Clinicopathological study on patterns of cervical lymph node metastases from squamous cell carcinomas (SCC) of the head and neck

In order to investigate the patterns of cervical lymph node metastases from head and neck SCC, serial sections were performed on 384 radical neck dissection (RND) specimens. Positive lymph node was found in 60.4% RNDs. The cervical lymph node spread from SCC in the head and neck regions including oral cavity, oropharynx, hypopharynx and larynx has some predictable patterns, i.e., for primary SCC of the oral cavity, the majority of cervical lymph node metastases were clustered at levels I, II and III; and for primary carcinoma of the oropharynx, hypopharynx and larynx, a majority of node metastases were located at levels II, III and IV. The positive lymph nodes mainly distributed at only one level or consecutive levels. The rates of pathologically positive lymph node and extranodal spread grew with the increase of the clinical N-staging. It is suggested that supraomohyoid neck dissection (levels I, II and III) is particularly applicable to carcinomas of the oral cavity, and lateral neck dissction (levels II, III and IV) is applicable to carcinomas of the oropharynx, hypopharynx and larynx in patients with limited (N0 and N1) neck nodules, but for patients with N2 and N3 nodules, RND is neccessary to eradicate the nodal metastases. Moreover, the postoperative radiotherapy is indispensable for ruling out the occult cervical lymph node metastaese in selective neck dissection.     

Superiority of extended en bloc esophagogastrectomy for carcinoma of the lower esophagus and cardia

The belief that transhiatal esophagogastrectomy results in the same survival as a more extensive en bloc resection was tested in 69 patients with carcinoma in the distal esophagus and gastric cardia. Preoperative and intraoperative staging defined three distinct subgroups of patients. Those with apparently limited disease and good general health (group I, n = 30) underwent en bloc resection. Those with apparently limited disease but poor physiologic reserve (group II, n = 16) underwent transhiatal resection, as did those with evidence of more advanced disease (group III, n = 23). Overall, survival was significantly better in the 30 patients who underwent en bloc resection (41%) than in the 39 patients who underwent transhiatal resections (14%; p < 0.001, log-rank). Clinical staging showed apparently limited disease in 46 patients (groups I and II). These groups differed only in the presence of poor physiologic reserve because the percentages of patients with tumors limited to the esophageal wall (group I 13/30, group II 6/16) and four or fewer lymph node metastases (group I 21/30, group II 15/16) at the time of pathologic staging were not significantly different. Survival after en bloc resection was, however, significantly better (41% versus 21%; p < 0.05, log-rank). According to the WNM system of pathologic staging, 19 patients had early lesions defined as intramural lesions associated with four or fewer lymph node metastases, 26 had intermediate lesions defined as either transmural or associated with more than four lymph node metastases, and 24 had late lesions defined as both transmural and associated with fewer than four lymph node metastases. Survival was significantly better in patients with early lesions after en bloc resection compared with transhiatal resection (75% versus 20%, p < 0.01), survival was also significantly better in patients with advanced lesions (27% versus 9%, p < 0.01). For intermediate lesions, the survival was similar (14% versus 20%), although the median survival after en bloc resection was longer (24 months versus 8 months).     

Axillary lymph node metastases of bronchogenic carcinoma

BACKGROUND: Metastasis of bronchogenic carcinoma to axillary lymph nodes is rare. The pathways and possible significance of axillary lymph node metastasis from bronchogenic carcinoma were investigated. METHODS: Seventeen patients with probable axillary lymph node metastases from bronchogenic carcinoma were identified by computed tomography. There were 15 nonsmall cell lung cancers and 2 small cell lung cancers. Axillary lymph node metastasis was proven by biopsy in six cases. Metastases were presumed because of an increase in the size of axillary lymph nodes compared with prior studies in six patients and enlarged axillary lymph nodes associated with biopsy-proven ipsilateral supraclavicular lymph node metastasis in five patients. RESULTS: Four of 10 right-sided lung cancers had ipsilateral and six had contralateral axillary lymph node metastases. Six of seven left-sided cancers had ipsilateral and one had contralateral axillary lymph node metastases. Patients with ipsilateral lymph node disease had chest wall involvement and/or supraclavicular and mediastinal lymph node metastases. All seven patients with contralateral axillary lymph node metastases had supraclavicular and/or mediastinal lymph node metastases. CONCLUSION: Bronchogenic carcinoma may involve ipsilateral axillary lymph nodes via either chest wall invasion or retrograde spread from supraclavicular lymph nodes. Contralateral axillary lymph node involvement requires involvement of contralateral mediastinal and supraclavicular lymph nodes with retrograde spread to the axillary lymph nodes.     

Intraoperative determinants of unresectability for patients with colorectal hepatic metastases

BACKGROUND: Intrahepatic and extrahepatic factors are utilized by the surgeon in the decision-making process for the performance of hepatic resection for patients with colorectal metastases. Accurate preoperative and intraoperative staging are mandatory to avoid unnecessary surgery. In this report the intraoperative determinants of hepatic unresectability were evaluated. METHODS: This was a retrospective review of medical records from January 1985 to March 1996 of 62 patients with colorectal hepatic metastases who at the time of exploratory laparotomy were deemed to have unresectable disease based on intrahepatic or extrahepatic factors. The stage of the primary tumor, disease free interval, preoperative carcinoembryonic antigen, computed tomography portography, intraoperative ultrasound, and assessment of intrahepatic and extrahepatic tumor extension were evaluated. RESULTS: Intraoperative determination of the extent of required hepatic resection, including trisegmentectomy (9 patients; 15%) and total hepatectomy (10 patients; 16%), accounted for the majority of unresectable patients. Patients with > 4 metastases (8 patients; 13%) and satellitosis (6 patients; 10%) accounted for 23% of unresectable patients. Four patients had extensive nonmalignant hepatic parenchymal disease precluding resection. Thorough abdominal exploration revealed extrahepatic disease in 13 of 62 patients (21%). Routine periportal/celiac lymph node biopsies revealed metastases in an additional 12 patients (19%), 7 of whom (11%) had only periportal/celiac lymph node metastases. CONCLUSIONS: A meticulous abdominal exploration prior to hepatic resection for patients with colorectal metastases is essential to identify those patients with extrahepatic disease. Periportal and celiac lymph nodes commonly are involved by tumor. Therefore, routine periportal/celiac lymph node biopsies should be performed in the absence of other extrahepatic disease.     

Lymph node sonography versus palpation for detecting recurrent disease in patients with malignant melanoma

The aim of this study was to examine the efficacy of lymph node palpation versus high resolution lymph node sonography for the detection of lymph node metastases in patients with malignant melanoma. We retrospectively evaluated 2256 pairwise lymph node examinations of the cervical, axillary and inguinal region by palpation and sonography in 264 patients with resected melanomas greater than 0.75 mm of invasion thickness. Lymph node metastases occurred in 50 patients (19%) which were detected in 38 (76%) by both methods in agreement. In 7 cases (14%) palpation failed, in 3 cases (6%) sonography failed and in 2 cases both methods failed to identify metastases. The overall sensitivity of detecting metastatic disease was 82% for palpation and 90% for sonography which was statistically not different. The overall specificity by sonography (99%) was significantly better than for lymph node palpation (88%). Taking into account the results of this analysis, we conclude that patients with a negative result by lymph node palpation do not need further sonography for verification. However, any suspect result by palpation should be additionally evaluated by lymph node sonography in order to rule in or out metastatic disease.     

Skip metastasis to the mediastinal lymph nodes in non-small cell lung cancer

BACKGROUND: Whether any difference exists in clinical characteristics between resected non-small cell lung cancer with either skip or ordinary mediastinal lymph node metastases (N2 disease) needs to be clarified. METHODS: There were 110 patients with stage IIIA N2 disease. Thirty-three patients demonstrating no metastasis at the hilar nodes [skip (+) group] were compared with the other 77 patients [skip (-) group]. To investigate the extent of nodal involvement, we classified the mediastinal lymph nodes into three regions (superior, inferior, or aortic). RESULTS: There were no significant differences regarding histologic type, T status, or the site of the primary tumors between the skip (+) and the skip (-) N2 groups. In the skip (+) group, mediastinal node metastasis was found in only one region (level 1) in 30 patients (90.9%) and in two regions (level 2) in 3 (9.1%), whereas 28 patients (36.4%) from the skip (-) group revealed mediastinal metastasis at two or three regions (level 2 or 3). The overall survival rate at 5 years after operation was 35% in the skip (+) group and 12.7% in the skip (-) group (p = 0.054). This favorable clinical outcome in the skip (+) group could be explained partially by the higher proportion of patients with level 1 metastases. Furthermore, regarding patients with level 1 disease, the skip (+) group tended to have a better prognosis than the skip (-) group (p = 0.096). CONCLUSIONS: These results suggest that patients with skip mediastinal lymph node metastases represent a unique subgroup of N2 disease.     

Assessment of axillary lymph node involvement in breast cancer patients with positron emission tomography using radiolabeled 2-(fluorine-18)-fluoro-2-deoxy-D-glucose

BACKGROUND: The presence of metastatic tumor cells in the axillary lymph nodes is an important factor when deciding whether or not to treat breast cancer patients with adjuvant therapy. Positron emission tomography (PET) imaging with the radiolabeled glucose analogue 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (F-18 FDG) has been used to visualize primary breast tumors as well as bone and soft-tissue metastases. PURPOSE: This study was undertaken to evaluate before surgery the diagnostic accuracy of PET for detection of axillary lymph node metastases in patients suspected of having breast cancer. METHODS: Women who were scheduled to undergo surgery for newly discovered, suspected breast cancers were referred for PET imaging of the axilla region. The women were first clinically examined to determine the status of their axillary lymph nodes (i.e., presence or absence of metastases). Fifty-one women were intravenously administered F-18 FDG and were studied by PET imaging. Attenuation-corrected transaxial and coronal images were visually evaluated by two nuclear medicine physicians (blinded to the patient's medical history) for foci of increased F-18 FDG uptake in the axilla region. All patients underwent surgery for their suspected breast cancers. Axillary lymph node dissection was also performed on all patients with breast cancer, with the exception of four patients who received primary chemotherapy for locally advanced breast cancer. A single pathologist analyzed breast tumor and lymph node tissue specimens. RESULTS: The overall sensitivity (i.e., the ability of the test to detect disease in patients who actually have disease) and specificity (i.e., the ability of the test to rule out disease in patients who do not have disease) of this method for detection of axillary lymph node metastases in these patients were 79% and 96%, respectively. When only patients with primary breast tumors larger than 2 cm in diameter (more advanced than stage pT1; n = 23) were considered, the sensitivity of axillary PET imaging increased to 94%, and the corresponding specificity was 100%. Lymph node metastases could not be identified in four of six patients with small primary breast cancers (stage pT1), resulting in a sensitivity of only 33%. Axillary PET imaging provided additional diagnostic information in 12 (29%) of 41 breast cancer patients with regard to the extension of disease to other sites (i.e., other lymph nodes, skin, bone, and lung). CONCLUSIONS: PET imaging with F-18 FDG allowed accurate and noninvasive detection of axillary lymph node metastases, primarily in patients with breast cancer more advanced than stage pT1. Detection of micrometastases and small tumor-infiltrated lymph nodes is limited by the currently achievable spatial resolution of PET imaging. IMPLICATIONS: In clinical practice, PET imaging cannot substitute for histopathologic analysis in detecting axillary lymph node metastases in breast cancer patients. PET imaging, however, improves the preoperative staging of the disease in breast cancer patients and, therefore, might alter therapeutic regimen options.     

Gamma-probe-guided resection of the sentinel lymph node in breast cancer

Regional lymph node metastases in patients with breast cancer have fundamental staging, prognostic, and treatment implications. Classically, axillary lymph node sampling requires a dissection under general anesthesia. The concept that a primary, or sentinel, lymph node is the first node to receive drainage from a tumor has been established in patients with malignant melanomas using radiolabeled tracers and vital dyes. This study proposed two hypotheses: (1) radiolabeled sentinel lymph nodes can be identified in most patients with breast cancer, and (2) radiolabeled sentinel lymph node biopsy accurately predicts axillary lymph node metastases in those patients. Patients with operable breast cancer had Tc-99 sulphur colloid injected around their breast tumors 1-6 hours preoperatively. Patients underwent gamma probe identification of sentinel lymph nodes that were biopsied. All patients underwent axillary lymphadenectomy in conjunction with lumpectomy or mastectomy. Fifty female patients ages 26 to 90 years underwent lumpectomies with axillary dissections (40 patients) or modified radical mastectomies (10 patients). Sentinel lymph nodes were identified in 42 of 50 patients (84%). Eight patients (16%) had metastases to the axillary lymph nodes. In 7 patients, sentinel lymph nodes correctly predicted the status of the axillary nodes. There was one false negative result. A total of 550 lymph nodes were resected for an average of 11.2 nodes per patient. Sentinel lymph node scintigraphy and biopsy accurately predicted the axillary lymph node status in 41 of 42 patients (98%). Scintigraphy can identify sentinel lymph nodes in a large majority of patients. Sentinel lymph node biopsy is an accurate predictor of axillary lymphatic metastases.     

Extended lymphadenectomy in carcinoma of the right colon

The Authors report on a retrospective study concerning 49 patients treated for a modified Dukes' stage B, C or D right colon cancer. A potentially curative right hemicolectomy with extended lymphadenectomy was performed. Locally advanced disease was treated by "en bloc" resection. Two (4.1%) patients died after surgery, in other 2 (4.1%) cases major postoperative complications were registered. Microscopic examination of the surgical specimens showed lymph node metastases in 44.9% of the cases: in this subgroup a metastatic involvement of the main (III level) nodal groups was detected in 22.7% of the patients. The Authors conclude that extended lymph node dissection does not increase postoperative complications and may play a role in the treatment of right colon cancer. A not negligible group of patients may be understaged or receive inadequate surgical treatment when submitted to traditional right colectomy.     

Is preoperative chemotherapy in locally advanced non-small-cell bronchial carcinoma of value?

Although surgeons are able to resect completely locally advanced non-small cell lung cancer with mediastinal lymph node involvement (stage IIIA), the majority of patients succumb from metastatic disease. Therefore, neoadjuvant therapy was introduced in the management of this disease in order to eradicate distant metastases at an early stage. Phase II trials with preoperative chemotherapy in stage IIIA patients have shown that the pathological response (amount of tumour necrosis) and the clearance of mediastinal lymph node correlate with a better survival and is the best predictor for eradication of distant metastases. Indeed, three small randomised phase III studies have demonstrated a survival advantage for preoperative chemotherapy compared to surgery alone. Further studies are required to determine the best neoadjuvant regimen inducing the largest amount of tumour necrosis.     

D-xylose test of resorption as a method to determine radiation side effects in the small intestine

Microscopic papillary carcinoma of the thyroid gland (MPC) measuring < or = 1.0 cm in diameter has a generally benign outcome, but is often overtreated with additional surgery. Ninety cases of MPC and 77 cases of nonmicroscopic papillary carcinoma of the thyroid gland (non-MPC) from 1970 to 1980 were retrieved from the Endocrine Registry of the Armed Forces Institute of Pathology (AFIP), Washington, D.C. Histologic features and patient follow-up were analyzed. Twenty-one patients with MPC had multifocal disease within the affected thyroid lobe, while a further 15 had either bilateral or intraglandular spread. Four of 10 patients who had additional surgery were found to have additional foci of tumor. Fourteen patients with lymph node metastases at initial surgery had no subsequent nodal metastases. All patients were either alive without disease or had died of unrelated causes after an average follow-up period of 17.3 years. Of the 77 non-MPC patients, 13 developed lymph node metastases or local recurrences, and one died of metastatic disease. Sixty-four of these patients were alive without evidence of disease after an average follow-up of 22 years. Present findings show that while MPC may present with perithyroidal lymph node metastases (15.56%), patients do not develop clinical tumors in the remaining thyroid tissue. Our experience indicates that close clinical follow-up without additional surgery is the preferable management for patients with MPC.     

Decreased paralysis and better motor coordination with microspinal versus PE10 intrathecal catheters in pain study rats

BACKGROUND: The sentinel lymph node is the first node or nodes to drain a cutaneous melanoma. Sentinel lymph node biopsy is performed to determine whether regional metastases are present. The authors' experience with the new technique of sentinel lymph node biopsy for melanoma of the head and neck is reported. PATIENTS AND METHODS: During the period of January of 1992 to December of 1995, 58 consecutive patients were identified from the melanoma database who had localization of the sentinel lymph node for primary cutaneous melanoma of the head and neck. Techniques for identification of the sentinel node(s) include preoperative lymphoscintigraphy and intraoperative Lymphazurin dye (vital blue dye) and technetium-99m-labeled sulfur colloid injection around the primary tumor site with Neoprobe mapping. RESULTS: Fifty-eight patients (13 female, 45 male), mean age 61 years, with melanoma of the head and neck with a mean Breslow thickness of 2.21 mm. (range, 0.82-6.87 mm.) and no regional lymphadenopathy underwent sentinel node mapping. The sentinel node was successfully identified in 55 patients (95 percent). Blue dye was visualized in 85 of 126 sentinel nodes excised (67 percent), whereas the remainder of the sentinel nodes were localized with the Neoprobe. Forty-nine patients who had successful mapping and sentinel node biopsy had no evidence of metastatic disease in the sentinel node or other nodes in the basin. Six of the fifty-five patients (11 percent) had evidence of micrometastatic disease, and all six had the sentinel node as the only site of metastasis. Five of six patients with micrometastases had a subsequent neck dissection and/or superficial parotidectomy. None of these patients had evidence of "skip metastases" with a negative sentinel node and higher level nodes positive for metastases. In total, 6 of the 18 sentinel nodes (33 percent) identified in these six patients contained micrometastatic disease, whereas none of the 139 other nodes sampled had any evidence of metastases. The exact probability that all six unpaired observations would consist of involvement of only the sentinel nodes is p = 0.0312. CONCLUSIONS: By combining the two mapping techniques in patients with melanoma of the head and neck, the sentinel node(s) can be mapped and identified individually, similar to melanoma in other locations. The sentinel nodes have been shown to contain the first evidence of regional metastatic melanoma. This staging information can be used to plan therapeutic node dissections and adjuvant therapy that may have a survival benefit in patients with stage III melanoma of the head and neck. Lymphatic mapping can be used to make the surgical care of the melanoma patient more conservative, so that only those patients with solid evidence of regional node metastases are subjected to the morbidity and expense of a complete node dissection and the toxicities of adjuvant therapy.     

Outcome of 309 patients with metastatic differentiated thyroid carcinoma treated with radioiodine

From 1969 to 1990 there were 309 patients with differentiated thyroid carcinoma (241 papillary and 68 follicular) treated with radioactive iodine for functioning node metastases alone (n = 191) or distant metastases (n = 118) with or without node metastases. These patients represented 32.7% of 945 patients treated in our institution during the same period. Initial treatment included near-total thyroidectomy and 131I ablation of postsurgical thyroid residue, followed by L-thyroxine suppressive therapy. At the end of follow-up (mean 5.8 years), 146 patients (76.4%) in the group with nodal metastases were considered cured, as assessed by clinical and laboratory evaluation including whole body scan (WBS) and serum thyroglobulin (Tg) levels; 32 patients (16.7%) had persistent disease. Loss of 131I uptake in persistent metastatic lesions occurred in five patients (2.6%), and newly developed distant metastases occurred in eight patients (4.2%). Of the patients with distant metastases, 36.4% were cured by 131I. Distant metastases from papillary carcinomas had a higher cure rate than follicular carcinomas (p < 0.01). The metastases of four patients (5.2%) lost the property to take up radioiodine. Lung and bone metastases detectable by WBS but not by radiography were most likely to be cured by 131I. The overall survival at the end of follow-up was 95.8% in patients with only lymph node metastases and 76.0% in those with distant metastases. Tumor-related deaths were 3.6% and 23.7%, respectively. Our data indicate that 131I therapy is highly effective in the treatment of lymph node metastases from differentiated thyroid carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Axillary node metastasis from T1N0M0 breast cancer: possible avoidance of dissection in a subgroup

BACKGROUND: Axillary lymph node dissection is now no longer considered to be the standard treatment in all patients with invasive breast cancer. We have attempted to identify a sub-group of patients with invasive breast carcinoma who may not need to undergo axillary lymph node dissection. METHODS: Patients (n = 823) with T1 N0M0 invasive breast cancer treated at our hospital between 1970 and 1994 were studied. We investigated the relationship between positive axillary lymph nodes and the following clinico-pathological factors: patient age, menopausal status, contralateral breast cancer (synchronous or asynchronous), tumor location, tumor size (T:cm), histopathology, histological grade, presence or absence of malignant microcalcification or spiculation on mammography and estrogen receptor status. RESULTS: The incidence of axillary lymph node metastases in patients with T1N0M0 invasive breast cancer was 25% (208/823). The node-negative group was significantly older than the node-positive group. Premenopausal patients had a higher rate of lymph node metastases although this was not significant. The frequency of nodal metastases when related to the tumor size was as follows: T< or =1.0 cm, 17%; T< or =1.5 cm, 25%; T< or =2.0 cm, 29%. Mammography revealed that patients with malignant calcification or spiculation had a significantly higher rate of nodal metastases than those without these findings. Certain tumor types (medullary, mucinous and tubular carcinomas) had lower positive rates for lymph node involvement. With regard to the histological grade, lymph node positivity increased significantly with high-grade tumors. No correlation was observed between any other factors and the presence or absence of lymph node metastases. CONCLUSIONS: It may be possible to avoid axillary lymph node dissection in postmenopausal patients (50 years or older) where the histological type is favorable when the tumor diameter is < or =1.0 cm and when microcalcification or spiculation is absent on mammography.     

Observation of inter-subunit nuclear Overhauser effects in a dimeric protein. Application to the Arc repressor

This study was undertaken to examine the incidence and conditions under which lymph node metastases are present and patterns of recurrence in women with uterine leiomyosarcoma (LMS) and endometrial stromal sarcoma (ESS), excluding malignant mixed mesodermal tumors. From 1981 through 1991, 21 women with LMS and 10 women with ESS were treated. Retroperitoneal lymph node dissections were performed in 15 women with LMS and 7 women with ESS. In the women with LMS, 4/15 (26.7%) had lymph node metastases; in each there was disseminated intra-abdominal disease. In the 7 women with ESS, there were no lymph node metastases present. Ten women (47%) with LMS developed recurrences, and 3 (14%) had persistent disease. In the 10 women with ESS, 3 (30%) had recurrences, and 1 (10%) had persistent disease. In total, recurrences involved the lung in 84% of cases. Of the 13 women with recurrences, 7 had undergone lymph node sampling, and all were negative; 4 additional women had no evidence of adenopathy on abdominal-pelvic CT scan. Lymph node metastases were found only with extrauterine disease, and in all of these cases there was rapid progression of the sarcoma. Women without extrauterine disease did not have lymph node metastases detected; however, there was still a high rate (40%) of distant failure. Knowledge of lymph node status had minimal impact on the clinical management of women with uterine LMS and ESS.     

Distribution pattern and risk factors of pelvic and para-aortic lymph node metastasis in epithelial ovarian carcinoma

The distribution of lymph node metastasis and the clinicopathologic risk factors for nodal involvement in ovarian carcinoma need to be clarified based on systematic lymph node dissection. We studied 115 patients with ovarian carcinoma who underwent systematic pelvic and para-aortic lymph node dissection between 1987 and 1997. The incidence and distribution of lymph node metastasis are described and the clinico-pathologic risk factors for nodal involvement are investigated. Based on the occurrence of lymph node metastasis in the early stages, the incidence of solitary node involvement and the distribution of lymph node metastasis, we conclude that the primary site of nodal involvement in ovarian carcinoma is the para-aortic node (PAN), especially PAN superior to the inferior mesenteric artery (IMA). By univariate analysis, clinical stage, histologic type (mucinous vs. others), grade, multiple peritoneal metastases, peritoneal cytology, volume of ascites and serum CA125 level were correlated with overall incidence of lymph node metastasis. By performing a multivariate analysis with the clinical stage excluded, it was revealed that grade and peritoneal cytology were independent factors for PAN metastasis (p < 0.0025 and < 0.001, respectively) and that multiple peritoneal metastases and PAN metastasis were significant predictors of pelvic node metastasis (p < 0.01 and < 0.005, respectively). In conclusion, the PANs superior and inferior to IMA should be explored in staging of ovarian carcinoma that appears to be confined to the ovaries. To determine accurately the extent of disease, both the para-aortic and pelvic areas may need to be sampled or dissected in the case of ovarian carcinoma involving the peritoneal surfaces.     

Role of axillary lymph node dissection after tumor downstaging with induction chemotherapy for locally advanced breast cancer

BACKGROUND: Induction chemotherapy has become the standard of care for patients with locally advanced breast cancer (LABC) and currently is being evaluated in prospective clinical trials in patients with earlier-stage disease. To better gauge the role of axillary lymph node dissection in patients with LABC this study was performed to assess initial axillary status on physical and ultrasound examination, axillary tumor downstaging following induction chemotherapy, and the accuracy of physical examination compared with axillary sonography in predicting which patients will have axillary lymph node metastases found on pathologic examination. METHODS: Between 1992 and 1996, 147 consecutive patients with LABC were registered in a prospective trial of induction chemotherapy using 5-fluorouracil, doxorubicin, and cyclophosphamide. Physical and ultrasound examinations of the axilla were performed at diagnosis and after induction chemotherapy. Segmental resection with axillary lymph node dissection or modified radical mastectomy was performed, followed by postoperative chemotherapy and irradiation of the breast or chest wall and regional lymphatics. RESULTS: Following induction chemotherapy, 43 (32%) of the 133 patients with clinically positive lymph nodes on initial examination had axillary tumor downstaging as assessed by physical and ultrasound examination. The sensitivity of axillary sonography in identifying axillary metastases was significantly higher than that of physical examination (62% vs. 45%, P=.012). The specificity of physical examination (84%) was higher than that of sonography (70%), but the difference did not reach statistical significance. Among the 55 patients in whom the findings of both physical and ultrasound examination of the axilla were negative following induction chemotherapy, 29 patients (53%) were found to have axillary lymph node metastases on pathologic examination of the axillary contents. However, 28 (97%) of these patients had either 1 to 3 positive lymph nodes or only micrometastases 2 to 5 mm in diameter. CONCLUSIONS: Preoperative clinical assessment of the axilla by physical examination combined with ultrasound examination is not completely accurate in predicting metastases in patients with LABC following tumor downstaging. However, patients with negative findings on both physical and ultrasound examinations of the axilla may be potential candidates for omission of axillary dissection if the axilla will be irradiated because minimal axillary disease remains. Patients who have positive findings on preoperative physical or ultrasound examinations should receive axillary dissection to ensure local control. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following induction chemotherapy is currently underway.     

Histopathologic validation of the sentinel lymph node hypothesis for breast carcinoma

BACKGROUND AND OBJECTIVE: The sentinel node hypothesis assumes that a primary tumor drains to a specific lymph node in the regional lymphatic basin. To determine whether the sentinel node is indeed the node most likely to harbor an axillary metastasis from breast carcinoma, the authors used cytokeratin immunohistochemical staining (IHC) to examine both sentinel and nonsentinel lymph nodes. METHODS: From February 1994 through October 1995, patients with breast cancer were staged with sentinel lymphadenectomy followed by completion level I and II axillary dissection. If the sentinel node was free of metastasis by hematoxylin and eosin staining (H&E), then sentinel and nonsentinel nodes were examined with IHC. RESULTS: The 103 patients had a median age of 55 years and a median tumor size of 1.8 cm (58.3% T1, 39.8% T2, and 1.9% T3). A mean of 2 sentinel (range, 1-8) and 18.9 nonsentinel (range, 7-37) nodes were excised per patient. The H&E identified 33 patients (32%) with a sentinel lymph node metastasis and 70 patients (68%) with tumor-free sentinel nodes. Applying IHC to the 157 tumor-free sentinel nodes in these 70 patients showed an additional 10 tumor-involved nodes, each in a different patient. Thus, 10 (14.3%) of 70 patients who were tumor-free by H&E actually were sentinel node-positive, and the IHC lymph node conversion rate from sentinel node-negative to sentinel node-positive was 6.4% (10/157). Overall, sentinel node metastases were detected in 43 (41.8%) of 103 patients. In the 60 patients whose sentinel nodes were metastasis-free by H&E and IHC, 1087 nonsentinel nodes were examined at 2 levels by IHC and only 1 additional tumor-positive lymph node was identified. Therefore, one H&E sentinel node-negative patient (1.7%) was actually node-positive (p < 0.0001), and the nonsentinel IHC lymph node conversion rate was 0.09% (1/1087; p < 0.0001). CONCLUSIONS: If the sentinel node is tumor-free by both H&E and IHC, then the probability of nonsentinel node involvement is <0.1%. The true false-negative rate of this technique using multiple sections and IHC to examine all nonsentinel nodes for metastasis is 0.97% (1/103) in the authors' hands. The sentinel lymph node is indeed the most likely axillary node to harbor metastatic breast carcinoma.     

Endothelin-1 concentrations and optimisation of arterial oxygenation and venous admixture by selective pulmonary artery infusion of prostaglandin E1 during thoracotomy

PURPOSE: To demonstrate a superselective intraarterial chemotherapy as a therapeutic alternative in the treatment of previously treated recurrent lymph node metastases in breast cancer. METHODS: 14 patients with recurrent lymph node metastases in cases of breast cancer were presented to be treated by intraarterial chemotherapy of 25 mg mitoxantrone/m2 over a period of 24 hours. In two patients with superclavicular lymph node involvement an intraarterial therapy could not be carried out because of a vascular connection to the anterior spinal artery. Involved lymph stations could be reached in superselective technique by side branches of the subclavian artery. Heparin coverage was given intravenously. Every patient had had surgery, radiation, systemic chemo- and hormonal therapy before and was now graded as inoperable. Therapy indication was given by local tumour-induced symptoms. RESULTS: In the 12 treated cases complete remission was seen in three, partial remission in 4, a steady state in two and a progressive disease in three. There were no complications or severe side effects. CONCLUSION: Intraarterial chemotherapy is an effective and well tolerated treatment in recurrent lymph node metastases in cases of breast cancer even if conventional therapies can no longer be used.