The carry-through of residues of maleic hydrazide from treated potatoes, following manufacture into potato crisps and ''jacket'' potato crisps

Primary nodal drainage basins in melanoma of the head and neck are often unpredictable. The ear is a notorious example of an anatomic site with ambiguous patterns of lymphatic drainage. Preoperative lymphoscintigraphy has recently emerged as one modality to assist in identifying clinically relevant nodes. We propose that the addition of intraoperative lymph node mapping techniques that utilize radioactive tracers ("intraoperative lymphoscintigraphy") can increase the accuracy of identifying sentinel nodes and help to determine which patients may benefit from a complete neck dissection. This report demonstrates the ambiguity in identifying drainage patterns in melanoma of the ear and offers a reliable method of sentinel lymph node mapping. This report also addresses current issues regarding treatment protocols of patients with micrometastatic disease in the periauricular region.     

Surgical management of aberrant sentinel lymph node drainage in cutaneous melanoma

BACKGROUND: Sentinel lymph node (SLN) mapping by lymphoscintigraphy has changed the surgical management of regional lymph node metastases for melanoma. SLNs lying outside of traditional nodal basins are now being identified. Our hypothesis is that when preoperative lymphoscintigraphy identifies aberrant SLNs, these nodes should be excised and, if histologically positive, lymphadenectomy of the aberrant nodal basin should be performed. METHODS: Patients with melanomas 1 mm or larger Breslow thickness and clinical stage N0M0 underwent lymphoscintigraphy and excision with SLN biopsy. Preoperative lymphoscintigraphy, intraoperative gamma probe, and intraoperative injection of isosulfan blue were performed to identify the SLN. Aberrant SLNs were defined as epitrochlear, supraclavicular, or popliteal nodes for extremity lesions and intramuscular nodes for truncal and head and neck lesions. RESULTS: Thirty-two patients were entered into the protocol. Seven (22%) were found to have aberrant nodes. Five of 19 patients with extremity melanoma had an aberrant SLN; 2 of 13 patients with truncal and head and neck melanoma had an aberrant SLN. CONCLUSIONS: This study demonstrates that (1) aberrant SLNs are encountered with similar frequency for extremity and truncal lesions, (2) biopsy should be performed on aberrant SLNs with intraoperative lymph node mapping with the gamma probe and blue dye, and (3) lymphadenectomy of the aberrant region should be considered if the aberrant SLN is positive.     

Predictors of careers in academic medicine for graduates of a community-based, primary-care-oriented medical school

OBJECTIVE: To determine whether intraoperative lymphatic mapping with isosulfan blue dye and sentinel lymph node biopsy accurately demonstrates the pathway of regional metastases from mucosal sites in squamous cell carcinoma of the head and neck. DESIGN: A prospective clinical study of intraoperative lymphatic mapping. SETTING: An academic tertiary referral center. PATIENTS: Patients with previously untreated squamous cell carcinoma of the head and neck whose surgical treatment included neck dissection. INTERVENTION: Injection of isosulfan blue dye into the mucosa surrounding squamous cell carcinomas of the upper aerodigestive tract during cervical lymphadenectomy. OUTCOME MEASURES: Correlation of the pathologic findings in the blue sentinel lymph node with those in the remaining cervical lymphatics. RESULTS: No blue-stained cervical lymphatics were identified after injection of the mucosa surrounding the primary squamous cell carcinoma with isosulfan dye. CONCLUSION: The technique of intraoperative lymphatic mapping with isosulfan blue dye requires further study before it can be used for the detection of occult cervical metastases in squamous cell carcinoma of the head and neck.     

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.     

Calcium and magnesium mass transfer in peritoneal dialysis patients using 1.25 mmol/L calcium, 0.25 mmol/L magnesium dialysis fluid

The percentage of melanoma patients diagnosed at an early stage is increasing. Many of these patients, particularly those with primary tumors thicker than 1.5 mm, harbor occult metastases in regional nodes and are eligible for regional lymphadenectomy as part of their primary management. Until the results of recently completed prospective randomized trials are available the role for elective lymphadenectomy in terms of survival benefit remains a controversial issue. A new technique, intraoperative lymphatic mapping and sentinel node biopsy, has emerged as a simple way to determine whether or not metastatic disease is present. An intradermal injection of a vital blue dye at the site of the primary tumor allows identification of a "sentinel" node in the regional basin. A study of 237 patients was recently reported by Morton et al. (Arch Surg 127:392-399, 1992; Surg Oncol Clin North Am 1:247-259, 1992) demonstrating that the sentinel node can be readily identified > 80% of the time and that histologic examination of the node results in at least a 95% accuracy rate in staging the nodal basin for metastases. Our present series substantiates the results of the original study. An international multicenter trial has been proposed to further confirm the accuracy and universal feasibility of this technique. Acceptance of this technique will lead to a selective approach to regional lymphadenectomy, as only patients with proven micrometastases will undergo lymph node dissections. This approach should satisfy both the advocates and the opponents of elective regional lymphadenectomy.     

Human D2 and D4 dopamine receptors couple through betagamma G-protein subunits to inwardly rectifying K+ channels (GIRK1) in a Xenopus oocyte expression system: selective antagonism by L-741,626 and L-745,870 respectively

OBJECTIVE: To develop a prognostic model, based on clinical and pathological data, to estimate the probability of micrometastasis in the sentinel lymph node in patients with malignant melanoma. DESIGN: Retrospective analytical study. SETTING: University medical center. PATIENTS: Two hundred fifteen patients with American Joint Committee on Cancer stages I and II cutaneous malignant melanoma underwent sentinel lymph node biopsy. MEASUREMENTS: Presence of microscopic melanoma in the sentinel lymph node(s). Clinical attributes recorded included age, sex, and location of the primary melanoma. Pathological attributes recorded before lymph node evaluation included ulceration, microsatellites, angiolymphatic invasion, mitotic rate, tumor infiltrating lymphocytes, and regression. RESULTS: Forty-six patients (21.4%) overall had a positive sentinel lymph node. Patients with tumor thickness ranging from 3.0 to 3.9 mm had the highest incidence (50%) of nodal involvement, followed by those with tumors 4.0 to 4.9 mm thick (41%). Patients with melanomas measuring greater than 4.9 mm thick and those between 1.0 and 2.9 mm had a similar rate of nodal involvement (16%-17%). Clinical characteristics had minimal correlation with nodal status in multivariate analysis. The total number of histological high-risk features was significantly correlated with sentinel lymph node involvement. Important pathological risk factors included ulceration, high mitotic rate, angiolymphatic invasion, and microsatellites. Patients with tumor thickness greater than 1.0 mm but lacking these features had a 14% risk of occult metastases. CONCLUSION: Among patients with clinically node-negative primary melanoma, the presence of 1 or more high-risk histological features significantly increases the incidence of microscopic nodal involvement and can be used to predict the likelihood of a positive sentinel lymph node biopsy.     

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.     

Prospective comparison of 18F-FDG PET with conventional imaging modalities (CT, MRI, US) in lymph node staging of head and neck cancer

The aims of this study were to investigate the detection of cervical lymph node metastases of head and neck cancer by positron emission tomographic (PET) imaging with fluorine-18 fluorodeoxyglucose (FDG) and to perform a prospective comparison with computed tomography (CT), magnetic resonance imaging (MRI), sonographic and histopathological findings. Sixty patients with histologically proven squamous cell carcinoma were studied by PET imaging before surgery. Preoperative endoscopy (including biopsy), CT, MRI and sonography of the cervical region were performed in all patients within 2 weeks preceding 18F-FDG whole-body PET. FDG PET images were analysed visually and quantitatively for objective assessment of regional tracer uptake. Histopathology of the resected neck specimens revealed a total of 1284 lymph nodes, 117 of which showed metastatic involvement. Based on histopathological findings, FDG PET correctly identified lymph node metastases with a sensitivity of 90% and a specificity of 94% (P<10(-6)). CT and MRI visualized histologically proven lymph node metastases with a sensitivity of 82% (specificity 85%) and 80% (specificity 79%), respectively (P<10(-6)). Sonography revealed a sensitivity of 72% (P<10(-6)). The comparison of 18F-FDG PET with conventional imaging modalities demonstrated statistically significant correlations (PET vs CT, P = 0.017; PET vs MRI, P = 0.012; PET vs sonography, P = 0.0001). Quantitative analysis of FDG uptake in lymph node metastases using body weight-based standardized uptake values (SUVBW) showed no significant correlation between FDG uptake (3.7+/-2.0) and histological grading of tumour-involved lymph nodes (P = 0.9). Interestingly, benign lymph nodes had increased FDG uptake as a result of inflammatory reactions (SUVBW-range: 2-15.8). This prospective, histopathologically controlled study confirms FDG PET as the procedure with the highest sensitivity and specificity for detecting lymph node metastases of head and neck cancer and has become a routine method in our University Medical Center. Furthermore, the optimal diagnostic modality may be a fusion image showing the increased metabolism of the tumour and the anatomical localization.     

The evaluation of 15q proximal duplications by FISH

BACKGROUND: Preoperative cutaneous lymphoscintigraphy (LS) to identify sentinel (first-tier) lymph nodes was performed in 250 consecutive melanoma patients before wide local excision only or wide local excision with sentinel node biopsy. METHODS: The location of the sentinel nodes was marked on the overlying skin in all patients. Whether or not tracer was present in second-tier lymph nodes on the delayed scans was recorded for each patient and related to the lesion site at which the tracer had initially been injected. For 100 consecutive patients the rate of tracer movement through the lymphatic channels was compared to the incidence of second-tier drainage. RESULTS: Second-tier nodes were visualized in all patients with melanomas on the leg and thigh, and in almost all patients with melanomas on the forearm and hand, but were seen less often in patients with more centrally located melanomas. There was a significant correlation between the rate of lymph flow and the incidence of demonstrable second-tier drainage. CONCLUSION: The results suggest that the physiology of the lymphatic system varies depending on the origin of the lymphatic vessel. These findings have important implications for application of the sentinel node biopsy technique in individual patients.     

Programming of enzyme specificity by substrate mimetics: investigations on the Glu-specific V8 protease reveals a novel general principle of biocatalysis

BACKGROUND: The purpose of the study was to determine the accuracy and role of the sentinel node technique in patients with non-small cell lung cancer. METHODS: This study was carried out on 36 consecutive patients undergoing lung resection. Peritumoral tissue was infiltrated with isosulfan blue dye and the first lymph node to stain was identified as a sentinel node. Sensitivity and specificity of the sentinel node in predicting the status of other lymph node stations were determined. RESULTS: Seventeen patients had sentinel lymph nodes. In 9 of these 17 cases neither the sentinel node nor any other lymph node contained metastatic carcinoma. In 5 cases the sentinel node was in the mediastinum and documented unexpected N2 disease. In 19 patients no sentinel node was found. Final lymph node statuses were N0 in 13 patients, N1 in 5, and N2 in 1. CONCLUSIONS: The use of isosulfan blue for intraoperative lymphatic mapping is feasible. The specificity in our experience was good; 9 of 9 patients with negative sentinel nodes were found to be N0 on the final pathology report. Unexpected N2 disease was found in 5 patients. The accumulation of further experience will determine the role of the sentinel node technique in patients with non-small cell lung cancer.     

MR imaging in squamous cell carcinoma of the head and neck with no palpable lymph nodes

PURPOSE: To assess the efficacy of MR imaging in the detection of lymph node metastasis in patients with no palpable lymph nodes ("N0 neck") who have squamous cell carcinoma of the head and neck region. MATERIAL AND METHODS: MR neck imagings in 18 patients who underwent neck dissection (bilaterally in 2) for squamous cell carcinoma of the head and neck region were examined preoperatively for the purpose of detecting lymph node metastases. The imaging features taken into consideration were: size (cutoff point 10 mm), grouping, presence of central necrosis, and appearance of extracapsular spread. The MR examinations comprised spin-echo T1- and T2-weighted sequences. The MR findings were compared with those of surgery and histopathological examination. RESULTS: MR suggested metastatic lymph node involvement in 5 necks. In 2 of these, central necrosis was seen in the enlarged lymph nodes. In a third, a grouping of the lymph nodes was noted. Extracapsular spread was not present. Histopathological examination revealed metastatic lymph nodes in 7 of the 20 necks, the rate of clinically occult disease being 35%, and 4 of them had been accurately graded by MR. There was one false-positive MR examination. The MR sensitivity was 57.1% and specificity 92.3%. CONCLUSION: MR may reveal metastatic lymph nodes in patients with no clinical evidence of metastasis. However, conventional MR techniques are not always sufficient for decision-making on surgery in cases of "N0 neck".     

A pivotal role for glutamate in the pathogenesis of schizophrenia, and its cognitive dysfunction

PURPOSE: To compare the outcome for patients with squamous cell carcinoma of cervical lymph nodes metastatic from an unknown primary site who were irradiated to both sides of the neck and potential mucosal sites with opposed photon beams, and for those irradiated to the ipsilateral side of the neck alone with an electron beam. METHODS AND MATERIALS: Fifty-two patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site were irradiated by two different methods. Thirty-six were irradiated with a bilateral technique (BT), i.e., to both sides of the neck, including the naso-oro-hypopharyngeal mucosa, and 16 were irradiated with an electron beam (EB) to the ipsilateral side of the neck alone. Twenty patients of the BT group and 11 of the EB group had cervical lymph node dissections, and the remaining 21 patients had lymph node biopsies, prior to radiotherapy. RESULTS: Tumor control in the ipsilateral side of the neck did not differ for either radiation technique, but was significantly higher after lymph node dissection than after biopsy (90 vs. 48%; p = 0.0004). Control of subclinical metastases in the contralateral cervical lymph nodes was higher for patients irradiated with BT than for patients irradiated with EB (86 vs. 56%; p = 0.03). The occult primary was later discovered in 8% of the patients in the BT group and 44% of the EB group (p = 0.0005). The disease-free survival rate at 5 years for patients who had lymph node dissection prior to irradiation was 61%, and was 37% for those who had biopsy (p = 0.05). Only 20% of patients who subsequently developed an occult primary were salvaged and survived for 5 years after salvage treatment. CONCLUSION: Bilateral neck and mucosal irradiation is superior to ipsilateral neck irradiation in preventing contralateral cervical lymph node metastases and the subsequent appearance of an occult primary cancer. Both techniques combined with cervical lymph node dissection were equally effective in controlling the ipsilateral neck disease.     

Sentinel lymphadenectomy: an alternative to axillary lymphadenectomy in breast carcinoma

BACKGROUND: Axillary lymph node status is an important determinant of prognosis in breast cancer. However, lymphadenectomy does not benefit half of the patients in whom axillary nodes are free of disease. Sentinel lymph node biopsy is a new technique which allows accurate staging of breast carcinoma without performing total axillary dissection. We describe our experience with the introduction of sentinel lymphadenectomy. METHODS: Thirty-seven sentinel lymphadenectomies were performed in 35 patients referred to the Department of Obstetrics and Gynaecology of the University of Berne between December 1997 and June 1998. Mapping procedures were performed using a combination of vital blue dye with preoperative lymphscintigraphy with 99mTechnetium-labelled colloidal albumin and intraoperative use of a gamma probe. Complete axillary lymphadenectomy was then performed in 34 patients. RESULTS: One or more lymph nodes were identified in 33 of 37 procedures (89%). With the combination of both localisation techniques the sentinel nodes were identified in all (100%) of the last 19 patients. Sentinel and non-sentinel lymph nodes were always concordant. In this series the negative predictive value is 100% (95% confidence interval: 87.7%-100%). Metastases were found in the sentinel node in 11 of 30 patients (37%). From these 11 patients, 3 (27%) had micrometastases. CONCLUSIONS: Histopathologic examination of the sentinel lymph node accurately predicts the axillary lymph-node status. Patients with sentinel nodes free of metastases could avoid the unnecessary peri- and postoperative complications of complete axillary dissection. Further studies are needed to assess whether the improved diagnosis of micrometastases by sentinel lymphadenectomy influences the long-term prognosis of breast cancer.     

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.     

Lymphatic mapping and selective lymphadenectomy as an alternative to elective lymph node dissection in patients with malignant melanoma

This article reviews the use of selective lymphadenectomy, otherwise known as sentinel lymph node biopsy, as a clinical alternative in patients with malignant melanoma. This represents a compromise between the two traditional treatment modalities, elective lymph node dissection or observation of the regional nodal basin followed by therapeutic lymph node dissection once disease becomes clinically apparent.     

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.     

Prognostic value of immunohistochemically identifiable tumor cells in lymph nodes of patients with completely resected esophageal cancer

BACKGROUND: Current methods of disease staging often fail to detect small numbers of tumor cells in lymph nodes. Metastatic relapse may arise from these few cells. METHODS: We studied 1308 lymph nodes from 68 patients with esophageal cancer without overt metastases who had undergone radical en bloc esophagectomy. A total of 399 lymph nodes obtained from 68 patients were found to be free of tumor by routine histopathological analysis and were studied further for isolated tumor cells by immunohistochemical analysis with the monoclonal anti-epithelial-cell antibody Ber-EP4. This antibody did not stain lymph nodes from 24 control patients without carcinoma. RESULTS: Of the 399 "tumor free" lymph nodes, 67 (17 percent), obtained from 42 of the 68 patients, contained Ber-EP4-positive tumor cells. Fifteen of 30 patients who were considered free of lymph-node metastases by histopathological analysis had such cells in their lymph nodes, and 5 of the 15 had small primary tumors. Ber-EP4-positive cells found in "tumor free" nodes were independently predictive of significantly reduced relapse-free survival (P=0.008) and overall survival (P=0.03). They predicted relapse both in patients without nodal metastases (P=0.01) and in those with regional lymph-node involvement (P=0.007). All 12 patients whose lymph nodes were negative on both histopathological and immunohistochemical analysis and who were available for follow-up survived without recurrence. The presence of micrometastatic tumor cells in bone marrow had no additional prognostic value. CONCLUSIONS: Immunohistochemical examination of lymph nodes may improve the pathological staging of esophageal cancer.