Likelihood Of Lymph Node Metastasis Research Articles

Can Sentinel Node Biopsy Be Avoided in Some Elderly Breast Cancer Patients?

The purpose of this study was to determine factors associated with lymph node metastasis among hormonally-responsive breast cancer patients > or = 70 years old, and to develop and validate a clinical prediction rule to predict the risk of lymph node metastasis in this population. Nodal evaluation in elderly women with breast cancer remains controversial. The ability to predict which elderly patients may be node-negative may spare them the morbidity of lymph node evaluation. Hormone-receptor positive breast cancer patients > or = 70 years old who participated in a prospective multicenter trial were divided into a training set (n = 554) and a test set (n = 146). Univariate and multivariate analyses were conducted to determine factors predictive of final nodal status. A clinical prediction rule was developed on the training set, and validated in the independent test set. Median patient age was 76; median tumor size was 1.4 cm. 15.9% and 16.2% were LN+ in the training and test sets, respectively. On univariate analysis, patient age, tumor size, palpability, grade, and lymphovascular invasion predicted lymph node status. On multivariate analysis, patient age, tumor size, and lymphovascular invasion remained significant. A prediction rule was created; patients were categorized into quartiles by predicted risk. 5.4% and 0% of patients in the lowest quartile were node positive in the training and test sets, respectively. Some elderly breast cancer patients at low likelihood of lymph node metastasis may be spared lymph node evaluation.

Endoscopic submucosal dissection for colorectal neoplasms

Although endoscopic submucosal dissection (ESD) gains acceptance as one of the standard treatments for esophageal and stomach neoplasms in Japan, it is still in the developing stage for colorectal neoplasms. In terms of indications, little likelihood of nodal metastasis and technical resectability are principally considered. Some of intramucosal neoplasms, carcinomas with minute submucosal invasion, and carcinoid tumors, which are technically unresectable by conventional endoscopic treatments, may become good candidates for ESD, considering substantial risks and obtained benefits. ESD as a staging measure to obtain histological information of the invasion depth and lymphovascular infiltration is acceptable because preoperative prediction is difficult in some cases. In terms of techniques, advantages of ESD in comparison with other endoscopic treatments are to be controllable in size and shape, and to be resectable even in large and fibrotic neoplasms. The disadvantages may be longer procedure time, heavier bleeding, and higher possibility of perforation. However, owing to refinement of the techniques, invention of devices, and the learning curve, acceptable technical safety has been achieved. Colorectal ESD is very promising and become one of the standard treatments for colorectal neoplasms in the near future.

Gastric Polyps With Intramucosal Carcinoma

Gastric polyps such as adenomas, hyperplastic polyps, fundic gland polyps, and pyloric gland adenomas can sometimes harbor carcinoma. Polyps with dysplasia rarely present a problem because they do not metastasize and are treated by polypectomy provided the stalk margin is clear of dysplasia. However, polyps with intramucosal carcinoma can be more challenging as there are certain histologic features which can impact on the likelihood of lymph node metastases. These features will determine whether a patient undergoes an endoscopic resection or a partial gastrectomy with lymph node dissection. Gastric polyps with intramucosal carcinoma can be treated with curative endoscopic resection provided they are well differentiated and free of lymphovascular invasion. Additional factors such as the presence or absence of ulceration, diameter of lesion, and rarely invasion into the submucosa can also provide useful information in this regard.

Perspective on the practical indications of endoscopic submucosal dissection of gastrointestinal neoplasms

Endoscopic submucosal dissection (ESD) is a new endoluminal therapeutic technique involving the use of cutting devices to permit a larger resection of the tissue over the muscularis propria. The major advantages of the technique in comparison with polypectomy and endoscopic mucosal resection are controllable resection size and shape and en bloc resection of a large lesion or a lesion with ulcerative findings. This technique is applied for the endoscopic treatment of epithelial neoplasms in the gastrointestinal tract from the pharynx to the rectum. Furthermore, some carcinoids and submucosal tumors in the gastrointestinal tract are treated by ESD. To determine the indication, two aspects should be considered. The first is a little likelihood of lymph node metastasis and the second is the technical resectability. In this review, practical guidelines of ESD for the gastrointestinal neoplasms are discussed based on the evidence found in the literature.

Prognosis of Early Cervical Cancer (FIGO Stages IA2, IB, and IIA) in Northern Norway Predicted by Malignancy Grading Score and Objective Morphometric Image Analysis

Recurrence of early-stage cervical cancer after primary surgery represents a considerable clinical problem, and, so far, few reliable markers for prediction of recurrence exist. Thus, the prognostic value of the malignancy grading score (MGS) classification system was evaluated in 82 patients with early-stage cervical cancer (International Federation of Gynecology and Obstetrics stages IA2, IB, and IIA) and long-time follow-up (5-16 years). Recurrence or not, the likelihood of lymph node metastases and reproducibility of the MGS semiquantitative system were tested. The prognostic power of the MGS to identify high-risk cases prone to recurrence in patients lacking lymph node metastases at primary surgery was a main purpose of the present study. The semiquantitative MGS classification system was performed independently by 2 pathologists unaware of prognosis and clinical data using light microscopy. Routine hematoxylin and eosin sections from surgical specimens were used, and investigation area was defined in the deep part of the tumor. Data-based image analysis was also used to investigate if objective morphometric parameters could add any prognostic power to MGS. The 5-year survival for the whole patient group was 92%. Malignancy grading score of greater than 17 risk points was statistically highly significant in predicting relapse and lymph node metastases (n = 82). High-risk cases lacking lymph node metastases (n = 70) were also statistically associated with high MGS. Depth of invasion and vascular invasion were statistically related to recurrence. Objective image analysis of nuclear parameters was of no additional statistical value for the prediction of outcome. The MGS classification system proved to be a useful tool in predicting recurrence and lymph node metastases and, most importantly, was a predictor of high-risk patients without metastases at primary surgery.

Intraluminal Endoscopic Surgery: The Scioto Returns

Intraluminal Endoscopic Surgery: The Scioto Returns

Histopathological and Lymphangiogenic Parameters in Relation to Lymph Node Metastasis in Early Stage Oral Squamous Cell Carcinoma

Lymph node metastasis from oral squamous cell carcinoma (SCC) correlates with a poor prognosis. Therefore, accurate assessment of lymph node status is crucial in treatment planning. Furthermore, prediction of delayed neck metastasis (DNM), especially in early stage tumors with a clinically negative (N0) neck, will determine the need for neck dissection or irradiation. In this study, we assess various clinical, histopathological and lymphangiogenic parameters in early stage oral SCC and their association with DNM. Clinical, histological, and immunohistochemical analyses were undertaken for 29 patients with T1N0M0 or T2N0M0 oral SCC affecting the tongue or floor of mouth and correlated with the development of DNM. Tumor thickness, nuclear pleomorphism, pattern of invasion, and immunohistochemical expression of the lymphangiogenesis-associated molecules VEGFR-3 and VEGF-C were associated with DNM. Analysis of these parameters may help to identify patients who would benefit from a neck dissection or irradiation by predicting the likelihood of lymph node metastasis.

Vascularity and expression of vascular endothelial growth factor in oral squamous cell carcinoma, resection margins, and nodal metastases

The role of vascularity as a predictor of the likelihood of lymph node metastases in oral cancer is not clear. To that end, the vascularity and expression of vascular endothelial growth factor (VEGF) was assessed at three specific regions: the tumour (inside and around the tumour); the resection margin; and the regional lymph nodes. Formalin-fixed paraffin-embedded specimens from 26 oral cancers (11 with no involved nodes and 15 with involved nodes) were stained immunohistochemically and examined. Staining for VEFG was significantly greater in the tumour than in the other sites. No significant differences were found in the intensity of staining in the primary tumour, resection margins, or nodes between cases in which the nodes were involved and in which they were not involved. We found no correlation between vascularity and VEGF staining, suggesting that VEGF is not the primary or only stimulator of angiogenesis in oral cancer. Greater understanding of the mechanisms of metastasis will lead to new treatments. The evidence that is accumulating for oral cancer suggests that such treatments may be better targeted at preventing lymphatic spread, rather than vascular spread.

The risk of nodal metastasis in early adenocarcinoma of the uterine cervix.

A functional and widely accepted definition of microinvasive cervical adenocarcinoma remains elusive. The purpose of this study was to determine at which depth of invasion the likelihood of lymph node metastasis or disease recurrence was so small that conservative surgery could be considered appropriate. Charts of patients with adenocarcinoma of the cervix (ACC) who underwent radical hysterectomy and pelvic lymphadenectomy (n = 98) at Indiana University Medical Center from 1987 to 1998 were retrospectively reviewed. Patients with stage IA1-IB1 lesions were included in the study. Patients treated with preoperative radiotherapy were excluded. Pathologic parameters evaluated included histologic type, depth of stromal invasion (DOI), and the presence of lymphatic vascular space invasion, or lymph node metastases. The patient median age was 39 years (20-65). The median time of follow-up was 30 months (4-124). Lymph node metastases were found in ten patients and 11 developed recurrences. The precise DOI could be measured in 84 patients. Of the 48 patients with cancers with a DOI </= 5 mm, none had involved parametria or nodes; whereas eight of the 36 with a DOI > 5 mm had nodal metastases (P = 0.00069). None of these 48 patients with a tumor DOI </= 5 mm developed a recurrence whereas six of the 36 patients with a tumor DOI > 5 mm developed recurrent disease (P = 0.0048). The risk of nodal metastases and recurrence is so low in patients with ACC and DOI </= 5 mm that for patients with such depth documented on conization with negative margins pelvic lymphadenectomy may be omitted.

The risk of nodal metastasis in early adenocarcinoma of the uterine cervix*

A functional and widely accepted definition of microinvasive cervical adenocarcinoma remains elusive. The purpose of this study was to determine at which depth of invasion the likelihood of lymph node metastasis or disease recurrence was so small that conservative surgery could be considered appropriate. Charts of patients with adenocarcinoma of the cervix (ACC) who underwent radical hysterectomy and pelvic lymphadenectomy (n = 98) at Indiana University Medical Center from 1987 to 1998 were retrospectively reviewed. Patients with stage IA1–IB1 lesions were included in the study. Patients treated with preoperative radiotherapy were excluded. Pathologic parameters evaluated included histologic type, depth of stromal invasion (DOI), and the presence of lymphatic vascular space invasion, or lymph node metastases. The patient median age was 39 years (20–65). The median time of follow-up was 30 months (4–124). Lymph node metastases were found in ten patients and 11 developed recurrences. The precise DOI could be measured in 84 patients. Of the 48 patients with cancers with a DOI ≤ 5 mm, none had involved parametria or nodes; whereas eight of the 36 with a DOI &gt; 5 mm had nodal metastases (P = 0.00069). None of these 48 patients with a tumor DOI ≤ 5 mm developed a recurrence whereas six of the 36 patients with a tumor DOI &gt; 5 mm developed recurrent disease (P = 0.0048). The risk of nodal metastases and recurrence is so low in patients with ACC and DOI ≤ 5 mm that for patients with such depth documented on conization with negative margins pelvic lymphadenectomy may be omitted.

A conceptual model integrating spatial information to assess target volume coverage for IMRT treatment planning

Purpose We propose a model that integrates the spatial location of each voxel within a clinical target volume (CTV) to differentiate the merit of intensity-modulated radiation therapy (IMRT) plans with similar dose–volume histogram (DVH). This conceptual model is based on the hypothesis that various subregions within a given CTV that may carry different degree of risk in containing microscopic disease. Methods and materials We hypothesize that a correlation between the probability of microscopic tumor extension and the risk of lymph node metastasis of a particular voxel point within CTV can be inferred based on its distance from the surface of radiographically evident gross disease. A preliminary observation was gathered from existing clinicopathologic data, and, based on these observations, a conceptual model for exponential-decay microscopic-extension probability function around primary tumor and linear function parameters relating the likelihood of lymph node metastasis to the distance from primary tumor was proposed. This model was generated to provide scoring functions to examine the merit of IMRT plans. To test the feasibility of this model, we generated two IMRT plans with similar and clinically acceptable DVH-based CTV coverage. Planning data were transferred to a data analysis software package (Matlab, The Mathworks Inc.). A 3D scoring function was calculated for each voxel inside the CTV. The adequacy of target coverage was evaluated by several novel approaches: 2D dose–volume scoring-function histograms (DVSH), the integral probability of relative residual tumor burden (RRTB), and tumor control probabilities (TCP) employing the scoring function as a pseudo-clonogen density distribution. Results Incorporating parameters for the risk of containing microscopic disease in each voxel into the scoring function algorithm, 2D DVSHs, RRTBs, integral RRTBs, and TCPs were computed. On each axial image, an RRTB map could locate the regions at greatest risk. These scoring functions were able to differentiate the merit of CTV coverage of clinically different IMRT plans but having very similar DVHs; one with cold spots centrally located over the gross tumor, and the other with more acceptable cold spots on the periphery of the CTV further away from the gross tumor volume. Conclusions We demonstrated the feasibility and potential utility of an IMRT scoring method derived from this conceptual modeling approach. These methods are capable of ranking treatment plans with similar DVH profiles but different underdosed regions within the target. We will examine the accuracy of model parameters by performing tumor-specific image-pathologic correlation studies. Upon validation of these parameters, incorporating this scoring function model into plan optimization may have the potential to avoid underdosing subvolumes within CTV that harbor a higher likelihood of microscopic disease.

Patterns of lymphatic spread in rectal cancer. A topographical analysis on lymph node metastases

The presence of lymph node (LN) metastases is the most important prognostic factor in rectal cancer. The exact LN status can only be known when an extended lymph node dissection (LND) has been performed, a process not routinely performed. If the likelihood of LN metastases can be more accurately assessed preoperatively, then an optimal multimodality treatment plan can be established. 605 patients with primary rectal cancer operated upon with wide LND (D3 level) were analysed for LN metastases combining topographical localisation and morphological features of the tumour. More distal rectal tumours tend to more LN metastases and more lateral lymphatic spread. Tumours ⩾3 cm show more LN metastases compared with those smaller than 3 cm. Depth of bowel wall invasion is strongly related to the presence of LN metastases. The peritoneal reflection has no discriminating role in the mode of spread. Intra-operative assessment by the surgeon for presence of LN metastases is not reliable. When localisation, depth of bowel wall invasion and diameter of a rectal tumour are known, a likelihood of LN metastases can be assessed pre-operatively, not intra-operatively.

Sentinel node study in early breast cancer.

Since October 1997 60 patients with early breast cancer (T <3 cm) were studied. All patients underwent lymphoscintigraphy with two types of colloid: the first (17 pts) with a particle size <1,000 nm; the second (43 pts) with a particle size <80 nm. The standard procedure consists of injection, on the day before surgery, of 70 MBq of the smaller nanocolloid in 0.4 cc saline divided over four sites, around the lesion or subdermally around the surgical scar. We utilize a low-energy, high-resolution LFOV camera for scintigraphy and a probe specific for the sentinel node during surgery. In 56/60 patients (93.3%) lymphoscintigraphy showed the sentinel node (SN). In two cases the SN was not detected presumably because of lymphatic interruption by an old surgical scar; in the other two cases the sites of injection were too close to the SN, thus masking it. In five cases (9%) the SN was not visualized with the surgical probe but in two of these drainage to the internal mammary chain was observed. The apparently lower sensitivity of intraoperative localization was due to the extra-axillary lymphatic drainage or to the vicinity of the SN to the primary lesion. The SN proved to be metastatic in 12 cases. No false-negative SNs were found. In five cases (10%) the radiolabeled lymph node was the only node containing tumor cells (micrometastases): this result depends on the combined use of hematoxylin-eosin and rapid cytokeratin staining. The application of blue dye was useful for easier identification of the SN but did not allow detection of more SNs. Our preliminary results are extremely encouraging. Considering that at the early stages of breast cancer the likelihood of lymph node metastases is low (20% in our series) and no false negative were reported in this study, we conclude that with SN biopsy axillary lymph node dissection can be avoided, making surgery less aggressive but maintaining accuracy.

Columnar mucosa and intestinal metaplasia of the esophagus: fifty years of controversy.

To outline current concepts regarding etiology, diagnosis, and treatment of intestinal metaplasia of the esophagus and cardia. Previously, endoscopic visualization of columnar mucosa extending a minimum of 3 cm into the esophagus was sufficient for the diagnosis of Barrett's esophagus, but subsequently the importance of intestinal metaplasia and the premalignant nature of Barrett's have been recognized. It is now apparent that shorter lengths of intestinal metaplasia are common, and share many features of traditional 3-cm Barrett's esophagus. Themes and concepts pertaining to intestinal metaplasia of the esophagus and cardia are developed based on a review of the literature published between 1950 and 1999. Cardiac mucosa is the precursor of intestinal metaplasia of the esophagus. Both develop as a consequence of gastroesophageal reflux. Intestinal metaplasia, even a short length, is premalignant, and the presence of dysplasia indicates progression on the pathway to adenocarcinoma. Antireflux surgery, as opposed to medical therapy, may induce regression or halt progression of intestinal metaplasia. The presence of high-grade dysplasia is frequently associated with an unrecognized focus of adenocarcinoma. Vagal-sparing esophagectomy removes the diseased esophagus and is curative in patients with high-grade dysplasia. Invasion beyond the mucosa is associated with a high likelihood of lymph node metastases and requires lymphadenectomy. Despite improved understanding of this disease, controversy about the definition and best treatment of Barrett's esophagus continues, but new molecular insights, coupled with careful patient follow-up, should further enhance knowledge of this disease.

P27 cell-cycle inhibitor is inversely correlated with lymph node metastases in right-sided colon cancer

p27, a cyclin-dependent kinase inhibitor, suppresses proliferation of normal and neoplastic cells. Expression of p27 is correlated with survival in colon cancer. To some degree, right-sided colon cancers differ biologically and clinically from left-sided colon cancers. We analyzed 41 patients with right-sided colon cancers, including 18 cases with regional lymph node metastases and 23 cases with negative lymph nodes. Immunostaining for p27 was performed on histologic sections of primary cancers and scored. Correlation of p27 protein expression with histologic parameters was performed by t-test and multivariate analysis. Decreased p27 protein expression was associated with large tumor size. As percentages of positively stained tumor cells decreased from 70 to 29%, the mean tumor size increased from 1.9 to 7.3 cm. p27 protein expression significantly decreased in primary cancers with angiolymphatic invasion or with positive lymph nodes in comparison with those without angiolymphatic invasion (26 +/- 6 vs. 44 +/- 5%, P < 0.03) or with negative lymph nodes (23 +/- 4 vs. 47 +/- 6%, P < 0.003). p27 expression was not statistically different in terms of depth of tumor invasion (T1/T2 vs. T3/T4), tumor type or tumor differentiation. Multivariate analysis revealed that low p27 expression in primary cancers was correlated with lymph node metastases (P = 0.01). However, it did not correlate with any other histologic parameters. In summary, decreased p27 expression was associated with an increased likelihood of lymph node metastases in colon cancers, independent of depth of tumor invasion. This implies that p27 is a potentially important predictor for tumor metastasis and patient's prognosis in right-sided colon cancers.

Retinoblastoma Protein Expression and Prognosis in Laryngeal Cancer

Expression of retinoblastoma (Rb) protein was immunohistochemically examined in laryngeal squamous cell neoplasias from 72 patients. Staining patterns were considered with reference to such prognostic factors as patient's age, histologic grade, tumour size and lymph node status, and 5-year survival rate. Rb protein negativity, either partial or complete, was noted in 28.8% of cases and was associated with a significantly lower 5-year survival rate, as well as with a higher likelihood of lymph node metastasis. This suggests that Rb alteration may be a prognostic indicator in patients with laryngeal carcinoma.

Epidermal Growth Factor Receptor in Vulvar Malignancies and Its Relationship to Metastasis and Patient Survival

Objective.To evaluate the level of epidermal growth factor receptor (EGF-R) expression in vulvar malignancies and to determine if a correlation exists between EGF-R levels and metastasis or patient survival.Methods.All patients with a diagnosis of invasive squamous cell carcinoma of the vulva who were treated at our institution with a primary radical vulvectomy and inguinal lymph node dissection from 1983 to 1993 were eligible for the study. Sixty-one patients with available tissue blocks of benign vulvar epithelium, the primary malignant vulvar lesion, and groin node metastasis (when positive) were included in the study. Semiquantitative EGF-R expression was determined in a blinded fashion utilizing immunohistochemical staining of appropriate tissue samples. Survival was calculated utilizing Kaplan–Meier life table analysis based upon disease-free survival.Results.A significant increase (P< 0.001) in mean EGF-R levels was demonstrated in the primary tumor (67%) versus benign vulvar epithelium (31%). In the 14 patients with lymph node metastasis, the mean EGF-R level in the primary tumor was 65% versus 88% in the metastatic lesion (P< 0.001). The likelihood of lymph node metastasis was elevated in those patients with a benign tissue EGF-R level ≥40% (P< 0.03) and in those patients with a primary tumor EGF-R level ≥90% (P< 0.025). Life table analysis revealed a cumulative disease-free survival of 45% for all patients. Disease-free survival in those patients with EGF-R levels ≥90% in the primary tumor was 25%, contrasting with a disease-free survival of 54% in those patients with EGF-R levels <90% (P< 0.05).Conclusions.There is a progressive increase in EGF-R expression from benign vulvar epithelium to primary malignant tissue to metastatic lesions within the same patient. Increased expression of EGF-R in the primary vulvar malignancy is significantly associated with lymph node metastasis and decreased patient survival. Increased expression of EGF-R in histologically benign vulvar epithelium has a significant association with lymph node metastasis and may predict decreased patient survival.

Laparoscopic approach to retroperitoneal lymph node dissection.

Laparoscopic retroperitoneal lymph node dissection is a new surgical procedure used to enhance staging in men with clinical stage I nonseminomatous germ cell tumors of the testis. The procedure has been performed in a limited number of patients at several centers with extensive laparoscopic experience. Laparoscopic retroperitoneal lymphadenectomy is a technically demanding procedure which can be successfully completed in the majority of patients. However, the risk of complications is greater than in patients who undergo standard open retroperitoneal lymph node dissection. The primary advantage of a laparoscopic approach is shortened hospitalization and rapid return to normal activity. The role of laparoscopy in the management of patients with testis malignancy has not been defined. The use of this staging procedure may help minimize the need for surveillance studies following surgery and may be best utilized in men with a lower likelihood of nodal metastases. Ultimately, prospective study in large groups of patients will be necessary to determine the role of laparoscopic retroperitoneal lymph node dissection in patients with testis cancer.

Expression of Sialyl-Tn in Breast Cancer Correlation with Prognostic Parameters

To investigate the expression of a simple mucin-type carbohydrate antigen (Sialyl-Tn/STn) and its putative relationship with established or potentially useful clinico-pathologic prognostic parameters in breast cancer, we studied forty-six cases of invasive breast carcinoma in formalin-fixed, paraffin-embedded tissue sections. STn antigen was detected by the HB-STn antibody using an avidin-biotin-peroxidase method. The parameters studied were tumour size, histologic grade, nodal status, proliferative index (with MIB-1), ER expression, ploidy, c-erbB-2 and p53 expression. STn expression was observed in 18 cases (39%) of breast cancer. The expression of STn was associated with axillary node metastasis, ER negativity and c-erbB-2 expression. A tendency towards an association between STn immunoreactivity and high histologic grade was also found. No correlation was observed between STn immunoreactivity and age, tumour size, proliferative index, ploidy and p53 expression. We conclude that the detection of STn immunoreactivity may be useful for predicting the likelihood of lymph node metastasis and that the outcome of patients with breast cancer should be further investigated in order to find whether or not the data of the present study are confirmed in larger series.

Correlation between sialyl Tn antigen and lymphatic metastasis in patients with Borrmann type IV gastric carcinoma.

The expression of sialyl Tn (STn) antigen in 180 patients with Borrmann type IV gastric carcinomas was examined immunohistochemically. The rate of positive STn staining was 32% (57/180) for the primary tumours, and this positive staining correlated well with tumour extension, lymph node metastasis (P < 0.05) and peritoneal dissemination (P < 0.01). One-third (5/15) of patients with positive STn-staining cancer cells had a high level of serum STn. Lesions with positive STn staining were related to a lower survival rate for the patients (P < 0.05). Proliferative activity of the tumour, as measured by proliferating nuclear antigen (PCNA) labelling percentage and argyrophilic nucleolar organiser region (AgNOR) count, was significantly higher (41.5 +/- 13.0%, 3.78 +/- 0.98) in the STn-positive group than in the STn-negative group (34.2 +/- 13.2%, 3.48 +/- 0.85) (P < 0.01, P < 0.05 respectively). Estimating STn antigen may be useful for predicting the likelihood of lymph node metastasis or peritoneal dissemination and the clinical prognosis for patients with Borrmann type IV gastric carcinoma.