High-dose epirubicin in platinum-pretreated patients with ovarian carcinoma: the EORTC-GCCG experience

A follow up study of 20 cases of renal cell carcinoma with regional lymph node metastasis at the department of urology in Niigata Cancer Center Hospital from 1979 to 1993 is presented. During this period, we treated 249 patients with renal cell carcinoma with or without lymph node metastasis. Lymph node metastasis could be estimated in 188 out of 249 patients. Histologically, lymph node metastasis was classified as pN1 in 8 cases, pN2 in 7 cases, and pN3 in 5 cases. The 3- and 5-year survival rates of 20 patients with lymph node metastasis were 45.0% and 16.4%, respectively. Nine of the 20 cases had no distant metastasis and 11 cases had distant metastasis. Three of the 9 patients with distant metastasis had no recurrence. Two of these 3 patients are still alive after 10 years and 3 years and 1 patient died because of acute heart failure. These 3 patients had pN1 metastasis smaller than 1 cm lymph node. Four of the 11 patients with distant metastasis had more than a two-year survival. However, 3 patients died due to renal cell carcinoma although primary and metastatic regions were resected and IFN with chemotherapy were given. Only one patient is still alive without recurrence after 3 years. This case detected as right renal cell carcinoma with pN2 metastasis and bilateral pulmonary metastasis was treated with radical nephrectomy with regional lymph node dissection and administered Methotrexate, VP16 and CisPlatinum chemotherapy and IFN.(ABSTRACT TRUNCATED AT 250 WORDS)     

The prognostic impact of metastatic pattern of lymph nodes in patients with oral and oropharyngeal squamous cell carcinomas

In patients with squamous cell carcinomas of the oral cavity and the oropharynx the presence or absence of nodal metastases still is the most important predictive factor. The discriminative significance of extracapsular spread and the influence of features of the primary tumor-such as size and depth of invasion-on metastatic pattern, treatment failure and survival were evaluated. Five-year postoperative follow-ups of 115 consecutively treated patients were studied retrospectively concerning the incidence of distant metastases, local and regional recurrences and the 5-year survival rate. Maximum depth of invasion of the primary tumor and lymph node metastases were evaluated on the basis of histological patterns, and patients were grouped according to their histological diagnosis. The T4 category has a plain discriminative influence on the incidence of distant metastases, recurrent tumors and survival rate in contrast to the other T sizes. The classification N0, intranodal growth and extranodal growth of lymph node metastases resulted in a 5-year survival rate of 67, 59 and 31%. According to the classification, 84, 87 and 59% were without nodal recurrence after 5 years, and 79, 82 and 46% without distant metastases. Size and depth of invasion of the primary tumor are not connected significantly with the occurrence of extracapsular spread. The status of the lymph nodes in squamous cell carcinomas of the oral cavity and the oropharynx metastases and in particular the capsular rupture has the most significant prognostic influence. The histological feature of extracapsular spread could distinguish reproducibly high risk patients with squamous cell carcinomas of the oral cavity and the oropharynx.     

Medical care in 7 Chilean cities

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is a recently recognized malignant neoplasm of the thyroid gland. Two additional cases of this condition which occurred in a 70-year-old woman and a 69-year-old woman are presented. The case of the 70-year-old woman (patient 1) is the first report of distant metastasis, besides lymph node metastasis, for this type of tumor. The patient initially presented with a thyroid mass, and the thyroid gland with surrounding cervical lymph nodes was removed. Because of focal keratin "pearl" formation, the tumor was misinterpreted as a metastatic squamous cell carcinoma to the thyroid. Approximately 4 years later, the patient developed a left supraclavicular mass and lung densities. A pathological fracture of the right humeral head followed, and the left supraclavicular mass recurred along with newly developed subcutaneous nodules on the chest wall and arm. Open lung and bone biopsies revealed metastatic SMECE, which was morphologically identical to that of the thyroid mass. The 69-year-old woman (patient 2) had, in 1983, undergone thyroidectomy with left radical neck dissection; this had been diagnosed as follicular carcinoma of the thyroid with lymph node involvement. After multiple isolated lymph nodes metastases, the patient developed locally extensive, recurrent tumor that showed microscopic features of SMECE. Review of the previous thyroid tumor and lymph nodes revealed the same type of histology. To our knowledge, only a single report containing eight cases of this distinctive carcinoma of the thyroid has been published. Herein we describe characteristic morphological features of two additional cases of this rare malignancy, one with distant metastasis, and we review the related literature.     

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.     

Tumor recurrence following resection for early gastric carcinoma and its implications for a policy of limited resection

Some patients suffer postoperative recurrence after curative resection of early gastric carcinoma. This study reviewed consecutive patients with a single primary lesion and analyzed the relation between the pathologic findings and recurrence of early gastric carcinomas for determining indications for limited surgery. Among the 1585 consecutive patients with a solitary primary lesion of an early gastric carcinoma who had undergone curative surgery between 1963 and 1989 at one general hospital, pathologic findings relating to recurrence were analyzed according to Japan's General Rules for Gastric Cancer Study in Surgery and Pathology. Of these carcinomas, mucosal carcinomas comprised 701 (44.2%) and submucosal ones 884 (55.8%). The total recurrence rate in this series was 1.0%. Submucosal carcinomas (1.6%) were significantly (p < 0.02) more recurrent than mucosal ones (0.29%). Of the 16 patients with recurrence, 10 (62.5%) died within 5 years after surgery, frequently because of blood-borne metastasis. Macroscopically elevated components, the degree of histologic differentiation, and lymph node metastasis significantly contributed to the postoperative recurrence. After detailed analysis of submucosal carcinomas, it is strongly suspected that carcinomas with a macroscopically elevated component were significantly associated with nodal involvement and microvessel invasion, and that these abnormalities lead to recurrence. Among the early gastric carcinomas, differentiated submucosal carcinomas with a macroscopically elevated component, lymph node metastasis, or both have the most potential of recurrence after surgery. Mucosal carcinomas must be restricted to limited surgery, but, blood-borne metastasis should be carefully avoided.     

Efficacy of radical hysterectomy as treatment for patients with small cell carcinoma of the cervix

BACKGROUND: This study was performed to identify pathologic and clinical features that best predict disease free survival of patients with early stage small cell carcinoma of the cervix treated by radical hysterectomy. METHODS: Three hundreds and seventy patients with cervical carcinoma were analyzed retrospectively to define those variable that best predict disease free survival (DFS). Variables included age, weight, race, marital status, economic status, tumor size, depth of invasion (DI), lymph-vascular space involvement (LVSI), cell type, tumor grade, lymph node metastasis (LNM), and total number of lymph nodes removed. Patients with lymph node metastasis, parametrial involvement, and positive or close surgical margins were offered postoperative radiation. RESULTS: Twelve patients were found to have small cell carcinoma (3.2%). One patient had microinvasive carcinoma of the cervix (MIC) as defined by the Society of Gynecologic Oncologists with a depth of invasion of 3 mm or less and no lymph-vascular space invasion, and has been reported previously. A detailed analysis of the other patients with nonsmall cell carcinoma is presented separately. Five patients achieved a DFS of at least 5 years, whereas 7 patients died with disease. Excluding the patient with MIC, the 5-year DFS rate was 36.4%. CONCLUSIONS: Relative to other cell types, small cell carcinomas of the cervix is an aggressive neoplasm with a higher rate of LVSI and LNM despite smaller DI and tumor size. These data suggest that multimodality therapy, combining radical surgery and radiation with cytotoxic chemotherapy, may provide these patients with the best chance for cure.     

Cricohyoidopexy in selected infrahyoid epiglottic carcinomas presenting with pathological preepiglottic space invasion

Nineteen patients who presented with infrahyoid epiglottic squamous cell carcinoma with gross pathological preepiglottic space invasion, not amenable to a partial horizontal supraglottic laryngectomy, were offered a supracricoid partial laryngectomy with a cricohyoidopexy technique; this was an attempt to preserve physiological phonation, respiration, and deglutition while achieving the same local control rate as with a total laryngectomy. Preoperative chemotherapy and bilateral jugulocarotid lymph node dissection were performed in all cases. Patients were monitored for at least 5 years or until death. No patients were unavailable for follow-up. The 5-year actuarial survival (Kaplan-Meier method) was 84.2%. Local recurrence, nodal recurrence, and distant metastasis occurred once in our series, while six patients presented with a second primary tumor. We present, analyze, and compare functional results with those of the previously reported series. Our experience with the supracricoid partial laryngectomy with a cricohyoidopexy, in the face of selected infrahyoid epiglottic squamous cell carcinoma invading the preepiglottic space, not amenable to a partial horizontal supraglottic laryngectomy, suggested that a total laryngectomy might be avoided without decreasing the cure rate.     

Unilateral lobectomy for Hurthle cell adenoma

Considerable controversy exists regarding the ability to predict the biologic behavior of Hurthle cell tumors. Some have found the clinicopathologic criteria used to differentiate benign from malignant lesions to be unreliable and have advocated total thyroidectomy for all Hurthle cell neoplasms. From January 1980 to December 1995, 39 patients had surgery for Hurthle cell tumors of the thyroid. The surgical pathologic findings were reviewed by an experienced pathologist (JP). Eight patients had histologic findings of capsular or vascular invasion consistent with carcinoma and had total thyroidectomy. Four of these patients had postoperative evidence of residual disease and were treated by radiation ablation. No evidence of invasion was found in 31 patients diagnosed with Hurthle cell adenoma. Twenty-three of these patients had unilateral lobectomy; total thyroidectomy was done in the remaining 8 patients, 5 of whom were found to have an associated papillary carcinoma at the time of operation. There were no operative deaths or significant morbidity. Twenty-two adenomas (71%) were found in females, whereas males had malignant tumors in 6 of 8 cases (P = 0.025). The mean age of adenoma patients is 54.1 years, and that of the carcinoma patients is 55.8 years. Mean size of benign tumors was 2.8 cm and of malignant tumors 4.1 cm (P = 0.04). Four of seven (57%) carcinomas were larger than 4 cm as compared with 6 of 30 (20%) adenomas (P = 0.069). Follow-up has ranged from 1 month to 15 years, with a mean of 3.2 years. There have been no deaths, and no patients with Hurthle cell adenoma have had evidence of recurrence or metastases during follow-up. Our data suggest that carcinoma patients tend to be male and tumor size is larger. An association was found when trying to predict malignancy by using 4 cm as a threshold size. We conclude that pathologic evidence of capsular or angioinvasion can accurately differentiate benign from malignant tumors. Unilateral thyroid lobectomy is adequate therapy for the treatment of Hurthle cell adenoma, with total thyroidectomy reserved for those patients with histologically proven carcinoma.     

Fibrotic focus in invasive ductal carcinoma of the breast: a histopathological prognostic parameter for tumor recurrence and tumor death within three years after the initial operation

We investigated whether the presence of a fibrotic focus (FF) in the primary lesion and in lymph node metastasis is a good predictor of early tumor recurrence or death in patients with invasive ductal carcinoma (IDC). Multivariate relative risk (RR) of tumor recurrence and death according to the presence of FF in the primary tumor was estimated using the Cox proportional hazards regression model with adjustment for other prognostic factors (histologic grade, T classification, nodal status, tumor necrosis, DNA ploidy, c-erbB-2 protein expression, p53 protein expression, and labeling index of proliferating cell nuclear antigen). For the evaluation of the metastatic status in the axillary lymph nodes, RR of multivariate analysis was adjusted for the presence of FF in the metastatic tumor and the number of lymph nodes involved (1-3 and > 3). The presence of FF increased the RR of tumor recurrence significantly for the cases in all stages, and especially for those in stages I and II (RR = 6.9, P < 0.05 and RR = 25.0, P < 0.005, respectively). All cases that died of disease had FF. Among IDCs with FF, 24 cases had FF in lymph node metastasis. Significantly higher RRs of tumor recurrence and death were observed in cases with FF in lymph node metastasis than in those without it (RR = 2.0, P < 0.001 and RR = 5.9, P < 0.05, respectively). It was suggested that the presence of FF is an important predictor of early tumor recurrence or death in patients with IDCs. The presence of FF in lymph node metastatic lesions is also a significant prognostic parameter.     

Radiotherapy for carcinoma of the nasal cavity

Twenty-five patients with primary epithelial carcinoma of the nasal cavity without nodal or distant metastases were treated by irradiation between 1967 and 1978. Small field, beam-directed techniques delivered 6,000 to 7,000 rads with conventional fractionation. Control of the primary tumor was achieved in 21 (84%) patients after irradiation. All five treatment failures (one infield only, three infield recurrence with lymph node metastases, and one regional cervical node metastasis) were evident within six months; all five patients died of cancer. The adjusted actuarial survival rate at three years was 76%. Failure in the untreated neck was only 5% when the primary carcinoma was controlled and 16% overall. The literature has been reviewed with attention to tumor control rates and survival.     

Prognostic significance of depth of invasion in cancer of the larynx

To determine the prognostic significance of depth of invasion in laryngeal cancer, the depth of invasion of tumor was measured with an ocular micrometer on the laryngectomy specimens of 94 surgically treated patients with T1, T2, and T3 laryngeal cancer and was expressed in millimeters. There was a significant negative correlation between the depth of invasion and disease-free survival. The tumors with no clinical involvement of regional lymph nodes in neck (NO neck) had significantly less depth of invasion than those with involvement (N+ neck). The tumors with pathologically confirmed cervical lymph node metastasis had significantly more depth of invasion than those without metastasis. For tumors with a depth of invasion equal to or greater than 3.25 mm, the rate of cervical metastasis in this study has always been significantly higher than for those with a depth of invasion less than 3.25 mm (P < .05). The mean depths of invasion for cases with and without recurrence were not significantly different. According to the multivariate analysis, depth of invasion (P = .047) and patient age (P = .113) significantly affected the disease-free survival independently. The depth of invasion did not significantly affect the recurrence and the interval between surgery and the development of recurrence (P > .15). The depth of invasion should be measured in every laryngectomy specimen. The depth of invasion influences the cervical metastasis and disease-free survival significantly but does not affect the recurrence rate. The depth of invasion plays an independent role in determining the disease-free survival.     

The role of human papillomavirus DNAs in cervical carcinoma and risk of lymph node metastasis: association with 72-kilodalton metalloproteinase immunostaining

BACKGROUND: The role of human papillomavirus (HPV) as a prognostic factor in cervical carcinoma is not understood completely and little is known regarding the intrinsic mechanisms involved in the metastatic process of HPV positive carcinoma. The authors evaluated HPV status with respect to clinical features in early stage cervical carcinoma, with special emphasis on lymph node spread. The authors also analyzed the relation between HPV, lymph node involvement, and 72-kilodalton (kDa) metalloproteinase immunostaining, an enzyme that cleaves Type IV collagen and may play a role in tumor metastasis. METHODS: Thirty-two patients with International Federation of Gynecology and Obstetrics Stage I and IIA squamous cell cervical carcinoma treated by primary radical surgery were reviewed. Histologic grade of differentiation, tumor size, fractional depth of invasion, and lymph node spread were evaluated with respect to HPV status and 72-kDa metalloproteinase immunostaining. HPV DNA was detected by polymerase chain reaction and the primers potentially recognized at least the following HPV subtypes: 6, 11, 16, 18, 31, 33, 34, 35, 42, 51, 56, and 58. Immunohistochemical staining was performed using the avidin-biotin complex technique. Affinity-purified rabbit anti-72-kDa metalloproteinase antibody was used. RESULTS: HPV DNA was detected in a total of 69% of cases, and HPV-16 was the most frequent type detected. HPV positive carcinomas showed a significantly higher rate of lymph node metastases than HPV negative carcinomas (45% vs. 10%; P = 0.03); similarly, 72-kDa metalloproteinase index was significantly higher (P = 0.001). CONCLUSIONS: These findings suggest a relation between HPV and risk of lymph node metastasis, which may be mediated by an increased production of 72-kDa metalloproteinase.     

Small-intestinal digestion of partially resistant cornstarch in healthy subjects

Primary adenocarcinoma of sweat glands is a rare tumor; approximately 220 cases have been reported in the last 30 years. We reviewed the charts of patients with primary diagnosis of this tumor treated at the Mayo Clinic between 1935 and 1995. We included only cases with initial histology slides available for re-examination. Tumors were classified into five recognizable histologic patterns (solid, ductal, mucinous, microcystic adnexal, and adenocystic carcinoma) and graded by the Broder system. Statistical analysis consisted of Kaplan-Meier product limit method and Cox multiple regression test. In total, 55 patients were identified, and age ranged from 13 to 85 years (mean 59 years). Thirty-six patients (65 percent) presented to the Mayo Clinic for initial treatment; all except one had disease limited to the primary site. Microcystic adnexal carcinoma was the most frequent type, and more than 50 percent were grade 2 tumors. Among these 36 patients, 4 had some type of recurrence. Patients who developed metastasis had a high-grade tumor in the initial biopsy. Nineteen patients were referred with recurrence; 13 had local recurrence, 4 had regional diseases, and 2 had distant metastases. The histologic distribution showed 47 percent solid tumors, and 37 percent of them were grade 3. Multiple regression analysis did not show a difference in recurrence or survival when gender, age, tumor location, or histologic pattern was evaluated. In addition, there was no difference in the outcome between wide surgical resection and micrographic surgery. The only predictive factor for distant metastases and/or death (p < 0.003) was histologic grade. Overall 10-year survival rate was 86 and 60 percent for primary and referred patients, respectively. We conclude that histologic diagnosis of sweat gland carcinoma must be complemented by clinical examination to evaluate metastases. Clinical behavior depends on the histologic type of tumor, degree of differentiation, and clinical stage. On recurrence, the likelihood of further recurrences and mortality increases dramatically. Aggressive initial local ablation with tumor-free margins is recommended. In high-grade tumors, prophylactic regional lymph node dissection may further characterize tumor aggressiveness and may justify adjuvant radiotherapy as part of the primary treatment.     

Effect of various forms of metastatic lymph node involvement on prognosis of squamous epithelial carcinomas of the upper aerodigestive tract

BACKGROUND: Based on a new histo-morphological rating scheme, we assessed the impact on patient prognosis of lymph node metastasis of squamous cell carcinoma (SCC) in the head/neck area. Special attention was given to possible capsular rupture. METHOD: In a retrospective study, 111 patients with squamous cell carcinoma of the head and neck with concomitant cervical lymph node metastases were evaluated to determine the importance of lymph node capsular rupture on the occurrence of disseminated disease, loco-regional recurrence as well as survival rate. To cover the broad morphological spectrum of cervical metastatic disease, a newly developed scheme (differentiating seven different histo-morphological types of lymph node metastasis) was applied. On the basis of this scheme, every single metastatic lymph node received a score from one to seven. These single scores were then added to obtain a total score for every individual patient. These total scores were then divided into four groups. RESULTS: Synthesis of histo-morphological pattern of metastasis in combination with the number of metastatic lymph nodes showed highest concordance/significance in respect of disseminated disease (p = 0.0029), local recurrence (p = 0.0008) and regional lymph node metastasis (p = 0.0000) as well as survival rate (p = 0.0000). CONCLUSION: The newly introduced histological scheme seems to provide more accuiate and detailed information on the prognosis of SCC in the head and neck area.     

Cardiac metastasis from squamous cell carcinoma of gallbladder

A 65-year-old woman was admitted to our hospital with the diagnosis of gallbladder tumor. Right extended hepatic lobectomy plus lymph node dissection of the hepatoduodenal ligament and left hepaticojejunostomy with Roux-en-Y reconstruction was performed in July, 1993. The gallbladder tumor was histologically proven to be squamous cell carcinoma. Seventeen months later, the patient experienced dyspnea and pitting edema of the lower legs and was admitted, in December 1994, with a diagnosis of heart failure. Despite intensive cardiac support, she died 12 days after the second admission. Autopsy revealed multiple cardiac tumors in the left and right ventricles, left atrium, left coronary artery, and left diaphragm. Histologically, these tumors were shown to be squamous cell carcinoma, considered to have metastasized from the primary gallbladder carcinoma. As neither local recurrence of the gallbladder carcinoma nor any lymph node metastasis was found, the cardiac metastasis of the gallbladder carcinoma may have occurred via the hematogenous route. Although rare, this route of cardiac metastasis of gallbladder carcinoma may be an important aspect of distant metastasis, which should be monitored for during follow-up after resection of the primary tumor.     

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.     

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.     

NM23 gene expression in human breast carcinomas: loss of correlation with cell proliferation in the advanced phase of tumor progression

NM23 is a protein associated with tumor progression, expressed in all tissues and in human tumors. Reduced expression of NM23.H1 is related to high incidence of lymph node and distant metastasis or to poor prognosis of the patient in several human malignant tumors. In this study we analyze NM23 expression in non-neoplastic mammary tissues surrounding the tumoral lesions, in human mammary carcinomas and in lymph node metastasis. Our analysis shows that NM23.H1 expression is lower in the mammary cells surrounding the tumor than in the tumor itself. In the primary tumors we observed a negative trend between degree of local invasion and level of NM23.H1 expression. A further decrease of NM23.H1 was detected in the invasive tumors that metastasized to axillary lymph nodes and in the metastasis. NM23.H2 was always more highly expressed than NM23.H1, and reduced expression of NM23.H1 but not NM23.H2 was concordant with the presence of lymph node metastasis or local invasiveness of the primary tumor. A positive correlation between NM23.H1 mRNA content and cell growth rate of breast tumor cells has been confirmed. However, this trend was not maintained in cancer cells from tumors that metastasized to axillary lymph nodes and in metastatic cells; in these 2 situations the NM23.H1 mRNA content varied without any relationship to the proliferative rate of the cells. In addition, in comparison with the initial tumor, the metastatic cell population showed a strong decrease of NM23.H1 expression and increased proliferative activity.     

Cyclin D1 amplification as a new predictive classification for squamous cell carcinoma of the esophagus, adding gene information

The cyclin D1, referred to as PRAD-1, has been mapped to the 11q13 region, and its expression has been detected in squamous cell lines and several primary esophageal carcinomas. We assessed cyclin D1 amplification in 122 squamous cell carcinomas of the esophagus. Samples for DNA extraction were obtained from formalin-fixed paraffin-embedded specimens, and 10 microgram of each DNA sample were subjected to slot blot analysis. The presence of more than three gene copies was considered evidence of gene amplification. Amplification of cyclin D1 was detected in 28 (23%) of 122 cases of squamous cell carcinoma of the esophagus. There were no significant differences between the clinicopathological background factors in groups positive and negative for cyclin D1 amplification, but the survival rate of patients exhibiting amplification was significantly lower (P < 0.001). The groups were stratified according to the pN (pathological N category) factor and pT (pathological T category) factor in the TNM classification, and the cumulative survival rates in the amplification groups were always significantly lower. Amplification of cyclin D1 was correlated with distant organ metastasis after curative operations, but there was no significant difference in lymph node recurrence rates of patients with or without amplification. Cyclin D1 amplification had the second highest partial regression coefficient in the multivariate analysis, after the pN factor. Amplification of cyclin D1 was independent of the TNM classification as a prognostic factor, and was a useful marker for predicting outcome and distant organ metastasis in patients with squamous cell carcinoma of the esophagus. It appears that appropriate treatment can be selected by evaluating both TNM factors and cyclin D1 amplification.     

Localization of recurrent disease after extended lymph node dissection for carcinoma of the thoracic esophagus

BACKGROUND: The role of aggressive locoregional dissection in the treatment of carcinoma of the thoracic esophagus is controversial. The extent of disease spread for which resection can be performed is not yet fully established. STUDY DESIGN: Of 230 patients who underwent extended lymph node dissection, including the cervical nodes, the overall hospital mortality rate was 4.8 percent. Recurrent carcinoma was clinically confirmed by periodic follow-up examination with diagnostic imaging in 83 patients. We examined the exact anatomic sites of recurrent lesions and the clinical courses of patients. Recurrence patterns were classified into locoregional, distant, and mixed types. RESULTS: Recurrence of the carcinoma was locoregional in 35 patients, distant in 38 patients, and mixed in ten patients. The frequency of locoregional recurrence was significantly lower in patients with less than eight positive nodes and in patients without invasion of neighboring organs. Locoregional recurrence in the dissected area was mainly found in the region around the recurrent nerves and the main bronchi. Lymph nodes outside of the dissected area developed recurrence only in cases of markedly advanced disease apart from the abdominal para-aortic nodes. The group with locoregional recurrence and the group with distant recurrence had similar clinical courses over time. In patients in whom recurrent lesions could be treated with resection and adjuvant therapy, the one-year survival rate after recurrence was 83 percent. CONCLUSIONS: Unless the disease was markedly advanced, systematic lymph node dissection in our procedures yielded good locoregional control. The relatively low rate of distant recurrence with acceptable hospital mortality rates favors an extensive operation. When recurrent lesions were localized macroscopically, surgical removal of the recurrent lesions offered good palliation.