases of squamous cell carcinoma as determined by histology. LN metastasis was detected in 24.4% (19/76) of patients. Factors associated with LN metastasis on univariate analysis included LVI (p < 0.001) and increased tumor dimensions (p < 0.05). Binary logistic regression analysis showed that the presence of LVI (p < 0.001) was the only predictor of LN metastasis. LVI is significantly associated with LN metastasis in patients with clinical stage I NSCLC. These findings may be helpful in determining the most appropriate operative strategy for patients if preoperative detection of LVI becomes feasible.

Clinical significance of lymphatic and blood vessel invasion in oral tongue squamous cell carcinomas

Although vascular invasion (VI) is recognized as an important predictor of lymph node metastasis and a significant prognostic factor in head and neck squamous cell carcinoma (HNSCC), there is currently no common definition for the pathological evaluation of VI status. We reviewed the medical records of 63 consecutive resected primary oral tongue SCCs (OTSCCs) without preoperative treatment between June 1999 and April 2008, and evaluated VI status by investigating lymphatic vessel invasion (LVI) and blood vessel invasion (BVI) by using immunohistochemistry (IHC) with monoclonal antibody D2-40 (D2-40) and Elastica van Gieson (EVG) staining, respectively. Subsequently, we analyzed their correlations with cervical lymph node metastasis and prognosis. LVI was found in 16 of the 63 tumors (25.4%) and BVI was in 32 tumors (50.8%). Univariate analysis revealed that the presence of LVI is statistically correlated with lymph node metastasis. Moreover, multivariate logistic regression analysis revealed that LVI is an independent risk factor of nodal metastasis (odds ratio=4.262, 95% confidence interval=1.262-14.397, p=0.020). In contrast, Kaplan-Meier survival analysis revealed that patients with BVI had a significantly shorter disease-free survival (DFS) and overall survival (OS) rates than those without BVI (68.6% versus 90.3%, p=0.028 and 68.6% versus 93.5%, p=0.013, respectively). The present study clearly demonstrated that LVI at primary OTSCC had significant correlation with lymph node metastasis, and that BVI was significantly associated with recurrence and poor prognosis. Evaluation of VI status, as LVI and BVI status separately, using IHC with D2-40 and EVG staining may be useful in predicting lymph node metastasis and poor prognosis in OTSCCs.

Lymphatic vessel invasion detected by the endothelial lymphatic marker D2-40 (podoplanin) is predictive of regional lymph node status and an independent prognostic factor in patients with resected esophageal cancer

The discovery of markers to lymphatic endothelial cells and the development of novel antibodies to these markers have brought increasing attention to the lymphatics and progress in the understanding of lymphangiogenesis and cancer metastasis. In this study, we investigate the presence of lymphatic vessel invasion (LVI) detected by D2-40 immunohistochemical staining in resected esophageal cancer and correlated with clinicopathologic data and patient survival. Sixty nine patients, who had a primary resection of esophageal cancer, were analyzed by univariate and multivariate logistic regression, and univariate and multivariate survival analysis. The total rate of LVI was 72% (50/69). Positive LVI was significantly correlated with lymph node metastasis (p < 0.001), tumor size (p < 0.001), histological grading (p = 0.017), tumor depth (p = 0.001), and stage (p < 0.001). Multivariate logistic analysis identified LVI (p = 0.036) as a predictor of regional lymph node metastasis. On univariate survival analysis, patients with LVI had a significantly shorter disease-free survival, cancer-specific survival and overall survival. Multivariate analysis proved that LVI diagnosed by D2-40 is an independent prognostic factor of both disease-free survival (p = 0.04) and overall survival (p = 0.032) in resected esophageal cancer. These results show that LVI assessment identifies patients at high risk for regional lymph node metastasis and that LVI is an independent prognostic factor in patients with esophageal cancer.

Intratumoral as well as peritumoral lymphatic vessel invasion correlates with lymph node metastasis and unfavourable outcome in colorectal cancer

The aim of this study was to assess the intratumoral and peritumoral distribution of lymphatic vessel density (LVD) and lymphatic vessel invasion (LVI) in colorectal cancer and their relationships with patients' clinicopathological characteristics and survival. Paraffin sections of 81 primary colorectal cancers were examined by immunohistochemical staining using monoclonal antibody D2-40. Peritumoral LVD was significantly higher than intratumoral LVD (P = 0.000). Both intratumoral LVD and peritumoral LVD were correlated with the presence of LVI (P = 0.006 and P = 0.003, respectively). LVI, intratumoral LVI and peritumoral LVI were identified, respectively in 38, 28 and 32% of the samples investigated. Both intratumoral LVI and peritumoral LVI were correlated with lymph node metastasis (P = 0.030 and P = 0.014, respectively). Lymph node metastasis, the presence of intratumoral LVI and peritumoral LVI were adversely associated with the 5-year overall survival in a univariate analysis (P = 0.001, P = 0.011 and P = 0.017, respectively). Multivariate analysis using Cox proportional hazard model showed that neither intratumoral LVI nor peritumoral LVI was an independent prognostic factor of overall survival. The results of this study demonstrated that intratumoral as well as peritumoral LVI was associated with lymph node metastasis and adverse outcome in colorectal cancer.

Risk Factors for Lymph Node Metastasis from Gastric Cancers with Submucosal Invasion

Accurate prediction of the metastatic status of lymph nodes (LNs) is clinically important for selecting treatment strategies in patients with gastric cancer with submucosal invasion (GCSM). In this study, we determined the risk factors for lymph node metastasis (LNM), including micrometastasis, in patients with GCSM. A total of 5610 LNs dissected from 189 patients with GCSM who had undergone a standard gastrectomy were immunostained with CAM 5.2 monoclonal antibody to detect LN micrometastasis. Clinicopathological risk factors for lymph node metastasis (LNM), including micrometastasis, were determined. LNM was detected in 216 LNs (107 macroscopic metastases, 72 micrometastases, and 37 isolated tumor cells) in 55 (29.1%) of the 189 patients with GCSM. A multivariate analysis revealed that a tumor size of more than 20 mm, a mixed- or undifferentiated-type histology, a vertical tumor invasion depth in the submucosal layer (VTIDSM) of more than 0.5 mm, and the presence of lymphatic vessel invasion (LVI) were independent risk factors for LNM. The incidences of LNM in patients with 0, 1, 2, 3, and 4 risk factors were 0, 4.5, 11.4, 36.1, and 52.9%, respectively. Among the patients with only 1 or 2 risk factors, all the metastatic lesions were located only in the first tier. On the other hand, LNM in the second tier was also detected in 24.5% of the patients with more than 3 risk factors. Tumor size, histologic type, VTIDSM, and LVI are important risk factors for predicting the presence and extent of LNM in patients with GCSM.

Characteristics of Invasive Micropapillary Carcinoma of the Breast: In Comparison with Invasive Ductal Carcinoma

Purpose: Invasive micropapillary carcinoma (IMPC) of the breast is a rare and associated with high incidence of lymph node metastasis and poor outcome. The aims of this study were to provide a comprehensive analysis of clinicopathologic and immunohistochemical characteristics of IMPC and to elucidate the differences between IMPC and invasive ductal carcinoma (IDC). Methods: Sixty-one patients of IMPC were identified by retrospective review of database from January 2004 to December 2008. 221 patients were randomly selected among the IDC patients who received operation during the same period. Two groups were compared with uni- and multivariate analysis. Results: We observed significant differences in mean number of metastatic lymph nodes (6.1 vs. 1.9, p= 0.001), positivity of lymph node (70.5% vs. 45.2%, p<0.001), and presence of lymphatic vessel invasion (75.4% vs. 34.8%, p <0.001) between IMPC and IDC patients. Although it has been known that triple negative breast cancer (TNBC) have lymphotropic tendency in their early T stage, 11.8% (26/221) of IDC and 3.3% (2/61) of IMPC patients were TNBC in this study (p=0.050). In multivariate analysis, IMPC histology showed no correlation with disease-free survival (DFS) and the lymphatic vessel invasion was a significant predictor of DFS. Conclusion: The results of this study confirm that IMPC is unique subtype of breast cancer that is commonly accompanied by axillary lymph node metastasis and shows poor outcome, although it rarely presents the pattern of TNBC. Lymphatic vessel invasion rather than histology of IMPC seems to be more closely related to DFS.

Marcadores moleculares em câncer de mama preditivos de metástases axilares

The aim of our study was to analyze morphologic and molecular markers of breast cancer relating them to the presence of metastases in axillary lymph nodes. We selected 123 cases of invasive mammary carcinomas stratified into three subgroups: with macrometastases, with micrometastases, and lymph node negative. Presence of metastases was evaluated relating them with morphologic factors (size of primary tumor, type and grade, presence of lymphatic and blood vessel invasion in hematoxylin and eosin-stained slides) and molecular factors of primary tumor (estrogen and progesterone receptors, E-cadherin, Ki67, p53, Her2 expression, and the presence of lymphatic and blood vessel invasion in immunostained sections for D2-40 and CD31). Axillary lymph node metastases were positively related to the presence of lymphatic vessel invasion in hematoxylin and eosin (H&E)-stained slides, when analyzed with or without metastases (p=0.04) and when analyzed in the three subgroups (p=0.002). Lymph node metastases were also positively related to presence of blood vessel invasion identified by immunohistochemistry (IHC) for CD31 (p=0.02). However other morphologic and molecular factors were not related to the presence of axillary node metastases. Lymphatic and blood vessel invasion identified in H&E and IHC-stained slides are positively related to the rmetastatic status of axillary lymph nodes and are predictive of axillary lymph node metastases in breast cancer.

Lateral peritumoral lymphatic vessel invasion can predict lymph node metastasis in esophageal squamous cell carcinoma

Lymph node metastasis is an important prognostic factor in many types of cancer. We investigated the clinical significance of lymphangiogenesis and lymphatic vessel invasion in esophageal squamous cell carcinoma. We evaluated lymphatic vessel density and lymphatic vessel invasion in the intratumoral, peritumoral and normal compartments using D2-40 immunostaining. In addition, the peritumoral compartment was divided into the lateral peritumoral compartment and the non-lateral peritumoral compartment. The lymphatic vessel density was higher in the peritumoral and intratumoral compartments than in the normal compartment. However, the lymphatic vessel density did not correlate with any pathological parameters including lymph node metastasis. Intratumoral and peritumoral lymph vessels were small and collapsed while normal lymphatic vessels and lymphatic vessels with lymphatic vessel invasion were dilated and large. The presence of lymphatic vessel invasion, in the lateral peritumoral compartment but nowhere else, significantly correlated with lymph node metastasis. These results suggest that lymphangiogenesis might occur with esophageal cancer, but it does not play a direct role in lymphatic vessel invasion and lymph node metastasis. Peritumoral lymphatic vessel invasion, especially in the lateral peritumoral compartment, should imply a high probability of regional lymph node metastasis.

Factors Influencing Axillary Node Metastasis in Breast Cancer

The status of the axillary lymph nodes at the time of diagnosis has been accepted as one of the most important prognostic factors for the overall and disease-free survival of patients with breast cancer. The aim of our study was to determine which factors influence axillary node involvement in invasive breast cancer. The data presented here were obtained from 344 patients who were treated for invasive breast cancer at the Department of Radiation Oncology, Uludağ University Medical College, Bursa, Turkey. Possible prognostic factors were categorized as patient related and tumor related. The Mann-Whitney U test was used for univariate analysis and logistic regression was used for multivariate analysis. In univariate analysis, a familial cancer history (P = 0.0042), age < 40 years (P = 0.0276), higher T stage (P < 0.0000), nipple involvement (P = 0.0345), skin involvement (P = 0.0270), perineural invasion (P = 0.0231), and lymphatic vessel invasion (P < 0.0000) were correlated with increased axillary node involvement. A higher incidence of > or = 4 involved lymph nodes was associated with higher T stage (P = 0.0004), nipple involvement (P = 0.0292), presence of an extensive intraductal component (P = 0.0023), skin involvement (P = 0.0008), perineural invasion (P = 0.0523), and lymphatic vessel invasion (P < 0.0000) in univariate analysis. In multivariate analysis, age < 40 years (P = 0.0454), cancer history within the family (P = 0.0024), higher T stage (P = 0.0339), lymphatic vessel invasion (P = 0.0003), and perineural invasion (P = 0.0408) were found to be independent factors for axillary lymph node positivity. Age < 40 years (P = 0.0221), perineural invasion (P = 0.0408), and an extensive intraductal component (P = 0.0132) were associated with an increased incidence of > or = 4 involved nodes in the logistic regression analysis. In patients with breast cancer, the incidence of axillary lymph node involvement was independently influenced by age < 40 years, presence of cancer history within the family, higher T stage, lymphatic vessel invasion, and perineural invasion. In conclusion, absence of familial cancer history, presence of lymphatic vessel invasion, higher T stage, and age below 40 years independently increased the risk of axillary node involvement. Presence of perineural invasion and lymphatic vessel invasion, age below 40, and an extensive intraductal component of more than 25% independently affected the risk of having > or = 4 nodes involved. Patients characterized by these factors may be classified into a higher risk group for nodal involvement, but more data are needed to define factors that can help in the decision-making regarding the omission of axillary treatment.

Proliferation activity in oral and cutaneous canine melanocytic tumours: correlation with histological parameters, location, and clinical behaviour

A total of 62 canine melanocytic tumours (10 melanocytomas and 52 primary malignant melanomas) were investigated to compare the accuracy of prognosis provided by MIB-1 proliferation index ( mib-1-pi) with classical histological criteria and location. mib-1-pi was assessed by means of quantitative image analysis of sections immunostained with MIB-1 monoclonal antibody. Tumour location, histological cell type, stromal or lymphatic vessel invasion, maximum tumour thickness, and presence of inflammation or necrosis were recorded for each case. Thirty-eight dogs were submitted to a 1-year follow-up and the clinical outcome of the disease determined. mib-1-pi in melanocytomas differed significantly from that detected in primary malignant melanomas ( P=0.0001). A significant difference in mib-1-pi was revealed between oral and cutaneous malignant melanomas ( P=0.015), and between presence and absence of lymphatic vessel invasion ( P=0.05). mib-1-pi was not correlated with the other parameters. In univariate analysis, only tumour location (oral vs cutaneous), presence of lymphatic vessel invasion, and mib-1-pi were associated with decreased overall survival ( P=0.0001, P=0.0144, and P=0.0489, respectively). In conclusion, the results of our study confirm that the assessment of the mib-1-pi may be of additional prognostic value for dogs with primary malignant melanomas.

Intratumoral concentrations of tissue inhibitor of matrix metalloproteinase 1 in patients with gastric carcinoma

Previously, the authors clarified that the plasma concentration of tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) in patients with gastric carcinoma was a significant predictor of tumor invasiveness and metastasis. To further clarify the clinical significance of TIMP-1, the authors used an enzyme-linked immunoassay to assess TIMP-1 protein concentrations in samples of tumor tissue from 86 patients who underwent primary resection for gastric carcinoma. Concentrations in samples of normal gastric mucosa from 73 of these patients also were assessed. Tissue TIMP-1 concentrations were significantly greater in gastric tumors than in normal gastric mucosa and were associated significantly with a variety of pathologic factors, including macroscopic type, depth of tumor invasion in the gastric wall, presence of lymphatic vessel invasion, pattern of tumor infiltration into the surrounding tissue, and disease stage. Significantly greater TIMP-1 concentrations were found in tumors that were exposed to the serosal surface compared with tumors that were limited to the submucosal layer. TIMP-1 protein was significantly greater in tumors with lymphatic vessel invasion, an infiltrative pattern into the surrounding tissue (INF-gamma), and in tumors from patients with Stage III disease. Survival was significantly poorer in patients with TIMP-1 concentrations > or = 10.0 ng/mg total protein. When patients were stratified by disease stage, survival was significantly different in patients with Stage III disease. Multivariate analysis demonstrated that intratumoral concentrations of TIMP-1 were the most significant independent factor for survival. These findings suggest that the intratumoral concentration of TIMP-1 protein may be a good indicator of tumor aggressiveness and can serve as a significant independent predictor of survival in patients with gastric carcinoma.

The relationship between lymphatic vessell invasion, tumor size, and pathologic nodal status: can we predict who can avoid a third field in the absence of axillary dissection?

Purpose: Tangential (2-field) radiation therapy to the breast and lower axilla is typically used in our institution for treating patients with early-stage breast cancer who have 0–3 positive axillary nodes, as determined by axillary dissection, whereas a third supraclavicular/axillary field is added for patients with 4 or more positive nodes. However, dissection may result in complications and added expense. We, therefore, assessed whether clinical or pathologic factors of the primary tumor could reliably predict, in the absence of an axillary dissection, which patients with clinically negative axillary nodes have such limited pathologic nodal involvement that they might be effectively treated with only tangential fields. This would eliminate both the complications of axillary dissection and the added complexity and potential morbidity of a supraclavicular/axillary field. Methods and Materials: In this study, 722 women with clinical Stage I or II unilateral invasive breast cancer of infiltrating ductal histology, with clinically negative axillary nodes, at least 6 lymph nodes recovered on axillary dissection, and central pathology review were treated with breast-conserving therapy from 1968 to 1987. Pathologic nodal status was assessed in relation to clinical T stage, the presence of lymphatic vessel invasion (LVI), age, histologic grade, and the location of the primary tumor. Results: LVI, T stage, and tumor location were each significantly correlated with nodal status on univariate analysis. Ninety-seven percent of LVI-negative patients had 0–3 positive axillary nodes compared to 87% of LVI-positive patients. There was no association between T stage and extent of axillary involvement within LVI-negative and LVI-positive subgroups. In a logistic regression model, only LVI remained a significant predictor of having 4 or more positive nodes, although tumor size was of borderline significance. The odds ratio for LVI (positive vs. negative) as a predictor of having 4 or more positive nodes was 3.9 (95% CI, 2.0–7.6). Conclusion: For patients with clinical T1–2, N0, infiltrating ductal carcinomas, the presence of LVI is predictive of having 4 or more positive axillary nodes. Only 3% of patients with clinical T1–2, N0, LVI-negative breast cancers had 4 or more positive nodes on axillary dissection. Such patients may be reasonable candidates for treatment with tangential radiation fields in the absence of axillary dissection.

The significance of extracapsular extension of axillary lymph node metastases in early-stage breast cancer

Purpose: To investigate if extracapsular extension (ECE) of axillary lymph node metastases predicts for a decreased rate of disease-free survival or an increased rate of regional recurrence of breast carcinoma. Methods: The study population consisted of 368 patients with T1 or T2 breast cancer and pathologically-positive lymph nodes treated with breast-conserving therapy between 1968 and 1986. The median number of sampled lymph nodes was 10. Median follow-up time for the surviving patients was 139 months (range 70–244). Twenty percent of the patients were treated with supraclavicular RT, and 64% received both axillary and supraclavicular RT, with a median dose to the nodes of 45 Gy. The following factors were evaluated: presence of ECE, number of sampled lymph nodes (LN), number of involved LN, size of primary tumor, histologic grade of tumor, presence of lymphatic vessel invasion (LVI), presence of an extensive intraductal component (EIC), radiation dose, use of adjuvant chemotherapy, and age of patient. Recurrences were reported as the 5-year crude sites of first failure, and were divided into breast recurrences (LR), regional nodal failure (RNF, defined as isolated axillary, supraclavicular, or internal mammary recurrence), and distant metastases (DM). Results: One hundred twenty-two patients (33%) had ECE and 246 patients did not. The median number of LN with ECE was 1 (range 1–10) and 20% of patients had ECE in ≥ 4 LN. Patients with ECE tended to be older (median age 51 vs. 47, p = 0.01), and had a higher number of involved LN (median 3 vs. 2, p = 0.005) than patients without ECE. Forty-three percent of patients with ECE had ≥ 4 involved LN compared to 15% of patients without ECE ( p < 0.0001). Models of ECE and the above factors revealed no significant correlation between ECE and either disease-free or overall survival. There was no statistically significant increase in local, regional nodal, or distant failures in patients with ECE as compared to patients without ECE. Conclusion: In this population of patients with nodal involvement, the presence of ECE correlates with the number of involved LN but does not appear to add predictive power to models of local, regional, or distant recurrence when the number of positive LN is included.

Topographic criteria in the diagnosis of tumor emboli in intramammary lymphatics

Topographic relationships to adjacent structures were used as criteria to identify intramammary lymphatics with tumor emboli in breast cancer patients, in addition to conventional morphologic criteria. Patterns of relationship to blood vessels, non-neoplastic lobules and ducts, and empty lymphatics were defined. Ninety-five cases were independently reviewed by two observers. Interobserver reproducibility of the diagnosis of lymphatic vessel invasion (LVI) was 82% (kappa 0.60). The observers agreed on the presence of LVI in 23 patients (24%), of whom 21 (91%) had positive lymph nodes. Only among patients in whom more than ten emboli were identified was the frequency of positive lymph nodes markedly higher than in the total material. The location of tumor emboli relative to the invasive tumor was of little significance. LVI was a more powerful predictor of lymph node status than tumor size, margin contour, histologic grade and histologic type, and was highly significant also when controlled for these features.

Nuclear DNA Content as a Prognostic Factor in T1−2N0 Breast Cancer

One hundred fifteen patients with postsurgical stage T1-2N0 breast cancer with the minimum follow-up of 22 years and from a defined population were studied to find reliable prognostic factors predicting long-term survival rate. The 30-year survival rate corrected for intercurrent deaths was 75%, and no deaths of breast cancer occurred after the nineteenth year of follow-up. The 30-year crude survival rate was only 28%, indicating that the great majority of these patients ultimately die of other causes than breast cancer. The nuclear DNA content could be determined by flow cytometry in 95 of the 115 cases, and 52 (55%) of them were nondiploid. DNA ploidy (diploid vs. nondiploid, P = 0.11) did not have a significant influence on long-term survival rate, but cancers with the DNA index less than 1.2 had more favorable prognosis in a univariate analysis than those with the DNA index more than 1.2 (P = 0.02). The most important independent prognostic factor in Cox's multivariate analysis was the presence of lymphatic vessel invasion of cancer cells (P less than 0.001). Several other factors, including histologic grade and type, extent of necrosis, type of tumor margin, age at diagnosis, and primary tumor size could be shown to be of prognostic value in univariate and/or multivariate analyses.

Resectable adenocarcinoma of the rectosigmoid and rectum. II. The influence of blood vessel invasion.

Several series have examined the influence of blood vessel invasion (BVI) by tumor on survival of patients with colorectal cancer; however, little data are available regarding its influence on patterns of failure. In an effort to determine the influence of BVI on the patterns of failure and survival in rectosigmoid and rectal cancer, a retrospective review of 168 patients who underwent potentially curative surgery at the New England Deaconess Hospital was performed. In patients who had tumors with extramural BVI, there was a significant decrease in five-year actuarial survival compared with patients who had tumors with intramural BVI or were BVI-negative (BVI-). When the intramural and extramural types of BVI were combined, no significant impact was noted on the patterns of failure or survival in patients with BVI+ versus those with BVI- tumors. In contrast, the presence of lymphatic vessel invasion was found to significantly decrease survival. By using a proportional hazards analysis, it was found that BVI was not an independent prognostic variable. Therefore, the use of BVI alone is not recommended for selecting patients with rectosigmoid and rectal cancer who may benefit from adjuvant therapy.