Value Of Lymph Node Metastasis Research Articles

The prognostic value of lymph node metastases and tumour regression grade in rectal cancer patients treated with long‐course preoperative chemoradiotherapy

The purpose of the present study was to investigate the impact of tumour regression and the post-treatment lymph node status on the prognosis of rectal cancer treated by preoperative neoadjuvant chemoradiotherapy. One hundred and thirty-five patients with locally advanced T3 and T4 rectal tumours received preoperative long-course chemoradiation, to a dose of 60 Gy external radiation and oral 5-fluorouracil 300 mg/m(2) daily and Leukovorin 22.5 mg/day 5 days a week. Surgery was performed 8 weeks after the end of treatment. The tumour response was evaluated according to the tumour regression grade system and lymph node status in the surgical specimen was assessed. The prognostic value of clinico-pathological parameters was analysed using univariate analysis and Kaplan-Meier methods for comparison of groups. All patients responded to treatment and 47% had a major response, including 25 (19%) complete responders. The median follow-up was 26 months (range 12-94 months). The cancer specific survival was 82% and there was a significant lower survival rate in the group of patients with post-treatment lymph node metastases compared to lymph-node negative patients [63% and 87% respectively (P = 0.007)]. Furthermore patients with a major tumour response and no lymph node metastases in the surgical specimen after treatment had a survival rate of 100% compared with 60% in the group of patients with major response but lymph node metastases after surgery (P < 0.01). The combined assessment of lymph-node status and tumour response has strong prognostic value in locally advanced rectal cancer patient treated with preoperative long-course chemoradiation.

HPV status in sentinel nodes might be a prognostic factor in cervical cancer

Although there have been studies that focused on the correlation between the HPV presence of pelvic lymph nodes and pathological metastasis in patients with cervical cancer, the biologic role of HPV DNA in lymph nodes still remains uncertain. We performed this study to investigate the correlation between the sentinel-node HPV status and pelvic lymph node metastasis in patients with cervical cancer. The patients were followed up for 3 years to evaluate the clinical role of HPV in sentinel nodes as a prognostic factor. From August 2001 to July 2003, 57 patients affected by stages IB-IIA cervical cancer had sentinel-node biopsies performed during radical hysterectomy and pelvic and paraaortic lymphadenectomy. Each detected sentinel node was divided into two parts. One part of them was submitted for frozen section examination and the other was submitted for HPV typing by oligonucleotide microarray. After follow-up, we analyzed the outcome of the patients with respect to the influence of sentinel-node HPV. Sentinel nodes were identified in all patients. A total of 79 nodes from 57 patients were detected as sentinel nodes. Metastasis in the sentinel nodes were found in 10 patients (17.6%) by frozen section and 11 patients by pathologic examination. The results of sentinel lymph node frozen biopsy were statistically significant for predicting the metastasis of the pelvic lymph nodes (P<0.05), but showed one false-negative case. HPV DNA was detected in the cervical cancer lesions of 55 patients (96.5%) and 80.0% (44/55) of them were found to have HPV DNA in the sentinel nodes as well. HPV DNA was detected in sentinel nodes of 10 patients among 11 patients with lymph node metastasis. Disease recurred in five patients and one of them did not show pelvic lymph node metastasis at surgery. But, all of these patients had HPV in sentinel nodes. The combination of sentinel-node frozen biopsy and HPV typing showed a negative predictive value of 100% in predicting non-metastasis of lymph node and no recurrence of disease. Our results suggested the possibility that sentinel-node HPV typing could play a supportive role to reduce the false-negative rate of the sentinel-node biopsy. All of five patients with recurrence had HPV infection in the sentinel nodes. Absence of HPV in sentinel nodes showed reliable negative predictive value for lymph node metastasis and recurrence. Additional study will be needed to confirm the clinical application of the sentinel-node procedure and to determine whether there is a correlation of HPV status of sentinel nodes to lymph node metastasis and recurrence in cervical cancer patients.

Extracapsular spread of nodal metastasis as a prognostic factor in rectal cancer

PurposeTo evaluate the prognostic value of lymph node metastasis with extracapsular extension (ECE) for local control and metastasis-free survival in rectal cancer. Methods and materialsA total of 145 rectal cancer patients were treated with surgery and postoperative radiochemotherapy. Patients were grouped according to nodal status (node negative, n = 49; node positive without ECE, n = 64; node positive with ECE, n = 32). In addition, well-known prognostic factors such as International Union Against Cancer (UICC) stage, T and N stage, presence of lymphangiosis, and grade were assessed. The end points were analyzed by the Kaplan-Meier method, and prognostic factors were compared in a Cox regression model. ResultsOf the entire group, the actuarial 5-year local control and distant metastasis-free survival rate was 85% and 66%, respectively, after a median follow-up of 47 months (range, 14–104). Patients with ECE of lymph node metastasis had an impaired 5-year local control rate (58%) compared with node-negative (83%) and node-positive without extracapsular involvement patients (87%, p = 0.041). Metastasis-free survival also differed for the three groups, with a rate of 40% for those with extracapsular involvement, 54% for those without ECE, and 78% for node-negative patients (p <0.0001). The impact of ECE on local control was confirmed in the regression model (risk ratio [RR] 1.6, 95% confidence interval [CI] 1.01–2.7, p = 0.044). T stage was only of borderline significance (RR 2.4, 95% CI 1.0–5.7, p = 0.052). However, only UICC stage (RR 5.1, 95% CI 2.0–13.1, p <0.001) and the presence of lymphangiosis (RR 2.8, 95% CI 1.4–5.3, p = 0.002) were of independent prognostic value for distant metastasis. ConclusionECE of node metastasis is connected with a substantial decline in local control. The frequency of distant metastasis is increased in this patient group as well, but stage and lymphangiosis are the independent factors for assessment of a patient's risk of systemic spread.

Comparison of EUS and magnifying colonoscopy for assessment of small colorectal cancers

Background: Prediction of invasion depth and lymph node metastasis is mandatory when local treatment is considered for small colorectal cancer. The aim of this study was to compare the accuracy of EUS with a catheter probe (probe-EUS) and magnifying colonoscopy for prediction of invasion depth and lymph node metastasis for small colorectal cancer. Methods: Small colorectal cancers were imaged by both probe-EUS and magnifying colonoscopy. Invasion depth by probe-EUS was determined by the presence or absence of distortion of the third sonographic layer. Findings by magnifying colonoscopy were divided into regular, distorted, and amorphous patterns. Histopathologically, depth of invasion was classified as intramucosa/slight or deep invasion. Findings by probe-EUS and magnifying colonoscopy were compared with respect to deep invasion and lymph node metastasis. Results: There were 22 small colorectal cancers with intramucosa/slight invasion and 28 with deep invasion. Four of 30 cancers had associated lymph node metastasis. Accuracy for depth of invasion was 91.8% for probe-EUS and 63.3% in magnifying colonoscopy, the difference being statistically significant ( p = 0.0013). Negative predictive value of probe-EUS for deep invasion was higher than that for magnifying colonoscopy (respectively, 90.9% vs. 54.1%) in the population studied (prevalence deep invasion 56%). The accuracy for lymph node metastasis was 24.1% for probe-EUS and 72.4% for magnifying colonoscopy, the difference being statistically significant ( p < 0.001). Positive predictive value for lymph node metastasis was higher when the amorphous pattern was noted by magnifying colonoscopy compared with the positive predictive value for deep invasion by probe-EUS (respectively, 33.3% vs. 8.7%) in the population studied (prevalence lymph node metastasis 13.3%). Conclusions: Probe-EUS is superior to magnifying colonoscopy for determination of invasion depth in small colorectal cancer. Magnifying colonoscopy may be predictive of lymph node metastasis, thereby suggesting that the procedures provide complementary information with respect to the decision for local versus surgical therapy. (Gastrointest Endosc 2002;56:354-60.)

Clinical results and prognostic factors of radiologically node-positive gastric carcinoma.

Lymph node metastasis determined by histologic examination is an important prognostic indicator in gastric carcinoma. However, prognostic value of lymph node metastasis detected by computed tomography (CT) is unknown. The aim of this study was to evaluate clinical results and prognostic factors of patients with radiologically node-positive gastric carcinoma. The study included 78 patients with primary gastric carcinoma and lymph node metastasis confirmed by CT. The level of lymph node metastasis was simply graded as follows: level I included perigastric nodes; level II included intermediate nodes along the left gastric, common hepatic, and celiac arteries; and level III included distant nodes along the hepatoduodenal ligament, pancreas, spleen, and abdominal aorta. Sixty patients (79%) had stage IV tumors showing one or more of the following: level III lymph node metastasis in 37, pancreatic invasion in 27, peritoneal dissemination in 23, and liver metastasis in 19. Overall 1- and 5-year survival rates were 29% and 6%, respectively, and the 1-year survival rate was significantly influenced by the level of lymph node metastasis on CT (55% for level I, 27% for level II, 7% for level III, P < 0.01). In patients with gastrectomy, prognostic factors were tumor size (<10 cm versus >10 cm, P < 0.01), gross type (localized versus infiltrative, P < 0.01), histologic type (well differentiated versus poorly differentiated, P < 0.01), and curability of the disease (curative versus noncurative, P < 0.01). Our study indicates that prognosis of patients with radiologically node-positive gastric carcinoma is poor because of high frequency of extensive tumor spreads. Patients having only positive level I nodes on CT are candidates for curative gastrectomy, which may offer long-term survival.

Prognostic Value of Preoperative Squamous Cell Carcinoma Antigen Level in Patients Surgically Treated for Cervical Carcinoma

Preoperative evaluation of squamous cell carcinoma antigen (SCCa) was performed in 220 patients with surgically treated early-stage carcinoma of the cervix. The median duration of follow-up was 1.9 years. SCCa was significantly higher in tumors with a squamous element (P< 0.001). There was a squamous element in 171 tumors. SCCa was elevated (>2 ng/ml) in 21.6%. Significantly higher levels were associated with stage II disease (P< 0.001), tumors >4-cm size (P< 0.001), and lymph node metastases (P< 0.001). The positive predictive value for lymph node metastases at >2, >4, and >8.6 ng/ml SCCa is 51.4, 70.0, and 100% and the sensitivity is 58.1, 45.2, and 22.6%, respectively. Low SCCa is a poor predictor of absence of lymph node metastasis. The median SCCa for patients who developed tumor recurrence was greater than those who remained disease free (1.7 and 1.0 ng/ml, respectively,P= 0.009); however, in a multivariate analysis only lymph node metastasis and tumor size were of independent prognostic significance (P= 0.002 andP= 0.004, respectively). SCCa level >8.6 ng/ml is highly predictive of lymph nodal disease. There is no independent prognostic significance in patients with early-stage surgically treated cervical carcinoma.

Lymph node excision in thyroid carcinoma

The prognostic value of lymph node metastases in thyroid cancer has been a matter of controversy for many years. However, during the past decade most multivariate analyses have shown a prognostic influence of lymph node metastases in papillary as well as medullary thyroid carcinoma constituting the basis for a standardized concept of lymphadenectomy oriented to the lymph node classification of the UICC (1993). Due to the frequency of lymph node metastases in the ipsilateral cervicocentral compartment (42-86%), in the ipsilateral cervicolateral compartment (32-68%), in the contralateral cervicolateral compartment (12-24%), and in the mediastinal compartment (3-20%), these compartments can be defined as the lymph node regions of the first, second, third and fourth order, respectively. Cervicocentral systematic lymphadenectomy should be part of the en bloc resection of the thyroid gland and the first lymph node region in any thyroid cancer. Cervicolateral as well as mediastinal lymphadenectomy should be performed according to the extent of lymph node involvement, i.e. systematically when multiple lymph node metastases are present, otherwise selectively. One exception is in medullary thyroid carcinoma, where a four-compartment lymphadenectomy is recommended in any patient with positive lymph nodes. Performing a gentle technique using magnifying glasses and bipolar coagulation forceps, systematic lymphadenectomy does not increase the rate of complications, can decrease the recurrence rate and improve survival.

Current status of cancer immunodetection with radiolabeled human monoclonal antibodies

The use of radiolabeled murine monoclonal antibodies (MoAbs) for cancer immunodetection has been limited by the development of human antimouse antibodies (HAMA). Human monoclonal antibodies do not elicit a significant human antihuman (HAHA) response. The generation and production of human monoclonal antibodies met with technical difficulties that resulted in delaying their clinical testing. Human monoclonal antibodies of all isotypes have been obtained. Most were immunoglobulin (Ig) M directed against intracellular antigens. Two antibodies, 16.88 (IgM) and 88BV59 (IgG3k), recognize different epitopes on a tumor-associated antigen, CTA 16.88, homologous to cytokeratins 8, 18, and 19. CTA 16.88 is expressed by most epithelial-derived tumors including carcinomas of the colon, pancreas, breast, ovary, and lung. The in vivo targeting by these antibodies is related to their localization in nonnecrotic areas of tumors. Repeated administration of 16.88 over 5 weeks to a cumulative dose of 1,000 mg did not elicit a HAHA response. Two of 53 patients developed a low titer of HAHA 1 to 3 months after a single administration of 88BV59. Planar imaging of colorectal cancer with Iodine-131 (131I)-16.88 was positive in two studies in 9 of 12 and 16 of 20 patients preselected by immunohistochemistry. Tumors less than 2 cm in diameter are usually not detected. The lack of immunogenicity and long tumor residence time (average = 17 days) makes 16.88 a good candidate for therapy. Radioimmunlymphoscintigraphy with indium-111 (111In)-LiLo-16.88 administered by an intramammary route was used in the presurgical staging of primary breast cancer. The negative predictive value of lymph node metastases for tumors less than 3 cm was 90.5%. Planar and single photon emission computed tomography imaging of colorectal carcinoma with technetium-99m (99mTc) 88BV59 was compared with computed tomography (CT) scan in 36 surgical patients. The antibody scan was more sensitive than the CT scan in detecting abdominal and pelvic tumors: 68% versus 40% (P < .05). The combination of antibody scan and CT scan was superior to CT scan alone: 80% versus 40% (P < .01). Lesions as small as 0.5 cm in diameter were detected by antibody scan. The CT scan appears superior to the antibody scan for liver metastases. Patients with a high serum titer of HAMA from previous exposure to murine antibodies were successfully imaged. Antibody scans obtained with 99mTc-88BV59 have imaging characteristics similar to murine antibody scans obtained with radiolabeled IgGs. The absence or weak immunogenicity of the human monoclonal antibodies makes them good candidates for radioimmunodetection and radioimmunotherapy.

Endosonography of pararectal lymph nodes

One hundred thirteen patients with carcinoma of the rectum were evaluated for lymph node metastases by endorectal ultrasound. With the use of 7.5 MHz and based on different echo patterns, two main groups of lymph nodes can be differentiated: hypoechoic and hyperechoic lymph nodes. Compared with pathologic findings, hypoechoic lymph nodes represent metastases, whereas hyperechoic lymph nodes are visualized due to unspecific inflammation. Lymph node metastases can be predicted with a sensitivity of 72 percent and inflammatory lymph nodes with a specificity of 83 percent. The physical basis of the differentiation of lymph nodes was assessed in vitro by the determination of ultrasound parameters (speed of sound, acoustic impedance, attenuation, and backscattered amplitude). The attenuation coefficient of benign lymph nodes [2.5 dB/(MHz x cm)] is significantly higher than the mean value of lymph node metastases [1.3 db/(MHz x cm)]. The results demonstrate that involved nodes can principally be differentiated from not involved nodes. Micrometastases, mixed lymph nodes, and changing echo patterns within inflammatory nodes explain the accuracy rate of 78 percent.