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A new American Joint Committee on Cancer staging system for cutaneous melanoma.

The Melanoma Staging Committee of the AJCC has proposed major revisions of the melanoma TNM and stage grouping criteria. The committee members represent most of the major cooperative groups and cancer centers worldwide with a special interest in melanoma; the committee also collectively has had clinical experience with over 40,000 patients. The new staging system better reflects independent prognostic factors that are used in clinical trials and in reporting the outcomes of various melanoma treatment modalities. Major revisions include 1) melanoma thickness and ulceration, but not level of invasion, to be used in the T classification; 2) the number of metastatic lymph nodes, rather than their gross dimensions, the delineation of microscopic versus macroscopic lymph node metastases, and presence of ulceration of the primary melanoma to be used in the N classification; 3) the site of distant metastases and the presence of elevated serum LDH, to be used in the M classification; 4) an upstaging of all patients with Stage I,II, and III disease when a primary melanoma is ulcerated; 5) a merging of satellite metastases around a primary melanoma and in-transit metastases into a single staging entity that is grouped into Stage III disease; and 6) a new convention for defining clinical and pathologic staging so as to take into account the new staging information gained from intraoperative lymphatic mapping and sentinel lymph node biopsy. The AJC Melanoma Staging Committee invites comments and suggestions regarding this proposed staging system before a final recommendation is made.

Biopsy↗

Cox multivariate regression models for estimating prognosis of patients with endometrioid adenocarcinoma of the uterine corpus who underwent thorough surgical staging.

The International Federation of Gynecology and Obstetrics (FIGO) adopted surgical staging criteria in 1988. Many studies have shown that histologic grade, nuclear grade, lymph-vascular space invasion and cell type are also important predictors of survival. It has not been clarified, however, how to integrate these histopathologic variables into the process of estimating individual prognosis. We performed Cox multivariate regression analysis to create models that incorporate various histopathologic factors for estimating the prognoses of patients with endometrioid adenocarcinoma of the uterine corpus. Our study was based on data from 206 patients who underwent complete surgical staging, including systematic pelvic and para-aortic lymph node dissection. Two models resulted: one included depth of myometrial invasion, para-aortic node metastasis and the number of sites involved by the tumor among the cervix, ovary and pelvic lymph nodes (which we designated as extracorporeal spread score, ECS) and the other incorporated nuclear grade and lymph-vascular space invasion as variables. These 2 models enabled the prognosis for patients with endometrioid adenocarcinoma to be stratified into several levels according to hazard ratio. Comprehensive integration of the histopathologic prognostic factors, categorized into those relating to tumor extent and those relating to tumor virulence, should facilitate the estimation of individual prognosis more accurately than FIGO staging alone.

Adenocarcinoma↗

Occult sporadic medullary microcarcinoma with lymph node metastases.

A sporadic form of medullary occult microcarcinoma was cytologically diagnosed, by fine-needle aspiration biopsy (FNAB), on metastatic cervical lymph nodes. The cytologic specimens were partially smeared and partially zinc-formalin-fixed, so that a microinclusion clot for immunohistochemical studies would be possible. The reactivity to calcitonin of neoplastic cells obtained from metastatic cervical lymph nodes supported the search for a thyroid tumor, which only a careful echographic study revealed. Under sonographic guidance, FNAB on a 0.5-cm hypoechoid nodule was performed. The smears were diagnostic of medullary carcinoma. A total thyroidectomy with node dissection was made. Diagn. Cytopathol. 1999;21:203-206.

Biopsy, Needle↗

Frequency and therapeutic implications of "skip metastases" in the neck from squamous carcinoma of the oral tongue.

BACKGROUND: Supraomohyoid neck dissection is an adequate operation for the elective treatment of the neck for patients with oral cavity cancer. Squamous cell carcinoma of the oral tongue, however, metastasize to clinically negative nodes in 20% to 30% of patients. These nodes usually are located in levels I-III. METHODS: The medical records of 277 previously untreated patients with squamous cell carcinoma of the oral tongue were reviewed between the years 1970 and 1990. All patients had a glossectomy and neck dissection as part of their initial treatment. Patients were evaluated as to the findings in their neck. The following group of patients were included: (1) patients who had level III nodes positive, without disease in levels I and II; (2) patients with disease in level IV; (3) patients with disease in level IIB or IIIB, and; (4) patients who were electively dissected and whose neck did not demonstrate any pathologically involved nodes, but level IV was not included in the dissection and the patient subsequently developed pathologically positive nodes in level IV. RESULTS: Of all patients, 15.8% had either level IV metastasis as the only manifestation of disease in the neck or the level III node was the only node present without disease in level I-II. CONCLUSION: The usual supraomohyoid neck dissection is inadequate for a complete pathologic evaluation of all the nodes at risk for patients with squamous carcinoma of the oral tongue. This may create a dilemma in determining whether postoperative radiotherapy is necessary. Consequently, all patients with squamous cell carcinoma of the oral tongue should have levels I-IV nodes removed if an elective neck dissection is part of their initial therapy.

Carcinoma, Squamous Cell↗

Can we detect or predict the presence of occult nodal metastases in patients with squamous carcinoma of the oral tongue?

BACKGROUND: When to do a neck dissection as part of the surgical treatment for a patient with squamous carcinoma of the oral tongue is controversial, particularly when the primary can be resected without entering the neck. If the patient who is at high risk for having occult nodal disease in the neck can be identified, node dissection with the glossectomy could be justified. To better identify patients for this procedure, we correlated various tumor and patient factors along with preoperative diagnostic studies with the presence or absence of pathologically positive nodes in a group of patients who underwent node dissection. METHODS: Ninety-one previously untreated patients with biopsy-proved squamous carcinoma of the oral tongue were prospectively studied. All patients had a glossectomy and neck dissection as their initial treatment. The pathology findings (ie, lymph nodes with squamous cancer) were correlated with many preoperative and intraoperative factors, and a statistical analysis was made. RESULTS: The use of computed tomography and ultrasound was not better than the clinical examination in determining the presence or absence of nodal metastases. The best predictors were depth of muscle invasion, double DNA aneuploidy, and histologic differentiation of the tumor. CONCLUSIONS: All patients with stage T2-T4 squamous cancers of the oral tongue should have an elective dissection of the neck. Patients with T1N0 cancer who have a double DNA-aneuploid tumor, depth of muscle invasion > 4 mm, or have a poorly differentiated cancer should definitely undergo elective neck dissection. Ultrasound and computed tomography are of little value in predicting which patients have positive nodes.

Adult↗

Improved survival for patients with clinically T1/T2, N0 tongue tumors undergoing a prophylactic neck dissection.

BACKGROUND: Prophylactic surgical treatment of the neck in "early tongue tumors" is a controversial issue. METHODS: From a database of 226 patients with squamous cell carcinoma of the tongue treated at Canniesburn Hospital, Glasgow, U.K., between 1980 and 1996, a total of 137 patients with a minimum follow up of 24 months or until death were clinically identified as being T1/T2, N0 (UICC) when first seen. These patients were divided into three groups according to the management of the neck; 53 patients did not have a neck dissection at any time (NKD0), 47 patients underwent a synchronous neck dissection at the time of treatment of the primary (NKDS), and 37 patients subsequently required a metachronous neck dissection when lymph node metastasis became clinically apparent (NKDM). These three groups were compared with respect to age, sex, site, duration of symptoms, previous treatment (if any), initial treatment protocol, resection margin, type of neck dissection (if any), loco-regional recurrence, systemic escape, number of positive lymph nodes, and presence of extracapsular spread. Disease-related survival was calculated using Kaplan-Meier survival curves with logrank test and chi-square statistical analysis. RESULTS: The pT stage was upgraded to T3/4 in 3/53 patients (6%) of the NKD0 group, 11/47 patients (23%) of the NKDS group, and 2/37 patients (5%) of the NKDM group (p < 0.001). The 5-year determinate survival rates for the three groups were: NKD0 59.7%, NKDS 80.5%, NKDM 44.8%, and (NKD0 + NKDM) 53.6% with a statistically significant improvement in survival for NKDS vs NKDM (logrank 10.58, p = 0.001) and for NKDS vs (NKD0 + NKDM) (logrank 6.06, p = 0.014). The incidences of positive nodes in the NKDS and NKDM groups were 18/47 patients (38%) and 32/37 patients (86%) respectively. Neck positive patients in the NKDM group had a significantly greater number of positive nodes in comparison with N positive patients in the NKDS group (chi trend, p = 0.001), a higher incidence of extracapsular spread, 30/32 vs 9/18 (chi test, p < 0. 0001), and decreased survival. The incidence of occult cervical metastasis for the whole group was 41%. CONCLUSION: Patients with clinical T1/2, N0 tongue tumors who underwent a synchronous neck dissection had an improved survival outcome even though as a group they had a higher incidence of occult metastasis, relatively more T2 lesions, a worse pT stage, and had more posterior third lesions requiring more difficult initial surgery. Tongue tumors have a high incidence of subclinical nodal disease, which is less curable when it presents clinically. The information gleaned from the nodal status allows a more informed plan of adjuvant therapy.

Adult↗

A suggested method for sentinel node biopsy in squamous cell carcinoma of the head and neck.

BACKGROUND: Debate continues over the management of the N0 neck in head and neck malignancy. Therefore, the possibility of performing sentinel node biopsy in these patients was investigated to formulate a method for the procedure. METHODS: Patients undergoing prophylactic or therapeutic neck dissections were injected with either Patent Blue V dye alone or with blue dye and 99m-Tc labeled Albures. The latter group underwent preoperative lymphoscintigraphy. During surgery, blue stained lymphatics were followed to blue nodes, and a neoprobe was used to identify radioactive nodes. RESULTS: In 5 of 13 patients receiving blue dye, a blue node was identified, but none contained tumor. Metastases were identified in other neck nodes in 3 of 5. Sentinel nodes were identified in 15 of 16 patients receiving dye, and Albures. Sentinel node biopsy was accurate in 7 of 7 necks containing impalpable metastases when all nodes had been evaluated after dissection. DISCUSSION: Sentinel node biopsy using blue dye and radiocolloid may prove to be a reliable technique in the N0 neck and warrants further investigation.

Biopsy↗

Prognostic significance of the distribution of neck node metastasis from oral carcinoma.

BACKGROUND: Carcinoma of the oral cavity presents a high risk for neck metastasis, which reduces the probability of regional control and survival. OBJECTIVES: The main objective of this study is to analyze prognostic implications of the distribution of neck metastasis in 513 patients with squamous cell carcinoma of the oral cavity. PATIENTS AND METHODS: All patients underwent surgery from 1970-1992. Tumor stages were I, 63; II, 120; III, 173; and IV, 157. Neck dissections were performed in 448 patients (115 bilateral). RESULTS: By use of multivariate regression techniques the level of lymph node involvement was the most important prognostic factor (relative risks from 1.8 to 2.5). The following variables were also associated with prognosis: mobility of lymph nodes, sex, T stage, age, and tumor thickness. CONCLUSIONS: The level of ipsilateral lymph node involvement was the most significant prognostic factor patients with in oral cancer who underwent surgical treatment. A significant decrease in survival also was seen with regard to the involvement of multiple contralateral lymph nodes. Our results support the indication of elective neck dissections in high-risk patients because among the cases that had metastases at follow-up, 50% were not candidates for salvage treatment.

Adult↗

Cyclin D1 expression is predictive of occult metastases in head and neck cancer patients with clinically negative cervical lymph nodes.

BACKGROUND: The aim of this study was to investigate the value of p53 and cyclin D1 gene expression in predicting the risk of occult lymph node metastases in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: The expression of cyclin D1 and p53 was evaluated by means of immunohistochemical analysis in 32 HNSCC patients with clinically and radiologically negative lymph nodes in whom metastatic involvement was subsequently demonstrated at histologic examination (pN+). A group of 64 head and neck cancer patients with histologically negative laterocervical lymph nodes (pN0) was used as a control. RESULTS: Cyclin D1 and p53 expression were observed respectively in 42 (43.7%) and 48 cases (50%). Cyclin D1 expression significantly correlated with tumor extension and advanced clinical stage (p =.002 and p =.001, respectively). At univariate regression analysis, cyclin D1 expression significantly correlated with the presence of occult lymph node metastases (p =. 0007), and it remained an independent predictor at multivariate regression analysis (p =.0059). CONCLUSIONS: Our study indicates that the expression of cyclin D1 correlates with the presence of occult cervical metastases in head and neck carcinoma patients, thus suggesting that its immunohistochemical evaluation in biopsy samples may be used as an additional tool for identifying patients to be treated with elective neck dissection.

Adult↗

Surgical management of stage I and II melanoma patients: approach to the regional lymph node basin.

The role for elective lymph node dissection in the management of clinically localized (Stage I and II) melanoma patients represents a long-standing controversy. Contemporary randomized elective lymph node dissection trials have been completed with recently presented results demonstrating some survival benefit for surgical therapy of micrometastases in specific subsets of patients. Lymphatic mapping and sentinel node biopsy offers a rational alternative to elective lymph node dissection for all high risk Stage I and II melanoma patients. Recent advances in lymphatic mapping techniques have resulted in improved identification of the sentinel node. Combined with advances in histologic evaluations of lymph nodes, accurate and minimally invasive mechanisms for assessing lymph node status are now available. This latter goal is critical in light of recently published data demonstrating improved survival with the use of high dose interferon alpha administered in the adjuvant setting for patients with nodal metastases.

Biopsy↗

Lymphatic mapping and sentinel lymphadenectomy for melanoma.

Intraoperative lymphatic mapping and sentinel lymphadenectomy (SLND) for patients with clinical Stage I melanoma was developed to determine the tumor status of the regional lymphatic basin without elective regional node dissection. Only individuals with histologically confirmed sentinel node (SN) metastases undergo complete regional node dissection, sparing those with tumor-free SN the morbidity of this procedure. Studies worldwide have confirmed the validity of the SN concept and the accuracy of SLND as a staging procedure. The incidence of false-negative SN and the rate of recurrence in the regional node basin have been low. Routine preoperative lymphoscintigraphy and refinements in surgical technique have improved the accuracy of SLND for melanoma, making it the nodal staging procedure of choice when undertaken by an experienced nuclear medicine physician, surgical oncologist and pathologist. Ongoing studies are investigating the impact of SLND on survival as well as the prognostic significance of micrometastasis detected by histopathologic and molecular techniques.

Humans↗

Sentinel lymph node mapping opens a new perspective in the surgical management of early-stage breast cancer: a combined approach with vital blue dye lymphatic mapping and radioguided surgery.

Recent studies have demonstrated the possibility of identifying the sentinel lymph node (sN) as a reliable predictor of axillary lymph node status in both cutaneous melanoma and breast cancer. However, some important issues need further definition: (1) optimization of the technique for intraoperative detection of the sN; (2) predictive value of the sN as regards axillary lymph node status, and (3) reliability of intraoperative histology of the sN. We report our experience in sN mapping in patients with Stage I-II breast cancer, with the aim of assessing: (1) the feasibility of lymphatic mapping with a combined approach (vital blue dye lymphatic mapping and radioguided surgery); (2) the agreement of the intraoperative histologic examination of the sN, by means of hematoxylin and eosin staining with final histology, and (3) the accuracy of sN histology as a predictor of axillary lymph node status.

Aged↗

Sentinel node biopsy in patients with cutaneous melanoma.

The role of elective lymph node dissection (ELND) for treatment of cutaneous melanoma is still debated. Initially, lymphatic mapping technique was performed by an intradermic injection of vital blue dye; subsequently, it was improved by the use of radioguided surgery (RGS). Preliminary experience with this technique proved effective for detection of clinical occult lymph node metastasis; it may also enable the surgeon to perform a selective lymph node dissection (SLND) to concentrate on pathologic node-positive patients for the same potential benefits that have been provided by ELND. We performed sentinel node biopsy on 48 patients with stage pT3N0M0 melanoma. Vital blue dye mapping only was carried out on 39 patients; the remaining nine patients had a combined lymphatic mapping with both blue dye and RGS. The sentinel lymph node (SLN) was identified in 46 of 48 patients (95.8%). Ten patients (20.8%) were found to have metastatic melanoma cells in their SLN(s); all these patients underwent SLND of the affected basin. Our findings confirm that the intraoperative lymphatic mapping of the SLN using both blue dye and radiodetection is an appropriate and simple technique for selecting patients who are more likely to benefit from lymph node dissection.

Adolescent↗

Clinicopathologic characteristics and outcome indicators in node-negative gastric cancer.

BACKGROUND AND OBJECTIVES: The relationship between the number of lymph nodes examined and the outcome in patients with node-negative (N(-)) gastric cancer was studied. We compared N(-) patients to those with nodal involvement (N(+)) to identify clinicopathologic characteristics of N(-) gastric cancer. Finally, we evaluated outcome indicators in this group of patients. METHODS: Of 367 patients, 130 (35.4%) were N(-). These patients were stratified according to the main prognostic variables, to assess differences with N(+) cases. A statistical analysis using the Cox model was performed to estimate outcome indicators. RESULTS: N(-) gastric carcinomas were significantly different from N(+) cases in terms of tumor depth and site, TNM stage, grading, residual disease, and vessel involvement. The overall 5-year survival rate was 72%. It was 82% in those patients with more than 15 nodes retrieved and 59% in the others. Serosal involvement, residual disease, and poor differentiation were independent prognostic factors. CONCLUSIONS: The clinicopathologic factors and outcome of N(-) cases were similar to those of early gastric cancer. At least 15 examined nodes appears to be necessary to define a case as N(-). The prognostic value of D2 lymphadenectomy in N(-) patients suggests a biologic role of micrometastases.

Adult↗

Sentinel lymph node mapping in early-stage breast cancer: technical issues and results with vital blue dye mapping and radioguided surgery.

BACKGROUND AND OBJECTIVES: Axillary lymph node status is the most important prognostic factor in patients with operable breast cancer. Recent studies have demonstrated the possibility of identifying the sentinel lymph node (sN) as a reliable predictor of axillary lymph node status in both cutaneous melanoma and breast cancer. Sentinel lymph node identification proved feasible by either peritumoral dye injection (Patent Blue-V) or radiodetection, with identification rates of 65-97% and 92-98%, respectively. However, some important issues need further definition, namely (a) optimization of the technique for intraoperative detection of the sN, (b) predictive value of the sN with regard to axillary lymph node status, and (c) reliability of intraoperative histology of the sN. We reviewed our experience in sN detection in patients with stage I-II breast cancer to assess the feasibility and accuracy of lymphatic mapping, by vital blue dye or radioguided surgery, and sN histology as a predictor of axillary lymph node status. METHODS: Two groups of patients (55 and 48) were recruited between May 1996 and May 1997 and between October 1997 and February 1998; the patients of the first series underwent vital blue dye lymphatic mapping only, whereas those of the second series had a combined approach with both vital blue dye mapping and radioguided detection of the sN. RESULTS: In the first set of patients, the sN was identified in 36/55 patients (65.4%); sN histology predicted axillary lymph node status with a 77% sensitivity (10/13), a 100% specificity (23/23), an 88.5% negative predictive value (23/26), and an overall 91.5% accuracy (33/36). The sN was the quasi-elective site of lymph node metastases because in clinically N0 patients nodal involvement was 20-fold more likely at histology in sN than in non-sN (30% and 1.5%, respectively). In the second set of patients, 49 lymphadenectomies were performed because 1 patient had bilateral breast cancer; the sN was identified in 45/49 lymphadenectomies (92%). The sN was intraoperatively negative at frozen-section examination in 33 cases, and final histology confirmed the absence of metastases in 31/33 cases (94%), whereas in 2 cases (6%) micrometastases only were detected. Final histology of the sN predicted axillary lymph node status with an 87.5% sensitivity (14/16), a 100% specificity (29/29), a 93.5% negative predictive value (29/31), and an overall 95.5% accuracy (43/45). CONCLUSIONS: Sentinel lymphadenectomy can be better accomplished when both mapping techniques (vital blue dye and radioguided surgery) are used. In this group of patients, agreement of intraoperative histology of the sN with the final diagnosis was 94%, and sN histology accurately predicted axillary lymph node status in 43/45 lymphadenectomy specimens (95.5%) in which an sN was identified.

Adult↗

Pattern of lymphatic drainage to the sentinel lymph node in breast cancer patients.

BACKGROUND AND OBJECTIVE: We performed a pilot study on 30 consecutive patients undergoing sentinel node (sN) biopsy by radioguided surgery and vital blue dye mapping to determine whether there is a single sN for each breast independent of tumor site or an sN specifically related to the site of the breast neoplasm. METHODS: There were 6 groups of 5 patients; each patient had a subdermal injection of radiotracer on the tumor site plus a second injection of radiotracer that was changed in every subset of patients to test whether modifying the site or the route of injection could have impaired the proper detection of the sN. RESULTS: "False" sN were detected only in patients who had a second injection of radiotracer away from the tumor site; this occurred in 2 of 5 patients (40%) in group I, in 3 of 5 patients (60%) in group II, in all patients in group III, and in 3 of 5 patients (60%) in group IV. The different route of injection (peritumoral or subdermal) always on the tumor site that was tested in groups V and VI did not impair the proper detection of the sN. CONCLUSIONS: Our findings support the hypothesis of a precise topographic correspondence between the primary tumor and its specific sN more than the existence of a first sN in the axillary basin, which indiscriminately drains all quadrants of the breast, like "a neck of a bottle." This should be considered for the proper selection of the injection site of either vital blue dye or radiopharmaceuticals.

Adult↗

Cervical lymph node metastasis in patients with submucosal carcinoma of the thoracic esophagus.

BACKGROUND AND OBJECTIVES: The effect of esophagectomy with three-field lymph node dissection for submucosal carcinoma of the thoracic esophagus remains controversial. The aim of this study was to evaluate the effect of esophagectomy with three-field lymph node dissection for submucosal carcinoma of the thoracic esophagus. METHODS: From January 1983 to December 1997, the records of 101 consecutive patients who underwent transthoracic esophagectomy with three-field lymph node dissection were retrospectively analyzed. RESULTS: The incidence of the operative complications was 70%. The 30-day and overall hospital mortality rates were 1.0% and 2.0%, respectively. The positive rate of histological cervical nodal metastasis was 17%. The 5-year survival rates for the patients with and those without cervical nodal metastasis were 55% and 71%, respectively. The difference between patients with and those without cervical nodal metastasis was not statistically significant. Cumulative 5-year survival rates for the patients with metastasis in the cervical, upper mediastinal, or abdominal lymph nodes were 55%, 65%, and 46%, respectively. There was no statistically significant difference between each survival. CONCLUSIONS: Three-field lymph node dissection may be indicated for patients requiring esophagectomy for submucosal carcinoma of the thoracic esophagus because the frequency of cervical lymph node metastasis is not negligible and acceptable overall hospital mortality and favorable survival rates of patients with histologically positive cervical nodes can be achieved.

Adult↗

Wider indications for the local resection of gastric cancer by adjacent lymphadenectomy.

BACKGROUND AND OBJECTIVES: A variety of minimal invasive treatment strategies for early gastric cancer without reducing the curability have been introduced, however, the indications for the local resection of early gastric cancer have not been precisely established. METHODS: Two approaches are adopted in this study to elucidate indications for local resection. One is a retrospective review of surgically resected, postoperatively histologically proven early gastric cancers between 1976 and 1996 (611 patients), and the other is the patient selection from those who underwent modified D(1) lymphadenectomy in a prospective manner between 1987 and 1996, based on the preoperative and intraoperative diagnoses of mucosal, node negative, nonpalpable gastric cancer (125 patients). In these approaches, patterns of nodal involvement in association with clinicopathological characteristics of gastric cancer were investigated. RESULTS: The depressed with ulceration type and histologically high grade type were predominant characteristics of mucosal, node positive gastric cancer patients. Of these patients, after the exclusion of those who were diagnosed to have submucosal or advanced cancer preoperatively or who had palpable cancer intraoperatively, the gastric cancer < or =4 cm in maximum diameter had positive nodes confined to only one station adjacent to the cancer without simultaneous nodal involvement in the other stations. CONCLUSIONS: Local resection can be performed for gastric cancers < or = 4 cm in maximum diameter that meet our criteria for modified D(1) lymphadenectomy, in association with the frozen section confirmation of cancer negative in the simultaneously dissected lymph nodes in the stations adjacent to the cancer. The adjacent lymphadenectomy and frozen section examination make the application of local resection possible for a wider segment of patients.

Adult↗