Assessment of cervical lymph node metastasis in esophageal carcinoma using ultrasonography

Cadherins are Ca2+-dependent cell-cell adhesion molecules, and are involved in the formation and maintenance of the organocellular architecture. Using a combination of molecular biologic and biochemical methods, we analyzed cadherins expressed on cultured human malignant lymphoma cell lines (adult T cell lymphomas, human T cell leukemia virus type 1-negative T cell lines, and thymus-derived lymphoma cell lines), and obtained evidence that N-cadherin is the major cadherin expressed on these cells. These cells were found to form cell aggregates in a Ca2+-dependent manner, and more importantly to coaggregate and adhere with cells expressing N-cadherin, suggesting that N-cadherin on lymphoma cells is functionally active. Therefore, N-cadherin expressed on lymphoma cells could underlie the frequent invasion of these cells into the mesenchymal tissue in the skin and the central nervous system.     

Prognostic factors of cervical lymph node metastasis in head and neck squamous cell carcinoma

AIMS AND BACKGROUND: The metastatic spread of squamous cell carcinoma of the head and neck (SCCHN) to the cervical lymph nodes is a negative prognostic factor in terms of survival. We have used multivariate analysis to identify the possible prognostic significance of a number of clinical and pathological characteristics in relation to possible involvement of the cervical lymph nodes in a series of 396 patients. METHOD: 396 patients with SCCHN were studied. Variables regarding the patient, the carcinoma and histology were analysed by multivariate analysis using BMDP's PLR programme. RESULTS: Some variables appear to represent predisposing factors for tumor spread to the lymph nodes: tumor site (supraglottic larynx: P = 0.005; base of the tongue: P = 0.02; hypopharynx: P = 0.02), grading (P = 0.001), and a number of histological parameters (lower degree of histological differentiation: P = 0.001; vascular permeation: P = 0.04; perineural invasion: P < 0.05; prevalently plasmocytic infiltrate: P < 0.05). CONCLUSION: The identification of cases at risk for metastasis can be improved by the assessment of prognostic factors, with a consequent improvement in treatment strategies.     

Papillary thyroid carcinoma: MR diagnosis of lymph node metastasis

We investigated the in vitro antifungal activity of amphotericin B, alone and in combination with rifabutin, an inhibitor of bacterial RNA polymerase, against 26 clinical isolates of Aspergillus and 25 clinical isolates of Fusarium. Synergy or additivism between these drugs was demonstrated against all isolates tested. Amphotericin B MICs were reduced upon combination with rifabutin from a mean of 0.65 microg/ml to a mean of 0.16 microg/ml against Aspergillus, and from a mean of 0.97 microg/ml to a mean of 0.39 microLg/ml against Fusarium (P < 0.000001 for both). Similarly, the MICs of rifabutin were reduced upon combination with amphotericin B from a mean of >32 microg/ml to a mean of 1.1 microg/ml against both fungi (P < 0.000001 for both). These positive interactions were corroborated by a colony count study with two Fusarium isolates, for which treatment with the combination of subinhibitory concentrations of amphotericin B (at concentrations 2- and 4-fold less than the MIC) and rifabutin (at concentrations ranging from 4- to 64-fold less than the MIC) resulted in 3.2-log reductions in colony counts compared to those after treatment with either drug alone. Inhibition of RNA synthesis was shown to be the mechanism of antifungal activity. These results suggest that inhibition of fungal RNA synthesis might be a potential target for antifungal therapy.     

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.     

The MRI of cervical lymph node metastasis with malignant tumor of the head and neck]

Ketamine has many properties that are advantageous to the practitioner in a rural setting, particularly if solo. The personal experience of the author is recounted, and a technique for using ketamine is outlined.     

Mediastinal lymph node metastasis from esophageal carcinoma: CT assessment with pathologic correlation

Computed tomographic (CT) scans were performed in 179 patients with esophageal carcinoma to evaluate mediastinal lymph node metastasis. Histopathologic findings were compared with CT findings in a total of 7,218 resected lymph nodes. First, the criterion for lymph node metastasis on CT scans was 10 mm or more in long transverse diameter. The overall sensitivity and positive predictive value (PPV) were 19% (60 of 317 nodes) and 33% (60 of 180 nodes), respectively. Analysis of each of the eight subgroups of mediastinal nodes revealed that the PPV was more than 70% in node Nos. 105, 108, 110, and 112. In other subgroups, however, the PPV was less than 60%. Sensitivity was less than 50% in all eight subgroups. Second, the criterion for metastasis was 10 mm or more in short transverse diameter. The overall sensitivity and PPV were 8% (26 of 317 nodes) and 63% (26 of 41 nodes), respectively. Analysis of subgroups showed that the PPV in No. 106 nodes increased to 92%. In No. 106 nodes, use of a 5 mm criterion in long transverse diameter increased sensitivity to only 55%. Of the 317 histopathologically proven metastatic lymph nodes, 90 nodes (28%) were 10 mm or more in size, 112 (35%) were 5-10 mm, and 115 (36%) were less than 5 mm. Of the 6,901 non-metastatic lymph nodes, 473 nodes (7%) were 10 mm or more in size. Small (less than 5 mm in size) metastatic nodes were present in all eight subgroups. Among No. 107 and 109 nodes, large (10 mm or more in size) nonmetastatic nodes were prominent, resulting in low sensitivity and PPV. We conclude that CT does not provide an accurate assessment of metastatic versus non-metastatic mediastinal lymph nodes in patients with esophageal carcinoma.     

Prediction of cervical lymph node metastasis in squamous cell carcinoma of the tongue/floor of mouth

BACKGROUND: Cervical lymph node metastasis has a major influence on survival in oral cancer. However, the factors influencing its occurrence are uncertain. Our aim was to improve the prognostic efficiency of the histologic assessment of the primary tumor in predicting metastasis in an individual patient. METHODS: The relationship between selected clinical and histologic features of the primary tumor of tongue/floor of the mouth and the actual metastatic status was investigated in 45 patients. Invasive cell grading was supplemented by histologic measurements of tumor size and assessments of vascular and perineural invasion. RESULTS: Ten histologic features showed significant differences in relation to metastasis. A logistic regression model with two predictor variables (total histologic malignancy score and vascular invasion) classified correctly 39 (87%) of the 45 cases. CONCLUSIONS: Histologic assessment of tumor size and malignancy grade are useful in predicting metastasis. Vascular and perineural invasion are important predictors and should be included in multifactorial malignancy grading schemes. Application of the prognostic index to the biopsy specimen would aid in treatment planning.     

Endoscopic treatment of submucosal invasive colorectal carcinoma with special reference to risk factors for lymph node metastasis

A clinicopathological analysis of the risk factors for lymph node metastasis was performed in 177 patients with submucosal invasive colorectal carcinoma (CRC). The submucosal deepest invasive portion was histologically subclassified as well (W), moderately (M), or poorly (Por) differentiated. M type was further subdivided into moderately-well (Mw) and moderately-poorly (Mp) differentiated. The pattern of tumor growth was classified as polypoid growth (PG) and non-polypoid growth (NPG). Lymph node metastasis was detected in 21 (12%) of the 177 patients. Macroscopically, type IIc and IIa + IIc lesions showed a significantly higher incidence of lymph node metastasis (44% and 30%) than type IIa and I (4% and 8%). Regarding the histologic subclassification, Por and Mp lesions showed a significantly higher incidence of lymph node metastasis (67% and 37%) than W and Mw lesions (4% and 14%). NPG tumors showed a significantly higher incidence of lymph node metastasis (29%) than PG tumors (7%). The depth of submucosal invasion and lymphatic invasion (ly) were also significantly correlated with the incidence of lymph node metastasis (submucosal scanty (sm-s) invasion 4%, massive invasion 20%; ly(+) 23%, ly(-) 5%). None of the lesions with both sm-s invasion and of W or Mw type showed lymph node metastasis. These results indicate that submucosal invasive CRC with both sm-s invasion and of W or Mw type, which shows no ly, is the appropriate indication for endoscopic curative treatment.     

Para-aortic lymph node metastasis in carcinoma of the distal bile duct

BACKGROUND/AIMS: Lymph node dissection plays an important role in radical surgery for pancreaticoduodenal carcinomas. The aim of this study was to identify the critical areas of lymph node dissection in carcinoma of the distal bile duct. METHODOLOGY: Between January 1995 and December 1996, 20 consecutive patients with distal bile duct cancer underwent pancreaticoduodenectomy with extended lymph node dissection (including the para-aortic nodes). Histopathologic findings were examined with special reference to lymph node metastasis. RESULTS: Histological evidence of lymph node metastasis was found in 11 patients (55%). The areas with frequent metastases were the posterior pancreaticoduodenal lymph nodes (35%), and the nodes around the hepatoduodenal ligament (35%) and around the common hepatic artery (30%). Para-aortic lymph node involvement was identified in 5 patients (25%). Most of these existed in the inter-aorticocaval space. Pancreatic parenchymal invasion was present in 10 patients. Half of the patients with pancreatic invasion had para-aortic nodal involvement. Para-aortic lymph node metastasis was significantly associated with pancreatic parenchymal invasion (p<0.05). CONCLUSIONS: In carcinoma of the distal bile duct with pancreatic parenchymal invasion, extended lymph node dissection (including para-aortic nodes) should be undertaken because of the relatively high incidence of metastasis.     

In situ detection of PCR-amplified metalloproteinase cDNAs, their inhibitors and human papillomavirus transcripts in cervical carcinoma cell lines

Current fluorescence-based adhesion assays that use a 96-well plate format rely on the assumption that the fluorescent label does not significantly leak from the cells. Thus, we evaluated a calcein-based, in vitro adhesion assay in 96-well plates using five different types of leukocytes (HL60 cells, human neutrophils, rat neutrophils, mouse progenitor T cells and EL4 cells). Each cell type leaked calcein at a different rate, with the highest rates found for rat neutrophils and progenitor T cells, which lost as much as 20%-40% of the label within 90 min, the time required to complete the assay. Thus, we developed a procedure to measure the dye leakage rate during the assay in order to obtain a correction factor, which was then used to calculate the "true" number of adherent cells. Data for the adhesion of FTF1 cells to endothelial monolayers, after correction for calcein leakage, deviated less than 10% of adhesion data obtained with a well-established 51Cr-based assay.     

Predicting regional lymph node metastasis in carcinoma of the penis: a comparison between fine-needle aspiration cytology, sentinel lymph node biopsy and medial inguinal lymph node biopsy

OBJECTIVE: To evaluate the accuracy of clinical examination and fine-needle aspiration cytology (FNAC) in detecting groin metastases in patients with carcinoma of the penis, and to assess the positive and negative predictive value (PPV, NPV) of a preliminary sentinel lymph-node biopsy (SNB) and biopsy of the most medial of the horizontal group of inguinal lymph nodes (MIN) in selecting patients for an ilio-inguinal block dissection. PATIENTS AND METHODS: The study comprised 28 patients (56 groins) with Stage I (one), Stage II (11) and Stage III (16) carcinoma of the penis. All patients underwent a detailed clinical examination followed by FNAC of the palpable inguinal nodes, and were subsequently submitted for block dissection. The MIN, the SN and the rest of the inguinal and iliac nodes were histologically examined separately for metastases. RESULTS: The clinical evaluation had a sensitivity of 74%, a specificity of 61%, a PPV of 57% and a NPV of 77%. The corresponding values for FNAC were all 100%, and the specificity and PPV for both MIN and SN were 100%. The sensitivity and NPV of MIN were higher than for SN, although not significantly so. CONCLUSION: Clinical examination alone is inaccurate in selecting patients with carcinoma of the penis for block dissection. FNAC is accurate and specific when nodes are palpable; in those with impalpable nodes a preliminary MIN biopsy followed by SNB if the MIN biopsy is negative will accurately select all patients with metastases in the groin nodes. This can be performed by examining frozen sections of the lymph nodes; if positive, block dissection can be carried out at the same time.     

Factors affecting prognosis of papillary thyroid carcinoma with bilateral cervical lymph node metastases

One hundred thirty nine cases of papillary thyroid carcinoma with bilateral lymph node metastases were reviewed. They were surgically treated at the Cancer Hospital of Shanghai Medical University in the years from 1956 through 1990. There were 73 men and 66 women with a median age of 35 (range 11-70) years. The median follow-up period was 11 years. Kaplan-Meier survival curves were calculated for the population. The overall survival rate was 94.7% at 5 years, 85.9% at 10 years, and 82.3% at 15 years. In univariate analysis, factors influencing prognosis are age at diagnosis, tumor size, extrathyroidal invasion, residual tumor and thoroughness of excision. When Cox proportional risk model was applied to analyze the survival data, factors of survival significance are the age at diagnosis and thoroughness of excision.     

Extracapsular invasion of lymph node metastasis is an indicator of distant metastasis and poor prognosis in patients with thyroid papillary carcinoma

BACKGROUND: In patients with thyroid papillary carcinoma, age and the presence or absence of distant metastasis are regarded as the main prognostic factors. However, the histologic characteristics of thyroid papillary carcinoma that develops distant metastasis have not yet been clarified. METHODS: The histologic findings and prognosis of 50 patients with thyroid papillary carcinoma who later developed distant metastasis (metastatic group) were compared with those of 50 patients without local recurrence or distant metastasis (control group). The age, tumor size, and gender ratio of the control group were matched with those of the metastatic group. Univariate analyses (chi-square test and/or Fisher's exact test) and multivariate analyses (logistic regression) were performed. RESULTS: Univariate analyses showed that the incidence of nonpure papillary carcinoma, absence of bone at the periphery of the tumor, invasion of the perithyroidal muscle, large lymph node deposits, and extranodal invasion were significantly higher in the metastatic group. Multivariate analyses revealed that only extranodal invasion was statistically significant (P = 0.0045) and that the odds ratio of extranodal invasion in distant metastasis was 9. Moreover, the risk of death from thyroid carcinoma was higher among the patients with extranodal invasion than those without (P <0.01). CONCLUSIONS: The presence of extranodal invasion in patients with thyroid papillary carcinoma is an indicator of distant metastasis and poorer prognosis.     

Relationship between nm23-H1 expression and lymph node metastasis and prognosis in cervical cancer

OBJECTIVE: To investigate the expression of nm23-H1 in cervical carcinoma and its significance. METHODS: Expression of nm23-H1 was examined by immunohistochemical method in 39 cases of adenocarcinoma and 39 cases of squamous cell carcinoma of the uterine cervix. The relationship between expression of nm23-H1 and clinic-pathologic factors and prognosis was analyzed by chi-square test. RESULTS: Positive staining rate of nm23-H1 was 44.6% in adenocarcinoma and 39.2% in squamous cell Carcinoma. The positive staining rate of nm23-H1 in stage I and II adenocarcinoma was 61.1% and 28.6% respectively (P = 0.044); in patients with recurrence nm23-H1 positive rate was lower than that in patients without recurrence (21.5% vs 56%, P = 0.39); in patients with lymph node negative, nm23-H1 positive staining was more than that in patients with lymph node positive (52% vs 28.6%), however, this difference was not statistically significant (P = 0.162). None of 14 cases of lymph node metastasis was strong positive stainig, whereas 7 of 25 without lymph node metastasis were demonstrated to have strong positive staining (P = 0.031). The 5-year survival rate in negative staining group was lower than that in the positive staining group (52.5% vs 82.4%, P = 0.042). In squamous cell carcinoma there was no statistically significant relationship between nm23-H1 expression and clinic-pathologic factors and prognosis. CONCLUSIONS: nm23-H1 expression was associated with biologic behavior in cervical adenocarcinoma.     

NDPK/nm23 expression and its correlation with lymph node metastasis in human lung cancer

Using labelled streptavidin-biotin (LSAB) method, we examined the expression of nucleoside diphosphate kinase(NDPK), the product of metastasis suppressor gene nm23, in human lung cancer. Of 88 patients tested, 48 (54.5%) showed positive staining. The positive staining rate was higher in adenocarcinoma (28/42, 66.7%) than in squamous cell carcinoma (20/46, 43.5%; P < 0.05). Higher incidence of positive staining was also found in squamous cell carcinoma without hilar or mediastinal lymph node metastasis (16/27, 59.3%) than in that with hilar or mediastinal lymph node involvement (4/19, 21.1%; P < 0.05). NDPK/nm23 was equally expressed in adenocarcinoma irrespective of lymph node status. In both cell types of carcinoma, expression of NDPK/nm23 was not correlated with tumor cell differentiation, nor was it correlated with the P-TNM staging. Our results suggest that NDPK/nm23 may play different roles in the pathogenesis and metastasis of human pulmonary squamous cell carcinoma and adenocarcinoma. Its expression levels are inversely correlated with lymph node metastasis in squamous cell carcinoma.     

Rare association of human herpesvirus 6 DNA with human papillomavirus DNA in cervical smears of women with normal and abnormal cytologies

We investigated by nested PCR the possible association of human herpesvirus 6 (HHV-6) and human papillomavirus (HPV) genomes in the cervixes of 109 women with normal and abnormal cytological smears. HPV DNA was detected in 8.33% of 24 women with normal cytologies and in 41.1% of 85 women with abnormal cytologies; the proportion of HPV DNA was directly related to the severity of the lesions. HHV-6 DNA was found in only one patient, who had a cytological pattern of koilocytosis. The HHV-6 genome was classified by restriction enzyme analysis as variant B. The study indicates that detection of the HHV-6 genome in the cervixes of women with a wide spectrum of gynecological complaints is a rare event and rules out the possible association between HHV-6 and HPV genomes in cervical cancer lesions.     

Surgical intervention for patients with stage IV-A hepatocellular carcinoma without lymph node metastasis: proposal as a standard therapy

OBJECTIVE: The aim of this study was to evaluate the effects of surgical treatments for patients with stage IV-A hepatocellular carcinoma (HCC) without lymph node metastasis. SUMMARY BACKGROUND DATA: Nonsurgical therapy for highly advanced HCC patients has yielded poor long-term survival. Surgical intervention has been initiated in an effort to improve survival. METHODS: The outcome of 150 patients who underwent hepatic resection was studied. Survival analysis was made by stratifying stage IV-A HCC patients into two groups-those with and those without involvement of a major branch of the portal or hepatic veins. Those with involvement were further divided into subgroups according to major vascular invasions. RESULTS: Patients who had multiple tumors in more than one lobe without vascular invasion had a significantly better 5-year survival rate (20%) than those with vascular invasion (8%) (p < 0.01). The survival rate of patients with hepatic vein tumor thrombi (10%) was better than the rate for those with tumor thrombi in the inferior vena cava (0%), in whom no patients survived more than 2 years, although the survival rate for those with portal vein tumor thrombi in the first branch (11%) was no different from the rate for that in the portal trunk (4%). The operative mortality decreased from 14.3% in the first 6 years to 1.4% in the following 5 years. CONCLUSIONS: Surgical intervention for stage IV-A HCC patients brought longer survival rates for some patients. We recommend surgical intervention as an effective therapeutic modality for patients with advanced HCC.     

Expression of p53 and p21 proteins in oral squamous cell carcinoma: correlation with lymph node metastasis and response to chemoradiotherapy

p53 protein, a product of the p53 cancer suppressor gene, and p21 protein, a cyclin-dependent kinase inhibitor, were immunohistochemically investigated in 150 oral squamous cell carcinomas (SCCs) and the relationship between their expression and clinicopathological findings were evaluated. The positivity for p53 and p21 proteins was not correlated with the T-stage, mode of tumor cell invasion or tumor cell differentiation. However, the expression of p53 and p21 proteins was correlated with lymph node metastasis. Of 62 SCCs with regional lymph node metastasis, 45 SCCs (72.6%) were positive for p53 while 45 (52.9%) of 88 SCCs without metastasis expressed p53 protein (p < 0.02). In addition, p21 protein was observed in 25 (38.5%) and 18 (21.2%) SCCs with and without metastasis, respectively (p < 0.05). Furthermore, p53 protein was inversely correlated with the histopathological effect of inductive chemoradiotherapy; the rate of chemoradiotherapy-induced lethal degeneration (56.7%) in p53-negative SCCs was significantly higher than that (28.9%) in p53-positive SCCs (p < 0.005). However, no clear difference in the effect was observed between p21-positive and p21-negative SCCs. Finally, the 5-year-survival rate was highest in p53(-)-p21(+) (80.0%) followed by 76.3% in p53(-)-p21(-), 65.9% in p53(+)-p21(+) and 65.4% in p53(+)-21p(-) SCCs. These results indicate that although the expression of p21 protein is only weakly correlated with the clinico-histopathological findings, p53 protein is a useful prognostic marker and that inductive chemoradiotherapy can be successfully planned by immunohistochemical examination of p53 protein.     

Two cases of gastric involvement of esophageal cancer: intramural metastasis and intramural lymph node metastasis

Cases of esophageal cancer with intramural metastasis to the stomach and esophageal cancer with metastasis to an intramural lymph node of the stomach are herein reported. The former patient was a 52 year-old male. Squamous cell carcinoma (SCC) of the lower esophagus with an intramural metastasis located at the gastric cardia and a small leiomyoma at the fornix were resected. The latter patient was a 70 year-old female. SCC of the lower esophagus and an intramural lymph node metastasis located at the anterior wall of the gastric cardia were resected. The patient died nevertheless of multiple liver metastases. These gastric involvements were detectable by endoscopy before surgery. The clinicopathological features of these esophageal cancers were characterized; the sites were the lower part of the esophagus, and extreme lymphatic and vascular invasions were shown histologically. The gastric tumors were located in the upper third of the stomach, and the findings revealed submucosal tumors. It is therefore important to discriminate other gastric tumors, and to resect them simultaneously with esophageal cancer when a gastric tube has been used for reconstruction after esophagectomy.